Adverse drug reactions associated with psychotropic medications combined with versus without lithium: A case/control pharmacovigilance analysis

Background: We assessed the association between different adverse drug reactions (ADRs) and patients with versus without lithium co-medication using data from the European drug surveillance program AMSP (German: “Arzneimittelsicherheit in der Psychiatrie,” i.e. Drug Safety in Psychiatry) Methods: We conducted a case/non-case pharmacovigilance study using AMSP data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of severe ADRs from patients with versus without lithium co-medication calculating reporting odds ratios (RORs). Additional analyses included comparisons with distinct pharmacological classes, reports where the imputation grade for ADRs was probable or certain, and where ADR rates were related to exposed patients. Results: In 8609 patients, lithium-treated patients ( n = 720) were less often associated with weight gain, dyskinesia, suicidality (as an ADR), hyponatremia, and mortality, but more often associated with various types of neurotoxicity ( p < 0.05 in all cases). Parkinson’s symptoms (ROR 1.8), tremor (ROR 4.6), serotonergic ADRs (ROR 3.0), ataxia or myoclonus (each, ROR 2.7), as well as drug-drug interactions leading to intoxication (ROR 26.3, p < 0.05 in all cases). When stratifying by pharmacological class, hyponatremia was more frequent in patients receiving different pharmacological classes ( p < 0.05 in all cases), whereas neurotoxicity and lithium intoxications were more frequently reported in lithium comedication groups ( p < 0.05 in all cases). Conclusions: Patients treated with lithium are associated with a reduced reporting of hyponatremia, but to an increased reporting of neurotoxicity, although findings represent reporting associations, rather than incidence estimates or causal effects.