Evidence-Based Reviews

Pharmacotherapy for comorbid depression and alcohol dependence

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Evidence is mixed for antidepressants, alcohol dependence medications, or a combination


 

References

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With a lifetime prevalence of 30%, alcohol use disorders (AUDs)—which in DSM-IV-TR include alcohol abuse and alcohol dependence—are among the most common psychiatric disorders.1 Depressive disorders, including major depressive disorder (MDD) and dysthymia, frequently co-occur with AUDs.2-4 This pattern of comorbidity adversely affects the prognosis, course, and treatment of both MDD and AUDs.5 High severity in 1 of these disorders is associated with high severity in the other.2,6 Alcohol dependence appears to prolong the course of depression7,8 and increases the risk of suicidal symptoms and behaviors.9,10 Patients with depression and AUDs are at increased risk of relapse to heavy drinking.7,11

Whether the high comorbidity rate of depressive disorders and AUDs is a result of 1 disorder causing the other (ie, AUDs leading to depression or vice versa) or can be attributed to shared etiology is unknown. Clinicians need to consider this question when treating patients with this pattern of comorbidity because distinguishing primary depression from secondary depression influences treatment decisions.12

There is a great need for pharmacologic interventions that can concurrently treat both depression and AUDs. This article reviews the evidence for current treatments for dually diagnosed patients and highlights novel agents that are worthy of further study for this complex patient population.

Current treatment options

Pharmacotherapy for MDD and alcohol dependence is common when these conditions occur alone. FDA-approved medications for treating depression include monoamine oxidase inhibitors, tricyclic antidepressants (TCAs), tetracyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors.

SSRIs are the most widely used class of antidepressants. They gained FDA approval based on studies conducted in non-comorbid patients because patients with comorbid conditions usually are excluded from research studies.13 Few trials have evaluated patients with depression and AUDs; TCAs and SSRIs are best studied in these patients.

Serotonergic antidepressants

SSRIs are first-line medications for MDD because of their low abuse potential, favorable side effect profile, and relative safety in overdose.

Findings regarding the efficacy of SSRIs in patients with comorbid depression and AUDs have been mixed (Table 1).14-20 Only fluoxetine and sertraline have been evaluated in double-blind, placebo-controlled trials; 4 studies were conducted with adults and 1 with adolescents. In a 12-week trial, Cornelius et al14 found that fluoxetine reduced depressive symptoms and alcohol use in 51 patients with MDD and alcohol dependence. Others researchers have reported that the SSRIs sertraline and fluoxetine reduced depressive symptoms but had few direct effects on drinking outcomes.15,16 A 2003 study17 compared sertraline, 200 mg/d maximum, with placebo for 12 weeks in 82 patients with MDD and alcohol dependence. Depressive symptoms and alcohol consumption decreased substantially over time for both groups. However, further analyses revealed that depression-related outcomes differed based on severity of depressive symptoms—patients with more severe depressive symptoms at baseline benefited the most from sertraline.

Table 1

Serotonergic antidepressants for patients with AUDs and depression

StudySampleResults
Cornelius et al, 199714Outpatients with severe major depression and AD
1. Fluoxetine (20 to 40 mg/d; n = 25)
2. Placebo (n = 26)
Greater reductions in depressive symptoms and drinking in patients treated with fluoxetine compared with placebo
Roy, 199815Inpatients with current major depression and AD who were abstinent for ≥2 weeks
1. Sertraline (100 mg/d; n = 18)
2. Placebo (n = 18)
Greater reductions in depressive symptoms in patients treated with sertraline compared with placebo. Drinking outcomes were not emphasized because 35 of 36 patients reported continuous abstinence throughout the trial
Kranzler et al, 199516Outpatients with AD. Fourteen percent had current major depression. All received weekly individual or group CBT focused on relapse prevention and skills building
1. Fluoxetine (mean daily dose: 48 mg; n = 51)
2. Placebo (n = 50)
Significant decrease in alcohol consumption for both groups during the trial. No significant differences in alcohol consumption between groups. Among those with current depression, patients treated with fluoxetine experienced greater reduction in depressive symptoms vs placebo
Moak et al, 200317Currently depressed, actively drinking, alcohol-dependent outpatients. All received individual CBT
1. Sertraline (mean daily dose: 186 mg; n = 38)
2. Placebo (n = 44)
Sertraline had an advantage over placebo in reducing depressive symptoms in women but not in men. Sertraline reduced drinks per drinking day but not other drinking-related outcomes
Cornelius et al, 200918Adolescents (age 15 to 20) with AA or AD and MDD. All received intensive manual-based therapy (CBT for MDD and AUD, MET for AUD) almost weekly
1. Fluoxetine (20 mg/d; n = 24)
2. Placebo (n = 26)
All improved during the course of trial. No significant differences between fluoxetine and placebo groups in depression- or drinking-related outcomes
Roy-Byrne et al, 200019Actively drinking alcohol-dependent outpatients with history of ≥1 depressive episode. All received weekly group therapy for alcoholism
1. Nefazodone (mean daily dose: 460 mg; n = 32)
2. Placebo (n = 32)
Greater reduction in depressive symptoms but not in drinking-related outcomes in patients treated with nefazodone
Hernandez-Avila et al, 200420Outpatients with AD and current major depression. All received supportive psychotherapy for 10 weeks
1. Nefazodone (mean daily dose: 413 mg; n = 21)
2. Placebo (n = 20)
Depressive and anxiety symptoms declined significantly over time, but no statistically significant differences in depressive or anxiety symptoms between nefazodone and placebo. Patients treated with nefazodone had significantly greater reductions in heavy drinking days and in total drinks compared with placebo-treated patients
AA: alcohol abuse; AD: alcohol dependence; AUDs: alcohol use disorders; CBT: cognitive-behavioral therapy; MDD: major depressive disorder; MET: motivational enhancement therapy

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