There is a paucity of research focused on patients with bipolar disorder and substance dependence. 33 In one trial, patients with bipolar disorder and a diagnosis of alcohol dependence were randomly assigned to receive either valproate or placebo. 34 Valproate therapy decreased the number of heavy consumption days and drinks per drinking day in these patients. In a study of 362 patients with bipolar disorder and alcohol dependence treated with lithium or valproic acid, there was no change in drinking days despite adding quetiapine to the regimen. 35
Pharmacotherapy and Depression
Lithium is not effective for patients with MDD and AUD. Lithium treatment for depressed patients with alcohol dependence did not improve abstinence, alcohol-related hospitalizations, or severity of either condition. 36
Aripiprazole is an antipsychotic that partially agonizes dopamine receptors. Dopamine implicates reward circuitry and has a role in AUDs. Aripiprazole was used as an adjunctive intervention in a randomized trial of 35 patients with comorbid alcohol dependence and depression. 37 There was less depression in both the aripiprazole plus escitalopram group and the escitalopram group. Imaging showed a change in activity in the left cingulate gyrus in the patients with comorbid alcohol dependence and MDD. The action of aripiprazole may be mediated through the anterior cingulate cortex.
Research on patients with alcohol dependence treated with fluoxetine found decreased Hamilton Depression Rating Scale (HDRS) scores but no change in alcohol consumption. 38
Sertraline diminishes depressive symptoms in abstinent alcoholics. In one study, depressed, recently abstinent alcohol users were randomly assigned to receive sertraline 100 mg daily or placebo. 39 Significant improvement was noted in HDRS and Beck Depression Inventory scores at 3- and 6-week intervals.
Citalopram was studied in patients randomly assigned to receive citalopram or placebo for alcohol abuse or dependence. 40 Patients in the citalopram group had more days of drinking and showed little change in frequency of alcohol consumption. There was no improvement in depression severity in the citalopram group relative to the placebo group. Citalopram also has been studied in combination with naltrexone. 41 Patients with depression and alcohol dependence were randomly assigned to receive either citalopram or placebo, as well as naltrexone. There were no significant differences in depression severity or drinking outcomes.
Treating depression with selective serotonin reuptake inhibitors (SSRIs) had variable results. Most SSRIs improve depression severity but largely have no effect on drinking outcomes.
A meta-analysis on the efficacy of antidepressant medications in treating patients with depression and substance abuse revealed that the antidepressants had a somewhat advantageous effect. 42 That finding was supported by the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. 43 About 33% of patients with citalopramtreated major depression endorsed concurrent SUD symptoms, 19% reported diagnosable alcohol use, 6% had other drug abuses, and 5% exhibited both alcohol and drug use. The groups did not differ in time needed to attain a better mood or in rate of response to citalopram.
Patients with citalopram-treated MDD and alcohol or drug abuse responded about as well as those without an SUD. However, those with alcohol and/or drug abuse had reduced rates of remission, and their remission was delayed, as compared with those without alcohol or drug abuse. There were more suicide attempts and psychiatric hospitalizations among the cohort with drug abuse.