Sudden Symptomatic Improvement Predicts Response to Antidepressant Therapy

older woman holding pills
elderly woman holding pills in hand
Recent evidence suggests that early sudden improvements have lasting effects and occur in most patients receiving antidepressants.

Sudden responses to antidepressants occur in approximately one-third of patients and can result in stable gains, even in a geriatric population, according to an article published in the Journal of Clinical Psychiatry.

True response to antidepressant therapy has long been held to occur incrementally, during a period of several weeks or more, and sudden responses that occur early during the course of a clinical trial are thought to be transient and characteristic of a placebo response. Yet despite the persistence of this idea, there is little evidence to support it. In fact, recent evidence suggests that early sudden improvements have lasting effects and occur in most patients receiving medication.

Sigal Zilcha-Mano, PhD, from the Department of Psychology, University of Haifa, Mount Carmel, Israel, and colleagues analyzed data collected during 1999 to 2002 from 174 patients who were aged 75 years or older who had unipolar depression and who had been randomly assigned to citalopram or placebo to evaluate the occurrence and effects of abrupt improvements in symptoms. Using chi-square analyses and linear regression models, the investigators tested differences between conditions in the prevalence of sudden gains and their effect on outcome.

The authors found that 36.2% of patients experienced sudden and stable improvements. The mean reduction in the Hamilton Depression Rating Scale score was 7.2 points. Patients with more severe pretreatment depression and higher processing speeds were more likely to experience sudden gains. Patients experiencing sudden gains were more likely to demonstrate better treatment outcome, as defined by changes in Hamilton Depression Rating Scale score from pre- to posttreatment. This outcome remained significant even after adjusting for pretreatment depression severity and processing speed (P <.0001). The mean Hamilton Depression Rating Scale reduction was 14.8 for those with sudden gains compared with 7.6 for those without sudden gains. Individuals who experienced sudden gains had a 66.7% chance of being treatment responders, whereas those who did not experience sudden gains had a 76.6% chance of being nonresponders. Sudden gains occurred most often in the first 4 weeks of treatment, and most particularly during the second week of treatment.

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The authors suggest that these findings should prompt greater attention to the timing of symptom response in depression studies.


Zilcha-Mano S, Roose SP, Brown PJ, Rutherford BR. Abrupt symptom improvements in antidepressant clinical trials: transient placebo effects or therapeutic reality? J Clin Psychiatry. 2018;80(1):18m12353.