Use of The Antibiotic Minocycline To Treat Catatonic Schizophrenia

Director of Outpatient Services, Tisch Hospital’s Department of Psychiatry, New York University Medical Center

Minocycline is a semisynthetic second-generation tetracycline which exerts anti-inflammatory effects that are separate and distinct from its anti-microbial action (MacDonald et al.  1973).  One of the more brain-penetrable tetracyclines, minocycline has been shown to have neuroprotective effects in models of ischemic injury (Yrianheikki et al.  1999) and the 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine model of Parkinson’s disease (Du et al.  2001).  While direct neuroprotective effects have been observed some of its actions result from indirect effects in inhibiting glial (astrocytic;/microglial) caspase 1 and iNOS activity (Amin et al.  1996; Yong et al.  2004).  Recent reports indicate that minocycline delays mortality or disease progression in mouse models of Huntington’s disease (Chen et al.  2000; Berger 2000) and amyotrophic lateral sclerosis (Zhang et al.  2003).  There is also a case report in humans of possible antidepressant effects of minocycline, which has been attributed mechanistically to the inhibition of noradrenaline-sensitive adenylate cyclase (Levine et al.  1996).  Now comes a report of 2 cases of acute schizophrenia with predominant catatonic symptoms that responded well to minocycline (Miyaoka et al.  2007).

In the first case, a 23 year-old man, college graduate employed by a company, with no prior neurologic or psychiatric history developed insomnia and anxiety.  Further, he became agitated and talked incoherently with persecutory delusions and paranoid ideation.  He was admitted to a Japanese hospital.  Examination of his mental state revealed auditory hallucinations, persecutory delusions, psychomotor excitement, catatonic stupor, and deterioration in the level of social functioning.  Physical and neurologic examinations were normal.  Complete work-up including laboratory testing of serum and urine, electroencephalography (EEG), computed tomography (CT) and magnetic resonance imaging (MRI) of the brain were all normal.  Diagnosed with catatonic schizophrenia, the patient was started on haloperidol, titrated to 20 mg/day.  One week later, his psychomotor excitement, auditory hallucinations, persecutory delusions, and catatonic stupor persisted.  In addition, his symptoms were complicated by severe pneumonia.  Serum creatine kinase and renal parameters were normal.  Minocycline 150 mg/day was initiated to treat the pneumonia.  Two weeks later, the pneumonia and psychiatric symptoms resolved.  Minocycline was discontinued for one week; subsequently the psychiatric symptoms significantly worsened.  As a result, minocycline 150 mg bid was resumed.  Within 3 days, a noticeable clinical improvement was observed.  The patient continued minocycline 150 mg/day and haloperidol 20 mg/day.  Twenty-four days later, the patient became practically symptom-free.  On the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), his score declined from approximately 38 to 12.  His haloperidol was reduced to 10 mg/day, then over the next 2 and ½ weeks to 2 mg/day.  Minocycline was maintained at 150 mg/day.  At last follow-up two years later, the patient continued to do well with no worsening of psychiatric symptoms.

 The second case involved a 61 year-old man with schizophrenia since the age of 20 and five prior psychiatric hospitalizations.  During his last admission, he deteriorated and became autistic, and so remained in the hospital for 4 years.  He was treated with haloperidol 10 mg/day and risperidone 2 mg/day.  Routine laboratory testing including blood, urine, and feces were within normal limits.  Electroencephalography (EEG), computed tomography (CT), and magnetic resonance imaging (MRI) of the brain were all negative.  One year prior, the patient had developed psychomotor excitement, catatonic stupor, and negativism.  In addition, a large decubitus formed on his left hip. Minocycline 150 mg/day was initiated.  Haloperidol and risperidone were continued at their previous doses.  Two weeks later, the decubitus healed.  Minocycline was discontinued for one week.  This was followed by a significant worsening of his psychiatric symptoms; his PANSS score which had declined from 25 to 10, now increased to 40.  As a result, minocycline was resumed at a dose of 150 mg bid.  Within 3 days, noticeable clinical improvement was observed (PANSS = 10).  Minocycline was reduced back to 150 mg/day while his antipsychotics were continued at their previous dosages.  After another 13 days, the patient became practically symptom-free.  Haloperidol was descreased to 3 mg/day while risperidone was discontinued.  Of note, throughout his course, the patient did not have fever or receives benzodiazepines.  At last follow-up one year later, the patient continued to do well with no worsening of psychiatric symptoms.

This appears to be the first published report on the successful use of minocycline to treat psychosis and catatonia.  While antipsychotics were also administered to these patients, the temporal sequence of events described is consistent with at least some of the benefit deriving from minocycline.  Furthermore, benzodiazepines and/or electroconvulsive therapy (ECT) usually are needed for effective treatment of catatonia. 

Typically used in the management of chronic conditions such as acne, rheumatoid arthritis, and rosacea, minocycline has an established safety record for long-term use (Thomas et al.  2003).  If confirmed by further research, minocyline’s action in schizophrenia and other neurodegenerative diseases may  result from its potent inhibition of microglial activation, a process normally associated with the production of neurotoxins and with apoptosis (Gehrmann et al.  1995).  Additional study is indicated to more fully evaluate the safety and utility of minocycline in the treatment of catatonic schizophrenia.

Disclosure: Dr. Ginsberg is a speaker for AstraZeneca, Cyberonics, Forest, and GlaxoSmithKline; and has received research support from Cyberonics.

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