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1.
Expert Opin Investig Drugs ; 28(12): 1081-1094, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31714807

RESUMO

Introduction: Binge eating disorder (BED) is the most common eating disorder and is frequently associated with psychiatric and medical comorbidities and functional impairment. Although psychological treatments have been the cornerstones of BED treatment, pharmacologic interventions also play an important part of the multimodal management of this condition.Areas covered: This review examines investigational, approved and other pharmacological agents for the treatment of BED. We searched PubMed and clinicaltrials.gov to identify pharmacological interventions for the management of this condition.Expert opinion: BED pharmacological studies have incorporated new drug targets based on our enhanced understanding of the pathophysiology of BED. Neurobiological dysregulation in the reward center and impulse control circuitry and related disturbances in dopamine neurotransmission are among the neurobiological explanations that have been suggested for BED. These mechanisms serve as a pharmacodynamic foundation for the development of new compounds such as lisdexamfetamine (LDX) and dasotraline. Despite these advances, pharmacological trials in BED have numerous challenges that must be overcome. For most compounds studied, larger and more definitive trials is a high priority.

2.
Clin Neuropharmacol ; 42(6): 214-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31725476

RESUMO

OBJECTIVES: The purpose of this retrospective chart review was to evaluate lisdexamfetamine dimesylate (LDX) in the treatment of pediatric binge eating disorder (BED). METHODS: We examined the clinical records of 25 patients, 12 to 19 years of age, who were prescribed LDX and had a diagnosis of BED between 2014 and 2017. RESULTS: Binge eating disorder in adolescents was highly comorbid with attention deficit hyperactivity disorder, mood and anxiety disorders, and severe obesity. Fifteen participants reported some level of improvement of their BED symptoms with LDX treatment. Posttreatment body mass index (BMI) percentile was not significantly reduced, and all but 2 participants remained in their same BMI classification. Lisdexamfetamine dimesylate treatment duration was not associated with change in BMI percentile, and the medication was well tolerated. CONCLUSIONS: Lisdexamfetamine dimesylate may have clinical utility for BED in adolescents, but randomized, placebo-controlled studies of its efficacy, tolerability, and safety in this population are needed.

3.
World J Biol Psychiatry ; : 1-22, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31749403

RESUMO

Objectives: To investigate the effect of sample handling on inflammatory cytokines in serum and highlight challenges with using samples pre-collected from biobanks for biomarker research.Methods: Cytokine concentrations (IL-1ß, IL-2, IL-6, IL-8, IL-10, TNFα, and IFNγ) were measured in serum samples of 205 patients with BD from the Mayo Clinic Bipolar Disorder (BD) Biobank and 205 non-psychiatric controls from the Mayo Clinic Biobank. As cytokine concentrations varied by recruitment site, post-hoc models were used to test the effect of clinical variables and pre-processing time on cytokines. To evaluate the effect of pre-processing time experimentally, cytokines were assayed in serum and plasma from 6 healthy volunteers processed at different time points.Results: Cytokine levels were significantly higher in the BD group. However, both cytokine levels and pre-processing times differed by recruitment site, and post-hoc analyses revealed that pre-processing time was significantly associated with several cytokines. An experiment using samples from healthy volunteers confirmed that concentrations for most cytokines increased with longer pre-processing times.Conclusions: Delays in processing influence cytokine concentrations in blood samples. Given the increasing use of biobanks in research, this study highlights the need to carefully evaluate sample collection and handling methods when designing biomarker studies.

4.
J Clin Psychiatry ; 80(6)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665571

RESUMO

OBJECTIVE: According to DSM-IV, criterion (A) for diagnosing a hypomanic/manic episode is mood change (ie, elevated, expansive, or irritable mood). Criterion (A) was redefined in DSM-5, adding increased energy or activity in addition to mood change. We sought to investigate the effect of adding increased energy or activity to criterion (A) for the diagnosis of hypomania/mania and, thus, bipolar disorder. METHODS: This analysis of prospectively collected data from the Bipolar Collaborative Network (1995-2002) includes 907 DSM-IV-TR-diagnosed bipolar outpatients (14,306 visits). The Young Mania Rating Scale (YMRS) was administered monthly and used to define DSM-IV and DSM-5 criterion (A) fulfillment during a hypomanic/manic visit. RESULTS: Patients were adults (median age = 40; IQR, 33-49), and over half (56%) were women. Median number of contributed visits was 10 (IQR, 4-23). Applying DSM-5 criterion (A) reduced the number of patients experiencing a hypomanic/manic visit by 34%, compared to DSM-IV. Visits fulfilling DSM-5 criterion (A) had higher odds of experiencing elevated levels of all other mania symptoms, compared to fulfilling DSM-IV criterion (A) only. Association between individual symptoms was strongest with mood elevation and energy or activity (OR [95% CL] = 8.65, [7.91, 9.47]). CONCLUSIONS: The 34% reduction in the number of patients being diagnosed with a hypomanic/manic visit shows that the impact of applying DSM-5 criterion (A) is substantial. Fewer hypomanic/manic episodes may be diagnosed by the stricter DSM-5 criterion (A), but the episodes diagnosed are likely to be more severe. The DSM-5 criteria may in general prevent overdiagnosis of bipolar disorder but possibly at the cost of underdiagnosing hypomanic/manic episodes.

5.
Bipolar Disord ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31643130

RESUMO

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the dopaminergic enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. METHODS: A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BPI) or bipolar II (BPII) depression. Data for response/remission and all-cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. RESULTS: Of 58 studies, Five RCTs (N=795 drug, N=792 placebo) met inclusion criteria. Four armodafinil studies included only BPI patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I2 = 34%, P = 0.19; I2 = 18%, P = 0.30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01-1.37; p=0.03) and remission (RR, 1.38; 95% CI, 1.10-1.73; p=0.005). All cause discontinuation was no different than placebo (RR, 1.08; 95% CI, 0.89-1.30, p=0.45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39-2.5, p=0.98; RR, 1.02; 95% CI, 0.37-2.85, p=0.97). CONCLUSION: This narrower scope meta-analysis of one drug for one disease suggests that adjunctive modafinil / armodafinil may represent a novel therapeutic intervention. Further studies delineating subtypes of bipolar depression responsive to these novel dopaminergic enhancing agents are encouraged.

6.
Qual Life Res ; 28(12): 3385-3394, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473907

RESUMO

PURPOSE: The Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) assesses the obsessiveness of binge eating thoughts and compulsiveness of binge eating behaviors. The findings of this study extend previously published Y-BOCS-BE psychometric evaluations in adults with binge eating disorder (BED). METHODS: Data from three phase 3 lisdexamfetamine dimesylate studies in adults with BED (two randomized, double-blind, placebo-controlled short-term efficacy studies; one double-blind, placebo-controlled, randomized-withdrawal maintenance-of-efficacy study) were used. Psychometric evaluations included assessment of Y-BOCS-BE dimensionality, internal consistency, convergent validity, test?retest reliability, and determinations of clinically meaningful improvement using distribution- and anchor-based methods. RESULTS: Domain specification analyses determined that the Y-BOCS-BE possessed a bifactor structure composed of a general binge eating severity domain and three subdomains (obsessive/compulsive, restraint, and control). Y-BOCS-BE internal consistency was maximized at week 12 (Cronbach?s ?, 0.95) and test?retest reliability was maximized in the 8-week retest interval from week 4 to week 12 across all no-change anchors (r?=?0.74?0.90). Likewise, convergent validity of the Y-BOCS-BE across all validators was maximized at week 12 (all r???0.66). Meaningful improvement for Y-BOCS-BE total scores was estimated to require score reductions of 12 to 17 points depending on the anchor. CONCLUSIONS: The Y-BOCS-BE is a valuable tool for assessing BED symptoms. Maximization of Y-BOCS-BE reliability and validity at later study time points may be related to both treatment effects and improved insight into BED by participants during the study.

7.
JAMA Psychiatry ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532468

RESUMO

Importance: Infection-associated immune activation and inflammation are increasingly recognized in the pathophysiology of bipolar disorder. Objective: To determine whether antibodies to common infectious agents, including cytomegalovirus (CMV), Toxoplasma gondii, and measles, as well as the inflammatory marker C-reactive protein, in serum samples differ between patients with bipolar disorder and control individuals without bipolar disorder. Design, Setting, and Participants: In this case-control study, antibody titers were measured in serum samples from 1207 patients with bipolar disorder and 745 controls that were obtained from biobanks with participating sites in Rochester and Minneapolis, Minnesota (n = 1537), and Cincinnati, Ohio (n = 415), from January 5, 2009, through May 12, 2014. A subset of case patients and controls from Minnesota were matched by age, sex, and educational level. Bipolar type, age at onset, and history of psychosis were assessed for case patients as well as current drug treatment at the time of blood sample obtainment from the biobank. Data were analyzed from February 5, 2018, to January 4, 2019. Exposures: The CMV and T gondii antibodies with IgM titers were expressed as z scores and IgG titers dichotomized into seropositive and seronegative based on expected prevalence in the US population and further classified based on the joint CMV-positive/T gondii-negative IgG status, C-reactive protein z score, and drug treatments with antitoxoplasma activity. Main Outcomes and Measures: Patients were stratified by bipolar disorder type I or type II, nonearly (>19 years of age) and early (≤19 years of age) onset, and history of psychosis during mania or no psychosis. Results: Of 1207 patients with bipolar disorder (mean [SD] age, 43.2 [15.1] years; 742 [61.5%] female), the CMV-positive/T gondii-negative IgG status was significantly higher (odds ratio [OR], 1.33; 95% CI, 1.09-1.62; P = .004) compared with that in the 745 controls (mean [SD] age, 44.5 [15.5] years; 444 [59.6%] female). The CMV-positive/T gondii-negative IgG status was associated with bipolar cases type I (OR, 1.41; 95% CI, 1.14-1.75; P = .001), nonearly age at onset (OR, 1.41; 95% CI, 1.16-1.72; P = .001), and history of manic psychosis (OR, 1.46; 95% CI, 1.13-1.88; P = .004). Patients with bipolar disorder who received drug treatment with antitoxoplasma activity (n = 272) had significantly lower T gondii IgM titers (median, 1.59; interquartile range, 1.30-2.07) compared with those (n = 900) who did not receive this treatment (median, 1.69; interquartile range, 1.35-2.25) (P = .03). Conclusions and Relevance: In this sample, increased long-term antibody response to CMV and decreased long-term antibody response to T gondii were associated with bipolar disorder and the subphenotypes of bipolar type I, nonearly disease onset, and manic psychosis. Further work appears to be needed to better understand genetic vs environmental disease risk and infection or immune activation contribution to overall disease pathogenesis with particular reference to disease onset.

8.
J Affect Disord ; 259: 164-172, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445343

RESUMO

INTRODUCTION: Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI. METHODS: 482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures. RESULTS: Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI. LIMITATIONS: Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk. DISCUSSION: Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions.

9.
Clin Transl Sci ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31386273

RESUMO

As with other psychiatric disorders, development of drugs to treat binge-eating disorder (BED) has been hampered by high placebo response and dropout rates in randomized controlled trials (RCTs). Although not approved for use in BED, several RCTs have suggested that topiramate is efficacious for BED in obese individuals. Using data from a positive investigator-initiated RCT of topiramate in 61 obese individuals with BED, the objective of the present study is (i) to develop a quantitative disease-drug-trial framework to inform future BED clinical trial designs, and (ii) to determine the optimal topiramate dose to achieve therapeutic efficacy. Disease-drug-trial models were developed separately for the two efficacy measures, namely, longitudinal normalized weekly binge-eating episode frequency (BEF) and binge day frequency (BDF). Model building consisted of (i) developing a placebo effect model that describes response from the placebo group, (ii) adding a drug effect to the placebo model to describe dose-response relationships, and (iii) developing a parametric time to event model to characterize patient dropout patterns. The placebo effect on normalized BEF and BDF over time demonstrated a maximum decrease of ~ 57% by 5 weeks. Participants had a higher dropout probability if no weight loss occurred during the trial period. The identified dose-response relationship demonstrated a daily dose of 125 mg was needed to exhibit a marked reduction in weekly BEF. The developed comprehensive disease-drug-trial model will be utilized to simulate different clinical trial designs to increase the success for future BED drug development programs.

10.
Expert Rev Neurother ; 19(9): 867-879, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31269819

RESUMO

Introduction: Clinical and genetic study of psychiatric conditions has underscored the co-occurrence of complex phenotypes and the need to refine them. Bipolar Disorder (BD) and Binge Eating (BE) behavior are common psychiatric conditions that have high heritability and high co-occurrence, such that at least one quarter of BD patients have BE (BD + BE). Genetic studies of BD alone and of BE alone suggest complex polygenic risk models, with many genetic risk loci yet to be identified. Areas covered: We review studies of the epidemiology of BD+BE, its clinical features (cognitive traits, psychiatric comorbidity, and role of obesity), genomic studies (of BD, eating disorders (ED) defined by BE, and BD + BE), and therapeutic implications of BD + BE. Expert opinion: Subphenotyping of complex psychiatric disorders reduces heterogeneity and increases statistical power and effect size; thus, it enhances our capacity to find missing genetic (and other) risk factors. BD + BE has a severe clinical picture and genetic studies suggests a distinct genetic architecture. Differential therapeutic interventions may be needed for patients with BD + BE compared with BD patients without BE. Recognizing the BD + BE subphenotype is an example of moving towards more precise clinical and genetic entities.

11.
Med Clin North Am ; 103(4): 669-680, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078199

RESUMO

Binge eating disorder (BED) is the most common eating disorder and an important public health problem. Lifetime prevalence of BED in the United States is 2.6%. In contrast to other eating disorders, the female to male ratio in BED is more balanced. BED co-occurs with a plethora of psychiatric disorders, most commonly mood and anxiety disorders. BED is also associated with obesity and its numerous complications. Although BED is similar in men and women in presentation and treatment outcomes, there are some key neurobiological differences that should be taken in consideration when personalizing treatment.


Assuntos
Transtorno da Compulsão Alimentar/diagnóstico , Transtorno da Compulsão Alimentar/epidemiologia , Transtornos do Humor/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos de Ansiedade/epidemiologia , Transtorno da Compulsão Alimentar/terapia , Bulimia/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Autoimagem , Fatores Sexuais , Estados Unidos
12.
Transl Psychiatry ; 9(1): 149, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123248

RESUMO

Glutamatergic dysregulation is implicated in the neurobiology of mood disorders. This study investigated the relationship between the anterior cingulate cortex (AC) glutamate, as measured by proton magnetic resonance spectroscopy (1H-MRS), and single-nucleotide polymorphisms (SNPs) from four genes (GLUL, SLC1A3, SLC1A2, and SLC1A7) that regulate the extracellular glutamate in 26 depressed patients with major depressive disorder (MDD; n = 15) and bipolar disorder (BD; n = 11). Two SNPs (rs3812778 and rs3829280), in perfect linkage disequilibrium, in the 3' untranslated region of the EAAT2 gene SLC1A2, were associated with AC glutamate, with minor allele carriers having significantly higher glutamate levels (p < 0.001) in comparison with common allele homozygotes. In silico analysis revealed an association of minor allele carriers of rs3812778/rs382920 with an upregulation of the astrocytic marker CD44 localized downstream of SLC1A2 on chromosome 11. Finally, we tested the disease relevance of these SNPs in a large group of depressed patients [MDD (n = 458); BD (n = 1473)] and found that minor allele carriers had a significantly higher risk for rapid cycling (p = 0.006). Further work is encouraged to delineate the functional impact of excitatory amino acid transporter genetic variation on CD44 associated physiology and glutamatergic neurotransmission, specifically glutamate-glutamine cycling, and its contribution to subphenotypes of mood disorders.

13.
Psychiatry Res Neuroimaging ; 286: 53-59, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30903953

RESUMO

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

14.
Eat Behav ; 33: 30-33, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30852343

RESUMO

PURPOSE: To examine the potential factor structure of the Eating Disorder Diagnostic Scale (EDDS) in a sample of individuals with bipolar disorder. METHOD: Exploratory common factor analyses were conducted in a sample of 1031 people with bipolar disorder as defined by the Structured Clinical Interview for DSM-IV-TR. RESULTS: Approximately 27% of participants had a comorbid eating disorder. Exploratory factor analysis yielded a 3 factor solution (i.e., shape/weight concerns; binge eating behaviors, compensatory behavior). CONCLUSIONS: The 3-factor solution of the EDDS in a bipolar disorder sample is consistent with major eating disorder symptom domains. Future research is necessary to replicate these findings in eating disorder samples with diverse comorbid psychopathology.

15.
Sex Med Rev ; 7(3): 380-392, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30803922

RESUMO

INTRODUCTION: Flibanserin, a multifunctional serotonin agonist and antagonist, is approved by the U.S. Food and Drug Administration (FDA) for treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. During the FDA's review of flibanserin, concerns were raised about the risks of hypotension, syncope, and sedation-related adverse events, which increase with alcohol use. Based on the results of an alcohol challenge study, the FDA required a boxed warning and alcohol contraindication in the flibanserin prescribing information, as part of a risk evaluation and mitigation strategy program. AIM: To evaluate the adverse event profile of flibanserin in the context of that seen with other medications that affect serotonin in the brain and are commonly prescribed for women. METHODS: This was a review of data provided in the product prescribing information for flibanserin, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, other serotonergic antidepressants, and triptans. MAIN OUTCOME MEASURES: The incidence of adverse events was assessed. RESULTS: The incidences of hypotension, syncope, and sedation-related adverse events (eg, dizziness, somnolence, fatigue) in studies of flibanserin were within the ranges observed for serotonergic antidepressants; the rates of these adverse events were generally lower with triptan medications. Other flibanserin-associated adverse events (eg, nausea, insomnia, dry mouth) occurred more commonly in patients taking antidepressant medications. CONCLUSION: Although medications that affect the serotonin system have varying adverse event profiles (likely mediated by differences in serotonin-related mechanisms of action, specific brain structures affected, and effects on other neurotransmitter systems), the occurrence of central nervous system-related adverse events was not dissimilar between flibanserin and serotonergic antidepressants. Kingsberg SA, McElroy SL, Clayton AH. Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications. Sex Med Rev 2019;7:380-392.

16.
Int J Obes (Lond) ; 43(10): 2085-2094, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30664661

RESUMO

BACKGROUND/OBJECTIVES: Prolonged-release (PR) naltrexone 32 mg/bupropion 360 mg (NB) is approved for chronic weight management as an adjunct to reduced-calorie diet and increased physical activity. Central nervous system-active medications have the potential to affect mood; therefore, post hoc analysis of clinical trial data was conducted to evaluate psychiatric adverse events (PAEs) and effects on mood of NB therapy versus placebo. SUBJECTS/METHODS: Data were pooled from 5 prospective, double-blind, randomized, placebo-controlled clinical trials (duration range, 24-56 weeks) of NB in subjects with overweight or obesity. PAEs were collected via AE preferred terms, organized into major subtopics (e.g., anxiety, depression, sleep disorders), and divided into category terms (e.g., anxiety, potential anxiety symptoms). Additionally, the Inventory of Depressive Symptomatology Self Report (IDS-SR; score range 0-84) and the Columbia Classification Algorithm of Suicide Assessment (C-CASA) evaluated treatment-emergent depressive/anxiety symptoms and suicidal behavior/ideation, respectively. RESULTS: Baseline characteristics and comorbidities were comparable for placebo (n = 1515) and NB (n = 2545). Most common PAEs in the NB group (using category grouping; NB vs placebo) were sleep disorders (12.7 vs 7.9%, P < 0.001), anxiety (5.4 vs 3.3%, P = 0.029), and depression (1.8 vs 2.7%, P = 0.014); PAEs were more frequent during dose escalation and generally mild or moderate. Mean (SD) changes in IDS-SR total score from baseline to endpoint were small in both groups: 0.13 (5.83) for NB and -0.45 (5.65) for placebo. Retrospective AE categorization via C-CASA confirmed no completed suicides, suicide attempts, or preparatory acts toward imminent suicidal behavior. CONCLUSIONS: This large pooled analysis of 5 clinical trials provides additional safety information about the NB PAE profile. Anxiety and sleep disorder-related PAEs were more frequent with NB versus placebo but were mostly mild to moderate and generally occurred early. Depression-related PAEs were less common with NB than placebo, and NB was not associated with suicidal ideation or behavior in this patient population.

17.
J Affect Disord ; 246: 126-131, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30580198

RESUMO

BACKGROUND: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial. METHODS: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS. RESULTS: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics. LIMITATIONS: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders. CONCLUSIONS: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Escalas de Graduação Psiquiátrica , Adulto , Ansiolíticos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Comorbidade , Pesquisa Comparativa da Efetividade , Feminino , Humanos , Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Fumarato de Quetiapina/uso terapêutico , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia
18.
CNS Drugs ; 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30523523

RESUMO

This paper reviews past and current progress in developing pharmacologic agents for the treatment of individuals with bulimia nervosa (BN). We searched the literature and clinical trial registries for compounds studied in BN, the related condition, binge eating disorder (BED), and preclinical models of binge-eating behavior. Drug classes evaluated included antidepressants, antiepileptic drugs, stimulants and other medications for attention-deficit/hyperactivity disorder, opioid antagonists, and weight loss agents, among others. The only available drugs with established efficacy in BN at this time include antidepressants (especially selective serotonin reuptake inhibitors [SSRIs]) and the antiepileptic topiramate, though the efficacy of these compounds is modest at best. The only medications we found currently receiving empirical study in people with BN were fluoxetine, other serotonergic antidepressants, intranasal naloxone, lisdexamfetamine dimesylate, phentermine-topiramate combination, the antiandrogenic oral contraceptive ethinyl estradiol plus drospirenone, and prazosin. Preclinical models suggest that nociceptin receptor antagonists, the selective serotonin 5-HT2C receptor agonist lorcaserin, monoamine stabilizers, and selective orexin-1 receptor antagonists might be helpful. We found no evidence of a drug developed specifically for the treatment of individuals with BN. Future areas for research in the pharmacotherapy of BN are suggested. Importantly, until drugs are developed specifically for eating disorders, drugs developed for other conditions that are centrally acting and associated with beneficial psychotropic effects and/or reduced appetite or weight loss might be considered for repurposing in BN.

19.
Bipolar Disord ; 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30447123

RESUMO

OBJECTIVE: Bipolar disorder has a wide range of clinical manifestations which may progress over time. The aim of this study was to test the applicability of a clinical staging model for bipolar disorder and to gain insight into the nature of the variables influencing progression through consecutive stages. METHODS: Using retrospectively reported longitudinal life chart data of 99 subjects from the Stanley Foundation Bipolar Network Naturalistic Follow-up Study, the occurrence, duration and timely sequence of stages 2 - 4 were determined per month. A multi-state model was used to calculate progression rates and identify determinants of illness progression. Stages 0, 1 and several other variables were added to the multi-state model to determine their influence on the progression rates. RESULTS: Five years after onset of BD (stage 2), 72% reached stage 3 (recurrent episodes) and 21% had reached stage 4 (continuous episodes), of whom 8% recovered back to stage 3. The progression from stage 2 to 3 was increased by a biphasic onset for both the depression-mania and the mania-depression course and by male sex. CONCLUSIONS: Staging is a useful model to determine illness progression in longitudinal life chart data. Variables influencing transition rates were successfully identified. This article is protected by copyright. All rights reserved.

20.
Bipolar Disord ; 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383333

RESUMO

INTRODUCTION: Depressive episodes are often prevalent among patients with bipolar disorder, but little is known regarding the differential patterns of development over time. We aimed to determine and characterize trajectories of depressive symptoms among adults with bipolar disorder during 6 months of systematic treatment. METHODS: The pragmatic clinical trial, Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE), randomized 482 outpatients with bipolar disorder to lithium or quetiapine. Depressive symptoms were rated at up to 9 visits using the Montgomery-Asberg Depression Rating Scale (MADRS). Growth mixture modeling was utilized to identify trajectories and multinomial regression analysis estimated associations with potential predictors. RESULTS: Four distinct trajectories of depressive symptoms were identified. The responding class (60.3%) with a rapid reduction and subsequent low level; the partial-responding class (18.4%) with an initial reduction followed by an increase during the remaining weeks; the fluctuating class (11.6%) with a fluctuation in depressive symptoms; and the non-responding class (9.7%) with sustained moderate-severe depressive symptoms. Bipolar type I predicted membership of the non-responding class and randomization to quetiapine predicted membership of either the responding or the non-responding class. CONCLUSION: Approximately 30% experienced a partial or fluctuating course, and almost 10% had a chronic course with moderate-severe depression during 6 months. Patients diagnosed with bipolar type 1 had higher risk of being categorized into a class with a worse outcome. While no differences in average overall outcomes occurred between the lithium and quetiapine groups, trajectory analysis revealed that the lithium group had more variable courses.

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