Brainstorms
Mechanism of action of vesicular monoamine transporter 2 (VMAT2) inhibitors in tardive dyskinesia: reducing dopamine leads to less “go” and more “stop” from the motor striatum for robust therapeutic effects
- Stephen M. Stahl
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- Published online by Cambridge University Press:
- 18 December 2017, pp. 1-6
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Tardive dyskinesia can now be successfully treated by inhibiting the vesicular monoamine transporter type 2 (VMAT2).
Reviewers
CNS Spectrums 2017 Peer Reviewers
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- Published online by Cambridge University Press:
- 19 February 2018, p. 7
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Guest Editorial
Standardization of MRI data and disability quantification in the post-EPIC era
- Jagannadha Avasarala
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- 09 February 2017, pp. 8-9
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Review Articles
Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson’s disease: a systematic review and metaanalysis
- Ahmed Elgebaly, Mohamed Elfil, Attia Attia, Mayar Magdy, Ahmed Negida
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- 27 February 2017, pp. 10-23
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Background
Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson’s disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS.
MethodsA computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows).
ResultsSeven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=–0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=–0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=–0.05, p=0.65; WAIS–R digit symbol: SMD=–0.16, p=0.29; Trail Making Test Part B: SMD=–0.14, p=0.23; Stroop color–word interference: SMD=–0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=–0.04, p=0.73, and unilateral DBS SMD=–0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=–0.09, p=0.37, and unilateral DBS SMD=–0.29, p=0.22; Boston Naming Test: SMD=–0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11).
ConclusionsThere was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.
Continuous circular cycling as a predictor of treatment response in bipolar disorders: a comprehensive review of the current literature
- Antonio Tundo, Paola Cavalieri
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- 15 March 2017, pp. 24-28
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Evidence from the literature suggests that, on average, 27% of patients with a bipolar disorder (BD) experience a continuous cycling course (CCC) and that this subgroup differs significantly from patients with a noncontinuous cycling course (N-CCC) with respect to sociodemographic characteristics and clinical presentation. The aim of the present paper is to review the studies that evaluated short- and long-term treatment responses in BD patients with CCC. The retrieved studies indicate that CCC is a significant predictor of poor response to long-term treatment with lithium (the odds of a response in the CCC group were 57% less than in the N-CCC group; p<0.01), as well as to polytherapies including lithium and/or an antiepileptic augmented, when necessary, with an antipsychotic and/or antidepressant. The percentage of patients without new episodes during follow-up was significantly lower in the CCC group compared with the N-CCC group (15.4 vs. 37.6% , p<0.01). Compared with patients in the N-CCC group, members of the CCC group had a poorer response and lower remission rates after 12-week antidepressant treatments for a major depressive episode (82.3 vs. 50%, p =0.002; 69.6 vs. 40.9%, p=0.013). These findings, underlining that CCC is a predictor of poor response to short- and long-term treatment in BD, should be interpreted considering the limitations of the reviewed studies (the small sample sizes, the small number of trials and their observational nature, the lack of randomization or placebo controls, and the unblinded nature of the outcomes). Clinical trials and observational studies with larger samples are warranted to confirm the conclusions of our review.
A systematic review of the heritability of specific psychopathic traits using Hare’s two-factor model of psychopathy
- Sapna Dhanani, Veena Kumari, Basant K. Puri, Ian Treasaden, Susan Young, Piyal Sen
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- 11 May 2017, pp. 29-38
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Background
There have been no systematic reviews that investigated the heritability of the two-factor model of psychopathy: interpersonal-affective and behavioral. Our review aimed, first, to examine the heritability of general psychopathic traits and, second, if genetic influences were suggested, to determine the heritability of various traits related to the interpersonal-affective and behavioral factors of psychopathy.
MethodA systematic literature search was conducted using articles from the PsycINFO, Embase, Global Health, Medline, PubMed, Web of Science, and Scopus databases (January of 1980 to December of 2015) in order to identify eligible literature that reported on the heritability of psychopathy-related traits. Papers were also found via manual examination and reference tracking. Papers were subjected to exclusion criteria and quality appraisal. We identified a total of 24 studies.
ResultsOur results were grouped into three categories: general, interpersonal-affective, and behavioral. All these areas demonstrated modest to high heritability. The highest heritability values were found in studies investigating callous-unemotional behaviors.
ConclusionsHeritability was found for all the psychopathic traits. Future research should include endophenotypic approaches that explore gene–environment correlations, which could aid in identification of the behavioral phenotype that is most amenable to early intervention by way of moderation of genetic risk.
Original Research
Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study
- Andrew J. Cutler, Suresh Durgam, Yao Wang, Raffaele Migliore, Kaifeng Lu, István Laszlovszky, György Németh
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- 08 May 2017, pp. 39-50
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Objective
Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The efficacy and safety of cariprazine was established in three randomized, double-blind, placebo-controlled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia.
MethodsThis was a multicenter, open-label, flexible-dose study of cariprazine 3–9 mg/d in adults with schizophrenia. Participants included new patients and patients who had completed one of two phase III lead-in studies (NCT01104766, NCT01104779). Eligible patients entered a no-drug screening period of up to 1 week followed by 48 weeks of flexibly dosed, open-label cariprazine treatment (3–9 mg/d) and 4 weeks of safety follow-up.
ResultsA total of 586 patients received open-label cariprazine treatment, ~39% of whom completed the study. No unexpected safety issues or deaths were reported. The most common (≥10%) adverse events (AEs) observed were akathisia (16%), headache (13%), insomnia (13%), and weight gain (10%). Serious AEs occurred in 59 (10.1%) patients, and 73 (12.5%) patients discontinued the study due to AEs during open-label treatment. Mean changes in metabolic, hepatic, and cardiovascular parameters were not considered clinically relevant. Mean body weight increased by 1.5 kg during the study, prolactin levels decreased slightly, and measures of efficacy remained stable.
ConclusionsLong-term cariprazine treatment at doses up to 9 mg/d appeared to be generally safe and well tolerated in patients with schizophrenia.
Unpacking the role of self-reported compulsivity and impulsivity in obsessive-compulsive disorder
- Luisa Prochazkova, Linden Parkes, Andrew Dawson, George Youssef, Gabriela M. Ferreira, Valentina Lorenzetti, Rebecca A. Segrave, Leonardo F. Fontenelle, Murat Yücel
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- 10 May 2017, pp. 51-58
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Objective
We aimed to determine whether individuals with obsessive-compulsive disorder (OCD) and demographically matched healthy individuals can be clustered into distinct clinical subtypes based on dimensional measures of their self-reported compulsivity (OBQ–44 and IUS–12) and impulsivity (UPPS–P).
MethodsParticipants (n=217) were 103 patients with a clinical diagnosis of OCD; 79 individuals from the community who were “OCD-likely” according to self-report (Obsessive-Compulsive Inventory–Revised scores equal or greater than 21); and 35 healthy controls. All data were collected between 2013 and 2015 using self-report measures that assessed different aspects of compulsivity and impulsivity. Principal component analysis revealed two components broadly representing an individual's level of compulsivity and impulsivity. Unsupervised clustering grouped participants into four subgroups, each representing one part of an orthogonal compulsive-impulsive phenotype.
ResultsClustering converged to yield four subgroups: one group low on both compulsivity and impulsivity, comprised mostly of healthy controls and demonstrating the lowest OCD symptom severity; two groups showing roughly equal clinical severity, but with opposing drivers (i.e., high compulsivity and low impulsivity, and vice versa); and a final group high on both compulsivity and impulsivity and recording the highest clinical severity. Notably, the largest cluster of individuals with OCD was characterized by high impulsivity and low compulsivity. Our results suggest that both impulsivity and compulsivity mediate obsessive-compulsive symptomatology.
ConclusionsIndividuals with OCD can be clustered into distinct subtypes based on measures of compulsivity and impulsivity, with the latter being found to be one of the more defining characteristics of the disorder. These dimensions may serve as viable and novel treatment targets.
Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)
- Bernardo Dell’Osso, Beatrice Benatti, Chiara Arici, Carlotta Palazzo, A. Carlo Altamura, Eric Hollander, Naomi Fineberg, Dan J. Stein, Humberto Nicolini, Nuria Lanzagorta, Donatella Marazziti, Stefano Pallanti, Michael van Ameringen, Christine Lochner, Oguz Karamustafalioglu, Luchezar Hranov, Martijn Figee, Lynne Drummond, Carolyn I. Rodriguez, John Grant, Damiaan Denys, Jose M. Menchon, Joseph Zohar
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- 16 March 2017, pp. 59-66
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Objective
Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients.
MethodsA total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson’s chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable.
Results14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables.
ConclusionsOur international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.
Abstracts
The following abstracts were presented as posters at the 2017 NEI Congress
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- 19 February 2018, p. 68
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Congratulations to the scientific poster winners:
1stPlace: #178—Gender Differences in Prodromal Symptoms of Dementia
2ndPlace: #146—Effect of Heroin Use on Changes of Brain Functions As Measured by fMRI, a Systematic Review
3rdPlace: #185—Second Generation Antipsychotics and Catatonia: A Literature Review
100 Reciprocal Relationship Between Olfactory Ability and Olfactory Hallucination
- Usama Bardan, Stefany Kress, Alan R. Hirsch
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- 15 June 2018, p. 68
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Introduction
Transient fluctuation of smell concurrent with phantosmia has not been reported. Four such cases are presented.
MethodsCase 1: A 27-year-old left handed (pathological) female, 7 years prior to presentation, noted constant olfactory hallucinations of dried blood and rotten sour eggs, level 8/10 in intensity.
Results: Without phantosmia: Alcohol Sniff Test (AST): 14 (hyposmia). Brief Smell Identification Test (BSIT): 10 (normosmia). Retronasal Smell Index: 0 (abnormal).
With phantosmia: AST: 1 (anosmia). BSIT: 12 (normosmia). Retronasal Smell Index: 0 (abnormal). Normal 72-hour EEG and MRI.
Case 2: A 19 year old right-handed woman presented with a 4 month history of unpleasant, fruity, rotten phantosmia occurring three times a day, 6-7/10 in intensity.
Results: Without phantosmia: Pocket Smell Test (PST): 3 (normosmia). AST: 30 (normosmia). With phantosmia: AST: 13 (hyposmia). CT scan: normal. MRI: normal.
Case 3: A 40 year old right-handed female presented with ashtray/cigarette phantosmia , occurring 10 times a day, lasting seconds to all day, 10/10 in intensity. Her sense of smell is normal except when the phantosmia is present, during which time it decreases to 70% of normal.
Results: Without phantosmia: BSIT: 11 (normosmia). AST: 30 (normosmia). With phantosmia: AST: 11 (hyposmia). PST: 3 (normosmia). EEG: normal. MRI: few subcortical white matter hyperintensities on flair imaging.
Case 4: A 60 year old right handed male with type 1 diabetes mellitus presented with four months of phantosmia of sweet tobacco, level 8/10 in severity, involves both nostrils, lasting 10 seconds and occurring two times a day. Over time, the hallucinated odor changed to a soapy smell 2-3/10 in intensity.
Results: Without phantosmia: AST: 6 (hyposmia). BSIT: 8 (hyposmia). With phantosmia: AST: 1 (anosmia). PST: 2 (hyposmia). CT scan: normal.
DiscussionOlfactory ability should be assessed in those with phantosmia, both during and in the absence of hallucinated odors, to detect transient olfactory deficits in order to direct treatment towards this condition.
104 Valproate-Induced Hyperammonemic Encephalopathy: Case Studies
- Dan Matthews, Glenda Matthews
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- 15 June 2018, pp. 68-69
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BACKGROUND
Hyperammonemia and carnitine deficiency with concomitant encephalopathy have been reported to result from valproic acid administration (Coulter DL, J Child Neurol 1991Jan; 6(1); 7-14 and Mock, CM, et al, Am J Health Syst Pharm, 2012 Jan; 69(1):35-9). Although there have been numerous publications regarding this adverse event in the neurology literature, there have been very few reports published in the psychiatric literature. The reported incidence of hyperammonemia in children treated with valproate is 19%. It is important that prescribers be aware of the risk of valproic acid induced hyperammonemic encephalopathy, as well as its diagnosis and management.
OBJECTIVEThe current study explores the feasibility of reversing Valproate Induced Hyperammonemic Encephalopathy (VHE) by discontinuing valproic acid and normalizing the carnitine level via L-carnitine supplementation.
METHODSThree males (ages 10-16 years), are reported with 12 - 24 month histories of cognitive decline during treatment for “Bipolar Disorder of Childhood” with valproate. All were referred with multi-year histories of explosive/impulsive aggression and multiple unsuccessful psychopharmacological regimes. The one consistent medication throughout treatment was sodium valproate. The subjects received serial neuropsychological testing, complex EEG, MRI, valproic acid, carnitine, and ammonia blood levels. Oxcarbazepine titrated to 30-50 mg/kg/day was substituted for valproate after initial testing was completed. Normative reference laboratory levels were as follows: (1) ammonia (reference interval 15-45 mcg/dl), (2) total carnitine (reference interval 34-77 nmol/ml), and (3) valproic acid (reference interval 50-125 mcg/ml).
RESULTSCase Study 1: Male, 10 years old, ammonia 78 mcg/dl; carnitine 17 nmol/ml; valproic acid 92 mcg/ml. IQ 79 (compared to 105 one year earlier); MRI cerebral atrophy; EEG - left temporal aberrancies.
Case Study 2: Male, 12 years old, ammonia 76 mcg/dL; carnitine 14 nmol/ml; valproic acid 104 mcg/ml. IQ 89 (compared to 109); MRI normal; EEG - left temporal aberrancies.
Case Study 3: Male, 16 years old, ammonia 72 mcg/dl; carnitine 24 nmol/ml; valproic acid 125 mcg/ml. IQ 45 (compared to 65); MRI normal; EEG - left temporal aberrancies.
In all three subjects, after valproate was removed (oxcarbazepine substituted) and supplemental L-carnitine added, ammonia and total carnitine levels normalized. At one year follow up, IQ’s returned to previous baselines, and MRI atrophy (Case 1) normalized. EEG aberrancies were unchanged. Patients were mood and behaviorally stable on oxcarbazepine.
CONCLUSIONEvidence of cognitive decline while on valproate warrants ammonia and carnitine level testing. If these levels are abnormal, VHE should be diagnosed and valproate should be removed as rapidly as feasible; L-carnitine supplementation (the lesser of 100 mg/kg/day or 2 grams/day) should be implemented to normalize the carnitine level.
Funding AcknowledgementsNo funding.
107 Using Brief Motivational Interviewing to Increase Healthy Lifestyle Habits in Overweight and Obese Adults in a Rural Family Practice Setting
- Amanda McNulty
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- 15 June 2018, pp. 69-70
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Obesity is a rapidly growing epidemic in the United States of America resulting in a multitude of comorbid conditions. Individuals living in rural areas have a higher prevalence of obesity than in urban settings. Effective treatment of obesity is needed to decrease the morbidity and mortality of this chronic disease. Using motivational interviewing (MI) techniques to address unhealthy lifestyle habits has previously proven to be effective in aiding individuals to achieve a healthier lifestyle.
ObjectivesThe main objective is to determine the effectiveness of brief MI used during regular office visits and with phone follow-ups on body mass index (BMI) at the initiation of the project, as well as at the 3-month follow-up. Secondary objectives are to determine the effect brief MI has on the amount of weekly physical activity, advancing the individual to the next stage on the Transtheoretical Model of Change (TTM) continuum and determining common barriers to leading a healthy lifestyle in a rural adult population.
MethodParticipants (n=15) were recruited using a convenience sampling method from the primary care practice. Using a pretest/posttest design, individuals were asked to complete a survey regarding their amount of weekly exercise, their perceived stage of change and their barriers to healthy lifestyle choices. A pre- and post-intervention BMI was collected. One in-office brief MI session and two monthly phone sessions were conducted, each lasting not longer than ten minutes.
ResultsA total of 14 participants, mostly female (67%), aged 36 to 45 years old (33%), Caucasian (73.3%), and had some college education (40%), completed the study. It was hypothesized that brief MI would result in decreased BMI, increased exercise and advancement along the TTM continuum. No significant difference in the pre-and post -intervention BMI ([M=37.88, SD=9.15] vs [M=37.01, SD=9.37]); t (27)=0.25, p=0.801 was found. Many participants (n=10), however, had a decrease in BMI. The difference in weekly activity (M=644.2 min vs M=268.57 min) was not found to be statistically significant; t (27)=1.40, p=0.17. An increase in readiness to change was noted, but, was not significant (p =0.52). Of 34 responses, chronic pain or health conditions (n=10) and scheduling conflicts (n=7) were the two top cited reasons for not practicing a healthylifestyle.
ConclusionsThis QI project did not demonstrate statistically significant improvement in BMI, weekly exercise or readiness to change after three months of brief MI. It is important to note, however, that many individuals did experience an overall decrease in BMI. It is also promising to note that more individuals were participating in healthylifestyle activities more frequently post-intervention when analyzed on the TTM continuum. Further studies are needed to analyze the most effective strategies to assist individuals in rural settings to make healthier lifestyle choices.
Funding AcknowledgementsNo funding.
108 Lurasidone in Children and Adolescents With Bipolar Depression Presenting With Mixed Features
- Cynthia Siu, Andrei Pikalov, Michael Tocco, Antony Loebel
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- 15 June 2018, p. 70
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Objective
To evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed features.
MethodsPatients 10 to 17 years of age, inclusive, with a DSM-IV-TR diagnosis of bipolar I depression, were randomized to 6 weeks of double-blind treatment with once-daily, flexible doses of lurasidone 20-80 mg or placebo. The presence of mixed features (subthreshold hypomanic symptoms) was defined as a YMRS score > 5 at study baseline. Efficacy analyses included change from baseline to week 6 in Children Depression Rating Scale, Revised (CDRS-R) score (the primary outcome), and Clinical Global Impressions, Bipolar Severity of Depression Score (CGI-BP-S), using mixed model for repeated measures (MMRM) analysis.
ResultsAt baseline, mixed features were present in 54.2% of patients (lurasidone, n=97/173; placebo, n=89/170). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in CDRS-R scores at week 6 in the mixed features group (-21.5 vs -15.9; P<0.01; effect size, 0.45), and in the group without mixed features (-20.4 vs -14.8; P<0.01; effect size, 0.45). Likewise, lurasidone was associated with greater effect size (vs placebo) for reductions inCGI-BP-S scores at week 6 in the mixed features group (-1.6 vs -1.1; P<0.001; effect size 0.57), and in the group without mixed features (-1.3 vs -1.0; P=0.05; effect size 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with mixed features(lurasidone 8.2% vs. placebo 9.0%) and without mixed features (lurasidone 1.3% vs. placebo 3.7%).
ConclusionsIn this post-hoc analysis, lurasidone was found to be efficacious for treating child and adolescent patients with bipolar depression presenting with mixed features(assessed cross-sectionally at study baseline). There was no increased risk of treatment-emergent mania observed in patients with or without mixed features.
Funding AcknowledgementsSunovion Pharmaceuticals Inc.
109 Comparative Efficacy and Tolerability of Lurasidone Versus Other Oral Atypical Antipsychotics for Pediatric Schizophrenia: A Network Meta Analysis
- Celso Arango, Daisy Ng-Mak, Elaine Finn, Aidan Byrne, Krithika Rajagopalan, Antony Loebel
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- 15 June 2018, pp. 70-71
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Study Objective
This analysis assessed the relative efficacy and tolerability of lurasidone versus other atypical antipsychotics in the treatment of pediatricschizophrenia.
MethodsA systematic literature review identified 13 randomized-controlled trials for the treatment of pediatric schizophrenia. A Bayesian network meta-analysis compared the efficacy and tolerability of the following atypical antipsychotics: aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, andziprasidone. Patients were 7-17 years old and trial duration ranged from 6-12 weeks. Outcomes included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), weight gain, all-cause treatment discontinuation, and extrapyramidal symptoms. Results from the fixed effect models were reported as mean differences for continuous outcomes and odds ratios for binary outcomes; each with a 95% credible interval.
ResultsLurasidone had significantly greater improvement compared with placebo for PANSS (-7.95 [-11.76, -4.16]) and CGI-S (-0.44 [-0.67, -0.22]), but did not differ from comparators. The differences in weight gain for lurasidone relative to comparators were as follows: clozapine (-3.81kg [-8.03, 0.42]), olanzapine (-3.62kg [-4.84, -2.41]), quetiapine (-2.13kg [-3.20, -1.08]), risperidone (-1.16kg [-2.14, -0.17]), asenapine (-0.98kg [-1.71, -0.24]), paliperidone (-0.85kg [-1.57, -0.14]), aripiprazole (-0.15kg [-0.88, 0.58]), and ziprasidone (0.38kg [-0.49, 1.24]); all were statistically significant except for clozapine, aripiprazole, and ziprasidone. Rates of all-cause discontinuation andextrapyramidal symptoms were similar for lurasidone and comparators, except aripiprazole and paliperidone, which had higher rates of all-cause discontinuation.
ConclusionsIn this network meta-analysis of atypical antipsychotics for the treatment of adolescent schizophrenia, lurasidone was associated with similar efficacy, but less weight gain than active comparators.
Funding AcknowledgementsThis study was funded by Sunovion Pharmaceuticals Inc.
110 Increased Intracranial Pressure induced Mal de Debarquement Syndrome
- Angela Rekhi, Alan R. Hirsch
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- 15 June 2018, p. 71
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Study Objective
Mal de Debarquement Syndrome (MdDS) is a prolonged rocking or swaying type of imbalance that occurs after lengthy exposure to motion, yet ensuing in the absence of motion. The provoking motion is most commonly following sea travel. MdDS has not heretofore been described in association with increased intracranial pressure. Such a case is presented.
MethodsCase Study: A 46-year-old female, with a history of hydrocephalus after infantile meningitis with ventriculoperitoneal shunt placement and multiple revisions, has a constant feeling of ‘rocking side to side’. One year and one-half year prior to presentation, she suffered two epochs of severe bilateral headaches coinciding with, as she describes, “the feeling of rocking, as if on a ship”. Both of these episodes were constant and lasted all day, progressively increasing in intensity for one week. During these events, she admits to nausea, but denied any vomiting, spinning, epigastric rising, or déjà vu or jamais vu. During the epochs there was no tinnitus, orthostatic hypertension, visual obscuration, loss of consciousness, syncope, seizures, weakness or falls. Prior to, or associated with the swaying sensation, she denies lightheadedness, pallor, salivation, blurred vision, tachycardia, visual auras or other neurological auras. There were no alleviating or aggravating factors, and were unrelated to position change, head movement, neck extension or rotation, coughing, or urination. She denies any recent air-travel, diving, sleeping on a waterbed, or alcohol use. In both epochs, shunt malfunction and associated increased intracranial pressure were discovered. Immediate resolution of the headache and dizziness episodes were achieved after shunt revision with correction of increased intracranial pressure.
ResultsAbnormalities in Cranial Nerve (CN) Examination: CN I: Alcohol Sniff Test: 14 (hyposmia). CN II: Visual Acuity OS 20/25. CN III, IV, VI: Saccadization of horizontal eye movement. Bilateral ptosis left > right. CN IX, X: Uvula deviated to the right. Motor Examination: Drift Testing: Left upward and outward drift with left Abductor Digiti Minimi sign. Reflexes: 3+ throughout.
ConclusionsTypically seen in middle aged woman, MdDS is a rare, self-limiting condition in which an abnormal sensation of rocking or swaying back and forth is perceived after exposure to air, car, land or sea travel (Nwagwu 2015). The phantom perception of self-motion occurs upon return to ground (Nwagwu 2015). This has been postulated to be due to maladaptation of the vestibulo-ocular reflex (Hain 2016) or disorder of connection between the entorhinal cortex and amygdala (Cha 2012). Increased intracranial pressure can affect the entire neural axis, including brainstem and cortical areas associated with MdDS. In those who present with intractable MdDS, measurement of intracranial pressure and treatment of any elevations may be warranted.
Funding AcknowledgementsSmell and Taste Treatment and Research Foundation
111 A Novel Dual-Channel Deep Transcranial Magnetic Stimulator for Major Depressive Disorder
- Eiran V Harel, Dikla Shmuel, Daniel Antler, Dana Katz, Elina Pushkarski, Ezekiel Ais, Anna Schvartz, Aron Tendler, Yiftach Roth, Abraham Zangen, Yechiel Levkovitz
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- 15 June 2018, pp. 71-72
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Background
Repetitive deep transcranial magnetic stimulation (dTMS) is efficacious for treatment resistant major depressive disorder (TRD) with the H1 coil by stimulating the prefrontal cortex, left more than right, at high frequency. Theoretically, the efficacy of dTMS could be optimized by simultaneously stimulating the right and left lateral prefrontal cortices (PFC) with different frequencies. This study tested the efficacy of a novel dual-channel dTMS stimulator with dual dTMS coils, in patients with TRD.
MethodsThis study recruited forty-seven outpatients diagnosed with TRD, age 18-65, Hamilton Depression Rating Scale (HDRS-21) score ≥25. Each patient received 20 open label treatment sessions, five days a week for 4 consecutive weeks. Treatments were administered with the dual-channel stimulator (Brainsway Multiway dTMS device) using two channels: a. 10 Hz over the left PFC. b. 1 Hz over the right PFC. Primary and secondary efficacy outcome measures were the change in HDRS-21 score and response/remission rates at week 5, respectively.
ResultsThe HDRS-21 score decreased from an average of 25.94 to 14.69 (P<0.001). Thirty-six patients completed four weeks of treatment. Of them, seventeen (47%) responded (HDRS-21 score decrease of ≥ 50% from their initial score) and eight (22%) remitted (HDRS-21 score of < 10 at the end of the study).
DiscussionThis open study shows promising results for multichannel simultaneous dTMS treatment of TRD using the Brainsway Multiway Device. Further randomized controlled studies are necessary to aid the high number of patients with TRD.
Funding AcknowledgementsBrainsway Ltd.
112 Healthcare Utilization and Costs for Patients With Tardive Dyskinesia
- Benjamin Carroll, Paul Juneau, Debra Irwin
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- Published online by Cambridge University Press:
- 15 June 2018, p. 72
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Introduction
Tardive dyskinesia (TD) is an often-irreversible movement disorder that usually results from prolonged use of antipsychotics. Although the burden of TD on patients’ quality of life has been reported, there is limited evidence of its impact on the healthcare system.
ObjectiveTo assess healthcare utilization and costs between TD and non-TD patients in a sample of patients from the commercially insured and Medicare Supplemental US populations.
MethodsA retrospective cohort analysis was conducted using Truven MarketScan Commercial/Medicare claims data. For each patient included in the analysis, the index date was set as the first TD diagnosis between 1/1/2008 and 9/30/2014. Patients with TD were then matched to similar patients without TD to compare resource utilization andcosts. Descriptive statistics on the incidence of resource utilization and costs of healthcare were reported.
ResultsA total of 1020 patients were included in this analysis. TD patients had significantly greater annual all-cause (TD: $54,656; non-TD: $28,777) and mental health-related (TD: $10,199; non-TD: $2,605) healthcare costs compared with non-TD patients (P<0.01). This was primarily because a higher proportion of the TD patientsexperienced hospitalizations (all-cause 56%; mental health 17%) and emergency room visits (all-cause 62%; mental health 27%) compared with non-TD patients(hospitalizations: all-cause 26%, mental health 5%; emergency room visits: all-cause 41%; mental health 13%) (all P<0.001).
ConclusionsPatients identified as being diagnosed with TD demonstrate significantly higher healthcare utilization and costs in the 12 months after diagnosis than do similar patients without TD.
Presented at: Psych Congress; September 16–19, 2017; New Orleans, Louisiana, USA.
Funding AcknowledgementsThis study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
113 Dasotraline for the Treatment of Moderate to Severe Binge Eating Disorder in Adults: Results From a Randomized, Double-Blind, Placebo-Controlled Study
- Bradford Navia, James I. Hudson, Susan L McElroy, Anna I. Guerdjikova, Ling Deng, Kaushik Sarma, Seth Hopkins, Kenneth Koblan, Antony Loebel, Robert Goldman
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- Published online by Cambridge University Press:
- 15 June 2018, pp. 72-73
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Objectives
Binge eating disorder (BED) is the most common eating disorder in the US, with a lifetime prevalence of 2.8%. Disturbances in reward circuitry have been implicated in its pathogenesis. Dasotraline is a novel and potent dopamine and norepinephrine reuptake inhibitor with slow absorption and a long half-life resulting in stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated the efficacy and safety of flexibly-dosed dasotraline (4, 6, and 8 mg/day) vs placebo in adults with moderate to severe BED over a 12-week period (NCT02564588).
MethodsKey inclusion criteria included moderate to severe BED based on a history of ≥2 binge eating days/week for ≥6 months prior to screening, and ≥3 binge eating days for each of2 weeks prior to randomization, as documented in participant’s binge eating diary. Patients were randomized 1:1 to flexibly-dosed dasotraline (4, 6, 8 mg/day) or placebo. Theprimary endpoint was change from baseline (CFB) in the number of binge eating days per week at Week 12. Key secondary endpoints were: CFB in Clinical Global Impression–Severity (CGI-S) Scale at Week 12; CFB in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) at Week 12; and the percentage ofsubjects with a 4-week cessation from binge eating prior to Week 12 or end of treatment (EOT). Except for 4-week cessation, the other three variables were analyzed using amixed model for repeated measures (MMRM).
Results317 subjects (84% female) received ≥1 dose of study medication (mean age was 38.2 years; mean number of binge eating days per week, 4.25; mean CGI-S score, 4.5; mean BMI, 34.7). The MMRM analysis of CFB at Week 12 in the number of binge days/week yielded a significant mean difference of –0.99 (95% CI: –0.65 to –1.33; p<0.001) infavour of dasotraline (–3.74 in the dasotraline group vs –2.75 in the placebo group). All three key secondary endpoints were met at Week 12 or EOT: 46.5% of subjects in thedasotraline group achieved at least 4 consecutive weeks’ cessation from binge eating vs 20.6% in the placebo group (p<0.001); CFB in CGI-S and YBOCS-BE scores were also statistically significant in favour of dasotraline (p<0.001). The treatment-emergent adverse events (TEAEs) that occurred more frequently with dasotraline vs placebo at >2% incidence included: insomnia (44.6% vs 8.1%), dry mouth (27.4% vs 5.0%), decreased appetite (19.7% vs 6.9%), anxiety (17.8% vs 2.5%), nausea (12.7% vs 6.9%) and decreased body weight (12.1% vs 0%). Discontinuation due to AEs occurred in 11.5% of patients taking dasotraline vs 2.5% taking placebo.
ConclusionsIn adults with moderate to severe BED, there were highly significant and clinically meaningful reductions with dasotraline vs placebo in the frequency of binge eating, global severity of illness, and obsessive-compulsive symptoms related to binge eating. These results suggest dasotraline may offer a novel, well-tolerated and efficacious treatmentfor BED.
Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.
116 Retrospective Analysis of Clozapine Augmentation in Treatment-Resistant Schizophrenia in an Outpatient Setting
- Charles Odom, Frozan Walyzada, Pankaj Manocha, Monika Gashi, Ashaki Martin, Raminder Cheema, Wen Gu, Ketki Shah, Panagiota Korenis
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- Published online by Cambridge University Press:
- 15 June 2018, pp. 73-74
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Study Objectives
This retrospective analysis hopes to add to the literature about Treatment Resistant Schizophrenia (TRS), augmentation strategies with antipsychotics used in our patient population with the hopes of clarifying what possibilities should be further studied. In addition, we aim to emphasize the need for focusing on individualized treatment and multidisciplinary efforts to ensure compliance and appropriate disposition options.
MethodWe reviewed retrospectively 3025 charts of patients between January 2017 to March 2017 in our outpatient department establishing which antipsychotic clozapineaugmentation strategies were being used. We also did a literature review to establish what augmentation strategies are recommended. These patients will then be compared to a random sample of patients in the clinic who were not prescribed clozapine and compared for readmission rate, side effect profile, length of stay while admitted, frequency of clinic attendance and compliance with outpatient appointments.
ResultsOut of 3025 patients 35 were prescribed Clozapine as monotherapy and 5 patients had clozapine plus psychopharmacological augmentation. Ages ranged from 21-86. Out of the 39 patients, there were 13 male and 26 female. The predominant diagnosis was mood disorder or MDD with psychotic features followed by schizophrenia. The augmentation antipsychotics used were aripiprazole and risperidone. In the literature, the most frequent augmentation strategy for TRS is adding another antipsychotic with more D2 receptor blockade. Other strategies involve identifying and treating the symptoms not controlled by clozapine.
ConclusionsCurrently augmentation of Clozapine in TRS is highly individualized due to lack of supporting evidence to state the contrary. When working with treatmentresistant patients who are not responding to clozapine alone, it is imperative to thoroughly review and consider all treatment options and augmentation strategies. More studies should be done in controlled settings to better evaluate possibilities as well as more evaluations to be done on other ways of augmentation of clozapine. Literature has stated between 20-60% of patients are defined as TRS. Clozapine is considered as one of the most effective treatment available at present time for TRS. Recent literature suggests despite its superior efficacy, as many as 70% of those suffering from TRS on clozapine continue to suffer from positive, negative or cognitive symptoms. The literature has abundant adjunctive treatment strategies such as the addition of antipsychotics, mood stabilizers, antidepressants, or even with the use of electroconvulsive therapy. We emphasize the importance of correctly identifying TRS patients who may benefit from the initiation of clozapine, what would be beneficial for them if they do not respond, how to tailor their treatment to target symptoms not being ameliorated, and recommend treatment in these complex cases be multidisciplinary.
Funding AcknowledgementsNo funding.