Alcoholism
Conditions
Keywords
Alcohol Drinking, Alcohol Dependence, Sertraline Pharmacotherapy, Alcoholism Subtypes, Early- versus Late-Onset Alcoholism
Brief summary
The purpose of this study is to determine whether Sertraline, compared to placebo, is effective in the treatment of alcohol dependence as a function of the subtype of alcoholic patient being treated. This involved administering sertraline (to a maximum of 200 mg/day) or an inactive placebo for a 14-week treatment period.
Detailed description
In an effort to broaden the options for pharmacotherapy of alcoholism, this study will examine the effects of sertraline, a selective serotonin reuptake inhibitor (SSRI), for the treatment of alcohol dependence. The study is based on evidence that, although SSRI therapy is not appropriate for all alcoholics, there exists a substantial subgroup of alcoholics for whom SSRIs appear to exert a clinically important effect. Sertraline is among the most widely prescribed psychotropic medications in the world. Consequently, this study will examine the safety and efficacy of sertraline, the mechanism and duration of those effects and the best method for subtyping alcoholics to identify individuals for whom the medication is most likely to produce a clinically important reduction in drinking behavior. The study employs a parallel-group, prospective design in which randomization is balanced on patient subtype (early-onset/late-onset) and other relevant pretreatment measures with an approximately equal number of subjects assigned to treatment with sertraline (to a maximum of 200 mg/day) or placebo. The study will include a 14-week treatment period; because the 2 weeks are for medication taper, efficacy will be evaluated over the first 12 treatment weeks. A total of 160 early-onset or late-onset alcoholics will be randomized. Daily process measures of positive and negative events, global perceived stress, mood, desire to drink, and drinking frequency and intensity, collected using interactive voice response technology, will provide insight into the mechanisms by which sertraline may exert its effects. Coping-skills training will be provided weekly for the first 6 weeks, then every other week for the last 8 weeks of the study. A 6-month post-treatment follow-up period will evaluate the duration of medication effects. This study will also examine the relation between genotypes at a number of relevant loci and both risk of alcohol dependence and response to sertraline treatment.
Interventions
DRUGSertraline
Sertraline (to a maximum of 200 mg/day) for 14-week treatment period
DRUGPlacebo
Placebo for 14-week treatment period
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
UConn Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Current episode (i.e., in the preceding month) of alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders 4th ed (DSM-IV) criteria * 18-65 years of age * Abstinent from alcohol for a period of at least 3 days prior to baseline research assessment * Able to read English and complete study evaluations * Male, or if female, without active reproductive potential * Participants will have signed informed consent
Exclusion criteria
* Currently meets criteria for dependence on a psychoactive substance other than alcohol and nicotine * Regular use of psychoactive drugs including anxiolytics and antidepressants * Current use of disulfiram or naltrexone * Current major depression or psychosis (or other severe psychiatric disability e.g., suicidality, current mania) * Significant underlying medical conditions such as hepatic, cerebral, renal, thyroid, or cardiac pathology, which in the opinion of the evaluating physician would preclude the patient from study adherence or be of potential harm to the subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days on Which Subjects Drank | 12-week treatment period | Obtained using daily interactive voice response data augmented by Timeline Followback data. Missing days were treated as drinking days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days of Heavy Drinking (Defined as Days on Which Women Drank >= 4 Drinks and Men Drank >= 5 Drinks) | 12-week treatment period | Obtained using daily interactive voice response data augmented by Timeline Followback data. Missing days were treated as heavy drinking days. |
| Change in the Level of Alcohol-related Problems | 12-week treatment period compared with baseline value | Measured using the SIP (Short Inventory of Problems), which was administered at pretreatment and at the end of treatment. The range of scores on the SIP is 0 (no alcohol-related problems) to 45 (most severe alcohol-related problems) and the time frame for reporting is the preceding 3 months. The data presented here represent a difference score of treatment minus baseline. |
Countries
United States
Participant flow
Recruitment details
Recruitment from Feb. 2004 to March 2009 through advertisements and referrals by area clinicians.
Pre-assignment details
All patients underwent physical examination and routine laboratory testing during screening. 143 prospective patients were screened, of which 4 did not meet study criteria and 5 chose not to participate.
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Sertraline plus coping skills therapy. Medication to a maximum of 200 mg/day orally in two doses. Coping skills therapy, aimed at improving patients' ability to change their drinking behavior, was provided at each visit. | 63 |
| Placebo Placebo plus coping skills therapy. Coping skills therapy, aimed at improving patients' ability to change their drinking behavior, was provided at each visit. | 71 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 4 |
| Overall Study | Lack of Efficacy | 4 | 9 |
| Overall Study | Withdrawal by Subject | 17 | 10 |
Baseline characteristics
| Characteristic | Placebo | Sertraline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 62 Participants | 133 Participants |
| Age Continuous | 47.3 years STANDARD_DEVIATION 9.5 | 47.7 years STANDARD_DEVIATION 10.1 | 47.5 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 71 participants | 63 participants | 134 participants |
| Sex: Female, Male Female | 14 Participants | 12 Participants | 26 Participants |
| Sex: Female, Male Male | 57 Participants | 51 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 63 | 14 / 71 |
| serious Total, serious adverse events | 3 / 63 | 0 / 71 |
Outcome results
Primary
Number of Days on Which Subjects Drank
Obtained using daily interactive voice response data augmented by Timeline Followback data. Missing days were treated as drinking days.
Time frame: 12-week treatment period
Population: All randomized subjects with missing days imputed as drinking days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Number of Days on Which Subjects Drank | 37.0 days | Standard Deviation 30.6 |
| Placebo | Number of Days on Which Subjects Drank | 33.8 days | Standard Deviation 27.3 |
Secondary
Change in the Level of Alcohol-related Problems
Measured using the SIP (Short Inventory of Problems), which was administered at pretreatment and at the end of treatment. The range of scores on the SIP is 0 (no alcohol-related problems) to 45 (most severe alcohol-related problems) and the time frame for reporting is the preceding 3 months. The data presented here represent a difference score of treatment minus baseline.
Time frame: 12-week treatment period compared with baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Change in the Level of Alcohol-related Problems | 6.0 Units on a scale | Standard Deviation 9.2 |
| Placebo | Change in the Level of Alcohol-related Problems | 9.0 Units on a scale | Standard Deviation 9.5 |
Secondary
Number of Days of Heavy Drinking (Defined as Days on Which Women Drank >= 4 Drinks and Men Drank >= 5 Drinks)
Obtained using daily interactive voice response data augmented by Timeline Followback data. Missing days were treated as heavy drinking days.
Time frame: 12-week treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Number of Days of Heavy Drinking (Defined as Days on Which Women Drank >= 4 Drinks and Men Drank >= 5 Drinks) | 31.9 days | Standard Deviation 29 |
| Placebo | Number of Days of Heavy Drinking (Defined as Days on Which Women Drank >= 4 Drinks and Men Drank >= 5 Drinks) | 26.4 days | Standard Deviation 26.4 |