Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

Depression Clinical Trial

Official title:

Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00563797
• Other study ID #: HSS # ER0004
• Status: Completed
• Phase: Phase 3
• First received: November 21, 2007
• Last updated: July 8, 2014
• Start date: August 2007
• Est. completion date: July 2014

Study information

• Verified date: July 2014
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcoholism
• Depression
• Depressive Disorder

Intervention

Drug:
• Mecamylamine
mecamylamine 10mg/day for 12 weeks

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Elizabeth Ralevski	National Alliance for Research on Schizophrenia and Depression

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	drinking - measured using the TLFB		25 weeks	Yes
Primary	depression - measured using the HAMD		25 weeks	Yes