Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review

BACKGROUND: Within the framework of individualized psychopharmacotherapy, therapeutic drug monitoring (TDM) has gained increasing relevance. In the absence of high-quality evidence, the TDM of citalopram (CIT) and the recommended therapeutic ranges of the plasma concentrations have been proposed by guidelines. However, the correlation between the plasma concentration of CIT and treatment outcomes has not been well established. Therefore, the aim of this systematic review was to evaluate the relationship between plasma CIT concentration and treatment outcomes in depression. RESEARCH DESIGN AND METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases (CNKI, Wanfang Data and Sinomed) were searched up to August 6, 2022. We included clinical studies evaluating the correlation between the plasma CIT concentration and treatment outcomes in patients with depression receiving CIT treatment. Outcomes measured included efficacy, safety, medication adherence, and cost-related outcomes. A narrative synthesis was performed to summarize findings from individual studies. This study was performed according to the Preferred Reporting Items for Systematic Reviews, Meta-Analysis (PRISMA) and the reporting guideline for Synthesis without meta-analysis (SWiM). RESULTS: Eleven studies involving 538 patients were included in total. The reported outcomes were mainly efficacy (n = 11) and safety (n = 3); one study reported the duration of hospitalization, and no study reported medication adherence. Regarding the efficacy outcomes, three studies revealed the plasma CIT concentration-response relationship and proposed a lower limit of 50 or 53 ng/mL, whereas this was not found in the rest of the studies. Regarding adverse drug events (ADEs), one study reported more ADEs in the low-concentration group (<50 ng/mL vs. >50 ng/mL), which is not convincing from the perspective of pharmacokinetics/pharmacodynamics. Regarding the cost-related outcomes, only one study reported that the high CIT concentration group (≥50 ng/mL) contributed to shortening the hospitalization duration, but it did not provide detailed information, including direct medical expenses and multiple potential factors contributing to longer hospital stays. CONCLUSIONS: A definite correlation between plasma concentration and clinical or cost-related outcomes of CIT cannot be drawn, whereas a tendency toward improved efficacy in patients with plasma concentration above 50 or 53 ng/mL was suggestive from limited evidence.