Patients with psychotic disorders often suffer from intercurrent major depressive episodes (MDEs). Case reports suggested successful antidepressive treatment with duloxetine, a selective dual reuptake inhibitor of serotonin and norepinephrine (SSNRI). We initiated this open prospective clinical trial in order to evaluate efficacy, safety and tolerability of this approach.

Patients with a psychotic lifetime diagnosis suffering from mildly severe MDEs were treated with duloxetine over a period of 6 weeks. We evaluated effects on mood, monitored the psychotic psychopathology and assessed side effects, basal clinical and pharmacological parameters.

Twenty patients were included and experienced a significant improvement of their MDE during the observation period (CDSS: Calgary Depression Scale for Schizophrenia, HAMD: Hamilton Depression scale). Psychotic positive symptoms remained stably absent while negative syndrome and global psychopathology considerably improved (PANSS: Positive and Negative Syndrome Scale). In general, the treatment was well tolerated, serum prolactin levels stayed unchanged, but pharmacokinetic interactions with a number of antipsychotic agents were observed.

This open prospective evaluation revealed antidepressive efficacy of duloxetine in patients with co-morbid psychotic disorders. With regard to the psychotic disorder, the treatment appears to be safe and well tolerable. Further investigations should involve a randomized control group.