Efficacy of Mirtazapine in Depressed Cocaine Dependent Subjects

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.