Efficacy of Mirtazapine in Depressed Cocaine Dependent Subjects
Condition: Cocaine Dependence; Depression
MeSH terms: Cocaine-Related Disorders
Intervention: Placebo; Mirtazapine
Intervention description: Placebo for days 1-4 Placebo for days 5-9 Placebo for days10-78 Placebo for days 79-81 Placebo for days 82-84; Days 1-4 15mg Days 5-9 30 mg Days 10-78 45mg Days 79-81 30mg Days 82-84 15mg
Intervention MeSH terms: Mirtazapine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cocaine; Substance Abuse

Summary:

      This research study is being done to look at the safety of the medication Mirtazapine
      (Remeron) in people who have cocaine dependence and depression. Hypotheses I. Cocaine usage
      will be less in the mirtazapine treatment group (MG) than in the control group (CG). II. A
      greater increase in Clinician Global Impression (CGI) score will be observed in the MG than
      in the CG. Secondary Hypotheses: I. A greater decrease in Hamilton Rating Scale for
      Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) scores will be observed in
      the MG than in the CG. II. A greater decrease in HIV risk behaviors will be observed in the
      MG than in the CG. III. A greater improvement in sleep structure will be observed in the MG
      than in the CG. IV. The proportion of subjects experiencing severe adverse drug reactions
      that necessitate termination from the study by one of the study clinicians will not differ
      between the MG and CG. V. Retention will be greater in MG than in CG.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnostic Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis
             of cocaine dependence.

          -  HAM-D score of 12 or above and history of autonomous depression, defined as meeting
             DSM-IV criteria for major depression or dysthymic disorder during any lifetime period
             of abstinence of 30 days or longer.

          -  At least one urine toxicology positive for cocaine benzoylecgonine (BE) over the
             consecutive two-week baseline screening period during which 6 urine samples have been
             obtained

          -  Males and non-pregnant, non-nursing females, 18-64 years of age (inclusive).

          -  Individuals able to give written informed consent and willing to comply with all study
             procedures.

        Exclusion Criteria:

          -  Any Axis I diagnosis that, in the opinion of the Principal Investigator, may interfere
             with the course of the trial.

          -  Physiological dependence on alcohol or opiates requiring medical detoxification.

          -  A medical or neurological illness that in the clinical judgment of the investigator
             would make study compliance difficult or contraindicate the use of mirtazapine.

          -  Any clinically significant abnormal lab values or liver function tests (LFTs) which
             are greater than 3 times the normal limit.

          -  The need or intention to use concurrently with or within four weeks prior to study
             drug administration, any of the following medications: monoamine oxidase inhibitors
             and/or sibutramine. In addition, other medications such as alpha2-agonists and
             medications which affect the enzymes Cytochrome P450 1A2 (CYP1A2), Cytochrome P450 2D6
             (CYP2D6), Cytochrome P450 3A4 (CYP3A4) (as inhibitors, substrates, or inducers), and
             serotonin modulators should be used with caution. The research physician will decide
             on this issue. A listing of these substances may be found in Appendix I.

          -  Females of childbearing potential who do NOT agree to use a medically acceptable
             method of birth control (barrier, intrauterine device (IUD), oral or depot
             contraceptive medication, or complete abstinence).

          -  Positive pregnancy test.

          -  Breastfeeding

          -  Known drug allergy or sensitivity to mirtazapine.

          -  Participation in an investigational drug or device study within 1 month of enrollment
             in the present study.

          -  Enrollment in an opiate-substitution (i.e., methadone, levo acetyl methadol (LAAM))
             treatment program within 45 days of enrolling in the present study.

          -  Individuals having taken LAAM, methadone or naltrexone within 14 days of enrollment in
             the present study.

          -  Individuals who, in the clinical judgment of the Investigator, are actively and
             acutely suicidal.

          -  Subjects, who in the opinion of the investigator, have a medical condition that may
             interfere with study assessments and/or put them at undue risk.

          -  Subjects, who in the opinion of the investigator, will have difficulty complying with
             study procedures.