Minocycline Augmentation to Clozapine
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Intervention: Minocycline
Intervention MeSH terms: Minocycline
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Schizophrenia; Clozapine; Minocycline

Summary:

      The proposed pilot study will compare minocycline augmentation with clozapine in individuals
      with high vs low inflammation as measured by CRP. Investigators hypothesize that minocycline
      will be well tolerated and will result in an improvement in the symptoms of schizophrenia,
      cognition, as well as improve the quality of life for patients preferentially in patients
      with high CRPs. Investigators plan to use a variety of different scales to measure
      improvement in the varying symptoms of schizophrenia as well as cognitive function, which
      will be administered to patients at three week intervals for a total study time of twelve
      weeks. Investigators hypothesize that minocycline could prove to be an effective, well
      tolerated, and inexpensive medication for treatment resistant patients with schizophrenia
      whom have particular difficulties with social interactions, obtaining and maintaining
      employment, and overall quality of life. Furthermore, investigators hypothesize that the data
      obtained in this study will contribute to the ongoing exploration of the role of inflammation
      in the brain of patients with schizophrenia and help understand and target the role of
      various inflammatory markers in the pathophysiology and treatment of treatment resistant
      schizophrenia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Mini International Neuropsychiatric Interview 6.0 diagnosis of schizophrenia or
             schizoaffective disorder

          -  Persistent symptoms of schizophrenia as measured by one of the following PANSS items:
             Total score ≥60, negative subscale ≥ 15, positive subscale ≥ 15, general
             psychopathology subscale ≥ 30

          -  Currently taking clozapine and the dose has been adjusted within 100 mg of study
             enrollment

          -  Currently taking clozapine for 3 months and documented clozapine level ≥ 350 ng/ml
             prior to study start

          -  No other psychotropic medication changes for one month prior to study enrollment

          -  No new psychosocial interventions for one month prior to study enrollment

          -  No prior experience on minocycline for greater than 1 week

          -  May be taking any other psychotropic, dermatologic, or gastrointestinal drugs

        Exclusion Criteria:

          -  History of organic brain disease

          -  Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-TR diagnosis of Mental
             Retardation or Dementia

          -  DSM-IV-TR diagnosis of Alcohol or Substance Dependence within the last six months
             (except nicotine)

          -  Pregnancy or lactation

          -  Known hypersensitivity to tetracyclines

          -  Current known infection

          -  Any known neurological disease or medical condition that could impact the measurement
             of the constructs being assessed

          -  Inpatient psychiatric hospitalization for worsening of psychiatric symptoms, OR
             worsening of symptoms requiring a new level of outpatient support, OR started on a new
             anti-inflammatory medication for greater than one week duration, OR addition of a new
             psychotropic medication for psychiatric symptom control

          -  A change in > 15% in PANSS score from the "Lead-In Visit" to the "M0 visit"