Mirtazapine for Treating Cocaine Dependent Individuals Who Also Suffer From Depression

Cocaine abuse and depression often occur together. Individuals suffering from both are
usually not able to quit abusing cocaine. Past research conducted on alcohol dependent
individuals also suffering from depression showed that these individuals were able to
successfully quit drinking with the addition of an antidepressant medication. Mirtazapine is
a medication currently used to treat depression. This study will evaluate the efficacy of
mirtazapine, used in combination with behavioral therapy, in treating cocaine dependent
individuals who also suffer from depression.

Participants in this 8-week trial will be randomly assigned to receive either mirtazapine or
placebo. Prior to starting medication treatment, participants will undergo an initial 2-week
phase consisting of psychosocial and behavioral therapy. The purpose of this lead-in phase is
to achieve initial reduction or abstinence in cocaine use, while observing cocaine withdrawal
symptoms and mood changes associated with depression. During these first 2 weeks,
participants will attend three study visits each week, at which time they will participate in
motivational interviews and cognitive behavioral relapse prevention therapy. During this
phase, participants who successfully remain abstinent from cocaine use will be rewarded with
high-value monetary vouchers.

Upon completing the lead-in phase, participants will be randomly assigned to receive either
mirtazapine or placebo. Participants will attend study visits twice each week for 8 weeks.
Mood and drug use will be evaluated at each study visit. Cognitive behavioral relapse
prevention therapy will continue throughout the study. In addition, participants will earn
low-value monetary vouchers contingent on cocaine abstinence.

At the end of Week 8, participants will enter the lead-out phase. At this time, those
participants whose mood has significantly improved will be able to continue treatment for an
additional 8 weeks. Participants whose mood has not shown improvement will be tapered off
their assigned medication treatment and will be offered treatment with an alternative
medication. Following completion of the lead-out phase, all participants will be referred for
continuing care in the community.

Inclusion Criteria:

- Meets DSM-IV criteria for current cocaine dependence

- Currently seeking treatment for cocaine dependence

- Used cocaine for at least one day per 2-week period in the month prior to study entry

- Meets DSM-IV criteria for current major depression or dysthymia syndrome

- Scores greater than 12 on the Baseline 21 Hamilton Depression Scale

- Ages 18-60

Exclusion Criteria:

- Meets DSM-IV criteria for past mania (e.g., bipolar disorder), schizophrenia, or any
psychotic disorder other than transient psychosis due to drug abuse

- Scores less than 11 on the Baseline 21 Hamilton Depression Scale

- History of seizures

- History of an allergic reaction to mirtazapine

- Chronic organic mental disorder

- Current suicidal risks or any history of suicidal behavior

- Pregnant, breastfeeding, or unwilling to use an adequate method of contraception for
the duration of the study

- Unstable physical disorders, including high blood pressure, acute hepatitis, or
diabetes

- Coronary vascular disease as indicated by history, or suspected by abnormal
electrocardiogram, or history of cardiac symptoms

- Cardiac conduction system disease, as indicated by an electrocardiogram QRS duration
greater than 0.11

- History of failure to respond to a previous trial of mirtazapine

- Currently taking psychotropic medication

- Meets DSM-IV criteria for opioid or sedative-hypnotic dependence

- Meets DSM-IV criteria for alcohol dependence with evidence of clinically significant
physiological dependence in need of medically supervised detoxification

- Current alcohol or marijuana dependence identified as the main problem for seeking
treatment; individuals with alcohol or marijuana dependence (without significant
physiological dependence) and cocaine dependence are eligible, as long as cocaine is
identified as the primary substance problem for which they are seeking treatment

- History of neutropenia (< 500 granulocytes /cc) or Agranulocytosis (<500
granulocytes/cc) with fever, infection. Concurrent intake of medications with possible
neutropenic effects: chlorpromazine, carbamazepine, clozapine, chemotherapeutic drugs,
immunosuppressant medications, interferons, ganciclovir, protease inhibitors.

- Patients not able to meet attendance requirement of 4/6 visits during the lead-in
period.

- Supplemental exclusion criteria for cold pressor test (CPT): history of frostbite,
open cut or sore on foot to be immersed, history of Raynaud's phenomenon.

- Supplemental exclusion criteria for CPT: hypertension (BP less than or equal 140/90)