Letter to the Editor
Adjunct minocycline to clozapine treated patients with persistent schizophrenia symptoms

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Case 1

AA was a 36 year-old Korean-American male with a 17-year history of Catatonic Schizophrenia (DSM-IV SCID diagnosis). After two years of clozapine and only partial improvement, several four to six week trials of adjunct medication were tried including topiramate (100 mg BID), risperidone (4 mg daily), olanzapine (15 mg daily), lithium (blood level of 0.74 mEq/L), and lamotrigine (200 mg daily). Aripiprazole was added with some benefit (15 mg/day). Minocycline was added and titrated to 100 mg BID, six

Case 2

BB was a 26 year-old Caucasian male with a diagnosis of schizophrenia (DSM-IV SCID diagnosis) with catatonic features since age 18. He was treated with 350 mg clozapine for three years with a recent clozapine plasma level of 424 ng/ml. His symptoms remained severe, with near continuous auditory and visual hallucinations, severely distressing feelings of external control and thought broadcasting, pre-occupying somatic and persecutory delusions, and moderately severe emotional withdrawal, affective

Discussion

Both cases suggest that adjunctive minocycline to clozapine is safe and effective in patients with schizophrenia who continue to have symptoms despite adequate clozapine treatment. Both patients had improvements in their symptoms, notably robust improvements in negative symptoms, and reported “just feeling better” on their medications. This is one of the first reports of adjunct minocycline to clozapine treatment in patients with persistent symptoms. Levkovitz et al. (Levkovitz et al., 2010)

Role of funding source

There was no funding for this case report.

Contributors

Dr. Kelly wrote the manuscript first draft and originated the idea of minocycline treatment. Drs. Richardson and Vyas treated the patients, performed the ratings and assisted in manuscript preparation. Drs. Buchanan, Wehring and Koola were part of the clinical team monitoring and assisted with the manuscript preparation. All authors have contributed to and approved the final manuscript.

Conflict of interest

Author Robert Buchanan has consulted for Abbott, Cypress Bioscience, Glaxo-Smith-Kline, Sanofi-Aventis, Schering-Plough, and Takeda. Dr. Buchanan is a member of Advisory Boards for Abbott, Astellas, Astra-Zeneca Merck, Pfizer, Roche, Solvay Pharmaceuticals, Inc., Takeda, and Wyeth. Dr. Buchanan is a DSMB member for Pfizer, Cephalon, and Otsuka.

All other authors have nothing to declare no conflicts of interest.

Acknowledgments

The authors have no acknowledgments.

References (13)

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    Subsequently, a case report and an open study with the addition of minocycline to the usual antipsychotic treatment of patients with schizophrenia showed significant improvement in positive, negative and cognitive symptoms (Miyaoka et al., 2007, 2008). Adjunctive minocycline to clozapine was also effective in improving positive and negative symptoms of two super-refractory patients (Kelly et al., 2011). Additionally, a randomized double-blind placebo-controlled clinical trial of minocycline add-on treatment showed an improvement in negative and cognitive symptoms in patients with schizophrenia (Levkovitz et al., 2010), and another randomized double-blind placebo-controlled clinical trial demonstrated an improvement mainly in the negative symptoms (Chaudhry et al., 2012).

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