Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

Depression with co-morbid alcohol dependence is very prevalent and it is very costly to
treat. The co occurrence of the two disorders leads to greater severity and worse long-term
outcome, including suicide. Although a number of treatment strategies have been implemented
for depressed patients with alcohol dependence the controversy concerning best treatment
options for those patients persists.

The clinical relationship between depression and alcohol dependence suggests some common
mechanism underlying both disorders. It has been hypothesized that medications that block
presynaptic nAChR may be effective in the treatment of alcoholism and depression.
Mecamylamine (Inversine ®) is a noncompetitive, high affinity nAChR antagonist with low
selectivity for the alpha-7 receptor. Mecamylamine has never been investigated as an
effective adjunct treatment for dually diagnosed patients with depression and alcohol
dependence. Methods: Thirty participants with a current diagnosis of depression and alcohol
dependence will be recruited for this 12-week treatment study. Fifteen participants will be
randomized to mecamylamine and fifteen to placebo. Participants will be included in the
study if: they meet current DSM-IV criteria for Major Depression and Alcohol Dependence and
have been on a stable SSRI dose for 2 weeks. All participants will come weekly to take their
medications and complete weekly assessments. Weekly assessments will consist of questioners
that will assess depressive symptoms and alcohol consumption over the entire treatment
period. Significance: This study is the first to evaluate the efficacy of mecamylamine as an
augmenting agent for treatment of depression and alcohol dependence.

Inclusion Criteria:

1. Individuals with the DSM-IV diagnosis of Major Depression (MD) and Alcohol Dependence
(AD) (using the SCID).

2. Individuals who have been on a stable SSRI dose for 2 weeks.

3. Smokers and non-smokers (smokers are defined as smoking more than 5 cigarettes per
day).

4. Individuals who have a history of substance dependence (other than alcohol, tobacco
and cocaine) but have not met criteria for substance dependence in the past 30 days
will be included (using the SCID).

5. Women of childbearing potential must have a negative pregnancy test and use an
acceptable method of contraception.

6. Individuals who are able to participate psychologically and physically; give informed
consent; complete the assessments; take the study medication; and otherwise
participate in the trial. A post-consent test will be given to assess patient's
capacity to give informed consent.

Exclusion Criteria:

1. Females who are pregnant or lactating.

2. Patients may not be taking medications thought to influence drinking behavior,
including: acamprosate, disulfiram, naltrexone, or ondansetron.

3. Patients with significant underlying medical conditions, such as cerebral, renal,
thyroid, hepatic or cardiac pathology, which in the opinion of the physician would
preclude the patient from fully cooperating or be of potential harm during the course
of the study.

4. Patients with a history of glaucoma, prostatic hypertrophy, urethral obstruction,
cerebral arteriosclerosis, pyloric stenosis, or a history of hypersensitivity to
mecamylamine.

5. Patients who meet current SCID criteria for the following major Axis I diagnosis
(Posttraumatic Stress Disorders (PTSD), Bipolar Disorders, Schizophrenia and
Schizophrenia-type Disorders).

6. Patients with a current unstable medical condition such as neurological,
cardiovascular, endocrine, renal, liver, or thyroid pathology (LFT more than 5 times
normal, abnormal BUN and creatinine, and unmanaged hypertension with BP higher than
200/120).

7. Patients on pharmacological treatments for alcohol and/or nicotine dependence. (8)
Patients taking bethanechol. (9) Patients at risk for suicide.