Sertraline effects in adolescent major depression and dysthymia: a six-month open trial.

This 6-month open-label study evaluated the efficacy, tolerability, and safety of sertraline in 21 adolescent psychiatric outpatients, ages 12 to 18 years, diagnosed with major depressive disorder (MDD, n = 13) or dysthymic disorder (DD, n = 8). Both groups showed clinically significant improvements on the Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale, and the Clinical Global Impression Scale-Severity (CGI-S). The MDD group showed maximal clinical response (based on the method of last observation carried forward) on the HAM-D and CGI at weeks 12 (76.9%) and 20 (76.9%), respectively. Response rates were maintained at week 24 with all six MDD study completers (100%) responding to treatment. The DD group achieved maximal response on the HAM-D (100%) and the CGI (75%) at week 6. Response rates in this group did not remain as elevated over time with two out of three (66.7%) DD study completers responding to treatment at week 24. Generally, sertraline was safe and well tolerated. Most adverse events were mild to moderate in severity and resolved with no action taken. Results suggest that sertraline may be efficacious in acute and continuation treatment of MDD in adolescents. DD patients showed evidence of clinical response and improvement, particularly in the acute treatment phase. Incorporating a longer evaluation period in the study of antidepressant therapy for adolescents with MDD and/or DD is emphasized.

World wide use of psychotropic drugs in child and adolescent psychiatric disorders.

1. Questionnaires were mailed to child psychiatrists world wide to obtain more precise information on views and approaches to the diagnosis and treatment of childhood psychiatric disorders. 2. Results indicated important problems related to the management of child psychiatry practice both overseas and in Canada. 3. The choice of medication was frequently restricted by lack of availability, and political or social attitudes. 4. A consensus on diagnosis and treatment guidelines in child and adolescent psychiatry remains an important issue.

Pharmacotherapy of attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder, characterized by poor sustained attention, diminished impulse control and excessive physical activity, is found in most cultures and most countries. However, diagnostic terminology and management vary from centre to centre. Pharmacotherapy in conjunction with individual and family therapy is generally accepted as the most effective treatment, while psychostimulants are the drug of choice. The results of clinical studies with indications, contraindications and side-effects are reviewed. The use of alternative pharmacotherapy for those who do not respond to treatment and long term therapy is discussed. The need for careful diagnosis and patient management is emphasized.

Use of anxiolytics in children.

Anxiety disorders are among the most frequent of childhood psychiatric disorders. These disorders can persist from childhood and adolescence into adulthood, resulting in impaired functioning at home, school or work. Some anxiety disorders like generalized or separation anxiety are acute requiring urgent, short-term treatment. Others like fears or inhibitions are chronic resulting in longterm handicaps. Other psychiatric disorders may be concurrent with, or misdiagnosed as, anxiety disorder. Anxiety can be associated with mood or behavioral disorders. When anxiety is symptomatic of another disorder, the primary disorder should be treated first. The pharmacology of childhood anxiety has been hindered by the lack of reliable quantitative evaluations, and the changes in the manifestations of anxiety. Various types of drugs have been used to treat anxiety and related disorders. The use of different drugs is reviewed. The results of a controlled clinical trial with alprazolam and two trials with buspirone in the treatment of child and adolescent anxiety are presented. While these results are promising, further clinical trials are a priority.

The placebo problem in child and adolescent psychiatry.

This paper is part of a special section on 'psychopharmacotherapy in children'. In contrast to adult psychiatry, research of placebo uses and effects in child and adolescent psychiatry is practically nonexistent, except in the context of clinical drug trials. Any type of therapy in pedopsychiatry may have positive or negative placebo effects, not only on the patients but also on their parents, teachers and therapists. The use of placebo in this population has controversial clinical, research, ethical and legal implications. Pedopsychiatrists should achieve consensus related to the clinical and research uses of placebo in their patients. Further research is needed to clarify the specific and nonspecific placebo factors related to short-term and long-term treatment outcome.

Clinical, cognitive, and neurophysiological effects of alprazolam in children and adolescents with overanxious and avoidant disorders.

In a double-blind, placebo-controlled study, the efficacy and safety of alprazolam was investigated in childhood and adolescent anxiety disorders. Thirty patients (mean, 12.6 years) diagnosed with overanxious or avoidant disorders participated in the study. Evaluations included clinical, laboratory, cognitive, and qualitative EEG measurements. On a clinical global rating, there was no statistical difference between alprazolam and placebo. Relative to baseline EEG, acute alprazolam administration increased beta power in the right occipital lead, and chronic administration increased beta power in both leads. Alprazolam was well tolerated, and adverse effects were few, mild, and transient.

Treatment of adolescent obsessive-compulsive disorder with a clomipramine-fluoxetine combination.

Clomipramine has been reported to be effective in the treatment of obsessive-compulsive disorder (OCD). Children and adolescents, however, tolerate poorly the adverse effects of tricyclics. Fluoxetine and other serotonin re-uptake inhibitors also appear useful in OCD, and are safer than clomipramine. To maximize the therapeutic effects and minimize adverse effects, 6 adolescents with OCD were treated in single trials with a clomipramine-fluoxetine combination. Duration of combined drug therapy ranged from 4 weeks to more than 28 weeks. Patients were first treated with clomipramine alone; if improvement or adverse effects were unsatisfactory, they received the drug combination. Clinical global improvement with clomipramine alone was moderate in 3 patients and minimal in 3. With a combined clomipramine-fluoxetine therapy, improvements were marked in 5 patients, and moderate in 1. These improvements were obtained with relatively low daily doses: clomipramine at 25 to 50 mg, and fluoxetine at 20 to 40 mg. Adverse effects appeared greater and much less tolerable with clomipramine alone than with the clomipramine-fluoxetine combination. This drug combination was well tolerated. These preliminary data suggest that relatively low doses of a clomipramine-fluoxetine combination may potentiate therapeutic effects and minimize adverse effects in OCD patients. Larger controlled trials are suggested.

Adolescent depression: a placebo-controlled fluoxetine treatment study and follow-up.

Forty patients aged 13 to 18 years participated in a placebo-controlled double-blind study of fluoxetine. Fifteen subjects in each group completed the eight week study. Approximately two-thirds of the patients showed marked or moderate clinical global improvement with both fluoxetine and placebo. Fluoxetine was superior to placebo on all clinical measures except for sleep disorder, but the differences were not statistically significant. Thirty-two of the patients and their parents were interviewed after a mean follow-up interval of 24 months (range: 8-46 months). Mean age at follow-up was 18 years (range: 15-22 years). Both groups had shown further improvement at follow-up but there were no significant group differences. Independent of the study, 19 patients (59%) had received intervening treatment following study termination and nine patients (28%) were still in treatment. Adolescent depression appears to respond to treatment but both mood disturbance and psychosocial adaptation problems persist, requiring active follow-through.

Depressive disorders in children and adolescents.

Depressive disorders in children and adolescents are valid clinical entities which can be identified using adult diagnostic criteria. Recent research has resulted in significant progress in the areas of diagnosis, epidemiology, family pathology, pharmacokinetics and psychopharmacology. Many rating instruments have been developed to screen, diagnose and measure changes of depression in children and adolescents. The prevalence of depressive disorders in prepubertal children is about 2% and in adolescents about 5%. Depressive episodes are usually of long duration, with high rates of relapse. These relapses are usually associated with school, family and social failure. Follow-up studies of depressed adolescents indicated that about half of the patients continue to suffer from mood disturbances and psycho-social adaptational problems. In North America suicidal behaviour in adolescents has increased 300% in the past 30 years. However, its relationship to depression is more complex than in adults. There is a significant excess of affective illness and alcoholism in the families of depressed adolescents. Similarly, there is a high rate of impairment among children of parents with affective disorders. During depressive episodes, prepubertal children show abnormalities of growth hormone and cortisol secretion. However, DST findings are contradictory. Polysomnographic findings in childhood depression appear unremarkable. In adolescent depression these findings are similar to those in depressed adults. Biological manifestations of depressive disorders may be significantly affected by developmental and hormonal changes. Antidepressants have been effective in the therapy of several disorders in childhood. These include enuresis, school phobias, attention deficit, conduct disorders and obsessive-compulsive disorders. Open drug studies suggest that antidepressants are useful in depressed children.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatric psychopharmacology.

This article is a brief and selected overview of pediatric psychopharmacology, a field which links medicine, behavioural sciences, and neurosciences to child psychiatry. It will summarize current knowledge and recent advances related to the indications, effects, limitations and research issues of psychostimulants, antidepressants, antipsychotics, anxiolytics, anticonvulsants and diets used in the treatment of child and adolescent psychiatric disorders.

Alprazolam effects in children with anxiety disorders.

Children with overanxious and/or avoidant disorder (DSM-III) were treated with alprazolam (Xanax, Upjohn) to determine its safety, clinical and cognitive effects. Ten male and two female patients (age range 8.8 to 16.5 years; mean 11.5) participated in an open clinical trial consisting of a baseline placebo period (1 week), alprazolam therapy (4 weeks), a drug-tapering period (1 week), and a post-drug placebo period (1 week). There was a drug-free follow-up approximately 4 weeks after termination of the study. Dosages were individually adjusted and the daily maximum ranged from 0.50 mg to 1.5 mg. Evaluations included clinical assessments, parent, teacher and self ratings, and cognitive tests. Clinical global improvement with alprazolam therapy was marked in 1 patient, moderate in 6, minimal in 4, and none in 1. Clinician ratings indicated significant improvements of anxiety, depression, and psychomotor excitation. Parent questionnaires indicated significant improvements of anxiety and hyperactivity while teacher questionnaires showed significant improvement of an anxious-passive factor. Significant improvements in the paired associate learning tasks, maze task and the block design tasks were maintained after drug withdrawal suggesting a practice effect. Adverse effects were infrequent, mild and transient. There were no clinically significant changes of laboratory values, blood pressure, pulse or respiration during the 4 weeks of alprazolam administration. Body weight increased significantly (mean increase was 0.87 kg). Double-blind trials with alprazolam are recommended in child psychiatry disorders.

Bupropion effects in attention deficit and conduct disorders.

Children with Attention Deficit and/or Conduct Disorders were treated with bupropion, a new antidepressant, to determine its clinical, cognitive, and EEG effects. Seventeen male patients (age range 7 to 13.4 years; mean 10.4) participated in an open clinical trial consisting of a baseline placebo period (4 weeks), bupropion therapy (8 weeks), and post-drug placebo (2 weeks). Evaluations included clinical assessments, parents, teachers, and self-ratings; cognitive tests and blood level measurements of bupropion. Fifteen patients received a daily maximum of 150 mg, one received 100 mg and one 50 mg. Clinical global improvement with bupropion therapy was marked in 5 patients, moderate in 7, mild in 2, and none in 3. The Children's Psychiatric Rating Scale indicated improvements of hyperactivity, withdrawal, anxiety, hostility/uncooperativeness, sleep disorder, antisocial behaviour, neuroticism, depression and eating disturbance. Parents' Questionnaires indicated significant improvements of conduct disorder, anxiety, hyperactivity, muscle tension and psychosomaticism. While no single cognitive test showed significant improvement, all nine tests changed in the positive direction. Adverse effects were infrequent, transient and mild. There were no clinically significant changes of the laboratory values and vital signs. Two weeks following bupropion discontinuation, clinical global improvement was maintained in 8 patients, 7 showed relapses, while 2 remained unimproved. Analyses of computerized EEG revealed that degree of clinical improvement was indexed by baseline EEG parameters and that there were significant bupropion effects on EEG measures. Double-blind trials of bupropion are recommended in child psychiatry disorders.

Recent developments in the use of antidepressant and anxiolytic medications.

In this article the authors review recent research contributions to the knowledge regarding the role of antidepressant and anxiolytic medications in the treatment of child psychiatry disorders. For each of the two classes of drug, recent data regarding a range of indications are evaluated. In addition, general methodologic issues and future research priorities are discussed.

Evaluating drug effects on children's cognitive functioning.

In our studies of drug therapy in child psychiatry disorders, we have been using a battery of tests to monitor any effects of medication on the various components of cognitive processing. Our intention was to measure skills required by the children for successful classroom performance. We have used this test battery approach in open clinical trials of bupropion (Wellbutrin) and of alprazolam (Xanax) with child psychiatry patients. On no single test was the effect of bupropion vs placebo significant; however, there was no indication of any cognitive deterioration with bupropion. Group performance with alprazolam was more variable, and again no individual test showed significant changes with medication. These initial applications of the cognitive battery indicate that bupropion, a new antidepressant and alprazolam, an anxiolytic have no adverse effects on cognition at therapeutically effective doses.