Psychotic Symptoms in Unipolar and Bipolar Depression and Their Impact on Disease Prognosis: A Systematic Review

Psychotic depression (PD) is a severe form of depression that can occur in both major depressive disorder (MDD) and bipolar disorder (BD). Although relatively prevalent, the prognostic impact of psychotic symptoms in depression remains controversial.

To systematically review the available evidence comparing PD and non-psychotic depression (NPD) in terms of clinical course, functional outcomes, and treatment outcomes.

A systematic search of electronic databases (PubMed, Cochrane Library and Web of Science) following PRISMA guidelines was conducted from inception to 31st January 2025 to integrate current evidence about the impact of psychotic symptoms in both unipolar and bipolar depressed patients. This study was registered in PROSPERO (CRD42024563172).

Fourty-one studies met inclusion criteria. Compared to NPD, PD was associated with greater clinical severity, longer hospitalizations, and higher inpatient treatment rates. Several studies showed lower remission rates and greater chronicity in PD. Relapse, readmission, or shorter time to recurrence were also more common in PD. Evidence indicated a higher risk of suicide and poorer functional outcomes in PD. Treatment patterns showed more frequent use of ECT and pharmacological combinations in PD, although no consistent drug-specific differences emerged. Overall, heterogeneity across designs and outcome measures was substantial.

Despite heterogeneity, evidence across 41 studies indicates that PD is a higher-risk depressive subtype, characterized by greater service use, higher relapse liability, lower sustained remission, increased suicidality, and poorer functioning. These findings support the need for intensified assessment and management and highlight the importance of large, standardized prospective studies, especially in BD.