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Patients with psychotic MDD at higher risk for psychosis in future episodes

Results from a systematic review and meta-analysis suggest that patients with current psychotic depression were at much higher risk for future psychotic depressive episodes than those with currently nonpsychotic MDD.

“Researchers have suggested that psychotic depression is a distinct subtype of depression that is semi-independent of severity,” J. Craig Nelson, MD, of the University of California, San Francisco, and colleagues wrote. “[Prior study] found that psychotic depression had greater stability over the course of episodes than other subtypes of depression. Although other authors have examined this question, we are not aware of any systematic reviews of this issue.”

Researchers conducted a systematic review of the literature and meta-analysis assessing the course of psychotic depression and the frequency of psychosis to determine whether the risk for psychosis was higher in previous or later episodes in patients with psychotic or nonpsychotic major depression.

The investigators searched PubMed, Embase, and PsycINFO to identify English-language studies that included patients with unipolar major depression, made diagnoses of psychosis based on reports of delusions or hallucinations and distinguished previous or later episodes as psychotic or nonpsychotic. Then they conducted two meta-analyses using data from patients who experienced index depressive episodes with or without psychosis at study entry to examine the risk for any prior or subsequent psychotic episode and the risk for psychosis in all episodes.

Twelve studies encompassing 546 psychotic and 1,583 nonpsychotic patients with major depression were included in this analysis. Of these, seven studies reported the risk for a previous or later psychotic episode in patients with a psychotic index depressive episode was nearly 10 times higher than patients with a nonpsychotic index episode (RR = 9.98; 95% CI, 4.75-20.94). There was also significant heterogeneity (I² = 80%; P < .001). The simple pooled risk for a patient having at least one psychotic episode was 65.3% for those with index psychotic episodes vs. 5.1% for those with nonpsychotic episodes.

In eight studies that examined the risk for psychosis among all episodes of depression across subgroups with psychotic and nonpsychotic index episodes, the total risk ratio was 7.24 (95% CI, 5.03-10.43). The heterogeneity was moderate and significant (I² = 54%; P = .03). The total percentage of psychotic episodes was 64% in the those with psychotic index depressive episodes and 6.1% in those with nonpsychotic episodes, according to the researchers. When examining potential sources of heterogeneity, differences in risk for psychosis between these subgroups stayed robust.

“The studies identified in this systematic review convincingly demonstrate that patients with psychotic major depression are at much higher risk for subsequent psychotic depressive episodes than patients with a psychotic index episode of major depression and that psychotic major depression runs ‘true to form,’” the authors wrote. “This finding supports the distinct nature of the subtype. If future episodes are likely to be psychotic, determination of the appropriate preventive treatments will be important.” – by Savannah Demko

Disclosures: Nelson reports serving as a consultant or advisor to Assurex, Corcept, Eisai, Janssen, Lundbeck, Otsuka and Sunovion, and receiving research supplies from Avid. Please see the full study for all other authors’ relevant financial disclosures.