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Randomized Controlled Trial
. 2024 Apr;54(6):1172-1183.
doi: 10.1017/S0033291723003008. Epub 2023 Oct 20.

Effect of next-step antidepressant treatment on suicidal ideation: findings from the VAST-D trial

Sidney Zisook  1   2 , Christine Yu Moutier  3 , A John Rush  4   5 , Gary R Johnson  6 , Ilanit Tal  2 , P J Chen  7 , Lori L Davis  8 , Paul B Hicks  9 , James Wilcox  10 , Beata Planeta  6 , Kimberly Weingart Lauro  2 , Alexandra A Scrymgeour  11 , John Kasckow  12 , Somaia Mohamed  13
Affiliations
Randomized Controlled Trial

Effect of next-step antidepressant treatment on suicidal ideation: findings from the VAST-D trial

Sidney Zisook et al. Psychol Med. 2024 Apr.

Abstract

Background: Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a 'next-step'. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted.

Method: The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored.

Results: Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to 'next-step' treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI.

Conclusion: SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Keywords: VA Augmentation and Swritching Treatments for Depression (VAST-D) study; antidepressant medications; difficult to treat depression; major depressive disorder; next-step treatments; safety; suicidal ideation; suicidal thoughts and behaviors; suicide; suicide risk; treatment emergent suicidality; treatment resistant depression.

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