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Bipolar Disorder: HELP
Articles from University of Texas San Antonio
Based on 24 articles published since 2010

These are the 24 published articles about Bipolar Disorder that originated from University of Texas San Antonio during 2010-2020.
+ Citations + Abstracts
1 Review Anger in psychological disorders: Prevalence, presentation, etiology and prognostic implications. 2016

Fernandez, Ephrem / Johnson, Sheri L. ·University of Texas, San Antonio, United States. Electronic address: ephrem.fernandez@utsa.edu. · University of California Berkeley, United States. ·Clin Psychol Rev · Pubmed #27188635.

ABSTRACT: Anger is present as a key criterion in five diagnoses within DSM-5: Intermittent Explosive Disorder, Oppositional Defiant Disorder, Disruptive Mood Dysregulation Disorder, Borderline Personality Disorder and Bipolar Disorder. This review amasses scientific literature demonstrating that within each of these disorders, anger is a central clinical feature that is highly prevalent and predictive of important outcomes. For each disorder, we also discuss the phenomenology and etiology of anger. Although models of anger have been quite distinct across these disorders, few empirical studies have truly tested whether anger stems from different etiological factors across these different conditions. We end with a discussion of transdiagnostic research that draws from cognitive psychology, affective science, and the neuroscience of anger, and that also fits with integrative approaches to treatment.

2 Review Lamotrigine (Lamictal IR) for the treatment of bipolar disorder. 2012

Bowden, Charles L / Singh, Vivek. ·The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. bowdenc@uthscsa.edu ·Expert Opin Pharmacother · Pubmed #23140205.

ABSTRACT: INTRODUCTION: Over the past decade the use of lamotrigine in bipolar disorder has increased. However, the evidence base suggests a more limited role for lamotrigine as part of an overall treatment regimen in bipolar disorder. AREAS COVERED: We reviewed publications of randomized clinical trials of lamotrigine, emphasizing studies in bipolar disorder. The low burden of adverse effects with lamotrigine has been confirmed in these studies. Its lack of benefit in acute mania is established. Despite modest benefits for a subset of depressive episodes in bipolar disorder, it was not superior to placebo in well-designed studies. As monotherapy, in randomized, blinded trials in rapid cycling bipolar disorder it was not superior to placebo. Its role in maintenance treatment is relatively well established as one component of combination therapy, with evidence for benefits when combined with lithium or valproate. Combination regimens including lamotrigine appear to be superior to monotherapy. Monotherapy utilization of lamotrigine for maintenance treatment is not supported by these studies. EXPERT OPINION: Lamotrigine has benefits in bipolar disorder management principally as a component of combination treatment which includes a mood stabilizer. The utility of lamotrigine in acute bipolar depression and major depressive disorder is modest.

3 Review Aims and results of the NIMH systematic treatment enhancement program for bipolar disorder (STEP-BD). 2012

Bowden, C L / Perlis, R H / Thase, M E / Ketter, T A / Ostacher, M M / Calabrese, J R / Reilly-Harrington, N A / Gonzalez, J M / Singh, V / Nierenberg, A A / Sachs, G S. ·Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. bowdenc@uthscsa.edu ·CNS Neurosci Ther · Pubmed #22070541.

ABSTRACT: The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP-BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP-BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP-BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP-BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders.

4 Review Methodological challenges in psychiatric treatment adherence research. 2010

Velligan, Dawn / Sajatovic, Martha / Valenstein, Marcia / Riley, William T / Safren, Steven / Lewis-Fernandez, Roberto / Weiden, Peter / Ogedegbe, Gbenga / Jamison, Julian. ·Department of Psychiatry, Mail Stop 7797, The University of Texas Health Science Center, 7704 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. velligand@uthscsa.edu ·Clin Schizophr Relat Psychoses · Pubmed #20643631.

ABSTRACT: Reflecting an increasing awareness of the importance of treatment adherence on outcomes in psychiatric populations, the National Institute of Mental Health (NIMH) convened a panel of treatment adherence researchers on September 27-28, 2007 to discuss and articulate potential solutions for dealing with methodological adherence research challenges. Panel discussions and presentations were augmented with targeted review of the literature on specific topics, with a focus on adherence to medication treatments in adults with serious mental illness. The group discussed three primary methodological areas: participants, measures, and interventions. When selecting patients for adherence-enhancing interventions (AEIs), a three-tier model was proposed that draws from the universal (targeting all patients receiving medication treatment for a specific condition, regardless of current adherence), selective (targeting patients at risk for nonadherence), and indicated (targeting patients who are currently nonadherent) prevention model and emphasizes careful patient characterization in relevant domains and appropriate matching of interventions to the selected population. Proposals were also made to reduce problematic selection biases in patient recruitment and retention. The panel addressed the pros and cons of various methods that can be used to measure adherence, and concluded that it is appropriate to use multiple measures whenever possible. Finally, the panel identified a broad range of intervention approaches, and conditions under which these interventions are likely to be most effective at reducing barriers to adherence and reinforcing adherence behavior.

5 Clinical Trial Relative effectiveness of adjunctive risperidone on manic and depressive symptoms in mixed mania. 2013

Singh, Vivek / Bowden, Charles L / Mintz, Jim. ·Department of Psychiatry, University of Texas Health Science Center at San Antonio, Texas 78229-3900, USA. singhv@uthscsa.edu ·Int Clin Psychopharmacol · Pubmed #23238761.

ABSTRACT: Mixed states are common and severe manifestations of bipolar disorder, with limited data on the differential efficacy of treatments on depressive and manic symptoms. This study assessed the effectiveness of open-label adjunctive risperidone in achieving sustained effectiveness in patients with mixed mania, with a specific focus on the differential benefits on manic and depressive symptomatology. Forty patients with bipolar disorder I, currently in a mixed manic episode, were treated with adjunctive risperidone. Behavioral measures at baseline and weeks 1, 2, 4, 8, 12, 16, and 20 were assessed using the following scales: the Young Mania Rating Scale, the Montgomery Asberg Depression Rating Scale (MADRS), and the Global Assessment Scale. The primary outcome measure was the proportion of patients who attained a sustained response on either depressive or manic symptomatology, defined as at least 50% reduction from the baseline on the Montgomery Asberg Depression Rating Scale or the Young Mania Rating Scale, maintained over at least 8 weeks without subsequent relapse during the 20-week trial. A significantly higher proportion of patients achieved a sustained response for mania than depression, 16/40 versus 6/40, respectively (McNemar's χ² 8.33, P=0.004). Higher elevated mood at baseline and lower apparent sadness (P<0.016) each predicted a sustained response for mania (P<0.0001). Mixed manic patients who were treated with risperidone adjunctive to mood stabilizer/s for 20 weeks were significantly more likely to achieve a sustained response for manic than for depressive symptomatology.

6 Article Psychiatric Aeromedical Evacuations of Deployed Active Duty U.S. Military Personnel During Operations Enduring Freedom, Iraqi Freedom, and New Dawn. 2018

Peterson, Alan L / Hale, Willie J / Baker, Monty T / Cigrang, Jeffrey A / Moore, Brian A / Straud, Casey L / Dukes, Susan F / Young-McCaughan, Stacey / Gardner, Cubby L / Arant-Daigle, Deborah / Pugh, Mary Jo / Williams Christians, Iman / Mintz, Jim / Anonymous6060958. ·Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7550 Interstate Highway 10 West, Suite 1325, San Antonio, TX. · Research and Development Service, South Texas Veterans Health Care System, 7400 Merton Minter Boulevard, San Antonio, TX. · Department of Psychology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX. · Wilford Hall Ambulatory Surgical Center, 2200 Bergquist Drive, San Antonio, TX. · Department of Psychology, Wright State University, 9 North Edwin C. Moses Boulevard, Dayton, OH. · Daniel K. Inouye Graduate School of Nursing, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD. ·Mil Med · Pubmed #30124915.

ABSTRACT: Introduction: The primary objective of this study was to describe the demographic, clinical, and attrition characteristics of active duty U.S. military service members who were aeromedically evacuated from Iraq and Afghanistan theaters with a psychiatric condition as the primary diagnosis. The study links the U.S. Transportation Command Regulating and Command and Control Evacuation System (TRAC2ES) data with the Defense Manpower Data Center (DMDC) to conduct an examination of the long-term occupational impact of psychiatric aeromedical evacuations on military separations and discharges. Materials and Methods: Retrospective analyses were conducted on the demographic, clinical, and attrition information of active duty service members (N = 7,023) who received a psychiatric aeromedical evacuation from Iraq or Afghanistan between 2001 and 2013 using TRAC2ES data. Additionally, TRAC2ES database was compared with DMDC data to analyze personal and service demographics, aeromedical evacuation information, and reasons for military separation with the entire 2013 active duty force. Chi-square tests of independence and standardized residuals were used to identify cells with observed frequencies or proportions significantly different than expected by chance. Additionally, OR were calculated to provide context about the nature of any significant relationships. Results: Compared with the active duty comparison sample, those with a psychiatric aeromedical evacuation tended to be younger, female, white, divorced or widowed, and less educated. They were also more likely to be junior enlisted service members in the Army serving in a Combat Arms military occupational specialty. The primary psychiatric conditions related to the aeromedical evacuation were depressive disorders (25%), adjustment disorders (18%), post-traumatic stress disorder (9%), bipolar disorders (6%), and anxiety disorders (6%). Approximately, 3% were evacuated for suicidal ideation and associated behaviors. Individuals who received a psychiatric aeromedical evacuation were almost four times as likely (53%) to have been subsequently separated from active duty at the time of the data analysis compared with other active duty service members (14%). The current study also found that peaks in the number of aeromedical evacuations coincided with significant combat operational events. These peaks almost always preceded or followed a significant operational event. An unexpected finding of the present study was that movement classification code was not predictive of subsequent reasons for separation from the military. Thus, the degree of clinical supervision and restraint of a service member during psychiatric aeromedical evacuation from deployment proved to be unrelated to subsequent service outcome. Conclusions: Psychiatric conditions are one of the leading reasons for the aeromedical evacuation of active duty military personnel from the military combat theater. For many active duty military personnel, a psychiatric aeromedical evacuation from a combat theater is the start of a military career-ending event that results in separation from active duty. This finding has important clinical and operational implications for the evaluation and treatment of psychiatric conditions during military deployments. Whenever possible, deployed military behavioral health providers should attempt to treat psychiatric patients in theater to help them remain in theater to complete their operational deployments. Improved understanding of the factors related to psychiatric aeromedical evacuations will provide important clinical and policy implications for future conflicts.

7 Article Investigating symptom domains of bipolar disorder for Spanish-speakers using the Bipolar Inventory of Symptoms Scale. 2016

Arnold, Jodi Gonzalez / Martinez, Cervando / Zavala, Juan / Prihoda, Thomas J / Escamilla, Michael / Singh, Vivek / Bazan, Melissa / Quiñones, Marlon / Bowden, Charles L. ·University of Texas Health Science Center, Department of Psychiatry, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States. Electronic address: arnoldjg@uthscsa.edu. · University of Texas Health Science Center, Department of Psychiatry, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States. · Texas Tech University Health Sciences Center, Department of Psychiatry, 5001 El Paso Drive, El Paso, TX 79905, United States. · University of Texas Health Science Center, Department of Pathology, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States. · Laurel Ridge Treatment Center, 17720 Corporate Woods Drive, San Antonio, TX 78259, United States. ·J Affect Disord · Pubmed #27454409.

ABSTRACT: BACKGROUND: A Spanish language rating scale which assesses the range of bipolar disorder symptoms is needed. There are rating scales commonly used, however they do not address commonly expressed symptoms associated with bipolar disorder and have varied rating systems. There are also few comparisons of symptom severity between Spanish and English speaking patients, due to limitations in available rating scales. METHODS: We conducted psychometric assessment of the Spanish language Bipolar Inventory of Symptoms Scale (BISS) (N=71) for persons with bipolar disorder, which assesses 5 domains: mania, depression, irritability, anxiety and psychosis. The Spanish BISS scores were then compared to the MADRS (Montgomery Asberg Depression Rating Scale) and the YMRS (Young Mania Rating Scale) as well as to BISS scores in an English speaking sample (N=102) with bipolar disorder from the same geographic locations. RESULTS: Chronbach's alphas for the Spanish BISS ranged from 0.6 to 0.93, with the psychosis domain displaying lower reliability. Correlations with the MADRS and YMRS were good and ranged from 0.70 to 0.88. The BISS differentiated well across mood states in English and Spanish versions, with mood state differentiated well using subscales and domains. For the irritability and anxiety domains, Spanish speaking participants had higher scores than English speakers across mood states. Females showed differences in symptom profiles compared to males. LIMITATIONS: The sample sizes in the Spanish speaking manic group were small. The Spanish BISS, tested here primarily in patients of Mexican ancestry, may require revision in other Spanish language populations. CONCLUSIONS: The Spanish BISS, a Spanish language symptom rating scale for bipolar disorder, demonstrates good reliability and validity. Clinical assessment in anxiety and irritability domains is particularly relevant in a Spanish speaking sample. Consistent with prior research, females report higher depression, irritability and anxiety scores irrespective of language spoken.

8 Article Common sources of disparate results and experience in clinical practice vs. results from phase 2 registration studies: lamotrigine as a prototype. 2015

Bowden, C L. ·University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. bowdenc@uthscsa.edu. ·Acta Psychiatr Scand · Pubmed #25968405.

ABSTRACT: -- No abstract --

9 Article An exploratory study of responses to low-dose lithium in African Americans and Hispanics. 2015

Gonzalez Arnold, Jodi / Salcedo, Stephanie / Ketter, Terrence A / Calabrese, Joseph R / Rabideau, Dustin J / Nierenberg, Andrew A / Bazan, Melissa / Leon, Andrew C / Friedman, Edward S / Iosifescu, Dan / Sylvia, Louisa G / Ostacher, Michael / Thase, Michael / Reilly-Harrington, Noreen A / Bowden, Charles L. ·University of Texas Health Science Center San Antonio, USA. Electronic address: arnoldjg@uthscsa.edu. · Massachusetts General Hospital - Bipolar Clinic and Research Program, USA. · Stanford University School of Medicine, USA. · Case Western Reserve University, USA. · University of Texas Health Science Center San Antonio, USA. · University of Pittsburgh School of Medicine, USA. · Mount Sinai School of Medicine, USA. · University of Pennsylvania School of Medicine, USA. ·J Affect Disord · Pubmed #25827507.

ABSTRACT: OBJECTIVES: Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS). METHODS: LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) vs. OPT alone in outpatients with bipolar disorder. Of 283 participants, 47 African Americans, 39 Hispanics, and 175 non-Hispanic whites were examined. We predicted minority groups would have more negative medication attitudes and higher attrition rates, but better clinical outcomes. RESULTS: African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study. African Americans in the OPT only group had marginal improvement on depression symptoms. For Hispanics, satisfaction with life did not significantly improve in the OPT only group, in contrast to whites and African Americans who improved over time on all measures. Attitudes toward medications did not differ across ethnic/racial groups. CONCLUSIONS: African Americans show some greater improvements with lithium than non-Hispanic whites, and Hispanics showed more consistent improvements in the lithium group. The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics. Given that the control group (regardless of ethnicity/race) had significant improvements, optimized treatment may be beneficial for any ethnic group.

10 Article Widespread white matter tract aberrations in youth with familial risk for bipolar disorder. 2015

Roybal, Donna J / Barnea-Goraly, Naama / Kelley, Ryan / Bararpour, Layla / Howe, Meghan E / Reiss, Allan L / Chang, Kiki D. ·Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine(,) Stanford University, Stanford, CA, USA. Electronic address: roybal@uthscsa.edu. · Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA. · Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine(,) Stanford University, Stanford, CA, USA. ·Psychiatry Res · Pubmed #25779034.

ABSTRACT: Few studies have examined multiple measures of white matter (WM) differences in youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the FR-BD group, we used three measures of WM structure and two methods of analysis. We used fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth with familial risk for bipolar disorder, defined as having both a parent with BD and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We conducted a whole brain voxelwise analysis using tract based spatial statistics (TBSS). Subsequently, we conducted a complementary atlas-based, region-of-interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was used, significant widespread between-group differences were found showing increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, and corpus callosum. Atlas-based analysis confirmed significant between-group differences, with increased FA and decreased RD in the FR-BD group in the SLF, cingulum, and SFOF. We found significant widespread WM tract aberrations in youth with familial risk for BD using two complementary methods of DTI analysis.

11 Article Cortical Volume Alterations in Conduct Disordered Adolescents with and without Bipolar Disorder. 2014

Olvera, Rene L / Glahn, David C / O'Donnell, Louise / Bearden, Carrie E / Soares, Jair C / Winkler, Anderson M / Pliszka, Steven R. ·Division of Child and Adolescent Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, 7703 Floyd Curl Drive, TX 78229, USA. olverar@uthscsa.edu. · Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT 06114, USA. winkler@fmrib.ox.ac.uk. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. winkler@fmrib.ox.ac.uk. · Division of Child and Adolescent Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, 7703 Floyd Curl Drive, TX 78229, USA. odonnelll@uthscsa.edu. · Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, USA. cbearden@mednet.ucla.edu. · Department of Psychiatry, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. jair.c.soares@uth.tmc.edu. · Oxford University Centre for Functional MRI of the Brain, Oxford OX1 2JD, UK. winkler@fmrib.ox.ac.uk. · Division of Child and Adolescent Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, 7703 Floyd Curl Drive, TX 78229, USA. pliszka@uthscsa.edu. ·J Clin Med · Pubmed #26237382.

ABSTRACT: BACKGROUND: There is increasing evidence that bipolar disorder (BD) and conduct disorder (CD) are co-occurring disorders. Magnetic resonance imaging has revealed differences in the structure and function of the frontal cortex in these disorders when studied separately; however, the impact of BD comorbidity on brain structure in adolescents with CD has not yet been examined. METHOD: We conducted an optimized voxel based morphometry (VBM) study of juvenile offenders with the following diagnoses: conduct disorder with comorbid bipolar disorder (CD-BD; n = 24), conduct disorder without bipolar disorder (CD; n = 24) and healthy controls (HC, n = 24). Participants were 13-17 years of age, in a residential treatment facility for repeat offenders. The three groups in this study were similar in age, gender, socioeconomic status and ethnicity. RESULTS: We found CD-BD subjects had decreased volume relative to controls at the voxel level in the right medial prefrontal cortex (PFC). Using a Threshold-Free Cluster Enhancement (TFCE) technique, the CD-BD subjects had significantly decreased volumes of the right medial prefrontal cortex and portions of the superior and inferior frontal gyrus, anterior cingulate and temporal gyrus. The CD subjects did not have differences in brain volume compared to control subjects or CD-BD subjects. CONCLUSIONS: Our findings suggest the comorbidity between CD and BD is associated with neurobiological impact namely volumetric differences from healthy controls. Furthermore subjects with this comorbidity had poorer lifetime functioning, more mood and attentional dysfunction, and more medication exposure than subjects with CD who were not BD.

12 Article PD_NGSAtlas: a reference database combining next-generation sequencing epigenomic and transcriptomic data for psychiatric disorders. 2014

Zhao, Zheng / Li, Yongsheng / Chen, Hong / Lu, Jianping / Thompson, Peter M / Chen, Juan / Wang, Zishan / Xu, Juan / Xu, Chun / Li, Xia. ·College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. zhaozheng0503@gmail.com. · College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. liyongsheng@ems.hrbmu.edu.cn. · College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. hongchench123@gmail.com. · College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. lujianping1992@gmail.com. · Southwest Brain Bank, Department of Psychiatry, UTHSCSA, San Antonio, TX, USA. ThompsonP@uthscsa.edu. · College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. chenjuan19901105@hotmail.com. · College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. zishan2009158029@163.com. · College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. xujuanbiocc@ems.hrbmu.edu.cn. · Department of Pediatrics, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA. chun.xu@ttuhsc.edu. · College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. lixia@hrbmu.edu.cn. ·BMC Med Genomics · Pubmed #25551368.

ABSTRACT: BACKGROUND: Psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) are projected to lead the global disease burden within the next decade. Several lines of evidence suggest that epigenetic- or genetic-mediated dysfunction is frequently present in these disorders. To date, the inheritance patterns have been complicated by the problem of integrating epigenomic and transcriptomic factors that have yet to be elucidated. Therefore, there is a need to build a comprehensive database for storing epigenomic and transcriptomic data relating to psychiatric disorders. DESCRIPTION: We have developed the PD_NGSAtlas, which focuses on the efficient storage of epigenomic and transcriptomic data based on next-generation sequencing and on the quantitative analyses of epigenetic and transcriptional alterations involved in psychiatric disorders. The current release of the PD_NGSAtlas contains 43 DNA methylation profiles and 37 transcription profiles detected by MeDIP-Seq and RNA-Seq, respectively, in two distinct brain regions and peripheral blood of SZ, BP and non-psychiatric controls. In addition to these data that were generated in-house, we have included, and will continue to include, published DNA methylation and gene expression data from other research groups, with a focus on psychiatric disorders. A flexible query engine has been developed for the acquisition of methylation profiles and transcription profiles for special genes or genomic regions of interest of the selected samples. Furthermore, the PD_NGSAtlas offers online tools for identifying aberrantly methylated and expressed events involved in psychiatric disorders. A genome browser has been developed to provide integrative and detailed views of multidimensional data in a given genomic context, which can help researchers understand molecular mechanisms from epigenetic and transcriptional perspectives. Moreover, users can download the methylation and transcription data for further analyses. CONCLUSIONS: The PD_NGSAtlas aims to provide storage of epigenomic and transcriptomic data as well as quantitative analyses of epigenetic and transcriptional alterations involved in psychiatric disorders. The PD_NGSAtlas will be a valuable data resource and will enable researchers to investigate the pathophysiology and aetiology of disease in detail. The database is available at http://bioinfo.hrbmu.edu.cn/pd_ngsatlas/.

13 Article Efficacy of olanzapine monotherapy in acute bipolar depression: a pooled analysis of controlled studies. 2013

Tohen, M / Katagiri, H / Fujikoshi, S / Kanba, S. ·University of New Mexico, Health Science Center, Department of Psychiatry, Albuquerque, NM, USA. tohen@uthscsa.edu ·J Affect Disord · Pubmed #23485111.

ABSTRACT: BACKGROUND: The efficacy and safety of olanzapine monotherapy in bipolar depression has been evaluated in 2 placebo-controlled studies. METHODS: We pooled data from 2 previously published studies examining olanzapine monotherapy in patients with bipolar I depression. Changes from baseline to 6 weeks in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, MADRS-6 (included items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts) score, and individual MADRS item scores were assessed with an analysis of variance (ANOVA) model. Influence of patient baseline characteristics (age, gender, MADRS total score, age at onset of bipolar disorder, psychotic features, melancholic feature, mixed features [≥2 on ≥3 Young Mania Rating Scale items], and racial origin) on the efficacy of olanzapine monotherapy was examined with an ANOVA model for each factor and stepwise multiple regression analysis. RESULTS: Included were a total of 690 olanzapine-group and 524 placebo-group patients. MADRS total, MADRS-6, and all individual MADRS item scores (except concentration difficulties and suicidal thoughts) showed significantly (P≤0.05) greater decreases from baseline to 6 weeks in olanzapine-treated patients than those on placebo. The only baseline characteristic associated with response to olanzapine was melancholic feature. LIMITATIONS: The study was limited by omission of patients with bipolar II disorder, post hoc analysis of data from only two clinical trials, and exclusion of suicidal patients. CONCLUSIONS: Olanzapine monotherapy improved core symptoms of depression in patients with bipolar I depression. Additionally, we identified melancholic feature as a baseline factor associated with improved treatment response to olanzapine.

14 Article Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression. 2012

Tohen, Mauricio / McDonnell, David P / Case, Michael / Kanba, Shigenobu / Ha, Kyooseob / Fang, Yi Ru / Katagiri, Hideaki / Gomez, Juan-Carlos. ·University of Texas Health Science Center, Division of Mood and Anxiety Disorders, 7526 Louis Pasteur Drive, San Antonio, TX 78229-3900, USA. tohen@uthscsa.edu ·Br J Psychiatry · Pubmed #22918966.

ABSTRACT: BACKGROUND: Atypical antipsychotics are widely used in bipolar mania. However, the efficacy of atypical antipsychotics in bipolar depression has not been comprehensively explored. AIMS: To evaluate olanzapine monotherapy in patients with bipolar depression. METHOD: Patients with bipolar depression received olanzapine (5-20 mg/day, n = 343) or placebo (n = 171) for 6 weeks. The primary outcome was change from baseline to end-point in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included: Clinical Global Impression - Bipolar Version (CGI-BP) scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young Mania Rating Scale (YMRS) scores, and the rate of response (≥50% reduction in MADRS at end-point), recovery (MADRS ≤12 for ≥4 weeks plus treatment completion) and remission (MADRS ≤8). The trial was registered with ClinicalTrials.gov (NCT00510146). RESULTS: Olanzapine demonstrated: significantly greater (P<0.04) improvements on MADRS (least-squares mean change -13.82 v. -11.67), HRSD-17 and YMRS total scores and all CGI-BP subscale scores v. placebo; significantly (P≤0.05) more response and remission, but not recovery; significantly (P<0.01) greater mean increases in weight, fasting cholesterol and triglycerides; and significantly more (P<0.001) patients gained ≥7% body weight. CONCLUSIONS: Olanzapine monotherapy appears to be efficacious in bipolar depression. Additional long-term studies are warranted to confirm these results. Safety findings were consistent with the known safety profile of olanzapine.

15 Article Variables as mediators or moderators in predicting relapse to any type of mood episode in a bipolar maintenance study. 2012

Tohen, Mauricio / Wang, Wei V / Leboyer, Marion / Jen, Kai Yu. ·Division of Mood and Anxiety Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. tohen@uthscsa.edu ·J Clin Psychiatry · Pubmed #22901362.

ABSTRACT: OBJECTIVE: Post hoc mediator/moderator analyses were designed to identify risk factors and their relationships in predicting relapse in olanzapine- or lithium-treated bipolar patients with an index manic or mixed episode. The aim was to identify moderators that precede and influence other variables to affect relapse and mediators that explain how or why a second variable affects relapse. METHOD: We examined DSM-IV-diagnosed bipolar I disorder patients who met symptomatic remission criteria of an index manic or mixed (6.3%) episode after acute (6-12 weeks), open-label, combined therapy with olanzapine (5-20 mg/d; mean dose = 13.5 mg/d) plus lithium (300-1,800 mg/d; mean dose = 1,003.3 mg/d) followed by double-blind randomization to lithium (n = 214) or olanzapine (n = 217) for up to 52 weeks. The study started on August 5, 1999, and finished on June 14, 2002. Mediator/moderator analyses with α cut at .05 were used to understand how variables work together to impact rate of relapse. RESULTS: For lithium-treated patients, variables identified for relapse were country of residence, smoking status, previous episode history, and previous lithium use. For olanzapine-treated patients, risk factors included smoking status, previous episode history, amount of time patients had a 21-Item Hamilton Depression Rating Scale (HDRS-21) score ≤ 8 at pre-randomization, and HDRS-21 score at randomization. For lithium-treated patients, no mediators/moderators were identified among relapse variables. For olanzapine-treated patients, several baseline variables--such as previous number of mood episodes (manic or depressive)--operate through severity of depressive symptoms prior to remission (mediator) to affect relapse rate. On the other hand, the effect of the patient's pre-remission depressive symptoms on outcome is moderated by the polarity of the first episode, whether manic, depressive, or mixed. CONCLUSIONS: Mediators and moderators may provide valuable information in the treatment planning of patients with bipolar disorder and potentially influence treatment outcomes.

16 Article Lamotrigine vs. lamotrigine plus divalproex in randomized, placebo-controlled maintenance treatment for bipolar depression. 2012

Bowden, C L / Singh, V / Weisler, R / Thompson, P / Chang, X / Quinones, M / Mintz, J. ·University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. bowdenc@uthscsa.edu ·Acta Psychiatr Scand · Pubmed #22708645.

ABSTRACT: OBJECTIVE: To compare the maintenance efficacy of lamotrigine (Lam) to combination therapy of Lam+divalproex ER (Div) in recently depressed patients with bipolar disorder (BD). METHOD: We randomized 86 BD I or II patients in a major depressive episode to 8 months of double-blind treatment with Lam+placebo or Lam+Div. To be eligible for randomization, patients had to achieve control of both depressive and manic symptoms during an open phase that included both Lam and Div. RESULTS: Time to depressive episode did not differ significantly by Kaplan-Maier survival analysis (χ2=1.82, df=1, P=0.18). However, several secondary outcomes did show significant differences. The proportion of Lam+placebo patients who had at least one Montgomery-Asberg Depression Rating Scale (MADRS) score≥15 during the maintenance phase was 67% (30/45) compared with 44% (18/41) for the Lam+Div group (χ2=4.51, P=0.03). Among BD I patients assigned to Lam+placebo, 71.4% (25/35) had at least one visit with MADRS score≥15 compared with 36.7% (11/30) among Lam+Div patients (χ2=7.89, df=1, P=0.005). CONCLUSION: Lam+Div generally provided greater maintenance efficacy than Lam alone for depressive indices in recently depressed BD patients.

17 Article Can medication management coordinators help improve continuity of care after psychiatric hospitalization? 2012

Maples, Natalie J / Copeland, Laurel Anne / Zeber, John E / Li, Xueying / Moore, Troy A / Dassori, Albana / Velligan, Dawn Irene / Miller, Alexander L. ·Department of Psychiatry, Division of Schizophrenia and Related Disorders, UT Health Science Center San Antonio, 7703 Floyd Curl Dr., MS 7797, San Antonio, TX 78229, USA. maplesn@uthscsa.edu ·Psychiatr Serv · Pubmed #22476107.

ABSTRACT: OBJECTIVE: This demonstration project examined whether medication management coordinators enhanced continuity of care from inpatient facilities to an outpatient public mental health clinic. METHODS: From 2004 to 2008, patients (N=325) hospitalized with schizophrenia or schizoaffective or bipolar disorder enrolled in a medication management program before discharge or at their first clinic appointment. Medication management coordinators supplemented existing clinic practices by identifying recently hospitalized patients, providing inpatient and outpatient prescribing clinicians with patients' complete medication history, meeting with patients for six months postdischarge to assess clinical status and provide medication education, and advocating guideline-concordant prescribing. Recently discharged patients (N=345) assigned to a different outpatient clinic within the same agency served as the comparison group. Intent-to-treat, repeated-measures analyses for mixed models compared the groups' number of hospital admissions, hospital days, and medication appointments kept and use of nurse or case manager contact hours and emergency or crisis services during the 12 months before enrollment, the six-month intervention, and the six-month follow-up period. RESULTS: After discharge, individuals enrolled in medication management were more likely than comparison patients to attend outpatient appointments, and they had more medication visits and nurse or case manager treatment hours than the comparison group. Use of hospital and crisis or emergency services by all patients decreased. Almost one-third of patients never attended an outpatient appointment after hospital discharge. CONCLUSIONS: Although this program succeeded in improving continuity of care, additional interventions may be required to reduce rehospitalization and crisis care.

18 Article Two-year outcomes in first-episode psychotic depression the McLean-Harvard First-Episode Project. 2012

Tohen, Mauricio / Khalsa, Hari-Mandir K / Salvatore, Paola / Vieta, Eduard / Ravichandran, Caitlin / Baldessarini, Ross J. ·University of Texas Health Science Center at San Antonio, United States; Department of Psychiatry, Harvard Medical School & McLean Hospital, Belmont, MA, United States. Electronic address: tohen@uthscsa.edu. · Department of Psychiatry, Harvard Medical School & McLean Hospital, Belmont, MA, United States. · Department of Psychiatry, Harvard Medical School & McLean Hospital, Belmont, MA, United States; Section of Psychiatry, Department of Neuroscience, University of Parma, Italy. · Department of Psychiatry, Harvard Medical School & McLean Hospital, Belmont, MA, United States; Department of Psychiatry, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Spain. · Laboratory for Psychiatric Biostatistics, McLean Hospital, Belmont, MA, United States. ·J Affect Disord · Pubmed #21943929.

ABSTRACT: OBJECTIVE: Early assessment can guide accurate diagnosis, prognosis, and treatment-planning for patients with major mental illnesses. Longitudinal studies in psychotic depression from onset are rare, encouraging the present study. METHOD: We followed 56 DSM-IV MDD patients with psychotic features prospectively and systematically to assess course and predictors of operationally-defined syndromal remission, syndromal recovery, symptomatic remission, functional recovery, and new episodes, and to evaluate diagnostic stability. RESULTS: Among 49/56 cases followed for ≥2 years, 59% retained the initial diagnosis and most achieved syndromal remission (86%) and recovery (84%); 58% remitted symptomatically, and only 35% (17/49) recovered functionally. Syndromal recovery was earlier following subacute onset, lower initial depression scores, and lack of moodincongruent psychotic features. Within 2 years, 45% (22/49) experienced new episodes - earlier with younger onset and higher CGI scores. DSM diagnosis changed in 41%, to bipolar (33%), or schizoaffective disorders (12%), which followed early mania-like or schizophrenia-like features, respectively. CONCLUSIONS: Within 2 years of first-hospitalizations, 41% of patients initially diagnosed with psychotic-depression met criteria for DSM-IV bipolar or schizoaffective disorders. Of the 59% retaining the initial diagnosis for 2 years, nearly half experienced new episodes, 42% remained symptomatic, and two-thirds failed to regain their own prior functional status.

19 Article Pharmacological treatments for bipolar disorder: present recommendations and future prospects. 2011

Bowden, Charles L. ·University of Texas Health Science Center, 7703 Floyd Curl Dr, San Antonio, TX, 78229-3900, USA, BowdenC@uthscsa.edu. ·Curr Top Behav Neurosci · Pubmed #25236560.

ABSTRACT: In selecting and adapting medications to treat the specific clinical features of a patient with bipolar disorder (BPD) over time, a foundation strategy is to have good working knowledge of up-to-date practice guidelines. The World Federation of Societies of Biological Psychiatry Guidelines has the reasoned advantage of weighing safety/tolerability as high as efficacy. Most successful treatments for BPD start to separate from placebo within 1 week; most differences between regimens occur within the first 4 weeks. This observation extrapolates to a strategy of discontinuing or adding a second drug for symptoms unimproved within 1 month of treatment initiation. The weight of evidence argues against starting treatment with combination regimens, despite evidence that over time most patients do receive combination drug regimens and appear to tolerate them well. The current design paradigm for adjunctive trials generally strongly weights trials in favor of the sponsor drug.Well managed, BPD is often compatible with fully good health, both symptomatically and functionally. Consequently, for whatever regimens are found to accomplish excellent symptom control, it is important to achieve regimens that are well tolerated by all bodily systems. This chapter emphasizes the tactics needed to accomplish this specific to individual medications. The chapter also addresses the serious, broad failure of pharmaceutical companies to develop new drugs with novel mechanisms for BPD therapy and proposes a series of steps that might reenergize drug development to the benefit of psychiatrists and patients alike.

20 Article Medication adherence, ethnicity, and the influence of multiple psychosocial and financial barriers. 2011

Zeber, John E / Miller, Alexander L / Copeland, Laurel A / McCarthy, John F / Zivin, Kara / Valenstein, Marcia / Greenwald, Devra / Kilbourne, Amy M. ·Veterans Affairs HSR&D: South Texas Veterans Health Care System (VERDICT), 7400 Merton Minter Boulevard, San Antonio, TX 78229-4404, USA. zeber@uthscsa.edu ·Adm Policy Ment Health · Pubmed #20549327.

ABSTRACT: Medication adherence is critical for patients with bipolar disorder to avoid symptom exacerbation and diminished quality of life. Most analyses consider adherence barriers individually rather than conjointly, while neglecting potential ethnic differences. 435 patients in the Continuous Improvement for Veterans in Care--Mood Disorders study reported multiple financial and psychosocial factors influencing adherence. Logistic regression modeled adherence as a function of perceived barriers, including cost burden, access, binge drinking, poor therapeutic alliance, and medication beliefs. Nearly half the cohort experienced adherence difficulty, averaging 2.8 barriers, with minority veterans reporting lower adherence than white patients, particularly financial burden and treatment access. Total barriers were significantly associated with worse adherence (OR = 1.24 per barrier), notably poor medication beliefs, binge drinking, and difficulty accessing psychiatric specialists (ORs of 2.41, 1.95 and 1.73, respectively). Veterans with bipolar disorder experience numerous adherence barriers, with certain obstacles proving especially pernicious. Fortunately tailored clinical interventions can improve adherence, particularly by addressing modifiable risk factors.

21 Article Sexual abuse and posttraumatic stress disorder in adult women with severe mental illness: a pilot study. 2010

Bonugli, Rebecca / H Brackley, Margaret / Williams, Gail B / Lesser, Janna. ·The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. bonuglir@uthscsa.edu ·Issues Ment Health Nurs · Pubmed #20521915.

ABSTRACT: Research indicates that women with serious mental illness (SMI) are vulnerable to sexual abuse, resulting in adverse health outcomes such as posttraumatic stress disorder (PTSD). The purpose of this pilot study was to examine the prevalence of undiagnosed PTSD among a cohort of 20 women with SMI and reporting past sexual abuse. Furthermore, the researcher sought to identify specific symptom manifestations of PTSD among women with SMI and sexual abuse histories. Finally, the feasibility of using specific data collection tools was examined. Results indicated that PTSD was not previously diagnosed or recognized in the study sample, in spite of the presence of a sexual trauma history. The screening tools were effective in identifying depression, guilt, emotional withdrawal, blunted affect, decreased psychomotor activity, suicidal ideations, sexual dysfunction, and substance abuse. Additionally, the data collection tools provided a framework for discussing sensitive issues related to sexual abuse. Implications of this pilot study suggest the need to evaluate all women with SMI and history of sexual abuse for PTSD.

22 Article One-year treatment outcomes of African-American and Hispanic patients with bipolar I or II disorder in STEP-BD. 2010

Gonzalez, Jodi M / Bowden, Charles L / Berman, Nancy / Frank, Ellen / Bauer, Mark S / Kogan, Jane N / Alegría, Margarita / Miklowitz, David J. ·Department of Psychiatry, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA. gonzalezjm1@uthscsa.edu ·Psychiatr Serv · Pubmed #20123822.

ABSTRACT: OBJECTIVE: Few studies have compared treatment outcomes of African-American, Hispanic, and non-Hispanic white patients with bipolar disorder. The U.S. Systematic Treatment Enhancement Program for Bipolar Disorder compared one-year outcomes for bipolar I or II disorder from each of these racial-ethnic groups. METHODS: African Americans (N=155) were retrospectively compared with a matched group of non-Hispanic whites (N=729), and Hispanics (N=152) were compared with a separate matched group of non-Hispanic whites (N=822). Response and recovery outcomes were examined. Survival analysis was used to compare time to treatment response for depression (Montgomery-Asberg Depression Rating Scale) and mania (Young Mania Rating Scale) as well as global assessment of functioning (Global Assessment of Functioning). RESULTS: For manic and depressive symptoms, time to response and proportion of responders were similar across groups. Over the study year the proportion of days well was similar across groups. A smaller proportion of African Americans met criteria for improved global functioning. Depression response among African Americans with psychotic symptoms was slower than the response among African Americans without psychotic symptoms and among non-Hispanic whites with or without psychotic symptoms. No differences between Hispanics and non-Hispanic whites in response times and recovery were observed. CONCLUSIONS: Results are consistent with U.S. clinical trials for other psychiatric disorders, which have reported similar outcomes for ratings of primary symptoms. Baseline psychotic symptoms are likely a significant contributor when African Americans with bipolar disorder are slow to recover. These results may be less generalizable to uninsured patients.

23 Article Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind trial. 2010

Bowden, Charles L / Vieta, Eduard / Ice, Kathleen S / Schwartz, Jeffrey H / Wang, Paul P / Versavel, Mark. ·Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX 78229, USA. bowdenc@uthscsa.edu ·J Clin Psychiatry · Pubmed #20122373.

ABSTRACT: OBJECTIVE: To evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania. METHOD: Subjects with DSM-IV bipolar I disorder with a Mania Rating Scale score > or = 14 were enrolled. Subjects achieving > or = 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or valproate (period 1) were randomly assigned in the 6-month, double-blind maintenance period (period 2) to ziprasidone plus mood stabilizer or placebo plus mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (log-rank test). The study was conducted from December 2005 to May 2008. RESULTS: A total of 127 and 113 subjects were randomly assigned to ziprasidone and placebo, respectively. Intervention for a mood episode was required in 19.7% and 32.4% of ziprasidone and placebo subjects, respectively. The time to intervention for a mood episode was significantly longer for ziprasidone than placebo (P = .0104). The median time to intervention for a mood episode among those requiring such an intervention (n = 61) was 43.0 days for ziprasidone versus 26.5 days for placebo. The time to discontinuation for any reason was significantly longer for ziprasidone (P = .0047). Adjunctive ziprasidone treatment was well tolerated. Among treatment-emergent adverse events occurring in > or = 5% of subjects in either treatment group during period 2, only tremor occurred more frequently in the ziprasidone versus placebo group (6.3% vs 3.6%). CONCLUSIONS: Ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00280566.

24 Article Efficacy of valproate versus lithium in mania or mixed mania: a randomized, open 12-week trial. 2010

Bowden, Charles L / Mosolov, Sergey / Hranov, Luchezar / Chen, Eric / Habil, Hussain / Kongsakon, Ronnachai / Manfredi, Robert / Lin, Hsin-Nan. ·Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. bowdenc@uthscsa.edu ·Int Clin Psychopharmacol · Pubmed #20101186.

ABSTRACT: The objective of this study was to compare the efficacy and safety of valproate and lithium in bipolar I patients experiencing a manic or a mixed episode. This international, randomized, open-label, parallel-group, equivalence study included 268 patients with bipolar I disorder. The starting dose of valproate was 20 mg/kg/day and that of lithium was 800 mg/day. Treatment duration was 12 weeks. The primary outcome measure was mean change in Young Mania Rating Scale score between baseline and study end. Secondary outcome measures were response and remission rates, change in Montgomery and Asberg Depression Rating Scale and Clinical Global Impression Bipolar Disorder instrument score, and occurrence of adverse events. The mean change from baseline in Young Mania Rating Scale score was 15.8+/-5.3 in the lithium group and 17.3+/-9.4 in the valproate group. The 90% confidence interval of the intergroup difference (-0.69; 3.31) was within prespecified equivalence limits. Response rates were 72.6% in the lithium group and 79.5% in the valproate group. Remission rates were 58.5 and 71.9%, respectively. No intergroup differences were observed in median time to treatment response (21 days) or change in Clinical Global Impression Bipolar Disorder instrument or Montgomery and Asberg Depression Rating Scale scores. Adverse events were reported in 42.8% of patients in the lithium group and 41.5% in the valproate group. Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks.