Mood-switching from depression into [hypo]mania is prevalent in bipolar disorder (BD) patients, particularly during treatment with an antidepressant, but many characteristics associated with such responses require clarification. Using standard bivariate and multivariate measures we compared characteristics of 1629 prospectively evaluated BD patients who did or did not become [hypo]manic during antidepressant treatment. Mood-switching occurred in 27.6% of BD patients (type II [BD2]: 31.4%; type I [BD1]: 24.5%) observed prospectively for 4.98 years, most often (65.5%) with new hypomania. Factors preliminarily associated with switching, ranked by statistical significance, included: DMI course, depressive first-episode, BD2 diagnosis, rapid-cycling, family psychiatric history, intake depression score, lithium treatment, less substance abuse, married, general-medical comorbidity, suicide attempts, older at onset and currently, more years ill, more recurrences/year and greater %-time ill (especially in depression), less co-occurring ADHD, and more children. By multivariable logistic regression modeling five factors significantly and independently associated with switching, ranked: DMI-course, older age, more episodes/year, more psychiatric family history, and suicide attempts. Limited ethnic diversity, single-country setting, and observational design may affect the generalizability of these findings and limit causal inference. Switching was significantly and independently associated with: DMI course, older age, more episodes/year, psychiatric family history, and suicide attempts. It remains unclear how to distinguish reliably antidepressant-associated from spontaneous mood-switching.
Psychol Med. 2026 Apr 27;56:e112. doi: 10.1017/S0033291726103444.ABSTRACTBACKGROUND: The positive valence systems (PVS) domain, a key focus of the Research Domains Criteria framework, divides reward-related processes...
