Prevalence of dermatologic side effects of mood stabilizers in bipolar disorder: A systematic review and meta-analysis

Background: Mood stabilizers are commonly used in bipolar disorder (BD) but are often associated with dermatologic adverse events (AEs). This systematic review and meta-analysis investigated the prevalence and types of dermatologic AEs associated with mood stabilizers in patients with BD. Methods: We searched Ovid MEDLINE®, Embase, Cochrane Library, Web of Science, Scopus, and PsycINFO from 1970 for studies on dermatologic AEs in BD patients treated with lithium, valproate, carbamazepine, or lamotrigine (CRD42022357268). Two reviewers handled study selection, data extraction, and bias risk assessment. Meta-analyses estimated prevalence rates for dermatologic AEs. Results: Out of 6980 studies identified, 50 met the inclusion criteria. Lithium was associated with acneiform eruptions in 4.2 % (95 % CI: 1.0-16.2 %), rash in 1.3 % (95 % CI: 0.4-4.3 %), and hair loss in 1.9 % (95 % CI: 0.5 %-6.3 %) of patients. For valproate, hair loss was observed in 4.6 % of patients (95 % CI: 3.0-6.7 %) and rash in 2.9 % (95 % CI: 1.6-5.3 %). Carbamazepine was associated with rash in 6.0 % of patients (95 % CI: 4.4-7.6 %), but severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrosis were not reported. Lamotrigine had the highest rash prevalence with 9.2 % (95 % CI: 7.2-11.8 %), while severe reactions were rare (0.04 %, 95 % CI: 0.00-0.62 %). Limitations: Heterogeneity in study designs and outcome definitions, reliance on self-reporting or assessments by non-dermatologists, frequent use of concomitant medications. Conclusions: Mood stabilizers showed varying levels of dermatologic AEs, but severe reactions were rare. Future studies should explore factors influencing these outcomes, their impact on quality of life and treatment participation, and potential management strategies.