Lithium Prescription in Unipolar Depression: Findings from a Nationwide Greek Cohort Study

INTRODUCTION: Lithium is a well-evidenced option for treatment-resistant unipolar depression. However, its use has globally declined over the past two decades and there is little evidence on exactly how unpopular the unipolar augmentation strategy is on the nosological characteristics of patients who still receive it and on primary agents. Real-world epidemiological studies can provide key relevant insights.

METHODS: We analysed all ICD-10 unipolar depression prescriptions in Greece in the period between 1/2/2019 and 31/1/2020 and identified unipolar depression patients who were prescribed lithium. To benchmark lithium rates against those of other alternatives, we estimated quetiapine and aripiprazole prescription rates in unipolar depression. Logistic regression models were used to locate the diagnostic predictors of lithium prescription. Polypharmacy patterns and co-prescription of potentially interacting drugs were examined.

RESULTS: Only 1,314 patients (0.174%) with unipolar depression were prescribed lithium, representing a small fraction of the assumed 30% of patients expected to have treatment-resistant depression. This was substantially lower than quetiapine (7.1%) and aripiprazole (1.1%) prescription rates for unipolar depression. Patients who were prescribed lithium were younger, more often men, and mostly managed by psychiatrists. More severe disorder profiles were apparent (24% vs. 6%), with psychotic symptoms and mixed symptomatology more prevalent. The sensitivity analysis showed that, after excluding patients prescribed lithium who received a diagnosis suggestive of bipolarity within the same period, only 785 patients (0.108%) consistently received unipolar diagnoses, with a further drop when other major diagnoses are factored in (0.08%). One in 13 people received a possibly interacting drug, especially thiazide diuretics.

DISCUSSION: Despite strong evidence for augmentation in treatment-resistant unipolar depression, lithium prescription remains an underappreciated treatment option. In Greece, it is reserved for severe cases, together with selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors and atypical antipsychotics. Possible reasons include a perception of alternatives as safer, further complicated by supply issues.