Publications by authors named "Mauricio Tohen"

224 Publications

Response and remission rates during 24 weeks of mood-stabilizing treatment for bipolar depression depending on early non-response.

Psychiatry Res 2021 Aug 29;305:114194. Epub 2021 Aug 29.

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.

Background: We aimed to study the probability of bipolar depression response at 24 weeks given initial non-response.

Methods: We combined two multi-site, 24-week trials including similar populations following the same evidence-based guidelines randomizing patients to lithium or quetiapine. Additional mood-stabilizing treatment was possible if clinically indicated. We report cumulative proportions of response (>50% improvement in MADRS) and remission (MADRS<10).

Results: We included 592 participants with bipolar depression (mean 39 years, 59% female, mean MADRS 25). Among 393 (66%) participants without response after 2 weeks, 46% responded by 24 weeks; for 291 (49%) without response at 4 weeks, 40% responded and 33% remitted by 24 weeks; for 222 (38%) without a response at 6 weeks, 36% responded and 29% remitted by 24 weeks; for 185 (31%) without a response at 8 weeks, 29% responded and 24% remitted by 24 weeks. Rates were similar for participants who had started an additional mood-stabilizing drug during the first 6 or 8 weeks.

Conclusions: Among patients with bipolar depression and non-response after 6 weeks treatment, representing an adequate bipolar depression trial, only one-third responded by 24 weeks. These results highlight the need for better treatment alternatives for non-responders to evidence-based treatments for bipolar depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2021.114194DOI Listing
August 2021

Preventing new episodes of bipolar disorder in adults: Systematic review and meta-analysis of randomized controlled trials.

Eur Neuropsychopharmacol 2021 Sep 3. Epub 2021 Sep 3.

Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, United States.

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p<0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19-0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25-0.55, p<0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euroneuro.2021.08.264DOI Listing
September 2021

Consensus on nomenclature for clinical staging models in bipolar disorder: A narrative review from the International Society for Bipolar Disorders (ISBD) Staging Task Force.

Bipolar Disord 2021 Jun 26. Epub 2021 Jun 26.

St. Joseph's Healthcare Hamilton McMaster University, Hamilton, ON, Canada.

Objectives: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking.

Methods: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders.

Results: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed.

Conclusion: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bdi.13105DOI Listing
June 2021

Increased Glutamate Plus Glutamine in the Right Middle Cingulate in Early Schizophrenia but Not in Bipolar Psychosis: A Whole Brain H-MRS Study.

Front Psychiatry 2021 7;12:660850. Epub 2021 Jun 7.

Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, United States.

Proton magnetic resonance spectroscopy (H-MRS) studies have examined glutamatergic abnormalities in schizophrenia and bipolar-I disorders, mostly in single voxels. Though the critical nodes remain unknown, schizophrenia and bipolar-I involve brain networks with broad abnormalities. To provide insight on the biochemical differences that may underlie these networks, the combined glutamine and glutamate signal (Glx) and other metabolites were examined in patients in early psychosis with whole brain H-MRS imaging (H-MRSI). Data were acquired in young schizophrenia subjects ( = 48), bipolar-I subjects ( = 21) and healthy controls ( = 51). Group contrasts for Glx, as well as for N-acetyl aspartate, choline, myo-inositol and creatine, from all voxels that met spectral quality criteria were analyzed in standardized brain space, followed by cluster-corrected level alpha-value (CCLAV ≤ 0.05) analysis. Schizophrenia subjects had higher Glx in the right middle cingulate gyrus (19 voxels, CCLAV = 0.05) than bipolar-I subjects. Healthy controls had intermediate Glx values, though not significant. Schizophrenia subjects also had higher N-acetyl aspartate (three clusters, left occipital, left frontal, right frontal), choline (two clusters, left and right frontal) and myo-inositol (one cluster, left frontal) than bipolar-I, with healthy controls having intermediate values. These increases were likely accounted for by antipsychotic medication effects in the schizophrenia subgroup for N-acetyl aspartate and choline. Likewise, creatine was increased in two clusters in treated vs. antipsychotic-naïve schizophrenia, supporting a medication effect. Conversely, the increments in Glx in right cingulate were not driven by antipsychotic medication exposure. We conclude that increments in Glx in the cingulate may be critical to the pathophysiology of schizophrenia and are consistent with the NMDA hypo-function model. This model however may be more specific to schizophrenia than to psychosis in general. Postmortem and neuromodulation schizophrenia studies focusing on right cingulate, may provide critical mechanistic and therapeutic advancements, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.660850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215955PMC
June 2021

Illness stage and predominant polarity in bipolar disorder: Correlation with burden of illness and moderation of treatment outcome.

J Psychiatr Res 2021 08 2;140:205-213. Epub 2021 Jun 2.

Dauten Family Center for Bipolar Treatment Innovation, Department of Psychiatry, Massachusetts General Hospital, 50 Staniford Street, Suite 580, Boston, MA, 02114, United States; Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, United States. Electronic address:

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo/manic episodes (termed predominant hypo/manic polarity). We examined the associations between staging and predominant polarity with measures of illness burden and treatment outcome utilizing data from a six-month comparative effectiveness trial of lithium and quetiapine in bipolar disorder (Bipolar CHOICE). We used number of self-reported lifetime mood (depressive and hypo/manic) episodes as a proxy for staging and ratio of depressive to manic episodes to define predominant polarity. Polarity and staging were correlated with several measures of burden of illness. Childhood abuse was correlated with more lifetime mood episodes, while more depressive episodes and depressive polarity were correlated with more anxiety disorder comorbidity. Depressive polarity was also correlated with more past trials of psychotropics, particularly antidepressants. However, neither staging nor predominant polarity moderated the randomized treatment effect of lithium vs. quetiapine. Number of depressive episodes in the past year was identified as a potential predictor of overall worse treatment outcome, regardless of medication condition. In conclusion, though staging and predominant episode polarity correlated with several measures of illness burden, they were not associated with differential treatment outcomes. This could be because many of our patients presented for treatment at advanced stages of illness and further highlights the need for early intervention in bipolar disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2021.05.082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319086PMC
August 2021

Development of a Patient-Centered Software System to Facilitate Effective Management of Bipolar Disorder.

Psychopharmacol Bull 2021 Mar;51(2):8-19

Bowden, M.D., Emeritus Professor, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Priesmeyer, PhD., Jurica Professor of Management, Department of Management and Marketing, St Mary's University, San Antonio, Texas. Tohen, M.D., Dr.P.H., M.B.A, University Distinguished Professor and Chairman, Department of Psychiatry and Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico. Singh, M.D., Deceased. Calabrese, M.D., Director, Mood Disorders Program, UH Cleveland Medical Center Case Western Reserve University School of Medicine, Cleveland, Ohio. Ketter, M.D, Emeritus Professor, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. Nierenberg, M.D., Director, Dauten Family Center for Bipolar Treatment Innovation Massachusetts General Hospital, Harvard Medical School. Thase, M.D., Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Gregg Siegel, M.S, Biomedical Development Corporation, San Antonio, Texas. Leslie H. Siegel, M.F.A, Biomedical Development Corporation, San Antonio, Texas. Mintz, PhD., Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Mallakh, M.D., Mood Disorders Research Program, Depression Center, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, Kentucky. McElroy, M.D., Professor of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio. Martinez, M.D., Professor and Mary Avis Weir Chair in Psychiatry, Director, Adult Mood Disorders Program, Co-Director, Mind, Brain, and Behavior, Department of Psychiatry and Behavioral Sciences University of Texas Health Science Center San Antonio, San Antonio, Texas.

Objective: Self-management of bipolar disorder (BD) is an important component of treatment.

Methods: We developed a patient-centered computational software system based on concepts from nonlinear systems (chaos) theory with mobile access to assist in managing BD known as KIOS. KIOS tracks interacting symptoms to determine theprecise state of a BD patient. Once the patient's state is identified and the trajectory of the patient established, specific advice is generated to help manage the course of the disease. KIOS also provides analytics that can be used by clinicians and researchers to track outcomes and the course of illness. A 12-week field test was completed.

Results: In 20 BD subjects, use of KIOS was associated with improvements in primary symptom categories of BD. Usability and generated advice were rated as a median of 6 out of a maximum of 7.

Conclusions: The KIOS focus on change illuminates problems in the same way that humans experience them, implying that the future state will be consequent to changes made to impact the current state. Randomized clinical trial is indicated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146566PMC
March 2021

Characteristics of Hispanics Referred to Coordinated Specialty Care for First-Episode Psychosis and Factors Associated With Enrollment.

Psychiatr Serv 2021 Jun 2:appips202000798. Epub 2021 Jun 2.

Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque.

Objective: The primary objectives of this study were to examine referral sources and demographic, clinical, and socioenvironmental characteristics of Hispanics referred to and enrolled in a program of coordinated specialty care (Early CSC program) for first-episode psychosis, to compare them with characteristics of other referred and enrolled racial-ethnic groups, and to identify factors associated with enrollment in the program.

Methods: A retrospective review was conducted for all individuals referred to and enrolled in the Early CSC program over a 2-year period. Extracted data included referral sources and demographic and clinical characteristics. Zip code-level data from publicly available sources were cross-referenced with individual records. Nonparametric tests and appropriate secondary analysis were used to determine significant differences across racial-ethnic groups referred to (N=180) or enrolled in (N=75) the Early CSC program. A random forest model was used to determine which factors or interacting factors were associated with enrollment among the eligible referrals (N=114).

Results: Hispanic individuals were more likely to be referred from inpatient or outpatient mental health providers and not from other community sources. Among eligible Hispanic referrals, those who lived in areas with a lower percentage of Spanish speaking in the home were more likely to enroll in services, compared with those who lived in areas with a higher percentage of Spanish speaking.

Conclusions: Continued exploration of factors associated with referral and enrollment in CSC programs for the growing Hispanic ethnic group in the United States can help determine best steps for developing these programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ps.202000798DOI Listing
June 2021

The efficacy of cariprazine on function in patients with bipolar depression: a  analysis of a randomized controlled trial.

Curr Med Res Opin 2021 09 7;37(9):1635-1643. Epub 2021 Jun 7.

AbbVie, Madison, NJ, USA.

Introduction: Individuals with bipolar depression often experience functional impairment that interferes with recovery. These analyses examined the effects of cariprazine on functional outcomes in patients with bipolar I disorder.

Methods: Prespecified analyses of data from a randomized, double-blind, placebo-controlled pivotal trial of cariprazine in bipolar I depression (NCT01396447) evaluated mean changes from baseline to week 8 in Functional Assessment Short Test (FAST) total score. analyses with no adjustment for multiplicity evaluated FAST subscale scores, functional recovery and remission (FAST total score ≤11 and ≤20, respectively), and 30% or 50% improvement from baseline.

Results: There were 393 patients with bipolar I disorder (placebo = 132; cariprazine: 1.5 mg/d = 135, 3 mg/d = 126) in the FAST analysis population. Statistically significant differences were noted for cariprazine 1.5 mg/d versus placebo in mean change from baseline in FAST total score (<.01) and on 5 of 6 subscale scores (<.05); cariprazine 3 mg/d was significantly different than placebo on the Interpersonal Relationship subscale (<.05). Rates of functional remission and recovery, and ≥30% or ≥50% improvement were significantly greater for cariprazine 1.5 mg/d versus placebo (<.05 all); the percentage of patients with ≥30% improvement was significantly different for cariprazine 3 mg/d versus placebo (<.05).

Conclusion: At week 8, statistically significant improvements in FAST outcomes were observed for cariprazine versus placebo in patients with bipolar I depression; more consistent results were noted for 1.5 mg/d than 3 mg/d. In addition to improving bipolar depression symptoms, these results suggest that cariprazine may improve functional outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03007995.2021.1932446DOI Listing
September 2021

Cariprazine as a Treatment Option for Depressive Episodes Associated with Bipolar 1 Disorder in Adults: An Evidence-Based Review of Recent Data.

Authors:
Mauricio Tohen

Drug Des Devel Ther 2021 12;15:2005-2012. Epub 2021 May 12.

Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.

Depressive episodes, the most frequent episodes in bipolar disorder, contribute in large part to poor functional outcomes. Very few treatments, however, have been approved by the Food and Drug Administration for the treatment of bipolar depression. Cariprazine, a broad-spectrum dopamine antagonist/partial agonist with dopamine D3/D2 (preferring D3) and serotonin 5-HT1A receptor partial agonist properties, was recently approved. A review of the literature suggests that it is an effective and well-tolerated treatment for bipolar depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S240860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126799PMC
May 2021

White Matter Abnormalities in Late Onset First Episode Mania: A Diffusion Tensor Imaging Study.

Am J Geriatr Psychiatry 2021 Mar 26. Epub 2021 Mar 26.

Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine.

Introduction: A first manic episode after 50 years of age is uncommon. Late Onset Mania might be indicative of abnormalities in white matter, probably related to vascular, degenerative, or inflammatory processes.

Objective: To determine if patients with late onset mania have reduced white matter integrity according to Magnetic Resonance Diffusion Tensor Imaging (DTI) and structural MRI.

Methods: Twenty-two patients with late onset mania (>50 years old) and 22 age-paired healthy subjects were included in the study. Fractional anisotropy (FA) was used as a quantitative measure of white matter integrity. Fazekas scale was assessed also to measure white matter abnormalities in the FLAIR sequence. The Frontal Assessment Battery, COGNISTAT and Trail making test A and B were used as cognitive measurements.

Results: According to DTI, commissural connections (left corpus callosum), and limbic connections (right and left uncinate fasciculus) were different between the patients and the comparison group. Fractional anisotropy values in the left corpus callosum showed significant correlations with neuropsychological measures, and with the Fazekas scale score. According to Fazekas scale, a pathological score in the FLAIR sequence was significantly more frequent in the patients as compared to the comparison group.

Conclusions: Patients with first episode mania in late life have relevant white matter abnormalities not explained by age, affecting interhemispheric and fronto-limbic networks probably related to executive functioning and emotional processing, at the level of the corpus callosum and the uncinate fasciculus. The etiology of this white matter loss of integrity in patients with late-onset mania is yet to be explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jagp.2021.03.007DOI Listing
March 2021

White Matter Abnormalities in Late Onset First Episode Mania: A Diffusion Tensor Imaging Study.

Am J Geriatr Psychiatry 2021 Mar 26. Epub 2021 Mar 26.

Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine.

Introduction: A first manic episode after 50 years of age is uncommon. Late Onset Mania might be indicative of abnormalities in white matter, probably related to vascular, degenerative, or inflammatory processes.

Objective: To determine if patients with late onset mania have reduced white matter integrity according to Magnetic Resonance Diffusion Tensor Imaging (DTI) and structural MRI.

Methods: Twenty-two patients with late onset mania (>50 years old) and 22 age-paired healthy subjects were included in the study. Fractional anisotropy (FA) was used as a quantitative measure of white matter integrity. Fazekas scale was assessed also to measure white matter abnormalities in the FLAIR sequence. The Frontal Assessment Battery, COGNISTAT and Trail making test A and B were used as cognitive measurements.

Results: According to DTI, commissural connections (left corpus callosum), and limbic connections (right and left uncinate fasciculus) were different between the patients and the comparison group. Fractional anisotropy values in the left corpus callosum showed significant correlations with neuropsychological measures, and with the Fazekas scale score. According to Fazekas scale, a pathological score in the FLAIR sequence was significantly more frequent in the patients as compared to the comparison group.

Conclusions: Patients with first episode mania in late life have relevant white matter abnormalities not explained by age, affecting interhemispheric and fronto-limbic networks probably related to executive functioning and emotional processing, at the level of the corpus callosum and the uncinate fasciculus. The etiology of this white matter loss of integrity in patients with late-onset mania is yet to be explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jagp.2021.03.007DOI Listing
March 2021

Real-World Patterns of Utilization and Costs Associated with Second-Generation Oral Antipsychotic Medication for the Treatment of Bipolar Disorder: A Literature Review.

Neuropsychiatr Dis Treat 2021 16;17:515-531. Epub 2021 Feb 16.

Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.

Objective: Treatment with second-generation antipsychotics (SGAs) for bipolar disorder, including bipolar I disorder (BD-I), is common. This review evaluated real-world utilization patterns with oral SGAs in the United States (US) for bipolar disorder (and BD-I specifically when reported) and economic burden associated with these patterns.

Methods: Structured, systematic searches of MEDLINE, EMBASE, and National Health Service Economic Evaluation Database identified primary research studies (published 2008-2018) describing real-world SGA use in adults with bipolar disorder/BD-I.

Results: Among 769 studies screened, 39 met inclusion criteria. Most studies (72%) were analyses of commercial or Medicare/Medicaid claims databases. Patient-related (eg, demographic, comorbidities) and disease-related (eg, mania, psychosis) factors were associated with prescribed SGA. Suboptimal utilization patterns (ie, nonadherence, nonpersistence, treatment gaps, medication switching, and discontinuation) were common for patients treated with SGAs. Also common were SGAs prescribed with another psychotropic medication and SGA combination treatment (use of ≥2 SGAs concurrently). Suboptimal adherence and SGA combination treatment were both associated with increased health care resource use (HCRU); suboptimal adherence was associated with higher total direct medical and indirect costs.

Limitations: Different definitions for populations and concepts limited between-study comparisons. Focusing on SGAs limits contextualizing findings within the broader treatment landscape (eg, lithium, anticonvulsants). Given the nature of claims data, prescribing rationale (eg, acute episodes vs maintenance) and factors influencing observed utilization patterns could not be fully derived.

Conclusion: Despite increased use of SGAs to treat bipolar disorder over the last decade, reports of suboptimal utilization patterns of SGAs (eg, nonadherence, nonpersistence) were common as was combination treatment. Patterns of SGA use associated with additional HCRU and/or costs were suboptimal adherence and SGA combination treatment; economic consequences associated with other utilization patterns (eg, nonpersistence) were unclear. Strategies to improve SGA treatment continuity, particularly adherence, may improve clinical and economic outcomes among people living with bipolar disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NDT.S280051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896797PMC
February 2021

Interpreting the Findings of a Meta-analysis of Psychosocial Interventions in Bipolar Disorder.

JAMA Psychiatry 2021 Apr;78(4):447-448

Department of Psychiatry and Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapsychiatry.2020.4412DOI Listing
April 2021

Neuroimaging Biomarkers in Schizophrenia.

Am J Psychiatry 2021 06 5;178(6):509-521. Epub 2021 Jan 5.

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham (Kraguljac); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (McDonald); Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis (Widge); Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif., and Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. (Rodriguez); Department of Psychiatry and Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque (Tohen); Department of Psychiatry, University of Texas Dell Medical School, Austin (Nemeroff).

Schizophrenia is a complex neuropsychiatric syndrome with a heterogeneous genetic, neurobiological, and phenotypic profile. Currently, no objective biological measures-that is, biomarkers-are available to inform diagnostic or treatment decisions. Neuroimaging is well positioned for biomarker development in schizophrenia, as it may capture phenotypic variations in molecular and cellular disease targets, or in brain circuits. These mechanistically based biomarkers may represent a direct measure of the pathophysiological underpinnings of the disease process and thus could serve as true intermediate or surrogate endpoints. Effective biomarkers could validate new treatment targets or pathways, predict response, aid in selection of patients for therapy, determine treatment regimens, and provide a rationale for personalized treatments. In this review, the authors discuss a range of mechanistically plausible neuroimaging biomarker candidates, including dopamine hyperactivity, -methyl-d-aspartate receptor hypofunction, hippocampal hyperactivity, immune dysregulation, dysconnectivity, and cortical gray matter volume loss. They then focus on the putative neuroimaging biomarkers for disease risk, diagnosis, target engagement, and treatment response in schizophrenia. Finally, they highlight areas of unmet need and discuss strategies to advance biomarker development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ajp.2020.20030340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222104PMC
June 2021

Long-term treatment of bipolar disorder type I: A systematic and critical review of clinical guidelines with derived practice algorithms.

Bipolar Disord 2021 06 7;23(4):324-340. Epub 2021 Jan 7.

Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, Institute of Neuroscience, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.

Objectives: This systematic review aimed at providing a critical, comprehensive synthesis of international guidelines' recommendations on the long-term treatment of bipolar disorder type I (BD-I).

Methods: MEDLINE/PubMed and EMBASE databases were searched from inception to January 15th, 2019 following PRISMA and PICAR rules. International guidelines providing recommendations for the long-term treatment of BD-I were included. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.

Results: The final selection yielded five international guidelines, with overall good quality. The evaluation of applicability was the weakest aspect across the guidelines. Differences in their updating strategies and the rating of the evidence, particularly for meta-analyses, randomized clinical trials (RCTs) and observational studies, could be responsible of some level of heterogeneity among recommendations. Nonetheless, the guidelines recommended lithium as the 'gold standard' in the long-term treatment of BD-I. Quetiapine was another possible first-line option as well as aripiprazole (for the prevention of mania). Long-term treatment should contemplate monotherapy, at least initially. Clinicians should check regularly for efficacy and side effects and if necessary, switch to first-line alternatives (i.e. Valproate), combine first-line compounds with different mechanisms of action or switch to second-line options or combinations.

Conclusions: The possibility to monitor improvements in long-term outcomes, namely relapse prevention and inter-episode subthreshold depressive symptoms, based on the application of their recommendations is an unmet need of clinical guidelines. In terms of evidence of clinical guidelines, there is a need for more efficacious treatment strategies for the prevention of bipolar depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bdi.13040DOI Listing
June 2021

Efficacy of cariprazine in bipolar I depression across patient characteristics: a post hoc analysis of pooled randomized, placebo-controlled studies.

Int Clin Psychopharmacol 2021 03;36(2):76-83

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

Patients who experience bipolar depression have diverse demographic and clinical characteristics that have the potential to impact treatment. The efficacy of cariprazine in bipolar I depression was evaluated in patient subgroups defined by baseline demographic and clinical characteristics. Post hoc analyses of data from three randomized, double-blind, placebo-controlled trials in bipolar I depression (NCT01396447, NCT02670538 and NCT02670551) evaluated mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores for pooled cariprazine 1.5-3 mg/d versus placebo in subgroups defined by demographic and clinical characteristics. The least-squares mean difference in MADRS total score change from baseline was statistically significant for cariprazine 1.5-3 mg/d versus placebo in all patient subgroups analyzed (P < 0.05 all subgroups): demographic characteristics (age, sex, white or black race and obese/nonobese BMI); episode characteristics (defined by current episode duration, number of previous manic/mixed and depressive episodes, and prior bipolar disorder medication use) and disease severity (groups above and below Clinical Global Impressions-Severity and MADRS cutoff scores). Cariprazine 1.5-3 mg/d consistently improved depressive symptoms in all patient subgroups without regard to differences in baseline demographic and clinical characteristics, suggesting broad efficacy across a spectrum of patients with bipolar I depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/YIC.0000000000000344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846289PMC
March 2021

Long-term morbidity in major affective and schizoaffective disorders following hospitalization in first psychotic episodes.

Acta Psychiatr Scand 2021 01 28;143(1):50-60. Epub 2020 Oct 28.

International Consortium for Mood & Psychotic Disorders, Mailman Research Center, McLean Hospital, Belmont, MA, USA.

Objective: To evaluate morbidity during long-term follow-up with clinical treatment of affective and schizoaffective disorder subjects followed from hospitalization for first major psychotic episodes.

Methods: We followed adult subjects systematically at regular intervals from hospitalization for first-lifetime episodes of major affective and schizoaffective disorders with initial psychotic features. We compiled % of days with morbidity types from detailed records and life charts, reviewed earliest antecedent morbidities, compared both with final diagnoses and initial presenting illness types, and evaluated morbidity risk factors with regression modeling.

Findings: With final diagnoses of bipolar-I (BD-I, n = 216), schizoaffective (SzAffD, 71), and major depressive (MDD, 42) disorders, 329 subjects were followed for 4.47 [CI: 4.20-4.47] years. Initial episodes were mania (41.6%), mixed states (24.3%), depression (19.5%), or apparent nonaffective psychosis (14.6%). Antecedent morbidity presented 12.7 years before first episodes (ages: SzAffD ≤ BD-I < MDD). Long-term % of days ill ranked SzAffD (83.0%), MDD (57.8%), BD-I (45.0%). Morbidity differed by diagnosis and first-episode types, and was predicted by first episodes and suggested by antecedent illnesses. Long-term wellness was greater with BD-I diagnosis, first episode not mixed or psychotic nonaffective, rapid onset, and being older at first antecedents, but not follow-up duration.

Conclusions: Initially, psychotic BD-I, SzAffD, or MDD subjects followed for 4.47 years from first hospitalization experienced much illness, especially depressive or dysthymic, despite ongoing clinical treatment. Antecedent symptoms arose years before index first episodes; antecedents and first episode types predicted types and amounts of long-term morbidity, which ranked: SzAffD > MDD > BD-I.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acps.13243DOI Listing
January 2021

Social media recruitment for mental health research: A systematic review.

Compr Psychiatry 2020 11 12;103:152197. Epub 2020 Aug 12.

Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA. Electronic address:

Background: Social media holds exciting promise for advancing mental health research recruitment, however, the extent and efficacy to which these platforms are currently in use are underexplored.

Objective: A systematic review was conducted to characterize the current use and efficacy of social media in recruiting participants for mental health research.

Method: A literature review was performed using MEDLINE, EMBASE, and PsychINFO. Only non-duplicative manuscripts written in the English language and published between 1/1/2004-3/31/2019 were selected for further screening. Data extracted included study type and design, participant inclusion criteria, social media platform, advertising strategy, final recruited sample size, recruitment location, year, monetary incentives, comparison to other recruitment methods if performed, and final cost per participant.

Results: A total of 176 unique studies that used social media for mental health research recruitment were reviewed. The majority of studies were cross-sectional (62.5%) in design and recruited adults. Facebook was overwhelmingly the recruitment platform of choice (92.6%), with the use of paid advertisements being the predominant strategy (60.8%). Of the reviewed studies, substance abuse (43.8%) and mood disorders (15.3%) were the primary subjects of investigation. In 68.3% of studies, social media recruitment performed as well as or better than traditional recruitment methods in the number and cost of final enrolled participants. The majority of studies used Facebook for recruitment at a median cost per final recruited study participant of $19.47. In 55.6% of the studies, social media recruitment was the more cost-effective recruitment method when compared to traditional methods (e.g., referrals, mailing).

Conclusion: Social media appears to be an effective and economical recruitment tool for mental health research. The platform raises methodological and privacy concerns not covered in current research regulations that warrant additional consideration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.comppsych.2020.152197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704547PMC
November 2020

The Economic Burden of Bipolar Disorder in the United States: A Systematic Literature Review.

Clinicoecon Outcomes Res 2020 7;12:481-497. Epub 2020 Sep 7.

Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.

Bipolar disorder (BD) is a mood disorder with subtypes characterized by episodes of mania, hypomania, and/or depression. BD is associated with substantial economic burden, and the bipolar I disorder (BD-I) subtype is associated with high medical costs. This review further evaluated the economic burden of BD and BD-I in the United States (US), describing health-care resource utilization (HCRU) and sources of direct medical and indirect costs. Data were obtained from systematic searches of MEDLINE, EMBASE, and National Health Service Economic Evaluation Database. Citations were screened to identify primary research studies (published 2008-2018) on the economic burden of BD/BD-I or its treatment in real-world settings. Reported costs were converted to 2018 US dollars. Of identified abstracts (N=4111), 56 studies were included. The estimated total annual national economic burden of BD/BD-I was more than $195 billion, with approximately 25% attributed to direct medical costs. Individuals with BD/BD-I used health-care services more frequently and had higher direct medical costs than matched individuals without the disease. Drivers of higher direct costs included frequent psychiatric interventions, presence of comorbid medical/psychiatric conditions, and both suboptimal medication adherence and clinical management. Indirect costs (eg, unemployment, lost work productivity for patients/caregivers) accounted for 72-80% of the national economic burden of BD/BD-I. Different definitions for study populations and cost categories limited comparisons of economic outcomes. This review builds on existing literature describing the economic burden of BD and confirmed cost drivers of BD/BD-I. Improved clinical management of BD/BD-I and associated comorbidities, together with better medication adherence, may reduce health-care costs and improve patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CEOR.S259338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489939PMC
September 2020

Adjunctive antidepressant treatment among 763 outpatients with bipolar disorder: Findings from the Bipolar CHOICE and LiTMUS trials.

Depress Anxiety 2021 02 29;38(2):114-123. Epub 2020 Jun 29.

Dauten Family Center for Bipolar Treatment Innovation, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.

Background: Adjunctive antidepressants are frequently used for bipolar depression but their clinical efficacy has been studied in few trials and little is known about how co-occurring manic symptoms affect treatment response.

Methods: Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (N = 482) and Lithium Treatment Moderate-Dose Use Study (N = 281) were similar comparative effectiveness trials on outpatients with bipolar disorder comparing four different randomized treatment arms with adjunctive personalized guideline-based treatment for 24 weeks. Adjunctive antidepressant treatment could be used if clinically indicated and was assessed at every study visit. Adjusted mixed effects linear regression analyses compared users of antidepressants to nonusers overall and in different subcohorts.

Results: Of the 763 patients, 282 (37.0%) used antidepressant drugs during the study. Antidepressant users had less improvement compared to nonusers on the Clinical Global Impression Scale for Bipolar Disorder and on measures of depression. This was particularly true among patients with co-occurring manic symptoms. Exclusion of individuals begun on antidepressants late in the study (potentially due to overall worse response) resulted in no differences between users and nonusers. We found no differences in treatment effects on mania scales.

Conclusions: In this large cohort of outpatients with bipolar disorder, clinically indicated and guideline-based adjunctive antidepressant treatment was not associated with lower depressive symptoms or higher mania symptoms. The treatment-by-indication confounding due to the nonrandomized design of the trials complicates causal interpretations, but no analyses indicated better treatment effects of adjunctive antidepressants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/da.23069DOI Listing
February 2021

Identifying Profiles of Patients With Bipolar I Disorder Who Would Benefit From Maintenance Therapy With a Long-Acting Injectable Antipsychotic.

J Clin Psychiatry 2020 06 16;81(4). Epub 2020 Jun 16.

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas

People with bipolar I disorder experience an illness course marked by potentially disastrous manic episodes, disabling depressive episodes, and functional impairment. A frequent obstacle to wellness in these individuals is nonadherence to treatment. Long-acting injectable (LAI) antipsychotics have the potential to address nonadherence and thereby increase patients' chances at sustained recovery and normal psychosocial functioning. LAI formulations of 2 second-generation antipsychotics-aripiprazole monohydrate and risperidone-have received approval from the US Food and Drug Administration as monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adult patients. In a recent roundtable meeting, a panel of 4 experts discussed the use of these medications in bipolar I disorder. This Academic Highlights summarizes their discussion, which included the impact of functional impairment, the potential benefits of employing an LAI antipsychotic at earlier stages of bipolar illness, and the characteristics of patients who may be good candidates for treatment with an LAI antipsychotic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4088/JCP.OT19046AH1DOI Listing
June 2020

Familial severe psychiatric history in bipolar disorder and correlation with disease severity and treatment response.

J Affect Disord 2020 08 16;273:131-137. Epub 2020 May 16.

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Background: Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder.

Methods: The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response.

Results: Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms.

Conclusions: Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.03.157DOI Listing
August 2020

Glutamatergic hypo-function in the left superior and middle temporal gyri in early schizophrenia: a data-driven three-dimensional proton spectroscopic imaging study.

Neuropsychopharmacology 2020 10 13;45(11):1851-1859. Epub 2020 May 13.

Departments of Psychiatry, University of New Mexico, Albuquerque, NM, 87131-0001, USA.

Proton magnetic resonance spectroscopy (H-MRS) studies have examined glutamatergic abnormalities in schizophrenia, mostly in single voxels. Though the critical brain nodes remain unknown, schizophrenia involves networks with broad abnormalities. Hence, glutamine plus glutamate (Glx) and other metabolites were examined with whole-brain H-MRS, in early schizophrenia. Three dimensional H-MRS was acquired in young schizophrenia subjects (N = 36, 19 antipsychotic-naïve and 17 antipsychotic-treated) and healthy controls (HC, N = 29). Glx (as well as N-acetylaspartate, choline, myo-inositol and creatine) group contrasts from all individual voxels that met spectral quality, were analyzed in common brain space, followed by cluster-corrected level alpha-value (CCLAV ≤ 0.05). Schizophrenia subjects had lower Glx in the left superior (STG) and middle temporal gyri (16 voxels, CCLAV = 0.04) and increased creatine in two clusters involving left temporal, parietal and occipital regions (32, and 18 voxels, CCLAV = 0.02 and 0.04, respectively). Antipsychotic-treated and naïve patients (vs HC) had similar Glx reductions (8/16 vs 10/16 voxels respectively, but CCLAV's > 0.05). However, creatine was higher in antipsychotic-treated vs HC's in a larger left hemisphere cluster (100 voxels, CCLAV = 0.01). Also in treated patients, choline was increased in left middle frontal gyrus (18 voxels, CCLAV = 0.04). Finally in antipsychotic-naive patients, NAA was reduced in right frontal gyri (19 voxels, CCLAV = 0.05) and myo-inositol was reduced in the left cerebellum (34 voxels, CCLAV = 0.02). We conclude that data-driven spectroscopic brain examination supports that reductions in Glx in the left STG may be critical to the pathophysiology of schizophrenia. Postmortem and neuromodulation schizophrenia studies focusing on left STG, may provide critical mechanistic and therapeutic advancements, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-020-0707-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608301PMC
October 2020

Methamphetamine Abuse Trends in Psychiatric Emergency Services: A Retrospective Analysis Using Big Data.

Community Ment Health J 2020 07 29;56(5):959-962. Epub 2020 Jan 29.

Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.

Objective: This exploratory retrospective study assessed demographic and hospital utilization characteristics of patients presenting with methamphetamine use to an urban psychiatric emergency service in New Mexico.

Methods: De-identified data from patients presenting to PES from 2011 to 2015 were extracted from our health system. Descriptive statistics were used to characterize the study population. We employed bivariate analyses to assess the relationship between methamphetamine use and patient demographics.

Results: Methamphetamine use increased faster than any other drug tested during the study's time period. Compared to non-methamphetamine patients, methamphetamine use was associated with a shorter PES stay when the patient was in the PES more than 12 h.

Conclusions: Patients with methamphetamine use are increasingly seeking emergency psychiatric evaluations. Methamphetamine use may impact certain racial, ethnic, and socioeconomic classes disproportionately. Further health service delivery studies are needed to develop clear, evidence-based interventions and policy recommendations to address the methamphetamine crisis in the United States.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10597-020-00563-1DOI Listing
July 2020

A Modified Delphi Consensus Study of the Screening, Diagnosis, and Treatment of Tardive Dyskinesia.

J Clin Psychiatry 2020 Jan 28;81(2). Epub 2020 Jan 28.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.

Objective: A nominal group process followed by a modified Delphi method was used to survey expert opinions on best practices for tardive dyskinesia (TD) screening, diagnosis, and treatment and to identify areas lacking in clinical evidence.

Participants: A steering committee of 11 TD experts met in nominal group format to prioritize questions to be addressed and identify core bibliographic materials and criteria for survey panelists. Of 60 invited experts, 29 (23 psychiatrists and 6 neurologists) agreed to participate.

Evidence: A targeted literature search of PubMed (search term: tardive dyskinesia) and recommendations of the steering committee were used to generate core bibliographic material. Inclusion criteria were as follows: (1) review articles, meta-analyses, guidelines, or clinical trials; (2) publication in English between 2007 and 2017; (3) > 3 pages in length; and (4) publication in key clinical journals with impact factors ≥ 2.0. Of 29 references that met these criteria, 18 achieved a score ≥ 5 (calculated as the number of steering committee votes multiplied by journal impact factor and number of citations divided by years since publication) and were included.

Consensus Process: Two survey rounds were conducted anonymously through electronic media from November 2017 to January 2018; responses were collected, collated, and analyzed. Respondent agreement was defined a priori as unanimous (100%), consensus (75%-99%), or majority (50%-74%). For questions using a 5-point Likert scale, agreement was based on percentage of respondents choosing ≥ 4 ("agree completely" or "agree"). Round 1 survey included questions on TD screening, diagnosis, and treatment. Round 2 questions were refined per panelist feedback and excluded Round 1 questions with < 25% agreement and > 75% agreement (unless feedback suggested further investigation).

Conclusions: Consensus was reached that (1) a brief, clinical assessment for TD should be performed at every clinical encounter in patients taking antipsychotics; (2) even mild movements in 1 body area may represent possible TD; (3) management requires an overall evaluation of treatment, including reassessment of antipsychotics and anticholinergics as well as consideration of vesicular monoamine transporter 2 (VMAT2) inhibitors; and (4) informed discussions with patients/caregivers are essential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4088/JCP.19cs12983DOI Listing
January 2020

The CINP Guidelines on the Definition and Evidence-Based Interventions for Treatment-Resistant Bipolar Disorder.

Int J Neuropsychopharmacol 2020 04;23(4):230-256

Psychiatric Department, Ludwig Maximilians University, Munich, Germany.

Background: Resistant bipolar disorder is a major mental health problem related to significant disability and overall cost. The aim of the current study was to perform a systematic review of the literature concerning (1) the definition of treatment resistance in bipolar disorder, (2) its clinical and (3) neurobiological correlates, and (4) the evidence-based treatment options for treatment-resistant bipolar disorder and for eventually developing guidelines for the treatment of this condition.

Materials And Methods: The PRISMA method was used to identify all published papers relevant to the definition of treatment resistance in bipolar disorder and the associated evidence-based treatment options. The MEDLINE was searched to April 22, 2018.

Results: Criteria were developed for the identification of resistance in bipolar disorder concerning all phases. The search of the literature identified all published studies concerning treatment options. The data were classified according to strength, and separate guidelines regarding resistant acute mania, acute bipolar depression, and the maintenance phase were developed.

Discussion: The definition of resistance in bipolar disorder is by itself difficult due to the complexity of the clinical picture, course, and treatment options. The current guidelines are the first, to our knowledge, developed specifically for the treatment of resistant bipolar disorder patients, and they also include an operationalized definition of treatment resistance. They were based on a thorough and deep search of the literature and utilize as much as possible an evidence-based approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ijnp/pyz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177170PMC
April 2020

Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder.

Psychoneuroendocrinology 2020 02 9;112:104511. Epub 2019 Nov 9.

Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Translational Informatics Division, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address:

Objective: To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM).

Methods: The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug".

Results: The annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to "No drug". A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed.

Conclusions: There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2019.104511DOI Listing
February 2020

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study.

Bipolar Disord 2020 06 6;22(4):372-384. Epub 2019 Nov 6.

Department of Psychiatry, Case Western Reserve School of Medicine, Cleveland, OH, USA.

Objective: To assess the efficacy, safety, and tolerability of cariprazine in the treatment of the depressed phase of bipolar I disorder in adults (NCT02670538).

Methods: In this phase 3 double-blind placebo-controlled study, adult patients with bipolar I disorder according to the Diagnostic and Statistical Manual - 5th Edition criteria and a current depressive episode were randomized to placebo (n = 167), cariprazine 1.5 mg/day (n = 168) or cariprazine 3.0 mg/day (n = 158). Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (primary) and Clinical Global Impressions - Severity (CGI-S) scores (secondary) from baseline to Week 6 compared to placebo. A mixed-model for repeated measures was used to estimate the least-squares mean differences (LSMD); P-values were adjusted for multiplicity. Adverse events (AEs), laboratory results, vital signs, and suicide risk were monitored.

Results: Cariprazine 1.5 mg/day significantly reduced depressive symptoms on the primary (MADRS LSMD = -2.5; adjusted P = .0417) and secondary (CGI-S LSMD = -0.3; adjusted P = .0417) efficacy parameters vs placebo; differences were not statistically significant for cariprazine 3.0 mg/day. Common treatment-emergent AEs (≥5% in either cariprazine group and at least twice the incidence of placebo) were akathisia, restlessness, nausea, and fatigue. Mean metabolic parameter changes were low and generally comparable among groups; mean weight increases were ≤0.5 kg for all groups.

Conclusions: Cariprazine 1.5 mg/day significantly reduced depressive symptoms in adults with bipolar I depression compared to placebo, but differences were not significant for cariprazine 3.0 mg/day. The safety and tolerability profiles were similar to previous studies of cariprazine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bdi.12852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318333PMC
June 2020

An International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder.

Bipolar Disord 2019 12 18;21(8):720-740. Epub 2019 Sep 18.

Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.

Objectives: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years.

Methods: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies.

Results: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention.

Conclusions: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bdi.12831DOI Listing
December 2019

An International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder.

Bipolar Disord 2019 12 18;21(8):720-740. Epub 2019 Sep 18.

Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.

Objectives: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years.

Methods: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies.

Results: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention.

Conclusions: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bdi.12831DOI Listing
December 2019
-->