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Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00563797
First received: November 21, 2007
Last updated: March 21, 2016
Last verified: March 2016
  Purpose
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).

Condition Intervention Phase
Alcohol Dependence
Depression
Drug: Mecamylamine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Number of Drinking Days [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]
    Measured with time line follow back measures

  • Depression - Measured Using the HAMD Total Score [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

    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)



Secondary Outcome Measures:
  • Mean Percentage of Number of Drinking Days by Smoking Status [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean Percentage of Heavy Drinking Days by Smoking [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 21
Study Start Date: August 2007
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mecamylamine
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
mecamylamine 10mg/day for 12 weeks
Placebo Comparator: Placebo
Placebo capsules were prepared by the pharmacy and were identical in size and color to the medication capsules.
Drug: Placebo
Placebo pill

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.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00563797

Locations
United States, Connecticut
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Elizabeth Ralevski, Ph.D. Yale University
  More Information

Additional Information:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00563797     History of Changes
Other Study ID Numbers: 0705002629 
Study First Received: November 21, 2007
Results First Received: November 16, 2015
Last Updated: March 21, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
treatment
alcohol dependence
depression
mecamylamine

Additional relevant MeSH terms:
Depression
Depressive Disorder
Alcoholism
Behavioral Symptoms
Mood Disorders
Mental Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Ethanol
Mecamylamine
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Antihypertensive Agents
Ganglionic Blockers
Autonomic Agents
Peripheral Nervous System Agents
Nicotinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 08, 2016