Background: Approximately 15-25% of depressed patients suffer from difficult-to-treat depression (DTD). Patients with DTD require a thorough examination to avoid the oversight of treatable (psychiatric/somatic) comorbidities or (pseudo-)resistance to antidepressant drugs (ADs). Polymorphisms of the cytochrome P450 (CYP) enzymes 2D6 and 2C19, which play a major role in the metabolism of ADs, may contribute to resistance to ADs. Patients with DTD might benefit from electroconvulsive therapy (ECT).

Methods: We enrolled 109 patients with DTD and 29 untreated depressed controls (UDC). We assessed risk phenotypes, comorbidities, and treatment, including ECT. We also performed pharmacokinetic analyses of CYP2D6 and CYP2C19.

Results: DTD patients significantly more often suffered from comorbid psychiatric diseases, especially ICD-10: F40-F48 (DTD:40.4%, UDC:17.2%, OR 11.87, =0.011) than UDC patients. DTD patients receiving ECT were more likely to achieve remission (37.7% vs. 11.8%, OR=3.96, =0.023). Treatment with ADs did not differ between remitters and non-remitters. No significant differences were observed in the distribution of and variants between both groups.

Conclusion: Patients with DTD appear to experience comorbid neurotic stress and somatoform disorders (ICD-10: F40 - F48) more frequently. Therefore, a comprehensive differential diagnosis is crucial when patients do not respond sufficiently to antidepressant medication. Genotyping and should be considered.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233224PMC
http://dx.doi.org/10.1055/a-2292-1438DOI Listing

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