Jovan Simeon

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.

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.

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.

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 tels 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 Childrens 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 andpsychosomaticism. 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.

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.

Minor physical anomalies in childhood autism. Part I. Their relationship to pre- and perinatal complications

In a study of minor physical anomalies and pregnancy complications in autistic children, 45 probands and 52 of their siblings were investigated. While there was a significant association between autism on one hand and minor physical anomalies and pregnancy complications on the other, no such association was found between physical anomalies and pregnancy and birth complications. Further, autistic children with higher anomaly scores had lower IQs, more frequent hospitalizations, and a more normal family history compared to autistic children with lower physical anomaly scores.

Effect of piracetam on EEG spectra of boys with learning disorders

Piracetam was compared with placebo in a double-blind cross-over study of 30 learning-disabled boys. Power spectral analyses revealed that piracetam caused a decrease in the amount of delta activity and an increase in the average EEG frequency. This result is in agreement with those obtained by other workers in adult patients. Some clinical effects of piracetam may be mediated by increased alertness and/or decreased fatigue.

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.

Treatment strategies in child and adolescent psychiatry

1. Diagnosis and Treatment of Attention Deficit and Conduct Disorders in Children and Adolescents.- 2. Adolescent Depression: A Treatment Review.- 3. Psychopharmacological Treatment of School Phobia.- 4. Treatment of Childhood Obsessive-Compulsive Disorder: A Review in the Light of Recent Findings.- 5. Autism and Aggression.- 6. Treatment of Children and Adolescents with Substance Abuse Disorders.- 7. Treatment of Anorexia Nervosa: Current Status.- 8. Child Adolescent Psychopharmacology.- 9. Recent Developments in Diet Therapy.- 10. Treatment of Developmental Language Disorders.- 11. Child Psychotherapy.- 12. Family Therapy: A Context for Child Psychiatry.- About the Editors.

Behavioral toxicity to medications in a six-year-old boy: a genetic marker?

Abstract The case of a 6-year-old boy is presented who developed a stereotyped behavioral response to a wide range of sympathomimetics and minor central nervous system stimulants. The behavioral changes closely resembled the existing descriptions of mania in childhood. Since the boys mother suffers from bipolar manic-depression, and some of her manic episodes have been secondary to sympathomimetics, we hypothesize that her son is showing a similar profile of behavioral reactivity and that in him, it is a behavioral marker of the genetic predisposition to bipolar manic-depression. The relevant literature is reviewed and certain ethical issues are highlighted.