A Randomized Controlled Trial of Structured Stepped-care Intervention for Psychiatric Comorbidity

In summary, the specific aims of this project are:

• To assess the effectiveness of a novel stepped care intervention for alcohol dependent patients with co-morbid anxiety and/or depression compared to usual treatment for alcohol dependence in promoting abstinence from alcohol and increased quality of life and in reducing symptoms of anxiety and depression.
• To describe important factors relating to the maintenance of alcohol-related psychiatric comorbidity.

Step 1: All subjects will complete 12 weeks of pharmacotherapy (n = 120) on naltexone (50 mg, 1 tablet daily), acamprosate (333 mg, 2 tablets 3 times daily, reduced to 4/day for women <65kg), or a combination of the two. After a 3 week stabilization period, subjects will undergo complete formal assessment for anxiety and depression. Those subjects with a diagnosis of anxiety or depressive disorder regardless of drinking outcome will be offered the next step of care and followed up at 12-16 weeks.

Step 2: Subjects to undergo the next step of care (n = 30 per group, 60 in total) will be randomized by referring to the consecutively assigned subject identification number to a matched numbered envelope containing a random assignment card. Randomization will be stratified according to concomitant SSRI use. The treatment groups will be:

• Intervention for comorbid anxiety or depression, and
• Usual counseling care.

Inclusion criteria

for Step 1:

• alcohol dependence according to DSM-IV criteria, with alcohol as the subject's drug of choice,
• age 18-65,
• adequate cognition and English language skills to give valid consent and complete research interviews (as assessed by the mini mental state examination),
• willingness to give written consent,
• abstinence from alcohol for between 3 and 21 days (standard clinical criteria for use of acamprosate or naltrexone),
• resolution of any clinically evident alcohol withdrawal (score 0-1 on RPA hospital alcohol withdrawal scale), and a positive score on the initial comorbidity suspicion checklist (CSC).

Exclusion criteria

for Step 1:

• sensitivity to study medications or therapy with these drugs within 6 months,
• active major psychiatric disorder associated with significant suicide risk,
• pregnancy or lactation,
• advanced liver disease (hepatocellular failure, variceal bleeding, ascites or encephalopathy),
• other serious medical illness that would interfere with adherence to the study protocol.

Entry criteria to step 2:

• Completion of 3 weeks on acamprosate and/or natlrexone and/or, resolution of any clinically evident alcohol withdrawal (score 0-1 on RPA hospital alcohol withdrawal scale),
• case formulation and diagnosis for anxiety or depression (see below).

Exclusion criteria

2:

• Non-compliance on acamprosate and/or naltrexone,
• alcohol consumption at baseline levels,
• resolution of clinically evident anxiety or depression as assessed by the case formulation (see below). These patients will be offered further treatment