SAN ANTONIO — There is ample evidence in modern literature to dispel the myth that there is a placebo response and that the largest incremental response is seen early in treatment, said Mark Zimmerman, MD, of Brown Medical School, Providence, R.I.
“I had a patient say to me this week, who after going on an SSRI began to feel better in a couple of days, say ‘I know it is probably placebo response but nonetheless I am feeling better.’ Quite frankly, I didn’t care. I love the placebo response,” Zimmerman said here at U.S. Psychiatric and Mental Health Congress.
The delayed antidepressant response hypothesis started in the 1980s by a group led by Frederic Quitkin, MD, at Columbia University. They found there was no difference between active drug and placebo in the first 3 weeks of treatment with tricyclic antidepressants, according to Zimmerman.
“In the modern era, there have been a number of companies that have claimed early onset of efficacy,” Zimmerman said. “And have demonstrated separation from placebo in the first week or two of starting medication.”
A meta-analysis in Journal of Clinical Psychiatry, published by Zimmerman and colleagues a decade ago, showed the “biggest difference between active drug and placebo is in the first 2 weeks of treatment. And as you go along the difference between active drug and placebo diminishes.”
Other meta-analyses have shown similar results.
“This isn’t just for major depressive disorder,” Zimmerman said, pointing to a meta-analysis of OCD treatment published in the Journal of Clinical Psychiatry “that essentially finds the same thing.”
The meta-analysis by Issaria and colleagues looked at 17 placebo-controlled studies for OCD and included over 3,000 patients.
“At the end of week 2, there was a 0.91 difference between active drug and placebo and at the end of 12 weeks it was 3.30. So about 30% of the improvement occurred within the first 2 weeks; more than half of the improvement occurred in the first month,” he said. “Yes, patients continue to get better but now we are talking about the relative improvement over and above the non-specific effects of treatment which is the placebo condition.”
Zimmerman challenged the audience to think about the clinical implications of this. “What expectations do you set for your patients? When you see a patient and start them on a medication do you tell them it takes 4 to 6 weeks to begin? Do you schedule them to come back in a month? The belief that early response to antidepressants equals placebo response — that is a myth,” Zimmerman said. – by Joan-Marie Stiglich
Zimmerman M. Things you think you know, that may not be true in the diagnosis and treatment of depression. Presented at: U.S. Psychiatric and Mental Health Congress; Oct. 21-24, 2016; San Antonio.
Posternak MA, et al. J Clin Psychiatry. 2005; 66(2):148-158.
Issaria Y, et al. J Clin Psychiatry. 2016; 77(5):e605-e611.
Disclosure: Zimmerman reports no financial disclosures.