Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the efficacy of mecamylamine (MEC, 10 mg/day) versus placebo in reducing depressive and alcohol symptoms in patients with depression and co-morbid alcohol dependence. The researchers hypothesize that MEC will significantly reduce depressive symptoms and decrease alcohol consumption compared to placebo in patients with depression and alcohol dependence who are on a stable dose of a selective serotonin reuptake inhibitor (SSRI).

Detailed Description
-----------------
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.

Official Title
-----------------
Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

Conditions
-----------------
Alcohol Dependence, Depression

Intervention / Treatment
-----------------
* Drug: Mecamylamine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals with the DSM-IV diagnosis of Major Depression (MD) and Alcohol Dependence (AD) (using the SCID). Individuals who have been on a stable SSRI dose for 2 weeks. Smokers and non-smokers (smokers are defined as smoking more than 5 cigarettes per day). 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). Women of childbearing potential must have a negative pregnancy test and use an acceptable method of contraception. 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: Females who are pregnant or lactating. Patients may not be taking medications thought to influence drinking behavior, including: acamprosate, disulfiram, naltrexone, or ondansetron. 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. Patients with a history of glaucoma, prostatic hypertrophy, urethral obstruction, cerebral arteriosclerosis, pyloric stenosis, or a history of hypersensitivity to mecamylamine. Patients who meet current SCID criteria for the following major Axis I diagnosis (Posttraumatic Stress Disorders (PTSD), Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders). 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). Patients on pharmacological treatments for alcohol and/or nicotine dependence. (8) Patients taking bethanechol. (9) Patients at risk for suicide.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mecamylamine<br>Mecamylamine is a noncompetitive, high-affinity nAChR antagonist with low selectivity for the alpha-7 receptor. Those receiving mecamylamine started at 2.5mg once daily (second dose was placebo). The dose was increased to 5.0 mg twice daily over 3 weeks. | Drug: Mecamylamine<br>* mecamylamine 10mg/day for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo capsules were prepared by the pharmacy and were identical in size and color to the medication capsules. | Drug: Placebo<br>* Placebo pill<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Drinking Days | Measured with time line follow back measures | 25 weeks | 
| Depression - Measured Using the HAMD Total Score | The Hamilton Depression Rating Scale (HAM-D) has proven useful for many years as a way of determining a patient's level of depression before, during, and after treatment. It should be administered by a clinician experienced in working with psychiatric patients. Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. The Scale ranges from 0 (normal) to >23 (Very Severe Depression) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage of Number of Drinking Days by Smoking Status | Two-way interaction between smoking and medication for percentage of drinking days captured by time line follow back surveys. Data are calculated as number of drinking days over the number of days in the study for smokers and nonsmokers receiving either mecamylamine or placebo. | 25 weeks | 
| Mean Percentage of Heavy Drinking Days by Smoking | The two-way interaction between medication by smoking status to measure percentage of heavy drinking days measured by time line follow back survey. Data were calculated as number of heavy drinking days (heavy drinking days is defined as 5 drinks on a single occasion for men and 4 for women) over the number of days in the study for smokers and non smokers receiving either mecamylamine or placebo. | 25 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
treatment, alcohol dependence, depression, mecamylamine