Give antidepressants at least a month to work

An antidepressant should be taken for at least a month before deciding it's ineffective, researchers have concluded based on a data they published online May 31st in the Journal of Clinical Psychiatry.

"There is very little empirical data to guide clinicians as to what an adequate antidepressant should be, though we do know that a substantial percentage of patients who show no improvement through 4, 6, or even 8 weeks of treatment will nevertheless improve if the antidepressant regimen is continued for several weeks more," said Dr Michael A. Posternak from Comprehensive Psychiatric Associates, Wellesley, Massachusetts said.

"Complicating the equation further, patients in clinical practice frequently become impatient if no improvement has occurred after many weeks of treatment."

The study

Dr Posternak and colleagues analysed the results of a 12-week trial with fluoxetine in 627 subjects with major depressive disorder in an effort to determine the likelihood that patients will respond to continued antidepressant therapy when little or no benefit has yet been observed.

"There is little reason to believe these findings would differ with other antidepressants with different mechanisms of actions," Dr Posternak said.

In particular, the researchers sought to determine the proportion of patients who ultimately responded at week 6, 8, or 12 in the subset of subjects who had never demonstrated a partial or full response in any prior week.

The findings

By week 6, 17% of patients who had demonstrated no improvement through the first 4 weeks of treatment had converted to a positive response.

At week 8, 23% of patients who demonstrated no improvement through the first 4 weeks of treatment and 10% of patients who demonstrated no improvement through the first 6 weeks had converted to a positive response.

By the week 12 end point, half the patients who demonstrated no improvement through the first 4 weeks of treatment, a third of those who demonstrated no improvement through the first 6 weeks, 30% of those who demonstrated no improvement through the first 8 weeks, and 10% of those who demonstrated no improvement through the first 10 weeks had converted to a positive response.

For subjects who were unimproved through 10 weeks, the likelihood of converting to a positive response with exactly 2 more weeks of treatment remained relatively consistent, between 10% and 20%.

"This provides some justification for extending antidepressant trials beyond the traditional 4 to 6 weeks," the researchers note. "However, the question treaters face in these situations is not whether some subjects might respond to continued treatment, but whether extending an antidepressant trial is the best course of action."

Unfortunately, based on the current research, they say, the question has no ready answer.

Antidepressant therapy

"While many patients may respond quickly to antidepressant therapy - even during the first week of treatment - others take much longer," Dr Posternak said. "Therefore, clinicians should instruct patients to remain on their antidepressant as long as it is tolerated and for at least for one month."

"Clinicians should also make sure to see patients back within two to four weeks of initiating an antidepressant to review side effects, monitor compliance, and to discuss with patients the best way to proceed," he said. "In fact, having regular check-ins after initiating antidepressant therapy has been shown to significantly improve response rates."

"Because there is no 'one size fits all' approach, it is imperative to engage in frequent discussions with patients after initiating antidepressant therapy," Dr Posternak concluded. "This minimises the risk that patients may become discouraged, and allows patients to collaborate in choosing among several reasonable treatment options."

Two of the 4 authors of the paper report extensive potential conflicts of interest with numerous manufacturers of antidepressant and other psychoactive medications. (Reuters Health)

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