Faria, A. D., de-Mattos-Souza, L. D., de-Azevedo-Cardoso, T., Pinheiro, K. A. T., Pinheiro, R. T., da-Silva, R. A., Jansen, K.

The influence of psychoeducation on regulating biological rhythm in a sample of patients with bipolar II disorder: a randomized clinical trial

Psychology research and behavior management, 7 : 167

de- Azevedo-Cardoso, T., de-Azambuja-Farias, C., Mondin, T., Del-Grande-da-Silva, G., de-Mattos-Souza, L., da-Silva, R., Pinheiro, K., do-Amaral, R., Jansen, K.

Brief psychoeducation for bipolar disorder: Impact on quality of life in young adults in a 6-month follow-up of a randomized controlled trial

There are scarce follow-up studies evaluating the role of psychoeducation in the treatment of bipolar disorder, especially in a young sample, with a recent diagnosis and that probably received a few previous interventions. This was a randomized clinical trial with young adults aged 18 - 29 years, who had been diagnosed with bipolar disorder through the Structured Clinical Interview for DSM (SCID). The evaluation of quality of life was carried out using the Medical Outcomes Survey 36-Item Short-Form Health Survey (MOS SF-36). All participants were randomized into two groups: combined intervention (psychoeducation plus medication) and treatment-as-usual (medication). The sample consisted of 61 patients divided in two groups (29 usual treatment; 32 combined intervention). The quality of life domains did not reveal statistically significant differences when comparing baseline, post-intervention and 6-month follow-up evaluations, which indicates that there is no difference between combined intervention and usual intervention regarding quality of life improvement. Both groups presented improvements in quality of life domains, except General Health and Bodily Pain, at post-intervention. Moreover, this improvement persisted at 6-month follow-up, except for the Role Physical Health domain, which remained reduced. Combined Psychoeducation plus pharmacological intervention is so effective in improving quality of life perception as it is pharmacological only intervention. (PsycINFO Database Record (c) 2014 APA, all rights reserved). (journal abstract)

Psychiatry Research, 220(3) : 896-902

Amerio, A., Odone, A., Marchesi, C., Ghaemi, S.

Treatment of comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review

Background: More than 20% of patients with bipolar disorder (BD) show lifetime comorbidity for obsessive-compulsive disorder (OCD), but treatment of BD-OCD is a clinical challenge. Although serotonin reuptake inhibitors (SRIs) are the first line treatment for OCD, they can induce mood instability in BD. An optimal treatment approach remains to be defined.; Methods: We systematically reviewed MEDLINE, Embase, PsychINFO and the Cochrane Library and retrieved data on clinical management of comorbid BD-OCD patients. Pharmacologic, psychotherapeutic and others alternative approaches were included.; Results: Fourteen studies were selected. In all selected studies BD-OCD patients received mood stabilizers. In the largest study, 42.1% of comorbid patients required a combination of multiple mood stabilizers and 10.5% a combination of mood stabilizers with atypical antipsychotics. Addition of antidepressants to mood stabilizers led to clinical remission of both conditions in only one study. Some BD-OCD patients on mood stabilizer therapy benefitted from adjunctive psychotherapy.; Limitations: Most studies are case reports or cross-sectional studies based on retrospective assessments. Enrollment of subjects mainly from outpatient specialty units might have introduced selection bias and limited community- wide generalizability.; Conclusions: Keeping in mind scantiness and heterogeneity of the available literature, the best interpretation of the available evidence appears to be that mood stabilization should be the primary goal in treating BD-OCD patients. Addition of SRI agents seems unnecessary in most cases, although it may be needed in a minority of BD patients with refractory OCD.; Copyright © 2014 Elsevier B.V. All rights reserved.

Journal of Affective Disorders, 166 : 258- 263

DelBello, M., Welge, J., Strawn, J., Patino-Duran, L. R., Stahl, L., Blom, T., Strakowski, S., McNamara, R.

A double-blind placebo-controlled study of long-chain omega-3 fatty acid supplementation for depression in youth at ultra-high risk for bipolar disorder

Background: Family studies demonstrate that offspring of bipolar parents have an elevated risk of developing mood disorders compared with the general population. When these offspring develop major depressive disorder, their risk of developing mania (and by definition bipolar I disorder) is increased further (ie, they are at ultra-high risk). Moreover, antidepressant medications that are commonly used to treat depressive symptoms may increase risk of developing manic symptoms. Therefore, studies of potential treatments for mood symptoms in ultra-high risk youth are urgently needed to establish early intervention, and ultimately prevention, strategies. The aim of our 12-week double-blind placebo-controlled study was to examine the efficacy and tolerability of long-chain omega-3 (LCn-3) fatty acids for the treatment of depressive symptoms in ultrahigh risk youth and to investigate predictors and mediators of treatment response. Methods: Sixty youth (ages 9-20 years) with a current DSMIV- TR diagnosis of Major Depressive Disorder or Depressive Disorder NOS, a Childhood Depression Rating Scale- Revised Version (CDRS-R) of score (greater-than or equal to) 28, and at least one biological parent with bipolar I disorder, were recruited to participate in this 12-week double-blind placebo-controlled study. Fifty-six subjects were randomized to LCn-3 fatty acid supplements (2100 mg/d) or placebo (olive oil). Symptom and tolerability ratings were performed weekly and red blood cell (RBC) LCn-3 fatty acid levels were obtained at baseline and endpoint from each participant. Results: The mean age of participants was 13.7 + 4.0 years, and a majority of participants were girls (82%) and White (67%). At baseline subjects displayed moderate symptoms of depression (mean CDRS-R: 47 + 8), and there was a trend for an inverse correlation between baseline CDRS scores and RBC LCn-3 fatty acid levels (R2=0.06, p=0.085). Among participants with post-baseline LCn-3 measurements, RBC LCn-3 fatty acid (EPA +DHA) levels increased and arachidonic acid (AA) to EPA +DHA (AA/EPA +DHA) ratios decreased, significantly from baseline to endpoint in the group treated with LCn-3 fatty acids (n=20) but not in the placebo group (n=20). There were statistically significant baseline to endpoint reductions in CDRS-R scores in both treatment groups (LCn-3 fatty acids: -21.1 + 8.9 and placebo: -18.9 + 8.4), although there was no significant group difference in improvement (p=0.42). The mean + SD percent reduction in CDRS-R score was 66 + 27% in the LCn-3 fatty acid group and 53 + 27% in the placebo group (p=0.11). The baseline AA/EPA +DHA ratio was inversely correlated with baseline to endpoint change in CDRS-R score (ie, smaller baseline ratios were associated with greater CDRS-R improvement, p=0.031), and larger baseline to endpoint decreases in the AA/DHA + EPA ratio were associated with smaller reductions in CDRS-R scores. In an ANCOVA model, this effect appeared to be similar in both treatment groups (p=0.044 for main effect of change in AA/EPA + DHA, and no significant interaction with treatment assignment, p=0.69). After adjusting for the baseline to endpoint change in the AA/EPA +DHA ratio, treatment with LCn-3 fatty acids was associated with greater reductions in CDRS-R scores than placebo (p=0.017). The most commonly reported adverse events were headache (Placebo: 83%, LCn-3: 77%) and drowsiness (Placebo: 72%, LCn-3: 77%). Reported gastrointestinal adverse events were nausea (Placebo: 52%, LCn-3: 54%), vomiting (Placebo: 38%, LCn- 3: 19%), diarrhea (Placebo: 17%, LCn-3: 27%), and heartburn (Placebo: 17%, LCn-3: 31%). Conclusions: This study provides preliminary evidence that LCn-3 fatty acid supplementation is well-tolerated and improves depressive symptoms in youth at high risk for developing mania. Additionally, we found that higher baseline LCn-3 fatty acid levels predicted greater improvement in depressive symptoms. Although the results suggest that supplementation may produce treatment benefits, in contrast to our expectation, larger decreases in A to DHA + EPA ratios were associated with less improvement in depressive symptoms. These findings indicate that the amount, duration, and/or rate of change in LCn-3 fatty acid levels may impact the therapeutic benefits of omega-3 fatty acid supplementation. Additional dose finding studies to identify a plausible biological mechanism for our findings and to determine whether omega-3 fatty acid supplementation is more effective and better tolerated than conventional antidepressant medications for the treatment of ultra-high risk youth are necessary.

Neuropsychopharmacology, 38 : S374-S375

Crowe, M., Inder, M., Moor, S., Luty, S. E., Carter, J.

Suicide attempts in young people with bipolar disorder: Results from a psychotherapy intervention and three years follow-up

Objective: Rates of attempting and completing suicide are high in Bipolar Disorder (BD) with death due to suicide in 10-15% of patients (Simon, Hunkeler et al. 2007), up to 60-fold higher than in the general population (Neves, Malloy-Dinez et al. 2009). The high lethality of suicidal acts in bipolar disorders is suggested by a much lower ratio of attempts: suicide (approximately 3:1) than in the general population (approximately 30:1) (Baldessarini, Tondo et al. 2006). The association between BD and suicide attempts is wellestablished, however there is fairly limited prospective data reported and many studies exclude patients who have alcohol and/ or drug abuse/dependence, other Axis 1 comorbidity or suicidal ideation (Crowe, Whitehead et al. 2010). Methods: One hundred young people (15-36 years) were recruited to take part in an 18-month randomised controlled trial of Interpersonal and Social Rhythm Therapy (IPSRT) and Specialist Supportive Care (SSC). Participants were randomised to each therapy in addition to medication management from a psychiatrist. Data on lifetime suicide attempts was collected as baseline weeks 26, 52, 78, 104, 130, and 156, with additional questions on suicidal behaviour. Descriptive analyses including frequencies, percentages, means and standard deviations were undertaken on demographic, clinical and suicide data. Chi-square analyses and independent t-test were done to compare the characteristics of those participants who completed with those who were non- completers. Results: At baseline previous suicide attempts were common with 48 participants (7 males, 41 females) assessed by the treating psychiatrist as having attempted suicide. In the six months preceding the study, a total of 11 (22.9%) individuals, all female, made suicide attempts. The vast majority of participants at the time of the attempt indicated they wished to die with 2/3rds believing their attempt would result in death. In the 6 months prior to the study commencement, there were a total of 11 individuals who made attempts with a total of 18 actual attempts made. Over the course of the intervention and follow up period (156 weeks), 15 individuals made subsequent suicide attempts with a total of 28 attempts. During the course of the study there was one death by suicide. There were no statistical differences found in demographic, clinical or suicidal behaviour characteristics indicating no significant differences in these groups. Discussion: There were no statistical differences in the characteristics of suicide risk factors (gender, age, age of onset, previous attempts, substance or alcohol use disorder and anxiety disorder) between those we were able to follow-up (n = 73) and those that were lost to follow-up (n = 27). While there may be an association between the psychotherapy interventions and the reduction in suicide attempts, there are also other possible factors that could explain this. Larger numbers would be required before an association could be made more definitively. However these results add to the growing evidence that adjunctive psychosocial interventions may contribute to a reduction in suicide risk in bipolar individuals.

Bipolar Disorders, 15 : 97

Brown, R., Taylor, MJ., Geddes, J.

Aripiprazole alone or in combination for acute mania

Background: Bipolar disorder is a mental disorder characterised by episodes of elevated or irritable mood (manic or hypomanic episodes) and episodes of low mood and loss of energy (depressive episodes). Drug treatment is the first-line treatment for acute mania with the initial aim of rapid control of agitation, aggression and dangerous behaviour. Aripiprazole, an atypical antipsychotic, is used in the treatment of mania both as monotherapy and combined with other medicines. The British Association of Psychopharmacology guidelines report that, in monotherapy placebo-controlled trials, the atypical antipsychotics, including aripiprazole, have been shown to be effective for acute manic or mixed episodes.Objectives: To assess the efficacy and tolerability of aripiprazole alone or in combination with other antimanic drug treatments, compared with placebo and other drug treatments, in alleviating acute symptoms of manic or mixed episodes. Other objectives include reviewing the acceptability of treatment with aripiprazole, investigating the adverse effects of aripiprazole treatment, and determining overall mortality rates among those receiving aripiprazole treatment.Search methods: The Cochrane Depression, Anxiety and Neurosis Group's Specialised Register (CCDANCTR-Studies and CCDANCTR-References) was searched, all years to 31st July 2013. This register contains relevant randomised controlled trials from: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We also searched Bristol-Myers Squibb clinical trials register, the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov (to August 2013).Selection criteria: Randomised trials comparing aripiprazole versus placebo or other drugs in the treatment of acute manic or mixed episodes.Data collection and analysis: Two review authors independently extracted data, including adverse effect data, from trial reports and assessed bias. The drug manufacturer or the trial authors were contacted for missing data.Main results: Ten studies (3340 participants) were included in the review. Seven studies compared aripiprazole monotherapy versus placebo (2239 participants); two of these included a third comparison arm-one study used lithium (485 participants) and the other used haloperidol (480 participants). Two studies compared aripiprazole as an adjunctive treatment to valproate or lithium versus placebo as an adjunctive treatment (754 participants), and one study compared aripiprazole versus haloperidol (347 participants). The overall risk of bias was unclear. A high dropout rate from most trials (> 20% for each intervention in eight of the trials) may have affected the estimates of relative efficacy. Evidence shows that aripiprazole was more effective than placebo in reducing manic symptoms in adults and children/adolescents at three and four weeks but not at six weeks (Young Mania Rating Scale (YMRS); mean difference (MD) at three weeks (random effects) -3.66, 95% confidence interval (CI) -5.82 to -2.05; six studies; N = 1819, moderate quality evidence) - a modest difference. Aripiprazole was compared with other drug treatments in three studies in adults-lithium was used in one study and haloperidol in two studies. No statistically significant differences between aripiprazole and other drug treatments in reducing manic symptoms were noted at three weeks (YMRS MD at three weeks (random effects) 0.07, 95% CI -1.24 to 1.37; three studies; N = 972, moderate quality evidence) or at any other time point up to and including 12 weeks. Compared with placebo, aripiprazole caused more movement disorders, as measured on the Simpson Angus Scale (SAS), on the Barnes Akathisia Scale (BAS) and by participant-reported akathisia (high quality evidence), with more people requiring treatment with anticholinergic medication (risk ratios (random effects) 3.28, 95% CI 1.82 to 5.91; two studies; N = 730, high quality evidence). Aripiprazole also led to more gastrointestinal disturbances (nausea (high quality evidence), and consti ation) and caused more children/adolescents to have a prolactin level that fell below the lower limit of normal. Significant heterogeneity was present in the meta-analysis of movement disorders associated with aripiprazole and other treatments and was most likely due to the different side effect profiles of lithium and haloperidol. At the three-week time point, meta- analysis was not possible because of lack of data; however, at 12 weeks, haloperidol resulted in significantly more movement disorders than aripiprazole, as measured on the SAS, the BAS and the Abnormal Involuntary Movement Scale (AIMS) and by participant-reported akathisia. By 12 weeks, investigators reported no difference between aripiprazole and lithium (SAS, BAS, AIMS), except in terms of participant-reported akathisia (RR 2.97, 95% CI 1.37 to 6.43; one study; N = 313).Authors' conclusions: Aripiprazole is an effective treatment for mania in a population that includes adults, children and adolescents, although its use leads to gastrointestinal disturbances and movement disorders. Comparative trials with medicines other than haloperidol and lithium are few, so the precise place of aripiprazole in therapy remains unclear.

Cochrane Database of Systematic Reviews, (12) : CD005000

Findling, R. L., Correll, C. U., Nyilas, M., Forbes, R. A., McQuade, R.D., Jin, N., Ivanova, S., Mankoski, R., Carson, W. H., Carlson, G. A.,

Aripiprazole for the treatment of pediatric bipolar I disorder: a 30-week, randomized, placebo-controlled study

Objective: To evaluate the long-term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder.; Methods: A randomized, double-blind, 30-week, placebo-controlled study of aripiprazole (10 or 30 mg/day) in youths (10-17 years) with bipolar I disorder (manic or mixed) ± psychotic features (n = 296) was performed. After four weeks, acute treatment completers continued receiving =26 weeks of double-blind treatment (n = 210). The primary outcome was Young Mania Rating Scale (YMRS) total score change.; Results: Of the 210 subjects who entered the 26-week extension phase, 32.4% completed the study (45.3% for aripiprazole 10 mg/day, 31.0% for aripiprazole 30 mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p < 0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol-specified last observation carried forward analyses, but not in observed case or mixed-model repeated measures at week 30. Overall time to all-cause discontinuation was longer for aripiprazole 10 mg/day (15.6 weeks) and aripiprazole 30 mg/day (9.5 weeks) compared with placebo (5.3 weeks; both p < 0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children's Global Assessment of Functioning and Clinical Global Impressions-Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder.; Conclusions: Aripiprazole 10 mg/day and 30 mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30 weeks. Despite the benefits of treatment, completion rates were low in all treatment arms.; © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Bipolar Disorders, 15(2) : 138-149

Findling, R. L., Cavus, I., Pappadopulos, E., Vanderburg, D. G., Schwartz, J. H., Gundapaneni, B. K., Delbello, M. P.

Efficacy, long-term safety, and tolerability of Ziprasidone in children and adolescents with bipolar disorder

Objective: The purpose of this study was to evaluate the short- and long-term efficacy and safety of ziprasidone in children and adolescents with bipolar I disorder. Methods: Subjects 10-17 years of age with a manic or mixed episode associated with bipolar I disorder participated in a 4 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized 2:1 to initially receive flexible-dose ziprasidone (40-160 mg/day, based on weight) or placebo. Primary outcome was the change in Young Mania Rating Scale (YMRS) scores from baseline. Safety assessments included weight and body mass index (BMI), adverse events (AEs), vital signs, laboratory measures, electrocardiograms, and movement disorder ratings. Results: In the RCT, 237 subjects were treated with ziprasidone (n=149; mean age, 13.6 years) or placebo (n=88; mean age, 13.7 years). The estimated least squares mean changes in YMRS total (intent- to-treat population) were -13.83 (ziprasidone) and -8.61 (placebo; p=0.0005) at RCT endpoint. The most common AEs in the ziprasidone group were sedation (32.9%), somnolence (24.8%), headache (22.1%), fatigue (15.4%), and nausea (14.1%). In the OLE, 162 subjects were enrolled, and the median duration of treatment was 98 days. The mean change in YMRS score from the end of the RCT to the end of the OLE (last observation carried forward) was -3.3 (95% confidence interval, -5.0 to -1.6). The most common AEs were sedation (26.5%), somnolence (23.5%), headache (22.2%), and insomnia (13.6%). For both the RCT and the OLE, no clinically significant mean changes in movement disorder scales, BMI z-scores, liver enzymes, or fasting lipids and glucose were observed. One subject on ziprasidone in the RCT and none during the OLE had Fridericia-corrected QT interval (QTcF) (greater-than or equal to)460 ms. Conclusion: These results demonstrate that ziprasidone is efficacious for treating children and adolescents with bipolar disorder. Ziprasidone was generally well tolerated with a neutral metabolic profile. Clinical Trials Registry: NCT00257166 and NCT00265330 at ClinicalTrials.gov. (copyright) Copyright 2013, Mary Ann Liebert, Inc. 2013.

Journal of Child & Adolescent Psychopharmacology, 23(8) : 545- 557

Miklowitz, D. J.

Psychosocial interventions for early-onset bipolar spectrum disorders

Delays to first treatment of BD spectrum disorders in childhood are associated with greater depressive morbidity and less time euthymic in adulthood. Without early intervention, the social, intellectual, and emotional development of youth at high risk for BD may be seriously compromised. Accordingly, well tolerated interventions that reduce affective morbidity and functional impairment could have dramatically favorable impact on individual suffering in BD. Psychosocial treatments can augment pharmacotherapy in the management of early-onset BD. These strategies can be adapted to complex presentations of BD, including comorbid substance abuse, rage reactions, and anxiety. This talk will examine major schools of psychosocial treatment for early-onset BD, common elements of these approaches, and how these approaches can be adapted to the different needs of older or younger patients, youth with subthreshold and threshold bipolar syndromes, and those with comorbid disorders. Four randomized trials with adults with BD have shown that combining familyfocused treatment (FFT) with pharmacotherapy delays recurrences, speeds recovery, and enhances functioning after an acute illness episode, when compared to treatment as usual or intensive individual psychoeducation and pharmacotherapy. Issues addressed in FFT for early onset youth with BD include (a) identifying early warning signs of recurrence; (b) implementing strategies to delay the onset of full episodes; (c) education regarding adherence with medications; (d) distinguishing personality, temperament, and variations in normal development from illness episodes; and (e) enhancing family communication and problem-solving skills. The speaker will describe new results from two recently completed randomized trials of FFT for adolescents (N = 145) and youth at risk for bipolar disorder (N = 40). In the latter study, FFT was more effective than brief psychoeducation in hastening recovery from baseline depressive symptoms and improving the trajectory of hypomanic symptoms over 1 year. Multifamily group models (Fristad et al.; West et al.) emphasize the role of psychoeducation and group support in helping families cope with the fluctuations of BD among school-aged children. A large-scale wait-list controlled trial (Fristad et al.) found that multifamily groups had a strong impact on symptom stabilization in depressed and bipolar youth. Interpersonal and social rhythm therapy (Frank & Hlastala), which emphasizes keeping youth on regular sleep/wake cycles and encouraging regulated routines, offers strategies that can be incorporated into brief medication management sessions. An adaptation of IPSRT for offspring of bipolar parents is now being tested in a clinical trial (T. Goldstein & Frank). Finally, the cognitive behavioral, family-focused nullRainbownull program has been shown to improve symptoms in school-aged children with bipolar spectrum disorders (West & Pavuluri). Common themes in these approaches will be highlighted, as will methodological issues relevant to testing psychosocial interventions in combination with pharmacotherapy in clinical trials.

Bipolar Disorders, 15 : 16-17

Miklowitz, D. J., Schneck, C. D., Singh, M. K., Taylor, D. O., George, E. L., Cosgrove, V. E., Howe, M. E., Dickinson, L. M., Garber, J., Chang, K. D.

Early intervention for symptomatic youth at risk for bipolar disorder: A randomized trial of family-focused therapy

Objective: Depression and brief periods of (hypo)mania are linked to an increased risk of progression to bipolar I or II disorder (BD) in children of bipolar parents. This randomized trial examined the effects of a 4- month family-focused therapy (FFT) program on the 1-year course of mood symptoms in youth at high familial risk for BD, and explored its comparative benefits among youth in families with high versus low expressed emotion (EE). Method: Participants were 40 youth (mean 12.3 ± 2.8 years, range 9 - 17) with BD not otherwise specified, major depressive disorder, or cyclothymic disorder who had a first-degree relative with BD I or II and active mood symptoms (Young Mania Rating Scale [YMRS] >11 or Child Depression Rating Scale >29). Participants were randomly allocated to FFT - High Risk version (FFT-HR; 12 sessions of psychoeducation and training in communication and problem-solving skills) or an education control (EC; 1 - 2 family sessions). Results: Youth in FFT-HR had more rapid recovery from their initial mood symptoms (hazard ratio = 2.69, p = .047), more weeks in remission, and a more favorable trajectory of YMRS scores over 1 year than youth in EC. The magnitude of treatment effect was greater among youth in high-EE (versus low-EE) families. Conclusions: FFT-HR may hasten and help sustain recovery from mood symptoms among youth at high risk for BD. Longer follow-up will be necessary to determine whether early family intervention has downstream effects that contribute to the delay or prevention of full manic episodes in vulnerable youth. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)

Journal of the American Academy of Child & Adolescent Psychiatry, 52(2) : 121-131

Pathak, S., Findling, R. L., Earley, W. R., Acevedo, L. D., Stankowski, J., DelBello, M. P.

Efficacy and safety of quetiapine in children and adolescents with mania associated with bipolar I disorder: A 3-week, double-blind, placebo-controlled trial

Objective: To evaluate the efficacy and safety of quetiapine monotherapy in children and adolescents with mania associated with bipolar I disorder. Method: Patients aged 10 to 17 years, with a DSM-IV-TR diagnosis of a manic episode associated with bipolar I disorder and Young Mania Rating Scale (YMRS) total score = 20 were randomized to 3 weeks of quetiapine (400 or 600 mg/d) or placebo. The primary efficacy measure was change in YMRS total score. The study was conducted at 34 centers in the United States between August 2004 and July 2006. Results: The intent-to-treat population included 277 patients. Least squares mean change in YMRS score from baseline to end point by mixed-model, repeated-measures analysis was -14.25, -15.60, and -9.04 for quetiapine 400 mg/d, quetiapine 600 mg/d, and placebo, respectively (P < .001, each quetiapine dose vs placebo). Significant improvement in YMRS score versus placebo was first observed at day 4 (P = .015) with quetiapine 400 mg/d and day 7 (P < .001) with quetiapine 600 mg/d. Mean changes in body weight at day 21 (observed cases) were 1.7 kg for both quetiapine doses and 0.4 kg for placebo. Numerically larger mean increases in total cholesterol, low- density lipoprotein cholesterol, and triglycerides were observed with quetiapine than placebo. Adverse events associated with quetiapine were mostly mild to moderate in intensity. Conclusions: In this 3-week study, quetiapine was significantly more effective than placebo in improving manic symptoms in youth with mania associated with bipolar disorder. Treatment was generally well tolerated and adverse events were broadly consistent with the known profile of quetiapine in adults with bipolar disorder. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)

Journal of Clinical Psychiatry, 74(1) : e100- e109

West, A. E., Weinstein, S. M., Peters, A.

Family functioning moderates psychosocial treatment outcome for pediatric bipolar disorder

Objective: Psychosocial treatment has been indicated as an essential component of effective treatment for pediatric bipolar disorder (PBD). However, patients demonstrate variable response to current evidence-based psychosocial interventions, implying that certain patient and family characteristics may moderate treatment outcomes. In particular, poor family functioning has emerged as a potential moderator of treatment outcome for youth with bipolar disorder (Miklowitz et al., 2009), with families demonstrating lower functioning showing poorer response to treatment. Methods: Data presented is from a randomized clinical trial of child- and family-focused cognitive-behavioral therapy (CFFCBT) versus treatment as usual (TAU) for PBD youth aged 7-13 (n = 60). Participants were recruited from a specialty pediatric mood disorders clinic in a large Midwestern medical center. All participants were diagnosed with bipolar disorder (I, II, or NOS) via the WASH-U-KSADS and randomly assigned to receive 12 weeks of CFF-CBT or TAU sessions. Participants were assessed (via a blinded rater) on a range of symptom, global functioning, child, parent, and family psychosocial functioning measures at baseline, weeks 4 and 8, post-treatment, and a 6-month follow-up. Family functioning was assessed using the Family Adaptability and Cohesion Evaluation Scale (FACES); family coping was assessed by the Family Crisis Oriented Personal Evaluation Scales (F-COPES). Results: Results demonstrate strong overall efficacy for CFF-CBT versus TAU; however, family characteristics at baseline emerged as a powerful moderator of outcomes in the CFF-CBT group (n = 26). Random intercept mixed-effects regression models demonstrated that families with low coping at baseline demonstrated a significantly worse treatment response as compared to those with higher coping across numerous child and family outcomes, including less improvement in: child symptom severity (CGI) (d = -1.08), child global functioning (CGAS) (d = 1.03), and child social skills (d = 1.05); all ps < 0.05. Families with lower functioning at baseline showed similar robust patterns of worse child and family outcomes versus families with higher functioning (ps < 0.05), including less improvement in: child CGI scores (d = -1.13) and CGAS scores (d = 1.04); child social skills (d = 0.99); and family satisfaction (d = -0.89). Discussion: Baseline family characteristics exerted a robust influence on CFF-CBT treatment effects, with consistently large effect sizes for high versus low functioning families. Families with lower coping and cohesion at baseline showed a poorer response to CFFCBT across a variety of child and family outcomes. These data strongly argue for the need to tailor CFF-CBT to better meet the needs of such families to optimize treatment outcomes. In particular, these families may benefit from an enhanced focus on coping and cohesion - which is currently one component of CFF-CBT - but could be expanded for indicated families to maximize treatment efficacy. This line of research is consistent with the overall NIMH Strategic Plan objective to examine how baseline patient characteristics can inform nullpersonalizednull treatment approaches to enhance treatment outcomes.

Bipolar Disorders, 15 : 150