Can the Effects of Antidepressants Be Observed in the First Two Weeks of Treatment?

Abstract

Recently the claim that there is a lag in the time of onset of antidepressant effects has been questioned. This issue rests on contrasting the time course of ultimate responders versus nonresponders on imipramine and amitriptyline. It is concluded that in 1 week on antidepressants "clinicians were capable of detecting changes in general states between the groups and the specific effects of depressed mood and anxiety and the physical expression of distress" (Katz et al. 1987). To examine this issue, we first used the design in which ultimate responders and ultimate nonresponders to antidepressants were compared at 1 and 2 weeks. Clearly there were statistically significant differences between ultimate responders and nonresponders on drug. However, the same was true on placebo. When the ultimate responders on placebo were contrasted to the ultimate responders on drug at 1 and 2 weeks using the Clinical global Impression (CGI) scale and the Hamilton Depression Rating Scale (HDRS), there was no difference between drug and placebo. This was also true for a subgroup of patients who met the criteria for melancholia. We conclude that, if the effects of nonspecific improvement are partialed out, there is no evidence of a medication effect at 1 and 2 weeks.

Early response and 8-week treatment outcome in GAD

“…More recently several authors reported that improvement observed after 1 week of treatment predicted patient response to clozapine [Stern et al, 1994] and haloperidol [Harvey et al, 1991;Stern et al, 1993]. Similar findings are evident in the depression literature [Coryell et al, 1982;Mitchell et al, 2000;Nierenberg et al, 1995Nierenberg et al, , 2000Quitkin et al, 1996;Szegedi et al, 2003]. Nierenberg et al [1995], for example, reported that more than half of all fluoxetine responders [defined as a change 450% in the Hamilton Depression Scale (HAM-D)] at 8 weeks had already responded by week 2, and the authors concluded that nonresponse to treatment as early as week 2 predicts 8-week outcome.…”

Early response in psychotherapy: Further evidence for the importance of common factors rather than “placebo effects”

“…This placebo response has been linked to poorer long-term outcomes, particularly relapse during follow-up of patients treated with antidepressant medications. Several studies have investigated this possibility and support the contention that a "premature" drug response (one that occurs before a therapeutic dose has been administered) foretells poor longterm therapeutic outcomes (Quitkin, McGrath, Stewart, Taylor, & Klein, 1996;Quitkin et al, 1987;Quitkin, Rabkin, Ross, & McGrath, 1984;Stewart et al, 1998). Few studies have investigated the timing of response in psychotherapy with the intent of understanding the active ingredients of treatment and the place of common and unique therapeutic factors.…”

Do early responders to psychotherapy maintain treatment gains?

“…Several studies have investigated this possibility and support the contention that a premature drug response foretells poor long-term therapeutic outcomes (Quitkin, Rabkin, Ross, & McGrath, 1984;Quitkin et al, 1987;Quitkin, McGrath, Stewart, Taylor, & Klein, 1996;Stewart et al, 1998).…”