Bicyclic Antidepressants - Therapeutic Efficacy

Therapeutic Efficacy

To establish efficacy, an antidepressant must show that it can produce a therapeutic effect for the condition for which it is taken. Antidepressants efficacy should outperform placebo to justify the risk associated with side effects. For depression, the Hamilton Depression Rating Scale (HAM-D) is often used as the metric used to rate the severity of depression. The maximum score for the 17-item HAM-D questionnaire is 52; the higher the score, the more severe the depression. What constitute an sufficient response to a drug has not been well established, but total remission or virtual elimination of all depression symptoms is the goal, however, remission rates are rarely published. For placebo, the percentage of symptom reduction is approximately 31 to 38%, compared to 46 to 54% for antidepressants.

On the basis of 234 studies, no clinically relevant superiority of one antidepressant over another was detected for the treatment of acute, continuation, and maintenance phases of depression, based on age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of health-related quality of life.

The largest and most expensive study conducted to date, on the effectiveness of pharmacological treatment for depression,was commissioned by the National Institute of Mental Health. The study was dubbed "The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. The results are summarized here.

• After the first course of treatment, 27.5% of the 2,876 participants reached remission with a HAM-D score of 7 or less. 21% dropped out.
• After the second course of treatment, 21 to 30% of the remaining 1,439 participants remitted. Only 310 participants were willing or available to continue the study., Switching medications can achieve remission in about 25% of patients.
• After the third course of treatment, 17.8% of the remaining 310 participants remitted.
• After the fourth and last course of treatment, 10.1% of the remaining 109 participants remitted.
• After a one year follow-up, of the 1085 remitted participants, 93% participants had either relapsed or dropped out of the study.

There were no statistical or meaningful clinical differences in remission rates, response rates, or times to remission or response among any of the medications compared in this study. These included bupropion sustained release, bupropion, citalopram, lithium, mirtazapine, nortriptyline, sertraline, triiodothyronine, tranylcypromine, venlafaxine extended release.

A 2008 review of randomized controlled trials concluded that symptomatic improvement with SSRIs was greatest by the end of the first week of use, but that some improvement continued for at least 6 weeks.

It has been suggested that the poor outcome of antidepressants is because depression is really a cluster of illnesses of different etiologies all exhibiting similar symptoms. The definition of major depressive disorder may be misguided.

Do antidepressants address the underlying causes of depression? A 2002 review concluded that there was no evidence that antidepressants reduce the risk of recurrence of depression when their use is terminated. The authors of this review advocated that antidepressants be combined with therapy, and pointed to Interpersonal Psychotherapy (IPT) and Cognitive Behavioral Therapy (CBT).