Disorders - Bipolar Disorders
Janicak, P. G., Rado, J. T.
Introduction: Bipolar disorder is characterized by mood instability, which can be challenging to manage. First-line pharmacological approaches usually involve lithium, anticonvulsants and antipsychotics. Over the past fifteen years, several second-generation antipsychotics have demonstrated benefits for various phases of this disorder. Areas covered: This article examines the pharmacodynamics and pharmacokinetics of quetiapine; its evidence base as an acute and maintenance monotherapy or adjunctive therapy for bipolar manic or mixed episodes is also discussed, along with the related issues of its safety and tolerability. Expert opinion: In the context of bipolar disorder, quetiapine is the only agent approved as a monotherapy or adjunct therapy for acute manic/mixed episodes in adults and adolescents; as a monotherapy for acute depressive episodes in adults; and as an adjunctive maintenance therapy for bipolar I and II disorder in adults. In addition to its antipsychotic properties, this broad mood-stabilizing potential may simplify the management of select patients. (copyright) 2012 Informa UK, Ltd.
Expert Opinion on Pharmacotherapy, 13(11) : 1645-1652
- Year: 2012
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Kozicky, J. M., Torres, I. J., Bond, D. J., Lam, R. W., Yatham, L. N.
Although associations between antipsychotic use and neuropsychological impairment in bipolar I disorder have been observed, there is a lack of studies comparing the effects of specific agents used in this population. We compared performance between patients receiving maintenance treatment with mood stabilizer monotherapy (n=15), adjunctive risperidone (n=15) or quetiapine (n=17), and a group of demographically matched healthy controls (n=28) on tests of executive function (working memory, set shifting, and inhibition) and verbal learning. Despite having a similar clinical profile, patients being treated with risperidone showed significantly impaired working memory, set-shifting, and verbal learning (P<0.05) compared with those either on mood stabilizer monotherapy or adjunctive quetiapine. Although randomized controlled trials are required to confirm the cognitive side effects of medications prescribed for maintenance treatment of bipolar I disorder, preliminary results indicate that addition of risperidone to a mood stabilizer has a negative impact on executive function and verbal learning, an effect not shared with quetiapine. (copyright) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
International Clinical Psychopharmacology, 27(2) : 91-99
- Year: 2012
- 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)
Macneil, C. A., Hasty, M., Cotton, S., Berk, M., Hallam, K., Kader, L., McGorry, P., Conus, P.
Aim: There is a scarce literature describing psychological interventions for a young, first-episode cohort who have experienced psychotic mania. This study aimed to assess whether a manualized psychological intervention could be effective in reducing symptomatology and relapse, and improve functional outcome in this population. Methods: The study was an open-label design, drawn from a larger pharmacotherapy trial. All participants in the pharmacotherapy trial were offered a manualized psychological intervention in addition to case management. Inclusion in the psychotherapy group was based on participant's choice, and on completion of four or more of the eight modules offered. All clinical files were audited to ensure accuracy of group allocation. Forty young people aged 15 to 25 years old who had experienced a manic episode with psychotic features were recruited into the study, with 20 people in the combined treatment as usual plus psychotherapy group (P+TAU), and an equal number of matched control participants who received treatment as usual (TAU) within the same service. All participants were prescribed antipsychotic and mood-stabilizing medication. Symptomatic, functional and relapse measures were taken both at baseline and at 18-month follow-up. Results: Manic symptoms improved significantly for both groups, with no differences between groups. Depression scores and overall symptom severity were significantly lower in the P+TAU group. No differences were evident between groups with regard to numbers or type of relapse. The P+TAU group had significantly better social and occupational functioning after 18months. Conclusion: This study suggests that a manualized psychological intervention targeted to a first-episode population can be effective in reducing depression and overall symptom severity, and can improve functional outcome following a first episode of psychotic mania. (copyright) 2012 Wiley Publishing Asia Pty Ltd.
Early Intervention in Psychiatry, 6(4) : 380-388
- Year: 2012
- Problem: Bipolar Disorders
- Type: Controlled clinical trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Other Psychological Interventions
Findling, Robert L., McNamara, Nora K., Stansbrey, Robert J., Wynbrandt, Jaime L., Adegbite, Clara, Rowles, Brieana M., Demeter, Christine A., Frazier, Thomas W., Calabrese, Joseph R.,
Background: This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders. Method: Outpatients aged 4 to 9 years meeting DSM-IV criteria for a bipolar disorder (I, II, not otherwise specified, cyclothymia) were eligible to receive up to 16 weeks of open-label treatment with aripiprazole (phase 1). Patients were randomized into the 72-week double-blind phase of the study once they met a priori response criteria for stabilization (phase 2). During phase 2, patients either remained on their current aripiprazole regimen or began a double-blind taper with aripiprazole discontinued and switched to placebo. The primary outcome measure for phase 2 was time to discontinuation due to a mood event. Result: Patients were recruited between May 2004 and November 2008. Following phase 1, in which 96 patients received aripiprazole, 30 patients (mean age = 7.1 years) were randomly assigned to continue aripiprazole and 30 patients (mean age = 6.7 years) were randomly assigned to placebo. The mean (SD) dose of aripiprazole prior to randomization for these patients was 6.4 (2.1) mg/d. Patients randomly assigned to aripiprazole were enrolled significantly longer until time to study discontinuation due to a mood event (6.14 median weeks, SE ± 11.88 weeks; P = .005) and discontinuation for any reason (including mood events) (4.00 median weeks, SE ± 3.91 weeks; P = .003) than those randomly assigned to placebo (mood event, 2.29 median weeks, SE ± 0.38 weeks; any reason, 2.00 median weeks, SE ± 0.31 weeks). Regardless of random assignment, both the aripiprazole and placebo groups showed substantial rates of withdrawal from maintenance treatment over the initial 4 weeks (15/30 [50%] for aripiprazole; 27/30 [90%] for placebo), suggesting a possible nocebo effect (ie, knowledge of possibly switching from active medication to placebo increasing concern about relapse). The most frequently reported adverse events during double-blind aripiprazole therapy included stomach pain (n = 10, 33%), increased appetite (n = 9, 30%), and headaches (n = 9, 30%). Conclusions: Despite the possibility of a nocebo effect, these results suggest that aripiprazole may be superior to placebo in the long-term treatment of pediatric patients following stabilization with open-label aripiprazole. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)
Journal of Clinical Psychiatry, 73(1) : 57-63
- Year: 2012
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Medication dose reduction/discontinuation
Doey, T.
Background: Aripiprazole is an atypical antipsychotic with unique pharmacological properties, used for a variety of indications, including psychotic and mood disorders in youth. Existing literature was reviewed to summarize experience with this agent in that population. Methods: A review of relevant literature using the key words aripiprazole, children, pediatric, all child, schizophrenia, bipolar disorder, and atypical antipsychotics was conducted. Results: A total of 140 articles and book chapters were identified, of which 7 reported double-blind controlled trials with aripiprazole, 5 were meta-analyses of pooled data, 11 were open label trials, 10 were chart reviews, and 17 were case reports or case series. Limitations: Although every effort was made to locate all available data, some information from posters or researchers was not available. Publication bias tends to report positive outcomes with a treatment, while negative studies are less likely to be reported. Most trials are of short duration. Conclusions: Treatment with aripiprazole is associated with significant reduction of the Positive and Negative Symptom Scale (PANSS) scores in youth with schizophrenia, and reductions in items in the negative symptom scores at higher doses (30 mg/day). Significant reductions in the Young Mania Rating Scale (YMRS) have been demonstrated in youth with bipolar disorder. In mixed populations, reductions in the Clinical Global Impressions Scale (CGI-S) have also been demonstrated when compared with treatment with placebo. Head-to-head comparisons are fewer in number, and overall aripiprazole compares favorably with other atypical antipsychotics (ATAs) in the populations studied. Treatment with aripiprazole is reported to have a lower incidence of weight gain, and less elevation of prolactin. At higher doses, it appears more likely to result in extrapyramidal symptoms (EPS) and tremor. (copyright) 2012 Elsevier B.V. All rights reserved.
Journal of Affective Disorders, 138(SUPPL.) : S15-S21
- Year: 2012
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Geller, Barbara, Luby, Joan L., Joshi, Paramjit, Wagner, Karen Dineen, Emslie, Graham, Walkup, John T., Axelson, David A., Bolhofner, Kristine, Robb, Adelaide, Wolf, Dwight V., Riddle, Mark A., Birmaher, Boris, Nusrat, Nasima, Ryan, Neal D., Vitiello, Benedetto, Tillman, Rebecca, Lavori, Philip
Context: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Objective: To investigate which medication to administer first to antimanic medication - naive subjects. Design, Setting, and Participants: The Treatment of Early Age Mania (TEAM) study recruited 6- to 15- year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patient-choice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments. Interventions: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg). Main Outcome Measures: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement - Mania and the Modified Side Effects Form for Children and Adolescents. Results: There were 279 antimanic medication - naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics: 100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) μg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; Χ²₁=16.9, P<.001) and vs divalproex sodium (68.5% vs 24.0%; Χ²₁=28.3, P<.001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (Χ²₁=6.4, P=.011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F[sub]1,212[/sub]=45.5, P<.001; F[sub]1,212[/sub]=39.1, P<.001; and F[sub]1,213[/sub]=191.4, P<.001, respectively) and vs divalproex sodium (F[sub]1,212[/sub]=34.7, P<.001; F[sub]1,212[/sub]=45.3, P<.001; and F[sub]1,213[/sub]=209.4, P<.001, respectively). The thyrotropin level increased in subjects taking lithium (t₆₂=11.3, P<.001). Conclusions: Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but had potentially serious metabolic effects. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)
Archives of General Psychiatry, 69(5) : 515-528
- Year: 2012
- 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), Lithium
Chiesa, A., Chierzi, F., De Ronchi, D., Serretti, A.
Quetiapine has been proposed for depression in bipolar patients but a quantitative analysis is lacking. In the present paper, we review and meta-analyze available data about the short-term and long-term efficacy and tolerability of quetiapine for the depressive phase of bipolar disorder or bipolar depression. A literature research was carried out using three electronic databases. Studies providing measures of efficacy and tolerability of quetiapine, either as monotherapy or as augmentation, for bipolar depression were considered. Seven short-term studies and four maintenance studies were included. Short-term studies suggested that patients treated with quetiapine monotherapy were significantly more likely than patients treated with placebo and further active comparators to achieve higher response and remission rates as well as more clinical improvements at the endpoint. Such benefits were significant from the first weeks of treatment onward. Maintenance studies suggested that the combination of quetiapine and mood stabilizers was significantly better than placebo plus mood stabilizers for the prevention of both depressive and manic relapses. Quetiapine was generally well tolerated. Furthermore, several clinical variables moderated outcomes under investigation. In conclusion, quetiapine could have some advantages over traditional treatments for the treatment of bipolar depression. (copyright) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
International Clinical Psychopharmacology, 27(2) : 76-90
- Year: 2012
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Biederman, J., Petty, C. R., Woodworth, K. Y., Lomedico, A., O'Connor, K. B., Wozniak, J., Faraone, S. V.
Objective: To examine the informativeness of open-label trials toward predicting results in subsequent randomized, placebo-controlled clinical trials of psychopharmacologic treatments for pediatric bipolar disorder. Data Sources: We searched journal articles through PubMed at the National Library of Medicine using bipolar disorder, mania, pharmacotherapy, treatment and clinical trial as keywords. This search was supplemented with scientific presentations at national and international scientific meetings and submitted manuscripts from our group. Study Selection: Selection criteria included (1) enrollment of children diagnosed with DSM-IV bipolar disorder; (2) prospective assessment of at least 3 weeks; (3) monotherapy of a pharmacologic treatment for bipolar disorder; (4) use of a randomized placebo-controlled design or an open-label design for the same therapeutic compound; and (5) repeated use of the Young Mania Rating Scale (YMRS) as an outcome. Data Extraction: The following information and data were extracted from 14 studies: study design, name of medication, class of medication, dose of medication, sample size, age, sex, trial length, and YMRS mean and standard deviation baseline and follow-up scores. Results: For both study designs, the pooled effect size was statistically significant (open-label studies, z = 8.88, P < .001; randomized placebo-controlled studies, z = 13.75, P < .001), indicating a reduction in the YMRS from baseline to endpoint in both study designs. In a meta-analysis regression, study design was not a significant predictor of mean change in the YMRS. Conclusions: We found similarities in the treatment effects between open-label and randomized placebo-controlled studies in youth with bipolar disorder indicating that open-label studies are useful predictors of the potential safety and efficacy of a given compound in the treatment of pediatric bipolar disorder. (copyright) Copyright 2011 Physicians Postgraduate Press, Inc.
Journal of Clinical Psychiatry, 73(3) : 358-365
- Year: 2012
- 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)
Davari-Ashtiani, R., Parvaresh, N., Akhondzadeh, S.
Objective: Pre-pubertal or early onset bipolar disorder commonly presents as a chronic and continuously cycling disorder with high rates of mixed states. There are no good results for monotherapy in the people suffering from this disorder and a few controlled trials exist for combined therapy in them. Some studies have been conducted about the role of gabapentin in the treatment of bipolar disorder in adults. So this study was designed to investigate the efficacy of combined gabapentin and lithium treatment in youths with bipolar disorder. Methods: In an 8-week, double-blind clinical trial, 31 adolescents with a diagnosis of bipolar disorder were randomized for treatment with lithium plus gabapentin (n = 16) or lithium plus placebo (n = 15). The primary outcome measure was Young mania rating scale score. Anxiety and depression were measured bi weekly with Hamilton rating scale and Beck depression inventory. Weight and side effects also were evaluated. Results: There was no significant difference between the gabapentin and placebo groups in Young mania rating scale scores and the secondary outcome measures at any stage during the 8 week trial (P> 0.05). Conclusion: Our findings do not support the efficacy of gabapentin as combination agent with lithium in the treatment of adolescents with bipolar disorder.
International Clinical Psychopharmacology, 26 : e40
- Year: 2011
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium), Lithium
Janicak, Philip G., Rado, Jeffrey T.
Introduction: Depression, in the context of bipolar disorder, is more prevalent than hypomania or mania and accounts for most of the disability. Furthermore, the treatment of bipolar depression is more complicated than the treatment of unipolar major depression. Finally, the evidence base for pharmacotherapy of bipolar depression is much smaller than for unipolar depression or hypomania/mania.; Areas Covered: The article examines the mechanism of action and pharmacokinetics of quetiapine, its evidence base as a treatment for bipolar depression and related issues of safety and tolerability.; Expert Opinion: In the context of bipolar disorder, quetiapine is the only monotherapy approved for the treatment of hypomania/mania, depression and as an adjunctive maintenance therapy. In addition to its antipsychotic properties, this broad mood stabilizing potential may uniquely benefit and simplify the management of some bipolar patients who can tolerate this agent.; © 2011 Informa UK, Ltd.
Expert Opinion on Pharmacotherapy, 12(10) : 1643-1651
- Year: 2011
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Gentile, S.
The onset of severe, chronic or recurrent psychiatric illnesses, such as schizophrenia-spectrum and bipolar disorders, is a dramatic clinical event often detectable during adolescence and even in childhood. At any age, pharmacotherapy, along with enhancement of social skills and family support, is the mainstay for the management of such disorders. The aim of this review is to critically analyze findings from randomized controlled trials (RCTs) that have investigated the clinical utility of second-generation antipsychotics (SGAs) for the treatment of early-onset schizophrenia and bipolar disorders. Eighteen studies were considered, all of which were unfortunately impaired by methodologic limitations, such as the paucity of long-term data and lack of a three-arm comparison (SGA vs SGA vs placebo).Nevertheless, the results of this review allow us to suggest the effectiveness of three SGAs (aripiprazole, olanzapine, and risperidone) in the short-term treatment of both early-onset schizophrenia and bipolar mania, although such agents show different safety profiles. The use of clozapine should be strictly limited to patients with non-affective, psychotic symptoms who do not respond to any of these three SGAs. In contrast, the use of quetiapine and ziprasidone in young patients with either affective or non-affective psychosis is not yet supported by evidence-based information.Given our findings, further studies are urgently required to identify the best treatment option(s) for pediatric bipolar disorder (especially the depressive phase) and the long-term management of early-onset schizophrenia.
Pediatric Drugs, 13(5) : 291-302
- Year: 2011
- Problem: Bipolar Disorders, Psychosis Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Fraguas, D., Correll, C. U., Merchan-Naranjo, J., Rapado-Castro, M., Parellada, M., Moreno, C., Arango, C.
To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders. Methods: Medline. /PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects. Results: In total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3. weeks and 12. months, with most studies (79.4%) lasting 3. months or less. Nine studies (n = 788) were conducted in patients with schizophrenia, 6 (n = 719) in subjects with bipolar disorder, and 19 (n = 1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8. kg to 16.2. kg in patients treated with olanzapine (n = 353), from 0.9. kg to 9.5. kg in subjects receiving clozapine (n = 97), from 1.9. kg to 7.2. kg in those on risperidone (n = 571), from 2.3. kg to 6.1. kg among patients taking quetiapine (n = 133), and from 0. kg to 4.4. kg in those treated with aripiprazole (n = 451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3. ng/mL to 49.6. ng/mL), followed by olanzapine (-1.5. ng/mL to +. 13.7. ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences. Conclusions: SGAs do not behave as a homogeneous group in children and adolescents with psychotic and mood disorders. Except for clozapine, the heterogeneity within the SGA group is mainly due to differences in the rates and severity of adverse events, especially regarding weight gain as a proxy for the risk of cardiometabolic disturbances. (copyright) 2011.
European Neuropsychopharmacology, 21(8) : 621-645
- Year: 2011
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)