It is worth wading through some slow moving stuff at the start of this post to get to the juicy bits.
The Things Drugs Do
Drugs do things. Company marketing divides these things into the one good thing the company wants you to focus on – good for a company bottom-line and the ninety-nine other “side effects” that we are doing our best to minimize.
This issue came up in the recent Dolin case in Chicago. Its comparatively unusual for an SSRI like Paxil- Seroxat to produce an overall benefit in nervous states beyond what you can get from placebo, but in most cases it will emotionally numb to some extent and in pretty well all cases as the Court heard it will cause some genital numbness. But the label for Paxil and other SSRIs mentions nothing about either emotional or genital numbness.
There is no mention in some cases because investigators in clinical trials were told not to ask questions about certain issues – like sexual issues or non-issues on SSRIs. Aside from that, clinical trialists are hypnotized to focus on what the company wants them to focus on and to miss anything else that might be happening.
The unfortunate thing about this is that the best way to discover new drugs is to get those who are taking them to report back just exactly what the drug did for them. Sometimes they will notice an effect because its something they wanted done – in which case bing you have a new drug for something that people really need that can be got on the market because its already there or just about there.
This is how we got Viagra. People in clinical trials of a drug for angina cleared their throats and said you know what…..
This is still the best way to find new drugs. In blocking efforts to report “side effects” or take them seriously, drug companies not only jeopardize our lives and safety, they also hit their own bottom line.
The culture companies have created means that even on RxISK we slip into talking about adverse effects and side effects. This implicitly accepts company claims about the primary effects. But more importantly it does nothing to help people on treatment notice unexpected or surprising helpful effects.
Unexpected
I know a lot about unexpected effects but recently someone who opened my eyes to a very surprising effect. Checking with others who know a lot about unexpected effects, none of them had heard about this surprise either, which was reassuring but added to the surprise.
The person I was chatting with had been diagnosed with benign prostatic hypertrophy – BPH – something that is supposedly very common in men of a certain age – and not so common in young women. Its a pain to live with.
Thirty years ago BPH was something every doctor had to take into account when prescribing antidepressants. The tricyclic antidepressants have anticholinergic effects and it was this we were told and all textbooks said and still say that could tip an older man with BPH into urinary retention.
I never fully bought the BPH story. Much more anticholinergic drugs like procyclidine and benztropine didn’t cause urinary retention. There was too much of a sense that companies wanted to pin all the good things an antidepressant might do on their catecholamine reuptake inhibiting effects and all the bad things on their anticholinergic actions. But the patients I met said far from causing problems strong anticholinergics were euphoriants – sufficient to support a market in them, unlike anything else in mental health.
And then a colleague in her mid-twenties told me the catecholamine reuptake inhibitor, nortriptyline, she was on caused her urinary retention.
Twenty years later we got duloxetine – Cymbalta – as a bladder stabilizer. At least we did in Europe. FDA blocked the license in the USA because women with bladder instability seemed to be committing suicide when they were put on it. The dual effects in duloxetine were catecholamine reuptake inhibition for bladder stabilization and serotonin reuptake inhibition for suicide and nightmares and other effects.
Many of the drugs now used for BPH have the opposite effect on catecholamine systems to nortriptyline and duloxetine. The idea is to increase urinary flow. The market leader is called Flomax. A terrible drug my colleague said as have several other people.
He then tried finasteride but didn’t like it either.
Finally he got Cialis online and bingo everything was vastly better. Turns out within four years of Viagra coming on the market people were reporting the same thing when using it. Lilly went ahead and did trials with Cialis to prove it was helpful but they don’t market it for this purpose and almost no-one seems to know about it.
Rewriting the Books
All sorts of people are now trying to work out what’s going on. There is talk of a neurotransmitter pathway that was new to me – an l-cysteine/hydrogen sulfide pathway. And there is also talk of LUTS – lower urinary tract symptoms. In other words, an enlarged prostate may be irrelevant. In older age, men can get bladder instability or overactivity. Chances are anyone who has it will also have BPH but the BPH may be irrelevant – women get LUTS too.
What is needed is some doing and on the basis of what happens we can try to explain what’s going on. My colleague couldn’t get his doctor to prescribe Cialis for him. I would happily have done so but he now has a regular supply from an online source. Its worth trying to get one of these drugs. They are relatively harmless compared to Flomax and Finasteride. And doctors can prescribe them, even though no company markets them for this purpose.
We also need a culture that believes what people report. This vignette popped up when I was trying to tell my colleague that the problem today is that no-one really listens to people who take drugs anymore. He didn’t seem to realize it was men like him taking Viagra who made this discovery – not Lilly when they did a clinical trial of Cialis.
We need more research. We need some of you to find out what might be going on in terms of other actions Viagra and Cialis and related drugs have – on hydrogen sulfide or pixie dust or whatever the latest neurotransmitter is.
But we also need people to find out what these drugs do by taking them and reporting back. The bedrock of everything that’s in the books and in any doctor’s head is what you notice when you take a drug. The books and patient information leaflets are close to worthless compared with you and any friends you may have on the same drug or your hairdresser – a great untapped source of observations about the effects of drugs that aren’t in the textbooks.
Women with bladder instability may have more to contribute than anyone else. Does Cialis or Viagra help you with LUTs? There is a lot of talk about interstitial cystitis these days but this might all need to be revised if some women with LUTs find they are helped by sildenafil, vardenafil or one of the other phosphodiesterase inhibitors.
Johanna says
From what I have read, the Viagra story didn’t even qualify as a rare example of researchers listening to unexpected stories from their patients. They only stumbled across the drug’s charming “side effect” after it had totally bombed as a heart-failure treatment. Protocol demanded they collect the leftover drugs from the former subjects — but this proved tough. Men kept claiming they had lost the pills or dropped them in the toilet by mistake. Or they would promise to drop them off, but never show up. It wasn’t until one research center found its entire supply had been stolen, that someone said hm, this stuff seems to be awfully popular. I wonder why?
What this says to me is that so-called “abusers” of prescription drugs may have just as much information about their real effects, good and bad, as proper patients. The worst consequences of this outright refusal to listen comes from the opioid addiction crisis (and concomitant benzo-addiction crisis) now ravaging the US. Doctors were sold the concept that patients taking opioids for real physical pain could not get hooked – and that extended-release 12-Hour OxyContin eliminated cravings. Slowly and painfully, doctors are at last getting the message that neither one is true. But any doc who actually listened to patients could have realized this 15-20 years ago.
In the past few years doctors in the UK have been warning that some patients are abusing and/or getting hooked on pregabalin and gabapentin, otherwise known as Lyrica and Neurontin. It started with docs working in prisons; now GPs are trying to warn the profession. In the US we don’t hear a word of this, although we seem to be swimming in both drugs. Oddly, Lyrica is marketed as a pain drug here, and primarily an anxiety drug in the UK. I wonder if the real reason Pfizer did not go for the “anxiety indication” in the US is so the addictive potential of this drug for some users would stay unnoticed?
annie says
What a surprise! Rxisk taking .. ?
New law lets doctors say sorry without having to take blame
https://www.politicshome.com/news/uk/health-and-care/health-professionals/press-release/medical-defence-union/86627/doctors
“Doctors in Scotland are being given legal protection when apologising to patients, the Medical Defence Union (MDU), explained today.
The Apologies (Scotland) Act 2016, the relevant part of which comes into force on 19 June 2017, makes it clear that an apology (outside of legal proceedings) is not an admission of liability. In the new Act, an apology is defined as:
“…any statement made by or on behalf of a person which indicates that the person is sorry about, or regrets, an act, omission or outcome and includes any part of the statement which contains an undertaking to look at the circumstances giving rise to the act, omission or outcome with a view to preventing a recurrence.”
Mr Jerard Ross, MDU medico-legal adviser, said:
“Saying sorry to a patient when something has gone wrong is the right thing to do and is an ethical duty for doctors. The Apologies (Scotland) Act provides further reassurance to doctors that apologising is not an admission of legal liability. In the MDU’s experience, a sincere and frank apology and explanation can help restore a patient’s confidence in their doctor following an error and help to rebuild trust. This is important for a patient’s future healthcare and can help to avoid a complaint or litigation.”
The GMC has published ethical guidance on the professional duty of candour which explains in more detail what constitutes an effective apology for healthcare professionals. This includes advice that apologies should not be formulaic and that the most appropriate team member, usually the lead clinician, should consider offering a personalised apology, rather than a general expression of regret.”
The GlaxoSmithKline Paroxetine means never having to say your sorry and it would be a dynamite piece of evidence to have a ‘non formulaic’ apology from the lead clinicians casting doubt on Seroxat prescribing by the associates involved and whose behaviour should have led to litigation.
More power to those doctors who thought they could just slip away ..
http://files.heraldscotland.com/news/health/15343071.Doctors_told_an_apology_does_not_mean_legal_liability/?ref=rss/
Harvey Vedder says
I’m still looking for the medical world to take note of the vast number of misdiagnosed BPH cases that are nothing more than rectal pouch impingements on the prostate, mimicking BPH symptoms — both squeeze the urethra shut.
Anecdotally, every male I’ve mentioned this to agrees that upon defecation urine flows much better. Retained stool or gas at the rectal level is a major contributor in any case and perhaps causal agent as well.
I’ve only had half dozen unfruitful searches since the web was there, interestingly this was one. It was three years before I found a lone notice (from a deceased MD) verifying the above.
So yes, listen to what people report — or fail to report as you cite above! Mention this to any male you know who has BPH symptoms and see what they say.
David Healy says
Dear David Healy
As a microbiologist, I am concerned that your sensible newsletter is recommending drugs such sildenafil (Viagra) and taladafil for women with recurrent lower urinary symptoms (LUTS), previously known as the ‘urethral syndrome’. Common side effects of these drugs include head-aches, flushing, heart-burn and abdominal pain. Lots more side effects are listed and caution is advised in people with cardio-vascular disease. Also, no drug should be taken without medical advice in women who may be pregnant.
With regard to women with LUTS, some will have coliform infections which need investigation and antibiotics. There are also quite a large number of women with recurrent LUTS whose microbiology test results are negative by conventional laboratory methods. If sexually transmitted infections (which can present similarly) have been excluded, it could be that these often distressing symptoms are due to disruption of the normal protective urethral flora by previous antibotics – see the attached article by Rosalind Maskell. More and sometimes longer courses of antibiotics are often prescribed by doctors but these may not help in the long run and symptoms may recur. (NB Although there is no evidence available, my own daughter found that after other risks and possibilities had been excluded, a dose of azithromycin, which has anti-inflammatory as well as antibiotic properties, helped reduce symptoms to manageable levels — she then used pain killers and alkalinised her urine to reduce the distressing symptoms while the normal flora recovered.) Alkalinising the urine can be done by using cymalon or equivalent sachets from the chemist (these primarily contain sodium citrate & sodium bicarbonate). The normal flora may take some weeks or longer to recover.
Women and others have set up their own internet sites when they find advice from doctors has not helped with distressing, sometimes life changing, LUTS. There is advice on the internet about alkaline diets to help alleviate symptoms. D- mannose has also been investigated in a pilot study from Italy (attached) and can be obtained from some chemists. Again the risk of drug side effects must be considered (and especially in pregnancy). All these measures need more formal study. Some internet sites advise against the commonly mentioned use of cranberry juice – they say that although this may give some initial relief by its anti-adhesive effects, it also acidifies the urine and symptoms could return because of this acidification.
As Dr Maskell says in her attached article, more work needs to be done on this area. Hopefully, new DNA techniques will make it easier to investigate and treat these very unpleasant symptoms more rationally!
With best wishes
Elizabeth (Price)
Dr. David Healy says
Elizabeth
Thank you for this. There was no intention to suggest all LUTS in women or men is likely to be sildenafil or vardenafil responsive but having seen someone’s like transformed and aware that the GU area is such a mush zone as it were with more than its fair share of myths it seems to me that some women and men who are not getting much joy from standard treatment approaches should think about this. Clearly there are problems with any drug that also need to be taken into account.
David
Johanna says
This makes a lot of sense—it seems like several different conditions could be involved. Maybe US-UK language differences are part of the problem?
Surfing around, I noticed UK websites often referred to bladder infections as “cystitis.” That’s not a word we use over here. Our doctors call a bladder infection a “UTI” or urinary tract infection. It’s diagnosed with a urine culture and treated with 7-10 days of antibiotics. Some women may suffer harm from endless repeat antibiotics (especially if Cipro or Levaquin are used?).
We hear a lot about detrusor instability, re-named “overactive bladder.” That’s portrayed as a common problem of female aging from time immemorial. Not painful, but it can be serious due to the embarrassment and isolation that go with incontinence. It’s treated (some say over-treated) with strongly anti-cholinergic meds like Detrol (tolterodine) which are often cited as part of the anti-cholinergic overload imposed on the elderly. Some people treat it as a muscle problem which exercises can help.
“Cystitis” is seldom if ever used in the USA for either condition. I’ve heard that word only for “interstitial cystitis.” I know of a couple people who have that, but until now I didn’t even realize peeing too much was involved. It’s treated as a chronic pelvic pain disorder of mysterious origin for which there are no easy or reliable treatments. Neither Detrol nor antibiotics are thought to help.
Dr. David Healy says
Jo
Thanks for this. One of the interesting things that happens a family doctor here in the UK if they think about prescribing Viagra for a woman is their computer screen lights up Red. Viagra is not to given to women. I imagine this is because women can’t have Bob Dole type erectile dysfunction. It would be interesting to know if there is any other reason, other than the fact that all drugs are risky – even coffee can give headaches. So if women want to try this here they will probably have to get their husbands to get it (and it will be doled out – yes doled is on purpose – you will only be let have a certain number of sexual experiences per week). The other options are private prescriptions or the internet.
D