Disorders - Bipolar Disorders
Delbello, Melissa P., Findling, Robert L., Kushner, Stuart, Wang, Daniel, Olson, William H., Capece, Julie A., Fazzio, Lydia, Rosenthal, Norman R.
OBJECTIVE: To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD: This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement. RESULTS: Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n=29, 52%) or placebo (n=27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p=.003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (-14.9 versus-5.9, p=.048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia. CONCLUSIONS: Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents.
Journal of the American Academy of Child & Adolescent Psychiatry, 44(6) : 539-47
- Year: 2005
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium)
Calabrese, Joseph R., Keck-Jr, Paul E., Macfadden, Wayne, Minkwitz, Margaret, Ketter, Terence A., Weisler, Richard H., Cutler, Andrew J., McCoy, Robin, Wilson, Ellis, Mullen, Jamie
OBJECTIVE: There is a major unmet need for effective options in the treatment of bipolar depression. METHOD: Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Asberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (> or =50% Montgomery-Asberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of patients meeting remission criteria (Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment-emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively). CONCLUSIONS: Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression.
American Journal of Psychiatry, 162(7) : 1351-60
- Year: 2005
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Findling, Robert L., McNamara, Nora K., Youngstrom, Eric A., Stansbrey, Robert, Gracious, Barbara L., Reed, Michael D., Calabrese, Joseph R.
OBJECTIVE: To determine whether divalproex sodium (DVPX) was superior to lithium carbonate (Li+) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX (Li+/DVPX) pharmacotherapy. METHOD: Youths ages 5-17 years with bipolar I or II disorder were initially treated with Li /DVPX. Patients meeting remission criteria for four consecutive weeks were then randomized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks. Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures. RESULTS: Patients were recruited between July 1998 and May 2002. One hundred thirty-nine youths with a mean (SD) age of 10.8 (3.5) years were initially treated with Li+/DVPX for a mean (SD) duration of 10.7 (5.4) weeks. Sixty youths were then randomized to receive monotherapy with Li+ (n = 30) or DVPX (n = 30). The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse (p = .55) or survival time until discontinuation for any reason (p = .72). CONCLUSIONS: DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy.
Journal of the American Academy of Child & Adolescent Psychiatry, 44(5) : 409-17
- Year: 2005
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium), Lithium
Kafantaris, Vivian, Coletti, Daniel J., Dicker, Robert, Padula, Gina, Pleak, Richard R., Alvir, Jose Maria J.
OBJECTIVE: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. METHOD: In this discontinuation study, participants received open treatment with lithium at therapeutic serum levels (mean 0.99 mEq/L) for at least 4 weeks. Responders were randomly assigned to continue or discontinue lithium during a 2-week double-blind, placebo-controlled phase. This study had 80% power to detect a 40% difference in exacerbation rates between groups (10% on lithium versus 50% on placebo). RESULTS: Twenty-three of 40 protocol participants (57.5%) experienced a clinically significant symptom exacerbation during the 2-week double-blind phase. However, the slightly lower exacerbation rate in the group maintained on lithium (10/19 or 52.6%) versus the group switched to placebo (13/21 or 61.9%) did not reach statistical significance. CONCLUSIONS: This study does not support a large effect for lithium continuation treatment of adolescents with acute mania, mostly due to the unexpectedly high rate of exacerbations in the group that continued on lithium. Further studies are warranted to clarify whether acute mania in adolescents is lithium responsive.
Journal of the American Academy of Child & Adolescent Psychiatry, 43(8) : 984-93
- Year: 2004
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Lithium, Medication dose reduction/discontinuation
Pavuluri, Mani N., Henry, David B., Carbray, Julie A., Sampson, Gwendolyn, Naylor, Michael W., Janicak, Philip G.,
OBJECTIVE: This prospective 6-month open trial examined the safety and efficacy of two combination therapies for manic or mixed episodes of pediatric bipolar disorder: (1) divalproex sodium plus risperidone (DVPX+Risp), or (2) lithium plus risperidone (Li+Risp). METHODS: Thirty-seven (37) subjects aged 5 and 18 (age=12.1+/-3.5 years) with DSM IV current mixed or manic episode and Young Mania Rating Scale (YMRS) score >20 were sequentially assigned to either DVPX+Risp or Li+Risp in a 6-month, prospective open-label trial. Outcome measures included the YMRS, Clinical Global Impression Scale for Bipolar Disorder (CGI-BP), Child Depression Rating Scale-Revised (CDRS-R) as well as measures of safety and tolerability. RESULTS: Effect sizes (Cohen's d) based on change of YMRS scores from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp. Response rates (>or=50% change from baseline YMRS score at the end of study) were 80% for DVPX+Risp and 82.4% for Li+Risp. Both combination treatments were well tolerated. Significant improvements (p<0.001) from baseline were seen for mean scores on all efficacy measures, i.e., YMRS, CGI-BP, and CDRS-R. There were no significant group differences in safety or tolerability, and no serious adverse events during the 6-month trial. CONCLUSION: Both DVPX+Risp and Li+Risp show strong effects coupled with safety and tolerability in treating children and adolescents with manic or mixed episodes associated with type I bipolar disorder.
Journal of Affective Disorders, 82 Suppl 1 : S103-11
- Year: 2004
- Problem: Bipolar Disorders
- Type: Controlled clinical trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Anticonvulsants/mood stabilisers (excl. lithium), Lithium
Rea, Margaret M., Tompson, Martha C., Miklowitz, David J., Goldstein, Michael J., Hwang, Sun, Mintz, Jim
Recently hospitalized bipolar, manic patients (N = 53) were randomly assigned to a 9-month, manual-based, family-focused psychoeducational therapy (n = 28) or to an individually focused patient treatment (n = 25). All patients received concurrent treatment with mood-stabilizing medications. Structured follow-up assessments were conducted at 3-month intervals for a 1-year period ofactive treatment and a 1-year period of posttreatment follow-up. Compared with patients in individual therapy, those in family-focused treatment were less likely to be rehospitalized during the 2-year study period. Patients in family treatment also experienced fewer mood disorder relapses over the 2 years, although they did not differ from patients in individual treatment in their likelihood of a first relapse. Results suggest that family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder.
Journal of Consulting & Clinical Psychology, 71(3) : 482-92
- Year: 2003
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Relapse prevention
-
Treatment and intervention: Psychological Interventions (any)
, Other Psychological Interventions
Colom, Francesco, Vieta, Eduard, Martinez-Aran, Anabel, Reinares, Maria, Goikolea, Jose Manuel, Benabarre, Antonio, Torrent, Carla, Comes, Merce, Corbella, Barbara, Parramon, Gemma, Corominas, Josep
BACKGROUND: Studies on individual psychotherapy indicate that some interventions may reduce the number of recurrences in bipolar patients. However, there has been a lack of structured, well-designed, blinded, controlled studies demonstrating the efficacy of group psychoeducation to prevent recurrences in patients with bipolar I and II disorder. METHODS: One hundred twenty bipolar I and II outpatients in remission (Young Mania Rating Scale score <6, Hamilton Depression Rating Scale-17 score <8) for at least 6 months prior to inclusion in the study, who were receiving standard pharmacologic treatment, were included in a controlled trial. Subjects were matched for age and sex and randomized to receive, in addition to standard psychiatric care, 21 sessions of group psychoeducation or 21 sessions of nonstructured group meetings. Subjects were assessed monthly during the 21-week treatment period and throughout the 2-year follow-up. RESULTS: Group psychoeducation significantly reduced the number of relapsed patients and the number of recurrences per patient, and increased the time to depressive, manic, hypomanic, and mixed recurrences. The number and length of hospitalizations per patient were also lower in patients who received psychoeducation. CONCLUSION: Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder.
Archives of General Psychiatry, 60(4) : 402-7
- Year: 2003
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Relapse prevention
-
Treatment and intervention: Psychological Interventions (any)
, Psychoeducation
Delbello, Melissa P., Schwiers, Michael L., Rosenberg, H. Lee, Strakowski, Stephen M.
OBJECTIVES: This randomized, double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex (DVP) for acute mania in adolescents with bipolar disorder. It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder. Furthermore, it was hypothesized that quetiapine would be well tolerated. METHOD: Thirty manic or mixed bipolar I adolescents (12-18 years) received an initial DVP dose of 20 mg/kg and were randomly assigned to 6 weeks of combination therapy with quetiapine, which was titrated to 450 mg/day (n = 15) or placebo (n = 15). Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale (YMRS) score and YMRS response rate. Safety and tolerability were assessed weekly. RESULTS: The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group (F(1,27) = 5.04, p =.03). Moreover, YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group (87% versus 53%; Fisher exact test, p =.05). No significant group differences from baseline to endpoint in safety measures were noted. Sedation, rated as mild or moderate, was significantly more common in the DVP + quetiapine group than in the DVP + placebo group. CONCLUSIONS: The findings of this study indicate that quetiapine in combination with DVP is more effective for the treatment of adolescent bipolar mania than DVP alone. In addition, the results suggest that quetiapine is well tolerated when used in combination with DVP for the treatment of mania.
Journal of the American Academy of Child & Adolescent Psychiatry, 41(10) : 1216-23
- Year: 2002
- 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)
Fristad, Mary A., Goldberg-Arnold, Jill S., Gavazzi, Stephen M.
OBJECTIVES: Multi-family psychoeducation groups (MFPG) have been developed and tested for adults, but not for children with bipolar disorder (BPD). We present data from a pilot study of our manual-driven MFPG treatment for families of children with mood disorders and address two questions: Do families of children with BPD and families of children with major depressive disorder/dysthymic disorder (MDD/DD): 1) differ at treatment entry?; 2) benefit equally from intervention? METHOD: A total of 35 children (n=16, BPD; n=19, MDD/DD) aged 8-11 years and their parents were randomized into immediate MFPG plus treatment as usual (TAU) or wait-list + TAU and assessed periodically. RESULTS: At baseline, there was a trend toward parents in BPD families being more knowledgeable about mood symptoms than parents in MDD/DD families (p < 0.04). Additionally at baseline, children with BPD evidenced greater mood severity historically and a trend toward more hospitalizations, day treatment, outpatient treatment, medication trials, and placement in special education classrooms than children with MDD/DD. Immediately following and 4 months post-treatment, both BPD and MDD/DD families described having gained knowledge, skills, support, and positive attitudes during treatment. MDD/DD families increased their knowledge of symptoms to the same level as BPD families. CONCLUSIONS: While BPD families enter treatment with more impaired children and more extensive treatment histories, both BPD and MDD/DD families benefit from intervention. The clinical issues concerning combining families of children with bipolar and depressive spectrum illnesses in groups are discussed. Clinical impressions suggest that such combinations are clinically feasible and potentially beneficial.
Bipolar Disorders, 4(4) : 254-62
- Year: 2002
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Psychoeducation
Kowatch, R. A., Suppes, T., Carmody, T. J., Bucci, J. P., Hume, J. H., Kromelis, M., Emslie, G. J., Weinberg, W. A., Rush, A. J.
OBJECTIVE: To develop effect sizes for 3 mood stabilizers--lithium, divalproex sodium, and carbamazepine--for the acute-phase treatment of bipolar I or II disorder, mixed or manic episode, in children and adolescents aged 8 to 18 years. METHOD: Forty-two outpatients with a mean age of 11.4 years (20 with bipolar I disorder and 22 with bipolar II disorder) were randomly assigned to 6 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale (Y-MRS). RESULTS: Using a > or = 50% change from baseline to exit in the Y-MRS scores to define response, the effect size was 1.63 for divalproex sodium, 1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were as follows: sodium divalproex, 53%; lithium, 38%; and carbamazepine, 38% (chi 2(2) = 0.85, p = .60). All 3 mood stabilizers were well tolerated, and no serious adverse effects were seen. CONCLUSIONS: Divalproex sodium, lithium, and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode.
Journal of the American Academy of Child & Adolescent Psychiatry, 39(6) : 713-20
- Year: 2000
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium), Lithium
Geller, Barbara, Cooper, Thomas B., Sun, Kai, Zimermann, Betsy, Frazier, Jeanne, Williams, Marlene, Heath, Janet
Performed a double-blind, placebo-controlled, random assignment, parallel group, pharmacokinetically dosed study of lithium for adolescents with bipolar disorders (BDs) and temporally secondary substance dependency disorders (SDDs). Ss were 12-18 yrs old and were comprehensively assessed during a 6-wk outpatients protocol that included random weekly urine collection for drug assays and random and weekly serum collection for lithium levels. Using both intent-to-treat (N=25) and completer (N=21) analyses, there were significant differences on continuous and categorical measures between the active and placebo groups for both psychopathology measures and weekly random urine drug assays. The mean scheduled weekly serum lithium level of active responders was 0.9 mEq/L. Addiction to both alcohol and marijuana was the most frequent category of SSD. Lithium treatment of BDs with secondary SDDs in adolescents was an efficacious treatment for both disorders. (PsycINFO Database Record (c) 2007 APA, all rights reserved).
Journal of the American Academy of Child & Adolescent Psychiatry, 37(2) : 171-178
- Year: 1998
- Problem: Bipolar Disorders, Substance Use Disorders (any)
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Lithium