MINOCYCLINE

Background

Minocycline is a broad-spectrum tetracycline antibiotic that has been available since the 1970s. It has better penetration into the central nervous system and a longer half-life than other tetracyclines. It has been widely used as an antibacterial for acne and a variety of other infections. It has excellent penetration of the blood-brain barrier. In recent years, it has generated interest among neurologists for its neuroprotective effects in animal models of multiple sclerosis; Parkinson’s disease; amyotrophic lateral sclerosis; Huntington’s disease; methamphetamine-induced neurotoxicity; and, focal cerebral ischemia. It has also been used in clinical trials of patients with multiple sclerosis, Huntington’s disease, and autoimmune encephalitis.39 It is generic and available in tablets of 50mg and 100mg, as well as in extended-release tablets under the trade name Solodyn.

Mechanism of Action

Minocycline appears to have a wide variety of actions in addition to being antibacterial. Its anti-inflammatory and neuroprotective effects are thought to be related to some combination of its inhibition of inducible nitric oxide synthase (iNOS); capsase 1 and 3; p-38 mitogen-activated protein kinase (MAPK); cytochrome C release; cyclooxygenase-2 expression; prostaglandin E2 formation; and, microglial activation. It has also been reported to have antiviral effects against HIV and antiprotozoal effects against Toxoplasma gondii. Its use in individuals with schizophrenia has been encouraged by its effects in rodent models of this disease. In one study, minocycline attenuated the behavioral changes following the administration of an NMDA antagonist in mice.40 In another study, minocycline reversed the effects of an NMDA antagonist in rats.41

Use in Schizophrenia

Two case report series have been published: one including two patients with schizophrenia42, and the other including three patients with recent-onset acute paranoid schizophrenia.43 An open-label study of 22 patients with treatment-resistant schizophrenia, using 150mg/day for 4 weeks, reported an improvement in both PANSS positive and negative symptoms.44,45 Two placebo-controlled, double-blind trials have been carried out. In one study, 73 patients with schizophrenia of less than 5 years’ duration were randomized to minocycline 200mg/day or placebo for 12 months; “all symptoms measures improved significantly,” especially the negative symptoms.46 In the other study, 54 “early phase” (symptoms of less than 5 years) patients were randomized to minocycline 200mg/day or placebo for 6 months; the authors reported a significant improvement on negative symptoms on SANS and CGI, and a significant improvement in some tests of executive function.47 SMRI is supporting two large studies of minocycline as an adjunct medication for schizophrenia.

Use in Bipolar Disorder

There is a single case report of significant improvement of depression in a woman with bipolar disorder being treated with minocycline 150mg/day for sinusitis.48 SMRI is supporting a large study in progress.

Assessment

Minocycline may be useful as an adjunct medication for the negative symptoms of schizophrenia, especially in patients with a relatively recent onset. It is generally welltolerated, with dizziness and ataxia occurring occasionally. Minocycline should not be used in pregnant women or young children, as it can permanently stain the children’s teeth. It should also not be used past the medication’s expiration date, as it can be toxic.