Alcohol, Anxiety, and Depressive Disorders

In this section, trials that used medication and psychotherapy treatments are discussed, as are the effects of those treatments on depressive symptoms and AUD symptoms. We use data from the Oregon Adolescent Depression Project (OADP) (23) to address these questions. The OADP is unique in combining 4 prospective assessment waves from adolescence to adulthood paired with retrospective recall between assessments, providing diagnostic coverage up to age 30. This design compares favorably to most prospective studies, which have more limited coverage, as well as retrospective studies, which are impacted by long-term recall bias. In keeping with the new DSM-5 (24), we investigate AUD as a single disorder, rather than abuse and dependence as separate disorders. We are warned that this absence of evidence is not the evidence of absence (a truism made famous by the infamous Donald Rumsfeld).

Table 1. Table of included studies.

Despite the availability of several evidence-based medications and behavioral therapy approaches for treating co-occurring AUD and depressive disorders, improvements in treatment for this population are clearly needed. Consideration of disorder heterogeneity and key subgroup differences may help develop more targeted and personalized treatments to improve outcomes for this population. More knowledge about optimal treatments for co-occurring AUD and depressive disorders is needed. Although medication and behavioral therapy have both shown promise, response rates have been somewhat modest. Efforts to enhance treatment outcomes would benefit from investigation into the characteristics of people who do not respond to existing treatments. A better understanding of the heterogeneity within this population will inform more personalized treatment approaches and might ultimately improve treatment response.

These psychological conditions are often intense enough to interfere with life functioning, and the symptoms are often recognized by physicians and other health care providers as serious enough to require treatment. When depressed or anxious alcohol-dependent people are asked their opinions about cause and effect, they often reply that they believe they drink in order to cope with their symptoms of sadness or nervousness. The relationship between alcohol-use disorders and psychiatric symptoms is both clinically important and very complex (Brady and Lydiard 1993). As a typical depressant, alcohol affects the brain in many ways, and it is likely that high doses will cause feelings of sadness (i.e., depression) during intoxication that evolve into feelings of nervousness (i.e., anxiety) during the subsequent hangover and withdrawal.

• We are confident only in estimates at postintervention about the benefits of CBTs (on depressive symptoms and alcohol use), SSRIs (on functional status and alcohol use), and TCAs (on depressive symptoms) to be sufficient enough to warrant their consideration for policy and practice.
• First, as cited in a review article, a survey of 18- to 25-year-old male students and staff at a university revealed no higher rates of depressive or anxiety disorders among COA’s compared with control subjects, a finding confirmed by a more intensive evaluation of men in a laboratory setting (Schuckit 1994).
• Using language from the GRADE approach, CBTs likely reduced depressive symptoms (moderate confidence) and may have reduced alcohol use (low confidence), SSRIs likely improved functional status (moderate confidence) and may have reduced alcohol use (low confidence), and TCAs may have reduced depressive symptoms (low confidence).
• This approach did not allow us to investigate the specific importance of dependence symptoms (1, 3, 15) and use of a broad definition may increase the possibility of conflicting findings across studies (36).

After searching the abstracts and checking for the eligibility criteria in identified potential abstracts, eight articles were regarded as a potential for inclusion in the present systematic review published between January 2010 and September 2020, covering 132,373 patients with depression and either alcohol dependence or SUD. Some of the limitations of the study do not need to be highlighted in the abstract, such as the lack of contact with some trial authors for missing information and data, or the use of SMDs rather than mean differences. Conversely, crucial limitations preventing a clear interpretation of the data are missing, namely the absence of demonstrated treatment effect over the long-term, and an attrition bias that cannot be ruled out (half of the studies had an unclear or high risk of bias related to completeness of outcome data at post intervention). Two reviewers independently extracted study-level descriptive data (SG and either GA or EH) and outcome data (SG and MB).

3) According to figure 1 (flow diagram), 86 citations were included, corresponding to 35 studies. Could the authors clarify the difference between the number of citations and the number of studies included? The number of citations identified through database searching should be provided before removing duplicates.

• Sean Grant and co-workers report on pharmacological and psychological treatments for patients with both alcohol-use and depressive disorders.
• Conversely, crucial limitations preventing a clear interpretation of the data are missing, namely the absence of demonstrated treatment effect over the long-term, and an attrition bias that cannot be ruled out (half of the studies had an unclear or high risk of bias related to completeness of outcome data at post intervention).
• The authors conclude that the available evidence suggests potential benefits of TCAs (tricyclic antidepressants) for depressive symptoms, and SSRIs (selective serotonin reuptake inhibitors) for total drinking and functional status.
• Please add a sentence to your abstract to summarize where the constituent studies were done and the timeframe, and the median study size.
• Only studies published in English were classified as related articles, which can be further evaluated in the second step.

Children of alcoholics (COA’s) do not have an increased risk for major depressive or anxiety disorders

We ultimately included 98 citations reporting 36 studies that randomized a total of 2,729 participants (see Fig 1). AID improves with alcohol abstinence, while MDD persists.4 Differentiating between these requires a thorough assessment of the onset, course and relationship of depressive symptoms to alcohol use (Table 1). Yule and Kelly, in Integrating Treatment for Co-Occurring Mental Health Conditions, consider the prevalence and treatment of co-occurring AUD and mental health conditions. They discuss screening tools, assessment, and the development of different treatment approaches.

2) Studies included in the analysis go back to 1971 when the DSM was only in its second edition. This is a potential weakness because the criteria for psychiatric diagnoses changed dramatically from DSM II to DSM III but then changed very little after DSM III. The reliability of pre-DSM III diagnoses were notoriously poor and served as a primary reason for the dramatic changes found in DSM III and beyond. Comparing DSM II diagnoses to diagnoses made by DSM III and later is comparing apples to oranges. All data underlying the findings in this review (including GRADE assessments of confidence in effect estimates) can be found in S2 Appendix.

Indeed, several disorders are more likely to be observed in COA’s than in control groups, including conduct problems, such as difficulties with discipline at home or in school (Schuckit and Hesselbrock 1994). As cited in our recent review, however, an evaluation by Hill and colleagues1 of 95 COA’s and control subjects at ages 8 to 18 showed no evidence of increased rates for depressive or anxiety disorders in the offspring of alcoholics (Schuckit and Hesselbrock 1994). That same review cited a second study of 283 COA’s and control subjects by Reich and colleagues1 that also reported no evidence for an increase in depressive disorders in COA’s, although evidence indicated a possible higher rate of anxiety symptoms. However, a prospective followup of 204 Danish COA’s and control subjects by Knop and colleagues1 demonstrated no differences between the 2 groups by age 20 with respect to either depressive or anxiety disorders. A subsequent followup of the Danish population revealed higher levels of anxiety disorders but not depressive episodes for the offspring of alcoholic parents, although by that age some of the symptomatology might already have resulted from high levels of alcohol or other drug (AOD) intake. Fortunately, several important ongoing studies will help answer some remaining questions regarding the treatment of coexisting depressive or anxiety disorders in the context of alcoholism.

Fig 2. Network structure.

This absence of evidence on interventions and very low confidence in effect estimates does not indicate evidence of an absence of effects, but rather that future studies are needed to overcome limitations in the current body of evidence (such as limited study duration and insufficient statistical power). Furthermore, given that identified effects in which we had at least low confidence were all at postintervention, applicability of evidence on drinking outcomes to inpatient and residential care settings may be limited. Second, the possibility that a longer term anxiety or depressive disorder exists in an alcoholic must always be considered. Perhaps 10 percent of men and 10 to 20 percent of women in the general population develop severe anxiety or depressive disorders (Regier et al. 1990); therefore, it would be logical to expect that at least this proportion of alcoholics also would have similar syndromes. Identifying when an alcohol-dependent person has an independent or long-term major anxiety or depressive disorder requires gathering a careful patient history that searches for evidence of severe psychiatric symptoms either before the onset of severe alcohol-related problems or during a subsequent period of extended abstinence. Vaillant (1995) has conducted a 40-year followup of 2 samples, one including more than 200 college men and the other including more than 450 blue-collar boys who were ages 11 to 16 at the time of the original study.

Depressive symptoms

We next examined temporal ordering and concurrency of MDD and AUD in individuals with cumulative comorbidity by T4. alcohol use disorder and depressive disorders pmc AUD occurred first in the remaining 41% of cases, except for rare instances of simultaneous onset (2%). Cumulative MDD+AUD comorbidity was equally divided between concurrent and successive comorbidity (51% v. 49%). Figure 1 depicts the proportion of comorbid subtypes as a function of lifetime temporal ordering and concurrency. 4) The table summarizing risk of bias across studies (eTable 4) should be included in the body of the manuscript instead of the appendix.

A preliminary evaluation of the lifetime rates of major depressive disorders in 2,409 interviewed relatives of alcoholics revealed a rate of 17.5 percent, a figure that was almost identical to the rate observed in control families. Co-occurring alcohol use disorder (AUD) and major depressive disorder (MDD) are prevalent and complex conditions in clinical practice.1 The bidirectional relationship between alcohol use and depression complicates diagnosis and treatment. Integrated care addressing both conditions is more effective than sequential treatment, yet often underutilized. This narrative review synthesizes current best evidence, including guideline-concordant care and recent meta-analyses, to provide clinician-oriented, practical guidance.

Integrated treatment addressing both disorders simultaneously has shown better outcomes compared to sequential treatments. This article provides evidence-based clinical guidance for managing patients with co-occurring AUD and MDD, focusing on pharmacotherapy, psychotherapy and integrated care models. Pharmacologically, selective serotonin reuptake inhibitors and tricyclic antidepressants are commonly used to treat depression in individuals with AUD, while naltrexone and acamprosate are first-line medications for AUD.

Medication trials

Also, an 18-year followup of 80 children who had experienced severe depressive episodes earlier in life revealed no evidence of an increased risk for alcoholism during the followup period (Harrington et al. 1990). Finally, Schuckit’s research group followed 239 alcoholic men 1 year after they received alcoholism treatment, and the data revealed no significantly increased rates of major depressive or anxiety disorders (Schuckit and Hesselbrock 1994). It is possible, however, that some of these studies might have excluded subjects with more severe anxiety or depressive disorders from the original samples, and consequently more work in this area is required (Kushner 1996). My main concern relates to the interpretation of the data and the conclusions of the study, which in my view do not accurately reflect the results of the study.

Integrated Management of Co-Occurring Alcohol Use Disorder and Depression: Clinical Approaches for Concurrent Disorders

A summary of outcome data across studies can be found in Table 4, while a summary of findings from the network meta-analyses (including effect estimates, intervention rankings, and confidence in the evidence) can be found in Tables 5 and 6. Only one notable study of COA’s has demonstrated a higher-than-expected risk for these major psychiatric disorders. However, as pointed out by Kushner (1996), larger studies of COA’s who have passed the age of risk for most disorders will need to be conducted before final conclusions can be drawn.