Review of: Lintunen J et al, J Affect Disord 2023;333:403–408

Study Type: Retrospective cohort study

People with bipolar disorder vote with their feet when it comes to medication adherence. This study tallied those votes, using data from a large national pharmacy database.

Researchers enrolled 33,131 patients from Finland’s national health records database who were under age 65 and diagnosed with bipolar disorder between 1987 and 2018. Patients were included if they were prescribed mood stabilizers (lithium, valproic acid, or carbamazepine) or antipsychotics (27 agents were included) between 2015 and 2018. 

The primary outcome was nonadherence, which was defined as either 1) at least one medication not dispensed or 2) at least 20% of prescribed medication not dispensed. Researchers controlled for age, sex, time since bipolar disorder diagnosis, and number of previous hospitalizations due to bipolar disorder. They also controlled for other comorbidities, including mental health conditions like substance use disorder, anxiety, and personality disorders, as well as physical conditions like diabetes, cancer, and cardiovascular disease. These are worthy attempts, but without randomization the study cannot control for all the variables that may have skewed the results.

Around one in three patients were nonadherent to at least 20% of prescribed medication, and nearly twice that (59.1%) had at least one non-dispensed medication. Lithium fared best among the mood stabilizers, with 11.3% not dispensed, compared to at least 14% for the other mood stabilizers. Clozapine came out on top among antipsychotics, with 9% not dispensed, compared to 13.5%–31.4% for other antipsychotics (clozapine is used off label for treatment-resistant bipolar I disorder, and rates of clozapine prescription are higher in Finland than in other countries).

Risks for nonadherence included psychiatric comorbidities, younger age (under 25), recent onset (diagnosis within past three years), benzodiazepine usage, and multiple hospitalizations (four or more). 

Previous studies have found nonadherence rates of 20%–60% in bipolar disorder, often relying on problematic measures of self-report. Using a more objective measure, this study arrived at the high end of that range (59.1%), but this still may underestimate the problem. Just because a prescription is filled doesn’t mean it is taken. 

CARLAT TAKE

Surprisingly, lithium and clozapine had the highest rates of adherence in this study, countering their reputation as difficult medications that are burdened by stigma, side effects, and lab draws.