Disorders - Bipolar Disorders
Forbes, A., Nyilas, M., Loze, J., Laughton, J., Johnson, B., Aurang, C., Iwamoto, T., Carson, W. H., Owen, R.
Background: Early onset of bipolar disorder is often chronic and associated with significant comorbidity, including substance abuse, violence, and suicide. Moreover, the long-term consequences of this illness greatly impact the ability of these youths to carry out normal daily functions, with devastating effects on social interactions, school performance, and family relationships/dynamics. Due to a lack of published long-term safety and efficacy data from large-scale, randomized, controlled trials in this patient population, physicians are most-often guided by data from adult studies to make important decisions on the selection of appropriate treatment as well as selection of a safe and potentially efficacious dose. This is problematic, as children and adolescents may show a different pattern of response and seem to be more sensitive to antipsychotic-related adverse events, such as sedation, extrapyramidal side effects, weight gain and endocrine and metabolic abnormalities [1,2]. Methods: 296 youths, ages 10-17 year-old with a DSM-IV diagnosis of bipolar I disorder were randomized to receive either placebo or aripiprazole (10 mg or 30 mg) in a 4-week double-blind trial. Completers continued assigned treatments for an additional 26 weeks (double-blind). A 5-member, independent, Data Safety Monitoring Board (DSMB) provided frequent assessment of patient safety. Efficacy endpoints included mean change from the pretreatment baseline to Week 4 and to Week 30 on the Young-Mania Rating Scale (Y-MRS); Children's Global Assessment Scale (CGAS), Clinical Global Impressions Scale-Bipolar Version (CGI-BP) severity score, Children's Depression Rating Scale-Revised (CDRS-R) score, General Behavior Inventory Scale (GBI) score, Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) score, time to discontinuation due to all reasons, and response rate (defined as > 50% reduction from baseline in the YMRS total score). Safety measures included frequency and severity of adverse events (AE), Simpson Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), as well as blood chemistries and body weight. Results: Over the 30-week course of double-blind treatment, aripiprazole (10 mg and 30 mg) was superior to placebo as early as week 1 (p < 0.002) and at all scheduled visits from week 2 through week 30 on mean change from baseline in the Y-MRS total score (p < 0.0001; all visits). Significant improvements were observed on multiple endpoints including the CGAS, GBI, CGI-BP, ADHD-RS-IV total score, time to discontinuation, and response and remission rates. Most AEs were mild to moderate in severity with 14% discontinuation due to adverse events over the course of 30 weeks (7% in the 4-week acute phase) in aripiprazole treated patients. The most common AEs in the combined aripiprazole groups were somnolence, extrapyramidal disorder, and fatigue. Significant difference from placebo was observed on the SAS (30 mg), but not on the BARS, at Week 30. Low prolactin levels were more frequent in aripiprazole treated patients than placebo. There were no clinically significant changes in weight z-scores at end of study. Conclusions: Over 30-weeks of treatment, both doses of aripiprazole were superior to placebo in the acute and long term treatment of pediatric bipolar patients. Aripiprazole was generally well tolerated.
European Neuropsychopharmacology, 18(S4) : S556-S557
- Year: 2008
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
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Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Hiremani, Raja M., Thirthalli, Jagadisha, Tharayil, Biju S., Gangadhar, Bangalore N.
Background: Method: Results: Conclusion: Bifrontal electrode placement is as efficacious as bitemporal placement during electroconvulsive therapy (ECT) in depression but is associated with fewer cognitive adverse effects. There are no studies comparing these techniques in acute mania. This study compared the short-term efficacy and adverse effects of bifrontal and bitemporal ECT in the treatment of acute mania.Thirty-six DSM-IV mania inpatients referred for ECT were recruited for study. They were randomized to receive bifrontal (BFECT; n = 17) or bitemporal (BTECT; n = 19) ECT. None of the subjects were on mood stabilizers during the course of ECT. Severity of mania was measured on the Young Mania Rating Scale (YMRS) before beginning ECT and then on Days 3, 7, 11, 14, and 21 of treatment. Cognitive functions were assessed eight hours after the fifth ECT session using the Mini-Mental Status Examination (MMSE), Paired Associate Learning Test, Complex Figure Test, Verbal Fluency Test (animals and fruits categories), and Trail Making Test, Part A.The subjects in the two groups were comparable on sociodemographic and clinical variables, including severity of mania at baseline. They were also similar in ECT parameters, including seizure threshold and seizure duration. Mean YMRS scores showed faster decline in the BFECT than in the BTECT group. Kaplan-Meier survival analysis showed that a greater proportion of subjects in the BFECT group responded (50% reduction in YMRS score) significantly earlier than in the BTECT group. There were no significant differences between the groups in performance on cognitive function tests.In this pilot study, mania patients treated with BFECT responded faster than those treated with BTECT, with comparable cognitive adverse effects. Since ECT is usually prescribed for rapid control of symptoms, BFECT may be preferred over BTECT in the treatment of acute mania.
Bipolar Disorders, 10(6) : 701-707
- Year: 2008
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Electroconvulsive therapy (ECT)
Fountoulakis, Konstantinos N., Vieta, Eduard
This paper is a systematic review of the available data concerning the treatment of bipolar disorder: a systematic Medline search concerning treatment guidelines and clinical trials. The search for treatment guidelines returned 583 articles and 913 papers for RCTs. The search was last performed on 1 March 2008. An additional search included repositories of clinical trials and previous systematic reviews in order to trace especially older trials. The literature suggests that lithium is useful during the acute manic and the maintenance phase. Both first- and second-generation antipsychotics are efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are also effective for treating bipolar depression, while olanzapine, quetiapine and aripiprazole are effective during the maintenance phase. Anticonvulsants, particularly valproate and carbamazepine have antimanic properties, whereas lamotrigine may be preferably effective in the treatment of depression but not mania. Antidepressants should always be used in combination with an antimanic agent because they were reported to induce switching to mania or hypomania, mixed episodes, and rapid cycling when given as monotherapy. The best evidence-based psychosocial interventions for bipolar disorder are group- and family-focused psychoeducation. Electroconvulsive therapy is an option for refractory patients. Although a variety of treatment options for bipolar disorder is currently available, their effectiveness is far from satisfactory, especially against bipolar depression and maintenance. Combination therapy may improve treatment outcome but it also carries the burden of more side-effects. Further research as well as the development of better guidelines and algorithms for step-by-step rational treatment are necessary.
International Journal of Neuropsychopharmacology, 11(7) : 999-1029
- Year: 2008
- Problem: Bipolar Disorders
- Type: Systematic reviews
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Psychological Interventions (any)
Consoli, Angele, Deniau, Emmannuelle, Huynh, Christophe, Purper, Diane, Cohen, David
The existence of bipolar disorder in adolescents is now clearly established. However, whether bipolarity exists in children is more controversial. We reviewed the literature on acute and prophylactic treatment of bipolar disorder in youths. The guidelines for the treatment of bipolar disorder in children and adolescents are generally similar to those applied in adult practice. But no evidence-based data support the use of mood stabilisers or antipsychotics since we only found two placebo-randomised controlled trials testing the efficacy of lithium in the paediatric literature. Therefore, we support the view that prescriptions should be limited to the most typical cases. In fact, the use of mood stabilisers or antipsychotics in the treatment of bipolar disorder in children and adolescents appears to be of limited use when a comorbid condition, such as attention deficit hyperactivity disorder, occurs unless aggressive behaviour is the target symptom. [References: 84]
European Child & Adolescent Psychiatry, 16(3) : 187-98
- Year: 2007
- Problem: Bipolar Disorders
- Type: Systematic reviews
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
Findling, Robert L.,
OBJECTIVE: To determine if divalproex sodium was superior to placebo in the treatment of symptomatic youths who suffer from a bipolar spectrum disorder and who also have a parent with a diagnosis of a bipolar illness. METHOD: Youths, ages 5 to 17 years, meeting DSM-IV criteria for bipolar disorder not otherwise specified (NOS) or cyclothymia who also had at least 1 biological parent with bipolar illness were randomly assigned in a double-blind fashion to receive treatment with either dival-proex sodium or placebo for up to 5 years. Study participation ended if the subject required additional clinical intervention, if the patient developed treatment-related adverse events, or if the participant was not adherent with study procedures. The primary outcome measure was time to study discontinuation for any reason. The study was conducted from August 1997 to April 2003. RESULTS: Fifty-six youths with a mean (SD) age of 10.7 (3.1) years were randomly assigned and received either divalproex sodium (N = 29) or placebo (N = 27). In spite of statistical power of 80% to detect hazard ratios of 2.2 or larger, the treatment groups did not significantly differ in survival time for discontinuation for any reason (p = .93) or discontinuation due to a mood event (p = .55). Changes in mood symptom ratings and psychosocial functioning from baseline to study discontinuation did not differ between groups (most significant p > .14). However, both groups did show improvements in mood symptoms and psychosocial functioning over time (all p values < .002). One patient, from the placebo group, ended study participation due to an adverse event. CONCLUSION: These results suggest that, although well tolerated, divalproex sodium does not produce clinically meaningful improvements in the treatment of symptomatic youths suffering from either bipolar NOS or cyclothymia who are at genetic risk for developing bipolar disorder.
Journal of Clinical Psychiatry, 68(5) : 781-8
- Year: 2007
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
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Stage: At risk (indicated or selected prevention)
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Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium)
Brahm, Nancy C., Gutierres, Sheryl L., Carnahan, Ryan M.
PURPOSE: The efficacy and tolerability of quetiapine in the treatment of acute mania were reviewed. SUMMARY: Five randomized, placebo-controlled trials involving quetiapine as monotherapy or adjunct therapy in combination with either divalproex or lithium in the treatment of bipolar mania in either adolescents or adults were identified and reviewed. The primary outcome measure used in the trials was a change in Young Mania Rating Scale total scores. Monotherapy trials evaluated quetiapine, lithium, haloperidol, and placebo. Quetiapine was superior to placebo in both trials. Quetiapine and lithium showed comparable efficacy in one study, though lithium serum concentrations may have been suboptimal. Haloperidol was superior to quetiapine in efficacy at day 21 but similar at day 84. In the two trials evaluating quetiapine or placebo as adjunct therapy to lithium or divalproex, quetiapine was significantly more efficacious than placebo in one trial. In adolescents, quetiapine was more effective than placebo as an adjunct to divalproex. The most common adverse effects clearly attributable to quetiapine in these trials were somnolence and dry mouth. Quetiapine did not induce extrapyramidal effects, but weight gain was notable with the drug. CONCLUSION: While quetiapine treatment demonstrated efficacy in the majority of the studies, the robustness of its efficacy is questionable. The use of quetiapine as first-line therapy for acute mania is not recommended based on the available results and cost considerations. However, it may be a useful second-line agent, particularly when sensitivity to extrapyramidal symptoms limits treatment options. [References: 25]
American Journal of Health-System Pharmacy, 64(10) : 1045-53
- Year: 2007
- Problem: Bipolar Disorders
- Type: Systematic reviews
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Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
Weng, S., Tang, J., Wang, G., Wang, X., Wang, H.
Background: Bipolar disorder (BD) is a common, recurrent, and often life-long major psychiatric condition characterized by manic, depressive, and mixed episodes. Without treatment, there is substantial risk for morbidity and mortality, making BD a considerable public health problem. Objective: The purpose of this study was to compare the relative effectiveness and tolerability of Acanthopanax senficosus (A senficosus)-an herb that is derived from eleutherosides and polysaccharides found in the plant's root- versus fluoxetine added to lithium in the treatment of BD in adolescents. Methods: This was a double-blind, 6-week study. The patients were randomized into 2 treatment groups-A senticosus plus lithium (A senticosus group) and fluoxetine plus lithium (fluoxetine group). The patients underwent a baseline assessment using the 17-Item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) during the screening period. Patients were scheduled for clinical visits at the end of weeks 1, 2, 4, and 6. At the end of the 6-week treatment period, each patient's condition was rated as follows: response (indicating an improvement of [greater-than or equal to]50% in the HAMD-17 score from baseline); remission (a HAMD-17 score of {precedes above single-line equals sign}7); and switching to mania (a YMRS score >16, and meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition, Text Revision] for a manic episode). At each visit (with the exception of the enrollment visit), the patients were queried as to whether they experienced any health problems since the previous visit, a Treatment Emergent Symptom Scale assessment was completed, and the serum lithium concentration was analyzed. The patients were instructed to report adverse events (AEs) at any time during the study. AEs were also observed by the investigator(s) at clinical visits. Results: Seventy-nine Chinese adolescents were initially enrolled into the study. However, 76 adolescents were assessed for inclusion (45 females, 31 males; mean [SD] age, 15.4 [30.0] years; age range, 12-17 years) in the study. All included patients completed the study. After 6 weeks of treatment, the response rate between the A senticosus and the fluoxetine groups was similar (67.6% vs 71.8%, respectively). The remission rate between both groups was also similar (51.4% vs 48.7%). Analyzed by a general line model, the HAMD-17 scores revealed there was a significant time effect (F = 183.06; P < 0.01), but not a significant group effect (F = 0.99) or group-by-duration of treatment interaction (F = 0.779). Three patients in the fluoxetine group experienced switching to mania compared with no patient in the A senticosus group. AEs reported by patients in the A senticosus group were as follows: nausea, 2 (5.4%); rash, 1 (2.7%); and diarrhea, 1 (2.7%). AEs reported by patients in the fluoxetine group were as follows: nausea, 4 (10.3%); anxiety, 3 (7.7%); insomnia, 3 (7.7%); constipation, 1 (2.6%); and tinnitus, 1 (2.6%). Conclusion: Our study found no significant difference in these adolescents with BD treated with lithium plus adjunctive A senticosus or fluoxetine. All treatments were generally well tolerated. copyright 2007 Excerpta Medica, Inc.
Current Therapeutic Research - Clinical & Experimental., 68(4) : 280-290
- Year: 2007
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Selective serotonin reuptake inhibitors (SSRIs), Complementary & Alternative Interventions (CAM)
, Homeopathic, plant-based medicines
Tohen, Mauricio, Kryzhanovskaya, Ludmila, Carlson, Gabrielle, Delbello, Melissa, Wozniak, Janet, Kowatch, Robert, Wagner, Karen, Findling, Robert, Lin, Daniel, Robertson-Plouch, Carol, Xu, Wen, Dittmann, Ralf W., Biederman, Joseph
OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents. METHOD: A 3-week multicenter, parallel, double-blind, randomized placebo-controlled trial was conducted at 24 sites in the United States and two sites in Puerto Rico. The participants were outpatient and inpatient male and female adolescents 13-17 years of age with an acute manic or mixed episode. Subjects received either olanzapine (2.5-20 mg/day [N=107]) or placebo (N=54). The mean change from baseline to endpoint in the Young Mania Rating Scale total score was the primary outcome measure. RESULTS: The mean baseline-to-endpoint change in the Young Mania Rating Scale total score was significantly greater for patients receiving olanzapine relative to patients receiving placebo, and a greater proportion of olanzapine-treated patients met response and remission criteria (44.8% versus 18.5% and 35.2% versus 11.1%, respectively). The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain > or =7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%). The mean baseline-to-endpoint changes in prolactin, fasting glucose, fasting total cholesterol, uric acid, and the hepatic enzymes aspartate transaminase and alanine transaminase were significantly greater in patients treated with olanzapine relative to patients receiving placebo. CONCLUSIONS: Olanzapine was effective in the treatment of bipolar mania in adolescent patients. Patients treated with olanzapine, however, had significantly greater weight gain and increases in the levels of hepatic enzymes, prolactin, fasting glucose, fasting total cholesterol, and uric acid.
American Journal of Psychiatry, 164(10) : 1547-56
- Year: 2007
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Wagner, Karen Dineen, Kowatch, Robert A., Emslie, Graham J., Findling, Robert L., Wilens, Timothy E., McCague, Kevin, D'Souza, Joseph, Wamil, Artur, Lehman, Robert B., Berv, Douglas, Linden, David
OBJECTIVE: This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. METHOD: A total of 116 outpatients 7 to 18 years of age with bipolar I disorder, manic or mixed, were recruited at 20 centers in the United States and randomly assigned to receive 7 weeks of double-blinded, flexibly dosed treatment with oxcarbazepine (maximum dose 900-2400 mg/day) or placebo. The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale (YMRS), using the last-observation-carried-forward method. RESULTS: Oxcarbazepine (mean dose=1515 mg/day) did not significantly improve YMRS scores at endpoint compared with placebo [adjusted mean change: oxcarbazepine, -10.90 (N=55); placebo, -9.79 (N=55)]. Dizziness, nausea, somnolence, diplopia, fatigue, and rash were each reported in at least 5% of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group. The majority of adverse events were mild to moderate and occurred during the titration period. Eleven patients (19%) in the oxcarbazepine group discontinued the study because of adverse events, compared with two (4%) in the placebo group. CONCLUSIONS: Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths. While the overall adverse event profile was similar to that reported for patients with epilepsy, the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population.
American Journal of Psychiatry, 163(7) : 1179-86
- Year: 2006
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium)
Robertson-Plouch, C.
Pharmacy & Therapeutics, 31(12) : 727
- Year: 2006
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
DelBello, Melissa P., Kowatch, Robert A., Adler, Caleb M., Stanford, Kevin E., Welge, Jeffrey A., Barzman, Drew H., Nelson, Erik, Strakowski, Stephen M.
OBJECTIVE: To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania. METHOD: Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days for this double-blind study, which was conducted from July 2002 through January 2004. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) score across the study period. RESULTS: Repeated measures analysis of variance using the last-observation carried forward data indicated no statistically significant group difference in YMRS scores across the 28 days of the study (p = 0.3). Mixed regression analyses (comparison of slopes) revealed that improvement in YMRS scores occurred more rapidly in the quetiapine than in the divalproex group for both the last-observation carried forward (p = 0.01) and observed data (p = 0.03). Response and remission rates were significantly greater in the quetiapine than in the divalproex group (p < .03). Rates of adverse events did not differ significantly between groups. CONCLUSIONS: The results suggest that quetiapine is at least as effective as divalproex in the treatment of acute manic symptoms associated with adolescent bipolar disorder; however, a quicker reduction of manic symptoms may occur with quetiapine as compared with divalproex. Quetiapine may be useful as monotherapy for the treatment of adolescents with manic or mixed episodes, although placebo-controlled studies are necessary.
Journal of the American Academy of Child & Adolescent Psychiatry, 45(3) : 305-13
- Year: 2006
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Anticonvulsants/mood stabilisers (excl. lithium)
Barzman, Drew H., Delbello, Melissa P., Adler, Caleb M., Stanford, Kevin E., Strakowski, Stephen M.
OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders. METHOD: Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point. RESULTS: Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28]. CONCLUSIONS: Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.
Journal of Child & Adolescent Psychopharmacology, 16(6) : 665-70
- Year: 2006
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Anticonvulsants/mood stabilisers (excl. lithium)