Thursday, May 07, 2009

Phase V, Abilify, and Vanishing Akathisia

If you've been reading about Abilify for depression on this site, you've probably noticed that I've been down on Abilify for causing akathisia in a frighteningly high percentage of patients. In two recent trials, akathisia occurred in 25% of Abilify patients compared to 4% of placebo patients. What, exactly, is akathisia? That's still a matter of some debate. Let's turn to a recent Journal of Clinical Psychiatry article on the topic. Entitled "Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics," the paper purports to provide "a review of the literature on the incidence of drug-induced akathisia associated with the use of second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs)."

It provides a few different characteristics associated with acute akathisia, including:
  • "Intense dysphoria
  • Awareness of restlessness
  • Complex and semipurposeful motor fidgetiness"
It mentions "...suicidal behavior has been described in patients with akathisia in case reports, both in patients receiving antipsychotic medication and in patients receiving selective serotonin reuptake inhibitors (SSRIs)."A couple of descriptions from another journal:
  • Increased tenseness, restlessness, insomnia and a feeling of being very uncomfortable
  • On the first day of treatment he reacted with marked anxiety and weepiness, on the second day felt so terrible with such marked panic at night that the medication was cancelled
So we can all agree that akathisia does not sound like fun.

Now back to the Journal of Clinical Psychiatry review article. What did the authors conclude? "The comparative incidence of akathisia among the newer antipsychotic agents remains poorly characterized." And "...SGAs are generally associated with a lower propensity for movement disorders compared with their FGA counterparts, an emerging body of comparative literature shows that second-generation medications are not completely free from inducing akathisia."

The authors go through a long list of second-generation antipsychotic medications. The drug that receives the least attention is aripiprazole (Abilify). The authors conclude that "in studies comparing aripiprazole with placebo, akathisia rates in the aripiprazole arm were similar in some studies, and higher in others. As with other SGAs, akathisia rates with aripiprazole were lower than those of FGAs." So Abilify causes less akathisia than older medications and it's unclear if it causes more akathisia than placebo. But, wait, wasn't akathisia related to much higher rates of akathisia than placebo in treating depression? Fortunately, the authors had a little trick to erase that inconvenient piece of evidence; they only examined trials trials involving people diagnosed with schizophrenia or bipolar disorder. So the depression studies -- POOF -- vanished, along with their damning data.

Why would the authors want to censor negative data about Abilify? Well, one author is an employee of Otsuka America Pharmaceutical, Inc., and another is an employee of Bristol-Myers Squibb, companies that market Abilify. And the other authors: All but one of them have a financial relationship with Bristol-Myers Squibb. The best part:
Editorial support provided by Maria Soushko, Ph.D., Phase Five Communications, Inc., New York, N.Y., with funding provided by Bristol-Myers Squibb.
So a paper that excludes the most inconvenient evidence regarding akathisia on Abilify had major parts of the writing done by... a medical writer hired by Bristol-Myers Squibb. If one goes to Phase Five's website , the first animation that pops up says "Spinning Your Science Into Gold." I'd say that this article was indeed 24 karat gold. I hereby nominate all authors of the study for a much coveted Golden Goblet Award.

Citation Below:

Kane, J., Fleischhacker, W., Hansen, L., Perlis, R., Pikalov, A., & Assunção-Talbott, S. (2009). Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics The Journal of Clinical Psychiatry DOI: 10.4088/JCP.08r04210

Update: See a related post at the Carlat Psychiatry Blog. A partial quote:
Publishing an article that was carefully crafted to draw attention away from Abilify's main liability was shameful, and is exactly the kind of deceptive editorial practice that we as a society can no longer tolerate.


Bernard Carroll said...

I second the nomination. Like, it’s not as if we didn’t know already that depressed patients are especially susceptible to the extrapyramidal side effects of antipsychotic drugs – you know, things like akathisia and tremor and muscle stiffness and parkinsonism and tardive dyskinesia. The data on akathisia with Abilify in depression are troubling. I fear that thousands of patients are being placed at unnecessary risk of tardive dyskinesia by the promotion of this drug for depression. After all, anecdotes aside, the evidence for efficacy of Abilify in depression is underwhelming.

CL Psych said...

Yeah. And the bipolar and schizophrenia studies on akathisia are generally highly confounded by patients having a history of treatment with a whole slew of antipsychotics, "mood stabilizers," anticholingergics, and God knows what else. So I think the depression studies are probably more telling regarding the propensity of inducing akathisia.

But who cares about the underwhelming evidence of efficacy? If memory serves correctly, a new study coming out in JCP found that 20% of VA patients with depression are on antipsychotics. And 10% of depression patients are likewise on AP's. The current scorecared is something like -- Marketing departments/crappy science: 200 Patient welfare: 3. And the antipsychotic for depression movement is apparently still growing rapidly.

On one hand, egregious key opinion leaders are falling by the wayside quickly (Keller, Nemeroff, Schatzberg, etc.), but drug marketing is a hyrda. Remove Nemeroff, and some other prestige-craving and/or money-hungry KOLs anxiously jump off the bench, ready to fulfill their roles as salespeople-"academics".

This is so depressing that I might need to drop a "broad spectrum psychotropic" to deal with the pain. But do I choose Risperdal, Seroquel, or Abilify? For depression, all are so darn well-supported by science that I don't know which to choose. Maybe I'll email a KOL and ask which of these wonder drugs is right for me...

Justin Marley said...

There's an overlapping phenomenon referred to as restless legs syndrome which is well recognised by neurologists and has a genetic association. This may reflect different naming systems by different professional groups. Both terms may represent a heterogenous group of conditions however in which case there would only be a partial overlap



Paul Harrison said...

Mmm, akathisia. Fscked up my life. Imagine compressing a century of hell into about three months. Imagine being unable to sit still, only comfortable while running.

Oh yeah, and the usual anti-anxiety benzodiazapines have no effect on it. The anti-psychotic they tried didn't help either. I eventually self-medicated with propranolol.

You evil bastards.

Bobby said...

Loved the story..

Really really great read!

Anonymous said...

i had to hold myself back from stabbing myself the akathesia was that bad.

Anonymous said...

the only thing that would work for abilify would either be 6 mg artane or the recommeneded dosage of mirapex, cogentin--- doesnt even touch that sh*t-what a shitty drug.

Anonymous said...

It is horrible the effect of psychotropic medications. We need to be educated about this topic and work actively with our mental health practitioners. If a person is under any medication, either the person or relative must know about side effects and how really this treatments work...if they really work.