Stan Kutcher

Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial

OBJECTIVE To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS Paroxetine is generally well tolerated and effective for major depression in adolescents.

Response to Desipramine Treatment in Adolescent Depression: A Fixed-Dose, Placebo-Controlled Trial

OBJECTIVE To determine the efficacy and tolerability of the tricyclic antidepressant desipramine (DMI) in the treatment of DSM-III-R-diagnosed major depressive disorder in adolescents. METHOD Sixty adolescents (42 female, 18 male; aged 15 to 19 years) diagnosed with major depressive disorder using clinical interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children were randomized to receive either DMI (200 mg daily in divided doses) or placebo for six consecutive weeks following a 1-week placebo period. Treatment outcome was determined using the Hamilton Depression Rating Scale and the Beck Depression Inventory. Tolerability was determined using a symptom side effects scale. In addition, a variety of laboratory and cardiovascular monitoring was performed. RESULTS No significant differences in treatment outcome between DMI- and placebo-treated groups were determined. Neither DMI, nor its metabolite 2-hydroxy-DMI, nor their ratio, was positively correlated to treatment outcome. The DMI group endorsed more side effects but there were no significant between-group differences in any laboratory, electrocardiographic, or other cardiovascular parameters apart from heart rate, which was increased in the DMI-treated group (p = .03). CONCLUSIONS Given the findings of this study and our review of previously published reports of tricyclic antidepressant treatment in this population, the routine use of short-term (6 weeks) DMI in the treatment of adolescent depression is not supported by the data on hand. Further investigations into what constitutes optimal psychopharmacological treatment of adolescent depression are warranted.

Diagnosis and Measurement of Adolescent Depression: A Review of Commonly Utilized Instruments

We surveyed 160 recent studies of adolescent depression (publication dates ranged from March 1996 to August 2000) and identified 33 different diagnostic and symptom measurement instruments being used by various investigators. We also found that more than one in three of the studies measuring depressive symptom severity in adolescents relied on instruments designed for use with adults. We then reviewed in detail the design features and psychometric properties of the 12 instruments most commonly used in studies of adolescent depression and attempted to characterize their strengths and weaknesses. Our main conclusions are as follows: Too many different instruments are being used by investigators, presumably due to a lack of consensus as to which are the most valid and reliable tools. Instruments designed for use in adults and never validated in adolescent populations are frequently used with no evidence for their developmental sensitivity. Many studies are using instruments that demonstrate substantial weaknesses in validity and/or reliability. The need for a parsimonious, easily administered, valid, and reliable tool(s) to diagnose and measure symptom severity in adolescent depression has not yet been met.

The efficacy and safety of divalproex sodium in the treatment of acute mania in adolescents and young adults: an open clinical trial.

This open clinical trial investigated the potential short-term efficacy and safety of divalproex sodium in the treatment of adolescents and young adults with bipolar affective disorder in an acute manic phase. Fifteen subjects were treated for 7 weeks with divalproex sodium (mean drug level in blood +/- the standard deviation at trial completion, 642.85 +/- 183.08 mumol/liter) and were assessed weekly with the Modified Mania Rating Scale (MMRS), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment Scale (GAS), and the Clinical Global Impressions Scale (CGI). Of the 15 subjects who entered the study, 8 showed marked improvement on the MMRS (pre-post decrease of > or = 75%), 4 showed moderate improvement (pre-post decrease of 50 to 74%), 1 showed some improvement (pre-post decrease of 25 to 49%), 1 showed no improvement and was withdrawn before the seventh study week because of lack of response, and 1 withdrew because of side effects. The mean MMRS score was significantly changed by 7 weeks of treatment in the 13 subjects who completed the 7-week trial (69.54 +/- 24.21 to 18.08 +/- 8.70; t = 7.72; p < 0.0001), as were the BPRS (36.31 +/- 12.22 to 12.00 +/- 4.22; t = 7.53; p < 0.0001), the GAS (30.23 +/- 9.05 to 54.69 +/- 9.40; t = 7.50; p < 0.0001), and the CGI (5.38 +/- 0.96 to 2.38 +/- 0.87; t = 10.01; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Premorbid functioning in adolescent onset bipolar I disorder : a preliminary report from an ongoing study

BACKGROUND This study reports on premorbid academic and peer functioning and psychiatric illness in a rigorously diagnosed sample (N = 28) of adolescent onset bipolar I patients. METHODS Premorbid functioning was assessed by parental report and review of the Ontario School Record (OSR). Premorbid psychiatric diagnoses were assigned on the basis of all information gathered. RESULTS Overall, findings suggest that this cohort demonstrates good to excellent peer and academic functioning prior to illness onset. Rates of premorbid psychiatric illnesses were similar to that described in epidemiologic samples. CONCLUSIONS Results are discussed in relation to current understanding of early onset bipolar illness and directions for future research.

Nocturnal Cortisol, Thyroid Stimulating Hormone, and Growth Hormone Secretory Profiles in Depressed Adolescents

Twelve depressed adolescents and 12 controls matched for age, sex, Tanner stage, time of menstrual cycle (females), weight, and time of year assessed were studied over 3 nights. Measurements for cortisol, thyroid stimulating hormone, and growth hormone were made on serum collected at 10 P.M., 12 midnight, 1 A.M., 2 A.M., 3 A.M., 4 A.M., and 6 A.M. in eight pairs and every 20 minutes from 8 P.M. to 7 A.M. in four pairs. Cortisol secretion did not significantly differentiate the groups. Thyroid stimulating hormone secretion was significantly elevated in the depressed group at one time point. Growth hormone secretion significantly differentiated the two groups at most time points, and the depressed adolescents significantly hypersecreted growth hormone (area under the curve). Implications for the diagnosis, etiology, and treatment of adolescent depression are discussed.

An open naturalistic trial of fluoxetine in adolescents and young adults with treatment-resistant major depression.

ABSTRACT Fifteen adolescents and young adults (ages 16-24) with a DSM-III-R diagnosis of major depression, who failed to respond to prior treatment with tricyclic antidepressants, were treated in an open trial using fluoxetine. Of the 11 patients who completed a 6-7 week trial, 64% showed a therapeutic response (>/=50% change) on the Hamilton Depression Rating Scale (HDRS), and 73% showed a positive response when rated by the Clinical Global Impression Scale (CGI). Side effects generally were mild, and the most common were tremor, dry mouth, nausea, sweating, and decreased appetite. Sweating, drowsiness, dry mouth, tremor, and alopecia appeared more commonly than in adult studies. One patient became manic, and none showed an increase in suicidal ideation. A starting dose of 20 mg daily often was tolerated poorly, and patients generally did better with 5-10 mg daily for the first week. Some patients appeared to exhibit antidepressant responses on 5-10 mg daily. These preliminary data suggest that fluoxetine, in doses ranging from 5 to 40 mg daily, when used in combination with psychosocial treatments, may be an effective antidepressant in adolescents or young adults who have not previously responded to adequate tricyclic therapy. Double-blind placebo-controlled studies are needed to evaluate the potential efficacy of fluoxetine in treating major depression in adolescents and young adults.

The effectiveness of school mental health literacy programs to address knowledge, attitudes and help seeking among youth

Conduct a systematic review for the effectiveness of school mental health literacy programs to enhance knowledge, reduce stigmatizing attitudes and improve help‐seeking behaviours among youth (12–25 years of age).

Screening for adolescent depression: comparison of the Kutcher Adolescent Depression Scale with the Beck depression inventory.

Self-report instruments commonly used to assess depression in adolescents have limited or unknown reliability and validity in this age group. We describe a new self-report scale, the Kutcher Adolescent Depression Scale (KADS), designed specifically to diagnose and assess the severity of adolescent depression. This report compares the diagnostic validity of the full 16-item instrument, brief versions of it, and the Beck Depression Inventory (BDI) against the criteria for major depressive episode (MDE) from the Mini International Neuropsychiatric Interview (MINI). Some 309 of 1,712 grade 7 to grade 12 students who completed the BDI had scores that exceeded 15. All were invited for further assessment, of whom 161 agreed to assessment by the KADS, the BDI again, and a MINI diagnostic interview for MDE. Receiver operating characteristic (ROC) curve analysis was used to determine which KADS items best identified subjects experiencing an MDE. Further ROC curve analyses established that the overall diagnostic ability of a six-item subscale of the KADS was at least as good as that of the BDI and was better than that of the full-length KADS. Used with a cutoff score of 6, the six-item KADS achieved sensitivity and specificity rates of 92% and 71%, respectively-a combination not achieved by other self-report instruments. The six-item KADS may prove to be an efficient and effective means of ruling out MDE in adolescents.

Adult ADHD and comorbid depression: A consensus-derived diagnostic algorithm for ADHD

Objective: Many patients present to their physician with depression as their primary symptom. However, depression may mask other comorbid disorders. This article presents diagnostic criteria and treatment recommendations (and monitoring) pertaining to the diagnosis of adult attention deficit hyperactivity disorder (ADHD), which may be missed in patients who present with depressive symptoms, or major depressive disorder (MDD). Other co-occurring conditions such as anxiety, substance use, and bipolar disorder are briefly discussed. Methods: A panel of psychiatrist-clinicians with expertise in the area of child and adolescent ADHD and mood disorders, adult mood disorders, and adult ADHD was convened. A literature search for recommendations on the diagnosis and treatment of co-occurring conditions (MDD, anxiety symptoms, and substance use) with adult ADHD was performed. Based on this, and the panel’s clinical expertise, the authors developed a diagnostic algorithm and recommendations for the treatment of adult ADHD with co-occurring MDD. Results: Little information exists to assist clinicians in diagnosing ADHD co-occurring with other disorders such as MDD. A three-step process was developed by the panel to aid in the screening and diagnosis of adult ADHD. In addition, comorbid MDD, bipolar disorder, anxiety symptoms, substance use and cardiovascular concerns regarding stimulant use are discussed. Conclusion: This article provides clinicians with a clinically relevant overview of the literature on comorbid ADHD and depression and offers a clinically useful diagnostic algorithm and treatment suggestions.