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Review
. 2026 Feb 20:145:111650.
doi: 10.1016/j.pnpbp.2026.111650. Online ahead of print.

Preclinical rodent studies support minocycline as an adjunctive anxiolytic

D R Skvarc  1 , S C Lin  2 , S Croce  3 , E M Bastawy  3 , C M Smith  4 , B Drum  5 , B Panizzutti  3 , O M Dean  6
Affiliations
Free article
Review

Preclinical rodent studies support minocycline as an adjunctive anxiolytic

D R Skvarc et al. Prog Neuropsychopharmacol Biol Psychiatry. .
Free article

Abstract

Anxiety disorders represent a significant public health burden with limited treatment options, particularly amidst the escalating rates observed over the past two decades. While psychological and pharmacological treatments are available, often these treatments do not facilitate complete symptom remission for many individuals. Consequently, there is a pressing need for innovative interventions. Current systematic reviews have provided clinical support for adjunctive minocycline in psychiatry, particularly schizophrenia and major depressive disorder. While anxiety symptoms have been investigated as secondary outcomes, there has been no direct clinical studies of minocycline and anxiety disorders. Additionally, there is no existing literature specifically exploring the biological mechanisms of minocycline relevant to the pathophysiology or presentation of anxiety disorders. This review investigated the potential of minocycline, a tetracycline antibiotic with anti-inflammatory, antioxidant, glutamatergic and neurogenic properties, as a potential treatment for anxiety disorders. Drawing upon existing preclinical literature, we explore the role of microglial activation in anxiety behavior, elucidating the relationship with neurotransmitter dysregulation, synaptic plasticity, and neuroendocrine functions. Preclinical evidence suggests that minocycline may modulate these pathways through its inhibitory effects on microglial activation, thereby mitigating neuroinflammation, restoring neurochemical balance, and alleviate anxious behaviors. Through a comprehensive analysis of available preclinical data, this review aims to inform future research on the potential utility of adjunctive minocycline in managing anxiety disorders.

Keywords: anxiety disorders; clinical trial; minocycline; preclinical; systematic review.

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Conflict of interest statement

Declaration of competing interest Authors DRS, SCL, SC, CMS, BD, and BP report no relevant funding for this work, and affirm that they no have conflicts of interest. Author EMB was supported by a Trisno Family Fellowship, funded in part by an NHMRC CRE (1153607). No other conflicts of interest to declare. OMD has received grant support from the Brain and Behavior Foundation, Simons Autism Foundation, Stanley Medical Research Institute, Deakin University, Lilly, National Health and Medical Research Council (NHMRC), Medical Research Future Fund (MRFF), Stroke Foundation, Department of Defense Congressionally Directed Medical Research Programs, Marion and EH Flack Trust, Trisno Family Gift, McIntosh Family Gift, Geelong Music Community Collective and ASBDD/Servier. She has also received in kind support from BioMedica Nutracuticals, NutritionCare and Bioceuticals.

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