What is an adequate trial of an antidepressant?

Since there are many antidepressants with varying dosage ranges, and many more degrees of variations between individual responses to particular antidepressants, psychiatrists have been unable to agree upon an operational definition of an “adequate trial” of an antidepressant.

However, it’s worth looking at some guidelines.

A 2003 study from the Journal of American Medical Association found that only 21.7% of Americans diagnosed with depression received “minimally adequate treatment” in the past 12 months. This study, defined minimally adequate treatment as meeting one of the following 2 criteria:

  • 4 visits in 12 months with a physician, with a medication trial (antidepressant or mood-stabilizer) lasting at least 30 days
  • 8 psychotherapy or counseling visits (average duration 30 minutes) in 12 months.

Conventional wisdom states that antidepressants take 4-6 weeks to show effectiveness. Clearly, calling the above treatment “minimally adequate” is a stretch. However, conventional wisdom falls short too. It does not say anything about what to do after 4-6 weeks if patient shows no response, 25% response, or 50% response.

The best guideline to what may be constitute an adequate trial of an antidepressant comes from STAR*D, the largest real world study of depression treatment under in both primary care and psychiatric settings.

In this study, proven rating scales were used to monitor depression severity at each patient visit. Side effects and functioning were also monitored using rating scales.

Medication dose was changed frequently, sometimes once a month, depending upon response, or lack of it. Side-effects would also prompt a quick change. Patients were not left, for months at a time, on medication dosages or combinations that did not work.

Under these conditions, STAR*D found that,

  • about 1/3 of those achieving response (i.e. 50% improvement) needed more than 6 weeks to do so
  • about 1/2 of those achieving remission needed more than 6 weeks to do so
  • many patients not reporting or showing improvement globally show up to 45% reduction in symptom severity by 6 weeks
  • the likelihood of remission with SSRI alone is only 37% and in those who don’t respond to SSRI alone, this likelihood keeps decreasing with each increasing complicated medication regimen

Overall, STAR*D showed that really vigorous and assertive treatment with a tolerated antidepressant should last about 12 weeks. However, duration criteria will never be enough to judge adequacy of a trial of an antidepressant. Instead, we should judge an antidepressant trial to be adequate only if it meets all of the following criteria:

  • proven rating scales were used to monitor severity of depression and/or functioning
  • medication dosages & combinations were adjusted frequently depending upon response and side-effects
  • proven augmentation and combination strategies were used, if necessary
  • an adequately tolerated medication regimen (with above criteria being met) was used for at least 3 months

Without this kind of assertive treatment, I am afraid our patients will continue to suffer longer than they must.

Dheeraj Raina is a psychiatrist who practices at the Depression Clinic of Chicago.

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