Bipolar Disorder: Dennehy EB

Dennehy EB. · Department of Psychiatry, University of Texas Southwestern Medical Center, Box 9141, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA. · Curr Psychiatry Rep. · Pubmed #11122975 No free full text.

Abstract: Medication guidelines are being incorporated into psychiatric care, and may serve multiple functions, including ensuring consistent quality care, minimizing or managing costs, integration of new treatments, and providing clinicians with information necessary to make informed clinical decisions. Methods of guideline development and the published guidelines for the medication treatment of bipolar disorder are briefly reviewed. Despite limited research on the clinical efficacy of using guidelines, they serve other useful functions such as prioritizing multiple treatment options and providing a framework for treatment. The future role of treatment algorithms in psychiatric practice will be determined, in part, by results of studies evaluating the clinical impact of their use.

Suppes T, Dennehy EB. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75390-9070, USA. · J Clin Psychiatry. · Pubmed #12392351 No free full text.

Abstract: Bipolar II disorder is a distinct, lifelong mental illness that affects at least 1.5 million people in the United States, is associated with a high incidence of comorbidity, and ends with completed suicide in 10% to 15% of diagnosed individuals. Bipolar II disorder is characterized by at least 1 major depressive episode with 1 or more hypomanic episodes, as opposed to manic or mixed episodes. While it is expected that there may be similarities in approaches to managing patients with bipolar I and bipolar II disorders, data suggest differential patient responses to pharmacologic treatments, supporting the need for research specifically in patients with bipolar II disorder. Despite the prevalence and severity of the disorder, a well-developed scientific database informing long-term treatment choices for bipolar II disorder as an illness differing from bipolar I disorder and major depressive disorder is virtually absent. A review of the limited and sometimes contradictory information stresses that more research is needed into prophylactic and maintenance treatment of bipolar II disorder.

Suppes T, Dennehy EB, Swann AC, Bowden CL, Calabrese JR, Hirschfeld RM, Keck PE, Sachs GS, Crismon ML, Toprac MG, Shon SP, Anonymous00056. · Department of Psychiatry The University of Texas Southwestern Medical Center Dallas, 75390-9070, USA. · J Clin Psychiatry. · Pubmed #12004801 No free full text.

Abstract: BACKGROUND: The process and outcome of a consensus conference to develop revised algorithms for treatment of bipolar disorder to be implemented in the public mental health system of Texas are described. These medication algorithms for bipolar disorder are an update of those developed for the Texas Medication Algorithm Project, a research study that tested the clinical and economic impact of treatment guidelines for major psychiatric illnesses treated in the Texas public mental health system (Texas Department of Mental Health and Mental Retardation [TDMHMR]). METHOD: Academic clinicians and researchers, practicing clinicians in the TDMHMR system, administrators, advocates, and consumers participated in a consensus conference in August 2000. Participants attended presentations reviewing new evidence in the pharmacologic treatment of bipolar disorder and discussed the needs of consumers in the TDMHMR system. Principles were enumerated, including balancing of evidence for efficacy, tolerability, and safety in medication choices. A set of 7 distinct algorithms was drafted. In the following months, a subcommittee condensed this product into 2 primary algorithms. RESULTS: The panel agreed to 2 primary algorithms: treatment of mania/hypomania, including 3 pathways for treatment of euphoric symptoms, mixed or dysphoric symptoms, and psychotic symptoms; and treatment of depressive symptoms. General principles to guide algorithm implementation were discussed and drafted. CONCLUSION: The revised algorithms are currently being disseminated and implemented within the Texas public mental health system. The goals of the Texas initiative include increasing the consistency of appropriate treatment of bipolar disorder, encouraging systematic and optimal use of available pharmacotherapies, and improving the outcomes of patients with bipolar disorder.

Suppes T, Dennehy EB, Gibbons EW. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75390-9070, USA. · J Clin Psychiatry. · Pubmed #10826657 No free full text.

Abstract: Course of illness is central to our focus on bipolar disorder due to the lifelong nature of this illness in the majority of patients. In this overview, we highlight areas of consensus and debate on factors that impact course of illness. Findings on age at onset, psychiatric comorbidity, frequency of episodes, cycle pattern, rapid cycling, mixed symptoms, and precipitants of episodes including use of substances and antidepressants and lithium discontinuation are discussed. The diversity and range of presentation and even course of illness become quickly apparent in this review. Highlighting these factors rather than seeking a unifying theory should be a productive way to refine our ability to identify additive factors contributing to course of illness for patients with bipolar disorder.

Kogan JN, Otto MW, Bauer MS, Dennehy EB, Miklowitz DJ, Zhang HW, Ketter T, Rudorfer MV, Wisniewski SR, Thase ME, Calabrese J, Sachs GS, Anonymous00283. · Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Bipolar Disord. · Pubmed #15541061 No free full text.

Abstract: OBJECTIVES: Bipolar disorder is a severe, recurrent, and often highly impairing psychiatric disorder. The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is a large-scale multicenter study funded by the National Institute of Mental Health (NIMH) to examine the longitudinal course of the disorder and the effectiveness of current treatments. The current report provides a context for interpreting studies resulting from STEP-BD by summarizing the baseline demographic and diagnostic characteristics of the first 1000 enrolled. METHODS: The majority of the sample met DSM-IV criteria for bipolar I disorder (71%). Mean age of patients was 40.6 (+/-12.7) years and mean duration of bipolar illness was 23.1 (+/-12.9) years. Among the first 1000 subjects enrolled, 58.6% are females and 92.6% Caucasian. This report compares the STEP-BD sample with other large cohorts of bipolar patients (treatment and community samples). RESULTS: Compared with US population and community studies, the first 1000 STEP-BD patients were less racially diverse, more educated, had lower income, and a higher unemployment rate. Results are discussed in terms of the contributions of STEP-BD (and other large-scale treatment studies) in understanding the nature, treatments, and outcomes of bipolar disorder for patients seeking care at academic treatment centers. CONCLUSIONS: The current report provides a context for interpreting future studies resulting from STEP-BD. The comparison of demographic and clinical characteristics between the samples across clinic-based studies suggests broad similarities despite the substantial differences in geography, payer mix, and clinical entry point.

Suppes T, Rush AJ, Dennehy EB, Crismon ML, Kashner TM, Toprac MG, Carmody TJ, Brown ES, Biggs MM, Shores-Wilson K, Witte BP, Trivedi MH, Miller AL, Altshuler KZ, Shon SP, Anonymous00228. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, 75390-9070, USA. · J Clin Psychiatry. · Pubmed #12716236 No free full text.

Abstract: BACKGROUND: The Texas Medication Algorithm Project (TMAP) assessed the clinical and economic impact of algorithm-driven treatment (ALGO) as compared with treatment-as-usual (TAU) in patients served in public mental health centers. This report presents clinical outcomes in patients with a history of mania (BD), including bipolar I and schizoaffective disorder, bipolar type, during 12 months of treatment beginning March 1998 and ending with the final active patient visit in April 2000. METHOD: Patients were diagnosed with bipolar I disorder or schizoaffective disorder, bipolar type, according to DSM-IV criteria. ALGO was comprised of a medication algorithm and manual to guide treatment decisions. Physicians and clinical coordinators received training and expert consultation throughout the project. ALGO also provided a disorder-specific patient and family education package. TAU clinics had no exposure to the medication algorithms. Quarterly outcome evaluations were obtained by independent raters. Hierarchical linear modeling, based on a declining effects model, was used to assess clinical outcome of ALGO versus TAU. RESULTS: ALGO and TAU patients showed significant initial decreases in symptoms (p =.03 and p <.001, respectively) measured by the 24-item Brief Psychiatric Rating Scale (BPRS-24) at the 3-month assessment interval, with significantly greater effects for the ALGO group. Limited catch-up by TAU was observed over the remaining 3 quarters. Differences were also observed in measures of mania and psychosis but not in depression, side-effect burden, or functioning. CONCLUSION: For patients with a history of mania, relative to TAU, the ALGO intervention package was associated with greater initial and sustained improvement on the primary clinical outcome measure, the BPRS-24, and the secondary outcome measure, the Clinician-Administered Rating Scale for Mania (CARS-M). Further research is planned to clarify which elements of the ALGO package contributed to this between-group difference.

Dennehy EB, Doyle K, Suppes T. · University of Texas Southwestern Medical Center at Dallas, Bipolar Disorder Clinic and Research Program, 75390, USA. · Int Clin Psychopharmacol. · Pubmed #12702892 No free full text.

Abstract: Randomized controlled trials have demonstrated the efficacy of olanzapine for treating acute mania or depression symptoms in patients with bipolar disorder. We aimed to evaluate the effectiveness of this medication in more usual care outpatient settings. A consecutive series of 15 patients entered an open, uncontrolled 8-week trial of olanzapine monotherapy. Inclusion criteria included significant hypomanic or manic symptoms greater than or equal to 15 on the Young Mania Rating Scale and no psychotic symptoms. The majority of patients experienced significant decreases in mania ratings and more limited improvement on depression ratings. Most patients reported adverse events consistent with other studies, but few discontinued due to these complaints. This case series highlights the individual variation in response to a proven medication. Furthermore, it highlights that those medications effective at one end of the mood spectrum may not be equally or simultaneously effective with other symptoms, emphasizing the complexity of treating bipolar illness.

Suppes T, Swann AC, Dennehy EB, Habermacher ED, Mason M, Crismon ML, Toprac MG, Rush AJ, Shon SP, Altshuler KZ. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75390-9070, USA. · J Clin Psychiatry. · Pubmed #11465521 No free full text.

Abstract: BACKGROUND: Use of treatment guidelines for treatment of major psychiatric illnesses has increased in recent years. The Texas Medication Algorithm Project (TMAP) was developed to study the feasibility and process of developing and implementing guidelines for bipolar disorder, major depressive disorder, and schizophrenia in the public mental health system of Texas. This article describes the consensus process used to develop the first set of TMAP algorithms for the Bipolar Disorder Module (Phase 1) and the trial testing the feasibility of their implementation in inpatient and outpatient psychiatric settings across Texas (Phase 2). METHOD: The feasibility trial answered core questions regarding implementation of treatment guidelines for bipolar disorder. A total of 69 patients were treated with the original algorithms for bipolar disorder developed in Phase 1 of TMAP. RESULTS: Results support that physicians accepted the guidelines, followed recommendations to see patients at certain intervals, and utilized sequenced treatment steps differentially over the course of treatment. While improvements in clinical symptoms (24-item Brief Psychiatric Rating Scale) were observed over the course of enrollment in the trial, these conclusions are limited by the fact that physician volunteers were utilized for both treatment and ratings. and there was no control group. CONCLUSION: Results from Phases 1 and 2 indicate that it is possible to develop and implement a treatment guideline for patients with a history of mania in public mental health clinics in Texas. TMAP Phase 3, a recently completed larger and controlled trial assessing the clinical and economic impact of treatment guidelines and patient and family education in the public mental health system of Texas, improves upon this methodology.

Perlis RH, Dennehy EB, Miklowitz DJ, Delbello MP, Ostacher M, Calabrese JR, Ametrano RM, Wisniewski SR, Bowden CL, Thase ME, Nierenberg AA, Sachs G. · Bipolar Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, ACC 812 15 Parkman Street, Boston, MA 02114, USA. · Bipolar Disord. · Pubmed #19500092 No free full text.

Abstract: OBJECTIVE: Symptoms of bipolar disorder are increasingly recognized among children and adolescents, but little is known about the course of bipolar disorder among adults who experience childhood onset of symptoms. METHODS: We examined prospective outcomes during up to two years of naturalistic treatment among 3,658 adult bipolar I and II outpatients participating in a multicenter clinical effectiveness study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Age at illness onset was identified retrospectively by clinician assessment at study entry. RESULTS: Compared to patients with onset of mood symptoms after age 18 years (n = 1,187), those with onset before age 13 years (n = 1,068) experienced earlier recurrence of mood episodes after initial remission, fewer days of euthymia, and greater impairment in functioning and quality of life over the two-year follow-up. Outcomes for those with onset between age 13 and 18 years (n = 1,403) were generally intermediate between these two groups. CONCLUSION: Consistent with previous reports in smaller cohorts, adults with retrospectively obtained early-onset bipolar disorder appear to be at greater risk for recurrence, chronicity of mood symptoms, and functional impairment during prospective observation.

Dennehy EB, Schnyer R, Bernstein IH, Gonzalez R, Shivakumar G, Kelly DI, Snow DE, Sureddi S, Suppes T. · Department of Psychological Sciences, Purdue University, West Lafayette, IN, USA. · J Clin Psychiatry. · Pubmed #19422756 No free full text.

Abstract: OBJECTIVE: There is growing interest in the utility of nonpharmacologic treatments for mood symptoms, including mood elevation and depression associated with bipolar disorders. The purpose of this research was to provide preliminary data on the safety, effectiveness, and acceptability of adjunctive acupuncture in the acute treatment of hypomania and depression associated with bipolar disorder. METHOD: Two randomized trials were conducted to assess the benefits of adjunctive acupuncture for symptoms of depression and hypomania in patients with bipolar disorder (DSM-IV criteria). For 20 patients experiencing symptoms of hypomania, targeted acupuncture (points specific to symptoms) was compared to acupuncture points off the acupuncture meridian over 12 weeks (from May 2000 through May 2003). For patients experiencing symptoms of depression (n = 26), targeted acupuncture was compared to acupuncture for nonpsychiatric health concerns over 8 weeks (from November 2001 through May 2003). Preexisting psychotropic medications were maintained at stable doses throughout study participation. RESULTS: Regardless of acupuncture assignment or symptom pattern at entry, all patients experienced improvement over the course of study participation. There was evidence that acupuncture treatment did target the symptom dimension of interest (mood elevation in Study I, depression in Study II). There were few negative side effects and no attrition directly associated with adjunctive acupuncture. CONCLUSIONS: Novel methodologies are needed to assess the utility of acupuncture as adjunctive treatment of mood episodes associated with bipolar disorder. We observed similar benefits associated with "placebo" acupuncture experiences and active treatment. Further studies are warranted. TRIAL REGISTRATION (STUDY II): (ClinicalTrials.gov) Identifier: NCT00071669.

Gyulai L, Bauer MS, Marangell LB, Dennehy EB, Thase ME, Otto MW, Zhang H, Wisniewski SR, Miklowitz DJ, Rapaport MH, Baldassano CF, Sachs GS. · Bipolar Disorders Program, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA. · Psychopharmacol Bull. · Pubmed #19015629 No free full text.

Abstract: Objectives: Our primary aim was to describe unique correlates of functioning in bipolar disorder (BD). Experimental Design: The study included the first 500 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Patients were 41.9 +/- 12.7 years old, and diagnosed with bipolar I, II or NOS, verified by structured interview. Overall functionality was determined by the Range of Impaired Function Tool (LIFE-RIFT). Stepwise multiple regression analysis tested the non-redundant-independent-association of 28 variables on functioning. Principal Observations: Severity of depression symptoms was significantly and uniquely correlated with impaired functioning in the context of a wide variety of demographic and clinical variables, contributing 60.9% to the total variance in overall functioning (ss = 0.254, p = 0.0001). Substantial variance in function remains unexplained. Conclusions: Intensity of depressive symptoms is the major determinant of impaired functioning in bipolar disorder, but longitudinal analyses may further explain the substantial variance in function not explained by this large and comprehensive model. Treatments and outcome assessment for patients with bipolar disorders should consider both functional and symptomatic change.

Marangell LB, Dennehy EB, Miyahara S, Wisniewski SR, Bauer MS, Rapaport MH, Allen MH. · Mood Disorders Center, Menninger Department of Psychiatry, Baylor College of Medicine, Houston, TX, United States. · J Affect Disord. · Pubmed #18708263 No free full text.

Abstract: BACKGROUND: This report describes baseline characteristics and functional outcomes of subjects who have prospectively observed subsyndromal symptoms after a major depressive episode (MDE). METHODS: All subjects were participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). We identified subjects with at least 2 years of observation whose prior or current episode was a MDE, and who were in a stable clinical state of either recovered (no more than 2 moderate symptoms for at least 8 weeks), a MDE by DSM-IV criteria, or with continued subsyndromal symptoms. The subsyndromal group was defined a priori as 3 or more moderate affective symptoms but without meeting diagnostic criteria for major depression. RESULTS: The final cohort included 1094 recovered, 112 subsyndromal, and 310 individuals in a MDE. The average time spent in each clinical status ranged from 120 to 132 days. The subsyndromal group was most similar to those in a MDE, differing only on the intensity of depressive symptoms and the number of work days missed due to ongoing symptoms. Reported sadness, inability to feel and lassitude were each associated with multiple measures of impairment. LIMITATIONS: This study is limited by the cross-sectional approach to defining outcomes. CONCLUSIONS: These findings are consistent with studies in unipolar major depression that indicate that functional impairment observed in the context of subsyndromal depressive symptoms is comparable to that of a full episode. This work underscores the need to include subsyndromal symptoms in study outcomes and to target full remission in clinical practice.

Marangell LB, Dennehy EB, Wisniewski SR, Bauer MS, Miyahara S, Allen MH, Martinez M, Al Jurdi RK, Thase ME. · Mood Disorders Center, Menninger Department of Psychiatry, Baylor College of Medicine and South Central Mental Illness Research and Education Core, Department of Veterans Affairs, Houston, Tex, USA. · J Clin Psychiatry. · Pubmed #18399724 No free full text.

Abstract: OBJECTIVE: Given high rates of suicide and suicide attempts in bipolar disorder and the data suggesting a suicide-protective effect of lithium, we evaluated the impact of pharmacotherapy on prospectively observed suicides and suicide attempts in subjects in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). METHOD: The STEP-BD study enrolled 4360 participants with DSM-IV bipolar disorder diagnoses from September 1998 through November 2004. There were 270 suicide events in STEP-BD (8 completed suicides, 262 attempts). These occurred in 182 of STEP-BD participants (cases). Inclusion criteria required cases to be white or Caucasian, have at least 1 postbaseline visit, and have prescription information within 30 days of the suicide event. This reduced the available cohort to 106 cases. Matching included age, gender, history of previous suicide attempt, and a propensity score that considered bipolar subtype, marital status, age at onset, and history of psychosis, resulting in 93 matched pairs. A secondary analysis added mood state status within 30 days of the suicide event to the propensity score (N = 54 pairs). The association of drug prescriptions with suicide attempts/completions was assessed using a conditional logistic regression model. RESULTS: The results do not indicate a relationship between lithium use and suicide attempts or completions (p = .41). Similar findings were found for exposure to valproate, carbamazepine, lamotrigine, and the atypical antipsychotic medications. An association between selective serotonin reuptake inhibitor (SSRI) prescription and suicide events was observed (p < .0001). Findings were similar in a secondary analysis that controlled for mood state. CONCLUSIONS: Our data are not consistent with a suicide-protective effect of lithium. The association between suicide events and SSRI prescriptions requires cautious interpretation due to complex relationships between treatment, severity, and suicidality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00012558.

Dennehy EB, Bauer MS, Perlis RH, Kogan JN, Sachs GS. · Department of Psychological Sciences, Purdue University, West Lafayette, IN. · Psychopharmacol Bull. · Pubmed #18007570 No free full text.

Abstract: Background: Concordance with evidence-based guidelines in the treatment of chronic mental disorders is typically low. The study assesses the degree of concordance to recommendations of published treatment guidelines for bipolar disorder in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Potential demographic and clinical predictors of adherence were examined. Methods: STEP-BD treating psychiatrists participated in extensive training in evidence-based pharmacological management focusing on published clinical practice guidelines. Recommended medications and dosing for each specific mood episode were extracted from published treatment guidelines and collapsed into a Composite guideline. Prescribed medication information for patients at the first visit in a prospectively observed new-onset mood episode (depressive, mixed, or hypomanic/manic) was then compared with guideline recommendations. Results: The current study included 964 STEP-BD patients, observed over 2 years, who experienced a prospectively observed episode (n = 716 depressive; n = 182 hypomanic/ manic; n = 66 mixed). Guideline concordant treatments were prescribed in 81.8% of mixed episodes, 81.9% of hypomanic/manic episodes, and 83.4% of depressive episodes, exceeding rates previously reported in randomized controlled trials of guideline implementation. Younger age of onset and receipt of adequate pharmacotherapy at STEP-BD entry predicted those more likely to receive guideline-concordant care. Conclusions: The use of guideline concordant pharmacological treatments was substantially higher than reported under naturalistic conditions. We speculate that basic provider education plus a collaborative approach to medication choice may have contributed to the high treatment concordance rates in this large national trial. As in other studies, few patient-specific factors were associated with the likelihood of receiving guideline-concordant care.

Truman CJ, Goldberg JF, Ghaemi SN, Baldassano CF, Wisniewski SR, Dennehy EB, Thase ME, Sachs GS. · Finney Psychotherapy Associates, Norfolk, Va., USA. · J Clin Psychiatry. · Pubmed #17960960 No free full text.

Abstract: OBJECTIVE: Antidepressant safety and efficacy remain controversial for the treatment of bipolar depression. The present study utilized data from the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) to examine the prevalence and clinical correlates of self-reported switch into mania/hypomania during antidepressant treatment. METHOD: Antidepressant treatment histories were examined from intake assessments for the first 500 subjects enrolled into the STEP-BD between November 1999 and November 2000. Affective switch was defined as a report of mania, hypomania, or mixed episodes within the first 12 weeks of having started an antidepressant. Demographic and clinical characteristics were compared for subjects with or without a history of acute switch during antidepressant treatment. RESULTS: Among the 338 subjects with prior antidepressant treatment and complete data on switch event outcomes, 44% reported at least 1 such occurrence. Patients with a shorter duration of illness (odds ratio [OR] = 1.02, 95% CI = 1.01 to 1.04) and a history of multiple antidepressant trials (OR = 1.73, 95% CI = 1.38 to 2.16) were more likely to report a history of switch than other patients. A significantly increased risk for affective polarity switch was identified in patients who had ever switched to mania/hypomania while taking tricyclic antidepressants (OR = 7.80, 95% CI = 1.56 to 28.9), serotonin reuptake inhibitors (OR = 3.73, 95% CI = 1.98 to 7.05), or bupropion (OR = 4.28, 95% CI = 1.72 to 10.6). Switch was less common during treatment with electroconvulsive therapy or monoamine oxidase inhibitors than other antidepressants. CONCLUSIONS: Antidepressants are associated with the potential risk for treatment-emergent mania or hypomania, particularly in bipolar patients with short illness duration, multiple past antidepressant trials, and past experience of switch with at least one antidepressant.

Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, Friedman ES, Bowden CL, Fossey MD, Ostacher MJ, Ketter TA, Patel J, Hauser P, Rapport D, Martinez JM, Allen MH, Miklowitz DJ, Otto MW, Dennehy EB, Thase ME. · Bipolar Clinic and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. · N Engl J Med. · Pubmed #17392295 links to  free full text

Abstract: BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. CONCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. (ClinicalTrials.gov number, NCT00012558 [ClinicalTrials.gov].).

Marangell LB, Bauer MS, Dennehy EB, Wisniewski SR, Allen MH, Miklowitz DJ, Oquendo MA, Frank E, Perlis RH, Martinez JM, Fagiolini A, Otto MW, Chessick CA, Zboyan HA, Miyahara S, Sachs G, Thase ME. · Mood Disorders Center, Menninger Department of Psychiatry, Baylor College of Medicine and the Department of Veterans Affairs, VISN 16 MIRECC, Houston, TX 77030, USA. · Bipolar Disord. · Pubmed #17042830 No free full text.

Abstract: OBJECTIVES: Bipolar disorders are associated with high rates of suicide attempts (SAs) and completions. Several factors have been reported to be associated with suicide in persons with bipolar disorder, but most studies to date have been retrospective and have not utilized multivariate statistics to account for the redundant prediction among variables submitted for analysis. METHODS: This study examined the association between baseline clinical and demographic variables and subsequent SAs and completions through 2 years of follow-up of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder using a pattern-mixture model. RESULTS: Of the sample with complete data (n = 1,556), 57 patients (3.66%) experienced an SA or completion (CS). Several variables predicted suicidality (SA + CS) in this data set when considered alone, but after controlling for redundant prediction from other baseline characteristics, only history of suicide [odds ratio (OR) = 4.52, p < 0.0001] and percent days depressed in the past year (OR = 1.16, p = 0.036) were significantly associated with SAs and completions. A secondary analysis included a greater number of variables but a smaller sample size (n = 1,014). In the secondary analyses, only prior SAs predicted prospective suicidality (OR = 3.87, p = 0.0029). CONCLUSIONS: These results indicate that patients with bipolar disorder who present with a history of SAs are over four times as likely to have a subsequent SA or completion. Further studies are needed to evaluate and prevent future attempts in this high-risk cohort.

Toprac MG, Dennehy EB, Carmody TJ, Crismon ML, Miller AL, Trivedi MH, Suppes T, Rush AJ. · TX, USA. · J Clin Psychiatry. · Pubmed #17017822 No free full text.

Abstract: OBJECTIVE: This article describes the implementation and utilization of the patient and family education program (PFEP) component of the Texas Medication Algorithm Project (TMAP). The extent of participation, types of psychoeducation received, and predictors of receiving at least a minimum level of education are presented. METHOD: TMAP included medication guidelines, a dedicated clinical coordinator, standardized assessments of symptoms and side effects, uniform documentation, and a PFEP. The PFEP includes phased, multimodal, disorder-specific educational materials for patients and families. Participants were adult outpatients of 1 of 7 community mental health centers in Texas that were implementing the TMAP disease management package. Patients had DSM-IV clinical diagnoses of major depressive disorder, with or without psychotic features; bipolar I disorder or schizoaffective disorder, bipolar type; or schizophrenia or schizoaffective disorder. Assessments were administered by independent research coordinators. Study data were collected between March 1998 and March 2000, and patients participated for at least 1 year. RESULTS: Of the 487 participants, nearly all (95.1%) had at least 1 educational encounter, but only 53.6% of participants met criteria for "minimum exposure" to individual education interventions. Furthermore, only 31.0% participated in group education, and 42.5% had a family member involved in at least 1 encounter. Participants with schizophrenia were less involved in the PFEP across multiple indicators of utilization. Diagnosis, intensity of symptoms, age, and receipt of public assistance were related to the likelihood of exposure to minimum levels of individual education. CONCLUSION: Despite adequate resources and infrastructure to provide PFEP, utilization was less than anticipated. Although implementation guidelines were uniform across diagnoses, participants with schizophrenia experienced less exposure to psychoeducation. Recommendations for improving program implementation and modification of materials are discussed.

Marangell LB, Suppes T, Ketter TA, Dennehy EB, Zboyan H, Kertz B, Nierenberg A, Calabrese J, Wisniewski SR, Sachs G. · Mood Disorders Center, Menninger Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA. · Prostaglandins Leukot Essent Fatty Acids. · Pubmed #16928441 No free full text.

Abstract: Several lines of evidence suggest that omega-3 fatty acids may be important in the pathophysiology, treatment or prevention of bipolar disorder (BD). Electronic and manual searches were conducted in order to review the literature relevant to the etiology and treatment of BDs with omega-3 fatty acids. We also present data from a randomized, double-blind, placebo-controlled pilot study conducted at three sites (N = 10) comparing an omega-3 fatty acid (docosahexaenoic acid, DHA) versus placebo, added to psychosocial treatment for women with BD who chose to discontinue standard pharmacologic treatment while attempting to conceive. While some epidemiologic and preclinical data support the role of omega-3 fatty acids in BD, clinical trials to date have yielded conflicting results. In our pilot study of 10 Caucasian women taking DHA while attempting to conceive (BP1 = 9, BPII = 1), age 27-42 years, DHA was well tolerated and suggests that a larger study would be feasible. The elucidation of the potential role of omega-3 fatty acids as a treatment for BD requires further study. The current data are not sufficient to support a recommendation of monotherapy treatment as a substitute for standard pharmacologic treatments. However, judicious monotherapy in selected clinical situations, or adjunctive use, may be warranted pending further data from adequately powered controlled clinical trials. Our pilot trial of DHA in women who plan to stop conventional psychotropics in order to conceive suggests that such trials are feasible.

Bauer MS, Wisniewski SR, Marangell LB, Chessick CA, Allen MH, Dennehy EB, Miklowitz DJ, Thase ME, Sachs GS. · Providence Veterans Affairs Medical Center and the Department of Psychiatry and Human Behavior, Brown University, VAMC-116R, 830 Chalkstone Avenue, Providence, R.I. 02908-4799, USA. · J Clin Psychiatry. · Pubmed #16426088 No free full text.

Abstract: OBJECTIVE: Depressive episodes are common in bipolar disorder, and the disorder is characterized by high suicide rates. Recent analyses indicate a possible association of antidepressant treatment and suicidality in children and adults with depressive or anxiety disorders. However, few data are available to inform the suicidality risk assessment of antidepressant use specifically in bipolar disorder. METHOD: Of the first 2000 participants followed for 18 months in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 425 experienced a prospectively observed, new-onset major depressive episode without initial suicidal ideation. Standardized ratings of suicidality and antidepressant exposure at index depressive episode and next evaluation were used to investigate the primary hypothesis that new-onset suicidality was associated with increased antidepressant exposure (antidepressant initiation or dose increase). Secondary analysis investigated correlates of new-onset suicidality and antidepressant exposure. Data were collected from November 8, 1999, to April 24, 2002. RESULTS: Twenty-four participants (5.6%) developed new-onset suicidality at follow-up, including 2 suicide attempts. There was no association of new-onset suicidality with increased antidepressant exposure or any change in antidepressant exposure, and no association with initiation of antidepressant treatment. New-onset suicidality was associated with neuroticism, prior attempt, and higher depressive or manic symptom ratings at index episode. Increased antidepressant exposure was negatively associated with higher manic symptom rating at index episode; control for this sole empirically identified confound did not alter the primary results. CONCLUSIONS: Although careful monitoring for suicidality is always warranted in bipolar disorder, this cohort study provides no evidence that increased antidepressant exposure is associated with new-onset suicidality in this already high-risk population. Correlates of both suicidality and antidepressant exposure indicate directions for further research.

Dennehy EB, Suppes T, Rush AJ, Miller AL, Trivedi MH, Crismon ML, Carmody TJ, Kashner TM. · Department of Psychological Sciences, Purdue University, West Lafayette, IN 47907-2081, USA. · Psychol Med. · Pubmed #16194283 No free full text.

Abstract: BACKGROUND: Despite increasing adoption of clinical practice guidelines in psychiatry, there is little measurement of provider implementation of these recommendations, and the resulting impact on clinical outcomes. The current study describes one effort to measure these relationships in a cohort of public sector out-patients with bipolar disorder.METHOD:Participants were enrolled in the algorithm intervention of the Texas Medication Algorithm Project (TMAP). Study methods and the adherence scoring algorithm have been described elsewhere. The current paper addresses the relationships between patient characteristics, provider experience with the algorithm, provider adherence, and clinical outcomes. Measurement of provider adherence includes evaluation of visit frequency, medication choice and dosing, and response to patient symptoms. An exploratory composite 'adherence by visit' score was developed for these analyses.RESULTS: A total of 1948 visits from 141 subjects were evaluated, and utilized a two-stage declining effects model. Providers with more experience using the algorithm tended to adhere less to treatment recommendations. Few patient factors significantly impacted provider adherence. Increased adherence to algorithm recommendations was associated with larger decreases in overall psychiatric symptoms and depressive symptoms over time, but did not impact either immediate or long-term reductions in manic symptoms.CONCLUSIONS: Greater provider adherence to treatment guideline recommendations was associated with greater reductions in depressive symptoms and overall psychiatric symptoms over time. Additional research is needed to refine measurement and to further clarify these relationships.

Suppes T, Dennehy EB, Hirschfeld RM, Altshuler LL, Bowden CL, Calabrese JR, Crismon ML, Ketter TA, Sachs GS, Swann AC, Anonymous00358. · Department of Psychiatry, the University of Texas Southwestern Medical Center, Dallas, TX 75390-9121, USA. · J Clin Psychiatry. · Pubmed #16013903 No free full text.

Abstract: BACKGROUND: A panel consisting of academic psychiatrists and pharmacist administrators of the Texas Department of State Health Services (formerly Texas Department of Mental Health and Mental Retardation), community mental health physicians, advocates, and consumers met in May 2004 to review new evidence in the pharmacologic treatment of bipolar I disorder (BDI). The goal of the consensus conference was to update and revise the current treatment algorithm for BDI as part of the Texas Implementation of Medication Algorithms, a statewide quality assurance program for the treatment of major psychiatric illness. The guidelines for evaluating possible medications, the criteria for selection and ranking, and the updated algorithms are described. METHOD: Principles from previous consensus conferences were reviewed and amended. Medication algorithms for the acute treatment of hypomanic/manic or mixed and depressive episodes in BDI were developed after examining recent efficacy and safety and tolerability data. Recommendations for maintenance treatments were developed. RESULTS: The panel updated the 2 primary algorithms (hypomanic/manic/mixed and depressive) based on clinical evidence for efficacy, tolerability, and safety developed since 2000. Expert consensus was utilized where clinical evidence was limited. Prevention of new episodes or prophylaxis treatment recommendations were developed based on recent data from longer-term trials. Maintenance recommendations are provided as levels versus a specified staged algorithm, as for acute treatment, due to the relatively limited database to inform treatment. CONCLUSIONS: These algorithms for the treatment of BDI represent the recommendations based on the most recent evidence available. These recommendations are meant to provide a framework for clinical decision making, not to replace clinical judgment. As with any algorithm, treatment practices will evolve beyond the recommendations of this consensus conference as new evidence and additional medications become available.

Dennehy EB, Suppes T, Crismon ML, Toprac M, Carmody TJ, Rush AJ. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA. · Psychiatry Res. · Pubmed #15261712 No free full text.

Abstract: The Brief Bipolar Disorder Symptom Scale (BDSS) is a 10-item measure of symptom severity that was derived from the 24-item Brief Psychiatric Rating Scale (BPRS24). It was developed for clinical use in settings where systematic evaluation is desired within the constraints of a brief visit. The psychometric properties of the BDSS were evaluated in 409 adult outpatients recruited from 19 clinics within the public mental health system of Texas, as part of the Texas Medication Algorithm Project (TMAP). The selection process for individual items is discussed in detail, and was based on multiple analyses, including principal components analysis with varimax rotation. Selection of the final items considered the statistical strength and factor loading of items within each of those factors as well as the need for comprehensive coverage of critical symptoms of bipolar disorder. The BDSS demonstrated good psychometric properties in this preliminary investigation. It demonstrated a strong association with the BPRS24 and performed similarly to the BPRS24 in its relationship to other symptom measures. The BDSS demonstrated superior sensitivity to symptom change, and an excellent level of agreement for classification of patients as either responders or non-responders with the BPRS24.

Dennehy EB, Suppes T, John Rush A, Lynn Crismon M, Witte B, Webster J. · Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA. · J Psychiatr Res. · Pubmed #15003434 No free full text.

Abstract: The adoption of treatment guidelines for complex psychiatric illness is increasing. Treatment decisions in psychiatry depend on a number of variables, including severity of symptoms, past treatment history, patient preferences, medication tolerability, and clinical response. While patient outcomes may be improved by the use of treatment guidelines, there is no agreed upon standard by which to assess the degree to which clinician behavior corresponds to those recommendations. This report presents a method to assess clinician adherence to the complex multidimensional treatment guideline for bipolar disorder utilized in the Texas Medication Algorithm Project. The steps involved in the development of this system are presented, including the reliance on standardized documentation, defining core variables of interest, selecting criteria for operationalization of those variables, and computerization of the assessment of adherence. The computerized assessment represents an improvement over other assessment methods, which have relied on laborious and costly chart reviews to extract clinical information and to analyze provider behavior. However, it is limited by the specificity of decisions that guided the adherence scoring process. Preliminary findings using this system with 2035 clinical visits conducted for the bipolar disorder module of TMAP Phase 3 are presented. These data indicate that this system of guideline adherence monitoring is feasible.

Trivedi MH, Rush AJ, Ibrahim HM, Carmody TJ, Biggs MM, Suppes T, Crismon ML, Shores-Wilson K, Toprac MG, Dennehy EB, Witte B, Kashner TM. · Department of Psychiatry and Academic Computing Services, University of Texas, Southwestern Medical Center at Dallas 75235, USA. · Psychol Med. · Pubmed #14971628 No free full text.

Abstract: BACKGROUND: The present study provides additional data on the psychometric properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief 16-item symptom severity rating scale that was derived from the longer form. Both the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and self-report (IDS-SR30; QIDS-SR16) formats. METHOD: The patient samples included 544 out-patients with major depressive disorder (MDD) and 402 out-patients with bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses including sensitivity to change with treatment were conducted. RESULTS: Internal consistencies (Cronbach's alpha) ranged from 0.81 to 0.94 for all four scales (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad mood, involvement, energy, concentration and self-outlook had the highest item-total correlations among patients with MDD and BD across all four scales. QIDS-SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at exit (c = 0.83). QIDS-C16 and IDS-C30 total scores were also highly correlated among patients with MDD (c = 0.82) and patients with BD (c = 0.81). The IDS-SR30, IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change, indicating high concurrent validity for all four scales. High concurrent validity was also documented based on the SF-12 Mental Health Summary score for the population divided in quintiles based on their IDS or QIDS score. CONCLUSION: The QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly acceptable psychometric properties and are treatment sensitive measures of symptom severity in depression.