Reducing relapses for patients with psychotic depression

Have you or has someone you know had psychotic depression? This recent paper uncovered important findings that could change how we treat psychotic depression and help avoid relapses.

@UofTPsych Vice Chair of Basic and Clinical Science Krista Lanctot (@KristaLanctot) interviewed lead author Dr. Alastair Flint to learn more.

KL: What is psychotic depression?

AF: Psychotic depression is depression with fixed false beliefs (delusions) or sometimes false perceptions (hallucinations).  The delusions frequently match the depressed mood, with themes such as guilt, poverty, sickness, hopelessness, and emptiness. Psychotic depression can be severe. Interestingly, older adults are more likely to experience psychotic depression than younger adults.

KL: What motivated this research in psychotic depression?

AF: A combination of 2 medications for psychotic depression is common. My colleagues and I previously found that an antidepressant (sertraline) plus an antipsychotic (olanzapine) were better than olanzapine alone. Importantly, this was true in both older and younger adults.

However, it was unknown whether both medications needed to be continued after improvement. This was a very important clinical question that needed to be answered since continuation and adverse effects needs to be balanced with the possibility of early relapse.

KL: What did you do?

AF: This study assessed the risks and benefits of continuing both medications together once psychotic depression has responded. We followed 126 people with psychotic depression who had improved for at least 8 weeks who volunteered for this study. Half the group continued olanzapine, while the other half had placebo slowly substituted for the olanzapine. Participants were then followed for 36 weeks to determine the risk of relapse and measures of tolerability.

KL: What did you find?

AF: The 2 medications together (sertraline plus olanzapine) reduced the risk of relapse to 1 in 5 compared to continuing just sertraline, where over half relapsed. For tolerability, the combination was associated with weight gain (average 6 lbs) but no increase in cholesterol, triglycerides, or blood sugar.

KL: How does this change treatment?

AF: We now know that after an episode of psychotic depression that has remitted with a combination of sertraline plus olanzapine, continuing the antipsychotic is necessary to decrease the risk of relapse. 

However, this study was not designed to answer the more precise question of how long to continue antipsychotic medication following improvement. A conservative approach would be to continue the combination for 6 months following remission, before deciding on whether to try slowly withdrawing the antipsychotic (whilst continuing the antidepressant) at that point.

KL: What's next?

AF: Importantly, 45% of participants treated with sertraline only did not experience a relapse and benefited from a decline in weight. Next, we will identify how to predict if it’s safe for a patient to begin decreasing the dosage of antipsychotic medications that they’re taking.


IMPACT Committee includes Krista Lanctôt, Alastair Flint, Meng-Chuan Lai and Simone Vigod.

This article profiles Dr. Flint’s paper based on his plenary presentation at Harvey Stancer Research Day, where it was identified as one of the highest impact papers in 2019 in the Department of Psychiatry.

Flint AJ, Meyers BS, Rothschild AJ, Whyte EM, Alexopoulos GS, Rudorfer MV, Marino P, Banerjee S, Pollari CD, Wu Y, Voineskos AN, Mulsant BH, on behalf of the STOP-PD II Study Group. Effect of continuing olanzapine versus placebo on relapse among patients with psychotic depression in remission: the STOP-PD II randomized clinical trial. Journal of the American Medical Association, 2019, 322(7): 622-631