Treating co-occurring alcohol use disorders and depression​

Treating major depression in the belief that once the depression improves the patient will be able to stop drinking does not work (Kranzler et al., 1995). Treatment must address both issues concurrently (Health Canada, 2001b).

In cases of treatment-refractory or repeatedly relapsing major depression, consider advising patients – regardless of their stated level of alcohol use – to completely eliminate alcohol use. The rationale for this suggestion is based on the following facts:

• Even relatively small amounts of alcohol can have a negative effect on treatment outcome for some patients.
• The clinician's ability to confirm the actual amounts of alcohol a patient consumes is very uncertain.
• Abstinence from alcohol is not associated with any health risks
• Alcohol use does not help to manage depression.

The simplest approach is to advise patients who have major depression that is responding poorly to treatment to abstain from alcohol.

Starting treatment

Assess risks

Concurrent alcohol use and major depression markedly increase the risk of intended and unintended harm to self and others. Intended risks include suicide, homicide and self-injury. Unintended risks include motor vehicle accidents, involvement with child welfare services and workplace injuries.

Major depression–related risks:

• suicide
• homicide
• child welfare
• driving.

Alcohol-related risks:

• driving
• child welfare (see the College of Physicians and Surgeons of Ontario's mandatory reporting policy for suspected child abuse and related child welfare issues)
• suicide risk, homicide risk or inability to care for self; consider emergency admission if warranted.

Initiate treatment

• Order blood work (complete blood count (CBC), gamma glutamyl transferase (GGT). 
• Initiate the Four-Week Test (see below).
• Book the next appointment, ideally in one to two weeks if the patient does not present as severely impaired or with risk-related symptoms.
• At the next visit (one to two weeks):
• review blood work
• perform additional physical exam, as indicated
• repeat review of safety risks.

The Four-Week Test

This test helps to assess the patient's level of alcohol use and readiness to change . It also helps to determine whether the patient's symptoms of depression are alcohol-related or idiopathic.

The Four-Week Test has been identified as a "clinical pearl," based on clinical experience and several key studies (Brown & Schuckit, 1988; Schuckit, 2006; Schuckit & Irwin, 1995), but it has not been validated through peer-reviewed empirical research.

The test is performed as follows:

• Indicate that you are concerned about the patient's symptoms of depression and that alcohol has a negative effect on depression.
• Advise the patient to avoid using alcohol for four weeks as the first step in reducing the symptoms of depression.

The response to your request indicates the patient's readiness to change. How the patient's symptoms of depression respond to the four weeks of abstinence indicates the relationship between the person's alcohol use and depression.

The patient may respond to your request for a four-week trial of abstinence in one of three possible ways:

1. The patient declines.

What this means:

• This response suggests that the patient is precontemplative with respect to changing alcohol use and that the patient has an alcohol use disorder.

What to do:

• Wait for opportunities to encourage and foster the patient's contemplation of the negative effects of alcohol use on depression. Use opportunistic brief interventions.
• Consider assessing the patient's alcohol history in greater depth, including appropriate physical exams and investigations.

2. The patient agrees to discontinue alcohol use for four weeks but returns to inform you of an unsuccessful attempt.

What this means:

• This situation suggests that the patient is in the preparation stage of change and may have an alcohol use disorder. It also suggests that the patient will need help making changes to alcohol use.

What to do:

• When possible, schedule several visits for motivational interventions with you or members of your team. If you do not have the resources, suggest that the patient connect with a mutual aid group such as Alcoholics Anonymous. Book regular monthly visits to track the patient's progress around alcohol use and to monitor functioning and depression symptoms.
• Consider prescribing medications for reducing alcohol use, such as naltrexone, acamprosate or topiramate.
• Consider starting an SSRI, especially for patients with suicidal ideation and a history of suicide attempts.

3. The patient abstains from alcohol for at least four weeks.

This response will result in one of three possible outcomes:

• Depression symptoms completely resolve. This suggests that the depression was alcohol induced. The next step is relapse prevention for the patient's alcohol use. Relapse prevention can include regular visits to reinforce and maintain the improvements or attending a mutual aid group such as Alcoholics Anonymous.
• The patient reports incomplete symptom improvement and your assessment confirms significant residual symptoms beyond sleep disturbance. Sleep disturbance and headache can persist for up to one year after a patient with an alcohol use disorder achieves abstinence. Incomplete improvement of depressive symptoms most likely indicates concurrent depression and alcohol use disorders. In this situation, the patient simultaneously begins alcohol relapse prevention and further depression treatment (the first intervention for depression was eliminating alcohol use).
• There is minimal to no improvement in depression symptoms or in daily functioning. This suggests idiopathic major depression with a low probability of concurrent alcohol dependence, although concurrent at-risk alcohol use cannot be completely ruled out. Initiate treatment for the depression immediately, and advise the patient against resuming alcohol use, pending functional and symptomatic remission of the depression.

Treating patients with suicidal ideation

Consider hospitalization

Patients who are using alcohol and have suicidal ideation are in the highest category of suicide risk. You should seriously consider hospital admission for these patients, including the possibility of involuntary admission.

Initiate antidepressant medication

For patients with suicidal ideation who are using alcohol but who do not currently require hospital admission, initiate an antidepressant if you are confident that the patient is motivated to take medication despite the alcohol use. Antidepressants may reduce suicidal ideation even if they do not significantly improve other symptoms of depression.

Exercise caution in selecting an antidepressant for patients who are using alcohol. Avoid antidepressants that carry an overdose risk, such as nortriptyline, venlafaxine, duloxetine, mirtazapine or bupropion. Also avoid benzodiazepines because they are contraindicated for patients who are using alcohol.

Supported self-care

Prescribe MoodGYM to patients who have Internet access at home. The program teaches people cognitive-behaviour therapy skills for preventing and coping with depression.

Although MoodGYM has not been specifically tested in patients with comorbid alcohol use disorders, evidence for the program's efficacy in treating major depression is strong and other studies have demonstrated the efficacy of computer-based cognitive-behavioural therapy (CBT) in patients with concurrent alcohol use disorder and major depression (Andersson et al., 2014; Dedert et al., 2013; Kay-Lambkin et al., 2009; McNaughton, 2009).

The Mind over Mood workbook is a useful self-help tool that teaches patients CBT techniques. It is an inexpensive intervention that requires minimal clinical resources.

In some cases, you may decide to start with Mind over Mood because the patient is ambivalent about using medication.

Clinicians without CBT training can support patients who are using self-help interventions by arranging regular brief follow-ups to confirm adherence, track progress and address the patient's questions (Andersson et al., 2014; Dedert et al., 2013).

It is best to initiate one intervention at a time to avoid diluting the patient's motivation across several interventions. Add the next intervention after the patient is fully adhering to the existing intervention. This is especially important with patients who have concurrent alcohol use and depression, because the patient is already engaged in both changing alcohol use and treating the depression.

Long-term management of co-occurring alcohol use disorder and major depression

Relapse to alcohol use is common. It exacerbates depression and in some cases, can do so even if the relapse is just for one day. The symptoms of depression tend to worsen over the course of several days after the relapse.

Relapses to alcohol use are often associated with stopping antidepressants, although the depressogenic effects of alcohol will occur even if the person continues to use medication throughout the relapse. Nonetheless, stopping the antidepressant during relapse may further aggravate the depressogenic effect of the relapse and may contribute to treatment failure. Advise patients to continue the antidepressant even if they relapse.

If patients with a co-occurring alcohol use disorder and major depression relapse to alcohol use or experience worsened depression symptoms after a clear period of unequivocal improvement, consider the deterioration to be alcohol related until proven otherwise.

If you definitively determine that alcohol is not involved in the depression symptoms, reconsider the diagnosis or missed features of the depression (e.g., bipolar, psychotic features, other substances, medical condition) and review the current treatment plan.

Key pharmacological approaches

Avoiding benzodiazepines

Avoid or stop prescribing benzodiazepines to patients with concurrent alcohol use and major depression. Reasons include:

• short- and long-term iatrogenic risks, including increased risk of serious falls, aspiration, cognitive impairment and death from multiple causes
• lack of long-term efficacy
• increased risk of misuse by patients with alcohol use disorders, due to cross-tolerance
• increased medico-legal risk: Primary care providers are not responsible for the effects of the alcohol, but are accountable for adverse events that occur while the patient is using benzodiazepines.
• possible diminished adherence to sustainable and effective treatments, due to immediate response to benzodiazepines.

If you have patients who are using benzodiazepines and alcohol concurrently, stop prescribing benzodiazepines via rapid titration. Organize medically managed withdrawal if a patient has been on high doses of benzodiazepines for a long period or if you are highly suspicious that the patient is taking more than prescribed.

Prescribing antidepressants

Recent evidence suggests that antidepressants should be considered even for patients who are drinking. However, the pattern of response to antidepressants can differ in the context of active alcohol use. Studies have found that response can be delayed to eight weeks and that the level of improvement is substantially diminished (Hashimoto et al., 2015; Ishikawa et al., 2013; Moak, 2003).

Suicidal ideation is an important indicator for initiating an antidepressant. Antidepressants are associated with decreased suicide risk in patients with suicidal ideation who are drinking.

When using antidepressants to treat patients with active alcohol use disorders, keep these facts in mind:

• The efficacy of the antidepressant is limited in the context of active drinking, especially in heavy drinkers.
• Lack of response to the antidepressant while a patient is drinking is often interpreted by the patient as a failure of the antidepressant; thus, the patient may be less likely to agree to a trial of a similar antidepressant in the future. Before beginning treatment, explain to the patient that alcohol use will reduce the medication's efficacy and that this lack of response should not be confused as a failure of the antidepressant.
• Rates of treatment non-adherence are higher among people with alcohol use disorders, further increasing the likelihood of a limited treatment response.

If a patient is binge drinking – which in this context means drinking at a hazardous level over a number of days or longer – but does not drink daily, prescribe an antidepressant when indicated. However, try to ensure that the patient does not stop the medication during the binge. Assess for decreased frequency, intensity and duration of binges over time.

Choosing an antidepressant

The evidence to support specific treatments for co-occurring alcohol use disorders and mood disorders is limited (Beaulieu et al., 2012). The treatment choice should be informed primarily by the risks associated with available treatments, with other factors then taken into consideration. Be aware of the following key risks:

• Avoid bupropion because of the risk of seizure (the manufacturer lists at-risk or heavy alcohol use, including a history of alcohol use disorder, as a contraindication for the use of bupropion).
• Avoid mirtazapine and tricyclic antidepressants because of the potential for increased sedative effects when they are used with alcohol.
• Target dosages of all antidepressants should be as high as the patient can tolerate, without going over dosage limits determined by standard practice.

Medications for alcohol use disorders that are safe to use with SSRIs and SNRIs include: 

• naltrexone
• acamprosate
• topiramate.

Duration of pharmacotherapy

Patients who have concurrent alcohol use and major depression should continue pharmacotherapy for longer than is typical for the general population – consider up to five years – because they have higher rates of relapse.

Also consider a period of five years for patients who took a long time to respond to treatment, demonstrated severe risks, were unable to work or experienced sever functional impairment.

Non-pharmacological options

Preliminary research suggests that deep transcranial magnetic stimulation (dTMS) may be effective in patients with co-occurring major depression and alcohol use disorders (Girardi, 2015; Rapinesi et al., 2015).

Cognitive-behavioural therapy and interpersonal therapy have also been shown to improve symptoms of depression in patients with alcohol use disorders (Markowitz, 2008; Riper, 2014). The impact of these interventions on alcohol use varies.

Key points about alcohol use and major depression

• Alcohol use is common in the general population, and thus in patients with major depression. Mood disorders may be associated with higher lifetime rates of alcohol use disorders.
• Alcohol can cause or exacerbate symptoms of major depression.
• The Four-Week Test can be helpful in assessing the patient's readiness for change and the effect of alcohol use on major depression.
• The stages of change model helps to determine the patient's readiness to change.
• Treating patients concurrently for the alcohol use disorder and the major depression is key.
• Eliminating alcohol use is associated with improved outcomes for depression.
• Antidepressants can be effective in treating the symptoms of depression in people with active alcohol use disorders, although the response is likely to be slower and less robust.
• Antidepressants may help to reduce alcohol use in patients with co-occurring depression.
• Antidepressants may reduce the risk of suicide in patients with concurrent alcohol use disorders and major depression who present with suicidal ideation.
• Buproprion should be avoided because of the much higher risk of seizure in patients with alcohol use disorders.
• Benzodiazepines should be avoided with patients who use alcohol regularly because they carry various risks, including increased risk of death from all causes.
• Alcohol-targeted medications can be useful adjuncts to antidepressant medication.