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Biomedical subjects

Lori Altshuler

Publications and source records attributed to Lori Altshuler.

At least 19 recordsLinked to original sources

Collaborative care for bipolar disorder: part I. Intervention and implementation in a randomized effectiveness trial.

Outcome for bipolar disorder remains suboptimal despite the availability of efficacious treatments. To improve treatment effectiveness in clinical practice, a Veterans Affairs study team created a care model conceptually similar to the lithium clinics of the 1970s but augmented by principles of more recent collaborative care models for chronic medical illnesses. This intervention consists of improving patients' self-management skills through psychoeducation; supporting providers' decision making through simplified practice guidelines; and enhancing access to care, continuity of care, and information flow through the use of a nurse care coordinator. In this article, which is part I of a two-part report, the authors summarize the conceptual background and development of the intervention, describe the design of a three-year, 11-site randomized effectiveness trial, and report data describing its successful implementation. Trial design emphasized aspects of effectiveness to support generalizability of the findings and eventual dissemination of the intervention. Part II (see companion article, this issue) reports clinical, functional, and overall cost outcomes of the trial.

Adult↗

Collaborative care for bipolar disorder: Part II. Impact on clinical outcome, function, and costs.

OBJECTIVE: The study addressed whether a collaborative model for chronic care, described in part I (this issue), improves outcome for bipolar disorder. METHODS: The intervention was designed to improve outcome by enhancing patient self-management skills with group psychoeducation; providing clinician decision support with simplified practice guidelines; and improving access to care, continuity of care, and information flow via nurse care coordinators. In an effectiveness design veterans with bipolar disorder at 11 Veterans Affairs hospitals were randomly assigned to three years of care in the intervention or continued usual care. Blinded clinical and functional measures were obtained every eight weeks. Intention-to-treat analysis (N=306) with mixed-effects models addressed the hypothesis that improvements would accrue over three years, consistent with social learning theory. RESULTS: The intervention significantly reduced weeks in affective episode, primarily mania. Broad-based improvements were demonstrated in social role function, mental quality of life, and treatment satisfaction. Reductions in mean manic and depressive symptoms were not significant. The intervention was cost-neutral while achieving a net reduction of 6.2 weeks in affective episode. CONCLUSIONS: Collaborative chronic care models can improve some long-term clinical outcomes for bipolar disorder. Functional and quality-of-life benefits also were demonstrated, with most benefits accruing in years 2 and 3.

Adult↗

Mood changes related to antidepressants: a longitudinal study of patients with bipolar disorder in a naturalistic setting.

This prospective, longitudinal study investigated the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. Eighty patients with bipolar disorder self-reported mood and psychiatric medications daily for 3 months using a computerized system (ChronoRecord) and returned 8662 days of data. Of the total group of 80 patients, 47 took antidepressants; 33 did not. Patients taking antidepressants reported depression twice as frequently (29% of days vs. 13.8% of days). In both groups, two-thirds of all mood changes over a 1-, 2- and 3-day period were small, between -5 and 5 on a 100-point scale. No statistically significant difference was found in the frequency of large mood changes (>10 on a 100-point scale) or in switches between depression and mania (0.7% if not taking antidepressants vs. 0.9% if taking), independent of diagnosis of bipolar I or II. Eighty-nine percent of patients taking antidepressants were also taking mood stabilizers. In this naturalistic setting, no significant difference between the rate of switches to mania or rapid cycling was found between those taking and not taking antidepressants, regardless of diagnosis. The primary difference in pattern between the groups was the time spent in depressed or normal mood, with minor daily mood variations.

Adult↗

Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder.

BACKGROUND: Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder. However, few studies have utilized public sector samples, and only one has attempted to separate contributions of each type of comorbidity. METHODS: 328 inpatient veterans with bipolar disorder across 11 sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports. RESULTS: Comorbidity was common (current: 57.3%; lifetime: 78.4%), with multiple current comorbidities in 29.8%. Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient samples (33.8% current, 72.3% lifetime). Selected anxiety comorbidity rates exceeded those in other inpatient samples and appeared more chronic than episodic/recurrent (38.3% current, 43.3% lifetime). 49% of PTSD was due to non-combat stressors. Major correlates of current substance comorbidity alone were younger age, worse marital status, and higher current employability. Correlates of current anxiety comorbidity alone were early age of onset, greater number of prior-year depressive episodes, higher rates of disability pension receipt, and lower self-reported mental and physical function. Combined comorbidity resembled anxiety comorbidity. LIMITATIONS: This is a cross-sectional analysis of acutely hospitalized veterans. CONCLUSIONS: Distinct patterns of substance and anxiety comorbidity are striking, and may be subserved by distinct neurobiologic mechanisms. The prevalence, chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted. Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built "from the patient out."

Adult↗

Medical comorbidity and health-related quality of life in bipolar disorder across the adult age span.

BACKGROUND: Little is known about medical comorbidity or health-related quality of life (HRQOL) in bipolar disorder across the adult age span, especially in public sector patients. METHODS: We obtained cross-sectional demographic, clinical, and functional ratings for 330 veterans hospitalized for bipolar disorder with Mini-Mental State score > or = 27 and without active alcohol/substance intoxication or withdrawal, who had had at least 2 prior psychiatric admissions in the last 5 years. Structured medical record review identified current/lifetime comorbid medical conditions. SF-36 Physical (PCS) and Mental (MCS) Component Scores, measured physical and mental HRQOL. Univariate and multivariate analyses addressed main hypotheses that physical and mental function decrease with age with decrements due to increasing medical comorbidity. RESULTS: PCS decreased (worsened) with age; number of current comorbid medical diagnoses, but not age, explained the decline. Older individuals had higher (better) MCS, even without controlling for medical comorbidity. Multivariate analysis indicated association of MCS with age, current depressed/mixed episode, number of past-year depressive episodes, and current anxiety disorder, but not with medical comorbidity, number of past-year manic episodes, current substance disorder or lifetime comorbidities. LIMITATIONS: This cross-sectional design studied a predominantly male hospitalized sample who qualified for and consented to subsequent randomized treatment. CONCLUSIONS: Medical comorbidity is associated with lower (worse) physical HRQOL, independent of age. Surprisingly, younger rather than older subjects reported lower mental HRQOL. This appears due in part to more complex psychiatric presentations, and several mechanisms are discussed. Both results suggest that age-specific assessment and treatment may enhance HRQOL outcome.

Adult↗

Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women.

The question of whether estrogen replacement therapy (ERT) is beneficial to cognitive functioning in postmenopausal women has become controversial in the past several years. Early studies suggested that ERT improved cognitive functioning and decreased the risk of Alzheimer's disease, but recent studies have failed to find any benefit. However, studies have varied in terms of the age of participants, the estrogen preparation used, whether progesterone is administered concurrently, and the study design. The present study used a randomized, placebo-controlled design and a transdermal estrogen preparation composed of 17-beta estradiol. A neuropsychological battery was administered at baseline and after completion of the 10-week trial, and test scores were grouped into four composite scores using psychometric techniques. Baseline to follow-up change was analyzed using multiple regression techniques. Results indicate that while little overall beneficial effect of estrogen was found, years since menopause was significantly related to change in executive functioning in the estrogen but not the placebo group, such that more recently postmenopausal women demonstrated greater positive change than older women. Body mass index, a gross estimate of circulating estrogen, was significantly positively related to change in attentional and psychomotor processes regardless of treatment group, and to a weaker extent, verbal memory, but only in the estrogen-treated group. These results suggest that reproductive events and levels of endogenous estrogen are related to the clinical response to ERT, but larger studies with longer follow-up periods are needed to determine the strength of these effects.

Administration, Cutaneous↗

Increased amygdala activation during mania: a functional magnetic resonance imaging study.

OBJECTIVE: This study sought to investigate neural activity in the amygdala during episodes of mania. METHOD: Nine manic subjects and nine healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while performing a neuropsychological paradigm known to activate the amygdala. Subjects viewed faces displaying affect (experimental task) and geometric forms (control task) and matched them to one of two simultaneously presented similar images. RESULTS: Manic subjects had significantly increased activation in the left amygdala and reduced bilateral activation in the lateral orbitofrontal cortex relative to the comparison subjects. CONCLUSIONS: Increased activation in the amygdala and decreased activation in the orbitofrontal cortex may represent disruption of a specific neuroanatomic circuit involved in mania. These brain regions may be implicated in disorders involving regulation of affect.

Adult↗

Practical Clues to Early Recognition of Bipolar Disorder: A Primary Care Approach.

Early treatment can favorably impact the course of bipolar disorder, a lifelong illness. Because bipolar disorder can masquerade as various mental and physical illnesses-primarily major depressive disorder-patients with this condition frequently go unrecognized for years. During this recognition lag, such patients may present to their primary care physician on multiple occasions. Accordingly, primary care physicians would benefit from knowing the "clues" to early recognition of the disorder, because early recognition and management can reduce disability, improve social and employment stability, and result in improved functional outcomes. This review describes 3 pathways to the diagnosis of bipolar disorder relevant to the primary care setting: detection of mania or hypomania, differential diagnosis of recurrent depressive episodes, and identification of interepisode disorder and its comorbidities. We summarize these pathways in terms of a practical tool that a primary care physician can use to trigger further evaluation or referral.

Journal Article↗

Management of bipolar disorder during pregnancy and the postpartum period.

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.

Adolescent↗

Birth outcomes after prenatal exposure to antidepressant medication.

OBJECTIVE: The purpose of this study was to examine prospectively the incidence of congenital anomalies and neonatal complications after prenatal exposure to antidepressant medication. STUDY DESIGN: Birth outcomes were obtained from a review of obstetric and neonatal records of 138 women who were treated with selective serotonin reuptake inhibitor antidepressant medications (SSRIs) during pregnancy. RESULTS: The incidence of congenital anomalies in this study was 1.4%, comparable to general population rates. Rates of low birth weight and preterm births were low, occurring in 2.9% and 6.5% of births, respectively. The low birth weight infants had been exposed to relatively high doses of fluoxetine (40-80 mg/d) throughout pregnancy. Average maternal weight gain in pregnancy was comparable across the three major medication categories (fluoxetine, paroxetine, sertraline). CONCLUSION: After prenatal use of selective serotonin reuptake inhibitor antidepressant medications, neonatal complications and congenital anomalies appear to occur within general population rates. However, maternal use of high doses of fluoxetine throughout pregnancy may be associated with a risk for low birth weight.

Abnormalities, Drug-Induced↗

Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up.

OBJECTIVE: While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode. METHOD: Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group"). RESULTS: A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse. CONCLUSIONS: The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.

Acute Disease↗

Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study.

OBJECTIVE: Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex. METHOD: This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest. RESULTS: Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness. CONCLUSIONS: In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.

Acute Disease↗

The Life Functioning Questionnaire (LFQ): a brief, gender-neutral scale assessing functional outcome.

The Life Functioning Questionnaire (LFQ) is a 5-min, 14-item, gender-neutral self-report questionnaire designed to assess role function over the preceding month in four domains: workplace, duties at home, leisure time with family and leisure time with friends. To validate the LFQ for use as an instrument assessing functional outcome in patients with a mood disorder, the LFQ was administered to three different samples of patients (N=87). Fifty-nine concurrently completed the self-report version of the Social Adjustment Scale (SAS-SR) and 32 concurrently had a Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) assessment. The LFQ proved to have high internal consistency reliability, high test-retest reliability, excellent concurrent validity with the SAS-SR, and high validity as a measurement of severity of illness when compared with the CGI-BP. The LFQ provides a reliable, consistent and valid assessment of function at work and home in both male and female patients with a mood disorder.

Activities of Daily Living↗

Correlates of overweight and obesity in 644 patients with bipolar disorder.

OBJECTIVE: Overweight and obesity are common clinical problems encountered in the treatment of bipolar disorder. We therefore assessed the prevalence and clinical correlates of overweight, obesity, and extreme obesity in 644 bipolar patients. METHOD: 644 outpatients with DSM-IV bipolar disorder in the Stanley Foundation Bipolar Treatment Outcomes Network were evaluated with structured diagnostic interviews and clinician- and self-administered questionnaires to determine bipolar disorder diagnoses, demographic and historical illness characteristics, comorbid Axis I diagnoses, medical histories, health habits, and body mass indices (BMMs). RESULTS: Fifty-eight percent of the patients with bipolar disorder were overweight, 21% were obese, and 5% were extremely obese. American patients had significantly higher mean (p < .0001) BMIs and significantly higher rates of obesity (p < .001) and extreme obesity (p < .001) than European patients. Significant associations (p < or = .001) were found between overweight, obesity. and extreme obesity and gender, age, income level, comorbid binge-eating disorder, hypertension, arthritis, diabetes mellitus, exercise habits, and coffee consumption. Current BMI and weight were each correlated with the number of weight gain-associated psychotropics to which patients had been exposed. Multinomial logistic regression (adjusted for site and eating disorder diagnosis and corrected for multiple comparisons) showed that (1) overweight was significantly associated with male gender and hypertension (p < .001), (2) obesity was significantly associated with hypertension (p < .001), and (3) extreme obesity was significantly associated with hypertension and arthritis (p < .001). CONCLUSION: Overweight, obesity, and extreme obesity were common in this group of bipolar patients, although it was unclear that their prevalence rates were truly elevated, because overweight and obesity are increasingly common public health problems among the general population. Correlates of overweight and obesity in bipolar disorder include patient and treatment variables such as gender, geographical location, comorbid binge-eating disorder, age, income level, degree of exposure to weight gain-associated psychotropics, medical disorders associated with obesity, and health habits.

Adult↗