The evidence regarding psychotropic drugs

via Heart & Soul of Change Project


Can’t Make It Up This Good–or Bad: TEOSS Follow-Up

Dr. Barry Duncan

Sometimes, people don’t believe me when I talk about the evidence regarding psychotropic drugs. It does sound far-fetched some times because the evidence is so much different than what you hear in everyday conversation.  The difference between what you hear or read in the media and the clinical trial data is striking, so much so that reporting the real evidence often leads to raised eyebrows. But you know, I couldn’t make it up near as well or as damning as the actual clinical trial evidence. For example consider the latest about antipsychotics and kids.

Prescriptions for antipsychotics for children continue to skyrocket, despite underwhelming evidence. Here is how we wrote about the NIMH funded Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS) (Sikich et al., 2008) in our recent chapter in the Heart and Soul of Change, 2nd Edition (Sparks, Duncan, Cohen, & Antonuccio, 2010):

“Described as a landmark trial (McClellan et al., 2007), TEOSS sought to examine the efficacy, tolerability, and safety of two second generation antipsychotics (SGAs; Risperdal and Zyprexa) for youths diagnosed with early-onset schizophrenia spectrum disorder and to compare these to a first generation antipsychotic FGA (molindone or Moban). Fewer than 50% of subjects completed 8 weeks of treatment and response rates were low and not significantly different for all three groups (Sikich et al.). Participants in the study were allowed concomitant use of antidepressants, anticonvulsants, and benzodiazepines, compromising even these disappointing findings. A 17-year old boy committed suicide and an unspecified number of participants were hospitalized due to suicidality or worsening psychosis. These events are particularly disturbing in light of the fact that youths considered at risk for suicide were excluded from the study. Weight gain was deemed serious enough to warrant suspension of the Zyprexa arm (McClellan et al.).”

It gets better or should I say worse? Follow up, available on line and soon to be published in the June issue ofJournal of the American Academy of Child & Adolescent Psychiatry (see the abstract at http://www.jaacap.com/article/S0890-8567(10)00294-7/abstract, revealed that only 14 of the 116 youth (12%) responded to the medication and stayed on it for one year. That’s right, you read it correctly–12%! Recall that in the famous adult trial of antipsychotics (the CATIE trial) that 74% dropped out. So it is even worse in youth—88% failed to benefit.

So let’s break this down. First, TEOSS was not placebo-controlled. The 116 youth enrolled into the trial were randomized either to a first generation antipsychotic (Moban) or to an atypical antipsychotic or so called second generation antipsychotic (Risperdal and Zyprexa). At the end of eight weeks, the response rate was 50% for those treated with Moban, 46% for Risperdal, and 34% for Zyprexa. Adverse events were “frequent” in all three groups.

Only those youth who “responded” during the initial eight weeks — 54 of the 116 — were entered into the 44-week maintenance study. Forty of the 54 youth dropped out during this period because of “adverse effects” or “inadequate response.” Thus, only 14 of the 116 youth who entered the study responded to the medication and stayed on it for as long as one year—only 12%.

Pharmacotherapy helps some children and adolescents, although apparently not very many. However, the preponderance of empirical research indicates that the risk may not be worth it. While pharmacotherapy involves considerable risk for young people, psychosocial interventions have a strong track record with virtually no adverse associated medical events. APA’s Working Group on Kids and Psychotropics (2006) concluded:

For most of the disorders reviewed herein, there are psychosocial treatments that are solidly grounded in empirical support as stand-alone treatments. Moreover, the preponderance of available evidence indicates that psychosocial treatments are safer than psychoactive medications. Thus, it is our recommendation that in most cases, psychosocial interventions be considered first. (p. 16. Italics added)

As the evidence regarding TEOSS suggests, the automatic prescription of antipsychotics for sure, but with any psychotropic, is unwarranted. Where children are concerned, the stakes are higher. They are, essentially, mandated clients—most do not have a voice to say no to treatments or devise their own, and depend on adults to safeguard their wellbeing (Sparks & Duncan, 2008). If you are seeing kids taking antipsychotics, you are on very firm ground to raise concerns and ensure the treatment is fitting client preferences.