Author Archive for dbma

The Early History of PSSD

Sherlock Holmes concept

When did it begin?

Post-SSRI Sexual Dysfunction (PSSD) officially made its debut in the peer-reviewed medical literature in 2006. Case reports were published that identified treatment-emergent sexual dysfunction that persisted after the antidepressant was stopped. The condition was given a name and its features were defined.

This new literature also noted the significance of a study dating back to 1999 by Montejo et al. It appears to be the first published clinical trial to have captured the persisting sexual side effects that SSRIs can cause. However, this wasn’t the purpose of the study and it seems that little was made of the finding at the time.

Between the efforts of drug companies to manage concerns about sexual side effects, through to the wider problem of doctors failing to engage with patients on the subject of treatment-related issues, it’s unsurprising that the condition took such a long time to appear in the medical literature.

We know that even today, people who are diagnosed with PSSD can discover that their doctor hasn’t reported it to the country’s drug regulator, and that their diagnosis can appear somewhat buried in the medical records. There remains a very real sense that PSSD is something that health professionals don’t like to talk about.

Who was talking about it?

Even though the condition didn’t appear in the medical literature until 2006, could it have been mentioned earlier in another type of publication?

We certainly know the condition was being seen in clinical practice. We also know that people were reporting it.

A paper by Hogan et al noted that the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK had received over 200 reports of persistent sexual side effects linked to SSRIs prior to the condition appearing in the literature, and without any public awareness of the issue.

If people were going to the trouble of reporting it to a country’s drug regulator, perhaps someone affected or someone in the health profession was also concerned enough to write about it – though it obviously wouldn’t have been called PSSD at the time.

It’s worth noting that while the problem is most commonly associated with SSRIs and SNRIs, it can also happen with some tricyclics that act as serotonin reuptake inhibitors. It’s therefore possible that something may have even appeared in print prior to the introduction of the SSRIs, although this is less likely as it wasn’t until the marketing of the SSRIs that the use of antidepressants became commonplace.

Were you there?

Perhaps you were working as a healthcare professional or medical researcher in the early 2000s, 1990s or 1980s and remember reading or hearing about the problem. Perhaps you wrote an article that appeared in a magazine, newspaper or some other publication. Maybe you mentioned it in a book that is no longer in print.

Are there any doctors or researchers who attempted to publish an article or case reports, but were turned down by a medical journal?

It would be interesting to hear from anyone working in psychosexual therapy. With the explosion of antidepressant use in the last two decades, they will undoubtedly be seeing patients with medication-related problems. It would be interesting to know when PSSD first came onto their radar.

On March 11th 2014, the Dutch newspaper Volkskrant featured an article about PSSD on its front page, prompted by a report about the condition from Lareb, the Netherlands Pharmacovigilance Centre. Is there a chance that the problem was mentioned in a European magazine or newspaper prior to 2006?

If you are aware of such material, we would like to hear from you. Please either leave a comment at the end of this post, or you can contact us through the website.

It would be interesting to fill out some of the early history of PSSD. Who knows what we might discover?

How Common is Post-SSRI Sexual Dysfunction (PSSD)?

Magnifying glass and a group of people

The level of risk of developing Post-SSRI Sexual Dysfunction (PSSD) from using an SSRI or SNRI antidepressant is currently unknown. Patients are never warned about persisting sexual side effects when these drugs are prescribed.

Calls for informed consent are often met with the response that PSSD appears to be quite rare. Given the huge number of antidepressants prescribed every year, the number of people complaining of PSSD is comparatively small. Doctors wouldn’t normally be expected to discuss every rare side effect of a medication when prescribing it.

To the uninformed, this might seem like a reasonable argument. However, there are a number of complex dynamics involved in the issue of PSSD that not only make it difficult to establish its true prevalence, but they also suggest that the condition may be significantly more common than is generally assumed.

Obtaining a diagnosis

One of the most obvious reasons for the under-diagnosis of PSSD is the inconsistency in awareness within the medical community.

It is difficult to get a clear picture of how this might differ across medical specialties, though there is some suggestion that urologists and those doctors who specialize in sexual medicine are usually more familiar with the condition, sometimes commenting that they have seen cases in their clinics from time to time. (See PSSD: Getting a Diagnosis)

While some PSSD sufferers are fortunate in their dealings with the healthcare system, others can face a more difficult experience.

The fact that antidepressants were originally prescribed can often present a barrier to having any subsequent health complaints assessed objectively and without significant bias towards an underlying mental health disorder. This not uncommonly results in PSSD being completely dismissed as a possible cause. It is also part of a more widespread issue of doctors failing to engage with patients on the subject of treatment-related problems.

In some cases, the symptoms only appear when the antidepressant is actually stopped or the person begins to taper the dosage. This undoubtedly adds another level of difficulty when trying to obtain a diagnosis. It is worth noting however that it matches the profile of antipsychotic-induced tardive dyskinesia, in which the problem can either develop while on the drug or when stopping.

The need to battle against an unhelpful medical community can prove too much for some PSSD sufferers, particularly if they are also dealing with other side effects such as withdrawal problems.

There is also the very legitimate concern that disagreeing with doctors will be regarded as evidence of an increasing mental health disorder and could put the person at risk, or at the very least affect how they are perceived in any future consultations due to comments in the medical records.

Faced with these difficulties, some simply abandon trying to obtain any assistance for their condition from the healthcare system, which means that these cases then disappear from clinical practice.

The value of seeking help

For most medical conditions, a patient seeks the assistance of the medical community because they are hoping to receive an effective treatment. If faced with an unhelpful doctor who isn’t knowledgeable about the condition or one who is unwilling to engage, the patient would usually persevere and take the matter further. They might ask to see a different doctor for a second opinion or request to see a specialist. They might even attempt to seek out and consult with known experts at their own expense.

However, in some ways there is much less value in pursuing this course of action in relation to PSSD. Anyone who researches the published literature and the various on-line information will soon realize that there is little that can be done for the condition. There is no cure and currently no viable treatments. Even with a formal diagnosis, there is ultimately very little that a doctor has to offer. There is therefore less incentive for a PSSD sufferer to pursue medical intervention, particularly if they encounter resistance from their doctor.

Sexual apathy

As part of the condition, men and women can sometimes be left with a reduced or loss of libido. This seems to produce two different results in terms of a sufferer’s reaction to it.

There are those who are acutely aware of this impairment and find the experience very disconcerting. Their reduced or lack of desire feels abnormal. They know that they are meant to be attracted to people and have a desire for sex, yet these feelings are strangely missing or subdued. Together with the other features of PSSD, this can produce a very distressing situation for those affected.

However, other sufferers are completely unconcerned by it, even when they seem to recognize that it is a drug side effect. They find that they simply no longer care about sex and relationships or they regard them as fairly unimportant in their life. Consequently, any accompanying physical difficulties that they might have also become less important.

Some sufferers note that they would rather have these abilities and feelings back and to once again be able to pursue sexual relations, but it seems to be regarded as something that would be nice to have as opposed to a pressing concern that is causing any particular distress.

This sexual apathy means that these people are less likely to seek medical assistance.

Near normal?

While some cases of PSSD involve sexual side effects that remain completely unchanged when the drug is stopped, there are a number of people who find that their sexual function improved on stopping the SSRI, but it isn’t the same as it used to be. Some of them remain a long way from their pre-drug baseline and fit a typical case of PSSD, but others seem to return to what could loosely be described as near normal.

Unlike some of the more severe cases, these people generally report being able to engage in normal or reasonably normal sexual activity, but nevertheless something isn’t the same. They can have less interest in sex or find it more difficult to become aroused. Orgasms are sometimes weaker. There can be a sense that sex doesn’t feel the same as it used to – something indefinable seems to be missing.

The fact that their sexual function showed a substantial improvement when the antidepressant was stopped leads them to assume that the drug is no longer involved, and that any remaining deficiency must be due to something else, despite the fact that they had completely normal functioning immediately prior to starting the medication.

Even those who deny any persisting effects and claim that their sexual function completely returned to normal after stopping an antidepressant will sometimes admit that on reflection it isn’t quite the same.

Some of those affected try to make sense of this by assuming that it must be related to other aspects of their health or other things going on in their life. They may not even regard themselves as having a significant sexual dysfunction, just a reduced interest or enjoyment of sex. Those who have been on an antidepressant for a while may assume that it is a normal part of life.

The important point is that these people generally aren’t complaining about the problem, and certainly not about the medication. They often only mention it because they were specifically asked. Even when the person recognizes a link to the drug, they are sometimes just pleased that their sexual function came back to the extent that it did, and they consider it a fair trade-off for helping with their mental health issue. Whether this represents a degree of sexual apathy or simply a pragmatic view is difficult to know.

Anyone who reports to their doctor that sex doesn’t seem as good as it used to will probably find the conversation steered very quickly towards mood, relationship issues, etc.

The bigger picture

A quick search of the medical literature and on-line information about PSSD will reveal cases of a complete loss of libido, profound genital anesthesia, pleasureless orgasm and an inability to engage in sexual activity.

These types of cases are important. They describe the potentially devastating consequences of the condition and help to define its characterizing features.

However, it is also becoming increasingly clear that the condition includes a broad range of cases, from the most severe to those people who notice that their sexual function just isn’t quite the same as before, and everything in between.

In efforts to raise awareness it is important to illustrate this diversity within the condition, otherwise there is a risk of PSSD being perceived solely as a rare and extreme side effect, and therefore something that can too easily be dismissed as being irrelevant to the majority of people.

Evidence of this misconception can be seen on-line. Some people comment that although they have a degree of persisting genital numbness and weaker orgasms, they are able to have sex and therefore they don’t have PSSD. Others have said that their condition improved naturally over time to a point where they are now able to have sex again, and therefore they have recovered and no longer have PSSD, despite reporting that there wasn’t a return to baseline.

Any impairment to a person’s sexual functioning or sensation that fails to return to a pre-drug state after stopping an antidepressant belongs firmly in the conversation about PSSD, regardless of the level to which it interferes with their ability to engage in normal sexual activity.

Far from diluting the seriousness of the condition, this actually brings into view the very real possibility that persisting sexual side effects may be more common than is generally assumed, and that many of these cases may be going under the radar.

Sensation: a missing side effect

A study published in 1999 looked at the effectiveness of fluoxetine as a possible treatment for premature ejaculation [1]. It found that the antidepressant increased the time to ejaculation and was therefore regarded as helpful.

The interesting point is that in addition to measuring time to ejaculation, a number of additional parameters were assessed using neurophysiological testing. One of these was penile sensory threshold. Electrodes were placed on the subject’s penis and very small electric currents were generated until the subject could feel the sensation. The current was then decreased until it could no longer be perceived. This second figure was taken as a measurement of penile sensitivity.

This test was carried out on both the study group (fluoxetine) and the control group (placebo), both prior to, and at the end of the treatment period of one month.

At the end of the study, it was discovered that fluoxetine had increased penile sensory threshold by almost 25% compared to placebo which remained the same as pre-treatment. In other words, fluoxetine was found to have reduced penile sensation. The study concluded that this reduction in sensation was likely responsible for the increased time to ejaculation.

An earlier study from 1990 found that the tricyclic antidepressant, clomipramine, also caused an increase in penile sensory threshold [2]. It is worth noting that while clomipramine is classed as a tricyclic antidepressant, it is also a serotonin reuptake inhibitor.

In addition to these studies, published case reports of genital numbness while on an SSRI have appeared in the literature since 1991, including a report of anesthesia of the nipples in 2000 [3-9]. This is without including the cases of genital anesthesia from the PSSD literature.

None of this is surprising as reduced genital sensitivity is a known and common side effect of SSRI antidepressants. If they pay close attention to it, most people who take an SSRI will notice a degree of reduced genital sensation within 30 minutes of taking the first dose.

However, a search of drug information leaflets and health websites will find very little mention of it. Instead, the information that dominates the public domain focuses on side effects such as libido, erectile/lubrication problems and difficulty having an orgasm.

If you were to ask your doctor whether SSRIs can reduce genital sensation, you would probably receive a strange look and be told that SSRIs don’t do this.

Most people seem to be aware that antidepressants can affect arousal and make it more difficult to have an orgasm, but the fact that they can reduce genital sensation (and sexual sensations more generally eg. reduced feeling of pleasure during orgasm) doesn’t appear to be in the public consciousness. It is completely missing from the general dialogue about antidepressant side effects.

Subsequent studies of premature ejaculation

In 2006-07, three large randomized placebo-controlled studies were published that looked at the effectiveness of citalopram, sertraline and escitalopram for premature ejaculation [10-12]. These are all SSRIs.

Unlike the earlier trials mentioned above, they didn’t test penile sensory threshold. However, they included something that the earlier trials did not: a 3- and 6-month follow-up.

It was discovered that the ejaculation-delaying effect of the SSRIs had continued for a significant number of participants, several months after the drugs had been stopped.

An analysis of the results from the citalopram and sertraline trials and their significance in relation to PSSD has previously been discussed in the literature [13]. Of particular note is the fact that the study participants had no pre-existing mental health disorder on which the persisting effect could be attributed.

But there may be another important point.

The fluoxetine study from 1999 concluded on the basis of its neurophysiological testing, that the drug’s ability to delay ejaculation was likely due to its effect of increasing penile sensory threshold. It also noted the findings of the 1990 trial in which clomipramine was found to have the same effect.

If this conclusion is correct and it is applied to the three large studies from 2006-07, then it means that in addition to showing a persisting effect of delayed ejaculation, these studies are also potentially evidence of a persisting reduction in genital sensation in a significant number of participants after stopping three different SSRIs.

Putting the pieces together

A common view of PSSD is that it is a severe condition that a person either does or doesn’t develop – and that the vast majority of people don’t. Therefore, prevalence is generally assumed to look something like example 1:

PSSD Example 1

However, this idea seems increasingly unconvincing. Taking everything into account, it raises the possibility that the true picture could look more like example 2 or some variation of it:

PSSD Example 2

The original question was – how common is Post-SSRI Sexual Dysfunction? This article may not have provided an answer, but perhaps it suggests a number of reasons why some sufferers may not identify with the condition, despite experiencing persisting sexual side effects.

SSRIs and SNRIs can have very complex sexual effects and can produce changes that some sufferers may find difficult to make sense of, particularly when it comes to altered sensations and muted sexual feelings. Depending on the level of severity, some people may feel that the severe dysfunction often associated with PSSD is not a good fit for what they are experiencing.

Perhaps the real question is:

Does anyone who takes an SSRI or SNRI actually regain 100% of their original sexual function and sensation, or are they almost always left with some degree of long-term alteration?

References

1. Yilmaz U, Tatlişen A, Turan H, Arman F, Ekmekçioğlu O. The effects of fluoxetine on several neurophysiological variables in patients with premature ejaculation. J Urol. 1999 Jan;161(1):107-11. PMID 10037380.

2. Colpi GM, Fanciullacci F, Aydos K, Grugnetti C. Effectiveness mechanism of chlomipramine by neurophysiological tests in subjects with true premature ejaculation. Andrologia. 1991 Jan-Feb;23(1):45-7. PMID 1897755.

3. Neill JR. Penile anesthesia associated with fluoxetine use. Am J Psychiatry. 1991;148:1603. PMID 1928483.

4. Measom MO. Penile anaesthesia and fluoxetine. Am J Psychiatry. 1992;149:709. PMID 1575264.

5. King VL, Jr, Horowitz IR. Vaginal anesthesia associated with fluoxetine use. Am J Psychiatry. 1993;150:984–5. PMID 8494083.

6. Ellison JM, DeLuca P. Fluoxetine-induced genital anesthesia relieved by Ginkgo biloba extract. J Clin Psychiatry. 1998;59:199–200. PMID 9590676.

7. Diesenhammer EA, Trawoger R. Penile anesthesia associated with sertraline use. J Clin Psychiatry. 1999;60:869–70. PMID 10665639.

8. Michael A, Mayer C. Fluoxetine-induced anaesthesia of vagina and nipples. Br J Psychiatry. 2000;176:299. PMID 10755087.

9. Michael A, Andrews S. Paroxetine-induced vaginal anaesthesia. Pharmacopsychiatry. 2002;35:150–1. PMID 12163985.

10. Safarinejad MR, Hosseini SY (2006). Safety and efficacy of citalopram in the treatment of premature ejaculation: a double-blind placebo-controlled, fixed dose, randomized study. Int J Impot Res. 18: 164–9. PMID 16107866.

11. Arafa M, Shamloul R (2006). Efficacy of sertraline hydrochloride in treatment of premature ejaculation: a placebo-controlled study using a validated questionnaire. Int J Impot Res. 18 (6): 534–8. PMID 16554853.

12. Safarinejad MR (October 2007). Safety and efficacy of escitalopram in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study. J Clin Psychopharmacol 27 (5): 444–50. PMID 17873675.

13. Bahrick AS. Persistence of sexual dysfunction side effects after discontinuation of antidepressant medications: Emerging evidence. The Open Psychology Journal. 2008;1:42-50. doi:10.2174/1874350100801010042.

Greg’s Dilemma

Editorial Note: This post on the difficulties of withdrawal comes from Greg. There will be 3 parts to it. In Part 2 Greg gets some standard psychiatric advice and in Part 3, we offer a response to the advice.

Way, way down in a hole, there is no feeling
Because when you’re so far below the floor, everything’s a ceiling
-Death Cab for Cutie

Unfortunately for me, being down in the hole I’m in is full of feeling. Unwanted, unnerving, frightening, and despairing.

I’m in a hole and I don’t know if I can get out. I need help, but I don’t know where to go. In fact, it occurs to me that maybe there is no help, there is no answer – not one I can live with anyway.

So let me just quickly go back and try to delineate the process that’s led me here.

History

In college, I smoked too much pot where I developed the unnerving feeling of depersonalization so extreme, I had a long panic attack. That, I believe, carved out a neural pattern that made it easier for me to have future panic attacks.

Later, in my young adult life, I made the same mistake with marijuana and had another debilitating panic attack that led me to the ER. And about a year later, I had another panic attack – this time without any chemical assistance. I was so frightened by this that I made a doctor’s appointment the next day. This was in 1999, when the growth of prescriptions of SSRIs was exploding. The information I was reading on the internet at the time said they were effective in 70-80% of people who took them.

Paxil had come out and was the first SSRI that was marketed with an “anti-anxiety” component in addition to anti-depressive. The doctor I saw prescribed that and xanax, as needed. He stressed the habit forming aspect of xanax but said Paxil was nonaddictive. When in a state of anxiousness, my decision making habits are made quickly, oftentimes without thought of long-term consequences. Which is exactly the model of psychiatry and the pharmaceutical companies they rely on – find medicines that provide relief to immediate crises.

Paxil

For two weeks, I became more obsessive and fearful of having another panic attack. I was told the Paxil wouldn’t start “working” for two weeks or more. In that time, I sank into the first depression I’d ever experienced. I attributed it to the nervous obsessing panic that wasn’t really abating unless I took a xanax. It didn’t occur to me then that the Paxil was contributing to the problem – that it was “temporarily” destabilizing my brain in that two-week window.

But just like they said, around two weeks later, I started to feel normal again. The Paxil “worked”. But, I would continue to have panicky, depressive episodes periodically that would last a few days and then remit. In no circumstance was there any specific life circumstance that I could attribute to these dips.

They were frequent enough that I started to see a psychiatrist regularly. I’d been switched over to the controlled release Paxil at some point but in 2005, there was a shortage and I had to take the standard Paxil. In that time period, I sank into the deepest depression I’ve ever experienced. In my emergency state of mind, I called my psychiatrist in crisis mode and he prescribed 1.5 mg of Xanax daily – I had only used it sparingly before that. As all times before, I “pulled out” of my depression about a week later.

Stopping Xanax

As the years went on, I developed problems from daily use of Xanax – extreme lethargy and intense inability to stay awake while driving long distances. I took frequent naps, I feel asleep watching movies a lot of the time. In 2011, I decided I didn’t want to be on Xanax anymore and I tapered off it quickly without any consultation with my doctor. Things weren’t right with me as I went off. I had heavy legs and strange sensations in my head. It got more extreme and several doctor visits before I made the connection with the medication. I found the Ashton Manual online and presented that to my doctor saying I wanted to go back on benzos – this time Valium – and taper per her 10% a month protocol.

As soon as I got on Valium, my symptoms remitted. I was so relieved and felt my troubles were over as long as I stuck to this tapering method. But I was naive. Even cutting 10% a month gave me horrible withdrawals – depersonalization, increased generalized anxiety, irritability, etc.

Eleven months later, I took my final dose, hoping I’d been through the worst. But the worst was still to come. I had extreme insomnia and emotional lability and myclonic jerks at night. I muscled through it at work, missing many days, until I couldn’t continue and took a three month leave of absence. In that time I went through the windows and waves of withdrawal well documented by others who’ve gone through this.

I was not much better when I went back to work, but I made myself go. Staying at home had only been making my ballooning self-loathing worse and being distracted by work helped pass the time. But pretty close to a year after my last dose of Xanax, my symptoms started to ease and my mood became more stable. I still couldn’t feel happiness strongly and felt little need to socialize. I wasn’t “healed”, but I was better.

Stopping Paxil

About two years after my last dose and having read about the potential long-term harms of antidepressants, I decided I was going to go off Paxil, which I’d taken daily for 15 years. I’d heard some talk of serious withdrawal from SSRIs but the accounts seemed fewer than those withdrawing from benzodiazepines. Because I had now turned on the profession of psychiatry, I wanted to purge myself of this last medication.

So in October of 2014, I started cutting 5 mg a week of my 25 mg dose – a rate I now realize was far too fast. I should have learned my lesson. Panic attacks and obsessive thinking took hold of me followed by a growing depression. By January, I was a mess. In that time, my mom developed stage 4 breast cancer and I decided I should go back on Paxil. But there was no response. In fact, things were getting worse day by day.

For the first time in all of my experience with these problems, I had the urge to kill myself. I tried it with a belt around my neck a couple of times but I couldn’t stand the choking feeling and stopped. On Super Bowl Sunday in February 2015, I was so depressed and unresponsive, that my wife took me to the ER where I was admitted to the in-patient psychiatric unit at our local hospital. I was a wreck – and I was visibly worse than everyone else I encountered. It was baffling – they were all dealing with extreme life circumstances in their lives that brought them to attempt suicide. My life, by comparison, was far better – I have a job I like, a wife I love, two kids and some great friends.

But they were getting better – the group sessions were helping them, but I felt horrible no matter what I was doing. That said, I was released a week later and felt slightly better. I returned to work for a few days, but began to sink again. I then re-admitted myself to the psych unit. I seemed to have complete amnesia about the failings of psychiatry and the nature of my illness, that I was willing to try anything they suggested.

After two more weeks there and no improvement, I pursued their suggestion of ECT. That took me to a hospital in Spokane (3 hours away) where I stayed for a month and received 11 treatments. But what has compounded the frustration of my current situation was that they prescribed 150 mg of Zoloft as well.

The first two days after an ECT session, I would feel better but over the weekend, when there weren’t any sessions, I got much, much worse. After a month in the hospital and 11 shock treatments, I was released and was no better.

I went back to work for a few days but then took myself back to the ER. The in-patient unit wouldn’t take me and I was told my only option was state hospitalization. I decided to go home and try to tough it out, but my future felt extremely bleak.

Strangely, I began to experience moments of improvement. I had been given a prescription of Ativan prn in addition to Zoloft. I did not want to take the Ativan. But I could literally not sit still or focus well at work and feeling like it was either that or suicide, I periodically took an Ativan before work. I noticed that on those days, I would improve. I didn’t want to take it daily so I fought through several days of unease. But I was developing what I believe was growing akathisia – I felt an internal restlessness and was constantly shifting in my seat at work. I could feel it up and down my spine – like my nervous system was in a vice and it didn’t relent at any time of day until I went to bed.

Faustian bargain

So I made a Faustian bargain.

I started taking Ativan three times a day. This was my last stand. If this didn’t work, I would take my life. The level of suicidal ideation I had at the time was intense. I’ve never experienced it so dramatically. In fact, just thinking of suicide gave me relief. I would tell myself just to wait until the evening and then slip out and hang myself. But in less than two days of taking Ativan regularly, I started feeling much, much better. Astoundingly better. At times, better than I felt before I went off benzos.

For about two weeks this went on and my goal was to go off the Zoloft slowly while staying stable on the Ativan. But the Ativan fix didn’t last. I slipped down again, where I’d wake up feeling both incredibly anxious and depressed. It would lessen as the day went through and I wasn’t nearly as bad by the end of the day. At times, I would have strongly over-emotional responses to negative thoughts or sudden changes. Thinking about anything in the future that I had to do – no matter how routine or insignificant – would give me an instant feeling of crushing despair. When I’d re-run the thoughts, the emotion wasn’t as strong. It seemed to be related to whatever part of the brain is involved with immediate emotional reactivity.

But it wasn’t monolithic – it came and went. I had times where I felt mostly normal. I started running two miles a day – exercising more than I ever have before. I was much better even at my worst than I was months before, but I was constantly worried I’d slip back to the point I’d been when I was hospitalized. I knew what I was going through was a reaction from the medication, but the psychiatrist I’m currently seeing unsurprisingly doesn’t see it through that lens. I had to underplay the severity of what I was feeling for fear she’d prescribe something else.

She switched me over to Klonopin in August (equivalent Ativan dose). About a week into it, I again had a resurgence of improvement – the morning restlessness abated and the over-emotional responses vanished. For about three whole days. And it all returned again. Only this time, there have been far fewer breaks and the malaise is lasting longer throughout the day. I haven’t missed a day of work due to this in six months, but each day is a fight to get to 5 pm. And it’s getting harder.

This is where I’m at now. And why I’m scared and despairing and have the same question going over and over in my mind.

What am I supposed to do?

Thinking it may be due to tolerance to the benzos, I’ve tried increasing my Klonopin dose, but it seems to have the perverse effect of making me more depressed while doing nothing to abate the internal restlessness – this feeling of being in a vice and the hyper-emotional (dis) response to any form of negative thought or thought of the future. I haven’t made significant increases in the dose because I’m not sure it would help and I already hate taking the benzos as it is.

I don’t know if this is withdrawal from the Paxil I took for 15 years or a response of akathisia from the Zoloft I’m taking. I’m scared that if I cut down on the Zoloft, I’ll get worse but I’m also afraid that the Zoloft is causing the problems. After harrowing responses to changes in my medication, I’m scared to do anything. I simply can’t stay home and endure another withdrawal process. I won’t make it. But doing nothing is increasingly untenable.

What’s making this worse, as anyone who has experienced severe withdrawal reactions to psych medications can attest, is there are no experts who believe this is a possible response from medication. The psychiatrist I’m currently seeing doesn’t see it that way – she’s told me that I control my thoughts and that I probably have to go to counseling to deal with these issues. The therapist that I see, and who I’ve seen for years and knows me far better than any psychiatrist ever could, absolutely believes that it’s a complicated response to psychiatric medication. He really doesn’t know what to do to help.

Nobody does.

What’s even worse for me is that the absolute dearth of people who know what I’m going through and the seemingly small numbers of people who experience severe reactions like this make me doubt myself. Complaining of unobservable internal nervous system symptoms sounds so vague and, frankly, annoying to others. And as someone who has struggled with self-confidence issues, it’s hard for me not to worry that this isn’t from the drugs – that it’s a personal failing of my own somehow.

Withdrawal Research Forum: Relief at Last?

What's standing between you and your life?

Editorial Note: There are tens of thousands of people affected by dependence on and protracted withdrawal from antidepressants, antipsychotics, benzodiazepines, dopamine agonists and other drugs. We will be opening up a Complex Withdrawal and PSSD research section in the very near future aimed at solving what is going on.

This post by DA who has a certified protracted withdrawal syndrome shows one of the ways forward – people staying alert to what happens to their withdrawal difficulties if they are put on another drug. There are two options here, one is that one of the two drugs DA was put on has cured the underlying problem or that it has alleviated it and the problem would come back if she stops. Either way, there are clues to what might be going on.

After being on 10mg of Seroxat (Paxil) for 7 years, I stopped it suddenly in 2006. Since then I have experienced a never ending range of symptoms which I associate with discontinuation from Seroxat. These are very similar to the experiences I have heard from others who have also experienced discontinuation problems.

In 2014 I developed atrial fibrillation. I felt very unwell with a persistent dry cough, lower abdominal pain, extreme fatigue and breathlessness. I was taken to hospital with a high heart rate and was given beta blockers and rivaroxaban. I had diarrhoea for a couple of days but my mood was quite high and I looked incredibly well.

I stopped taking the beta blocker (bisoprolol) because I hated the side effects of dry mouth and a feeling of slowing down. My head felt as though it had cotton wool inside – a feeling I first had when I went onto seroxat. I continued with the rivaroxaban as I was scared by the hospital doctors and their warnings of stroke if I didn’t take them.

At first when I missed a dose of rivaroxaban, I would feel a bit fuzzy headed. I didn’t seem to be able to think clearly. When I took the dose, I felt better. After a while I got used to taking the rivaroxaban and I felt quite well on it despite having an erratic heart rate.

The dizziness, which had plagued me in the early stages of withdrawal and had returned again after 5 years, completely disappeared. The dry cough and abdominal pain disappeared.

I was given cardioversion in February 2015 but this only worked for 2 weeks before my heart went back into arrhythmia. After this the doctor decided to put me on Digoxin, Multaq (dronedarone) and keep on with the rivaroxaban. I felt very unwell taking the digoxin which I used to take early morning. Within minutes of taking this, I would feel sick and very dizzy and the symptoms would last a few hours.

The Multaq which was supposed to be 400 mg twice a day, did not give me any problems at all, although I decided to halve the dose and just take 400 mg once a day. After 6 weeks I had another cardioversion which proved successful. I was taken off the digoxin with only a few problems (diarrhoea, general ill feeling for a few weeks). I was left on the Multaq and rivaroxaban and as far as the doctors knew, the bisoprolol which I only take if I feel my heart is going out of rhythm and then I only take one dose.

When I was told I had to take these drugs, I was very scared of the reactions, as I have had a lot of problems with food intolerance and have never been able to take any vitamin or herbal tablet since coming off Seroxat. When I tried some homeopathic tablets, I had terrible headaches. The only tablet I was able to take, and only when absolutely necessary, was paracetamol.

Over the 9 years, the food intolerance has improved and I am still unable to take any natural medicine but to my surprise I can tolerate the drugs for A.F. I am told I will remain on these for 2 years as long as my heart is stable.

Some of the original symptoms from discontinuation of Seroxat still remain, head zaps occasionally, fatigue, joint and muscle aches occasionally, some food intolerance still remains, but I do not have any dizziness now or the flu type symptoms I used to get.

What is interesting, I used to find that any type of stress intensified the discontinuation symptoms and I seemed to have very little tolerance to manage even a small amount of stress. However, for the past 6 months, I have been under a huge amount of stress which should have caused intolerable symptoms and left me unable to cope, but something has changed in me and I am a lot stronger than I was a year ago. I no longer feel hypervigilant and my sleep is a lot better although I am having menopausal hot flushes now so this sometimes wakes me up.

I am pretty certain something, whether Multaq or Rivaroxaban has made a difference to me not just with the A.F. although I am worried about the side effects when I have to stop taking them.

Editorial Note: In terms of the way we on RxISK have been thinking about withdrawal, Multaq which acts on Sodium and other channels would seem the best bet for the drug that has made the difference but the way DA tells the story it looks more like Rivaroxaban. We need someone who uses these drugs more often, especially Rivaroxaban to come onboard if they can see what might be going on.

DRESS Syndrome: No Way to Treat a Lady

Hannah Was Here by Nancy Szakacsy

Black out

Five minutes into yoga class, my sixteen year old daughter Hannah blacked out. Her face, white as a ghost. When she came to, she said she couldn’t see. Her pulse was almost nothing, and panic set in. I ran to my car to grab my phone and dial the infectious disease doctor Hannah had recently seen about an allergic reaction to a commonly prescribed antibiotic acne drug Minocycline traded under the name Solodyn.

The voice on the line said the doctor was with a patient. “He can call you back in twenty minutes.”

I wasn’t going to wait. As I pulled into the parking lot, my cell rang. It was the doctor. I felt a sense of relief and started telling him the details. “We were in yoga class, and she just blacked out.”

The Doctor sounded annoyed: “Look, I am not concerned. Hannah will be fine.”

“With all due respect, doctor, she blacked out cold for a significant amount of time. She looks completely white. We were doing yoga!”

Before I finished, he interrupted. “I’m not concerned with what you’re telling me. Just take a break from the yoga. She is fine.”

I wanted to scream at him, but Hannah was so sick. I thought, This guy has issues with women, or maybe he’s… fuck it.

“Well, I’ll let Hannah speak to you then,” I said and handed her the phone. Maybe he would believe her. Hannah told him what had happened. I put my ear to the phone.

“Hey look, I think you’re just having anxiety,” he said, his tone at least gentler, if still patronizing. “Don’t do any more yoga. I’ll see you next Tuesday for your appointment.”

We were in shock. The whole thing seemed weird. Our emergency was reduced to a fit of anxiety. It didn’t feel right.

Hannah seemed to be feeling better and asked for a smoothie. We spent the next few days watching movies, staying mellow. That Friday, she felt terrible. I dialed the doctor again and left a message. His nurse returned my call instead of him, and I blew up.

“What makes the doctor so confident? Hannah is getting worse. When we were in crisis the other day, he was condescending. He acted annoyed. If he ever treats me like that again, in front of my daughter, in an emergency situation, we will have a huge problem. I’m not comfortable seeing him, but I need his care for Hannah right now.”

Medical facial please

Ok, lets back up. It’s February 2011, and Hannah and I are awaiting her first appt. with a “Stanford-trained, board-certified dermatologist” with a skincare institute. She wanted to begin regular medical facials. The doctor asked Hannah questions and examined her skin. He discussed the facials and insurance and then prescribed a topical cream. Hannah’s appointment seemed a wrap, but then he asked about a few more things. Before we knew it, we had a prescription for an acne drug. I jumped in and told him we didn’t take medications except in extreme situations. I told him that my husband taught chemistry and was adamantly against unnecessary medications, especially antibiotics.

The doctor smiled when I told him about his long lectures and how we would never hear the end of it. Still, he reassured us of his professional comfort with the medication and how it was absolutely safe. So I asked him if he’d give it to his kid, and he said yes. I could hear the lectures in my head, so I mentioned another acne drug that had caused serious side effects; colon issues and suicidal ideation that I had heard were associated with acne drugs. The doctor smiled kindly, shook his head, and just said no.

Three weeks later at her best friend Maggie’s sleepover, Hannah woke up with golf ball-sized glands behind her neck. She was scared and called, “I wish I had listened when you when you said not to sleep on wet hair. I really feel crappy.”

She felt so uneasy she didn’t take the Minocycline that morning and never took it again. I found a family doctor to see her. We didn’t have one in place, a perk of good health. Neither Hannah nor I told the doctor about the pimple medication. Neither of us had made the connection being several weeks had passed. We showed the doctor Hannah’s giant glands and other swollen areas. “It may be mononucleosis.” Blood work would tell.

A few days later, a full body rash appeared; Hannah had lumps, bumps, and nodules from neck to toe, including her private parts. I called the doctor and started searching for answers online. That’s when I connected the drug and returned to see the doctor insistently that Saturday afternoon. Five minutes in, he said, “Honestly, this is out of my family practice area.” and referred us to an infectious disease doctor, who then quickly diagnosed Hannah as having an allergic reaction to Minocycline.

Excerpts from a letter from Dr. S to Dr. R

History of Present Illness: The patient is a 16 year old Caucasian girl who has enjoyed generally excellent health. Her only significant past medical history was excision of a sebaceous cyst from the medial left knee at about age 12.

Sometime in February 2011, the patient saw Dr. P, dermatologist, who prescribed minocycline to control facial acne. She took the medication as prescribed for 21 doses, and then during the first week of March, she developed an acute illness, initially characterized by the development of posterior cervical lymphadenopathy, which was not tender, associated with fever, malaise, and fatigue. This was followed by the onset of a maculopapular rash, which initially presented on the face and then spread to the trunk and extremities. This rash was pruritic. Her fever only lasted a few days, as did the generalized malaise. Associated with the rash there was pruritis, and the skin seemed swollen in the rash affected areas, especially about the upper and lower extremities.

Ultimately, the patient presented to Dr. R—— for this problem, and a week or so ago, she was prescribed a Medrol Dosepak, which did not significantly improve her symptoms. After about the fourth day of this treatment, she was switched to a tapering dose of prednisone, beginning with 60 mgs daily, of which she has taken her last 60-mg dose today, i.e., the fourth day of prednisone treatment. On this treatment, her rash had somewhat improved, although she is still pruritic and notes some increase in puffiness of the hands and feet. The patient has not developed any new symptoms apart from the puffiness in the last several days.

Discussion: This very pleasant patient does not look toxic or septic. She has some residual rash as described above with perhaps minimal puffiness of the hands and feet. The puffiness may be due to the ongoing prednisone therapy. Okay for almost one month for her acne. As long as she continues to slowly improve, I would not change her current treatment. I think that the syndrome in its entirety is almost certainly due to an adverse reaction; i.e., allergy to Minocycline, which she took, although it is entirely possible that, with further tapering of her prednisone, her rash and possibly other symptoms may recrudesce somewhat. But ultimately symptoms should all resolve over the next few weeks. The patient has been cautioned about the potential for cutaneous hypersensitivity to sun exposure and was instructed to stay out of the sun for the next month or so.

Wrong!

When we got home, Hannah and I ordered a medical bracelet that read, “allergic to all tetracyclines”. When it arrived, it would have brought relief if her current state were not so challenging. Turns out that the first round of 60 milligrams of prednisone taper failed. After her final 20-milligram dose, Hannah’s face swelled up completely. She would have to do another cycle. The doctor wrote a referral for “home hospital” and the second round of prednisone seemed to be working. The doctor kept reassuring us the reaction was on its way out, that it just needed more “undoing.” He promised she would be “100 percent” sometime soon.”

That’s when we decided to take the yoga class and get out a bit. On the way, Hannah said she was having a little chest pain. I asked her if she needed a bathroom, but then the pain stopped. The next day, Hannah wanted to go again. That is when she blacked out.

Who knew?

Just after Hannah’s final taper, she started having trouble breathing.

When the doctor came in, he took one look at her and said, “You look really sick.”

Hannah said, “I am really sick. I can’t breathe and can barely talk.”

She leaned on me, exhausted. The doctor called for an EKG. I held her as we waited. When the EKG came, the doctor took a good look at it and said, “You’re a very sick girl. You’re very sick.”

“Pneumonia?” I asked. “My God, what’s going on?”

He had us wait some more. With the hospital literally next door, he just had us wait. He wanted a blood sample, but Hannah was afraid that, if he drew blood, she’d pass out. She was weak and nauseous, and her chest pain was increasing. She was afraid of throwing up, her chest was in massive pain, and she hadn’t eaten. She was in pain, and he wanted to draw blood.

“I’ll be right back,” he said.

When he returned, in came a strong smell of breakfast burrito. Hannah and I looked at each other. Oh my God…. we’re struggling and he’s eating a breakfast burrito. That’s when he said he was admitting her. We got in the car to drive next door to admitting, but Hannah couldn’t breathe.

I yelled to the parking attendant out front, “Help! Get a wheelchair, a wheelchair!”

When they rolled Hannah to admitting, we began the intake process, but she was getting worse. They took her to emergency, and standing there, I heard the doctor ask to see the EKG. Then, I heard him say, “He didn’t send it! Get me another one.”

Hannah and I locked faces while he read the graph. The doctor turned to me and said, “Ma’am, call your loved ones. Your daughter could die any minute.”

I looked at Hannah with all my love and stepped back out of the room. When we arrived at the emergency room, alarms were sounding. Two nurses were wheeling Hannah into surgery. Her heart had stopped. She was in full cardiac arrest. CPR went on for almost an hour. The hospital representative came out and brought us to private room.

“I’m sorry. We don’t think she’s going to make it.”

We were hysterically crying, huddled in a corner on the floor. About a half hour passed, and the door opened.

“We got a pulse,” a doctor said. Then he told us that he’d surgically implanted an Impella device, adding that it wasn’t the right size for a young girl but seemingly relieved that he’d got it in. “We called for a helicopter to fly her to Cedars-Sinai Medical Center,” he said flatly, before adding, “You can see her briefly now.”

Getting to Cedars

We arrived just minutes before Hannah. We would later find this letter in her admissions paper work.

Ms. Hannah Szakacsy is a sixteen-year-old white female who presented in cardiogenic shock from probable fulminant acute myocarditis.

Following the diagnostic coronary angiogram, the patient required one-to-one physician care for the following six hours, including emergency helicopter medical transport to Cedars-Sinai, a physician at the patient’s side throughout the transport.

She was triggering the ventilator, but she did not have spontaneous movements upon arrival. Lungs were clear. There was urine production. On arrival to Cedars-Sinai, both Dr. C—— and Dr. T—— were at the patient’s bedside within 10 minutes, and the patient was taken immediately to the Cedars-Sinai surgical suite for extracorporeal membrane oxygenation therapy, in preparation for biventricular placement later.

Signed, Dr. P – –

Hannah had arrived with no pulse or heartbeat. A group of doctors came to greet us. One of them told us sternly his eyes more sympathetic than his tone, “It doesn’t look good, but we will try and do what we can.”

“102 days begins”

A team of doctors got Hannah on ECMO (extracorporeal membrane oxygenation), which provides patients oxygen for both cardiac and respiratory support; the chance of the ECMO working is just 50 percent. Hannah had no major organ function; all five major organs were failing. Her legs were turning black due to lack of circulation. She needed open heart surgery.

How could the infectious disease and the dermatologist have missed this? What is this drug! I was focused and furious, but Hannah was dying. I spoke with every doctor and pharmacist at the hospital, no one knew anything. We wrote to Dr. Vincent Descamps in France for help, then photocopied his case studies on DRESS for Hannah’s team of just about 30 doctors.

They were treating symptoms. No one fully understands drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, even experiencing its magnitude and destruction. Worse, the head of immunology, whom I blasted for sending interns instead of seeing Hannah himself, doesn’t even believe D.R.E.S.S. exists. He revealed this while patronizing me with superficial responses, his lips speaking ten gulps of bullshit. As with Humpty Dumpty, all the king’s horses and all the Queens’s men couldn’t put Hannah together again.

Ultimately, Hannah Victoria Szakacsy, passed 11 times, had fasciotomies flaying open both her legs; two open heart surgeries; and the loss of all her major organs. A BiVAD artificial heart implanted and later removed due to her own heart’s striving for life. She endured hundreds of x-rays, scans, severe starvation, lost her colon and part of her pancreas. I could add more. Hannah was in and out of consciousness, until she ultimately lifted, out of her very heavy weighted body, 102 days later, two weeks after her seventeenth birthday.

Hannah’s medical case was published in the Sage Journal’s Publication ICU Director, May 2012 vol. 3 no. 3 139-143, Journal of Intensive Care. The title read “Minocycline Induced Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome: Myocarditis and Multiple Organ Failure.”

One click and a Google search links me directly to Hannah’s contribution, the fourth published case. This is an astonishing success, until you realize the entire text is public but can only be accessed for a fee of twenty-five dollars. Is this why DRESS is considered “rare”?

All rare means to me, is that it happened.

Six million dollars were spent trying to save Hannah during those 102 days in the hospital. Very few doctors had even heard of DRESS.

There are many defining explanations on DRESS, but no real guidance for those in the midst of it.

DRESS syndrome stands for Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms. The term was coined in a 1996 report in an attempt to simplify terminology for a syndrome recognized as early as 1959. DRESS is an immune-mediated reaction to a drug. Also known as drug-induced hypersensitivity syndrome (DHS).

D.R.E.S.S. symptoms occur 12 weeks after initiation of the prescribed drug and can occur after a dose increase or recur for several weeks after stopping the culprit drug.

Hypersensitivity reactions are unpredictable and not dose-dependent, usually occurring at normally tolerated doses.

In June 2010, after a multitude of adverse event reports, the FDA conducted and concluded its own investigation into the widely prescribed acne medication. The study found it could and did in fact cause DRESS, black thyroid, severe lupus, and other autoimmune responses. The FDA then contacted the makers of the drug and had them amend the adverse effects stated on their warning labels. The pharmaceutical company who made Solodyn the brand name version of the drug Hannah took waited until March of the following year to add DRESS—one month before Hannah’s organs failed.

I travelled to France to meet and thank Dr. Descamps. When I returned home, I received this from the kind French doctor.

Dear Nancy,

Here is the “official information about minocycline” given in France by the HAS (Haute Autorité de Santé, High Authority for Health). It is written (in 2010) that minocycline must not be used as a first treatment for acne but only exceptionally.

Translated from French to English:

Tetracyclines (doxycycline 100 mg/day or lymecycline 300 mg/day) orally are particularly indicated in acne predominantly inflammatory (papulopustular) in extensive and/or prolonged forms development and limited to three months of treatment continuously.

Because of the risk of rare but serious adverse effects (hypersensitivity syndrome, hepatitis, autoimmune), it is not recommended to use minocycline in first intention but only exceptionally in case of failure of other cyclins and the inability to use oral isotretinoin.

Minocycline-induced DRESS cases and risk to benefit [is] not worth it for acne treatment when other safer options [exist].

In mid-2008, the French National Pharmacovigilance Committee examined:

  1. Spontaneous reports of adverse effects observed during tetracycline therapy
  2. When sales figures are taken into account, reports were more frequent with minocycline than with doxycycline. The proportion of severe adverse effects was also higher with minocycline than with doxycycline
  3. Life-threatening hypersensitivity reactions and autoimmune adverse effects were more frequent with minocycline than with doxycycline
  4. In practice, minocycline has a less favorable risk-benefit balance than doxycycline, particularly in the treatment of acne.

Europe says no. America says yes. It can only mean greed.

Here are the drugs that commonly induce DRESS.

Phenobarbital, Carbamazepine, Phenytoin, Lamotrigine, Minocycline, Sulfonamides, Allopurinol, Modafinil and Dapsone.

Please pause before automatically taking prescription medication. The sky isn’t falling, but we are big consumers. Acne medications in the US alone treat 50 million people. With the current wrath of unwarranted, serious adverse events being reported, including death, I had to share.

Thank you for taking this in, Hannah Was Here

Nancy Szakacsy M.S. LMFT 

Author of Hannah Was Here: D.R.E.S.S. an alarm that must be heard.

http://dresssyndrome.org

Abilify, Tourette Syndrome and You

Bureaucrat thinks

Editorial Note: This post follows on from one of the most compelling RxISK stories ever – Abilify, Tourette Syndrome and Me, posted last week. It comes in two parts. The first by last week’s author and the second by the series editor, Johanna Ryan.

In our efforts to get our story told, raise awareness about the dangers of antipsychotics, and fight for better treatments for Tourette’s Syndrome and its associated conditions, it was important to get our voice heard at the FDA. When we first discovered that a clinical trial called the Archer Study was seeking FDA approval of Abilify for the treatment of Tourette Syndrome, we were horrified and realized that we had to do something to stop it! This was the very drug that disabled me and made us realize just how awful the treatments for TS are!

This study was particularly unsettling because it was sponsored by the manufacturer itself (Otsuka Pharmaceuticals). It was a shameful hot mess because it appeared that Otsuka wasn’t familiar enough with their own product, let alone Tourette’s, to even recognize that there were serious problems. As we would tell the FDA, when comparing how TS was categorized in the study vs. Abilify’s Prescribers Guide, it was unclear if Otsuka could even decide if they thought tics were a neurological or a mental illness.

We spent a year of our lives gathering information and writing a letter to the FDA in an effort to stop their approval of Abilify for the treatment of Tourette Syndrome. We were asking the FDA to investigate the Archer Study for possible negligence and lack of informed consent of their research subjects. We were also requesting that the FDA determine that TS, OCD and ADHD are contraindications for this drug. When completed, our FDA letter was 16 pages long and it would have been even longer had we not compromised to leave items out. Especially because of my condition caused by Abilify, it became quite overwhelming for us to write this letter. There were so many negative things to write about because it is so complex with all its detrimental effects. We were really hoping the sheer content of our letter would make a statement to the FDA on just how wrong this drug is in treating TS.

We sent our letter to the Director of the Center for Drug Evaluation and Research (CDER) and a copy to the Director of ODE I. The FDA’s website is not user friendly and so locating the correct departments was a job in itself. After not hearing back from anyone at the FDA, we decided to call the ODE I office. After weeks of leaving voice messages, the secretary from ODE I finally returned our call. If not for the consideration of the ODE I office, who forwarded our letter to the Division of Drug Information, we probably would have never received any communication from them at all! It was approximately another month later when we received a response from the Division of Drug Information.

In the response that we received from the FDA, one of their only suggestions to help us was to file a report with MedWatch about our experience with Abilify. It was interesting to us because we had already filed a report with MedWatch months before we had received their letter. Almost a year later, we’re still waiting for someone to contact us concerning our report. It is also important to note when we reached out to other organizations, they too, put so much weight on us contacting MedWatch. This was even more discouraging to us since our experience with MedWatch made us feel as if this is simply a place to get your “medication story” lost in a sea of reports.

At first, we felt that our letter was well-received by the FDA because they told us that our letter was “well-written and informative,” and that they would be taking our information into account during the approval process of Abilify for TS. But they went on to say that “information about a drug or drug indication that is under FDA review and not yet approved is subject to strict confidentiality laws.”

We responded to the FDA and included even more information about why we feel Abilify is a poor choice for treating TS. Due to the confidentiality laws, it made any further communication with them impossible. Our concern is that these laws seem to be in favor of the pharmaceutical companies and not the health and welfare of patients. The current process does not seem to allow for government transparency and why a drug is or is not approved remains much of a secretive process to the public.

In our continued efforts to move our mission forward, we have also reached out to the CDC, NAMI, Tourette Syndrome Association (TSA), Yale Child Study Center (a TSA Center of Excellence), Harvard University/Massachusetts General Hospital, the First Lady and various other organizations. In the last year and a half, even with our multiple attempts to connect, many did not respond. When they did, they were confident that the FDA would be the organization to properly address our concerns. We have since realized that working with the FDA is ineffective, so we have changed our direction to focus more on educating patients and the medical community.

Bureaucrats think when their ass, not yours, is on the line

Otsuka filed to have Abilify approved as a treatment for children with Tourette’s in 2014, almost 12 years after its 2002 debut for schizophrenia and bipolar disorder. The FDA approved it in December 2014. Then something really bizarre took place: FDA decided the drug deserved approval for adults with Tourette’s as well – and Otsuka was outraged! It’s not often you hear of a drug company objecting to being offered a bigger market. What on earth was going on?

The answer, as explained by Ed Silverman in the Wall Street Journal and in other legal and financial blogs, was breathtaking in its cynicism. Otsuka’s move had nothing to do with the welfare of children – and didn’t even have much to do with the money to be made selling Abilify to people with Tourette’s! They were playing a highly technical game with U.S. patent law in which Tourette’s sufferers young or old were no more than pawns. The game focused on two well-meaning laws intended to give drug companies incentives to do the right thing: the Orphan Drug law, and pediatric exclusivity.

The 1985 Orphan Drug law aimed to encourage companies to develop drugs for rare diseases. Such drugs could be lifesavers for a few thousand people, but the market might be too small to be profitable. Classification as an “orphan drug” results in seven extra years of patent protection. “Pediatric exclusivity” was added to US drug law due to concerns that many drugs tested on adults were being used on children without any research into the special precautions or lower doses that children might need. A drug tested and approved for children can get three extra years of patent protection, at least for pediatric use. In some cases – and this made Otsuka’s ears perk up – the three-year extension can apply to any use of the drug, if FDA feels that putting a generic version on the market without those special instructions for pediatric use might endanger children.

So Otsuka attempted a double-whammy. It applied for orphan-drug status for Abilify as a treatment for “Tourette’s in children.” If they’d applied for Tourette’s in adults too, they could have kept generic rivals out of the Tourette’s market for seven years. Otsuka, however, then sued to block ANY generic competition for seven years, arguing that putting generic copies on the market without that patented labeling would endanger adults with Tourette’s as well as children! Its lead attorney was Ralph Tyler of Venable LLP, former lead counsel for the FDA.

At stake was the huge overall market for Abilify, which brought in $6.5 billion in the U.S. in 2013. The patent was set to expire in April 2015. Otsuka has pushed the U.S. price of Abilify to close to $1,000 a month, and the cost of this one drug has become particularly painful for state and federal programs that insure most people with severe mental illness. Otsuka had known for years that doctors were using Abilify off-label to treat Tourette’s, but had held off on seeking FDA approval. Their eleventh-hour “Tourette’s maneuver” was aimed at locking up the entire market until late 2021.

On April 28, they got their (disappointing) answer. The FDA agreed to approve Abilify only for pediatric Tourette’s. In the name of children’s safety, it granted a seven-year exclusive patent on Tourette’s in general. However, it argued there was no need to keep generic versions of Abilify off the market for other uses, as long as the makers were not allowed to label or market them for Tourette’s. Consumers on both public and private insurance will get a huge break. Hopefully we’ll all get a break from Otsuka’s aggressive marketing of Abilify, allowing us to think logically about who really needs to take it and for how long. Otsuka will have to look elsewhere to plug a huge hole in its sales.

Otsuka is not the first company to manipulate the Orphan Drug law to make megabucks. My favorite example is the Lidocaine Patch, until recently available only from Endo Pharma for $800 – $1100 per month. It was approved in 1999 as an orphan drug for post-herpetic neuralgia (“shingles”), a nerve infection that causes painful itching and burning. It was obvious this patch could be useful to lots of people with pain from injuries involving a “pinched nerve” or similar condition. By wisely refraining from seeking that approval, Endo forced people with extremely common disorders to pay through the nose for its “orphan drug.” All this from a simple reformulation of a very old medicine!

Lidocaine has been around for over fifty years – I can remember parents spraying “Solarcaine” on sunburned children in the sixties. For people with back pain, it’s clear the Patch works better and lasts longer than the lidocaine creams they could buy at the drugstore, and may help them limit their use of more harmful narcotics. It’s not clear why so many should pay more for their Patches than for their monthly rent or groceries.

Lots of other drug companies have made a killing with similar maneuvers. Approval for pediatric use produces a three-year patent extension, even for a drug like Celebrex which few children actually use. Just testing a drug on children yields a six-month extension, even if the company never files for pediatric use. Eli Lilly played that game with its antidepressant Cymbalta, despite knowing the drug was unlikely to test well in children. Lilly enjoyed the extra six months of patent protection; we don’t know how the children in the clinical trial felt.

Otsuka is extorting more than money, however. It’s pretty hard to hurt yourself with lidocaine. But the overuse and over-promotion of Abilify has already been ruinous for thousands of patients. It may be particularly risky for people with Tourette’s, although it apparently works for some. Ironically, allowing sky-high prices for Abilify in the U.S. may have helped it become far more dominant here than in the U.K. or Europe. The financial incentives to promote the drug were so huge that patients and doctors alike were bombarded with propaganda about its virtues. People like the author of this and the previous post have become pawns in this game to an even greater degree than the rest of us.

The final part of the series looks at Abilify Maintena.

Abilify, Tourette Syndrome and Me

Tourette Syndrome

Editorial Note: This post is by DG. It’s number three in the Abilify series, following Dodging Abilify and Abilify from the Inside Out.

I was diagnosed with Tourette Syndrome (TS) as a child. It was always manageable. I did well in school and was actively involved with music programs at church and school. At 17, my tics suddenly became severe and despite extensive testing, doctors were unable to figure out why.

An hour after my first dose

After months of waiting, I was treated by a top neurologist and was prescribed Abilify to help manage my tics. Only an hour after taking my first dose, I started experiencing anxiety that was so scary I already wanted to get off the drug. I had an ominous feeling not of this earth that something bad was going to happen. A voice in my head kept telling me I wasn’t going to get any sleep, so I developed a fear of insomnia. Despite my shock about the fact that a medication could be this horrible, my neurologist wasn’t at all concerned about my initial reaction, and told me that I needed to give it a chance to work. Since she didn’t give me any other viable options, my parents and I agreed I would stay on the medication.

After a week, I started noticing bizarre changes to my tics. I started experiencing tormenting tics that no longer had the usual sense of satisfaction afterwards. No matter how much I would tic, it didn’t satisfy the urge. What made these “new tics” even more uncomfortable is that they felt like they were only “half” coming out, which isn’t normal for TS and I had never experienced before.

My neurologist didn’t recognize this as serious. At the time, my family and I trusted her judgment. I thought the medication was only half suppressing my tics because I was taking a low dose. The neurologist’s solution was to raise the dose. Although this did help these uncomfortable changes go away at first, the mental torment progressed. I wish the neurologist had listened more closely to what I was telling her and picked up on the fact that something was terribly wrong.

Tormenting improvement

The drug had basically given me “tormenting improvement” and that should have been a sign that no real improvement was being made. I couldn’t leave my house and my quality of life in many ways was even worse.

I began to experience visual hallucinations that frightened me because of how realistic they were. Every night I would see bright flickering strobe lights that lit up the whole room. My neurologist didn’t see any problems with this, and informed me that this was “simply my brain adjusting to the new medication.” She was completely wrong, because my hallucinations only got worse from there. Years later, I still experience serious hallucinations, sometimes on a daily basis. I see faces in the carpet, I have seen a demon that looks like the grim reaper lurking in my doorway, and I see photos on the wall change to have satanic faces. I have even seen my private parts fly out of my pants, through the air, and go crashing out the window. It is absolutely embarrassing and bizarre that a medication has a side effect like this!

I developed severe restlessness that forced me to pace constantly, and at certain times, I was even unable to sit and eat at the table with my family due to extreme anxiety. I developed a severe loss of interest in everything. Even with my tics now being suppressed, I still couldn’t sit and play the piano. I literally lost my ability to experience pleasure. Every day I woke up with an intense dread of having to face the day. I had such severe exhaustion as if I had never even slept. There were times I felt too exhausted to even breathe and I had to crawl on the floor because I was unable to stand up. My parents didn’t realize what this was at the time because my extreme exhaustion presented itself as if I was drowsy and sedated from the medication. When I tried to do Yoga, the longest I was able to hold a pose was a few seconds. I developed hand and full body tremors and other involuntary movements such as my leg kicking by itself.

The fear drug

I nicknamed Abilify “the fear drug,” because of the unbelievably severe and debilitating anxiety side effects I developed all throughout the treatment. From the very moment I got on Abilify, I lived my life in constant fear of everything, even my little dog and air! I would become paralyzed with fear even when I walked outside to get the mail. My teeth were constantly chattering even when I wasn’t cold. Every evening, all I could do was lie on the floor and shiver and tremble convulsively. My life on medication was nothing more than one big panic attack, and it would literally take me a whole week to recover from the trauma of leaving my house, even to simply see my doctors. Abilify put so many thoughts, fears and feelings into my head about Satan, hell and torment. My dreams were made as much of a nightmare as my reality, giving me no escape. It blurred the lines between dreams and reality, I often questioned whether I was actually sleeping or awake.

I found the treatment to have a complete “dog chasing its tail” effect the entire time. Abilify would help with my tics, only to very quickly replace them with anxiety that was as severe as the original symptoms being treated, which in turn aggravated the tics to bring them right back again.

One of the most concerning side effects I experienced all throughout treatment was very bizarre breathing problems. I was forced to constantly think about my breathing. My lungs felt as if they were no longer “automatic” and had become “manual.” It felt as if my lungs had stopped breathing on their own and I had to constantly control my breathing to keep myself alive! The torment from this aggravated all my other symptoms, and the distraction it caused me made it extremely difficult to even function.

Most of my side effects locked me inside a hell that only I could see, and since I could not tell others of my suffering, I simply suffered in silence. To everyone around me, I looked far healthier than I really was. At the time, I was so delusional, I actually believed I was having minimal side effects and lost my ability to recognize that the drug was hurting me.

Tough it out

Abilify caused me such severe anxiety that in order to stay on it, my doctor added an SSRI to counteract the side effects. The SSRI wasn’t helping near enough and my doctor wanted to keep raising the dose, but my family and I decided against it because I had severe headaches that felt as if my head was going to crack open. It only further aggravated my restlessness and even more alarming was the fact that I was now developing obsessive compulsive behavior such as touching rituals.

My doctor’s answer to any concern I ever had when reporting side effects was almost always “to tough it out” and that “the side effects will eventually level off.” There was one time she even said this while I was experiencing life threatening reactions from another medication such as severe nausea and vomiting where I was unable to keep a sip of water down. It got to the point where my mother was literally embarrassed to report back to me how the neurologist was answering our concerns about the medication in her email responses.

Before treatment, I was one of the few patients with TS to not have any of the co-morbid conditions, which is usually referred to as TS only. Because of medication, I went from being one of the few without OCD to developing one of the most severe cases imaginable! Medication has caused me the “OCD on steroids.” Because of my drug-induced OCD, my life consists of one compulsion after another, many of which do not make any sense. It can take me hours to be able to complete even the simplest of tasks. I cannot just enter or leave a room, lie down to go to sleep, etc. without activating countless compulsions which I need to perform. I have lost all self-control and I am forced to give in to every single compulsion, no matter how much I try to fight it.

I also developed a severe case of ADHD. I was a 4.0 student and now it can take me an hour to write a simple sentence or process new information. I space out and am so easily distracted that I have to listen to things several times because I miss half of the information. My memory has been greatly affected because at times I can’t remember anything. Abilify was supposed to help me get through school by suppressing my tics, but quickly deserved its purpose by interfering with my learning abilities. I wish my neurologist would have been more concerned about the development of my new co-morbid conditions while on the medication. She realized how it was “sacred” for me to have TS only, and she so easily let the medications ruin that for me.

A little bumpy

After over a year of drug therapy, my family and I decided I needed to discontinue all the medications since they weren’t helping. My neurologist agreed and I got off each medication slowly. Our only preparation was that she told us it might be “a little bumpy.”

A nightmare began to unfold. The side effects got worse as I got off the medication and I began experiencing the withdrawal symptoms. I became a completely different person totally unrecognizable to my parents. I was suicidal, homicidal and paranoid delusional and remained that way for over 4 months. My parents had to watch me 24/7. When they turned to the medical community for help, the doctors’ only solution was to put me in an institution and medicate me further. My parents refused to do this to me since they loved me and now realized it was the medication doing this to me; so we toughed it out as a family.

Years later, I still have all the side effects of medication. Even the mildest of side effects, including dilated pupils, are still so prominent. It’s very important to note that I’m now off all medication and have been for a few years. Sadly, I develop new side effects on a daily basis. I have a wide variety of new involuntary movements such as: my torso twists, my back arches backwards, my mouth takes loud dramatic gasps of air, my eyes rapidly shake back and forth and my muscles slide out of place! Many of these occur at the same time as some of my tics.

I’m the expert in me

A lot of the ways that I am able to distinguish between my tics and Tardive Dyskinesia involve aspects of the movements that only I can experience. The tics feel like you’re doing them to yourself compared to Tardive Dyskinesia which feels more involuntary. For example, I developed neck movements, including one where my neck thrusts back by itself. I brought it to my neurologist’s attention, but she was not concerned because she thought it was normal for TS and simply dismissed it as being a tic. But I’ve had neck tics before and this did not feel like a neck tic. The neck movement had some aspects to it that are not normal for TS including how the actual movement itself was painful.

Even my original TS progressed, not only in severity, but also many new tics I never had before medication. What is really upsetting is the fact I now have severe Coprolalia, and never swore in any way or form prior to medication.

The biggest concern of all is how my mental health has been left in absolute ruins. I have such severe emotional symptoms that there are times when I have been unable to eat, sleep, or go to the bathroom without hysterical crying, screaming at the top of my lungs and violence that I did not have whatsoever before medication. My mental health since medication has drastically changed and is not at all normal for TS.

With everything being so different, it is hard to imagine why my neurologist didn’t pick up on any of this. I experience countless emotions and feelings that include: depression, anger, jealousy, hatred, disgust, happiness, calmness, indignant, paranoia and euphoria, none of which are my own.

I now have constant voices in my head that never stop talking. The voices often “fuse” together with my new tics and compulsions creating hybrid illnesses. Medication has transformed my regular urges to tic into voices that now order me to move my body. For this reason and others, my TS is now more of a mental illness than it is a movement disorder. I now spend all my days pacing around the house talking to the voices in my head. To this day, I stand to eat and sleep on the floor and I am unable to leave my house.

Not too long ago, my mother told my neurologist that I was still severely disabled. My neurologist seemed surprised. Had it not been for my family’s love and support, perseverance and research about medication, we still to this day would have no idea the medications are to blame, because my neurologist barely told us anything about their safety and did not listen to any of our concerns throughout my entire treatment and thereafter.

See Abilify, Tourette Syndrome and You.

Abilify from the Inside Out

doctor holding timebomb

Editorial Note: This is part 2 of Johanna Ryan’s series that started with Dodging Abilify. Abilify is at present the best-selling drug in North America – how come?

In last week’s column, Dodging Abilify, I described the fan-club enthusiasm for this drug among doctors I’ve met, my own reluctance to try it, and what I’d learned about Abilify from casual research.

This week we’ll hear some first-hand accounts of Abilify from the 34 people who have completed RxISK reports – twenty-seven patients, six relatives and one doctor. As a group, they’re a lot less gung-ho on Abilify. I’ll summarize what they told us, then consider why the drug’s still a bestseller.

First, while Abilify was developed as an antipsychotic, only five out of 34 had taken it for a “psychotic” diagnosis: two for schizoaffective disorder, two for schizophrenia, and one after a brief psychotic breakdown. Fourteen were taking it for depression. Six took it for bipolar disorder, which can include psychotic symptoms; however, none of the six reported such symptoms prior to using Abilify. Three took Abilify for other diagnoses, two for poorly-defined “stress” and three for unknown reasons. (One said that “someone, probably a psych doctor of some sort, told my mom I should take this stuff.”)

Fifteen were taking Abilify with antidepressants. One took both Cymbalta and Wellbutrin, another took Wellbutrin and Zoloft. Three were on Cymbalta only, and four on Wellbutrin only. (Two others took Wellbutrin just before or after taking Abilify, but never took them together.) Four were on Celexa or Lexapro; four were on Effexor or Pristiq, and one each on Paxil and Prozac. Other medications people reported taking with Abilify were anticonvulsants (6), stimulants (4), benzodiazepines (3) and lithium (2).

The reports were hard to read. They included three confirmed suicides, possibly four. Many described frightening episodes, severe emotional distress or physical misery. Since most patients were on several meds, some weren’t sure if Abilify alone was the culprit; however, they were sure these were drug-induced states, distinct from the problems they’d originally sought help for. There were three main types: akathisia or agitation, sedated-depressed states, and abnormal movements.

Akathisia and aggression

Eight people reported akathisia, and six reported unusual aggression or anger. The latter included two violent physical assaults on family members. Three reported a first episode of psychosis. One woman’s episode came on when she stopped Abilify. “Bizarre and frightening thoughts” led her to assault her husband, whom she remembers confusing with someone from her childhood. She restarted Abilify, then tapered off the drug more gradually and has now been drug-free for a year “with no bipolar symptoms whatsoever.” Another woman diagnosed as depressed reported a first-ever “hypomanic” episode, with racing thoughts and rash decisions, on stopping Abilify.

Two people described their akathisia as intense physical restlessness, saying they literally could not keep still. One woman felt Abilify had helped her depression, but the restlessness was so intense she had to decrease the dose to one too low to be helpful. Another described having to pace up and down while reading, as she could not sit down. The problem embarrassed her: “People can tell there’s something wrong when you make a lot of movement unnecessarily.”

Others described a more emotional akathisia which led to suicidal urges and outbursts of anger. One woman described “wanting to crawl out of my skin”, with agitation, anxiety, insomnia and thoughts of suicide – a “horrible torturous existence.” Another man described a less intense yet pervasive anger and irritation. He felt he couldn’t complete familiar tasks, like replacing a part in his car, because the simplest obstacle would make him too angry to focus.

Sedation and depression

At the other extreme, 14 people reported over-sedation and cognitive slowing, with memory, concentration and word-finding problems. About half felt a profound emotional numbing, an inability to feel pleasure or care about anything. One man regretted this state, but felt it was better than his prior severe depression. For the rest, however, it brought new or worse depression. Three felt trapped at home by “total lack of interest in life” along with anxious depression; loss of the ability to pursue, or even care about, formerly cherished goals was painful for others. Most reported suicidal thoughts of varying intensity.

Suicide

Three confirmed suicides and one possible suicide were reported. One was a college student prescribed Abilify and Wellbutrin for depression and stress. According to his parents, this led to intrusive thoughts, worsening depression and emotional numbness, including loss of his longtime passion for music. Rather than preventing suicide, they felt the drugs had pushed him to the brink. The second was a middle-aged man who went to his doctor with back pain, admitted to mild work-related stress, and was started on antidepressants. This led to a four-year downward spiral of akathisia, hostility, depression and more medications. His doctor’s final strategy was to double his Cymbalta and add 15 mg Abilify. Three days later he hanged himself. Less was reported about the third suicide, a young woman treated for schizophrenia. She was already on two antipsychotic drugs and a barbiturate; her suicide came a few days after Abilify was added.

The fourth man, already on Effexor, developed paranoid ideas for the first time on starting Abilify, along with a compulsion to search out conspiracy information on the Internet. It wasn’t the thoughts themselves that distressed him, however, so much as his resulting inability to concentrate and work on his creative writing, the main source of meaning and purpose in his life. His family described increasing despair and low self-esteem. They also reported him as deceased; whether by suicide or some other cause wasn’t clear.

Movement disorders

Three people had tremors in a single limb or hand. Two of these cleared up on stopping the drug; one man still had leg tremors a month later. Four others had tardive dyskinesia (TD), a pattern of severe involuntary movements linked to antipsychotic drugs; one woman also had seizures. Their symptoms started after taking Abilify for at least a year, and continued despite stopping the drug. They found their condition painful, debilitating, disfiguring and socially isolating. Two reported shortness of breath; one was newly diagnosed with “asthma”, but her breathing problems may be TD-related. While akathisia affected some patients even at low doses, all those with TD were taking unusually high doses, ranging from 15 mg for a year, to ten years on 30 mg.

Other problems

One man reported a gambling compulsion that began two months after starting Abilify, and gradually escalated until it ruined his finances and personal relationships. Nine people reported gaining large amounts of weight. Four men reported sexual dysfunction. For two, this was part of a broader numbness and apathy; a third man, newly on the drug, reported erectile problems and agitation. The fourth had severe genital pain that not only ruined his sex life but made any physical activity difficult.

Stopping vs. staying on

Of the nine people still taking Abilify, two reported that lowering the dose had solved the problem. One was a doctor reporting on a patient with schizophrenia; we don’t know whether the patient agreed with his assessment. The other worked out for himself the dose that would help him manage his schizo-affective disorder without too many side effects (about half what his doctor prescribed). Two patients had sedation, cognitive problems and weight gain, but feared the return of their original symptoms (delusions in one case, severe depression in the other) if they stopped.

Three people reported being coerced or pressured to keep taking Abilify: one by her employer, another by her doctor, while a third said simply “because I am obligated to.” One man did not explain why he stayed on the drug. Finally, one woman was quite happy with Abilify, although she had taken it for only five days. She had gained a lot of weight on a previous antipsychotic, and felt she was already beginning to shed some of it. I’ve heard from several other people who liked taking Abilify, and a few more who found it easy to tolerate for months before problems set in. In all cases, they had taken other antipsychotics first, and felt Abilify caused less sedation and weight gain than their old drug.

Eight people had their worst problems on stopping Abilify; the others primarily had problems while taking the drug. Akathisia and agitation plagued some while on Abilify, and others only when they stopped. Sedation and cognitive problems, however, always began on the drug, and improved on stopping in most cases. Several people reported one set of problems while taking Abilify, and others on stopping. One woman quit after several years of feeling too sedated to function; she suffered from tardive dyskinesia and seizures, but felt her “clarity of thought” returning.

Short-term studies on a “tardive drug”

After reading these reports, I began to think of Abilify as a Tardive Drug. The benefits, if any, would show up early, while the problems could take months or years to emerge. Some, like TD, might not show up till the drug was stopped. Clearly, a six-week study would tell you almost nothing about the overall impact of a drug like this. Yet everything my doctors were being told about Abilify was based on six-week studies, including the ones the FDA had used to approve it for depression.

Some of the animal studies, by contrast, had lasted for a year or more. A summary was posted on the FDA website, and it wasn’t encouraging. After 39 weeks, monkeys on Abilify were underactive, with whole-body tremors and hunched posture. You might almost think they had TD. You might also see it as a preview of what long-term studies on humans would show. Was that why Abilify clinical trials continued to be so short?

The latest one, done by Otsuka in Japan, went by the jazzy English acronym ADMIRE. The abstract explained it involved 3 groups of depressed patients: “fixed dose” (3 mg), “flexible dose” (3-15 mg) and placebo. Both the fixed and flexible-dose Abilify groups improved “to a significantly greater extent” than the placebo group, and Abilify was “well-tolerated.” Higher akathisia rates in the flexible-dose group, it said, might reflect the higher instance of a certain gene affecting drug metabolism among Asians. A closer look at the numbers, however, told the same old story: very modest improvement according to doctors’ ratings, no difference according to patient self-ratings, and high rates of akathisia.

They also showed me what the abstract was hiding: The “flexible-dose” group were not given individually tailored doses from 3 to 15 mg, as one might think. They were actually a “high-dose” group: all had their doses ratcheted up in unison, 3 mg at a time, to 15 mg by the study’s end. They actually “improved” slightly less than the 3-mg group – and 36% suffered akathisia, more than twice the rate of the 3-mg group.

ADMIRE had actually found what many in the RxISK group learned the hard way: Higher doses of Abilify led to worse side effects, with no extra benefit. Akathisia was not an Asian problem, but a dose-dependent problem.

Little baby doses? Yes and no

Fifteen of the RxISK group were taking Abilify plus an antidepressant, yet there was no clear favorite among the pills prescribed. Did it matter? In trying to research this question, I stumbled across the secret of those “little baby doses” being touted for depression.

Most antidepressants are broken down in the liver by the same enzymes that process Abilify. When you take two such drugs, the resulting “traffic jam” will effectively increase the level of Abilify in your blood. Some pills create a bigger traffic jam than others. Paxil and Prozac have a strong effect, with Wellbutrin and Cymbalta not far behind. Celexa and Lexapro have a smaller effect. Your actual Abilify levels might be 150% to 300% of your official dose. Since no exact figures are available, let’s assume your effective dose could double. A 2-mg dose could pack the same punch as 4 mg, a 5-mg dose the same as 10 mg – and for those poor ADMIRE patients, 15 mg may have felt like 30. In addition, side effects like agitation, anxiety, insomnia and nervousness are considered “common” on all these antidepressants, which might increase your odds of having Abilify Akathisia.

In other words, the “little baby dose” was an illusion. Even 2 mg was bigger than it seemed – and doses over 5 mg could put you on a par with patients taking Abilify for psychosis. (Those patients may be taking excessive doses as well: Two patients with psychotic symptoms in the RxISK group found they did better on half the dose their doctor initially prescribed.)

At the very least, Otsuka should warn doctors about combining antidepressants with higher doses of Abilify, and educate them as to how it interacts with various antidepressants in different strengths. Instead, the Prescribing Information states that doses should NOT be adjusted for drug interactions when prescribing Abilify for depression–although elsewhere it warns that Abilify doses should be “at least” cut in half if combined with drugs such as Prozac and Paxil!

It made no sense—until I recalled the selling power of that “little baby dose” pitch, which sounds so reassuring to patients. It had almost worked with me; it made my fears seem a bit silly. It also reassures doctors that they don’t have to make complex choices about which antidepressant to use, in which dose. Just add Abilify and serve! Why worry about two (or five) little milligrams?

A drug that looks better from the outside?

Abilify is a stimulating or “activating” drug for the majority of people, although some feel sedated and slowed down. Five in the RxISK group took it with Wellbutrin, and two more just before or after trying Wellbutrin. Doctors may be using it as they use stimulants, when patients appear fatigued or slowed down and “activation” seems a good idea. Yet activation is a two-edged sword: welcome at times, but irritating or even agonizing in excess. It might look to the doctor like progress, even while the patient starts to feel nervous or agitated. I thought of those trials where doctors rated the patients more “improved” than the patients rated themselves. Perhaps Abilify looks better from the outside than it feels from the inside.

Abilify marketing records, released during court cases, suggest Bristol-Myers recognized this. (In 2007, they paid $515 million to settle charges alleging bribery and other shenanigans to promote Abilify for unapproved uses.)

The huge nursing home market, full of elderly patients with dementia and “difficult” behavior, was one Abilify sales reps coveted. The sales pitch they crafted invited staff to picture a new resident who sat hunched over, staring into space all day – supposedly due to depression, since antipsychotic drugs are officially off-limits for frail elders with dementia. Who wants to see that when they come to visit Mom on a Saturday? the reps asked. Wouldn’t we like to see her up and about, looking lively? The sales pitch worked; whether Mom felt better or worse in the long run, apparently, was not their concern.

A sales pitch with a drug attached

I was glad I had dodged Abilify, and a bit spooked to see how close I’d come to being taken in. To see the entire medical profession falling for it made me really scared—and angry. “Not really an antipsychotic?” Gimme a break. “Little baby doses?” Not really. “True happiness”? Good luck! My doctors’ best arguments turned out not even to be their own – just marketing pitches they’d absorbed without realizing it, possibly sold as Continuing Education. There might be a legitimate use for this drug somewhere, but we’d never find out with marketing in the saddle and medicine trailing behind. Everything, from the drug’s name to the “scientific” studies, seemed built around the sales pitch.

“I have seen many commercials about how drugs like Abilify can perk people right up,” one woman wrote to RxISK. “So I was not only disappointed and frightened by the results, but felt once again tricked and exploited by the big promises that drug companies make but never seem to keep.” Amen, sister.

See Abilify, Tourette Syndrome and Me.

Dodging Abilify

Abilify cartoon lady

Editorial Note: This post is by Johanna Ryan, who has a unique ability to capture the American Nightmare.

The best-selling drug in the United States isn’t a blood pressure pill, a painkiller or even an antidepressant. It’s Abilify, an antipsychotic agent with $6.3 billion in 2013 sales. Granted, Abilify isn’t the most prescribed pill, but its #1 status is sealed by popularity and high price: the current retail price of a 30-day supply is now a whopping $900, and it’s 23rd in sheer numbers of prescriptions. In 2011 the Medicaid program in my home state of Illinois spent $53.6 million on Abilify for its poorest citizens, more than it spent on any other drug.

I’m not the first to ask, what the hell is going on here? However, my interest in Abilify is personal: Wherever I go in the healthcare system, people have been urging me to take it, and even suggesting there’s something irrational about my reluctance.

Phase 1: Dodging bipolar disorder

A brief word about my situation: I’ve been treated for depression, at times severe, since 1975. Over the years I’ve been unable to work for brief periods, fairly miserable but officially “functional” more often. Still, I’ve never once experienced psychotic symptoms. No voices, no visions, no strange beliefs or fears, and no “manic” periods of wild activity and grandiose plans. Back in the 1980’s I was hospitalized a few times as actively suicidal, and was once given antipsychotics – but only for the first week or so. I didn’t like them then; I felt more passive than truly calm, and unable to complete an intelligent thought.

Having watched the rollout of “new and improved” antipsychotics in the 1990’s that turned out to have just as many problems as the old ones, I still don’t like them. However, it wasn’t until 2006 that I really got skeptical about psychiatric drugs in general. Despite a long trail of meds that had done me no good, stopped working or had miserable side effects, I was always willing to try the next milestone in the march of science – unless it was an antipsychotic.

Ten years ago, the new antipsychotics were easy to refuse. The theory behind giving them to people like me was that repeatedly depressed people might have “bipolar disorder type II”, a mood disorder without actual mania, and should take these drugs as “mood stabilizers.” My longtime psychiatrist, Dr. A, knew me too well to really believe I was bipolar; he told me he thought it made little difference what label he put on my depression since none of them could be verified. Still, he thought these drugs well worth a try. “They’re not necessarily antipsychotics,” he said. “That’s just a label, they’re used for lots of things.” “I know,” I replied, “but they’re still neuroleptics. I want to hang on to all the brain function I can.”

“Oh, come on,” he coaxed. “We’re talking about little baby doses here, just a fraction what they give people for schizophrenia.” That sounded somewhat reassuring – but I still said no. (Today I’m glad I didn’t listen to that particular sales pitch, as I’ll explain later.)

Back in those days, I could tell a family doctor, OB/GYN or nurse that Dr. A wanted me to take antipsychotics, and they’d look bewildered. Even flinch a bit. “But you’re not… I mean …” “Right,” I’d say. “Not psychotic. And unless and until I start hearing voices, I’m not touching that stuff. Even if I do start hearing voices, I’m not taking it a day longer than I have to.” They all thought that made sense.

Phase 2: Nowhere to hide

Then came Abilify. Now no one flinched anymore. Instead, they all seemed to think I should try it. “I’ve heard tremendous things about that drug,” they’d say. “It’s different.” Some even told me they’ve seen it work wonders for this patient or that. Even those who were usually skeptical of Pharma’s newest miracle drugs seemed won over. What the hell was happening?

I knew of one big event: Abilify had been officially approved for depression alone, for those who did not “fully recover” after six weeks on an antidepressant. And that, the TV ads informed us, included two-thirds of patients. Everyone had seen these ads, featuring the little cartoon woman who could get up and go back to work, but was still followed around by that small black cloud of unresolved depression. They’d also listened, mouths agape, to the recital of possible side effects, from suicidal thoughts and hallucinations to involuntary movements, coma and death. For awhile, the ads were fodder for late-night comics. Yet these warnings came with a new twist: Abilify, “like all antidepressants”, could lead to thoughts of suicide, they said. Dr. A’s “not really an antipsychotic” gambit was becoming an official line.

Reading up on Abilify told me its side effects were no joke. Like other antipsychotics, it blocked certain dopamine receptors; unlike them, it was a “partial agonist” or stimulator for others. While this made it less likely than Zyprexa or Seroquel to cause obesity, diabetes and sedation, some patients were still plagued with all three. Moreover, “less sedation” had a nasty catch: Abilify caused lots of akathisia, an agonizing mental and physical restlessness that can lead to suicide. The official FDA leaflet said that 10-12% of patients experienced akathisia and an incredible 25% had “agitation,” which I figured was either a layman’s word or a polite euphemism for the same thing.

There were also reports of tardive dyskinesia and similar disabling or disfiguring involuntary movements. This was a problem the new “atypical” antipsychotics were supposed to have greatly decreased, if not eliminated, but Abilify’s record made it look more like the bad old drugs. And tardive dyskinesia, I knew, could linger long after the drug was stopped.

What about the benefits? The FDA’s decision to approve Abilify as an add-on to antidepressants had been based on two studies done by the drugmaker itself. Even they had shown Abilify only slightly better than placebo on a scale used by doctors to rate depression. On a rating scale filled out by the patients themselves, there’d been no difference at all. This despite a study design that had favored Abilify by first putting everyone on an antidepressant alone, and screening out those who did well.

Worse yet, patients in many Abilify studies were being allowed as many benzodiazepine tranquilizers as they needed to tolerate the side effects – and up to 70% had said yes, please. Perhaps a lot more than 25% of them were feeling that famous agitation. If they felt slightly better at study’s end, could that be due more to the tranquilizers than Abilify? It alarmed me to think this drug was being given to teenagers diagnosed as bipolar, patients with depression linked to borderline personality disorder, and irritable and disruptive autistic children. Most of these people would be considered “agitated” to begin with. How many would feel worse without realizing Abilify was the cause – or even if they did, would be unable to convince their doctors?

Phase 3: Going underground

A few years after Abilify’s debut, I found myself consulting a psychiatrist again, after several years’ absence. Listening to Dr. B, I could tell a lot had changed in that time. You didn’t need to be shoehorned into the bipolar category anymore to need a mood stabilizer; they were essential for everyone. There was a large motley heap of mood stabilizers, ranging from antipsychotics to seizure drugs, and Abilify was king of the hill. Again I heard there was no need to label it an antipsychotic, and in any case a “little baby dose” was enough to combat depression.

Soon I found myself dodging Abilify at every appointment. This had to be done in stages: starting with denial (“But really, I don’t think I’m doing THAT badly!”); moving on to bargaining (“I’ll take lithium instead. Or Lamictal. Or something”), and then to simple delay (“Give me three months, and if I’m not feeling better I promise I’ll take it.”). The coaxing grew stranger: “Why don’t you think of these awful depressions you get as a type of seizure,” suggested Dr. B. (Abilify, by the way, is not an anti-convulsant; it actually lowers your seizure threshold.) Finally, it seemed like every session was spent dodging Abilify. “Sure, you’re functional,” Dr. B. told me. “But that’s not much of a goal. I’d hate to see you miss a chance at true happiness.”

Holy crap. Had I just heard a psychiatrist say “true happiness”? Either this was quite some drug, or quite some advertising campaign! I had felt lucky to be seeing Dr. B, since at least he listened and was open to negotiation. But if I didn’t give in on this, he might just unload me onto the hospital clinic. It’s my way or the highway in those places, and their way would be Abilify for sure. Finally, reluctantly, I agreed to give it a try. But on the train home, I found myself eyeing that prescription slip like it was an improvised explosive device. Was I really going to fill it?

No, as it turned out, I wasn’t. Instead I did something I wasn’t entirely proud of: I simply e-mailed Dr. B a week later, telling him I was taking 2 mg per day. I didn’t feel better or worse, I said, just kind of scatterbrained, with some trouble concentrating. He emailed back: So you’re sedated and mentally slowed on 2 mg? He sounded skeptical. I hurriedly assured him I wasn’t sedated, not really. It was more like having a bit of ADHD, but without being hyperactive. OK, said Dr. B, don’t go up to 4 mg yet. Wait another week or so. Ten days later I e-mailed him saying I still felt the same, and it was making things difficult at work. To my relief, he told me I could stop. I had gotten my “trial of Abilify” under my belt, without taking any actual Abilify, and could now move on.

If this was what it took to dodge Abilify, I decided, we had a real problem—and I wanted serious answers. First I dug into some of that official research for myself. More importantly, I asked RxISK to give me access to the reports patients had made on the website about Abilify, minus the names and other identifiers, of course. I promised to sort through these, compare them with the clinical trials and the FDA side effect statistics on RxISK, and write a report for a blog.

My friends at RxISK were all for it. Next week, I’ll report on what I learned.

Abilify and me

Becoming Suicidal on an Antibiotic

Acne

Editorial Note: The last post on Lariam and suicide mentioned an alternate treatment for malaria prophylaxis – doxycycline. Doxycycline is not without its problems. It can cause suicide – Suicide is Painless. It and other tetracycline antibiotics can also cause sexual dysfunction including enduring post-treatment sexual dysfunction – makes you wonder if they also inhibit serotonin reuptake.

I am 33 years old and have had mild acne for 19 years. I have tried topical solutions, which tend to calm things down during treatment. Once stopped, the acne always returns. Feeling quite sensitive about my skin, I went back to see my GP.

She suggested Doxycycline tablets. I had heard that particular tablets for skin problems could make you feel depressed and suicidal. I mentioned this to my doctor, in the hope that she would tell me that the drug she was prescribing would not cause this. She did. I happily took the prescription to the chemist. The pharmacist then dispensed a loading dose of 200mg and a three month supply of 100mg tablets, one to be taken daily.

Things started well…

I began the course feeling hopeful. The tablets did seem to be an effective treatment for the acne, although I noticed a change in how I was feeling. Initially this was not a problem, I felt good. Apart from a nagging headache and some nausea, I felt subtly dis-inhibited; freer in general. I actually found this quite liberating. This lasted for 3 days, at which point I started to notice that my mood was fluctuating quite quickly. I felt great one minute and extremely irritable the next. My tolerance for stress was decreasing rapidly. It would take one comment to switch my mood and I would become withdrawn and feel like screaming to be left alone. I would visit family feeling bright and upbeat but very shortly end up sitting in a completely separate room trying to calm down before making an excuse to leave. It’s only in retrospect that I can see that this was odd behaviour. Outwardly, I think I must have just appeared quieter, duller. Inwardly, I felt frustrated and angry. Although I can be quite sensitive under usual circumstances, this was heightened way beyond this. I did feel that it could have escalated further, had I continued with the medication.

Disconnected, anxious & unhappy

Family members felt the need to speak to me, specifically to ask how I was feeling. Apparently I had been acting ‘oddly’, they used the words ‘withdrawn’ and ‘down’. These descriptions puzzled me as I had felt that I had swung to and fro from happy to angry, but did not have the insight to see that I was feeling low in mood, as they were describing it. Although, under normal circumstances, I would connect the two things together, under the influence of Doxycycline, it seems that I could not make those connections. Looking back, I felt somewhat disconnected from external events and overly concerned, even locked into internal thoughts. These thoughts turned in to viciously negative ruminations, which made me feel anxious and unhappy.

It was after 3 days of the treatment that I began to notice that I was feeling anxious, escalating as the days and treatment went on. I was worrying about things that I would not usually worry about. I felt an increased heart rate; I could feel my heart thumping in my chest when I lay in bed, silly thoughts whirling through my head most of the night. Unsurprisingly, I found it difficult to sleep. Whilst I was searching for a solution to all my perceived problems, an idea literally popped into my head. I felt relief for the moment that I thought I would carry out this idea; to commit suicide, to kill myself. I brushed this aside as a non-solution and carried on being unable to sleep; obsessing over minor issues that just a second ago I had thought were worthy of ending my life over. At this point I could not see that this was absurd.

Making the connection?

I continued taking the Doxycycline, feeling quite pleased with its effect on my skin. Over the next few days I continued to feel anxious almost constantly, the feel good moments had gone. I was thinking more and more of that absurd solution to all of my problems that seemed to just get worse and worse. I would be driving in my car, at any time of day and suddenly think…I could just crash my car. The words repeated themselves in my mind for the remainder of the journey. I was struggling not to give in. By this time I had heard some stories about others taking Doxycycline, with disastrous results that ended in suicide. Even then, I felt like there needed to be some deliberation about stopping the drug; it was working as a treatment for the acne. I felt like I couldn’t quite grasp the reality of the situation, I was somewhat removed. I would like to think that if I was to choose to end my life that I would not try to take other lives with me. Crashing my car would likely cause other injury or fatalities. Looking back, this seems like a very selfish and ‘disconnected’ thought to have.

In the end, I bargained with myself. I would stop taking the tablets to see if I ‘felt’ better. I could always re-start to cure the acne. Even though acne makes me feel sensitive about the way I look, I can’t ever imagine wanting to take the risk of death in the hope that it could be cured. I think this is another example of how I experienced feeling disconnected.

Without doxycycline I felt more like me again

I gradually started to feel more like me as the days without Doxycycline went by. After 2 weeks I felt much better. After the first few days the impulsive suicidal thoughts had stopped, although I continued to feel anxious and ruminate about things. This reduced in intensity over the 2 weeks until I just felt my kind of normal again. A relief!

I did get the sense that the tablets had affected my hormones in some way. I can compare how I felt then to symptoms of PMT and my cycle had been set off course by 11 days. This may sound circumstantial but this is less than rare in my case; it has never happened to me before. These 11 days were days that came after I had stopped the tablets, so at first I did not think it was related. I searched the internet for things that could be the cause; I found quite a few cases implicating Doxycycline in women with the same problem. This strengthened my suspicion that the effect may have been, at least in part, hormonal. The whole experience has deterred me from taking medications in future. It’s frightening to think that a tablet I take for acne can make me want to take my own life. It’s even more frightening that I nearly didn’t make the connection.

The experience wasn’t fatal in my case, but others haven’t been so lucky.