|WATCH THIS DOCUMENTARY ON THE ANTIDEPRESSANTS GIVEN TO MANY CHILDREN|
Harvard researcher Irving Kirsch told Lesley Stahl that the difference between taking an antidepressant and taking a sugar pill is minimal for most people.NICE in the U.K. had similar findings for up to moderate depression,
Harvard psychologist Irving Kirsch, PhD, commented, “the difference between the effect of a placebo and the effect of an antidepressant is minimal for most people.” 1 However, a newly published “panoramic overview” of 127 meta-analyses challenges that asser-tion by demonstrating how psychiatric drugs, including antidepressants, are as efficacious as drugs used to treat general medical conditions.2
“Our study puts the effectiveness of psychiatric drugs and general medical drugs into perspective,” lead author Stefan Leucht, MD, Assistant Professor in the Department of Psychiatry and Psychology at Munich Technical University in Germany, said in a press announcement. “There is a deep mistrust of psychiatry, fostered by reports suggesting that the efficacy of psychiatric drugs is very small. Psychiatrists, patients, carers, and the media are often unsettled by these findings, and some may think that psychiatric medication is not worth the bother.”
Later, in a 60 Minutes Overtime show, interviewer Lesley Stahl acknowledged that her husband has taken antidepressants for years, and she noted, “we know they work.” She found the placebo-effect discussion very “confusing” and worried about Americans discontinuing their antidepressants without consulting their physician.
“I personally know of patients who have quit taking their medications and ended up back in the hospital,” he said. “And I know of others who went off their meds, had a recurrence of depression and committed suicide.”
The meta-analyses review, Davis said, is particularly important for primary care and other physicians who may “think that psychiatric drugs are not efficacious, may not prescribe them, and may discourage their patients from taking them. Such perceptions and actions,” he noted, “can cause great harm to patients.”
Davis added he has tried for years in his lectures to make psychiatrists aware that the effect sizes of the psychiatric drugs are in “the ballpark with most of the internal medicine drugs” and that “most medical drugs were not the breakthroughs they [psychiatrists] thought they were.”
“With this review,” he told Psychiatric Times, “we finally got it done.”
In a commentary published in BMC Medicine, Seemuller and colleagues3 from the Department of Psychiatry and Psychotherapy at the Ludwig-Maximilian University of Munich described the review as “a milestone in destigmatizing psychiatry and its pharmacological treatments.” They described Leucht as “an experienced member of the Cochrane collaboration” who is very familiar with the pitfalls of meta-analyses.
Similarly, Davis is highly experienced with meta-analyses. “I wrote the first ones in psychiatry in 1975 and 1976, even before they were called meta-analyses,” he said.4,5
For their article, Leucht and colleagues searched Medline and the Cochrane Library for systematic reviews on the efficacy of drugs compared with placebo and then systematically presented the effect sizes for primary efficacy outcomes. They included 94 meta-analyses of 48 drugs in 20 medical diseases (eg, cardiovascular disease, hypertension, rheumatoid arthritis, chronic asthma, type 2 diabetes mellitus, and hepatitis C) and 33 meta-analyses of 16 drugs in 8 psychiatric disorders (eg, schizophrenia, bipolar disorder, MDD, obsessive-compulsive disorder, ADHD, and Alzheimer disease). They excluded meta-analyses of subgroup studies and, if available, chose reviews of classes of drugs rather than single drugs.
“To be up to date, we also chose more recent studies,” he said. “And when there were several meta-analyses on the same topic, we looked to see if they agreed or not; if they disagreed, we called the authors to find out why. So there is extensive information in the fine print.”
While the review paper “covers all our important findings,” Davis explained, the team made available some 55 pages of Tables and Figures online at bjp.rcpsych.org “for individuals interested in all the data that lie behind the analysis.”
According to the research team, an effect size of 0.2 is considered significant but low, while an effect size of 0.8 or above is considered high. The median of all effect sizes was 0.40.
There was a lot of variability in effect size for medical conditions, Davis said. For example, there was a high effect size (1.39) for proton pump inhibitors to treat reflux esophagitis and a high effect size (2.27) for interferon to treat chronic hepatitis C. But many commonly used general medicine drugs, such as statins and aspirin(Drug information on aspirin) in cardiovascular disease and stroke, had small effect sizes (0.12 for aspirin for secondary prevention of cardiovascular events and 0.15 for statins for cardiovascular events).
“As a generalization, the effect sizes of psychiatric drugs are right in the middle of most of the drugs used in internal medicine,” Davis said.
Antidepressants used as “maintenance treatment” to prevent a relapse of MDD had an effect size of 0.64; antipsychotics used to prevent relapse in schizophrenia had an effect size of 0.92. Less pronounced was the effect size of 0.26 for cholinesterase inhibitors for dementia. In between were atypical antipsychotics and haloperidol(Drug information on haloperidol), with an effect size of 0.44 for acute mania in bipolar disorder.
In the discussion section of their review, Leucht and colleagues commented on several controversial issues, including outcomes measures, duration of studies in a meta-analysis, and decrease of drug efficacy over the decades.