Mixed features in depressive and bipolar disorders: An updated systematic review

Mixed features in mood disorders are widely recognized but prevalence estimates are inconsistent, leading us to update of our 2018 systematic review of mixed features in major depressive disorder (MDD) and bipolar disorder (BD).

We systematically searched 5 databases for reports on adults with episodes of BD or MDD assessed for mixed features by DSM-5 definitions or ≥3 opposite-polarity features. Data were extracted thrice independently, and pooled prevalence rates calculated with confidence intervals (95 % CI).

We identified a total of 26 studies from 5 world regions, reporting on mixed features in 3107/17,164 MDD episodes (18.1 %; [CI: 17.5-18.7]), 1886/5750 BD-depressions (32.8 % [31.6-34.0]), and 721/2069 BD-[hypo]manic episodes (34.8 % [32.8-36.9]). Mixed features were thus nearly twice as frequent in BD versus MDD and similar with BD depression and [hypo]mania. Rates varied markedly by diagnostic criteria: ≥3 opposite-polarity features yielded higher prevalence than DSM-5 criteria (MDD: 23.8 % vs. 3.60 %; BD-depression: 35.0 % vs. 29.3 %; BD-[hypo]mania: 36.9 vs. 31.2 %).

Heterogeneous study-design and definitions, with under-representation of some world regions, may affect generalizability.

Mixed features were prevalent in mood disorders, particularly in BD, but rate-estimates depend strongly on diagnostic criteria. Harmonization of definitions is required to support prognostic and therapeutic implications.