A Trial of Long-Acting Injectable Risperidone in the Treatment of Methamphetamine Dependence
Condition: Methamphetamine Dependence
Study type: Interventional
Phase: Phase 2

Summary: 
      Objective of the Project.

      -Methamphetamine (MA) use is growing to epidemic proportions and existing treatments for MA
      dependence demonstrate sub-optimal efficacy. Research implicates heavy use of MA as at least
      a contributing agent to a variety of neuropsychiatric impairments including psychosis, mood
      disturbance, anxiety, cognitive deficits, and motor dysfunction. Initial study by this
      investigator suggests that agents like risperidone may also be beneficial to MA dependent
      individuals by decreasing MA use and improving cognitive function in early abstinence.
      Long-acting injectable risperidone may prove more efficacious given its receptor binding
      characteristics and potential to increase medication adherence. The study objective is to
      determine the safety and efficacy of treating MA dependence and the associated cognitive and
      psychiatric symptomatology with long-acting injectable risperidone.
    

Detailed description: 
      Objective of the Project.

      -Methamphetamine (MA) use is growing to epidemic proportions and existing treatments for MA
      dependence demonstrate sub-optimal efficacy. Research implicates heavy use of MA as at least
      a contributing agent to a variety of neuropsychiatric impairments including psychosis, mood
      disturbance, anxiety, cognitive deficits, and motor dysfunction. Initial study by this
      investigator suggests that agents like risperidone may also be beneficial to MA dependent
      individuals by decreasing MA use and improving cognitive function in early abstinence.
      Long-acting injectable risperidone may prove more efficacious given its receptor binding
      characteristics and potential to increase medication adherence. The study objective is to
      determine the safety and efficacy of treating MA dependence and the associated cognitive and
      psychiatric symptomatology with long-acting injectable risperidone.

      Research Plan.

      -This is an open-label trial of long-acting injectable risperidone administered 25mg every
      2-weeks for the treatment of methamphetamine (MA) dependence. Participation will last
      approximately 14 weeks. A total of 20 subjects (veterans and non-veterans) aged 18 to 65
      years old who meet DSM-IV criteria for current MA dependence, have a stable address or
      alternative contact, and expect to be in the Puget Sound area for the length of the study
      will be enrolled at the Seattle and American Lake Divisions of the VA PSHCS. Exclusionary
      criteria include: 1) known sensitivity or allergy to risperidone; 2) current treatment with
      an antipsychotic agent, a mood stabilizer, or CYP 2D6 inhibitor; (3) transaminase levels >5X
      ULN; (4) albumin levels <3.5g/dl; (5) random serum glucose levels >200mg/dl; (6) diabetes
      mellitus or history of myocardial infarction; (7) baseline Brief Psychiatric Rating Scale
      score >72; (8) presence of tardive dyskinesia; (9) Barnes Akathisia Rating Scale global item
      score >2; (10) Simpson-Angus Scale total score > 0.3; (11) involvement with the legal system
      that could compromise study participation; (12) pregnancy or nursing; (13) receiving current
      mental health treatment.

      Methodology

      -Potential subjects will complete a screening, including medical history and physical,
      laboratory, EKG, assessment of MA and other drug use, psychiatric screening and cognitive
      testing, to determine eligibility. Eligible subjects will repeat the cognitive testing
      instruments prior to starting medication. After completing the screening period, subjects who
      continue to be eligible will receive 7 days of oral risperidone to assess tolerability
      followed by administration of long-acting injectable risperidone, 25mg. For 3 weeks following
      the first IM injection, participants will take oral risperidone each night to achieve a
      therapeutic plasma level of risperidone. During the oral co-administration phase,
      participants will have medication pill counts during their weekly visit to evaluate adherence
      and corroborate self-report data. Participants will receive additional 25mg risperidone
      injections every 14 days (at weeks 2, 4, and 6 after the first injection).

      Following the first injection, subjects will return to the study center for weekly visits for
      8 weeks. At each study visit, patients will be evaluated for possible adverse events, use of
      concomitant medications, and use of methamphetamine. Safety labs will be repeated at week 4
      and 8. Plasma levels of risperidone and 9-OH-risperidone will be obtained at 3, 6, and 8
      weeks. If intolerable adverse events occur, risperidone dosage will be reduced, or, if
      indicated, risperidone will be discontinued. Psychiatric symptoms and cognitive functioning
      will be evaluated at Baseline, and 4 and 8 weeks. A follow-up visit will take place at 12
      weeks. Subjects will receive behavioral treatment consisting of individual, once weekly,
      standardized, manual guided, relapse prevention therapy.

      Findings, results, or conclusions reached to date.

      -None to date.
    

Intervention name(s): long-acting injectable risperidone
Intervention type(s): Drug
Intervention MeSH terms: Risperidone
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: methamphetamine, cognition, outpatient, risperidone