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.
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.
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.
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.