Objective: To assess the efficacy and safety evidence for adjunct minocycline in treatment-resistant depression (TRD).

Data Sources: In this systematic review, PubMed, PubMed Central, Embase, and Google Scholar were searched from inception to October 2022. The following keywords were utilized in the search: "depression" AND "minocycline" AND "treatment, pharmacological intervention, management." Medical Subject Heading terms for "minocycline" and "depression, depressive disorder, treatment-resistant," and "disease management" were also used. Relevant peer-reviewed, English-language articles that included adults and children were selected for final evaluation.

Study Selection: Two authors independently searched and selected 1,004 relevant articles. Only randomized controlled trials were considered. Five articles were identified that fulfilled the inclusion criteria.

Data Extraction: The PICO algorithm (Population, Intervention, Comparison, Outcomes, and Study Design) framework was utilized, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria guidelines were followed. The Cochrane risk of bias tool was used to categorize the included study as a low, unclear, or high risk of bias.

Results: Minocycline as an adjunct immunomodulator shows inconsistent benefit in TRD. Minocycline has some beneficial effect on depression scale scores and inflammatory markers in TRD patients with inflammatory disequilibrium (C-reactive protein elevation exceeds 3 mg/L). However, minocycline showed an inconclusive effect in TRD with no clear immunologic dysregulation. Minocycline might have a neuroprotective, rather than therapeutic, effect at a small dose.

Conclusions: The results were inconsistent regarding the clinical and neuroprotective role of minocycline in TRD. More study is needed to clarify the pathophysiologic and clinical role of minocycline as an immunomodulator in TRD.

Prim Care Companion CNS Disord 2023;25(5):22r03467.

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