USPSYCH: Antidepressants May Work More Quickly Than Thought

NEW ORLEANS, Nov. 22 -- Research has challenged the conventional wisdom that depressed patients need three to four weeks to respond to antidepressant medication and that any earlier response is due to the placebo effect, said an investigator here.

Measurable non-placebo responses may occur during the first week of treatment, studies published last year suggest, said Ronald W. Pies, M.D., of the Tufts New England Medical Center in Boston, at the U.S. Psychiatric & Mental Health Congress here.

Previous studies, some published in the 1980s, found that while a placebo response was evident at week one and continued unabated, a true drug response did not appear until at least week three. Almost no drug-placebo separation occurred before three weeks, Dr. Pies said.

However, more-recent research has uncovered a different pattern. One meta-analysis published last year included 47 double-blind trials of antidepressants. The trials included more than 5,000 patients on active drug and more than 3,000 patients on placebo. Drugs used included selective-serotonin reuptake inhibitors (SSRIs), tricyclics, and heterocyclics, Dr. Pies said.

This meta-analysis found that 57% of the drug-placebo separation occurred during the first two weeks of treatment. The magnitude of improvement in symptoms diminished after two weeks in both the active treatment and placebo patients, Dr. Pies said.

Other studies published in 2005 found that the best predictor of long-term response to antidepressant drugs was in fact the degree of symptom improvement during the first two weeks, Dr. Pies said.

These findings raise the question of whether physicians should be switching antidepressant drugs sooner, rather than having patients bear the cost of four to six weeks on a drug that isn't working after the first two weeks, Dr. Pies said.

However, Dr. Pies said, .the newer data does not exclude the possibility that the full drug benefit might take longer to emerge -- perhaps three to 10 weeks.

In addition, although the meta-analysis found statistically significant improvements in depressive symptoms, these may not translate to robust, clinically significant changes in the real world, Dr. Pies said.

Furthermore, some symptoms of depression may improve quickly with treatment while others take longer. For example, guilt and anxiety may improve during the first week of treatment, but libido and insomnia might not improve until nine weeks of treatment, Dr. Pies said.

"Therefore, waiting three to four weeks to asses a patient's response to an antidepressant is still reasonable," Dr. Pies said.

However, a patient reporting symptom improvement extremely early -- within two to 48 hours of treatment-is likely to be experiencing a placebo response, he said.

And it is important to realize that comprehensive recovery from depression takes time -- perhaps four or more months, Dr. Pies said.