Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

University of Maryland Baltimore (UMB)

Status

Completed

Conditions

Schizophrenia

Treatments

Drug: Minocycline

Drug: Placebo

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01433055

HP-00048900

1R21MH091184-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Schizophrenia is a devastating and costly illness. One-third to one-half of people with schizophrenia do not respond to the most current drugs leaving clozapine as the best alternative for treatment. However, over 60% of people treated with clozapine continue to have persistent symptoms and cognitive impairments. Little data is available to support evidence-based recommendations to guide clinicians in treating these patients. Preliminary data has suggested that adjunct treatment with minocycline may offer robust symptom improvement in patients with schizophrenia, including those taking clozapine. Minocycline has had interesting effects; including suggesting it may have a significant role in treatment of neurologic and psychiatric disorders. Minocycline is currently available generically; its side effects are well-described and minimal. The proposed double-blind treatment study seeks to demonstrate that adjunctive minocycline offers patients superior efficacy for persistent positive symptoms, cognitive impairments, and/or other components of schizophrenia pathology. This knowledge could lead to the more effective treatment of patients with schizophrenia. The research itself may lead to a better understanding of the pathophysiology of positive symptoms and cognitive impairments, which could contribute to improved treatments in the future.

Enrollment

52 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

DSM-IV diagnosis of schizophrenia or schizoaffective disorder
Male or Female
Age: 18 to 65 years
Caucasian or Non-Caucasian
At least six months of clozapine treatment
Clozapine treatment for incomplete symptoms response (evidence of two failed previous trials of antipsychotics)
Current dose of 200 mg/day for at least 3 months AND a documented clozapine blood level 350 ng/ml prior to study start (maximum clozapine dose of 900 mg/day)
BPRS total score of 45 or more on the 18 item version (scale: 1-7)
BPRS positive symptom item total score of 8 or more
BPRS positive symptom score of 4 or greater on at least one item

Exclusion criteria

History of organic brain disease
DSM-IV diagnosis of Mental Retardation
DSM-IV diagnosis of Alcohol or Substance Dependence within the last six months (except nicotine)
DSM-IV diagnosis of Alcohol or Substance Abuse within the last one month (except nicotine)
Pregnancy or lactation
Significant renal or liver impairment
Previous known hypersensitivity to tetracyclines
Current treatment with tetracycline or derivative
Current treatment with lamotrigine
Treatment with oral contraceptives
Current known infection
Treatment with cholestyramine or colestipol
Treatment with Urinary alkalinizers (e.g., sodium lactate, potassium citrate)
Treatment with warfarin
Abnormal (considered positive) Lyme titer