Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors.

OBJECTIVE: The objective was to study the efficacy of sertraline on symptoms of psychic and somatic anxiety in patients suffering from moderate-to-severe generalized anxiety disorder (GAD). METHOD: Out-patients with DSM-IV GAD were randomized to 12 weeks of double-blind treatment with placebo. The psychic and somatic anxiety factors of the Hamilton Anxiety Rating Scale (HAM-A) and the Quality of Life, Enjoyment, and Satisfaction Questionnaire were analyzed. RESULTS: Treatment with sertraline resulted in significantly greater last observation carried forward (LOCF)-endpoint improvement than placebo on both the HAM-A psychic and somatic anxiety factors. At LOCF-endpoint, all items on the HAM-A psychic factor were more improved on sertraline than placebo, as were three of seven items on the somatic factor. Reduction of secondary depressive symptoms was more correlated with endpoint improvement in quality of life than either psychic- or somatic anxiety. CONCLUSION: Sertraline treatment demonstrated efficacy for both the psychic and somatic anxiety symptoms of GAD.

Impact of early onset bipolar disorder on family functioning: adolescents' perceptions of family dynamics, communication, and problems.

OBJECTIVE: This research investigated the impact of adolescent onset bipolar illness on perceived family functioning in stabilized bipolar I (B) and unipolar (U) probands, and normal controls (C). METHOD: Sample N=119: 44 bipolar 1(17 M, 27 F), 30 unipolar (9 M, 21 F), and 45 controls (19 M, 26 F). Mean ages: 19.9, 18.5 and 18.2 years, respectively. INSTRUMENTS: Family Adaptability and Cohesion Scale (FACES II), Parent-Adolescent Communication Scales (PACS), Social Adjustment Inventory for Children and Adolescents (SAICA). RESULTS: There were no significant group or sex differences between controls and mood disordered youth--assessed intermorbidly--in ratings of relationship with either parent. Bipolars acknowledged significantly more minor conflicts with parents than either unipolars or controls. Ratings by mood disordered subjects were significantly less positive in terms of shared activities and communication with siblings. Mood disordered youth and controls were not differentiated on the basis of family adaptability, and all family cohesion scores were within population norms. No significant group differences were observed in communication with parents. LIMITATIONS: This self-report study was conducted intermorbidly, does not include objective measures of family functioning, nor does it assess the effect of psychiatric illness in other family members on family functioning. CONCLUSIONS: Assessed intermorbidly, bipolar adolescents' perceptions of family dynamics do not seem to diverge significantly from controls. Further research is needed to investigate the impact of adolescent bipolar illness on family life during acute phases of the illness, as well as the effect on family functioning of psychiatric disorders in other family members.

Update and recommendations for the use of antipsychotics in early-onset psychoses.

A review was undertaken of studies evaluating the efficacy and tolerability of antipsychotic medications for the management of psychosis in children and adolescents. All identified published and unpublished studies from 1996 onward were included for review. The search located one randomized control trial, seven open-label trials, six retrospective chart reviews, and nine case reports. The studies assessed the use of haloperidol, clozapine, risperidone, olanzapine, and quetiapine in the management of psychosis in children and adolescents. Most studies reported reasonable treatment response; however, extrapyramidal side effects, sedation, and weight gain are concerning. This points to the need for appropriate baseline assessments prior to initiating treatment with these agents. Particular attention should be given to assessment of the extrapyramidal system as well as to baseline weight, lipid profile, and blood glucose. Further study is needed to refine the use of antipsychotic medications in children and adolescents in order to minimize adverse effects while conferring an optimum therapeutic response. The importance of instituting effective early treatment in youth with psychoses is an important goal that may serve to lessen the long-term morbidity of the illness.

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.

Clinical guidelines for the treatment of depressive disorders. VI. Special populations.

BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments partnered to produce clinical guidelines for psychiatrists for the treatment of depressive disorders. METHODS: A standard guidelines development process was followed. Relevant literature was identified using a computerized Medline search supplemented by review of bibliographies. Operational criteria were used to rate the quality of scientific evidence, and the line of treatment recommendations included consensus clinical opinion. This section, "Special Populations," is 1 of 7 articles that were drafted and reviewed by clinicians. Revised drafts underwent national and international expert peer review. RESULTS: This section reports on the prevalence, course, and outcome of depression for specific populations. Psychological, pharmacologic, and other biological treatment options for these populations--children and adolescents, the elderly, women at times of increased risk within the reproductive cycle, and specific ethnocultural groups--are critically evaluated. CONCLUSIONS: Major depressive disorder (MDD) is prevalent across the lifespan. In general, clinical presentations are more similar than different across age, sex, and cultural divides. Although less evidence is available for the efficacy of treatments in these subpopulations than in mid-life patients, comparable rates of response for pharmacotherapies, electroconvulsive therapy (ECT), and, in some cases, evidence-based psychotherapies have been reported.

An exploratory approach to the serotonergic hypothesis of depression: bridging the synaptic gap.

In this exploratory review, we attempt to integrate pre and post synaptic theories of the biochemical basis of depression--in particular with regard to 5-HT. We will be providing evidence that in major depressive disorder, there is a continuity of dysfunction of neural function, i.e. pre and post synaptic serotonergic symptoms are affected. Furthermore, we will also be providing the implications of this approach for normal treatments for depressive disorder.

An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria.

Serotonin-related adverse side-effects of psychotropic drugs were first recorded in humans in 1960. However, since 1991, these related cases have been diagnosed as 'serotonin syndrome (SS)' according to the criteria reported by Sternbach. In this article, we have reviewed and further explored the validity of these criteria. The clinical profile of 24 cases of the SS published between 1991 and 1995 has been analysed in detail and compared with the symptomatology of 38 previous cases which were also further analysed. Mainly Medline and references from other reports were used to review these cases. The general concept put forward by Sternbach has been approved. On the basis of the severity of overall clinical presentation, it appeared that there is a need to further classify SS into three main groups as: (1) mild state of serotonin-related symptoms; (2) serotonin syndrome (full-blown form); (3) toxic states. Furthermore, the detailed analysis of the SS cases published so far suggests that 'the diagnostic criteria for SS' also require further revision, and these are presented here. We also review, present and discuss the guidelines for the management and treatment of SS.

High-dose vitamin E plus vitamin B6 treatment of risperidone-related neuroleptic malignant syndrome.

We present a case of a 74-year-old patient with schizoaffective disorder, who developed risperidone-related neuroleptic malignant syndrome. This patient responded satisfactorily to the supportive management and vit E plus vit B6.

The foundations of effective management of bipolar disorder.

OBJECTIVES: To understand the epidemiology and course of bipolar disorder; to outline the importance of accurate and reliable diagnosis of bipolar disorder both on a cross-sectional and longitudinal basis; and to emphasize the value of a collaborative therapeutic relationship, psychoeducation, and psychotherapy. METHODS: A brief review of relevant literature to deal with the issues of diagnosis and laying the foundations for effective treatment. RESULTS: Bipolar disorder may well be a heterogeneous group of conditions with varying forms of biphasic mood dysregulation and a changing course across a lifetime. A collaborative therapeutic relationship, psychoeducation, and psychotherapy can be the basis for effective management. CONCLUSIONS: As the concept of bipolar disorder has broadened, the condition is being identified with increasing frequency in many clinical settings. It is a relapsing and recurring condition. It is now recognized that in addition to rational pharmacotherapy, there is a need to encourage a high level of treatment adherence while providing a holistic package of interventions.

Continuation and prophylactic treatment of bipolar disorder.

OBJECTIVES: To summarize the evidence for efficacy from published literature of biological treatments in the continuation and maintenance phases of bipolar disorder, as well as the recommendations about different treatment options made by the working group within the Bipolar Sub-Committee of the Canadian Network for Mood and Anxiety Treatments (CANMAT). METHODS: A review of relevant published literature and proceedings of international conferences was conducted. The quality of evidence was assessed and classified according to the Periodic Health Examination criteria. Treatment recommendations of the working group were based on quality of evidence, a consensus of expert views, and the opinions of psychiatrists and family physicians from across Canada. RESULTS: There is overwhelming evidence for the efficacy of lithium in the prophylaxis of bipolar disorder. The evidence for carbamazepine is less robust. There are no published double-blind studies with adequate numbers of subjects treated with divalproex sodium. CONCLUSIONS: During and at the end of the continuation phase it is recommended that mood stabilizers should remain the mainstay of therapy and that other treatments should be gradually discontinued or maintained only if there is valid reason to do so. Efficacious maintenance treatment can reduce morbidity and mortality significantly and improve patients' quality of life.

Changes in thyroid hormone levels associated with desipramine response in adolescent depression.

1. The authors recently reported that acutely ill depressed adolescents have elevated plasma T4 and fT4 compared to controls. Studies in adult depression suggest antidepressant response is associated with decreases in these elevated levels. The effect of antidepressant treatment on adolescent thyroid indices has not been examined. 2. Thyroid indices were examined in 12 adolescent patients (4 male, 8 female; age 14-19y) in the active treatment arm of a double-blind, placebo-controlled desipramine trial (200 mg/day for 6 weeks). Antidepressant responders had higher pre-treatment levels of T4 and larger decreases were observed responders vs. nonresponders. 3. These results replicate findings observed in adult depressed patients and suggest similar alterations in the hypothalamic-pituitary-thyroid (HPT) axis function in adolescent depression.

Nocturnal melatonin and 24-hour 6-sulphatoxymelatonin levels in various phases of bipolar affective disorder.

Nine bipolar patients (2 men and 7 women) and 12 healthy control subjects completed overnight sampling for serum melatonin (MT) and urinary 6-sulphatoxymelatonin (aMT6s). The patients were investigated during manic, depressed, and/or euthymic states. Although serum MT levels did not differ significantly across the bipolar groups, in all cases serum MT levels were significantly lower than in control subjects. Differences in MT levels were also present between bipolar patients who were in a depressed phase and control subjects. There were no statistically significant differences in urinary aMT6s levels among the patients and control subjects, although in all cases nocturnal aMT6s levels were significantly higher than daytime levels. This study provides tentative evidence for decreased serum MT as a trait but not a state marker in bipolar affective disorder.

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)

A Canadian multicentre placebo-controlled study of a fixed dose of brofaromine, a reversible selective MAO-A inhibitor, in the treatment of major depression.

In a 6-week double-blind study, 220 patients with major depression (mostly outpatients) were randomly assigned to receive a fixed dose of brofaromine 150 mg daily (n = 111) or placebo (n = 109) after a 1-week single-blind placebo washout. Except for the HAM-D sleep items, brofaromine was superior to placebo on measures of depression as determined by the four methods of assessing drug efficacy: (1) psychiatric symptom rating (HAM-D 17-item less the three sleep items); (2) self-rating scale (Beck Depression Inventory); (3) Clinical Global Assessment of Efficacy; and (4) drop-out rate due to lack of efficacy. Most commonly reported adverse events with brofaromine were: headache, nausea, dizziness and sleep disturbance. Brofaromine was found to be an effective antidepressant, superior to placebo with a good tolerability profile.

Basal thyroid indices in adolescent depression and bipolar disorder.

OBJECTIVE: Abnormalities of the thyroid axis are documented in adult mood disorders. The most consistent findings have been observed in major depressive disorder with elevations of thyroxine (T4) or free-T4 (fT4) within the euthyroid range that decrease with treatment. The literature on adolescents is limited, and it is unknown whether similar findings might be present in this population. METHOD: First admissions to a university hospital adolescent psychiatry unit were reviewed. Fourteen depressed and 13 manic patients satisfied inclusion and exclusion criteria. None had a history of thyroid illness or medical illness or were taking medications known to affect thyroid function. Basal serum thyrotropin, T4, fT4, triiodothyronine (T3), reverse-T3, free thyroxine index (FTI), and T3 resin uptake levels were compared with those of a group of adolescent normal controls. RESULTS: T4 (but not fT4) was elevated in depressed and manic patients compared with controls (p < .05). In manic patients, T3 was decreased and reverse-T3 was increased (p < .05). There were no significant differences in relation to age, sex, or suicidality. CONCLUSIONS: We observed significant differences in basal thyroid hormone levels in depressed and manic adolescents. Our results suggest the presence of abnormalities of thyroid function in adolescent mood disorders similar to those described in mood-disordered adults.

Brofaromine in depression: a Canadian multicenter placebo trial and a review of standard drug comparative studies.

Brofaromine is a new, reversible, and selective type-A monoamine oxidase inhibitor (MAOI) that also has serotonin reuptake inhibitory properties. Its dual pharmacologic effects offer promise in the treatment of a wide spectrum of depressed patients while producing less severe anticholinergic side effects in comparison with standard drugs. A multicenter, double-blind, placebo-controlled study including 220 patients was undertaken to evaluate the efficacy and safety of brofaromine in major depression. This study of a fixed-dose design and 6 weeks' duration found that brofaromine was significantly better than placebo on the Overall Evaluation of Efficacy, Beck self-rating scale, HAM-D Bech subscale, HAM-D total 14 items (minus the three sleep items), HAM-D depressed mood item and retardation factor, and worse than placebo on the insomnia items of HAM-D. Significantly more patients on placebo than on brofaromine did not complete the trial due to lack of efficacy. In comparative controlled studies (n = 899), brofaromine was found to be at least as efficacious as tricyclic antidepressants (imipramine) and standard MAOIs (tranylcypromine and phenelzine). Reductions of at least 50% in the HAM-D total score were seen in 58-66% of patients treated with either brofaromine or imipramine (n = 609). Brofaromine also was found to be of comparable efficacy to tranylcypromine in two clinical trials (n = 132), one of which included patients considered to have a treatment-resistant depression (n = 39). In another double-blind study that compared brofaromine (150 mg/day) to phenelzine (45 mg/day) (n = 158), there was no difference between brofaromine and phenelzine.

Divalproex sodium treatment in late adolescent and young adult acute mania.

This is a preliminary report on 6 subjects in an ongoing open trial of divalproex sodium in the treatment of adolescents with bipolar affective disorder who are experiencing an acute manic episode. The 7-week study was designed to determine the relative potential efficacy and safety of divalproex sodium in this condition before further assessment of the medication with a comparative lithium condition. Patients were assessed weekly with the Modified Mania Rating Scale (MMRS), the Brief Psychiatric Rating Scale (BPRS), and the Global Assessment Scale (GAS). The primary outcome measure was the MMRS. Of the 6 patients, 5 showed marked improvement (pre-post decrease > 60%), 1 showed some improvement (pre-post decrease of 20-60%), and none failed to improve (pre-post decrease of < 20%). The mean MMRS score was significantly reduced by 7 weeks of treatment (pre to post mean score: 77 +/- 25.79 to 29 +/- 24.97, t = 9.45, p < .0002), as were the BPRS (40.67 +/- 14.91 to 18.67 +/- 11.83, t = 5.98, p < .0019) and the GAS (28.5 +/- 12.78 to 48 +/- 15.03, t = 6.71, p < .0011). All patients were on ancillary psychotropic medications during this study.