Adjuvant valproate therapy for patients with suspected mixed-depressive features

Mixed-depressive features imply an occult bipolarity and might be linked to resistance to antidepressant therapy and a higher risk of suicide. Currently, there is no consensus about or any clinical guidelines available for this ill-defined clinical entity. The aim of this study was to assess the effectiveness, safety, and tolerability of mood stabilizers, such as valproate, for adjuvant therapy in patients suspected of having mixed-depressive features.

This retrospective observational study reviewed medical records of psychiatric outpatients attended by the author from 2008 to 2013. Patients who presented with inadequately treated, long-lasting atypical depressive- and/or anxiety-spectrum symptoms, and who started adjuvant valproate therapy for the first time in their course of treatment, were identified. Patient demographics, clinical profiles, treatment responses, and treatment-emergent adverse events (AEs) were examined in detail.

A total of 22 patients (7 men and 15 women) ranging in age between 25 and 78 years were treated with valproate 100-1250 mg/day and observed for 3-60 months. The majority exhibited much or moderate improvement, and only four showed a limited response. During follow up, 12 continued adjuvant valproate, 3 were intermittent users, and 3 quit after no apparent response; 4 experienced an aggravation of symptoms after discontinuation but were stabilized soon after reinstitution. AEs were reported by 12 patients and 4 stopped valproate for intolerability despite improvement.

Adjuvant valproate therapy seems to be a promising approach to treating patients who manifest atypical neurotic or mood disorders with subthreshold bipolarity at a dosage around the lower end of that used to treat full-syndromal bipolar disorders.