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clinical psychology and psychiatry a closer look atypical antipsychotics for depression now with considerable evidence skip to main skip to sidebar clinical psychology and psychiatry a closer look psychiatric medications science marketing psychiatry in general and occasionally clinical psychology questioning the role of key opinion leaders and the use of science to promote commercial ends rather than the needs of people with mental health concerns wednesday december 16 2009 atypical antipsychotics for depression now with considerable evidence i ve been wanting to write about this for months here goes we know that antipsychotics are the new panacea for all things mental health related including depression 1 2 3 but critics kept pointing to a pesky lack of evidence that such treatments actually worked bristol myers squibb manufacturer of abilify has been running a disinformation campaign in medical journals to tout its drug as an antidepressant their attempts to paint a positive picture of abilify s antidepressant properties and its allegedly fantastic safety tolerability profile have been simultaneously tragic and amusing 1 2 3 we re now moving on to something bigger it ain t just abilify folks it s all the atypicals they are all antidepressants according to the authors of a recent meta analysis for atypical antipsychotics at present this body of evidence is considerably larger than that for any other augmentation strategy in the treatment of major depressive disorder in other words if you are not prescribing atypicals for your patients who don t show adequate response to antidepressants you are not practicing evidence based medicine you are a bleeping cowboy who is willfully disregarding science you are denying your patients the best possible treatment the authors don t actually say any of those things but those are the implications if the evidence for using antipsychotics is considerably larger than the evidence for anything else then the implications are clear cut and this is exactly how this study will be cited salespeople from drug reps to academic psychiatrists to practitioners looking to earn a few thousand extra bucks on the side through pharma speaking gigs will discuss this study as if it were a landmark finding response and remission but the evidence is not all that convincing here s why the authors pooled together the results of 16 randomized controlled trials in these studies patients had failed to respond adequately using various definitions to an antidepressant patients were then assigned to receive either an atypical antipsychotic or a placebo in addition to their antidepressant outcomes were then tabulated somewhere between 4 and 12 weeks later the results seem clear cut if your brain is turned to off the response rates for atypicals was 44 compared to 30 for placebo the remission rates were 31 for atypicals and 17 for placebo the advantage for atypicals is statistically significant well there you have it done deal ask your doctor about abilify zyprexa seroquel today but the most important thing in a treatment outcome study is the outcomes the authors of the meta analysis did not bother to actually measure change in scores on rating scales instead they only used response and remission rates there is absolutely no good reason for doing this it s potentially quite misleading doctors like remission and response rates because they provide the illusion that we are measuring depression exactly a responder got a lot better and is functioning reasonably well whereas a non responder is in bed 12 hours a day while spending the rest of her time watching the e network eating bon bons and sobbing constantly but it s not nearly that scientific a responder is usually defined as someone who got 50 better on his or her depression rating score during the study period so bob s depression rating score improved by 52 he s a responder but amy s score only improved by 48 so she s a nonresponder is this 4 difference really meaningful let s look at the following dataset for 20 participants in a fictional study improvements in depression over course of 10 week study drug placebo 40 30 55 60 50 45 55 48 52 48 60 55 60 55 10 25 20 10 25 30 using a 50 improvement to determine if a patient is a responder we get a 60 response rate on drug and a 30 response rate on placebo lazy logic says oooh the drug is twice as effective as placebo but is we take the average for each group we get an average improvement of 42 7 on the drug compared to 40 6 on placebo see the problem with response and remission rates similar arguments have been made by smarter people than myself putting outcomes into convenient little categories makes good sense when the categories themselves make sense events like having a heart attack getting pregnant or dying if the death rate on a drug is 4 compared to 2 on a placebo then the drug really reduced death by 50 but if the remission rate or response rate for depression is 40 on drug compared to 20 on placebo that does not mean the drug is twice as effective as placebo in treating depression if you need to score a 7 or below on a depression rating scale to be in remission but you score an 8 are you really much worse off than the person who scored a 7 am i saying that the drugs really just squeaked by placebo in these studies well i ve read the abilify studies and posted on them previously in those studies abilify barely beat the placebo and in the opinion of the patients themselves abilify didn t beat placebo at all and the studies were designed to benefit abilify not to actually see if the drug worked as i noted previously patients were initially assigned to receive an antidepressant plus a placebo for eight weeks those who failed to respond to treatment were assigned to abilify antidepressant or placebo antidepressant those who responded during the initial 8 weeks were then eliminated from the study so we ve already established that antidepressant placebo didn t work for these people yet they were then assigned to treatment for 6 weeks with the same treatment and compared to those who were assigned antidepressant abilify so the antidepressant placebo group started at a huge disadvantage because it was already established that they did not respond well to such a treatment regimen no wonder abilify came out on top albeit by a modest margin here s an analogy a group of 100 students is assigned to be tutored by tutor a regarding math the students are all tutored for 8 weeks the 50 students whose math skills improve are sent on their merry way that leaves 50 students who did not improve under tutor a s tutelage so tutor b comes along to tutor 25 of these students while tutor a sticks with 25 of them tutor b s students do somewhat better than tutor a s students on a math test 6 weeks later is tutor b better than tutor a not really a fair comparison between tutor a and tutor b is it i ve not read the other antipsychotics for depression studies i ll even give them the benefit of the doubt and assume they were not designed in the same biased manner as the abilify trials it is however worth noting that the benefit of abilify in terms of response and remission rates compared to placebo was about the same as for the other atypicals which leads me to think that the other atypicals probably show similar marginal benefits for depression but now based solely on potentially quite misleading response and remission rates an article appears in the american journal of psychiatry a piece that has the potential to ramp up the prescribing of antipsychotics for depression to an even more ridiculous level let the good times roll source of ironclad evidence that atypical antipsychotics are antidepressants until you actually read the paper nelson j papakostas g 2009 atypical antipsychotic augmentation in major depressive disorder a meta analysis of placebo controlled randomized trials american journal of psychiatry 166 9 980 991 doi 10 1176 appi ajp 2009 09030312 posted by cl psych at 12 16 2009 12 46 00 pm labels abilify antidepressants antipsychotic depression evidence 11 comments anonymous said well done thursday december 17 2009 12 40 00 pm anonymous said an unbiased review would have presented toxicity adverse event data but these authors finessed that the pernicious meme of mass marketing antipsychotic drugs for millions of nonpsychotic depressed patients has now reached ucsf and mgh harvard friday december 18 2009 8 23 00 am cl psych said what adverse events what toxicity perhaps that is fodder for another post on a side note the lead author has also been spotted pushing for cymbalta to treat pain in depression the evidence for that is apparently not so strong but this antipsychotics for depression meta analysis was published in a top tier journal so it must be legit right no need to read past the abstract or think about it much the veneer of legitimacy is growing thicker with each publication that proves these drugs work for depression friday december 18 2009 8 40 00 am philrs said interesting of the 16 studies in the metaanalysis 14 used the madrs and only 2 the hamd the hamd is said to capture more somatic complaints so we can assume that the outcomes would have been worse than the madrs scores both hamd studies produced non significant results while out of the remaining 14 madrs studies 7 were positive if we count one small quetiapine trial with a 95 ci of 1 00 30 29 as positive friday december 18 2009 11 39 00 am anonymous said thanks for taking the time to cut through the bs its getting so that my default response to an article in the am j of psychiatry is to wonder which drug company wrote it friday december 18 2009 1 02 00 pm anonymous said re antipsychotic drugs for millions of nonpsychotic depressed patients as a schizophrenic my brain never was chemically psychotic for an antipsychotic to work on antipsychotic is an euphemism for a brain tranquilizer poison in the long run legal chemicals to fix emotional problems do not work any better than illegal ones short term they might help but continual use of a chemical to compensate for ones cognitive dissonance can not work except for the drugs of tabbaco and the bottle of beer or rum saturday december 19 2009 6 15 00 pm anonymous said cl you are like an irish monk during the dark ages trying to preserve truth in the midst of rampant untruth as doled out by big pharma and supposedly academic psychiatrists who simply take money and act as shills for their financial benefactors i applaud your efforts please continue to keep the flame of truth alive saturday december 19 2009 6 34 00 pm neuroskeptic said what you ve said about the response rate being a poor outcome measure echoes what kirsch moncrieff said here thursday december 24 2009 2 57 00 pm vancouver therapist said wow what a great post on this stuff i seem to have more and more clients getting prescribed abilify which confused me at first i guess after reading this it still does yet i m at all surprised well done monday december 28 2009 8 52 00 pm cl psych said neuroskeptic thanks for the link i read one of their pieces in bmj and linked it in my original post but hadn t seen the link you noted monday december 28 2009 8 55 00 pm manchester said anxiety disorders are a unique group of illnesses that fill people s lives with persistent excessive and unreasonable anxiety worry and fear they include generalized anxiety disorder gad obsessive compulsive disorder ocd panic disorder posttraumatic stress disorder ptsd social anxiety disorder sad and specific phobias although anxiety disorders are serious medical conditions they are treatable an anxiety disorder and a co occurring chronic pain disease can make a person s health more difficult to treat but a variety of treatments and lifestyle changes can offer relief possible health complications are noted below increased disability or reduced functioning poorer quality of life poorer response to treatment poorer treatment adherence increased perception of disease severity chronic pain sufferers who also have an anxiety disorder may have lower pain tolerance or a lower pain threshold people with an anxiety disorder may be more sensitive to medication side effects or more fearful of harmful side effects of medication than chronic pain suffers who aren t anxious and they may also be more fearful of pain than someone who experiences pain without anxiety tuesday january 05 2010 10 47 00 am post a comment newer post older post home subscribe to post comments atom email email me blog archive 2011 1 february 1 2010 8 october 1 may 1 april 1 march 3 february 1 january 1 2009 33 december 1 atypical antipsychotics for depression now with october 1 september 2 august 1 july 4 june 4 may 2 april 5 march 5 february 2 january 6 2008 103 december 3 november 2 october 7 september 9 august 8 july 5 june 6 may 8 april 14 march 11 february 13 january 17 2007 328 december 11 november 16 october 14 september 24 august 8 july 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probably pick up on these pet peeves before long view my complete profile translate this page select a language english to spanish english to french english to german english to portuguese english to italian english to chinese english to russian english to japanese english to arabic onchange subscribe via email enter your email powered by feedblitz