Jack R. Cornelius, MD, MPH

Alcohol is the drug of choice for adolescents, with cigarettes and marijuana being second and third.

 Contrary to widespread belief, alcohol dependence is most common in 18- to 20-year-olds, with progressively decreasing rates of alcohol dependence in older age groups.

 Similarly, the age at onset of alcohol dependence is typically highest among those in their later teen years and early 20s, with a much lower rate of onset after the age of 25 years.

Comorbidity, particularly with major depressive disorder (MDD), is the rule rather than the exception in young people.

 Alcohol use disorders (AUDs), including alcohol dependence and alcohol abuse, and MDD co-occur more frequently than would be expected by chance alone. A number of studies have shown an even stronger association between AUDs and comorbid MDD in clinical samples of adolescents and young adults than in community samples.

AUDs also commonly co-occur with bipolar disorder. Bipolar disorder can present as either depression, mania, or a combination of depression and mania, so care must be taken to distinguish between major depression and bipolar disorder when an adolescent presents with depressive symptoms.

The depressive symptoms of adolescents with comorbid AUD and MDD are similar to those of adults. The acute clinical presentation in adolescents tends to focus on depressive symptoms, while chronic difficulties--including social and health problems--typically result more often from AUDs. Adolescents typically drink less frequently but more heavily than adults.

 Adults with comorbid AUD and MDD demonstrate a much higher rate of suicidal indicators than either single-diagnosis comparison group (AUD or MDD alone).

 Adolescents in whom comorbid disorders have been diagnosed are at a higher risk for attempting suicide.

 Among those with comorbid disorders, suicide attempts are most common following a recent period of very heavy drinking.

 concluded that for most children and adolescents, the index episode of MDD is the beginning of a chronic, recurrent, lifelong disorder. They also found that major depression among children and adults is usually accompanied by other disorders, and continued treatment is generally needed to prevent recurrences of major depression. Similarly, Emslie and coauthors

 reported that 40% of the adolescents they studied with MDD (with no comorbid drug use or AUD) suffered a recurrence of major depression within 12 months of successful treatment with fluoxetine, which they concluded was a higher rate of recurrence of depression than is generally noted among adults.

 undertook a follow-up study of adolescents with comorbid AUDs in combination with major depression and found a high rate (80%) of recurrence of depression in the 5 years following acute-phase treatment with fluoxetine. Thus, it appears that adolescents with major depression display a higher rate of recurrence of major depression than do adults and that adolescents with comorbid disorders display a higher risk of recurrent depressive episodes than do adolescents without comorbidities.

Rapid relapse to alcohol and other substance use has been shown to generally occur following treatment for alcohol and other substance use disorders (SUDs) among adolescents, with two thirds of adolescents relapsing to alcohol or drug use within 6 months after treatment.

 Major depression comorbidity has been shown to be associated with earlier relapse to alcohol and other substance use in adolescents.

 However, the level of substance use typically declines somewhat in the year following treatment.

 Preliminary data from a small sample suggest that the long-term prognosis for adolescents with an AUD and a comorbidity may be better than that for adults with an AUD and a comorbidity.

 A high degree of heterogeneity characterizes adolescents' courses after treatment, involving multiple trajectory subgroups.

 Thus, the long-term course of depressive symptoms and alcohol use in adolescents with comorbidities is variable, but often problematic, so longer-term treatment is warranted--particularly for adolescents with significant residual symptoms.

Adolescents with major depression should be routinely screened for the presence of alcohol and other SUDs, and conversely, adolescents with an AUD should be routinely screened for the presence of major depression because of the high levels of co-occurrence of those disorders. If an SUD or AUD is detected on initial screening, then a follow-up urine drug screening and Breathalyzer or other measure of blood alcohol concentration should also be considered. As noted above, the comorbid presence of an SUD and major depression is often associated with suicidal ideation or suicidal behavior, so assessment of suicidality should be routine clinical practice if an SUD or major depression is noted.

 If these conditions are detected during screening, then appropriate referral should be made for further evaluation and subsequent treatment.

Some recent studies have suggested that several forms of psychotherapy may be promising in treating adolescent AUDs and other SUDs. These types of psychotherapy include several forms of family therapy, such as functional family therapy, multidimensional family therapy, multisystemic therapy, and the community reinforcement approach. Other promising forms of treatment in this population include motivational interviewing, cognitive-behavioral therapy, the 12-step approach, and contingency management reinforcement. However, the studies used in evaluating those therapies consisted primarily of patients without comorbidities, so their applicability to patient samples with comorbidities remains unclear.

A recent review of adolescent substance abuse treatment studies evaluated the effectiveness of 5 main psychotherapy treatment modalities: family-based and multisystemic intervention, behavioral therapy, cognitive-behavioral therapy, pharmacotherapy, and 12-step approaches.

 The authors concluded that the results of those studies looked promising for cognitive-behavioral therapy and family-based and multisystemic therapies for adolescents with SUDs but that various methodologic limitations made it difficult to evaluate whether one treatment approach is clearly more effective than another.

 concluded that virtually no studies have documented the differential efficacy of various therapies for treating adolescent AUDs and other SUDs and that no clear optimal dosage or length of treatment has been identified. These conclusions also apply to adolescents with comorbidities, since far less treatment research has been conducted involving these adolescents than adolescents with AUDs or SUDs but without comorbidities.

To date, there have been no reported adequately powered randomized placebo-controlled trials comparing various pharmacotherapies for the treatment of adolescents with comorbid major depression and AUD. Only 3 studies have evaluated the efficacy of any SSRI antidepressant in adolescents with depression and AUDs or SUDs, and all of these have used fluoxetine as the study drug.

 patients displayed either cannabis abuse or cannabis dependence and conduct disorder in addition to an AUD and MDD. The study was an open-label trial involving 8 adolescent boys. All were treated with  20 mg/d of fluoxetine for 7 weeks. Of the 8 adolescents, 7 demonstrated marked improvement in depressive symptoms and wished to continue to take fluoxetine after the trial. The study was conducted in a residential treatment center, so the patients could not drink alcohol or use substances. The authors of the study concluded that fluoxetine appeared to be safe and effective in treating adolescents with MDD and substance dependence.

A double-blind placebo-controlled study involving 126 adolescents with comorbidities was recently conducted by the same research group.

 The findings from that study showed that fluoxetine had a good safety profile in adolescents with comorbidities and that it had greater efficacy than placebo did in treating depression in adolescents with comorbid SUDs. At the end of the treatment trial, past 30-day drug use had decreased significantly in both treatment groups, but the difference between the treatment groups was not significant.

Our group conducted a pilot study of fluoxetine in adolescents with comorbid major depression and AUD.

 The study included a 12-week acute-phase trial involving 13 patients and a 5-year follow-up study. Data from the acute-phase (12-week) trial suggest that fluoxetine may be promising for treating both the depressive symptoms and the excessive alcohol use of adolescents with comorbidities. No patients displayed side effects from fluoxetine, and none became hypomanic or manic during the treatment trial. Data at 1-, 3-, and 5-year follow-ups suggest that continued treatment is often needed to prevent recurrences of major depression. The promising results of these preliminary studies involving adolescents with comorbidities are consistent with the results of our previous double-blind placebo-controlled trials in adults with comorbidities.

 demonstrated a 3-fold increase from 1991 to 2000 in the use of antidepressant medication in adolescents with comorbid AUD and MDD. These striking increases in the use of antidepressants among adolescents have occurred despite the lack of empiric evidence supporting or refuting the effectiveness of these medications for treating comorbid disorders in this age group.

Co-occurring disorders are the norm rather than the exception among adolescents with AUDs, and depressive disorders are the most common of the comorbid psychiatric disorders in adolescents. The use of medication for the treatment of this population has increased dramatically in the last 10 years, despite the relative paucity of empiric evidence regarding the safety and effectiveness of these treatments. 

Available data in the adult literature are inadequate to fully assess the safety and efficacy of the various treatments of AUDs in combination with various comorbid disorders, and the data that are available are particularly lacking in information concerning adolescents with these dual diagnoses. This lack of data is particularly problematic because treatments that are effective for adults with comorbidities are not necessarily safe and effective for adolescents with comorbidities. Acute-phase studies and long-term follow-up studies are warranted to clarify the safety and efficacy of various psychotherapy and pharmacotherapy treatments for comorbid adolescents. The results of several ongoing studies by our group will become available in the next few years.

Unfortunately, no treatment recommendation can be made at this time. Currently, double-blind placebo-controlled studies are the only recognized basis on which to make recommendations concerning treatment. Clinical experience without double-blind placebo-controlled studies is not considered sufficient evidence for making treatment recommendations. To date, no double-blind placebo-controlled studies dealing with this topic have been completed and published.

Dr Cornelius is professor of psychiatry and pharmaceutical sciences, Dr Bukstein is associate professor of psychiatry, and Dr Clark is associate professor of psychiatry and pharmaceutical sciences in the department of psychiatry at the University of Pittsburgh School of Medicine. The authors report that they have no conflicts of interest regarding the subject matter of this article.

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Articles

Alcohol is the drug of choice for adolescents, with cigarettes and marijuana being second and third. Contrary to widespread belief, alcohol dependence is most common in 18- to 20-year-olds, with progressively decreasing rates of alcohol dependence in older age groups.

Jack R. Cornelius, MD, MPH

Articles

Treating Adolescents With Major Depression and an Alcohol Use Disorder