Diagnostic Considerations in Major Depressive Disorder With Psychotic Features

Male silhouette screaming behind a thin gray fabric (back lit studio shot).
Investigators sought to determine the prevalence of psychotic features in patients with major depressive disorder.

Investigators highlighted the need for adequate diagnosis of psychotic features in patients with major depressive disorder (MDD) during routine clinical care, according to study findings published in Journal of Clinical Psychiatry 1

Patients with MDD may present with psychotic features, including hallucinations and delusions. In these patients, neurobiologic findings, clinical characteristics, family medical history, and treatment response patterns have been reported to differ significantly from patients with non-psychotic MDD.2-8

This observational, cross-sectional study included 1410 adults 18 years and older who met the criteria for MDD9 and had received treatment from one of ten European tertiary centers between 2011 and 2016. Investigators evaluated the presence of psychotic features using the Mini-International Neuropsychiatric Interview. Using various rating scales, specialists from the referral centers collected clinical, pharmacologic, and sociodemographic data from participants. The investigators examined the association between these variables and the occurrence of psychotic features using binary logistic regressions.

Related Articles

Of the total participants, 10.92% exhibited psychotic features. Compared with patients who had non-psychotic MDD, those with psychotic features exhibited higher rates of suicide risk (60.39% vs 44.27%), inpatient treatment (55.84% vs 32.01%), melancholic features (73.38% vs 59.16%), augmentation or combination treatment strategies (81.17% vs 58.12%), and add-on therapy with antipsychotics (50.00% vs 22.69%) and benzodiazepines or benzodiazepine-like drugs (47.40% vs 31.29%).

Patients with MDD with psychotic features also had a more than 2.2-fold higher likelihood for treatment resistance than those without (79.87% vs 35.75%). Only 3.25% of the patients with psychotic MDD achieved treatment response, compared with 27.15% of patients who had non-psychotic MDD. There were no significant sociodemographic differences between patients with psychotic and non-psychotic MDD.

Study limitations include a lack of diversity in study participants; 96.17% of the participants were white. Most of the patients were recruited from academic psychiatric treatment centers, and patients with recent substance disorders were excluded from the study. Results might not represent MDD populations in primary care settings. In addition, the ≥4-week antidepressant treatment period before study entry might not have been long enough for patients suffering from psychotic depression to achieve sufficient treatment response.

Further research projects could identify biomarkers or use neuroimaging techniques to differentiate patients with psychotic MDD from patients without psychotic symptoms earlier in the course of the disease, the investigators concluded. “Subsequently, patients could receive appropriate treatment in the early phase of their depressive episode.”


1.Dold M, Bartova L, Kautzky A, et al. Psychotic features in patients with major depressive disorder: a report from the european group for the study of resistant depression. J Clin Psychiatry. 2019;80(1).

2.Schatzberg AF, Rothschild AJ. Psychotic delusional major depression: should it be included as a distinct syndrome in DSM-IV? Am J Psychiatry. 1992;149(6):733-745.

3.Simpson S, Baldwin RC, Jackson A, et al. The differentiation of DSM-III-R psychotic depression in later life from nonpsychotic depression: comparisons of brain changes measured by multispectral analysis of magnetic resonance brain images, neuropsychological findings, and clinical features. Biol Psychiatry. 1999;45(2):193-204.

4.Cubells JF, Price LH, Meyers BS, et al. Genotype controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression. Biol Psychiatry. 2002;51(5):358-364.

5.Nelson JC, Davis JM. DST studies in psychotic depression: a meta-analysis. Am J Psychiatry. 1997;154(11):1497-1503.

6.Coryell W, Leon A, Winokur G, et al. Importance of psychotic features to long-term course in major depressive disorder. Am J Psychiatry. 1996;153(4):483-489.

7.Østergaard SD, Bille J, Søltoft-Jensen H, et al. The validity of the severity-psychosis hypothesis in depression. J Affect Disord. 2012;140(1):48-56.

8.Glassman AH, Roose SP. Delusional depression: a distinct clinical entity? Arch Gen Psychiatry. 1981;38(4):424-427.

9.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth edition, text rev. Washington, DC: American Psychiatric Association; 2000.