Tokyo psychiatrist, Dr. Douglas Berger, comments on “Key Studies That Inform Clinical Practice: Child and Adolescent Psychiatry”, by Nadyah Janine John, MD and Sy Atezaz Saeed, MD, MS, June 21, 2016 issue of the Psychiatric Times.
On the first paper they review on the treatment of depression, the authors state that, “Combination medication and psychotherapy has been identified as first-line treatment in the evidence base” in depressed adolescents.
The TADS study they quoted (https://www.ncbi.nlm.nih.gov/pubmed/17909125) had unblinded subjects and treaters (and thus there was no blind placebo) in both the CBT and combined CBT+fluoxetine groups, while the fluoxetine-only group was blinded. This means the blind fluoxetine group was handicapped compared to the unbinded CBT or CBT+Fluoxeting groups. The design and rigor of blinded study arms is very different from unblinded arms because bias in unblinded arms that have subjective endpioints can not be filtered out. Thus, blinded and unblinded study arms are not logically comparable.
In the TORIDA study they quoted (https://www.ncbi.nlm.nih.gov/pubmed/20478877), participants, clinicians, and independent evaluators were blind to medication type but not blind to taking medication (thus there was no blind placebo). Independent evaluators were blind to CBT assignment, but blind evaluators just record whatever bias comes out of the subject-treater system and are not single (=subject) nor double blind. In other words, there is now way to filter out hope and expectation of receiving CBT openly given to patients and given by treaters trained in, and who are assumed to strongly believe in the efficacy of CBT.
On top of ignoring this huge methodologic flaw in the evidence base to begin with, the authors of the PT article then emphasized the importance of placebo and double-blinding in the 2nd article they reviewed on tics and stimulants. Do the authors want to say that double blinding is needed when we can blind but we should “turn a blind eye” to studies that can’t be blinded?
Just to emphasize the importance of blinding: controlling for placebo and blindedness, a meta-analysis of data from published trials of CBT that showed CBT fared no better than non-specific control interventions in the treatment of schizophrenia and did not improve relapse rates, CBT showed no effect in prevention of bipolar disorder episodes, and only small treatment effects were seen in studies of MDD (Lynch D, Laws KR, McKenna PJ: Cognitive behavioural therapy for major psychiatric disorder: does it really work? A meta-analytical review of well-controlled trials. Psychol Med. 2010; 40(1): 9–24.)
Psychiatrists and psychiatric researchers need to have a better understanding of the importance of blinding and blind placebo, and the differences in rigor this makes in a clinical trial where most all the endpoints are subjective and subject to the effects of hope and expectation as they are in psychiatric disorders.
Doug Berger, M.D., Ph.D.
U.S. Board Certified Psychiatrist
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