Biomedical subjects

Susan L McElroy

Publications and source records attributed to Susan L McElroy.

At least 19 recordsLinked to original sources

PubMed2003

Maintenance efficacy of divalproex in the prevention of bipolar depression.

Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2 : 1 : 1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divalproex when manic, and among patients with a more severe course of illness.

Adolescent↗

PubMed2003

Advances in the pharmacologic treatment of bipolar depression.

The pharmacologic treatment of bipolar depression has not been well studied in randomized, controlled trials. Thus important clinical questions regarding the efficacy in bipolar depression of mood stabilizers, antidepressants, and new antiepileptic and atypical antipsychotic agents have been relatively unaddressed. Until recently there were few data regarding the degree to which mood stabilizers reduce the risk of switching associated with antidepressant treatment. Likewise, although treatment guidelines have often recommended limiting antidepressant exposure in the maintenance treatment of bipolar depression, the potential risks of depressive relapse after antidepressant discontinuation were largely unknown. We review here data from new randomized, controlled trials published or presented during the past 5 years regarding the efficacy of antidepressants, mood stabilizers, lamotrigine, and olanzapine in the acute and maintenance treatment of bipolar depression. We also review new studies clarifying the protective effect of coadministration of mood stabilizers from antidepressant-associated switching and the risk of depressive relapse when antidepressants are discontinued during maintenance treatment.

Acute Disease↗

PubMed2003

Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders.

Impulsive aggressive behavior is common in psychiatric disorders and accounts for significant morbidity and mortality. However, little systematic treatment data exist from placebo-controlled trials for this symptom domain. This was a multicenter, randomized, double-blind, placebo-controlled study in which outpatients with a score of > or =15 on the Aggression scale of the Overt Aggression Scale-Modified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n=96), intermittent explosive disorder (n=116), or post-traumatic stress disorder (n=34) were randomized to divalproex sodium or placebo for 12 weeks duration. Based on average OAS-M Aggression scores over the last 4 weeks of treatment, a treatment effect was not observed in the intent-to-treat data set (combined across the three psychiatric disorders), but was observed in both intent-to-treat and evaluable data sets for patients with Cluster B personality disorders. In the Cluster B evaluable data set, statistically significant treatment differences favoring divalproex were also observed for component items of the OAS-M Aggression score, including verbal assault and assault against objects, as well as OAS-M Irritability score, and Clinical Global Impression (CGI)-Severity at multiple time points throughout the study. No treatment group difference was noted for overall premature discontinuation rate; however, across psychiatric diagnoses, 21 (17%) patients in the divalproex group prematurely discontinued because of an adverse event, as compared to 4 (3%) patients in the placebo group (p <0.001). While a treatment effect was not observed when all diagnostic groups were combined, in a large subgroup of patients with Cluster B disorders, divalproex was superior to placebo in the treatment of impulsive aggression, irritability, and global severity.

Adult↗

PubMed2003

Pharmacologic treatment of binge eating disorder.

OBJECTIVE: To review the findings from pharmacologic trials of binge eating disorder (BED) and to provide guidelines for pharmacologic treatment. METHODS: The literature was searched for studies of pharmacologic treatment of BED and related conditions, such as nonpurging bulimia nervosa. RESULTS: Placebo-controlled studies of desipramine, fluvoxamine, fluoxetine, sertraline, citalopram, dexfenfluramine, sibutramine, and topiramate have demonstrated the efficacy of these agents in the treatment of BED. An open trial of venlafaxine has offered preliminary evidence for the efficacy of this medication. Guidelines for pharmacologic management of BED are provided. CONCLUSIONS: The literature offers support for the use of agents from three categories of medication (antidepressants, appetite suppressants, and anticonvulsants) in the treatment of BED.

Anticonvulsants↗

PubMed2003

Redefining mood stabilization.

This review considers the definition of the term 'mood-stabilizer' in the context of new pharmacological agents for the treatment of bipolar disorder. Three definitions of a mood-stabilizer are described and the available data from randomized, double-blind, controlled trials for putative mood-stabilizers studied in the treatment of different aspects of bipolar disorder (mania, mixed states, depression, maintenance) are reviewed. No available agent meets the criteria for a comprehensive mood-stabilizer, although lithium comes the closest.

Affect↗

PubMed2003

Olanzapine versus placebo in acute mania: treatment responses in subgroups.

Two double-blind, placebo-controlled trials of olanzapine in acute mania showed significant overall antimanic efficacy, based on reductions in mania ratings. Their subject-level data were pooled to increase statistical power to test for differences in treatment responses among 10 subgroup pairs of interest using generalized estimating equations methods. Similar drug/placebo superiority and responsiveness to olanzapine was found in men versus women, psychotic versus nonpsychotic subjects, and those presenting in mania versus mixed states, and responses were independent of onset age, current age, or prior illness based on episodes, hospitalizations, recent rapid cycling, lifetime substance use, or previous antipsychotic treatment. Olanzapine and placebo responses paralleled closely (r(s) = 0.73). Patients were relatively more responsive to olanzapine who were younger at illness onset, lacked prior substance abuse, and had not previously received antipsychotic treatment (efficacy ratios 1.5-1.7, all P < 0.01). These well-powered comparisons of subgroups of interest indicate broad efficacy of olanzapine in the treatment of acute mania.

Acute Disease↗

PubMed2003

Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial.

OBJECTIVE: Binge eating disorder is associated with obesity. Topiramate is an antiepileptic agent associated with weight loss. The objective of this study was to evaluate topiramate in the treatment of binge eating disorder associated with obesity. METHOD: For this 14-week, double-blind, flexible-dose (25-600 mg/day) topiramate trial, 61 outpatients (53 women, eight men) with binge eating disorder who were obese (body mass index >/=30 kg/m(2)) were randomly assigned to receive topiramate (N=30) or placebo (N=31). The primary efficacy measure was binge frequency. The primary analysis of efficacy was a repeated-measures random regression with treatment-by-time as the effect measure. RESULTS: Compared with placebo, topiramate was associated with a significantly greater rate of reduction in binge frequency, binge day frequency, body mass index, weight, and scores on the Clinical Global Impression severity scale and the Yale-Brown Obsessive Compulsive Scale (modified for binge eating). Topiramate was also associated with significantly greater reductions in binge frequency (topiramate: 94%, placebo: 46%) and binge day frequency (topiramate: 93%, placebo: 46%) and with a significantly higher level of response than placebo. The mean weight loss for topiramate-treated subjects who completed the study was 5.9 kg. Median topiramate dose was 212 mg/day (range=50-600). Nine patients (three receiving placebo, six given topiramate) discontinued because of adverse events. The most common reasons for discontinuing topiramate were headache (N=3) and paresthesias (N=2). CONCLUSIONS: Topiramate was efficacious and relatively well tolerated in the short-term treatment of binge eating disorder associated with obesity.

Ambulatory Care↗

PubMed2003

Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder.

OBJECTIVE: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. METHOD: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. RESULTS: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. CONCLUSIONS: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study.

Adolescent↗

PubMed2003

Aripiprazole: a partial dopamine D2 receptor agonist antipsychotic.

This paper reviews the clinical pharmacology, efficacy and safety of the novel antipsychotic drug aripiprazole. All published citations regarding aripiprazole were reviewed using a Medline((R)) search (completed for citations through mid-year, 2002). In addition, abstracts from recent scientific meetings presenting data not yet published (nor peer-reviewed) were reviewed. Aripiprazole has a unique mechanism of action as a dopamine D2 partial agonist, serotonin 5-HT(1A) partial agonist and serotonin 5-HT(2A) antagonist. Like other new antipsychotics, aripiprazole has the profile of an atypical agent, with efficacy in the treatment of positive and negative symptoms of psychosis as well as mood symptoms, a low rate of neurological side effects and no significant adverse effect on serum prolactin concentrations. In addition, aripiprazole was not associated with significant weight gain or QTc prolongation in both acute and long-term treatment trials.

Animals↗

PubMed2003

Screening for bipolar disorder in the community.

BACKGROUND: Our goal was to estimate the rate of positive screens for bipolar I and bipolar II disorders in the general population of the United States. METHOD: The Mood Disorder Questionnaire (MDQ), a validated screening instrument for bipolar I and II disorders, was sent to a sample of 127,800 people selected to represent the U.S. adult population by demographic variables. 85,358 subjects (66.8% response rate) that were 18 years of age or above returned the survey and had usable data. Of the nonrespondents, 3404 subjects matched demographically to the 2000 U.S. Census data completed a telephone interview to estimate nonresponse bias. RESULTS: The overall positive screen rate for bipolar I and II disorders, weighted to match the 2000 U.S. Census demographics, was 3.4%. When adjusted for the nonresponse bias, the rate rose to 3.7%. Only 19.8% of the individuals with positive screens for bipolar I or II disorders reported that they had previously received a diagnosis of bipolar disorder from a physician, whereas 31.2% reported receiving a diagnosis of unipolar depression. An additional 49.0% reported receiving no diagnosis of either bipolar disorder or unipolar depression. Positive screens were more frequent in young adults and low income households. The rates of migraine, allergies, asthma, and alcohol and drug abuse were substantially higher among those with positive screens. CONCLUSION: The positive MDQ screen rate of 3.7% suggests that nearly 4% of American adults may suffer from bipolar I and II disorders. Young adults and individuals with lower income are at greater risk for this largely underdiagnosed disorder.

Adolescent↗

PubMed2003

Impact of bipolar disorder on a U.S. community sample.

BACKGROUND: Bipolar disorder is a chronic psychiatric illness characterized by depression and at least 1 manic or hypomanic episode during the lifetime of the illness. Bipolar symptoms have been associated with significant functional impairment. We conducted a study to determine the psychosocial impact of bipolar disorder in a U.S. community sample. METHOD: 3059 subjects were selected from a large epidemiologic study of bipolar prevalence that used the Mood Disorder Questionnaire (MDQ) to screen for bipolar I and II disorder. Subjects were surveyed from April 24, 2001, to August 6, 2001, using the Sheehan Disability Scale and the Social Adjustment Scale-Self Report. Comorbid disease data were also collected. RESULTS: Of the 3059 subjects surveyed, 2450 (80%) returned completed surveys: 1167 (48%) subjects screened positive for bipolar disorder based on MDQ scores; 1283 (52%) screened negative. MDQ-positive subjects reported significantly (p <.0001) more difficulties with work-related performance, social/leisure activities, and social/family interactions compared with MDQ-negative subjects. Younger subjects, aged 18 to 34 years, reported significantly (p =.003) more symptom days than did older MDQ-positive subjects. MDQ-positive women reported more disruption in social and family life, while MDQ-positive men reported being jailed, arrested, and convicted for crimes. Anxiety (30% vs. 6%), panic attacks (18% vs. 4%), migraine (24% vs. 11%), asthma (17% vs. 10%), and allergies (42% vs. 29%) were significantly (p <.05) more common in MDQ-positive versus MDQ-negative subjects. CONCLUSION: Bipolar disorder, as identified in a community sample using the Mood Disorder Questionnaire, was significantly associated with negative impact on the performance of work-related, leisure, and interpersonal activities.

Adolescent↗

PubMed2003

Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network.

BACKGROUND: Clinical factors related to suicide and suicide attempts have been studied much more extensively in unipolar depression compared with bipolar disorder. We investigated demographic and course-of-illness variables to better understand the incidence and potential clinical correlates of serious suicide attempts in 648 outpatients with bipolar disorder. METHOD: Patients with bipolar I or II disorder (DSM-IV criteria) diagnosed with structured interviews were evaluated using self-rated and clinician-rated questionnaires to assess incidence and correlates of serious suicide attempts prior to study entry. Clinician prospective ratings of illness severity were compared for patients with and without a history of suicide attempt. RESULTS: The 34% of patients with a history of suicide attempts, compared with those without such a history, had a greater positive family history of drug abuse and suicide (or attempts); a greater personal history of early traumatic stressors and more stressors both at illness onset and for the most recent episode; more hospitalizations for depression; a course of increasing severity of mania; more Axis I, II, and III comorbidities; and more time ill on prospective follow-up. In a hierarchical logistic regression, a history of sexual abuse, lack of confidant prior to illness onset, more prior hospitalizations for depression, suicidal thoughts when depressed, and cluster B personality disorder remained significantly associated with a serious suicide attempt. CONCLUSION: Our retrospective findings, supplemented by prospective follow-up, indicate that a history of suicide attempts is associated with a more difficult course of bipolar disorder and the occurrence of more psychosocial stressors at many different time domains. Greater attention to recognizing those at highest risk for suicide attempts and therapeutic efforts aimed at some of the correlates identified here could have an impact on bipolar illness-related morbidity and mortality.

Adolescent↗

PubMed2003

Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH life chart method.

BACKGROUND: A number of recent longitudinal outcome studies have found substantial long-term morbidity in patients with bipolar disorder. The detailed course and pattern of illness emerging despite comprehensive treatment with mood stabilizers and adjunctive agents have previously not been well delineated. METHOD: 258 consecutive outpatients admitted from 1996 to 1999 to the Stanley Foundation Bipolar Network who had a full year of prospective daily clinician ratings on the National Institute of Mental Health-Life Chart Method were included in the analysis. Patients were diagnosed by the Structured Clinical Interview for DSM-IV, with the majority (76%) having bipolar I disorder. They completed a questionnaire on demographics and prior illness course, and variables associated with outcome were examined in a hierarchical multinomial logistic regression analysis. Patients were treated naturalistically with a mean of 4.1 psychotropic medications during the year. RESULTS: Despite comprehensive pharmacologic treatment, mean time depressed (33.2% of the year) was 3-fold higher than time manic (10.8%); 62.8% of patients had 4 or more mood episodes per year. Two thirds of the patients were substantially impacted by their illness; 26.4% were ill for more than three fourths of the year, and 40.7% were intermittently ill with major affective episodes. After logistic regression analysis, those who were ill most of the year, compared with the largely well group, had a significantly greater family history of substance abuse, 10 or more depressive episodes, and limited occupational functioning prior to Network entry. CONCLUSION: A majority of outpatients with bipolar illness, even with intense monitoring and treatment in specialty clinics, have a considerable degree of residual illness-related morbidity, including a 3-fold greater amount of time spent depressed versus time spent manic. A personal or family history of substance abuse, 10 or more prior depressions, and limited occupational functioning predicted the poorest outcomes. Additional interventions, particularly those targeted at treating depressive phases of bipolar illness, are greatly needed.

Adult↗

PubMed2003

Citalopram in the treatment of binge-eating disorder: a placebo-controlled trial.

BACKGROUND: Binge-eating disorder is a newly recognized eating disorder characterized by recurrent episodes of binge eating without compensatory weight loss behaviors. It commonly co-occurs with depressive disorders and obesity. Citalopram is a highly selective serotonin reuptake inhibitor antidepressant. The purpose of this study was to assess the efficacy and safety of citalopram in the treatment of binge-eating disorder. METHOD: Thirty-eight outpatients with a DSM-IV diagnosis of binge-eating disorder were enrolled in the study between August 2000 and July 2001 and were randomly assigned to receive either citalopram (N = 19) or placebo (N = 19) in a 6-week, double-blind, flexible-dose (20-60 mg/day) study. The primary measure of efficacy was frequency of binge-eating episodes. Secondary measures included frequency of binge days, body mass index (BMI), weight, Clinical Global Impressions-Severity of Illness scale scores, Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) scores, Hamilton Rating Scale for Depression (HAM-D) scores, and response categories. The outcome measures were analyzed using 2 random regression methods, with a time trend analysis (primary analysis) and an endpoint analysis. In addition, response categories were analyzed using an exact trend test. RESULTS: Compared with placebo-treated subjects, subjects receiving citalopram (mean dose of 57.9 mg/day) had a significantly greater rate of reduction in frequency of binge eating (p =.003), frequency of binge days (p <.001), BMI (p <.001), weight (p <.001), severity of illness (p =.028), and YBOCS-BE score (p =.007) and a marginally significant rate of reduction in HAM-D score (p =.053). Differences between groups in response categories were marginally significant (p =.068 for intent-to-treat analysis). CONCLUSION: In a 6-week, placebo-controlled, flexible-dose trial, citalopram was efficacious in reducing binge-eating frequency, weight, and severity of illness and was generally well tolerated in subjects with binge-eating disorder.

Adolescent↗

PubMed2003

New approaches in managing bipolar depression.

Historically, the pharmacologic treatment of bipolar depression has not been well studied. New data are beginning to emerge regarding the efficacy of new medications and the use of combinations of mood stabilizers and antidepressants in acute and long-term treatment of bipolar depression. We reviewed data from recent randomized, controlled trials of mood stabilizers and antidepressants in the treatment of bipolar depression and naturalistic studies examining the risk of switching and depressive relapse with ongoing antidepressant treatment.

Anticonvulsants↗

PubMed2002

High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure.

BACKGROUND: We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and thyroid failure in outpatients with bipolar disorder compared with two control groups. METHODS: The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226), a population control group (n = 252), and psychiatric inpatients of any diagnosis (n = 3190) were measured. Thyroid failure was defined as a raised thyroid stimulating hormone level, previously diagnosed hypothyroidism, or both. Subjects were compared with attention to age, gender, and exposure to lithium. RESULTS: The TPO-Abs were more prevalent in bipolar patients (28%) than population and psychiatric controls (3-18%). The presence of TPO-Abs in bipolar patients was associated with thyroid failure, but not with age, gender, mood state, rapid cycling, or lithium exposure. Thyroid failure was present in 17% of bipolar patients and more prevalent in women. It was associated with lithium exposure, especially in the presence of TPO-Abs, but not with current rapid cycling, although an association may have been masked by thyroid hormone replacement. CONCLUSIONS: Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment. These variables appear to be independent risk factors for the development of hypothyroidism, especially in women with bipolar disorder.

Adult↗

PubMed2002

Early physical and sexual abuse associated with an adverse course of bipolar illness.

BACKGROUND: There is growing awareness of the association between physical and sexual abuse and subsequent development of psychopathology, but little is known, however, about their relationship to the longitudinal course of bipolar disorder. METHODS: We evaluated 631 outpatients with bipolar I or II disorder for general demographics, a history of physical or sexual abuse as a child or adolescent, course of illness variables, and prior suicide attempts, as well as SCID-derived Axis I and patient endorsed Axis II comorbidity. RESULTS: Those who endorsed a history of child or adolescent physical or sexual abuse, compared with those who did not, had a history of an earlier onset of bipolar illness, an increased number of Axis I, II, and III comorbid disorders, including drug and alcohol abuse, faster cycling frequencies, a higher rate of suicide attempts, and more psychosocial stressors occurring before the first and most recent affective episode. The retrospectively reported associations of early abuse with a more severe course of illness were validated prospectively. CONCLUSIONS: Greater appreciation of the association of early traumatic experiences and an adverse course of bipolar illness should lead to preventive and early intervention approaches that may lessen the associated risk of a poor outcome.

Adult↗

PubMed2002

The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues.

BACKGROUND: Although symptoms of anxiety as well as anxiety disorders commonly occur in patients with bipolar disorder, the pathophysiologic, theoretical, and clinical significance of their co-occurrence has not been well studied. METHODS: The epidemiological and clinical studies that have assessed the overlap of bipolar and anxiety disorders are reviewed, with focus on panic disorder and obsessive-compulsive disorder (OCD), and to a lesser extent, social phobia and post-traumatic stress disorder. Potential neural mechanism and treatment response data are also reviewed. RESULTS: A growing number of epidemiological studies have found that bipolar disorder significantly co-occurs with anxiety disorders at rates that are higher than those in the general population. Clinical studies have also demonstrated high comorbidity between bipolar disorder and panic disorder, OCD, social phobia, and post-traumatic stress disorder. Psychobiological mechanisms that may account for these high comorbidity rates likely involve a complicated interplay among various neurotransmitter systems, particularly norepinephrine, dopamine, gamma-aminobutyric acid (GABA), and serotonin. The second-messenger system constituent, inositol, may also be involved. Little controlled data are available regarding the treatment of bipolar disorder complicated by an anxiety disorder. However, adequate mood stabilization should be achieved before antidepressants are used to treat residual anxiety symptoms so as to minimize antidepressant-induced mania or cycling. Moreover, preliminary data suggesting that certain antimanic agents may have anxiolytic properties (e.g. valproate and possibly antipsychotics), and that some anxiolytics may not induce mania (e.g. gabapentin and benzodiazepines other than alprazolam) indicate that these agents may be particularly useful for anxious bipolar patients. CONCLUSIONS: Comorbid anxiety symptoms and disorders must be considered when diagnosing and treating patients with bipolar disorder. Conversely, patients presenting with anxiety disorders must be assessed for comorbid mood disorders, including bipolar disorder. Pathophysiological, theoretical, and clinical implications of the overlap of bipolar and anxiety disorders are discussed.

Antidepressive Agents↗