There is consensus amongst experts that pharmacotherapy (i.e., antidepressants; see Table 47) for co-occurring depression and alcohol use disorders can be effective, provided an individualised approach is used [1098, 1099]; however, it has been suggested that using pharmacotherapy to treat only depression or only AOD use is not likely to be sufficient to achieve improvements for both conditions [1100].
A number of systematic reviews have examined the effectiveness of antidepressant medication among people with co-occurring AOD use disorders and depression [1100–1103]. Most studies to date have focused on alcohol use disorders, but other AOD use disorders examined include cocaine use disorder, opiate use disorder, and nicotine use disorder [1101].
Systematic reviews and meta-analyses have shown that, while their effect on AOD has been mixed, the effect of antidepressants on depression among people with AOD use disorders is comparable to that observed among people with single disorder depression [34, 1100–1102]. There is some evidence to suggest that their effectiveness may vary depending on the type of AOD use disorder a person presents with. For example, although studies of co-occurring alcohol dependence and major depression support the use of antidepressants [1102], most studies of cocaine and opiate dependent clients do not [1101].
The majority of studies to date have examined the use of SSRIs and few have directly compared the effectiveness of different types of antidepressants among people with AOD use disorders. As such, there is insufficient evidence to recommend the use of one over another [1102]. Despite a lack of comparative research, there is some evidence to suggest that particular antidepressants may be more effective in treating depression among people with AOD use disorders than others. In a systematic review of pharmacotherapy among people with co-occurring AOD use and depressive disorders (either major depressive disorder or dysthymia), Stokes and colleagues [1101] found that imipramine (a tricyclic antidepressant, TCA) improved depressive symptoms among people with co-occurring alcohol dependence and opiate dependence, however, SSRIs showed no effects on depression. The lack of effects for SSRIs was observed both when SSRIs were used alone and in combination with other relapse prevention medications (e.g., naltrexone). Consistent with these findings, the addition of citalopram to naltrexone and case management has not been shown to confer any added benefit over naltrexone and case management among people with either independent or substance-induced depression and alcohol dependence [1104]. Antidepressants that do not come under the umbrella of SSRIs or TCAs have been found to be effective in single studies, with improvements observed on outcomes such as depression, alcohol consumption, cravings, and time to relapse [1100].
It has also been suggested that different types of antidepressants seem to be suitable for different types of substance use disorders [1105]. In particular, people with AOD use disorders tend to respond better to antidepressants that have a similar direct or side effect profile to their substance use. Hence, the more sedating antidepressants such as doxepin or paroxetine are more effective among people who use alcohol, heroin, and sedatives, and the more stimulating antidepressants such as desipramine and bupropion have greater efficacy among those with depression who use stimulants and nicotine. As there is insufficient evidence for the use of antidepressants for treating depression among people who use psychostimulants such as amphetamines and ecstasy [1106, 1107], the use of the more stimulating antidepressants for these clients provides the best guidance at this time.
As with any medication, the choice of antidepressant used should be made with the client and take into consideration the safety and tolerability of the medication, and any potential contraindications. SSRIs and other atypical antidepressants are typically better tolerated, associated with fewer adverse effects, and are safer in overdose relative to TCAs [1102, 1108, 1109]. For all AOD clients, extreme caution should be taken when prescribing monoamine oxidase inhibitors (MAOIs). These medications are potentially dangerous because of the dietary and medication restrictions involved [1105, 1106]. Hypertensive crisis with intracranial bleeding and death can occur if combined with a tyramine-rich diet or contraindicated medications (including opioid and psychostimulant substances, such as over-the-counter cold and flu medications) [1110, 1111]. Further MAOIs have a number of possible/theoretical interactions with alcohol (tyramine in some wines/beers) and other drugs of abuse [1105]. For these reasons, MAOIs should only be used when other antidepressant medication options have failed.
Esketamine, an NMDA-receptor antagonist recently approved for the treatment of depression by the Australian Therapeutic Goods Administration, is another pharmacotherapy that may be considered for people who have not demonstrated an adequate response to at least two other antidepressants [1112]. Caution should be used however, due to its abuse potential and significant adverse effects (e.g., dizziness, nausea, dissociation) [1113–1116]. Relative to placebo, people are more likely to discontinue esketamine due to the intolerability of these side effects [1116].
Suicide risk should be carefully monitored when a person commences any antidepressant, given ongoing uncertainty and controversy regarding initiation of antidepressants and increased suicide risk; in particular, suicide attempts within the first three to four weeks of acute treatment [1117, 1118]. Thus, although it is suggested that the benefits of antidepressant use outweigh the risks, and appropriate use actually protects depressed patients from suicide, it is important to maintain appropriate monitoring of suicidality [1098, 1109]. It is important to note that it can take up to four weeks for an antidepressant to reach therapeutic levels. Responses to antidepressants are typically noticeable within two to four weeks, with continued improvement in symptoms for up to 12 weeks [1098]. With these issues in mind, early follow-ups after initiation of an antidepressant medication are recommended [1098]. If little or no improvement in mood occurs over the induction time specified by the drug manufacturer, and the medication is being taken as prescribed (usually a minimum of three weeks), consideration should be given to increasing the dose within the recommended range. If still little or no improvement is observed, switching or augmenting with another antidepressant may be considered. It is recommended that there be at least one within-class switch before considering augmentation or other options, keeping in mind the potential for drug interactions, and the adverse effects of some antidepressants [1098].
Thase and colleagues [1099] comment on the sometimes over-restrictive attitudes towards pharmacological treatments for depressive disorders among people with AOD use disorders, where clients can present in a state of physical and emotional despair that requires immediate intervention. Considering the safety of most of the newer antidepressants such as SSRIs, such caution as waiting for a minimum number of weeks of abstinence cannot be justified. This would particularly apply where a client has a history of depression during periods of abstinence, or where the person has had successful antidepressant intervention in the past.
Some clients may be reluctant to take SSRIs due to the misconception that they are ‘addictive’. SSRIs are not habit-forming; however, people may experience a discontinuation syndrome if medication is stopped abruptly [1109]. Symptoms typically appear within three to four days of stopping and are similar to some of those experienced during alcohol and opiate withdrawal (e.g., flu-like symptoms, light-headedness, headache, nausea) [1109]. When discontinuing SSRIs, the dose should be gradually tapered.
Naltrexone and acamprosate, medications commonly used in the treatment of alcohol use disorders, have shown moderately positive outcomes in depression as a single disorder [1120]. However, in a 2019 review of trials examining the use of alcohol medications among people with co-occurring alcohol dependence and depression, naltrexone and acamprosate produced mixed findings. As such, the authors concluded that their efficacy for alcohol use disorder and depression together remains unclear [1100]. More promising results have been found in relation to the use of disulfiram in this population, which has been associated with improvements in both depression and alcohol-related outcomes in some studies [1100, 1103]. While both acamprosate and naltrexone are available on the Pharmaceutical Benefits Scheme for alcohol dependence, disulfiram is expensive and only available with a private prescription.
Recent reviews have noted emerging evidence of the efficacy of anticonvulsants/antiepileptics for alcohol abstinence in people with co-occurring depression [1100, 1103], and recent trial results have demonstrated that a single high-dose of buprenorphine may rapidly reduce depression and suicidal ideation in people with opiate dependence and co-occurring depression [1121, 1122]. These findings suggest that buprenorphine may prove to be an especially useful pharmacotherapy for this sub-group, however, further research is needed.