D. Scott Wood

Cannabis withdrawal is common among treatment-seeking adolescents with cannabis dependence and major depression, and is associated with rapid relapse to dependence☆

Recently, reports have suggested that cannabis withdrawal occurs commonly in adults with cannabis dependence, though it is unclear whether this extends to those with comorbid depression or to comorbid adolescents. We hypothesized that cannabis withdrawal would be common among our sample of comorbid adolescents and young adults, and that the presence of cannabis withdrawal symptoms would be associated with a self-reported past history of rapid reinstatement of cannabis dependence symptoms (rapid relapse). The participants in this study included 170 adolescents and young adults, including 104 with cannabis dependence, 32 with cannabis abuse, and 34 with cannabis use without dependence or abuse. All of these subjects demonstrated current depressive symptoms and cannabis use, and most demonstrated current DSM-IV major depressive disorder and current comorbid cannabis dependence. These subjects had presented for treatment for either of two double-blind, placebo-controlled trials involving fluoxetine. Cannabis withdrawal was the most commonly reported cannabis dependence criterion among the 104 subjects in our sample with cannabis dependence, being noted in 92% of subjects, using a two-symptom cutoff for determination of cannabis withdrawal. The most common withdrawal symptoms among those with cannabis dependence were craving (82%), irritability (76%), restlessness (58%), anxiety (55%), and depression (52%). Cannabis withdrawal symptoms (in the N=170 sample) were reported to have been associated with rapid reinstatement of cannabis dependence symptoms (rapid relapse). These findings suggest that cannabis withdrawal should be included as a diagnosis in the upcoming DSM-V, and should be listed in the upcoming criteria list for the DSM-V diagnostic category of cannabis dependence.

The Utility of Neuropsychological Tests in Evaluation of Attention-Deficit/ Hyperactivity Disorder (ADHD) versus Depression in Adults

A comparison was made between adults with depression and with Attention-Deficit/ Hyperactivity Disorder (ADHD) on a battery of cognitive tests of attention span and memory. Both the ADHD and depression groups were subdivided with regard to comorbid depression in the ADHD group and developmental learning disorder in both groups. Utilizing Discriminant Function Analysis, it was found that variables derived from the California Verbal Learning Test, the Paced Auditory Serial Addition Test, and the Stroop Test discriminated among the various subgroups at a level significantly exceeding chance. However, although the great majority of the ADHD participants were correctly classified, there were numerous misclassifications among the depressed groups. It was concluded that the tests used were highly sensitive to ADHD, but were also sensitive to a subgroup of depressed individuals.

Double-blind fluoxetine trial in comorbid MDD-CUD youth and young adults.

OBJECTIVE This study compared the acute phase (12-week) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the cannabis use of adolescents and young adults with comorbid major depression (MDD) and a cannabis use disorder (CUD) (cannabis dependence or cannabis abuse). We hypothesized that fluoxetine would demonstrate efficacy versus placebo for the treatment of the depressive symptoms and the cannabis use of adolescents and young adults with comorbid MDD/CUD. METHODS We conducted the first double-blind placebo-controlled study of fluoxetine in adolescents and young adults with comorbid MDD/CUD. All participants in both treatment groups also received manual-based cognitive behavioral therapy (CBT) and motivation enhancement therapy (MET) during the 12-week course of the study. RESULTS Fluoxetine was well tolerated in this treatment population. No significant group-by-time interactions were noted for any depression-related or cannabis-use related outcome variable over the 12-week study. Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in depressive symptoms and in number of DSM diagnostic criteria for a CUD. Large magnitude decreases in depressive symptoms were noted in both treatment groups, and end-of-study levels of depressive symptoms were low in both treatment groups. CONCLUSIONS Fluoxetine did not demonstrate greater efficacy than placebo for treating either the depressive symptoms or the cannabis-related symptoms of our study sample of comorbid adolescents and young adults. The lack of a significant between-group difference in these symptoms may reflect limited medication efficacy, or may result from efficacy of the CBT/MET psychotherapy or from limited sample size.

Double-blind placebo-controlled trial of fluoxetine in adolescents with comorbid major depression and an alcohol use disorder.

OBJECTIVE This study compared the acute phase (12-week) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the drinking of adolescents with comorbid major depression (MDD) and an alcohol use disorder (AUD). We hypothesized that fluoxetine would demonstrate efficacy versus placebo for the treatment of both the depressive symptoms and the drinking of comorbid MDD/AUD adolescents. METHODS We conducted the first double-blind placebo-controlled study of fluoxetine in adolescents with comorbid MDD/AUD. All participants in both treatment groups also received intensive manual-based Cognitive Behavioral Therapy (CBT) and Motivation Enhancement Therapy (MET). RESULTS Fluoxetine was well tolerated in this treatment population. No significant group-by-time interactions were noted for any depression-related or drinking-related outcome variable. Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in both depressive symptoms and level of alcohol consumption. End-of-study levels of depression and drinking were low in both treatment groups. CONCLUSIONS The lack of a significant between-group difference in depressive symptoms and in drinking may reflect limited medication efficacy, or may result from limited sample size or from efficacy of the CBT/MET psychotherapy. Large multi-site studies are warranted to further clarify the efficacy of SSRI medications in this adolescent MDD/AUD population.

A Longitudinal Study of Insomnia and Other Sleep Complaints in Adolescents with and without Alcohol Use Disorders

BACKGROUND Sleep disturbances are both common and well-characterized in adults with alcohol use disorders (AUDs), but have received little study in adolescents with AUDs. Furthermore, a handful of studies suggest that sleep complaints are a risk factor for AUDs. However, no published studies have yet examined the longitudinal course of sleep complaints in adolescents with AUDs; in particular, it remains unclear how persistent AUD-associated sleep complaints are in this age group, and what types of sleep complaints are most relevant to alcohol-use symptoms. We investigated these questions in a 5-year longitudinal study of adolescents with and without AUDs at baseline. METHODS Participants were 696 adolescents (age 12 to 19) from a longitudinal study at the Pittsburgh Adolescent Alcohol Research Center. At baseline, 347 participants had a current AUD (AUD+), while 349 had no current or past AUD (AUD-). We examined sleep and alcohol involvement at baseline as well as 1-, 3-, and 5-year follow-up visits. Sleep variables included self-reported insomnia and hypersomnia, as well as variability in weekday-weekend sleep duration, all at baseline. Covariates included sex, age, current alcohol symptoms, and depression severity. RESULTS The AUD+ group reported more overall sleep disturbance at baseline, including greater insomnia and hypersomnia complaints, and greater variability in weekday-weekend sleep duration. Group differences in insomnia and hypersomnia complaints persisted to the 5- and 3-year follow-ups, respectively. In the AUD- group, greater insomnia complaints at baseline predicted an increase in alcohol symptoms at the 1-year follow-up, while greater variability in sleep duration at baseline predicted an increase in alcohol symptoms at the 3- and 5-year follow-ups. CONCLUSIONS These results complement previous findings in other samples, indicating that insomnia and other sleep problems are a chronic predicament for adolescents with AUDs. The findings also suggest that sleep disturbances may place adolescents without AUDs at an elevated risk of developing alcohol problems.

Fluoxetine in Depressed AUD Adolescents: A 1-Year Follow-up Evaluation

The authors conducted the first naturalistic 1-year follow-up evaluation of 10 adolescents with comorbid major depressive disorder and an alcohol use disorder (AUD) who had previously participated in an acute phase study of open-label fluoxetine plus psychotherapy (Cornelius et al. 2001). The goal of this follow-up evaluation was to determine whether the decreases in drinking and in depressive symptoms that were noted during the acute phase study persisted at the follow-up evaluation. At the 1-year follow-up evaluation, the group continued to demonstrate significantly fewer depressive symptoms (according to the 24-item Hamilton Rating Scale for Depression) and a lower frequency of drinking (drinking days in the last 30 days) than they had demonstrated at the baseline of the acute phase study. Surprisingly, all of the subjects had chosen to discontinue their antidepressant medication by the second month of their naturalistic follow-up period. Three subjects had experienced a relapse of their major depression during the follow-up period, and three others demonstrated a persistence of their original depressive episode throughout the follow-up period. Also, the number of drinks per drinking day continued to be high (about five per day), which was not significantly different from the baseline level. Thus, the long-term therapeutic effects of an acute phase trial of fluoxetine plus psychotherapy were limited. The high rate of recurrence or persistence of major depression in our sample and in a previous sample of nonalcoholic adolescents with major depression (Emslie et al. 1998) and the significant levels of drinking of our comorbid adolescents suggest that longer term treatment may be needed for at least some adolescents with major depressive disorder and alcohol use disorder.

Clinical practices in the pharmacological treatment of comorbid psychopathology in adolescents with alcohol use disorders

This study examined the use of psychiatric medications in 277 adolescents in treatment for alcohol use disorders. Subjects were recruited from addictions treatment sites, psychiatric programs, and juvenile justice settings. Characteristics studied included the use of and indications for specific medications, changes in clinical practices from 1991 through 2000, and continuation of psychopharmacological treatment over a 1-year followup period. Among adolescents taking psychiatric medications at baseline (n = 51), indicated DSM-IV mental disorders were typically present, use of antidepressants was most common (n = 41), benzodiazepine prescription was rare, and about one third reported continuing pharmacological treatment at one-year followup. In those with comorbid major depressive disorder and alcohol use disorders (n = 110), antidepressant medication use increased significantly from 18% to 55% over the decade studied. The treatment setting did not significantly influence antidepressant prescribing practices. The common and increasing use of psychiatric medications in this population emphasizes the urgent need for empirically based clinical guidelines.

Fluoxetine in adolescents with comorbid Major depression and an Alcohol Use disorder: A five-year follow-up study

ABSTRACT The goal of this five-year follow-up evaluation was to characterize the long-term (five-year) clinical course following the completion of an acute phase study with fluoxetine in comorbid adolescents. At the five-year follow-up evaluation, the group continued to demonstrate significantly fewer DSM criteria for an Alcohol Use Disorder (AUD) and fewer BDI depressive symptoms, and also consumed fewer standard drinks than they had demonstrated at the baseline of the acute phase study. Also, between the three- and five-year follow-up assessments, the level of self-reported depressive symptoms showed a significant decrease. Three of the 10 participants demonstrated Major Depressive Disorder (MDD) at the five-year follow-up assessment, but only one demonstrated Alcohol Dependence (AD), and none demonstrated Cannabis Dependence (CD). Eight of the 10 participants (80%) had demonstrated MDD at some time during the five-year follow-up study. The presence of a current AUD was significantly associated with the presence of a current MDD episode at both the one-year and the three-year follow-up evaluations. Six of the participants (60%) restarted SSRI medications at some point during the five-year follow-up period, but none were still taking SSRI antidepressants at the time of the 5-year assessment. Despite their substantial residual depression and alcohol use, a strong majority (8/10, 80%) of the subjects graduated from college during the five-year follow-up period. We conclude that the long-term (5-year) prognosis for the AUD, CD, and academic functioning of comorbid adolescents following acute phase treatment with SSRIs is surprisingly good. However, the long-term prognosis for their depression was surprisingly poor, and was worse than is typically seen among non-comorbid adolescents or adults.

Mirtazapine in Comorbid Major Depression and Alcohol Dependence: An Open-Label Trial

Objective: This was a first pilot study evaluating the acute phase (8-week) efficacy of the antidepressant medication mirtazapine for the treatment of depressive symptoms and drinking of subjects with comorbid major depressive disorder and alcohol dependence (MDD/AD). We hypothesized that mirtazapine would demonstrate within-group efficacy for the treatment of both depressive symptoms and drinking in these subjects. Methods: We conducted a first open-label study of the second-generation antidepressant mirtazapine in 12 adult outpatient subjects with comorbid MDD/AD. The pharmacological profile of that medication is unique among antidepressants, unrelated to tricyclics or selective serotonin reuptake inhibitors. Results: Mirtazapine was well tolerated in this treatment population. Self-reported depressive symptoms decreased from 31.8 to 8.3 on the Beck Depression Inventory (BDI), a 74.0% decrease (p < .001), and drinking decreased from 33.9 to 13.3 drinks per week, a 60.8% decrease (p < .05). None of the subjects were employed full time at baseline, but 9 of the 12 (75%) were employed full time at the end the of study. Conclusions: These preliminary findings suggest efficacy for mirtazapine for treating both the depressive symptoms and excessive alcohol use of comorbid major depressive disorder and alcohol dependence. Double-blind studies are warranted to further clarify the efficacy of mirtazapine in this population.

A Hierarchical Factor Model of Executive Functions in Adolescents: Evidence of Gene-Environment Interplay

Executive functions (EF) are a complex set of neurodevelopmental, higher-ordered processes that are especially salient during adolescence. Disruptions to these processes are predictive of psychiatric problems in later adolescence and adulthood. The objectives of the current study were to characterize the latent structure of EF using bifactor analysis and to investigate the independent and interactive effects of genes and environments on EF during adolescence. Using a representative young adolescent sample, we tested the interaction of a polymorphism in the serotonin transporter gene (5-HTTLPR) and parental supervision for EF through hierarchical linear regression. To account for the possibility of a hierarchical factor structure for EF, a bifactor analysis was conducted on the eight subtests of the Delis-Kaplan Executive Functions System (D-KEFS). The bifactor analysis revealed the presence of a general EF construct and three EF subdomains (i.e., conceptual flexibility, inhibition, and fluency). A significant 5-HTTLPR by parental supervision interaction was found for conceptual flexibility, but not for general EF, fluency or inhibition. Specifically, youth with the L/L genotype had significantly lower conceptual flexibility scores compared to youth with S/S or S/L genotypes given low levels of parental supervision. Our findings indicate that adolescents with the L/L genotype were especially vulnerable to poor parental supervision on EF. This vulnerability may be amenable to preventive interventions.