TY - JOUR
T1 - Adjunctive Minocycline in Clozapine-Treated Patients with Schizophrenia
T2 - Analyzing the Effects of Minocycline on Clozapine Plasma Levels
AU - Wehring, Heidi J.
AU - Elsobky, Teresa
AU - McEvoy, Joseph Patrick
AU - Vyas, Gopal
AU - Richardson, Charles M.
AU - McMahon, Robert P.
AU - DiPaula, Bethany A.
AU - Liu, Fang
AU - Sullivan, Kelli
AU - Buchanan, Robert W.
AU - Feldman, Stephanie
AU - McMahon, Elizabeth M.
AU - Kelly, Deanna L.
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.
AB - Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.
KW - Clozapine
KW - Drug interaction
KW - Minocycline
KW - Schizophrenia
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U2 - 10.1007/s11126-017-9515-x
DO - 10.1007/s11126-017-9515-x
M3 - Article
C2 - 28466366
AN - SCOPUS:85018447457
SN - 0033-2720
VL - 89
SP - 73
EP - 80
JO - Psychiatric Quarterly
JF - Psychiatric Quarterly
IS - 1
ER -