Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine

OBJECTIVE: In a placebo-controlled, double-blind study, the authors investigated the efficacy and safety of olanzapine as monotherapy in relapse prevention in bipolar I disorder. METHOD: Patients achieving symptomatic remission from a manic or mixed episode of bipolar I disorder (Young Mania Rating Scale [YMRS] total score < or =12 and 21-item Hamilton Depression Rating Scale [HAM-D] score or =15, HAM-D score > or =15, or hospitalization). RESULTS: Time to symptomatic relapse into any mood episode was significantly longer among patients receiving olanzapine (a median of 174 days, compared with a median of 22 days in patients receiving placebo). Times to symptomatic relapse into manic, depressive, and mixed episodes were all significantly longer among patients receiving olanzapine than among patients receiving placebo. The relapse rate was significantly lower in the olanzapine group (46.7%) than in the placebo group (80.1%). During olanzapine treatment, the most common emergent event was weight gain; during the open-label phase, patients who received olanzapine gained a mean of 3.1 kg (SD=3.4). In double-blind treatment, placebo patients lost a mean of 2.0 kg (SD=4.4) and patients who continued to take olanzapine gained an additional 1.0 kg (SD=5.2). CONCLUSIONS: Compared to placebo, olanzapine delays relapse into subsequent mood episodes in bipolar I disorder patients who responded to open-label acute treatment with olanzapine for a manic or mixed episode.     

Olanzapine versus placebo in the treatment of adolescents with bipolar mania

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents. METHOD: A 3-week multicenter, parallel, double-blind, randomized placebo-controlled trial was conducted at 24 sites in the United States and two sites in Puerto Rico. The participants were outpatient and inpatient male and female adolescents 13-17 years of age with an acute manic or mixed episode. Subjects received either olanzapine (2.5-20 mg/day [N=107]) or placebo (N=54). The mean change from baseline to endpoint in the Young Mania Rating Scale total score was the primary outcome measure. RESULTS: The mean baseline-to-endpoint change in the Young Mania Rating Scale total score was significantly greater for patients receiving olanzapine relative to patients receiving placebo, and a greater proportion of olanzapine-treated patients met response and remission criteria (44.8% versus 18.5% and 35.2% versus 11.1%, respectively). The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain > or =7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%). The mean baseline-to-endpoint changes in prolactin, fasting glucose, fasting total cholesterol, uric acid, and the hepatic enzymes aspartate transaminase and alanine transaminase were significantly greater in patients treated with olanzapine relative to patients receiving placebo. CONCLUSIONS: Olanzapine was effective in the treatment of bipolar mania in adolescent patients. Patients treated with olanzapine, however, had significantly greater weight gain and increases in the levels of hepatic enzymes, prolactin, fasting glucose, fasting total cholesterol, and uric acid.     

Interpersonal and social rhythm therapy for adolescents with bipolar disorder: treatment development and results from an open trial

Background: In adolescents and adults, bipolar disorder (BD) is associated with significant morbidity, mortality, and impairment in psychosocial and occupational functioning. IPSRT is an empirically supported adjunctive psychotherapy for adults with bipolar disorder, which has been shown to help delay relapse, speed recovery from a bipolar depressive episode, and increase occupational and psychosocial functioning in adults with BD. This study is designed to describe the adolescent‐specific developmental adaptations made to IPSRT (i.e., IPSRT‐A) and to report the results from an open trial of IPSRT‐A with 12 adolescents with a bipolar spectrum disorder. Method: Interpersonal and Social Rhythm Therapy was adapted to be developmentally relevant to adolescents with bipolar disorder. Twelve adolescents (mean age 16.5±1.3 years) diagnosed with a bipolar spectrum disorder participated in 16–18 sessions of adjunctive IPSRT‐A over 20 weeks. Manic, depressive, and general symptoms and global functioning were measured at baseline, monthly during treatment, and at post‐treatment. Adolescent satisfaction with treatment was also measured. Results: Feasibility and acceptability of IPSRT‐A were high; 11/12 participants completed treatment, 97% of sessions were attended, and adolescent‐rated satisfaction scores were high. IPSRT‐A participants experienced significant decreases in manic, depressive, and general psychiatric symptoms over the 20 weeks of treatment. Participants' global functioning increased significantly as well. Effect sizes ranged from medium‐large to large. Conclusions: IPSRT‐A appears to be a promising adjunctive treatment for adolescents with bipolar disorder. A current randomized controlled trial is underway to examine effects of adjunctive IPSRT‐A on psychiatric symptoms and psychosocial functioning. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Health-related quality of life in adolescents with bipolar I disorder

OBJECTIVE: To examine abnormalities in health-related quality of life (HRQOL) and to determine whether pharmacological intervention with divalproex or quetiapine alters HRQOL abnormalities in bipolar adolescents. METHOD: Parents of 23 adolescents diagnosed with a manic or mixed episode associated with bipolar I disorder were asked to rate their child's health using the Child Health Questionnaire-Parental Form 50 (CHQ-PF 50) at baseline, prior to receiving medication and then at 28 days later. RESULTS: Manic adolescents exhibited significantly worse HRQOL than national norms at baseline on all subscales of the CHQ-P50 except for those assessing physical well-being. Twenty eight days later, similar results were obtained for the divalproex group. Significant improvements in HRQOL, particularly on the psychosocial subscales, occurred for both groups. CONCLUSIONS: HRQOL for bipolar youth improves following pharmacological treatments. However, distinct effects of specific treatments may exist, and impairment in several domains persists.     

A Double-Blind,Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

ObjectivesTo compare the efficacy and safety of divalproex extended-release (ER) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study.MethodIn the double-blind study, 150 patients (manic or mixed episode, aged 10-17 years) with baseline Young Mania Rating Scale (YMRS) score of 20 or higher were randomized to once-daily placebo or divalproex ER, which was titrated to clinical response or serum valproate concentration of 80 to 125 μg/mL. Sixty-six patients enrolled in the extension study.ResultsIn the double-blind study, a treatment effect was not observed with divalproex ER based on change in mean YMRS score (divalproex ER ?8.8 [n = 74]; placebo ?7.9 [n = 70]) or secondary measures. Divalproex was similar to placebo based on incidence of adverse events. Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events. Mean ammonia levels increased in the divalproex ER group, but only one patient was symptomatic. In the long-term study, YMRS scores decreased modestly (2.2 points from baseline). The most common adverse events were headache and vomiting.ConclusionsThe results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study.     

Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial

OBJECTIVE: Psychosocial interventions are effective adjuncts to pharmacotherapy in delaying recurrences of bipolar disorder; however, to date their effects on life functioning have been given little attention. In a randomized trial, the authors examined the impact of intensive psychosocial treatment plus pharmacotherapy on the functional outcomes of patients with bipolar disorder over the 9 months following a depressive episode. METHOD: Participants were 152 depressed outpatients with bipolar I or bipolar II disorder in the multisite Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. All patients received pharmacotherapy. Eighty-four patients were randomly assigned to intensive psychosocial intervention (30 sessions over 9 months of interpersonal and social rhythm therapy, cognitive behavior therapy [CBT], or family-focused therapy), and 68 patients were randomly assigned to collaborative care (a 3-session psychoeducational treatment). Independent evaluators rated the four subscales of the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) (relationships, satisfaction with activities, work/role functioning, and recreational activities) through structured interviews given at baseline and every 3 months over a 9-month period. RESULTS: Patients in intensive psychotherapy had better total functioning, relationship functioning, and life satisfaction scores over 9 months than patients in collaborative care, even after pretreatment functioning and concurrent depression scores were covaried. No effects of psychosocial intervention were observed on work/role functioning or recreation scores during this 9-month period. CONCLUSIONS: Intensive psychosocial treatment enhances relationship functioning and life satisfaction among patients with bipolar disorder. Alternate interventions focused on the specific cognitive deficits of individuals with bipolar disorder may be necessary to enhance vocational functioning after a depressive episode.     

Analyses of treatment-emergent mania with olanzapine/fluoxetine combination in the treatment of bipolar depression

BACKGROUND: Treatment-emergent mania is a potential risk when patients with bipolar disorder are treated with antidepressant agents. These subanalyses compare treatment-emergent mania rates in bipolar I depressed patients treated with olanzapine, placebo, or olanzapine/fluoxetine combination. METHOD: In this 8-week, double-blind investigation, patients with bipolar I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression Rating Scale total score > or = 20) were randomly assigned to olanzapine (5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination (6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar Edition (CGI-BP) Severity of Mania scale, and adverse events records. RESULTS: Overall rates of study discontinuation due to mania were low and not significantly different among the therapy groups (p = .358). Incidence of treatment-emergent mania (defined as a YMRS score < 15 at baseline and > or = 15 at any subsequent visit) did not differ significantly among therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination 6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine combination had greater mean decreases in YMRS scores than those receiving placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine combination also had greater mean decreases in CGI-BP scores than those receiving placebo (p = .040 and p = .003, respectively). CONCLUSION: These results suggest that olanzapine/fluoxetine combination does not present a greater risk of treatment-emergent mania compared to olanzapine or placebo over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical nature of bipolar disorder, patients taking olanzapine/fluoxetine combination for bipolar depression should still be monitored for signs or symptoms of emerging mania.     

Asenapine versus olanzapine in acute mania: a double‐blind extension study

Objective: To assess the efficacy and tolerability of asenapine versus olanzapine in the extended treatment of bipolar mania. Methods: Patients with bipolar I disorder experiencing acute manic or mixed episodes who completed either of two 3‐week, double‐blind trials with asenapine 5 or 10 mg twice daily, olanzapine 5 to 20 mg once daily, or placebo were eligible for this 9‐week, double‐blind extension study. Patients receiving active medication in the 3‐week trials continued the same regimen; those who had received placebo were blindly switched to asenapine but were assessed for safety outcomes only. The primary efficacy measure was the change from baseline to day 84 on the Young Mania Rating Scale (YMRS) total score in the per‐protocol population. Results on the primary efficacy outcome were used to determine the noninferiority of asenapine versus olanzapine. Results: A total of 504 patients (placebo/asenapine, n = 94; asenapine, n = 181; olanzapine, n = 229) were enrolled in the extension study. At day 84, the mean (SD) change from baseline in YMRS total score was ?24.4 (8.7) for asenapine and ?23.9 (7.9) for olanzapine. Prespecified statistical analysis for noninferiority indicated no significant difference between asenapine and olanzapine. The overall incidence of treatment‐emergent adverse events was similar across treatment groups (77% placebo/asenapine, 77% asenapine, 78% olanzapine). Clinically significant weight gain occurred in 10%, 19%, and 31% of the placebo/asenapine, asenapine, and olanzapine groups, respectively. Conclusions: Asenapine was efficacious, showed noninferiority to olanzapine, and was well tolerated in the extended treatment of patients experiencing manic symptoms associated with bipolar I disorder.     

Long-term management strategies to achieve optimal function in patients with bipolar disorder

Predictors of poor functional outcome in patients with bipolar disorder include psychiatric and medical comorbidity, interepisode subsyndromal symptoms, psychosis during manic or mixed episode, and low premorbid functioning. Cognitive dysfunction may also contribute to functional impairment. Psychosocial intervention has shown success in improving syndromal outcomes for people with bipolar disorder. Lithium, lamotrigine, olanzapine, and aripiprazole have all shown substantial improvements in relapse rates compared with placebo. Combination therapy with antipsychotics and antidepressants has also been shown to produce improvement in symptoms in people with bipolar disorder. However, limited evidence is available for the effects of these treatments on cognitive outcomes. This review discusses treatment strategies for the long-term management of bipolar disorder and functional outcome measures associated with these treatments.     

The use of atypical antipsychotics in pediatric bipolar disorder

Diagnosis of bipolar disorder in children and adolescents is increasing, and the early-onset form of bipolar disorder usually carries more morbidity than later-onset forms. Patient education and psychotherapeutic and psychosocial interventions should be used in conjunction with carefully planned medication regimens. Recent data support the use of atypical antipsychotics for manic or mixed states in children and adolescents. However, more information is needed about long-term treatment of mania, treatment of bipolar depression, and treatment of comorbid psychiatric conditions.     

Placebo effect in randomized, controlled studies of acute bipolar mania and depression.

Randomized, double-blind, placebo-controlled, parallel group clinical trials have been the standard methodology for establishing the efficacy of new treatments for patients with bipolar disorder in manic, mixed, or depressive episodes. We examine the placebo response rate in acute treatment trials of acute mania (and mixed states) and bipolar depression. Also addressed are potential variables associated with placebo response, strategies to minimize placebo response, the optimum duration of placebo-controlled acute treatment trials, possible alternatives to the use of placebo, and the ramifications of these issues with regard to the design of studies in children, adolescents, and older adults with bipolar disorder.     

Long-term olanzapine therapy in the treatment of bipolar I disorder: an open-label continuation phase study

BACKGROUND: Olanzapine has demonstrated efficacy in the treatment of acute mania in 2 double-blind, placebo-controlled trials. We describe the results of the open-label extension from one of these trials. METHOD: In a 3-week, double-blind study of patients with DSM-IV bipolar I disorder, olanzapine was superior to placebo for the treatment of acute manic symptoms. Of the 139 patients who entered the double-blind phase of the 3-week study, 113 patients continued into the 49-week open-label extension. Efficacy measurements including the Young Mania Rating Scale (YMRS), the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Clinical Global Impressions scale-Bipolar Version, and the Positive and Negative Syndrome Scale and safety measurements including the Simpson-Angus scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale were completed throughout. The analysis considered all treatment results, starting with the first olanzapine dose. Adjunctive lithium and fluoxetine were allowed during the open-label extension. RESULTS: The mean length of olanzapine treatment was 6.6 months, with a mean modal dose of 13.9 mg/day. A significant mean improvement in the YMRS total score, baseline to endpoint (-18.01, p < .001), was observed. During treatment, 88.3% of patients experienced a remission of manic symptoms (YMRS total score < or =12), and only 25.5% subsequently relapsed (YMRS total score > or = 15). Significant improvement in HAM-D-21 scores was observed (p < .001). Forty-one percent of patients were maintained on olanzapine monotherapy. The most common treatment-emergent adverse events reported were somnolence (46.0%), depression (38.9%), and weight gain (36.3%). CONCLUSION: During up to 1 year of olanzapine therapy, either as monotherapy or in combination with lithium and/or fluoxetine, patients with bipolar disorder demonstrated significant improvement in mania and depression symptoms with a favorable safety profile. Further double-blind, controlled studies are needed to confirm these results.     

A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder

Aripiprazole has been approved by regulatory agencies for the treatment of schizophrenia and bipolar I disorder. Although it is a dopamine partial agonist, it also has substantial binding affinity for the serotonin 5HT2A receptor. Several double-blind randomized clinical trials have established the efficacy and tolerability of aripiprazole within the dose range of 10–30 mg/day for schizophrenia, and 15–30 mg/day for manic or mixed states associated with bipolar I disorder. Relatively few comparative trials with other second-generation antipsychotics have been published for schizophrenia, with none available for bipolar disorder. The evidence so far suggests that in terms of efficacy for schizophrenia, aripiprazole is superior to placebo and haloperidol (long term), similar to perphenazine and risperidone, and inferior to olanzapine. Its tolerability profile in patients with schizophrenia appears superior to haloperidol, perphenazine, risperidone, and olanzapine. Efficacy in treating manic or mixed states was established in placebo-controlled trials. Among some patients with bipolar disorder, akathisia and gastrointestinal (GI) complaints can emerge at the start of treatment; however, the GI symptoms were time-limited in many instances. Appropriate dosing may also be important in individualizing therapy to improve tolerability, with lower starting doses becoming more important when adding to, or switching from, another antipsychotic. Aripiprazole appears to have a low propensity for weight gain, a favorable metabolic profile, and no association with hyperprolactinemia.     

Psychosocial predictors of mood symptoms 1 year after acute phase treatment of bipolar I disorder

Objective

The aim of the current study was to evaluate family functioning, social support, and functional impairment as predictors of mood symptoms 1 year after acute phase treatment of bipolar I disorder. This study builds upon the extant literature by evaluating these putative psychosocial risk factors simultaneously to determine whether they account for unique variance in clinical outcomes.

Method

Patients (N = 92) were recruited from hospital settings during an acute mood episode to participate in pharmacologic or combined family and pharmacologic interventions. The Modified Hamilton Rating Scale for Depression, Bech-Rafaelson Mania Scale, Family Assessment Device, Interpersonal Support Evaluation List, and UCLA Social Attainment Survey were administered at acute phase treatment completion and again at 1-year follow-up. Controlling for mood symptom severity at acute phase treatment completion, multiple regression analyses were used to examine longitudinal associations between the psychosocial variables and subsequent depressive and manic symptoms.

Results

None of the aforementioned psychosocial variables predicted manic symptomatology, and social support alone emerged as a unique predictor of depression at the 1-year follow-up. Effects of social support were moderated by recovery status, such that the strength of association between social support and subsequent depression was stronger for those who had not fully recovered during the acute phase of treatment than for those who had.

Conclusions

Low levels of social support at acute phase treatment completion, especially in concert with residual symptomatology, may place individuals with bipolar I disorder at risk for subsequent depressive symptoms. These data suggest that maintenance therapies focused on improving level of social support might be especially important to consider in the management of bipolar depression, and add to a growing literature focused on unique vs shared effects of psychosocial risk factors for poor illness course in bipolar disorder.     

Child behavior checklist profiles in adolescents with bipolar and depressive disorders

ObjectiveWe aimed to evaluate the Child Behavior Checklist (CBCL) profiles in youths with bipolar and depressive disorders.MethodsSeventy-four subjects with a mean age of 14.9 ± 1.6 years (36 boys) with mood disorders and their parents were recruited from September 2011 to June 2013 in the Department of Psychiatry, Asan Medical Center, Seoul, Korea. Diagnosis of mood disorder and comorbid psychiatric disorder was confirmed by child psychiatrists using the Schedule for Affective Disorders and Schizophrenia for School Age Children - Present and Lifetime version (K-SADS-PL). The parents of the subjects completed the Parent General Behavior Inventory-10-item Mania Scale (P-GBI-10M), Parent-version of Mood Disorder Questionnaire (P-MDQ), ADHD rating scale (ARS) and CBCL. The adolescents completed the 76-item Adolescent General Behavior Inventory (A-GBI), Beck Depression Inventory (BDI), and Adolescent-version of Mood Disorder Questionnaire (A-MDQ).ResultsWhen adjusted for gender and the comorbidity with ADHD, the Withdrawn and Anxious/Depressed subscale scores of the CBCL were higher in subjects with bipolar disorder than in those with depressive disorder. Higher scores of A-GBI Depressive subscale, A-MDQ and BDI were shown in subjects with bipolar disorder than in those with depressive disorder. There was no significant difference on CBCL-DP, P-GBI-10M, P-MDQ, A-GBI Hypomanic/Biphasic subscale and ARS between two groups. All eight subscales of the CBCL positively correlated with the P-GBI-10M and P-MDQ scores, and seven of all eight subscales of the CBCL positively correlated with A-GBI Depressive and Hypomanic/Biphasic subscales. The BDI score was positively associated with the Withdrawn, Somatic Complaints, Anxious/Depressed, and Social Problems subscale scores. CBCL-DP score was strongly correlated with manic/hypomanic symptoms measured by P-GBI-10M and P-MDQ (r = 0.771 and 0.826).ConclusionsThis study suggests that the CBCL could be used for measuring mood symptoms and combined psychopathology, especially internalizing symptoms, in youth with mood disorder. However, CBCL-DP had limited ability to differentiate bipolar from depressive disorder, at least in adolescents.     

Neurocognitive dysfunction and psychosocial outcome in patients with bipolar I disorder at 15‐year follow‐up

Burdick KE, Goldberg JF, Harrow M. Neurocognitive dysfunction and psychosocial outcome in patients with bipolar I disorder at 15‐year follow‐up. Objective: Despite increasing interest in cognitive dysfunction in bipolar disorder, little is known about its impact on functional outcome relative to affective symptoms. Method: A total of 33 bipolar I subjects were evaluated at index hospitalization and prospectively followed up 15 years later. Affective symptoms, cognition, global functioning, work, and social adjustment were assessed at follow‐up and analyzed by linear regression. Results: Global functional impairment was significantly associated with poor performance on a cognitive measure of processing speed (WAIS Digit Symbol). Digit symbol performance also was the sole significant predictor of social functioning. Neither symptom severity nor course of illness features significantly contributed to global and social functioning. In contrast, verbal learning deficits, recent depression, and lifetime hospitalizations all were independently associated with work disability. Conclusion: Processing speed is robustly associated with social and global functioning in bipolar disorder. Poor work functioning is significantly related to subsyndromal depression, course of illness, and verbal learning deficits. Cognitive and mood symptoms warrant consideration as independent determinants of functioning in patients with bipolar disorder many years after an index manic episode.     

Comparison of rapid-cycling and non-rapid-cycling bipolar I manic patients during treatment with olanzapine: analysis of pooled data

INTRODUCTION: Rapid-cycling (RC) bipolar disorder patients experience high levels of morbidity, typically respond unsatisfactorily to available treatments, and, so, require additional studies of novel treatments. We report on the first controlled study comparing acute and continuous clinical outcomes in RC and non-RC manic patients treated with olanzapine. METHOD: We analyzed data pooled from 2 placebo-controlled, double-blind, 3- to 4-week trials of olanzapine in mania (N = 254), 1 with an open-label extension up to 1 year (N = 113) and controlled supplementation with lithium or fluoxetine as needed, to compare demographic, clinical, and outcome measures between RC and non-RC subgroups of 254 DSM-IV bipolar I manic subjects. RESULTS: RC (N = 90, 35%) versus non-RC subjects (N = 164, 65%) were younger at intake (p = .02), less often psychotic (p < .0001), and more likely to have familial bipolar disorder (p < .0001), abused substances (p = .01), more previous hospitalizations (p = .004), and many more illness episodes (p < .001). In initial blinded trial outcomes, relative responses (> or = 50% improvement of mania) to olanzapine/placebo were similar in RC and non-RC subjects, though early responses to olanzapine favored RC over non-RC subjects (p = .003), and long-term outcomes favored non-RC subjects (p = .05). Fewer RC subjects achieved strictly defined initial symptomatic remission (p = .014) within a year; RC subjects were more likely to experience recurrences (p = .002), especially of depressive illness (< .001), and had more rehospitalizations (p = .01) and suicide attempts (p = .03). CONCLUSIONS: RC bipolar I patients showed major initial differences and more rapid initial clinical changes, especially toward depression, with less favorable long-term outcomes than non-RC cases during treatment with olanzapine. Inclusion of RC bipolar disorder patients can complicate therapeutic trials, but these patients require further study for differential responsiveness to innovative treatments with methods of assessing clinical response that take their mood instability into account.     

Three-dimensional mapping of hippocampal anatomy in adolescents with bipolar disorder

ObjectiveEarly-onset bipolar disorder is thought to be a particularly severe variant of the illness. Continuity with the adult form of illness remains unresolved, but preliminary evidence suggests similar biological underpinnings. Recently, we observed localized hippocampal decreases in unmedicated adults with bipolar disorder that were not detectable with conventional volumetric measures. Using the same three-dimensional mapping methods, we sought to investigate whether a similar pattern exists in adolescents with bipolar disorder.MethodHigh-resolution brain magnetic resonance images were acquired from 16 adolescents meeting DSM-IV criteria for bipolar disorder (mean age 15.5 ± 3.4 years, 50% female) and 20 demographically matched, typically developing control subjects. Three-dimensional parametric mesh models of the hippocampus were created from manual tracings of the hippocampal formation.ResultsControlling for total brain volume, total hippocampal volume was significantly smaller in adolescent patients with bipolar disorder relative to controls (by 9.2%). Statistical mapping results, confirmed by permutation testing, revealed significant localized deformations in the head and tail of the left hippocampus in adolescents with bipolar disorder, relative to normal controls. In addition, there was a significant positive correlation between hippocampal size and age in patients with bipolar disorder, whereas healthy controls showed an inverse relation.DiscussionLocalized hippocampal deficits in adolescent patients with bipolar disorder suggest a possible neural correlate for memory deficits observed in this illness. Moreover, age-related increases in hippocampal size in patients with bipolar disorder, not observed in healthy controls, may reflect abnormal developmental mechanisms in bipolar disorder. This possibility must be confirmed by longitudinal studies.     

Associations between domains of health-related quality of life and co-occurring emotional and behavioral problems in youth with autism spectrum disorder

BackgroundHealth-related quality of life (HRQoL) can be used as a measure of the impact of a particular disorder on one’s daily functioning. Previous studies have found that comorbid psychiatric disorders in children and adolescents with autism spectrum disorder (ASD) are associated with poorer HRQoL than ASD alone. Less is known about potential associations between specific symptoms of co-occurring psychopathology (i.e., emotional and behavioral problems) and domains of functioning or HRQoL in youth with ASD.MethodParticipants were 470 children with ASD 2–14 years old recruited from one of three sites. Hierarchical multiple regressions were conducted with Pediatric Quality of Life Inventory 4.0 (PedsQL; Varni, Seid, & Kurtin, 2001) HRQoL domains of physical functioning, emotional functioning, school functioning, and social functioning as the dependent variables. Covariates were entered at step 1, followed by the independent variables of interest at step 2: irritability, social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech.ResultsThe study found that increased irritability was associated with poorer emotional and physical functioning and that greater social withdrawal was associated with worse social functioning. Furthermore, findings showed that more hyperactivity/noncompliance was associated with worse school functioning.ConclusionsResults demonstrated that certain emotional and behavioral symptoms are differentially associated with domains of HRQoL. This indicates that emotional and behavioral problems should be considered when measuring HRQoL in children with ASD. It also suggests that treating co-occurring emotional/behavioral problems could improve HRQoL and functioning in certain domains for this population.     

Frequency and effects of psychosocial interventions additional to olanzapine treatment in routine care of schizophrenic patients

Background Guidelines for the treatment of schizophrenia recommend the combination of pharmacologic and psychosocial interventions. There is a lack of data on the utilization and effects of psychosocial interventions additional to neuroleptic treatment in routine care of schizophrenic patients. Method In a drug utilization study 495 psychiatrists documented patient and disease characteristics of 1,711 schizophrenic outpatients treated with olanzapine. Data were recorded at five visits during an observation period of 6 months. Results Psychosocial interventions were reported in 30% of all patients. Compared to patients who were treated with olanzapine alone (nPSI), patients receiving psychosocial interventions (PSI) were more likely to be unmarried and unemployed, and showed significantly higher impairment on relevant psychopathological and psychosocial parameters (e.g. PANSS, GAF, LQLP). After 6 months of treatment with olanzapine patients improved significantly in respect to their schizophrenic symptoms, psychosocial functioning, and quality of life. Patients receiving psychoeducation showed a higher degree of improvement than the other patients. They were more ill at the beginning of the study, but less ill at the end of the study. Patients receiving psychoeducation showed a trend to better medication compliance. Conclusions The data suggest that psychosocial interventions are a frequently used mode of treatment especially for severe cases of schizophrenia Psychoeducation appears to be especially effective for this patient group with a positive impact not only on psychosocial but also on psychopathological criteria of outcome.