Suicidal Ideation Linked to Major Depressive Disorder Despite Antidepressant Therapy

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Approximately one in five patients with major depressive disorder experienced an episode of high or fluctuating suicidal ideation despite treatment with nortriptyline or escitalopram.

In patients with major depressive disorder (MDD), high or fluctuating suicidal ideation was common despite antidepressant therapy with nortriptyline or escitalopram, according to study results published in the Journal of Clinical Psychiatry.

Researchers conducted a secondary analysis of data from the Genome-Based Therapeutic Drugs for Depression study, a multicenter randomized clinical study of 811 patients with MDD treated with nortriptyline or escitalopram for 12 weeks. The team utilized item response theory to incorporate a suicidality measure using three different rating scales. In the analysis, latent growth mixture modeling and multinomial logistic regression were used to detect trajectories of suicidal ideation and to measure associations with possible predictors.

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After analysis, the researchers found that approximately one in five patients experienced an episode of high or fluctuating suicidal ideation, despite antidepressant therapy. In total, five specific classes of suicidal ideation were detected. The persistent-high (9.8%) and persistent-low (53.7%) classes exhibited high and non-existent suicidal ideation over 12 weeks, respectively. The fluctuating class resulted in a low level of suicidal ideation (5.3%) and the slow-response-relapse (4.8%) class experienced a large increase of high suicidality. The final class, fast-response, exhibited high baseline severity but responded quickly to treatment.

“Previous suicide attempts and higher mood symptom severity were associated with worse suicidal ideation trajectories,” the researchers wrote.

One key study limitation was the lack of biomarker analysis in the predictive models.

“[Future] studies should investigate whether suicidal ideation may persist for longer periods and more targeted treatment possibilities,” they concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Madsen T, Buttenschøn HN, Uher R, et al. Trajectories of suicidal ideation during 12 weeks of escitalopram or nortriptyline antidepressant treatment among 811 patients with major depressive disorder. J Clin Psychiatry. 2019;80(4):18m12575.