The current investigators analyzed national healthcare claims from the US Medicaid program from 2001 to 2010 for 39,582 Medicaid beneficiaries (mean age, 44.5 years; 78.5% women) diagnosed with depression. Patients with alternative indications for anti-psychotic therapy, such as schizophrenia, psychotic depression or bipolar disorder, were excluded.

After a period of at least 3 months of treatment with a single antidepressant, more than half of the patients (56.6%) augmented their treatment with one of these atypical anti-psychotics: quetiapine, risperidone, aripiprazole or olanzapine. The remaining patients (43.4%) added a second antidepressant. The average chlorpromazine-equivalent starting dose for all atypical anti-psychotics was 68 mg/day, which increased to 100 mg/day during follow-up.

A total of 153 patients died during 13,328 person-years of follow-up, including 105 who augmented with an atypical anti-psychotic and 48 who augmented with a second antidepressant.

Compared with those who added a second antidepressant, those who added an anti-psychotic had a 45% increased risk of dying during follow up (adjusted hazard ratio,1.45; 95% CI, 1.02 – 2.06).

Antipsychotic Added to Antidepressant Linked to Higher Mortality – Medscape – Oct 07, 2020. https://www.medscape.com/viewarticle/938707?src=rss#vp_1