Disorders - Bipolar Disorders
Garrett, A., Reiss, A., Miklowitz, D., Howe, M., Singh, M., Kelley, R., Taylor, D., George, E., Chang, K.
Background: Subthreshold forms of bipolar disorder (BD), such as BD NOS, cyclothymia, and MDD with family history of BD, affect 3 - 9% of youth (Birmaher et al., 2009 ; Miklowitz et al., 2008). Without intervention, these youth are at high risk for progressing to full BD. We recently demonstrated that a 12-week adaptation of Family Focused Therapy for youth at high risk for BD (FFT-HR) reduced symptoms of depression and mania (Miklowitz et al., 2011). We therefore conducted a randomized trial of FFT-HR in 40 at-risk youth, and conducted fMRI pre- and post-treatment in a subset of patients to study the neural correlates and predictors of clinical response. Because our previous studies found that clinical improvement was associated with decreased amygdalar activation and increased DLPFC activation (Chang et al., 2008; 2009), we hypothesized that improvements in symptom severity would be accompanied by changes in activation of the amygdala and prefrontal cortex. Methods: Subjects: Twelve subjects at risk for BD were scanned (8 male; mean age = 14.1 yrs). Each participant was 9 to 17 years old, had at least one first-degree relative with bipolar I disorder (confirmed by SCID interview), and had either BD-NOS, cyclothymia, or major depressive disorder (by WASH-U-KSADS), and active depressive (CDRS-R>29) or manic (YMRS>11) symptoms in the last 2 weeks. Treatment: 6 subjects received FFT and 6 received TAU (one feedback session and up to 3 crisis sessions). MRI Acquisition: Subjects were scanned on a 3T GE Signa scanner using a custom-built fMRI head coil. Thirty axial slices (4mm thick, .05 mm skip), parallel to the axis of anterior and posterior commisures, covering the entire brain (FOV = 20cm, 64x64 matrix, in-plane spatial resolution = 3.4 mm) were acquired using a spiral pulse sequence with the following parameters: TR = 2000 msec, TE = 30 msec, flip angle = 80 degrees and one interleave. Faces Task: Subjects performed a gender identification task while viewing blocks of fearful, calm, and neutral faces, and scrambled images. There were 4 blocks for each condition. Each block included 8 pictures. Each picture was presented for 3 sec, with no inter-stimulus interval. Data Analysis: Functional data were analyzed using SPM8. FMRI images were reconstructed, spatially realigned to the third image, analyzed and repaired for motion, high-pass filtered, and spatially normalized into standard stereotactic space using the individuals' anatomical scan and an age-appropriate group template (CCHMC) and smoothed with a 7 mm Gaussian filter. Fearful minus scrabmbled faces was the main contrast used. Group analyses used a repeated measures ANOVA in SPM8 to identify clusters of activation that changed significantly from baseline to follow-up. A dual threshold of p=0.01 height and k=40 cluster extent was used. Activation clusters were localized using roimod2 spm toolbox, then superimposed on a single-subject high-resolution T1-weighted image to verify neuroanatomical locations. Mean activation in clusters that fell in apriori hypothesized regions were extracted to SPSS. In SPSS, Spearman's correlations were conducted between activation and CDRS and YMRS scores. Results: CDRS and YMRS scores decreased significantly following treatment (p=0.007), but not differentially by treatment group (p=0.53). For all subjects, whole-brain analysis showed that activation in the right amygdala declined and in the right DLPFC increased significantly from baseline to follow-up. Greater activation in the amygdala at baseline was associated with greater improvement in depression severity following treatment by FFT, but not TAU (p=0.001; Figure 1). For both treatment groups, greater increases in DLPFC from baseline to follow-up was associated with greater improvement in mania severity following treatment (p=0.02). Two of the subjects in the FFT group and four in the TAU groups were taking medications, which had no discernible effect on amygdala or DLPFC activations. Discussion: This is the first study to demonstrate neural predictors of response to famil therapy in youth at high-risk for BD. Decreased amygdala activation following both active and comparator treatments may reflect overall improved regulation of amygdala reactivity to emotion-related stimuli. Greater activation in the amygdala at baseline may predict better response to FFT. Increased DLPFC activation following both treatments may reflect improved executive control over emotional responses. Limitations of this study include the small sample size and medications taken by the subjects. Future studies with larger samples are needed to confirm these findings and explore further neural mechanisms of response to psychotherapy in this population.
Neuropsychopharmacology, 36 : S401
- Year: 2011
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions (any)
, Family therapy
Findling, R. L., Youngstrom, E. A., McNamara, N. K., Stansbrey, R. J., Demeter, C. A., Rowles, B. M., Frazier, T. W., Calabrese, J. R.
Background: Aripiprazole (APZ) is an atypical antipsychotic indicated by the United States Food and Drug Administration for the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy and adjunctive to lithium or valproate in pediatric patients ages 10-17. Owing to the severity and chronicity of pediatric bipolar disorder in children younger than 10 years of age, safe and effective long-term interventions are needed for that patient population. This study tested the long-term efficacy of APZ compared to placebo in children under age 10 suffering from a bipolar disorder. Methods: Medically healthy outpatients, ages 4-9 years, meeting DSM-IV criteria for a bipolar disorder were eligible to receive up to 16 weeks of open-label treatment with APZ (Phase I) (Findling et al., in press). Patients ended participation in Phase I and were randomized into the double-blind phase of the study, Phase II, once they met a priori response criteria (treatment with APZ for a minimum of 6 weeks and 3 of 4 consecutive weeks with: Children's Depression Rating Scale-Revised (CDRS-R)o29; Young Mania Rating Scale (YMRS)o10; and Children's Global Assessment Scale (CGAS)4 50). Phase II, the primary focus of this poster, was a randomized, double-blind clinical trial in which stabilized patients received either ongoing APZ treatment or placebo for up to 72 weeks. Patients either remained on their current APZ dose, or began a double-blind taper during which APZ was discontinued and replaced by placebo. The treatment groups were compared on demographics, psychiatric diagnoses, weeks enrolled in Phase II, symptom ratings at time of randomization, adverse events, weight gain, and changes in safety laboratory values. Treatment efficacy was examined using two separate Kaplan-Meier survival analyses: one used nulldiscontinuation for any reasonnull as the event of interest, and the other used nulldiscontinuation due to the development of a mood episodenull to quantify risk of discontinuation. Cox regression analyses were computed to examine the effects of covariates. For all analyses, significance was set at p<0.05. Results: Thirty patients were randomized to APZ while receiving an average daily dose of 0.23 (0.07) mg/kg/day after a mean of 14.3 (2.8) weeks of open-label treatment with APZ. Also, 30 patients who were being treated with 0.22 (0.07) mg/kg/day of APZ were randomized to placebo after 14.2 (2.4) weeks of open-label treatment. The two groups did not significantly differ in the time until stabilization and randomization in Phase I (p=0.88). The APZ group did not significantly differ from the placebo group in mean weight adjusted total daily dose at randomization (p=0.64). No significant differences were observed between treatment groups at baseline for any demographic, diagnostic, or symptom rating variables (all p values 4 0.05). Six patients randomized to receive APZ and 0 patients randomized to placebo completed the entire 72 weeks of Phase 2. For patients randomized to continued APZ therapy, time to study discontinuation for any reason and as a result of a mood event was longer compared to those randomized to placebo (any reason: p=0.003; mood event: p=0.005).Regardless of randomized assignment, both APZ and placebo showed substantial rates of withdrawal from maintenance treatment over the initial 4 weeks (15/30, 50% for APZ; 27/30, 90% for placebo) suggesting a possible nocebo effect. Children treated with APZ were more likely to report both stomach (n=10 (33%) vs. n=1 (3%)) and musculoskeletal pain (n=8 (27%) vs. 0) than those who received placebo (both p<0.01). There was a significant difference in weight gain from time of randomization between patients who received APZ (mean=2.61 kg, S.D.=3.88 kg) versus those that received placebo (mean=0.42 kg, S.D.= 1.26 kg; p=0.006). There was a significant time-treatment interaction in prolactin levels (F=19.76, df=1, 56, p<0.001). Compared to the randomization time point, prolactin levels decreased at EOS in the APZ group, while prolactin levels at EOS in th placebo group increased. Discussion: Results from this double-blind, placebo-controlled maintenance trial suggest that APZ may be beneficial in the longterm treatment of pediatric patients with a bipolar disorder following stabilization with open-label APZ. Considering the low completion rate, further treatment research is needed in order improve long term outcomes in this population.
Neuropsychopharmacology, 36 : S349-S350
- Year: 2011
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Medication dose reduction/discontinuation
Cohen, D., Bonnot, O., Bodeau, N., Consoli, A., Laurent, C.
Objective: In adults, second-generation antipsychotics (SGAs) have shown a good benefice/risk ration in bipolar disorder (BD) and low frequency of extrapyramidal syndrome (EPS) and a moderate frequency of metabolic adverse effects. Here we aimed to assess this ratio in children and adolescents. Methods: We searched for relevant studies MEDLINE and EMBASE (1996-2010), FDA and EMEA clinical trial registries, reference list of review articles. We found 41 were short-term (3-12 weeks) controlled studies that evaluated SGAs adverse effects in youths, including 12 in youths with BD. Using Bayesian meta-analysis, we analyzed odds ratios (OR) or mean average effects. Results: Numbers of arms (subjects) in the 41 trials were: aripiprazole: 10 (N = 671); olanzapine: 14 (N = 413); quetiapine: 10 (N = 446); risperidone: 25 (N = 1,040); ziprasidone: 4 (N = 228); clozapine: 5 (N = 79); placebo/untreated: 23 (N = 1,138); totaling 93 arms (4,015 patients). Clozapine was only assessed for weight gain and somnolence. Compared to placebo, significant treatment-related increases were observed for: weight gain with olanzapine, clozapine, risperidone, quetiapine, and aripiprazole; glucose levels with risperidone and olanzapine; cholesterol levels with quetiapine and olanzapine; triglyceride levels with olanzapine and quetiapine; hyperprolactinemia with risperidone, olanzapine and ziprasidone; and EPS with ziprasidone, olanzapine, aripiprazole, risperidone. All SGAs increased the risk of somnolence/sedation. Regarding efficacy on BD, aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone were superior to placebo in one or more large placebo controlled trial. Conclusion: In youths treated with SGAs, short-term metabolic effects and EPS are frequent, despite evidence of efficacy in youth BD. SGAs have diverse profiles of secondary effects, which should be considered in making treatment decisions and optimizing benefice/risk ratio.
European Neuropsychopharmacology, 21 : S206
- Year: 2011
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Liu, H. Y., Potter, M. P., Woodworth, K. Y., Yorks, D. M., Petty, C. R., Wozniak, J. R., Faraone, S. V., Biederman, J.
Objective: A growing body of literature has documented pediatric bipolar disorder to be a severely impairing form of psychopathology. However, concerns remain as to the inadequacy of the extant literature on its pharmacotherapy. Furthermore, treatment studies have not been systematically reviewed for treatment effects on core and associated symptoms. Thus, a systematic evaluation and synthesis of the available literature on the efficacy of antimanic pharmacotherapy for pediatric bipolar disorder on symptoms of mania, depression, and attention-deficit/hyperactivity disorder was undertaken. Method: A systematic search was conducted through PubMed from 1989 through 2010 for open-label and randomized controlled trials published in English on the pharmacotherapy of pediatric mania. Results: There have been 46 open-label (n = 29) and randomized (n = 17) clinical trials of antimanic agents in pediatric bipolar disorder encompassing 2,666 subjects that evaluated a range of therapeutic agents, including traditional mood stabilizers, other anticonvulsants, second-generation antipsychotics, and naturopathic compounds. This literature has documented that the available armamentarium has different levels of efficacy in the treatment of pediatric mania. Because all psychotropic classes are associated with important adverse effects, a careful risk-benefit analysis is warranted when initiating pharmacologic treatment with any of these compounds. In the limited data available, the effects of antimanic agents on depression and symptoms of attention-deficit/hyperactivity disorder have been, in general, modest. Few studies have evaluated the effects of antimanic agents in children younger than 10 years. Conclusions: A substantial body of scientific literature has evaluated the safety and efficacy of various medicines and drug classes in the treatment of mania in pediatric bipolar disorder. More work is needed to assess the safety and efficacy of psychotropic drugs in children younger than 10 years, to further evaluate the efficacy of naturopathic compounds, and to further evaluate the effects of antimanic treatments for the management of depression and attention-deficit/hyperactivity disorder. (copyright) 2011 American Academy of Child and Adolescent Psychiatry.
Journal of the American Academy of Child & Adolescent Psychiatry, 50(8) : 749-762.e39
- Year: 2011
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Anticonvulsants/mood stabilisers (excl. lithium), Lithium
Vasudev, A., Macritchie, K., Vasudev, K., Watson, S., Geddes, J., Young, AH.
Background: Oxcarbazepine, a keto derivative of the 'mood stabiliser' carbamazepine, may have efficacy in the treatment of acute episodes of bipolar disorder. Potentially, it may offer pharmacokinetic advantages over carbamazepine.Objectives: To review the efficacy and acceptability of oxcarbazepine compared to placebo and other agents in the treatment of acute bipolar episodes including mania, mixed episodes and depression.Search methods: Electronic databases were searched up to 2 September 2011. Specialist journals and conference proceedings were handsearched. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published and unpublished trials.Selection criteria: Randomised controlled trials (RCTs) which compared oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the acute treatment of bipolar affective disorder were sought. Participants with bipolar disorder of either sex and of all ages were included.Data collection and analysis: Data were extracted from the original reports individually by two review authors. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI).Main results: Seven studies were included in the analysis (368 participants in total). All were on mania, hypomania, mixed episodes or rapid-cycling disorder. Overall, their methodological quality was relatively low.There was no difference in the primary outcome analysis - a fall of 50% or more on the Young Mania Rating Scale (YMRS) - between oxcarbazepine and placebo (N=1, n=110, OR =2.10, 95% CI 0.94 to 4.73) in one study, conducted in children; no studies were available in adult participants.In comparison with other mood stabilisers, there was no difference between oxcarbazepine and valproate as an antimanic agent using the primary outcome (50% or more fall in YMRS, OR=0.44, 95% CI 0.10 to 1.97, 1 study, n=60, P=0.273) or the secondary outcome measure (differences in YMRS between the two groups, SMD=0.18, 95% CI -0.24 to 0.59, 2 studies, n=90, P=0.40). No primary or secondary efficacy outcome measures were found comparing oxcarbazepine with lithium monotherapy.As an adjunctive treatment to lithium, oxcarbazepine reduced depression rating scale scores more than carbamazepine in a group of manic participants on the Montgomery-Åsberg Depression Rating Scale (MADRS) (SMD=- 1.12, 95% CI -1.71 to -0.53, 1 study, n=52, P=0.0002) and on the Hamilton Depression Rating Scale (HDRS) (SMD=- 0.77, 95% CI -1.35 to -0.20, 1 study, n=52, P=0.008).There was a higher incidence of adverse effects, particularly neuropsychiatric, in participants randomised to oxcarbazepine compared to those on placebo (1 study, n=115, 17% to 39% of participants on oxcarbazepine had at least one such event compared to 7% to 10% on placebo).There was no difference in adverse events rates between oxcarbazepine and other mood stabilisers or haloperidol.Authors' conclusions: Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability. Studies predominantly examine the treatment of mania: there are data from subgroup analysis on mixed affective, hypomania and rapid-cycling states.From the few studies included in this review, oxcarbazepine did not differ in efficacy compared to placebo in children and adolescents. It did not differ from other active agents in adults. It may have a poorer tolerability profile compared to placebo. No data were found on outcomes relevant to patients and clinicians, such as length of hospital admission. There is a need for adequately powered randomised controlled trials of good methodological quality to inform us of the therapeutic potential of oxcarbazepine across the spectrum of acute episodes in bipolar disorder.
Cochrane Database of Systematic Reviews, (12) : CD04856
- Year: 2011
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium)
Zuddas, Alessandro, Zanni, Roberta, Usala, Tatiana
In children and adolescents the Second Generation Antipsychotics (SGAs) represent the class of psychotropic drugs whose use has grown more significantly in recent years: they are primarily used for treatment of patients with disruptive behavior disorders, mood disorders and pervasive developmental disorders or mental retardation. In order to compare the efficacy and tolerability of antipsychotics against placebo or each other, a systematic Medline/PubMed search for randomized, double blind studies on SGA in patients younger than 18 years of age at enrolment, was conducted. Papers on schizophrenia, discussed in another article of this specific issue, were excluded by the efficacy analysis. A set of standard efficacy and safety indices, such as treatment effect sizes (ES), the Numbers Needed to Treat (NNT) and Numbers Needed to Harm (NNH), was used to compare medications. 32 studies analyzing efficacy and/or tolerability of SGAs in children and adolescents with bipolar, autistic or disruptive behavior disorders, and Tourette syndrome were identified. SGAs efficacy on mania, extreme mood variability, irritability, aggression and disruptive behavior appears to be greater than for psychotic symptoms in schizophrenia: average NNT was 2 - 5, whereas for schizophrenia it varies between 3 for risperidone and 10 for olanzapine, quetiapine, and aripiprazole. As for schizophrenia, different SGAs show a similar efficacy for specific non-psychotic disorders, but they significantly differ in their safety profile. In randomized studies, adverse effects were usually relatively minor, easily predictable and manageable, whereas long-term open-label studies have indicated that some adverse event, such as the metabolic effects, may be severe and potentially life threatening on the long-term. Taken together, these findings suggest that the choice of a specific treatment should be guided primarily by the safety profile of specific antipsychotics, considering specific risk factors (i.e. obesity and BMI, family history of diabetes or cardiovascular disorder, etc) for the single patient. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)
European Neuropsychopharmacology, 21(8) : 600-620
- Year: 2011
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Sekhar, Susmit, Kalra, Bhupinder, Mendhekar, D. N., Tekur, Uma
This study was carried out to compare the efficacy of intravenous sodium valproate with intramuscular haloperidol in patients with acute mania. A total of 30 patients meeting DSM-IV criteria for acute manic episodes were enrolled. They were randomly assigned to 2 groups of 15 patients each. Both groups were treated twice daily with haloperidol (10 mg, intramuscular) and sodium valproate (500 mg, intravenous). The patients were assessed on days 1, 5, 9, and 13. Improvement in symptoms was assessed by reduction in the Young Mania Rating Scale (YMRS). Outcome criterions for analysis were latency of response and remission; additional drugs were required for sedation. At the end of the 2-week study period, overall response rate in both the groups was similar (P > .1). In comparison to haloperidol group, patients treated with sodium valproate showed faster response, and on day 5, significant reduction in YMRS score was observed in the group treated with sodium valproate (P < .05). Total amount of lorazepam was less in patients treated with sodium valproate. Extrapyramidal symptom episodes were observed in 60% of patients treated with haloperidol. Sodium valproate in the treatment of acute mania is as efficacious as haloperidol but provides a faster response. It is safer compared to haloperidol.
Journal of Clinical Pharmacology, 50(6) : 688-692
- Year: 2010
- 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)
Singh, M. K., Ketter, T. A., Chang, K. D.
The diagnosis of bipolar disorder (BD) in children is increasing, and often requires a comprehensive treatment plan to address a complex array of symptoms and associated morbidities. Pharmacotherapy, in combination with psychotherapeutic interventions, is essential for the treatment and stabilization of disrupted mood. Current evidence collectively demonstrates, by randomized controlled design, that atypical antipsychotics have efficacy for the treatment of acute manic or mixed symptoms in children and adolescents with BD. Additional longitudinal and biological studies are warranted to characterize the effects of atypical antipsychotics on all phases and stages of bipolar illness development in children and adolescents. (copyright) 2010 Adis Data Information BV. All rights reserved.
Drugs, 70(4) : 433-442
- Year: 2010
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Youngstrom, J. K., Freeman, A., Carpenter Song, E., Feeny, N., Youngstrom, E. A.
Objective: This project evaluates changes in mood and behavioral functioning and qualitative interviews following cognitive behavioral treatment (CBT) or treatment as usual (TAU) in a diverse sample of youths with research diagnoses of bipolar disorder. Methods: Investigated effectiveness of manualized CBT for youth ages 7-18 years with bipolar spectrum disorders (bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise specified, and cyclothymia) treated in community mental health. Clients were assessed via the Kiddie Schedule for Affective Disorders and Schizophrenia and randomly assigned to CBT or TAU. Nineteen CBT and 25 TAU cases were evaluated prior to treatment, after treatment, and four months later. Age ranged from 7 to 17 years; participants are 73% African-American, 16% European- American, 7% Latin-American, and 5% Other ethnicities; 52% are male. Mood and behavioral ratings were completed by: parent, youths age 11 or older, and clinician interview. Qualitative semistructured interviews were conducted with a subset of clients and guardians about skills, therapist alliance, and barriers to treatment. Results: CBT and TAU groups improved significantly with large effect size reductions in mood severity by parents and clinicians (ps < 0.05). Outcomes were not significantly different between CBT and TAU as rated by clinicians, parents, or youths, (ps > 0.05). In qualitative interviews, both CBT and TAU groups reported strong clinical relationships, characterized by open and supportive communication. Communication skills and de-escalation techniques were reportedly most useful skills. Conclusion: Similarities across qualitative interviews revealed possible reasons similarities in amount of improvement. The dimensions of treatment considered by clients/guardians to be most helpful - strong clinical relationships and improved communication skills - cross-cut both CBT and TAU approaches.
Bipolar Disorders, 12 : 59
- Year: 2010
- Problem: Bipolar Disorders
- Type: Controlled clinical trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
McCormack, Paul L.
Olanzapine is an atypical antipsychotic that, in addition to its use in adults, is now indicated for the treatment of schizophrenia, and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13-17 years. In a randomized, double-blind, multicentre, 6-week trial in adolescents aged 13-17 years with schizophrenia, the least squares mean reduction from baseline to 6 weeks in the Brief Psychiatric Rating Scale for Children (BPRS-C) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In a randomized, double-blind, multicentre, 3-week trial in adolescents, aged 13-17 years, with manic or mixed episodes associated with bipolar I disorder, the mean reduction from baseline to 3 weeks in the Adolescent Structured Young Mania Rating Scale (YMRS) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In extensions of each of the pivotal placebo-controlled trials in schizophrenia and bipolar mania, open-label treatment with olanzapine for up to 26 weeks produced significant reductions from baseline to endpoint in BPRS-C and YMRS total scores, respectively. Oral olanzapine was generally well tolerated in adolescents with schizophrenia or bipolar mania. Sedation and weight gain were the most common adverse events in placebo-controlled trials. Extrapyramidal symptoms were reported by 10% of olanzapine recipients compared with 6% of placebo recipients. Olanzapine-treated adolescents were likely to experience greater increases in bodyweight, sedation, blood lipids, serum prolactin and liver transaminase levels than olanzapine-treated adults. Therefore, careful consideration of risk-benefit is recommended before using olanzapine in adolescents.
CNS Drugs, 24(5) : 443-452
- Year: 2010
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Pavuluri, M. N., Henry, D. B., Findling, R. L., Parnes, S., Carbray, J. A., Mohammed, T., Janicak, P. G., Sweeney, J. A.
Objective: To determine the relative effects of risperidone and divalproex in pediatric mania. Methods: This is a double-blind, randomized, outpatient clinical trial with 66 children and adolescents (mean age = 10.9 (plus or minus) 3.3 years; age range = 8-18 years) with mania who were randomly assigned to either risperidone (0.5-2 mg/day, n = 33) or divalproex (60-120 (mu)g/mL, n = 33) for a six-week period. Measures included the Young Mania Rating Scale (YMRS) and Child Depression Rating Scale-Revised (CDRS-R). Results: Mixed-effects regression models, with interaction between time and the active drug as predictors, found that the risperidone group had more rapid improvement than the divalproex group (p < 0.05), although final scores did not differ significantly between groups. Mixed models using only those subjects who completed the six-week study found similar results. The response rate on YMRS was 78.1% for risperidone and 45.5% for divalproex (p < 0.01). The remission rate for risperidone was 62.5%, compared with 33.3% for divalproex (p < 0.05). Improvement on the CDRS-R was significantly higher for the risperidone group relative to the divalproex group (p < 0.05). There were no significant differences between groups in safety, but subject retention was significantly higher at study endpoint in the risperidone group (p < 0.01). Dropout rate was 24% in the risperidone group and 48% in the divalproex group, with increased irritability being the most common reason for dropout in the latter. There was no significant weight gain in either group. Conclusion: Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex. Although the results suggest that both drugs are safe, risperidone's lower attrition rate and lower rate of adverse events may suggest better toleration. Clinical trials with larger samples are required to confirm these preliminary findings. (copyright) 2010 John Wiley and Sons A/S.
Bipolar Disorders, 12(6) : 593-605
- Year: 2010
- 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)
Correll, C. U., Sheridan, E. M., DelBello, M. P.
Objective: To compare antipsychotic and mood stabilizer (MS) efficacy and tolerability in youth and adults with bipolar mania. Methods: Medline/PubMed search for studies including: (i) youth (< 18 years) or adults ((greater-than or equal to) 18 years); (ii) bipolar I disorder; (iii) double-blind, randomized, placebo-controlled trial (DB-RPCT); (iv) (less-than or equal to) 12 weeks of treatment; and (v) calculable effect sizes (ES) and/or numbers needed to treat/harm (NNT/NNH) (plus or minus) 95% confidence intervals (CI). Non-overlapping 95% CIs determined significant group differences. Results: We identified nine DB-RPCTs in youth (n = 1,609), 5 evaluating second-generation antipsychotics (SGAs) (n = 1,140) and 4 evaluating MSs (n = 469). We also identified 23 DB-RPCTs in adults (n = 6,501), 14 including SGAs (n = 3,297), 5 using haloperidol as an active comparator (n = 580), and 11 including MSs (n = 2,581). Young Mania Rating Scale scores improved significantly more with SGAs than MSs in youth (ES = 0.65, CI: 0.53-0.78 versus 0.24, CI: 0.06-0.41) and adults (ES = 0.48, CI: 0.41-0.55 versus 0.24, CI: 0.17-0.31). After excluding topiramate studies, SGAs had larger ES than MSs only in youth (ES = 0.65, CI: 0.53-0.78 versus 0.20, CI: 0.02-0.39), but not adults (ES = 0.48, CI: 0.41-0.55 versus 0.46, CI: 0.37-0.55). However, in adults SGAs had significantly larger ES regarding Clinical Global Impressions scores than MSs, even without topiramate (ES = 0.75, CI: 0.68-0.82 versus 0.24, CI: 0.07-0.41). Rates of response, remission, and discontinuation due to any reason compared to placebo were similar between medication and age groups, except for more favorable NNTs for remission with SGAs than MSs in adults after excluding topiramate. SGAs caused more weight gain than MSs in youth (ES = 0.53, CI: 0.41-0.66 versus 0.10, CI: -0.12-0.33), but not in adults (ES = 0.13, CI: 0.05-0.22 versus 0.00, CI: -0.08-0.08). However, results were heterogeneous and not significant in either age group after excluding topiramate. Nevertheless, SGA-related weight gain was significantly greater in youth than adults. In youth, SGA-related somnolence was greater than with MSs (NNH = 4.7, CI: 3.9-6.0 versus 9.5, CI: 6.3-23.5), and more likely than in adults (NNH = 7.1, CI: 6.1-8.8). Conversely, youth experienced less akathisia with SGAs than adults (NNH = 20.4, CI: 14.1-36.5 versus 10.2, CI: 8.1-13.7), likely due to lower doses/slower titration. Conclusions: In treating mania, potentially greater short-term efficacy compared to placebo with SGAs versus MS needs to be balanced against increased adverse events, especially in youth. (copyright) 2010 The Authors. Journal compilation (copyright) 2010 John Wiley & Sons A/S.
Bipolar Disorders, 12(2) : 116-141
- Year: 2010
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Anticonvulsants/mood stabilisers (excl. lithium)