PM412. Emergence of Tardive Dyskinesia upon Clozapine Treatment: A Case Report

s | 49 Improvements in PANSS scores following OL PP1M were similar in recent RIS/PALI (mean [SD] of -18.3 [17.96]) and no prior RIS/PALI (-21.1 [16.40]) subgroups at OL endpoint. Relapse-free rates during DB phase were comparable across recent RIS/PALI (PP3M: 89.7%; PP1M: 87.1%, 95% CI for difference: [-4.7; 10.0]) and no RIS/PALI subgroups (PP3M: 91.6%; PP1M: 90.8%, 95% CI for difference: [-4.5; 6.0]). Incidences of extrapyramidal symptomrelated adverse events were: recent RIS/PALI (OL PP1M:12.4%; DB: PP3M:7.8% vs PP1M:7.0%) and no RIS/PALI (OL PP1M: 11.4%; DB: PP3M: 7.1% vs PP1M: 6.7%). Conclusion: This exploratory analysis suggests comparable treatment outcomes and tolerability following PP3M or PP1M administration in patients with schizophrenia, irrespective of prior treatment with/without oral RIS/PALI. PM410 Comparison of 3-Monthly versus 1-Monthly Paliperidone Palmitate for Time to Onset and Time to Resolution of Extrapyramidal Symptoms in Patients with Exacerbated Schizophrenia Maju Mathews1*, Isaac Nuamah1, Adam Savitz1, David Hough1, Dean Najarian2, Edward Kim2, Srihari Gopal1 1Janssen Research & Development, LLC, New Jersey, USA 2Janssen Scientific Affairs, LLC, New Jersey, USA *Presenting author Abstract Background: This post-hoc analysis was performed to compare the overall incidence, time-to-onset (TTO) and time-to-resolution (TTR) of extrapyramidal symptoms (EPS)-related adverse events (AEs) after treatment with paliperidone palmitate (PP) 3-monthly (PP3M) vs. 1-monthly (PP1M) long-acting injectable in patients with schizophrenia. Methods: EPS-related AEs were summarized by grouped terms (Overall and further classified into Dystonia, Dyskinesia, Hyperkinesia, Parkinsonism and Tremor), study phases (openlabel [OL]: PP1M, double-blind [DB]: PP1M or PP3M), TTO and TTR, and descriptively compared. TTO and TTR were further analyzed by final OL dose (50/75 mg eq., 100 mg eq. and 150 mg eq.) and age (18–25, 26–50 and 50+ years) subgroups. Results: Overall incidence of EPS-related AEs was 12.6% (PP1M) during OL phase, reducing to 8.3% (PP3M) and 7.4% (PP1M) during DB phase. Median TTO for all EPS-related AEs was 17 days (range: 1–120) after PP1M OL treatment; 115 days (range: 1–323)Background: This post-hoc analysis was performed to compare the overall incidence, time-to-onset (TTO) and time-to-resolution (TTR) of extrapyramidal symptoms (EPS)-related adverse events (AEs) after treatment with paliperidone palmitate (PP) 3-monthly (PP3M) vs. 1-monthly (PP1M) long-acting injectable in patients with schizophrenia. Methods: EPS-related AEs were summarized by grouped terms (Overall and further classified into Dystonia, Dyskinesia, Hyperkinesia, Parkinsonism and Tremor), study phases (openlabel [OL]: PP1M, double-blind [DB]: PP1M or PP3M), TTO and TTR, and descriptively compared. TTO and TTR were further analyzed by final OL dose (50/75 mg eq., 100 mg eq. and 150 mg eq.) and age (18–25, 26–50 and 50+ years) subgroups. Results: Overall incidence of EPS-related AEs was 12.6% (PP1M) during OL phase, reducing to 8.3% (PP3M) and 7.4% (PP1M) during DB phase. Median TTO for all EPS-related AEs was 17 days (range: 1–120) after PP1M OL treatment; 115 days (range: 1–323) and 98.5 days (range: 1–322) after treatment with PP3M and PP1M, respectively (DB phase). Median TTR was 36.5 days (range: 1–127) in PP1M group (OL), and was generally similar for PP3M (91 days [range: 1–336]) vs. PP1M (85.5 days [range: 1–337]) during DB phase. Overall median TTO and TTR values were comparable between PP3M and PP1M formulations. Subgroup analysis revealed no clear dose-response or age-related differences in TTO and TTR of EPS-events for the two formulations. Discussion: The overall incidence of EPS-related AEs, TTO and TTR of EPS-events were found to be comparable in patients with schizophrenia receiving either PP3M or PP1M long-acting injectable. PM411 Evaluation of Paliperidone Palmitate Long-Acting Injectable Therapy by Duration of Illness in Patients With Schizophrenia Brianne Brown,1 Ibrahim Turkoz,2 Branislav Mancevski,1 Maju Mathews2 1Janssen Scientific Affairs, LLC, Titusville, NJ, USA 2Janssen Research and Development, LLC, Titusville, NJ, USA Abstract Introduction: Guidelines specify long-acting injectable (LAI) antipsychotic use earlier in schizophrenia because it may delay functional deterioration. Paliperidone palmitate (PP) LAI therapy in patients with schizophrenia was evaluated by duration of illness. Methods: Post hoc analysis of a randomized, double-blind (DB), parallel-group, multicenter, noninferiority study (NCT01515423). Subjects with schizophrenia were treated with PP once-monthly (PP1M) in a 17-week open-label (OL) phase. Upon meeting clinical stabilization criteria, they were randomized 1:1 to PP1M or PP once-every-3-months (PP3M) in a 48-week relapse-prevention phase. Subjects were evaluated based on duration of illness (≤5, 6–10, and >10 years since diagnosis); PP1M and PP3M results were combined. Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale scores and functional remission rates (PSP >70 from week 13 [OL] and during DB phase for ≥6 months) were analyzed. No adjustment was made for multiplicity. Results: 532, 337, and 558 subjects diagnosed with schizophrenia ≤5, 6–10, and >10 years ago, respectively, entered OL phase. Of these, 379 (71.2%), 235 (69.7%), and 380 (68.1%) met clinical stabilization criteria and entered DB phase. Significant differences were observed in the ≤5 and 6–10 groups versus the >10 group from DB baseline to DB endpoint for PANSS and PSP total scores (P<0.03 for all). More patients achieved functional remission in the ≤5 (26.4%) and 6–10 (30.2%) groups versus the >10 group (18.6%). Conclusion: Improvements were observed with PP LAIs in all subgroups, with greater improvements among patients earlier in the illness (<5 or 5–10 years) compared to those with more chronic illness (>10 years). Support: Janssen Scientific Affairs, LLC PM412 Emergence of Tardive Dyskinesia upon Clozapine Treatment: A Case Report Sun-Young Moon, MD(1,2), Corresponding co-author Hanson Park, MD(2, 3) 1 Department of Psychiatry, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea 2 Department of Psychiatry, St. Andrews Neuropsychiatric Hospital, Icheon, Korea 3 Department of Anthropology, College of Social Science, Seoul National University, Seoul, Korea Abstract Objective: Clozapine is an atypical antipsychotic drug famous for its low propensity to cause extrapyramidal symptoms, one of those mainly being tardive dyskinesia(TD). Mechanism underlying this so-called anti-TD property of clozapine is largely in a veil as well as the pathophysiology of TD itself. Furthermore, terminologies referring to TDs of varying mechanisms heretofore lack consensus among clinicians. This study introduces a case of newly emergent TD after clozapine usage, and discusses the plausible mechanism of how TD develops in varying clinical situations. Methods & Results: We reviewed a case of a 57-year-old female with schizophrenia. She had been treated intermittently with haloperidol and a few types of small-dosage atypical antipsychotics for 5 years. She was admitted to closed ward for worsening of psychotic symptoms. Prior to that, she had been medicationfree for at least 1 month. We first used paliperidone for a month, and medication was changed to clozapine due to unsatisfactory response. 1.5 month into clozapine use, the patient developed aObjective: Clozapine is an atypical antipsychotic drug famous for its low propensity to cause extrapyramidal symptoms, one of those mainly being tardive dyskinesia(TD). Mechanism underlying this so-called anti-TD property of clozapine is largely in a veil as well as the pathophysiology of TD itself. Furthermore, terminologies referring to TDs of varying mechanisms heretofore lack consensus among clinicians. This study introduces a case of newly emergent TD after clozapine usage, and discusses the plausible mechanism of how TD develops in varying clinical situations. Methods & Results: We reviewed a case of a 57-year-old female with schizophrenia. She had been treated intermittently with haloperidol and a few types of small-dosage atypical antipsychotics for 5 years. She was admitted to closed ward for worsening of psychotic symptoms. Prior to that, she had been medicationfree for at least 1 month. We first used paliperidone for a month, and medication was changed to clozapine due to unsatisfactory response. 1.5 month into clozapine use, the patient developed a 50 | International Journal of Neuropsychopharmacology, 2016 severe degree(grade 4 of Abnormal Involuntary Movement Scale, or AIMS) of TD in whole body including orofacial, truncal, limb areas. Clozapine was drastically reduced and TD ameliorated to minimal degree(AIMS grade 1) in a 3-months-time, but still persisting. Conclusion: The emergence of TD in this case cannot best be explained by withdrawal, covert or spontaneous TD like most of the previous case reports of TD after clozapine use. Rather, the relatively acute onset of TD and the risk factors for TD the patient held sums up for the likeliness of association with neuronal degenerative changes in striatum. Previous genetic and epidemiologic evidences suggest for possible association of genetic alteration. This calls for further studies regarding pathophysiology of TD and according genetic markers. PM413 Metabolic Syndrome in Patients With Schizophrenia Receiving Long-Term Treatment With Lurasidone, Quetiapine XR, or Risperidone John W. Newcomer, MD1; Michael Tocco, PhD2; Andrei Pikalov, MD, PhD2; Hanzhe Zheng, PhD2; Josephine Cucchiaro, PhD2; Antony Loebel, MD2 1Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, USA; 2Sunovion Pharmaceuticals Inc., Fort Lee, NJ, and Marlborough, MA, USA Topic: Clinical Sub-Topic by Disorder: Schizophrenia Sub-Topic by Drug and Methodology: Antipsychotics ABSTRACT Objective: This post hoc analysis evaluated metabolic syndrome occurrence during long-term treatment of schizophrenia with lurasidone or other antipsychotic agents. Methods: Metabolic syndrome rates (as defined by the US National Cholesterol Education Program-Adult Treatment Panel III without using drug treatment criteria) were evaluated in adult patients with schizophrenia treated with lurasidone in 2 longterm, active-controlled studies (quetiapine XR or risperidone). In the quetiapine XR–controlled study, patients completing a 6-week, double-blind, placebo-controlled, fixed-dose trial of lurasidone (80 mg/d or 160 mg/d) or quetiapine XR (600 mg/d) continued on double-blind, flexibly dosed lurasidone (40–160 mg/d) or quetiapine XR (200–800 mg/d) for up to 12 months. In the risperidone-controlled study, patients received double-blind, flexibly dosed lurasidone (40–120 mg/d) or risperidone (2–6 mg/d) for up to 12 months. Results: Among patients without metabolic syndrome at baseline in the quetiapine XR–controlled study, 2.4% (2/84) of patients treated with lurasidone and 7.4% (2/27) of patients treated with quetiapine XR developed metabolic syndrome at month 12; risk for developing metabolic syndrome was not significantly different between treatment groups (odds ratio=0.305; 95% CI, 0.041, 2.277; P=NS). Of patients without metabolic syndrome at baseline in the risperidone-controlled study, 10.3% (12/117) of patients treated with lurasidone and 23.2% (16/69) of patients treated with risperidone developed metabolic syndrome at month 12; risk for developing metabolic syndrome was significantly lower for lurasidone-treated versus risperidone treated patients (odds ratio=0.379; 95% CI, 0.167, 0.858; P=0.02). Conclusions: In this post-hoc analysis, long-term treatment with lurasidone was associated with significantly lower rates of metabolic syndrome in patients with schizophrenia compared with treatment with risperidone; metabolic syndrome rates were numerically lower (but not significantly different) for lurasidone compared with quetiapine XR. Sponsored by Sunovion Pharmaceuticals Inc. Disclosures Dr Newcomer has received grant funding from National Institutes of Health and Otsuka America Pharmaceutical, Inc.; served as an independent scientific member on a Data Safety Monitoring Board for Amgen Inc.; and served as a consultant for Reviva Pharmaceuticals, Inc. Drs Tocco, Pikalov, Zheng, Cucchiaro, and Loebel are employees of Sunovion Pharmaceuticals Inc. PM414 The impact of long acting paliperidone palmitate on clinical outcomes and hospital stay in routine clinical practice: a UK service evaluation Sofia Pappa, Darren Bishop, Fintan Larkin, Rebecca Marriott, Katy