Treating depression in patients with alcohol or drug use disorders: A need for clearer guidelines

Depressive symptoms are widespread among patients seeking help with an alcohol or other drug use disorder. As most drugs of abuse have immediate, direct biological effects on mood, it can be extremely challenging to determine whether the depression represents an independent disorder or is substance-induced, particularly in the context of ongoing substance use. Furthermore, in contrast to the substance-specific mood effects seen during intoxication and withdrawal, depressive symptoms are common in long-term heavy users of virtually all drugs of abuse, including nicotine and alcohol. Experiencing such symptoms can also be an effect of struggling to cope with major psychosocial stressors, which ongoing drug use may further exacerbate. As such, even in patients whose depressive symptoms occur only after heavy substance use, it is often unclear if this relates to direct biological effects, social problems and/or lifestyle factors caused by their substance use.

For example, stimulant use often promotes a lifestyle which disrupts diurnal rhythms, affects diet and impairs physical health, while heavy use of any substance can impact upon work and relationships. In other cases, the presence of depression may promote substance use as a way of trying to cope with dysphoria, poor sleep or anxiety. Finally, substance use disorders and mood disorders share overlapping genetic and environmental aetiologies. For any individual, more than one causal mechanism may be present, and the contribution of each mechanism to the current presentation may vary over time. Co-occurring problems such as personality disorders and posttraumatic stress disorder are common among patients with substance use disorders, and these may also contribute to mood symptoms, further complicating the picture.

The Feighner criteria of the early 1970s promoted a categorical approach to diagnosis, labelling mood disorders as primary or secondary according to whether another pre-existing condition explained the mood disorder. This schema strongly influenced later editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). DSM-5 and the draft version of ICD-11 both still recognise substance-induced mood disorders as diagnostic categories. They note that substance-induced depression (SID) resembles other forms of depression in its symptom profile, but differs only insofar as symptoms are judged to be a direct consequence of substance use.

DSM and ICD take similar approaches to determining whether a mood disorder is substance-induced. Both systems focus on determining the temporal relationship between substance use and depression to make a diagnosis of SID, and they essentially frame SID as a diagnosis of exclusion. DSM does this by defining independent depression (ID), which is mutually exclusive with SID. ID is diagnosed when there is a history of depression preceding the onset of substance use, or at least 1 month after the cessation of acute withdrawal or severe intoxication. While intuitively appealing, identifying a history of ID requires patients to recall accurately the temporal relationship between past mood problems and substance use. This procedure is prone to bias, therefore the reliability of a diagnosis of ID or SID is often low.

Despite substance use disorders being prevalent in Australia and New Zealand, population surveys find SID difficult to detect. For example, the lifetime prevalence of substance-induced mood disorders was only 0.1% in a recent study in Australian men, compared to 18.2% for mood disorders in total (Williams et al., 2016). This suggests current procedures to identify SID do not work well in population settings. In substance treatment settings, it is easier to identify patients who appear to have SID, but follow-up studies show that over time many of these patients are re-categorised as having ID.

The Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines for mood disorders note the importance of assessing substance use in patients with depression, and trying to differentiate primary mood disorders from SID (Malhi et al., 2015: 112). The guidelines also recommend that ‘a definitive psychiatric diagnosis should be withheld until symptoms of intoxication, detoxification, or of withdrawal, have completely abated’. However, in a nod to pragmatism the guidelines also suggest ‘often in outpatient practice settings, treatment of the mood disorder and substance use disorder needs to occur concurrently’.

Given the limitations of current diagnostic approaches, and the lack of specificity in current guidelines, how could treatment guidelines be improved for depressed patients with an alcohol or drug use disorder? First, although expert consensus (including the RANZCP guidelines) stresses the importance of determining whether a mood disorder is attributable to the effects of substance intoxication or withdrawal, this is very difficult in patients with an active alcohol or drug use disorder (McKetin et al., 2011). This suggests a low emphasis should be placed on determining whether mood symptoms are substance-induced or independent in early treatment contacts. Current evidence supports integrated psychotherapies targeting substance use, mood and anxiety as the first line intervention regardless of whether depression appears to be independent or substance-induced (Baker et al., 2012). Pharmacotherapy for depression can usually be safely delayed until it is clear that the mood symptoms remain present despite psychological treatment and reduced substance use.

Second, while antidepressants are likely to be more efficacious for patients with ID than those with SID, in general there is limited evidence for antidepressant treatment in either ID or SID if patients continue using alcohol or other drugs heavily. Indeed, antidepressants may produce side effects (e.g. sexual dysfunction), which may aggravate unwanted effects of the substance use itself. Despite this, antidepressant and antipsychotic medications are frequently prescribed to patients who are using substances heavily (Foulds et al., 2016). Potential explanations for these findings include prescribers’ under-recognition of substance use disorders, limited confidence and competency in managing such disorders without pharmacotherapy, lack of availability of psychosocial treatments and unrealistic expectations from prescribers and/or patients about the effectiveness of medications in this context.

Third, treatment guidelines need to be informed by future studies which provide more accurate ways of identifying groups of patients with similar trajectories and patterns of treatment response. While landmark studies in the addiction field, such as Project MATCH, suggest this task may be challenging, better evidence to guide individualised treatment strategies for patients with comorbidity is needed.

The RANZCP clinical practice guidelines for mood disorders provide well-grounded and pragmatic advice about the treatment of depression in patients with substance use disorders, but they need to be refined so as to be more specific and reduce ambiguity. Better quality evidence from clinical trials is also urgently needed in this area, and the current paucity of high-quality studies remains a challenge for future versions of clinical guidelines.