The use of the GBI as predictor of bipolar disorder in a population of adolescent offspring of parents with a bipolar disorder

OBJECTIVE: To assess the usefulness of the General Behavior Inventory (GBI) to predict the development of mood disorders in the offspring of parents with bipolar disorder. METHOD: The GBI and the K-SADS (first measurement) and the SCID (last measurement) were used to assess psychopathology among 129 adolescent and young adult offspring of a bipolar parent with an interval of 5 years. Based on the SCID results at the last measurement, the offspring were assigned to one of four groups: with bipolar mood disorder, with unipolar mood disorders, with non-mood disorders and without disorders and GBI-scores at the first measurement were compared across the four groups. RESULTS: The scores on the Depression scale of the GBI for the offspring who later developed a bipolar or any mood disorder were significantly higher than for the offspring who did not develop a mood disorder across a 5-year interval. For the offspring with a unipolar mood disorder at the first measurement, the scores on the Depression scale were significantly higher for those who switched to bipolar disorder versus those who remained unipolar. CONCLUSIONS: The GBI can be used in a high-risk sample of offspring of parents with bipolar disorder as a self-report measure as an aid to detect those who will develop bipolar disorder across a 5-year interval.     

Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course

Background: EEG sleep measures in child and adolescent subjects with depression have shown considerable variability regarding group differences between depressed and control subjects. This investigation was designed to assess whether some of the observed variability is related to undifferentiated unipolar and bipolar disorders in a sample that was reported previously. Methods: Twenty-eight adolescents who met criteria for unipolar major depression and 35 controls with no lifetime psychiatric disorder participated in a cross-sectional sleep polysomnography study. Approximately 7 years later, follow-up clinical evaluations were conducted in 94% of the original cohort. Clinical course during the interval period was assessed without knowledge of subjects’ initial diagnostic and psychobiological status. Re-analysis of the original sleep data were performed with the added information of longitudinal clinical course. Results: Depressed subjects who had a unipolar course showed reduced REM latency, higher REM density, and more REM sleep (specifically in the early part of the night) compared with depressed adolescents who converted to bipolar disorder and controls who remained free from psychopathology at follow-up. In contrast to the unipolar group, depressed subjects who would later switch to bipolar disorder had demonstrated more stage 1 sleep and diminished stage 4 sleep. Conclusions: These preliminary results indicate that some of the observed variability in EEG sleep measures in adolescent depression appear to be confounded by latent bipolar illness. The findings also suggest that sleep regulatory changes associated with unipolar versus bipolar mood disorders may be different.     

Psychopathology in the adolescent offspring of bipolar parents

BACKGROUND: The aim of this study was to determine the prevalence and 14-months incidence of psychopathology in adolescent offspring of a bipolar parent. METHOD: Parent, teacher and self-report rating scales and Kiddie-SADS were used to assess 132 13-23-year-old offspring of bipolar parents. RESULTS: Compared to the general population, there were few differences between rating scale scores for bipolar offspring and problem scores for normative adolescents. Of the sample 49% had a lifetime psychiatric disorder, most commonly (33%) a mood disorder. LIMITATIONS: There was no suitable control group and there are no comparison data for psychiatric diagnoses (DSM-IV), based on semi-structured interviews in the adolescent age group in the Netherlands. CONCLUSIONS: The overall level of psychopathology of bipolar offspring was not particularly elevated, but when there were more problems, they tended to be mood disorders.     

Use of topiramate, a new anti-epileptic as a mood stabilizer

Rationale: Because some anti-epileptic drugs (AEDs) are effective in bipolar affective disorders, the new AED topiramate (TPM) may be effective in psychiatric illnesses. TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs. Methods: Charts of 58 consecutive patients, 39 outpatients (15 males, 24 females) and 19 inpatients (6 males, 13 females) were reviewed. TPM 25 mg. b.i.d. was added to existing therapy and titrated in 50 mg increments every 3–7 days. Improvement was rated on a Likert global assessment scale of marked, moderate, mild, or no improvement or worse, based on quality of sleep, appetite, mood, and concentration. Results: Of the 58 patients with psychiatric disorders, 44 patients had rapid cycling bipolar disorders characterized by manic, hypomanic, or mixed episodes. Eighteen patients had previously failed to respond to lamotrigine and/or gabapentin in addition to conventional mood stabilizers. Fourteen were Bipolar I, six Bipolar II, and seven mixed, ten patients had cyclothymic disorder, seven had bipolar disorder not otherwise specified. Of the remaining 14 patients, nine had schizoaffective disorder, three patients had dementia and two had psychosis. Mean duration of TPM treatment was 16.0 weeks; mean TPM dosage approximately 200 mg/day. Thirty-six of 58 (62%) patients exhibited marked or moderate improvement, usually within days or weeks. Twenty-three of 44 (52%) patients with bipolar affective disorders showed marked or moderate improvement. Minimal/no improvement was observed in 16; six were rated as worse. Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM (800 mg) and tranylcypromine sulfate (170 mg) combined with alcohol. Other adverse effects were minor and included: paresthesias, somnolence, fatigue, impaired concentration and memory, nausea, and diarrhoea. Limitations: This study was performed in a nonrandom open and retrospective fashion. Therefore, any findings are limited by the design of this study. Conclusion: TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation.     

Pre- and perinatal complications and risk for bipolar disorder: a retrospective study

Background: Many studies have reported that obstetric complications are risk factors for schizophrenia, but few studies have examined whether complications increase risk for bipolar disorder. Methods: Bipolar-disorder probands and their adult siblings were diagnosed using DSM-III-R criteria. Obstetrical data from maternal reports were scored, blind to diagnosis, applying published scales that take into account number and severity of complications. Results: Obstetric complication scores were significantly worse in probands than siblings without mood disorders. Limitations: Probands had relatively severe symptoms; research using more heterogeneous samples is needed. Conclusion: Results suggest obstetric complications are etiologically significant in bipolar disorder.     

Social functioning of bipolar offspring

BACKGROUND: Bipolar patients have impaired social functioning compared to people in the general population. It has been suggested that children of bipolar patients also have impaired social functioning. The objective of this study was to compare social functioning of adolescent and young adult offspring of bipolar parents with social functioning of adolescents and young adults in the general population. METHOD: Subjects were 140 offspring of bipolar parents and 1122 adolescents and 1175 young adults from the general population. Parent, teacher and self-report ratings were used to assess social functioning. RESULTS: Analyses revealed no differences in scores on social functioning for offspring aged 11 to 18 years, and few differences for ages 18 to 26 years compared to same aged individuals from the general population. Offspring with a DSM-IV disorder showed a lower level of social functioning compared to Dutch subjects from the general population in the same age range. LIMITATIONS: The limitations of this study are lack of information on the representativeness of the sample and use of one measure for social functioning. CONCLUSIONS: Bipolar offspring in the adolescent age range have good overall level of social functioning. Social functioning in offspring aged 18 years or older with a bipolar or other mood disorder is impaired.     

Behavioral and gene expression analyses of Wfs1 knockout mice as a possible animal model of mood disorder

Wolfram disease is a rare genetic disorder frequently accompanying depression and psychosis. Non-symptomatic mutation carriers also have higher rates of depression and suicide. Because WfS1, the causative gene of Wolfram disease, is located at 4p16, a linkage locus for bipolar disorder, mutations of WfS1 were suggested to be involved in the pathophysiology of bipolar disorder. In this study, we performed behavioral and gene expression analyses of Wfs1 knockout mice to assess the validity as an animal model of mood disorder. In addition, the distribution of Wfs1 protein was examined in mouse brain. Wfs1 knockout mice did not show abnormalities in circadian rhythm and periodic fluctuation of wheel-running activity. Behavioral analysis showed that Wfs1 knockout mice had retardation in emotionally triggered behavior, decreased social interaction, and altered behavioral despair depending on experimental conditions. Wfs1-like immunoreactivity in mouse brain showed a similar distribution pattern to that in rats, including several nuclei potentially relevant to the symptoms of mood disorders. Gene expression analysis showed down-regulation of Cdc42ep5 and Rnd1, both of which are related to Rho GTPase, which plays a role in dendrite development. These findings may be relevant to the mood disorder observed in patients with Wolfram disease.     

The sleep of remitted bipolar outpatients: a controlled naturalistic study using actigraphy

Background: Several sleep laboratory studies suggest sleep abnormalities in bipolar disorder. However, this is the first study to compare remitted bipolar subjects with controls on actigraphic and subjective sleep parameters in a naturalistic setting over 5 nights. Methods: Nineteen subjects with Bipolar I Disorder and 19 age- and gender-matched healthy controls were included. Objective sleep parameters were estimated using wrist actigraphs. Subject-rated sleep diaries and mood ratings were also completed. Sleep data were averaged for each subject across nights, and raw score standard deviations were calculated as a measure of within-subject variability. Results: Multivariate analyses of variance found significant group differences for both actigraphic (F(4,33)=3.80, P=0.012) and subjective measures (F(4,31)=3.18, P=0.027). Univariate analyses identified reliable differences in sleep onset latency (subjective), sleep duration (subjective), and variability of sleep duration and night wake time (actigraphic). Binary backward stepwise logistic regression demonstrated that a combination of three sleep measures correctly predicted disorder status in 84% of cases. Limitations: Failure to match on sociodemographic and employment status is a limitation that may provide an alternative explanation for some findings. Furthermore, in the bipolar group 18 of 19 subjects were in receipt of psychotropic medication, compared to none of the healthy control group. Also, no information was recorded about family history of mental disorders in the control group. Conclusions: The study suggests that the sleep of remitted bipolar outpatients measured in naturalistic settings is characteristically different from controls: bipolar subjects sleep longer, report longer onset latencies, and display greater variability across nights.     

Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents.

The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family.     

Bipolar mood disorders among Polish psychiatric outpatients treated for major depression

BACKGROUND: Significant proportion of patients treated for depression may have various types of bipolar mood disorders. The aim of the study was to assess the frequency of bipolar disorders among outpatients having at least one major depressive episode, treated by 96 psychiatrists, representing all regions of Poland. METHODS: The study included 880 patients (237 male, 643 female), identified to following diagnostic categories: bipolar I, bipolar II, bipolar spectrum disorder and major depressive disorder. RESULTS: Bipolar mood disorders were found in 61.2% of patients studied, bipolar I more frequent in men and bipolar II in women, and bipolar spectrum in 12% of patients. Patients with age ranges 19-49 and 50-65 years did not differ as to the percentage of diagnostic categories. Patients with bipolar mood disorders compared to major depressive disorder had significantly more frequent family history of bipolar disorder, premorbid hyper- or cyclothymic personality, early onset of depression, symptoms of hypersomnia and hyperphagia, psychotic depression, post-partum depression, and treatment-resistant depression. Bipolar spectrum patients had most clinical features similar to classic types of bipolar disorders. LIMITATIONS: Neither structured interview for family history, nor formal criteria for a number of clinical manifestations were used. The population treated by psychiatrists may not be representative and present a subgroup with more severe mood disorders. CONCLUSIONS: Bipolar mood disorders may be very prevalent among depressive outpatients treated by psychiatrists in Poland, which is confirmed by the results of recent studies. Bipolar patients (including bipolar spectrum) significantly differ from major depressive disorder as to numerous clinical features related mostly to depressive episode.     

Psychotherapy of bipolar disorder: a review

Background: Bipolar disorder is often only partially treated by medication alone, which has led to recent developments in the adjunctive psychological treatment of bipolar disorder. This paper aims to examine the current evidence for effectiveness of psychological interventions for bipolar disorder and to identify issues for future research in this area. Method: A review of outcome studies of psychological interventions reported since 1990, including psychoeducation, cognitive-behavioural, interpersonal and social rhythm and psychoanalytic therapy. Results: The research to date indicates that a range of psychological approaches appear to benefit people with bipolar disorder. The clearest evidence is for individual CBT which impacts on symptoms, social functioning and risk of relapse. Limitations: Many studies lack appropriate control groups and standardised measures of symptoms and diagnosis. Better designed studies would reduce the risk of over-estimates of effect sizes and subsequent failure to replicate. Further developments of psychotherapy need to be based on clear theoretical models of bipolar disorder. Conclusions: Many current studies are uncontrolled and of poor quality leading to a risk of over-estimating effectiveness of some interventions. Suggestions are made for future research including improving quality of studies, basing treatment developments on clear theoretical models and identifying specific treatment components for particular phases of the bipolar illness course.     

Childhood antecedent disorders to bipolar disorder in adults: a controlled study

OBJECTIVE: The aim of the study was to examine antecedent childhood psychiatric disorders in adult patients with bipolar disorder. METHOD: Using structured diagnostic interviews, childhood psychiatric diagnoses of 83 referred patients with diagnosed DSM-IV bipolar disorder were compared to those of 308 adults without mood disorders. RESULTS: Patients with bipolar disorder had significantly higher rates of childhood disruptive behavior disorders (ADHD, oppositional-defiant disorder, and conduct disorder), childhood anxiety disorders (separation anxiety and overanxious disorder), and enuresis, compared to patients without mood disorders. The presence of these childhood disorders was associated with an earlier age of onset of bipolar illness. LIMITATIONS: The retrospective nature of the study may have affected both the rates of disorders recalled, as well as the ages of onset of disorders. Different referral sources for bipolar and comparison participants may have also impacted findings. CONCLUSIONS: Bipolar disorder in adults is frequently preceded by childhood disruptive behavior and anxiety disorders. These childhood disorders may be important markers of risk for adult bipolar disorder.     

Early-onset bipolar disorder: a family treatment perspective

Mood disorder symptoms and their associated functional impairments are hypothesized to come about as the result of the conjoint, interactive influences of genetic, biological, and psychological vulnerabilities, family distress, and life stress at different points of development. We discuss a developmental psychopathology model that delineates pathways to high family conflict and mood exacerbation among early-onset bipolar patients. New data from a treatment development study indicate that adolescent bipolar patients in high expressed emotion families have more symptomatic courses of illness over 2 years than adolescents in low expressed emotion families. Chronic and episodic stressors are also correlated with lack of mood improvement while adolescents are in treatment. Family-focused treatment (FFT) given in conjunction with pharmacotherapy appears to ameliorate the course of bipolar disorder in adults. This treatment has recently been modified to address the developmental presentation of bipolar disorder among adolescents. We present data from an open trial of FFT and pharmacotherapy (N = 20) indicating that bipolar adolescents stabilize in mania, depression, and parent-rated problem behaviors over 2 years. Future research should focus on clarifying the developmental pathways to early-onset bipolar disorder and the role of protective factors and preventative psychosocial interventions in delaying the first onset of the disorder.     

Lifetime psychopathology among the offspring of Bipolar I parents

BACKGROUND:

Recent studies have demonstrated high rates of psychopathology in the offspring of parents with bipolar disorder. The aim of this study was to identify psychiatric diagnoses in a sample of children of bipolar parents.

METHOD:

This case series comprised 35 children and adolescents aged 6 to 17 years, with a mean age of 12.5±2.9 years (20 males and 15 females), who had at least one parent with bipolar disorder type I. The subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime version (K-SADS-PL). Family psychiatric history and demographics were also evaluated.

RESULTS:

Of the offspring studied, 71.4% had a lifetime diagnosis of at least one psychiatric disorder (28.6% with a mood disorder, 40% with a disruptive behavior disorder and 20% with an anxiety disorder). Pure mood disorders (11.4%) occurred less frequently than mood disorders comorbid with attention deficit hyperactivity disorder (17.1%). Psychopathology was commonly reported in second-degree relatives of the offspring of parents with bipolar disorder (71.4%).

CONCLUSIONS:

Our results support previous findings of an increased risk for developing psychopathology, predominantly mood and disruptive disorders, in the offspring of bipolar individuals. Prospective studies with larger samples are needed to confirm and expand these results.     

Neurological soft signs in bipolar I disorder patients

Background: Neurological soft signs (NSS) have been reported to be more prevalent in patients with schizophrenia compared to other psychiatric and non-psychiatric controls. However, this issue in bipolar I disorder seems to be understudied. Aims: The aims of the study were to examine the extent to which NSS are associated with bipolar I disorder cases compared to healthy controls, to assess the possible relationship between NSS and clinical dimensions of the disorder, and to explore the association of sociodemographic characteristics with the occurrence of NSS in cases with this disorder. Methods: Predominantly treatment naïve cases of bipolar I disorder from rural communities were assessed for NSS using the Neurological Evaluation Scale (NES). Results: This study showed that patients with bipolar I disorder performed significantly worse on two NES items from the sensory integration subscale, on one item from motor coordination and on four items from the ‘others’ subscale, the highest difference in performance being in items under the sequencing of complex motor acts subscale. Clinical dimensions and sociodemographic characteristics appeared to have no relationship with NES total score. Conclusions: Bipolar I disorder patients seem to have more neurological dysfunction compared to healthy controls particularly in the area of sequencing of complex motor acts. In addition, the finding suggests that NSS in bipolar I disorder are stable neurological abnormalities established at its onset or may be essential characteristic features of the disorder representing stable disease process that existed long before its onset.     

Anxiety disorders comorbidity in mood disorder subgroups: data from a mood disorders clinic

BACKGROUND: Previous research has identified a high rate of anxiety disorders comorbidity in patients with a primary mood disorder diagnosis. Discrepancies between studies in the comorbidity prevalence of specific anxiety disorders in mood disorders, and of anxiety disorders comorbidity between unipolar depression and bipolar mood disorder are in part due to differences in sampling and diagnostic assessment methodology. METHOD: The authors reviewed the charts of 138 patients who received the SCID-P for DSM-III on enrollment in a Mood Disorders Clinic during the period 1982 through 1988. The comorbidity of specific DSM-III Anxiety Disorders with specific mood disorders was determined and comparatively examined using non-parametric statistics. RESULTS: There was high overall comorbidity of anxiety disorders that did not differ between bipolar and unipolar subjects. There were no differences in the comorbidity of individual anxiety disorder diagnoses in the unipolar vs. bipolar groups. However, in unipolar patients with, compared to those without an additional diagnosis of dysthymia, there was greater overall anxiety disorders comorbidity, with a particularly high prevalence of generalized anxiety disorder. LIMITATION: The subgroup of patients with bipolar I disorder was relatively small (N=8). CONCLUSION: Mood and anxiety disorders comorbidity is complex and presents a continuing challenge for both clinicians and researchers.     

Cyclothymic disorder: a critical review

Cyclothymic disorder is a subtype of bipolar disorder included in the Diagnostic and Statistical Manual of Mental Disorders since 1980, but largely neglected in research. Additionally, it is rarely diagnosed clinically, in spite of evidence that it may be the most prevalent form of bipolar disorder. Neglect has contributed to confusion about the diagnosis and clinical presentation of cyclothymic disorder. Its status as a mood disorder is also ambiguous due to overlap in terminology and symptoms with temperament and personality disorders. Subthreshold bipolar disorder appears more prevalent among young people than previously thought, and follows a range of trajectories from remission to escalation-raising questions about risk factors and traits associated with the varied course. Cyclothymic disorder may be an important diathesis for major mood disorders. Constructs such as cyclothymic disorder link major mood disorder and peri-clinical fluctuations of mood, thus warranting a prominent role in dimensional models of mood and psychopathology. Current evidence indicates that cyclothymic disorder is a prevalent and highly impairing disorder on the bipolar spectrum, with the potential to make unique contributions to our understanding of the risk factors and outcomes associated with bipolar disorder. The inclusion of cyclothymic disorder in future research studies is essential to accurate diagnosis and effective treatment for the full spectrum of bipolar disorder, as well as understanding the developmental trajectory of bipolar spectrum disorders.     

Alcoholism and drug abuse in three groups — bipolar I, unipolars and their acquaintances

Objective: Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. Method: Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls=469; bipolars=277; unipolar depressives=678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. Results: The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. Limitation: As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. Conclusions: (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. Clinical implications: The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.     

Correlates of high expressed emotion attitudes among parents of bipolar adolescents

High expressed emotion (EE) attitudes among parents are associated with an increased likelihood of relapse among bipolar patients, but the origins of these attitudes are unclear. This study examined characteristics of bipolar disorder in adolescents that might be associated with high EE attitudes among parents. We hypothesized that an earlier onset of mood disorder and greater current illness severity would predict higher levels of criticism and emotional overinvolvement among parents. Demographic, diagnostic, and EE data were collected from interviews with parents of 44 bipolar adolescents (mean age 14.5 yrs.). Current illness severity and functioning were not associated with high-EE attitudes. Parents of girls, however, were more likely to be high in criticism than parents of boys. Parents of girls expressed more critical comments when the child had an adolescent compared to a childhood onset of bipolar disorder, whereas the reverse pattern was evident among parents of boys. We encourage prospective investigations of the developmental correlates of parental EE attitudes in larger, more heterogeneous samples of bipolar adolescents and children.     

Olanzapine in the treatment of adolescent acute mania: a report of seven cases.

BACKGROUND: Clozapine may be effective in adults and adolescents with treatment-resistant bipolar disorder. Olanzapine has a receptor affinity profile similar to that of clozapine. METHODS: The responses of seven consecutive adolescents (ages 12-17) with DSM-IV bipolar disorder, manic episode, treated with olanzapine were evaluated. Response to olanzapine was rated as marked, moderate, minimal, none or worse. RESULTS: Five (71%) adolescents showed a marked or moderate response. The mean+/-SD olanzapine dose was 0.146+/-0.086 mg/kg/day (11+/-6 mg/day). CONCLUSION: Olanzapine may have antimanic effects in some adolescents with acute mania. Controlled studies of olanzapine in adolescent bipolar disorder appear to be warranted.