Study Title:

Antidepressants Useless for Mild to Moderate Depression

Study Abstract

Context Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression.

Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression.

Data Sources PubMed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews.

Study Selection Randomized placebo-controlled trials of antidepressants approved by the Food and Drug Administration in the treatment of major or minor depressive disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, they included a medication vs placebo comparison for at least 6 weeks, they did not exclude patients on the basis of a placebo washout period, and they used the Hamilton Depression Rating Scale (HDRS). Data from 6 studies (718 patients) were included.

Data Extraction Individual patient-level data were obtained from study authors.

Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with HDRS scores below 23, Cohen d effect sizes for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline depression severity and crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant difference at a baseline HDRS score of 25.

Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

From press release:

Combining data from six studies that examined the effectiveness of two commonly prescribed antidepressants -- paroxetine and imipramine -- found the drugs produced benefits only slightly greater than a placebo in patients with mild to severe depression.
"They would have done just as well or just about as well with a placebo," said Robert DeRubeis, a psychologist at the University of Pennsylvania, Philadelphia, who with colleagues performed the meta-analysis.

Paroxetine is one of a popular class of drugs, selective serotonin reuptake inhibitors, and is sold under the brand name Paxil by GlaxoSmithKline. Imipramine is an older tricyclic antidepressant drug developed in the 1950s.
The so-called placebo effect is powerful in treating depression, where people believe they are helped even though they are taking an inactive sugar pill, DeRubeis said.

CONSIDER ALTERNATIVES?

In the report published in the Journal of the American Medical Association involving nearly 800 patients, the drugs' impact was noticeably stronger than a placebo in people diagnosed with very severe cases of depression.

Using a scoring system for depression where a diagnosis of 24 or above indicates a very severe case, the researchers said patients treated with drugs saw their scores drop by 13 points, compared to a drop of 9 points for those given a placebo.
But for those with initial depression scores of 23 or below the drop averaged 8 points for those given antidepressants and 7 points for those given a placebo. Roughly half of those prescribed antidepressants fit into the mild to severe categories.

"Our data should give some pause" to doctors and patients weighing antidepressants, DeRubeis said in a telephone interview. "They should give some consideration to other alternatives."

Exercise has been shown to be helpful to stem depression, as does psychotherapy, and even "self-treatment" with the aid of the plethora of self-help literature, he said.

A spokeswoman for GlaxoSmithKline said the report "contributes to the extensive research" into antidepressants, noting that Paxil received U.S. government approval in 1992 and has helped "millions of people battling mental illness.
"The studies used for the analysis in the JAMA paper differ methodologically from studies used to support the approval of paroxetine for major depressive disorder, so it is difficult to make direct comparisons between the results," spokeswoman Sarah Alspach said.

At least 27 million Americans take antidepressants, nearly double the number that did in the mid-1990s, according to a study by Columbia University and University of Pennsylvania researchers reported in the Archives of General Psychiatry.
More than 164 million prescriptions for antidepressants were written in 2008, totaling nearly $10 billion in U.S. sales, according to IMS Health. Global sales were twice that.

Study Information

Jay C. Fournier; Robert J. DeRubeis; Steven D. Hollon; Sona Dimidjian; Jay D. Amsterdam; Richard C. Shelton; Jan Fawcett
Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis
JAMA
2010 January
Departments of Psychology and Psychiatry, University of Pennsylvania, Philadelphia.

Full Study