REVIEW OF: Zazula R et al, Aust N Z J Psychiatry 2021;55(8):784–798

Recent data suggest inflammation may play a role in depression, prompting research into the efficacy of minocycline—a tetracycline antibiotic with anti-inflammatory effects—as an augmentation agent in the treatment of major depressive disorder (MDD).

This study was a pooled data analysis from two multisite, double-blinded, placebo-controlled trials of minocycline 200 mg/day taken over 12 weeks. Participants were healthy adults who had a diagnosis of non-treatment-resistant, moderate-to-severe MDD and had already been receiving treatment for depression for the prior 2–6 weeks. Treatments included antidepressants (86%–89%), antipsychotics (29%–30%), and benzodiazepines (36%–40%).

Patients (n = 112) who were randomized to adjunctive minocycline (n = 57) were twice as likely as those on placebo (n = 55) to show a response to treatment, defined as a reduction in the Hamilton Rating Scale for Depression (HAM-D) score > 50%. They were also twice as likely to experience remission, defined as a HAM-D score < 7. Specifically, 57% of the minocycline group showed a response to treatment and 32% achieved remission. In comparison, 23% of the placebo group responded to treatment and 11% experienced remission.

Rates of adverse effects were comparable in the minocycline and placebo groups. Interestingly, the best responders were participants who used pain medications, had a longer duration of illness, and were older.

Minocycline is affordable, readily available, and has a low likelihood of producing antibiotic resistance (Husain MI et al, J Psychopharmacol 2017;31(9):1166–1175). Be cautious when prescribing to women of reproductive age: Minocycline reduces the efficacy of hormonal contraceptives and should not be used during pregnancy (category D).

CHPR’S TAKE
Consider adding minocycline to your list of augmentation strategies for the treatment of major depression. It’s a safe and well-tolerated treatment that might be particularly effective for depressed patients with pain and longer duration of illness.