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Objective. To identify space-time clusters of changes in prescribing aripiprazole for bipolar disorder among providers in the VA. Data Sources. VA administrative data from 2002 to 2010 were used to identify prescriptions of aripiprazole for bipolar disorder. Prescriber characteristics were obtained using the Personnel and Accounting Integrated Database. Study Design. We conducted a retrospective space-time cluster analysis using the space-time permutation statistic. Data Extraction Methods. All VA service users with a diagnosis of bipolar disorder were included in the patient population. Individuals with any schizophrenia spectrum diagnoses were excluded. We also identified all clinicians who wrote a prescription for any bipolar disorder medication. Principal Findings. The study population included 32,630 prescribers. Of these, 8,643 wrote qualifying prescriptions. We identified three clusters of aripiprazole prescribing centered in Massachusetts, Ohio, and the Pacific Northwest. Clusters were associated with prescribing by VA-employed (vs. contracted) prescribers. Nurses with prescribing privileges were more likely to make a prescription for aripiprazole in cluster locations compared with psychiatrists. Primary care physicians were less likely. Conclusions. Early prescribing of aripiprazole for bipolar disorder clustered geographically and was associated with prescriber subgroups. These methods support prospective surveillance of practice changes and identification of associated health system characteristics. Key Words. VA, space-time cluster, antipsychotic, diffusion, innovation, Two components of the Institute of Medicine definition of a learning health care system are that best practices are embedded seamlessly in the care process and that new knowledge is [...]

The diagnosis and treatment of bipolar disorder poses challenges to both primary care providers (PCPs), whose patients often present with a variety of physical rather than psychological complaints, and psychiatric [...]

CASE DISCUSSION. Mr R, a 23-year-old man, is brought into the primary care provider's (PCP) office by his mother, who accompanies him into the examining room. Mr R states he [...]

Background: This study examines the effectiveness of long-term outpatient psychodynamic group psychotherapy for individuals with bipolar disorder who may have psychiatric comorbidity. Method: The Integrative Outpatient Model (IOM) includes psychoeducation regarding illness, illness management, and exploration of dynamic and interpersonal issues. Results: At one-year follow up, group members had significantly less depressive symptomatology and were less likely to be in a mood episode, compared to controls. There were no between-group differences in manic symptoms or global assessments of functioning. For group-treated patients, the number of days well per week improved significantly; there were no significant improvements in the control group. Conclusions: This pilot study indicates that psychodynamic group psychotherapy is feasible as a component of treatment for bipolar disorder diagnoses. The results suggest benefits on depressive, but not manic symptoms. The 73% retention rate suggests that further study of this treatment is warranted, especially in the cases of patients for whom pharmacotherapy alone is not sufficient.

A 41-year-old divorced woman with a 17-year history of bipolar I disorder is receiving outpatient treatment consisting of lithium pharmacotherapy and psychotherapy. She is currently living with her sons, ages 7 and 9. Her history is notable for several onsets of mania during or immediately following vacation travel. By the time the patient entered treatment with her current therapist, she was vacation phobic. Yet, as the now-single mother of two active young boys, she also recognized how much she would benefit from a change of scenery and some relief from the constant responsibility for her children and her home. Her brother and sister-in-law had offered to send to her a ticket out to the West Coast for a visit. As much as the idea of a vacation with them appealed to her, it also terrified her. When she mentioned the possibility to her psychiatrist, he agreed that there were some risks involved but that if she planned carefully, she might be able to minimize those risks.

Objective: This study reviewed the evidence from randomized, controlled trials on the efficacy and safety of antidepressants in the short-term treatment of bipolar depression. Method: The authors performed a systematic review and meta-analysis of randomized, controlled trials. They searched the Cochrane Collaboration Depression, Anxiety, and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE, EMBASE, CINAHL, PsycLIT, PSYNDEX, and LILACS. The main outcome measures were the proportion of patients who clinically responded to treatment and the rate of switching to mania. Results: Twelve randomized trials were included, with a total of 1,088 randomly assigned patients. Five trials compared one or more antidepressants with placebo: 75% of these patients were receiving a concurrent mood stabilizer or an atypical antipsychotic. Antidepressants were more effective than placebo. Antidepressants did not induce more switching to mania (the event rate for antidepressants was 3.8% and for placebo, it was 4.7%). Six trials allowed comparison between two antidepressants. The rate of switching for tricyclic antidepressants was 10%, and for all other antidepressants combined, it was 3.2%. Conclusions: Antidepressants are effective in the short-term treatment of bipolar depression. The trial data do not suggest that switching is a common early complication of treatment with antidepressants. It may be prudent to use a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor rather than a tricyclic antidepressant as first-line treatment. Given the limited evidence, there is a compelling need for further studies with longer follow-up periods and careful definition and follow-up of emerging mania and partial remission.

Objective: Bipolar disorder affects 0.5%-1.5% of individuals in the United States. The typical age at onset is late adolescence or early adulthood, placing women at risk for episodes throughout their reproductive years. General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when these guidelines are applied in the treatment of peripartum women. The authors summarize knowledge regarding the management of bipolar disorder during pregnancy and the postpartum period, with a focus on managing mania, hypomania, and the psychotic components of the illness. Method: An expert panel reviewed articles that address the management of bipolar disorder and the consequences of the use of mood stabilizers during pregnancy, and a consensus document was generated. Results: The treatment of bipolar disorder in pregnant women involves significant challenges. Some mood stabilizers, e.g., sodium valproate and carbamazepine, are human teratogens. On the other hand, the teratogenicity associated with lithium may have been overestimated in the past. Conclusions: Since treatment can be managed most effectively if pregnancy is planned, clinicians should discuss the issue of pregnancy and its management with every bipolar disorder patient who has childbearing potential, regardless of future reproductive plans. Additional research should address the risks of disturbed sleep to pregnant and postpartum women with bipolar disorder, as well as structural and behavioral consequences to offspring when mood stabilizers are used during pregnancy. Longitudinal and cohort studies can promote these efforts. Given the rate of bipolar disorder in the general population, research efforts will need to be broad based and include multiple collaborating centers.

Objective: The age at onset of bipolar disorder is associated with clinical features of the illness, including duration, severity, and pattern of comorbidity with other disorders. Age at onset is familial and heritable, and it correlates inversely with the prevalence of bipolar disorder among relatives. Because age at onset may have utility in resolving the complexity and heterogeneity of the disorder, the authors sought to identify chromosomal loci that harbor the genes influencing this trait. Method: A genome scan of 539 genotyped people in 97 families ascertained for the NIMH Bipolar Disorder Genetics Initiative was performed by using multipoint variance-components linkage analysis. Results: The age at onset of mania was significantly heritable in these families. Three chromosomal regions yielded non-significant but suggestive multipoint lod scores greater than 2.5, with the strongest evidence observed at markers D12S1292, GATA31B, and GATA50C, on chromosomes 12p, 14q, and 15q, respectively. Conclusions: Although firm conclusions await an independent replication, these results suggest that three regions of the genome may contain genes influencing the age at onset of mania in bipolar disorder. To the authors' knowledge, these regions have not been implicated previously in risk for the disorder, suggesting that separate sets of genes influence disease susceptibility and the age at which it appears.

Objective: The diagnosis of bipolar disorder in juveniles is controversial. This study was designed to compare proton magnetic resonance spectroscopy ([sup.1]H MRS) in patients with bipolar disorder or intermittent explosive disorder, two groups with symptomatic overlap but categorical distinction. Children with intermittent explosive disorder designate patients whose illness clinically resembles pediatric bipolar disorder but does not satisfy DSM-IV criteria for mania. Based on the authors' previous report of higher levels of [sup.1]H MRS cingulate myo-inositol/ creatine in youngsters with bipolar disorder than in normal comparison subjects, they hypothesized that patients with bipolar disorder would have higher cingulate myo-inositol/creatine-phosphocreatine measurements than patients with intermittent explosive disorder and normal comparison subjects. Method: Myo-inositol levels were measured with a 2x2x2 [cm.sup.3] voxel placed in the anterior cingulate for acquisition of [sup.1]H MRS in 10 patients with bipolar disorder, 10 patients with intermittent explosive disorder, and 13 normal comparison subjects. N-Acetylaspartate, choline moieties, creatine-phosphocreatine, and glutamate-glutamine metabolite levels were also measured. Results: The patients with bipolar disorder showed significantly higher anterior cingulate myo-inositol/creatine-phosphocreatine and myo-inositol (mmol/liter) levels than the patients with intermittent explosive disorder and the normal comparison subjects. No significant differences were found across groups for myo-inositol or other metabolites in the occipital cortex. Conclusions: These data provide evidence that differences in the concentration of myo-inositol (mmol/liter) in the anterior cingulate cortex in [sup.1]H MRS may differentiate these two populations. Follow-up studies involving larger samples may conclusively estimate the biological specificity between pediatric bipolar disorder and other disorders, which overlap clinically.

Objective: The premorbid intellectual, language, and behavioral functioning of patients hospitalized for schizophrenia, schizoaffective disorder, or nonpsychotic bipolar disorder was compared with that of healthy comparison subjects. Method: The Israeli Draft Board Registry, which contains measures of intellectual, language, and behavioral functioning for the unselected population of 16- to 17-year-olds, was merged with the National Psychiatric Hospitalization Case Registry, which contains diagnoses for all patients with psychiatric hospitalizations in Israel. The database was used to identify adolescents with no evidence of illness at their draft board assessment who were later hospitalized for nonpsychotic bipolar disorder (N=68), schizoaffective disorder (N= 31), or schizophrenia (N=536). The premorbid functioning of these subjects was compared to that of nonhospitalized individuals matched for age, gender, and school attended at the time of the draft board assessment. The diagnostic groups of hospitalized subjects were also compared. Results: Relative to the comparison subjects, subjects with schizophrenia showed significant premorbid deficits on all intellectual and behavioral measures and on measures of reading and reading comprehension. Subjects with schizophrenia performed significantly worse on these measures than those with a nonpsychotic bipolar disorder, who did not differ significantly from the comparison subjects on any measure. Subjects with schizoaffective disorder performed significantly worse than the comparison subjects only on the measure of nonverbal abstract reasoning and visual-spatial problem solving and performed significantly worse than subjects with nonpsychotic bipolar disorder on three of the four intellectual measures and on the reading and reading comprehension tests. Conclusions: The results support a nosologic distinction between nonpsychotic bipolar disease and schizophrenia in hospitalized patients.

Objective: Ventriculomegaly has been reported in bipolar disorder, although whether it occurs at illness onset or progresses during the course of the disorder is unknown. In addition, it is unknown whether ventriculomegaly in bipolar disorder reflects acquired volume loss or under-development of periventricular structures. Method: Magnetic resonance imaging was used to measure the volumes of the lateral and third ventricles and periventricular structures (caudate, putamen, thalamus, hippocampus). Patients with DSM-IV bipolar disorder, 18 who were having a first episode and 17 with multiple episodes, were compared with 32 healthy subjects. Results: The lateral ventricles were significantly larger in the patients with multiple-episode bipolar disorder than in the first-episode patients or the healthy subjects, even after periventricular and total cerebral volumes were taken into account. Having larger lateral ventricles was associated with a higher number of prior manic episodes. The multiple-episode patients had a smaller total cerebral volume than the healthy subjects but not the first-episode patients. The putamen was significantly larger in the first-episode patients (and nearly so in the multiple-episode patients) than in the healthy subjects, although there was no difference between patient groups. Conclusions: Lateral ventriculomegaly was greater in bipolar disorder patients who had had repeated manic episodes, but it does not appear to be secondary to small critical periventricular structures. A larger than normal striatum, which has been reported in previous studies, was observed in first-episode patients. These results support the importance of prospectively studying neuroanatomic changes in bipolar disorder.

Vincent van Gogh (1853-1890) had an eccentric personality and unstable moods, suffered from recurrent psychotic episodes during the last 2 years of his extraordinary life, and committed suicide at the age of 37. Despite limited evidence, well over 150 physicians have ventured a perplexing variety of diagnoses of his illness. Henri Gastaut, in a study of the artist's life and medical history published in 1956, identified van Gogh's major illness during the last 2 years of his life as temporal lobe epilepsy precipitated by the use of absinthe in the presence of an early limbic lesion. In essence, Gastaut confirmed the diagnosis originally made by the French physicians who had treated van Gogh. However, van Gogh had earlier suffered two distinct episodes of reactive depression, and there are clearly bipolar aspects to his history. Both episodes of depression were followed by sustained periods of increasingly high energy and enthusiasm, first as an evangelist and then as an artist. The highlights of van Gogh's life and letters are reviewed and discussed in an effort toward better understanding of the complexity of his illness.

This case report is presented to highlight the importance of recognizing the warning signs and understanding the risk factors for clinically significant self-mutilation. By recognizing the warning signs and understanding the risk factors, clinicians will be better equipped to treat patients who have a recurrent history of serious self-mutilation.

Melanie begam demonstrating symptoms of severe bipolar disorder at the age of 14. Melanie's disorder was treated repeatedly in a variety of mental health hospitals, however, never long enough to stabilize the manic depression. Marc Kiefer and David Weisburd both suffered from schizophrenia, a condition which affects 1 in 100 people. Both Marc and David were highly intelligent. Marc died in a Richmond psychiatric hospital of an overdose of psychiatric medication.

Objective: The authors report a large family in which bipolar disorder appears to cosegregate with autosomal-dominant medullary cystic kidney disease. Method: Information regarding diagnostic criteria for bipolar disorder and medullary cystic kidney disease were gathered from family members through formal research interviews, hospital admission records, imaging reports, and laboratory data. Results: Of the seven members with medullary cystic kidney disease, five had bipolar I disorder, one had unipolar depression, and one had a hyperthymic phenotype. Information was not available on two members. Conclusions: The cosegregation in this family suggests a close proximity between genes for the two disorders. The two known loci of medullary cystic kidney disease are in regions of chromosomes 1 and 16 that have been previously linked to bipolar disorder and schizophrenia. This family may be a useful resource for positional cloning of bipolar candidate genes.

Objective: This study characterized cognitive functioning in elderly patients with bipolar disorder. Method: The cognitive functioning of 18 euthymic patients with a history of bipolar disorder I or II, ages 60 years and older, was tested with the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale, and the Executive Interview. Cognitive functioning in these subjects was compared with that of an age- and education-matched group of 45 comparison subjects without mood disorders. Results: Approximately half of the bipolar subjects scored one or more standard deviations below the mean of the comparison subjects on the MMSE (N=8, 44%) and the Mattis Dementia Rating Scale total (N=10, 56%). On the Executive Interview, three subjects (17%) scored between one and two standard deviations below the mean of the comparison subjects. Conclusions: A significant proportion of older bipolar subjects exhibited neuropsychological deficits when they were clinically euthymic.

Objective: This study ascertained family planning decisions by women with bipolar disorder after psychiatric consultation. Method: The authors surveyed 116 women with DSM-IV bipolar disorder after specialized consultation about treatment options and risks regarding pregnancy. Results: Of 70 respondents, 45% had been advised to avoid pregnancy by a health care professional before consultation. After consultation, 63% decided to pursue pregnancy. Conclusions: Women with bipolar disorder often encounter obstacles from health care professionals regarding pregnancy. Individualized comprehensive review of risks and benefits of treatment options during specialized preconception consultation can support thoughtful clinical planning.

A case report is presented that describes the treatment of a woman with bipolar disorder. It portrays problems associated with the management of bipolar disorders and the applications of psychotherapy in the several aspects of treatment. The treatment concerns include the establishment of a therapeutic alliance, assisting patients to overcome denial of illness and encouraging other people to promote mental status information initiatives.