Abstracts
170 Prospective Evaluation of the Economic Utility of Combinatorial Pharmacogenomics in Generalized Anxiety Disorder and Major Depressive Disorder
- Nathan Roe, Catherine Passariello, Lisa Brown, James Li, Michael Jablonski, Bryan M Dechairo
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- Published online by Cambridge University Press:
- 15 June 2018, pp. 99-100
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Abstract
Mental illness is one of the leading causes of disability, with direct and indirect costs posing a significant financial burden. Previously, a large prospective economic utility study (n>13,000) showed that the GeneSight® test, a psychiatric pharmacogenomic decision support tool powered by CPGx® technology, reduced medication costs, increased adherence, andreduced polypharmacy for patients who had failed monotherapy for psychiatric disorders. The current study, which is a sub-analysis of this larger study, assessed cost savings associated with combinatorial pharmacogenomic testing in patients with generalized anxiety disorder (GAD) and major depressive disorder (MDD). Medication costs were extracted using pharmacy claims data provided by Medco, a large pharmacy benefits manager, for patients with GAD (n=318) and MDD (n=459). Medication cost savings per member per year (PMPY) for 1 year following the test were compared between patients whose medication regimens were congruent with the test recommendations and those whose medication regimens were incongruent with these recommendations. When healthcare providers’ decisions were congruent with combinatorial pharmacogenomic testing, PMPY savings was $6,747 (p<0.004) for GAD patients and $3,738 (p<0.004) for MDD patients versus incongruent decisions within these disease states. Among the congruent group, GAD patients experienced greater savings in central nervous system (CNS) medications (2-fold) compared to MDD patients. Additionally, analysis of a subset of patients prescribed at least one benzodiazepine six months prior to testing (n=660) demonstrated a significant decrease in benzodiazepine drug counts (p<0.001) and refills (p<0.001) after testing. Using the GeneSight test as a treatment decision support tool for patients with GAD or MDD resulted in significant medication cost savings when HCPs made congruent decisions with the combinatorialpharmacogenomic results. Furthermore, use of the GeneSight test decreased the use of benzodiazepines.
Funding AcknowledgementsResearch was funded by Assurex Health, Inc.
174 Pseudogout Induced by Vortioxetine
- Priya Batta, Davinder Dhillon, Alan R Hirsch
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- 15 June 2018, p. 100
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Study Objective
Vortioxetine induced monoarticular pain has not heretofore been described. Such a case is presented.
MethodCase study: A 49 year old right handed female with a past history of multiple hospitalizations for chronic severe migraine, presented with complaints of depression and stress. She has had depression for 20 years, which has been constant and worsened in the past 5 years. As her migraines became more frequent, her depression also worsened. She has never been suicidal, but does endorse sadness, crying spells, fatigue, demotivation, lack of interest, poor concentration, irritability, anger, guilt, hopelessness, helplessness, anorexia, PM insomnia with frequent awakenings, absent libido and racing thoughts.
ResultsAbnormalities in her mental status examination: Orientated times 2. Disheveled. Defensive. Motor retardation. Mood: depressed, anxious and irritable with blunted affect. Remote memory: President: Obama,?. Beck Depression Inventory II: 23 (moderate depression). Beck Anxiety Inventory: 25 (moderate anxiety).
The patient was begun on 5 mg of vortioxetine every night. Within two days, she developed pain and swelling of the distal interphalangeal joint of the left great toe. The pain was so severe that she demonstrated an antalgic gait. After five days the medication was discontinued and two days later, there was full resolution of the swelling and pain, and ambulation returned to normal.
ConclusionsThe mechanism whereby vortioxetine induced this monoarticular pain is unclear. Underlying depression alone can precipitate arthritic exacerbation (Trivedi, 2004). This was unlikely given the long duration of her depression as well as the timing of the precipitant (vortioxetine use) and resolution shortly after the medication was discontinued. Alternatively, in the depressed state, there may be a greater perception of somatic pain, which allowed her to appreciate any arthritic pain which may have pre-existed the use of vortioxetine (Howard, 1991). As such, this may have represented a correspondence bias (Gilbert, 1995). Furthermore, mild new pain is perceived as more intense in those who are depressed (Howard, 1991). Thus, any minimal arthritic injury may be viewed as more intense. Vortioxetine may have paradoxically exacerbated anxiety and anxiety can precipitate pain (Narasimhan & Campbell). Alternatively, vortioxetine could have caused a generalized allergic reaction, which may have initially manifest in the great toe. If the patient continued the medication, she may have developed a generalized systemic reaction including involvement of multiple joints. Another possibility is that it caused an allergic histamine mediated hive like reaction, generalized, as well as on the toe. Continued use of the joint may have caused this to be intensified, with associated swelling, while the general reaction subsided. Inquiry about monoarticular involvement in those taking vortioxetine is warranted.
Funding AcknowledgementsSmell & Taste Treatment and Research Foundation
175 Burning Mouth Syndrome Equivalent to Restless Leg Syndrome
- Priya Batta, Sarosh Majeed, Davinder Dhillon, Alan R Hirsch
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- 15 June 2018, p. 101
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Study Objective
Stuginski-Barbosa reported a patient with Burning Mouth Syndrome (BMS), whose symptoms were transiently improved with tongue movement, postulated to be an oral equivalent of restless leg syndrome (RLS) (Stuginski-Barbosa, 2008).
MethodsFour Case Studies are described.
ResultsCase 1: A 35 year old pathological left handed woman presented with one-year history of burning and stinging sensations on the sides of the tongue and lips without any known precipitant. It is reduced with chewing gum and eating. For the last few months she noticed tongue movement reduced the burning sensation. Two to three seconds of tongue movement alleviated the burning from 3/10 to 0/10 in intensity, which persists for one minute after cessation of tongue movement.
Case 2: A 57 year old right handed female, three years prior to presentation, had multiple teeth extractions. Four months later, she perceived a rough sensation of her tongue, which has gradually changed to a burning sensation which has persisted since then. The burning is 10/10 in severity and constant. Chewing 24 pieces of gum a day reduces the pain. Movement of the tongue including anterior-posterior protrusion and retraction, side to side movements without contacting surrounding oral mucosa, converted pain from 9/10 to 5/10, which lasted approximately 1 minute.
Case 3: Eight years prior to presentation, this 60 year old woman developed BMS, after dental extraction. The pain involves the tongue (right and center of palate) accompanied by a gritty sandpaper-like sensation. The burning is a level 5/10 in intensity and progressively worsens throughout the day. Burning mouth pain is made less intense with chewing gum and using dental wax. Baseline burning mouth severity is at level 5/10 however, with protrusion, retraction, and side-to-side movement of the tongue, the intensity dropped to 3/10.
Case 4: Three years prior to presentation, a 59 year old female patient suffered severe allergies with onset of burning mouth and absent taste. The burning is in the middle of her tongue, rarely, her palate, but never on her lips. Severity is 2/10 and is worse in the morning, with drinking red wine, and hot drinks. It is better with cold drinks and ice cream. Movement of her tongue side-to-side eliminates the burning severity from 2/10 to 0/10, lasting one minute.
ConclusionLike the patients described by Stuginski & Barbosa 2008, these four patients showed reduced pain in response to tongue kinesia (Stuginski-Barbosa, 2008). Their mandibulation of gum as an analgesic maneuver may have been due, not to the taste of the gum, but rather to the associated tongue movement that mastication induces. Through moving, large nerve fibers of proprioception are stimulated, which may act through the Gate Controlled Theory of Pain of Melzac and Wall, to reduce unrestricted small nerve fiber discharge, thus inhibiting pain. Query regarding movement or gum chewing inhibition of BMS is warranted.
Funding AcknowledgementsSmell & Taste Treatment and Research Foundation.
176 The Influence of Chronic Stress on the Development of Psychiatric Conditions
- Pwint Phyu, Rhaisa Dumenigo, Juan D. Oms, Luxhman Gunaseelan, Golbon Foroughi, Syed A. A. Rizvi
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- Published online by Cambridge University Press:
- 15 June 2018, p. 101
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Abstract
A 20-year-old woman with a history of bipolar disorder (BD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD) presented to the emergency department with suicidal ideation. This report compares her clinical course with that of her twin brother, who also had received a BD diagnosis but grew up in a less stressful environment than his sister. It also describes the possible genetic and environmental etiologic factors associated with BD, PTSD, BPD, and other psychiatric conditions. Chronic stress is strongly associated with the development of these conditions; pathologic processes involving the effect of stress hormones and neurotransmitters on the brain and central nervous system are described, along with pharmacologic and nonpharmacologic approaches to reducing chronic stress in persons with BD and other psychological disorders.
Funding AcknowledgementsNo funding.
177 Management of Treatment-Resistant Schizophrenia With Clozapine Augmentation
- Pwint Phyu, Emelina Arocha, Juan D. Oms, Luxhman Gunaseelan, Golbon Foroughi, Syed A. A. Rizvi
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- Published online by Cambridge University Press:
- 15 June 2018, p. 102
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Abstract
A 44-year-old woman with a history of chronic schizoaffective disorder, epilepsy, social phobia, anxiety, and panic attacks presented with concern for “feeling anxious.” After a history, physical examination, and laboratory tests, the woman received a diagnosis of treatment-resistant schizophrenia. While clozapine is the standard therapy for schizophrenia, certain patients such as the woman in this case do not respond well to clozapine monotherapy, requiring clozapine to be augmented with other antipsychotics or antidepressants. This case outlines the unique challenges of managing patients with treatment-resistant schizophrenia, especially when they present with comorbid conditions such as epilepsy that can limit treatment options. A multipronged approach, including pharmacologic therapy as well as cognitive behavioral therapy, should also be considered.
Funding AcknowledgementsNo funding.
178 Gender Differences in Prodromal Symptoms of Dementia
- Richard Wallis, Sheryl Bishop, Brian Downer, Thomas Méndez, Mukaila Raji, Aida Sapp
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- 15 June 2018, p. 102
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Study Objectives
This study proposed to test the postulate that the anxiety and insomnia symptom cluster (A/I) is a predictor of dementia.
MethodsA retrospective data analysis was conducted on the Aging, Demographics, and Memory Study (ADAMS) dataset in order to determine whether A/I symptoms or treatment were associated with subsequent dementia or cognitive impairment (DOCI). The study used logistic regression analysis and comparison of incidence rates on a sample of 249 participants.
ResultsThere was a significant relationship between A/I symptoms and subsequent DOCI in the male gender that was not found in the total sample or in females. No association with subsequent DOCI was found for benzodiazepine usage or non-benzodiazepine A/I medication usage.
ConclusionsThe gender differences identified suggest prodromal dementia phenotypes that are differentially expressed in males and females. By triangulating the approaches from multiple disciplines—such as neuroimaging and genetics—with prodromalsymptoms, it is possible that reliable early prediction may be accomplished.
Funding AcknowledgementsNo funding.
179 Dasotraline in Children With Attention Deficit Hyperactivity Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Study
- Robert Goldman, Lenard Adler, Thomas Spencer, Robert Findling, Seth C. Hopkins, Kenneth K. Koblan, Kaushik Sarma, Jay Hsu, Antony Loebel
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- Published online by Cambridge University Press:
- 15 June 2018, pp. 102-103
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Objectives
Once-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated dasotraline in children aged 6–12 years (NCT02428088).
MethodsPatients were randomized 1:1:1 to 6 weeks of once-daily, fixed-dose dasotraline 2 or 4 mg/day, or placebo. The primary efficacy endpoint was change from baseline (CFB) at Week 6 in ADHD Rating Scale Version IV – Home Version (ADHD RS-IV HV) total score, using a mixed model for repeated measures (MMRM) in the intent-to-treat (ITT) population. Secondary endpoints included Clinical Global Impression-Severity (CGI-S) score and safety endpoints.
ResultsThe mean age of 342 randomized patients was 9.1 [SD: 1.9] years; 66.7% were male. Overall, 79% of patients completed the study. In the ITT population (N=336), ADHD RS-IV HV total score improved significantly with dasotraline 4 mg/day vs placebo(least squares [LS] mean [SE] CFB at Week 6: –17.53 [±1.31] vs –11.36 [±1.29], respectively, p<0.001; effect size [ES]: 0.48). Inattentiveness and hyperactivity/impulsivity subscale scores significantly improved with 4 mg/day vs placebo at Week 6 (p=0.001, p=0.003, respectively). Improvement in CGI-S score was statistically significant with dasotraline 4 mg/day vs placebo(LS mean [SE] CFB at Week 6: –1.39 [±0.12] vs –1.04 [±0.12], respectively, p=0.040; ES: 0.29). No significant improvement was observed on the ADHD RS-IV HV total score and the CGI-S score for dasotraline 2 mg/day vs placebo. The most frequent treatment-emergent AEs (≥5% and higher than placebo) were (2 mg/day; 4 mg/day; placebo): insomnia (15.3%; 21.7%; 4.3%, all terms combined), decreased appetite (12.6%; 21.7%; 5.2%), weight loss (5.4%; 8.7%; 0%), irritability (3.6%; 7.0%; 6.0%), nasopharyngitis (0.9%; 5.2%; 0.9%), and nausea (0%; 5.2%; 2.6%).
ConclusionsCompared with placebo, dasotraline 4 mg/day significantly improved ADHD symptoms in children, as assessed by ADHD RS-IV HV total score and inattentiveness and hyperactivity/impulsivity subscale scores. Dasotraline was generally well tolerated; most common AEs were insomnia, decreased appetite, weight loss and irritability.
Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.
180 Efficacy of Dasotraline in Children With Attention Deficit Hyperactivity Disorder in a Laboratory Classroom Setting
- Robert Goldman, Ann Childress, Sharon B Wigal, Seth C Hopkins, Kenneth S Koblan, Kaushik Sarma, Jay Hsu, Antony Loebel
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- Published online by Cambridge University Press:
- 15 June 2018, p. 103
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Objectives
Once-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours. This phase 3 study evaluated the efficacy and safety of dasotraline in children with attention deficithyperactivity disorder (ADHD) throughout the day, in a laboratory classroom setting (NCT02734693).
MethodsChildren (6–12 years) meeting DSM-5 criteria for ADHD were randomized to 2 weeks of dasotraline or placebo (dosed daily at home at approximately 8 PM). Following an abbreviated practice day, laboratory classroom evaluations took place at baseline and on Day 15. The primary endpoint was mean change from baseline at Day 15 in ADHD symptoms, as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Combined Score (SKAMP-CS), obtained from the average of 7 assessments collected across the 12-hour laboratory classroom day (12–24 hours post-dose). Secondary endpoints included SKAMP scores obtained throughout the day at individual timepoints from 8 AM through 8 PM (12–24 hours post-dose), and measures of safety and tolerability.
ResultsThe ITT population comprised 112 patients. Mean age was 9.5 years, 68.8% were male; 92% completed the study. Dasotraline 4 mg/day significantly improved mean SKAMP-CS versus placebo (p<0.0001, effect size 0.85) with significant effects persisting throughout the day. Mean SKAMP subscores improved significantly versus placebo (Attention p<0.0001, effect size 0.81; Deportment p<0.001, effect size 0.70). Treatment-emergent adverse events were generally mild or moderate in severity; most frequent (with dasotraline 4 mg/day; placebo) included: insomnia (19.6%; 3.6%, all terms combined), decreased appetite (10.7%; 3.6%), headache (10.7%; 8.9%), affect lability (8.9%; 7.1%), irritability (5.4%; 3.6%), postural orthostatic tachycardia syndrome (5.4%; 0%), and perceptual disturbances (5.4%; 0%).
ConclusionsIn this 2-week, randomized, double-blind, laboratory classroom study in children with ADHD, once-daily dasotraline significantly improved ADHD symptoms (including deportment and attention), compared with placebo, and demonstrated sustained efficacyup to 24 hours post-dose. The most common adverse events were insomnia, decreased appetite, and headache.
Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.
181 Triple Trouble: A Rare Case Report of PCDH19, Autism and Epilepsy in a 7-Year-Old Male Child
- Sailaja Bysani, Jusleen Kendhari, Cale Robert
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- 15 June 2018, p. 104
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Background
A 7-year-old Caucasian male presented to the emergency department with worsening aggression andbehavioral problems. He was diagnosed with seizure disorder at 9 months old and was started on Keppra. He also had delayed developmental milestones including failure to roll until 6 months, and failure to crawl until after 9 months. At 16 months he was aggressive towards other children including unprovoked attacks of biting and assault. When he was 6yrs old he underwent genetic testing which showed positive for PCDH19 mutation. The most consistent feature of this condition is the early onset ofseizures between 3 months to 3 years of age. He has been on nine anti-seizure medications since his diagnosis. For behavioral problems, he was placed on Focalin, Ritalin, Adderall patch which did not seem to work. He was then on non-stimulants, Zoloft, Prozac, Effexor, Zyprexa and Abilify all with little success.
During this admission, patient’s mother described increasing acts of severe physical violence toward multiple people leading to significant bruising. He has a known past psychiatric history of ASD, ADHD,ODD and PCDH19 mutation associated epilepsy. On admission, his medications included Buspirone 5mg BID, Olanzapine 7.5mg BID, Methylphenidate 7.5mg, Ritalin 7.5mg, Zonisamide 150mg qhs, Clonidine 0.1mg qhs. He had significant sensory processing difficulties and lack of communication with peers. He was continued on Clonidine 0.1mg po qhs, Methylphenidate 7.5mg po qam and at noon, Zonisamide 150mg daily. Tapered down Olanzapine and initiated him on Risperidone. His condition improved. He was referred to Thompson center for ABA therapy. He is more interactive and has a smile.
DISCUSSIONPCDH19 gene mutations have long since been known to cause epilepsy and behavioral disturbances in females. Males, on the other hand, present as asymptomatic transmitters. PCDH19 is a gene located on Chromosome X and is responsible for the formation of a protein known as protocadherin 19. This protein is especially important as it functions as a Ca2+ dependent cell adhesion in the brain. The PCDH19 mutation, however, impedes protein formation leading to epilepsy and behavioral disturbances. Approximately 90% of symptomatic females possess the mutated gene on one of their X chromosomes. Males similarly carry the mutation on their X chromosome, however are typically asymptomatic. A rare mosaic variant of PCHD19 mutations has been seen in symptomatic males.
CONCLUSIONAlthough it is more difficult to think in terms of ASD if a PCDH19 patient has coexisting psychiatric comorbidities like ODD andADHD, clinicians must be keenly aware of other mood disorders. Seizures do not respond well to medications. Family education, psychopharmacological treatment, ABA and CBT were successful in treating the patient. Little is known about the long-term sequela and prognosis of PCDH19 mutation in the male patient population and thus further research is warranted.
Funding AcknowledgementsNo funding.
182 Unintentional Overdose on Long-Acting Injectable Risperidone
- Saira Pasha, Shirin Schilling
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- Published online by Cambridge University Press:
- 15 June 2018, pp. 104-105
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Study Objectives
Understand the mechanism and pharmacokinetics involved in an unintentional overdose of injectableantipsychotic medication; identify how to transition between long acting injectable antipsychotics; formulate steps to ensure patient safety in an event of an unintentional overdose of injectable antipsychotic
MethodReview of a case study involving a 47-year-old male, with history of schizoaffective disorder and previous episodes of loss of consciousness of unknown etiology, who was admitted to the inpatient psychiatry unit at UConn Health John Dempsey Hospital for stabilization of psychotic symptoms and monitoring of unintentional overdose after initially being admitted to the ICU. He was found unconscious at home following a period of days where he self-injected four of 37.5mg Risperidone injections (estimated 150mg) along with limited adherence to prescribed oral clozapine, doxepin and lorazepam. He reported self-injecting additional medication to treat paranoia, auditory, visual and olfactory hallucinations. In the ICU, he was evaluated by Toxicology and Neurology for loss of consciousness thought to be from seizures, with no clear outcome. He was awake and alert within 24 hours of medical admission but became agitated, hostile, and psychotic prompting psychiatric admission. When his worsening paranoia had resulted in termination of his visiting nurse services that administered injections and in home assessments, his outpatient psychiatrist allowed him to self-administer bi-monthly injections. Over three weeks in the hospital, he was evaluated for signs and symptoms of antipsychotic overdose.
ResultsInitial literature review did not reveal information involving an overdose of injectable Risperidone. Thus, the time frame and symptoms to monitor were uncertain. As the injectable medication was expected to peak in 2-3 weeks and persist for 4-6 weeks, there was a concern about delayed potential side effects such as EPS, sedation, QTC prolongation and electrolytes imbalances. He was treated with oral antipsychotic medication. Clozapine and doxepin were discontinued due to patient non-adherence, side effects, and drug interactions. He exhibited signs of EPS and was started on benztropine. To simplify his regimen, he was switched to another long acting injectable, Paliperidone Palmitate, prior to his discharge.
ConclusionsGiven the nature of the presentation, he was advised not to self-administer injectable medication and was referred for visiting nurse services. He was educated on the potential side effects of injectable antipsychotic medication. As there was a change in antipsychotic medications, follow up was recommended in an intensive outpatient program for psychotic symptoms and prolonged side effects. Due to the patient’s concordant episode of loss of consciousness, he was advised to follow up with an outpatient long term EEG monitoring and complete Neurology evaluation.
Funding AcknowledgementsNo funding.
183 AXONA (Caprylidene): Medical Food Therapy For Alzheimer’s Disease
- Shanila Shagufta, Venkatesh Sreeram, Faisal Kagadkar
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- 15 June 2018, p. 105
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Evaluate the current novel food therapy for Alzheimer and its adverse effects. What is the response to Axona (Capylidene) in different ethnicities and determine the generalizability of the drug use in diverse populations.
What genes are linked with positive responses? What are the implications of its use in high risk populations? Its role in early detection of Alzheimer’s and the arrest of the neurodegeneration in APO E4 (-) patients.
METHODPubMed was queried with the search terms ‘Axona’ OR ‘Caprylidene’ and the following articles were collected and reviewed.
RESULTSAmong the articles collected and reviewed, two studies extensively evaluated the safety and efficacy of using Medium Chain Triglycerides (MCT) in Alzheimer’s disease. These studies genotyped patients for APO E4 status (positive/negative). According to the Reger et al. study in 2002, treatment of APOE4 (-ve) patients with MCTs reported a considerable improvement in comparison to placebo-treated patients (P=0.04). The second study by Henderson et al. in 2009 demonstrated an improvement in cognitive functioning determined by Alzheimer’s disease Assessment Scale- cognitive subscale (ADAS-Cog) scores in those treated with MCTs versus placebo in APOE4 -ve patients. An open label Japanese pilot study also showed improvement in cognitive functioning with Caprylidene in APOE4 (-ve) patients with Mini Mental Status Exam (MMSE) score>14.
DISCUSSIONThe FDA approved treatment options in Alzheimer’s disease include acetylcholinesterase inhibitors (Rivastigmine, Donepezil and Galantamine), NMDA receptor antagonist (Memantine). These drugs only delay the progression of the disease in these patients.
MCTs are classified as medical foods, which are defined as substances that provide a specific nutritional need in a patient that cannot be satisfied by modification of a normal diet alone The FDA approved Axona as medicalfood for specific dietary management of the disease in 2009. Early metabolic changes in Alzheimer’s Diseaseprior to cognitive decline and plaque deposition can possibly be prevented by early intervention with Axona, especially in high risk population (APOE4 (þ), Downs syndrome).
These trials highlight the benefits of MCT in a discrete group, and the importance of routine genomic testing in Alzheimer patients in clinical settings. A better understanding into Caprylidene’s pharmacokinetics and pharmacodynamics will help us in the prevention and intervention of patients based on their genetic profiles.
Funding AcknowledgementsNo funding.
185 Second Generation Antipsychotics and Catatonia: A Literature Review
- Ryan Slauer, Mina Boazak, Michael Lowley, Jeffrey Lawrence, Zachary Hudson, David Goldsmith, Robert Cotes
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- 15 June 2018, pp. 105-106
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Introduction
Catatonia is an underrecognized neuropsychiatric syndrome affecting approximately 10% of individuals hospitalized on inpatient psychiatric units. First-line treatments for this condition include benzodiazepines (BZD) and/or electroconvulsive therapy (ECT). However, 20-40% of individuals do not respond to BZD alone and ECT is not always accessible. Second generation antipsychotics (SGA) have been used to treat catatonia in these circumstances. Here, we review the literature pertaining to the efficacy and safety of SGA in the treatment of catatonia.
MethodsWe conducted a PubMed search for articles linking catatonia to antipsychotics, under the search heading “catatonia” or “kahlbaum” and “risperidone”, “amisulpride”, “iloperidone”, “olanzapine”, “aripiprazole”, “paliperidone”, “clozapine”, “brexpiprazole”, or “cariprazine”. Reports commenting on SGA treatment efficacy and/or their role in the development of catatonia were included in the analysis. Selected articles were reviewed for patient demographics, psychiatric/medical history, symptoms, cause of catatonia and treatment, and co-administered agents. For each SGA, we calculated the number of cases in which catatonia was likely improved with antipsychotic treatment, and the number of cases in which catatonia was precipitated or worsened with antipsychotic treatment (improved/worsened ratio). Case data was assessed using the Naranjo Adverse Drug Reaction Probability Scale. Descriptive statistics were used to analyze the data.
ResultsAt the time this abstract was written, we reviewed 480 of the original 507 articles. One hundred and seventeen of the 480 met inclusion criteria. There was one randomized controlled trial (RCT), five prospective studies, four retrospective studies and 107 case reports. Of all reviewed literature quetiapine (34:3, 92%), aripiprazole (16:2, 89%), amisulpride (18:1, 95%), andclozapine (19:1, 95%) had the highest improved/worsened ratio, conversely paliperidone (0:5, 0%) had the lowest improved/worsened ratio.
ConclusionOf the available literature quetiapine, amisulpride, aripiprazole, and clozapine were found to be relatively safe andeffective as treatment options in catatonia, while palipderidone was found to have reports pointing to its role in the development/worsening, but none on the improvement, of catatonia. These results need to be interpreted with caution. In the majority of cases where SGA’s were effective, patients were co- treated with other pharmacologic agents (most frequently benzodiazepines), making it difficult to assess the role of the antipsychotic alone. Also, given that the preponderance of studies were case reports, publication bias may be an important limitation. Further studies are needed to examine the safety and efficacy of SGA in treating catatonia.
Funding AcknowledgementsNo funding.
186 Hospital Utilization Rates Following Antipsychotic Dose Reductions Among Patients With Schizophrenia
- Stanley N. Caroff, Fan Mu, Rajeev Ayyagari, Traci Schilling, Victor Abler, Benjamin Carroll
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- 15 June 2018, pp. 106-107
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Introduction
Tardive dyskinesia (TD), an often-irreversible movement disorder, develops in patients treated withantipsychotics. Although antipsychotic dose reduction has been utilized in the management of TD, the benefits and risks of lowering doses have not been well studied and could cause additional burden to patients.
ObjectiveTo analyze the healthcare burden of antipsychotic dose reduction in patients with schizophrenia.
MethodsMedical claims from six US states spanning 6 years are retrospectively analyzed for ≥10% or ≥30% antipsychotic dosereductions and compared with those from patients receiving stable doses. Outcomes measured include inpatient admissions and emergency room (ER) visits for schizophrenia, all psychiatric disorders, and all causes.
ResultsBaseline analysis revealed 17,984 patients with ≥10% and 14,029 patients with ≥30% dose reduction. Patients with≥10% dose reduction and matched controls were similar in age (mean 45.5 years), gender (51% male) and healthcare plan type. Preliminary analyses indicate that ≥10% dose reduction is associated with increased risk of admission or ER visit for schizophrenia (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.18, 1.35; P<0.001) and all psychiatric disorders (HR 1.18; 95% CI 1.11, 1.25; P<0.001) versus controls, which may be even greater with ≥30% dose reduction. Final updated results of ongoing analyses will be presented at the meeting.
ConclusionsPatients with antipsychotic dose reductions may be at risk for significant increases in hospital utilization rates. This suggests that dose reductions may increase overall healthcare burden in some schizophrenia patients, and highlights the need for alternative strategies in the management of 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.
187 Buprenorphine/Naloxone (Suboxone and Bunavail)-Induced Glycolimia, an Indication of Undermedication?
- Stefany Kress, Alan Hirsch
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- 15 June 2018, p. 107
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INTRODUCTION
Buprenorphine/Naloxone combination drugs such as Suboxone and Bunavail have not been reported to induce glycolimia. Two such cases are presented.
METHODSCASE STUDY: Case 1: A 30-year-old, right-handed, white female with a history of opioid abuse was started on 4.2 mg buprenorphine/0.7 mg naloxone (Bunavail) BID and began sweet cravings and consumption of sweet foods. In a typical day she would eat 16 strawberry pop-tarts and 2 boxes of Little Debbie cookies. This may have provoked the 10 pound weight augmentation in the first two weeks of treatment. She denied any craving for opioids and no evidence of opioid withdrawal was present. Her Clinical Opiate Withdrawal Scale (COWS) score =4 (normal).
Case 2: A 51-year-old, right-handed, male with opiate dependence, four days following the initiation of Suboxone (8 mg buprenorphine/2 mg naloxone) BID, developed strong cravings for sugary foods including donuts and ice cream, of which he was previously never inclined to eat and gained 10 pounds in one month. His COWS score= 7 (mild symptoms).
DISCUSSIONThere are myriad mechanisms that may be acting to induce sugar cravings with buprenorphine/naloxone. Humans and rats acutely withdrawing from opiates, such as heroin, develop strong urges for consumption of sugary substances (Lieblich et al., 1991; Sapira, 1968; Weiss, 1982). Glycolimia in the above cases may reflect early or subclinical withdrawal, which if becoming more severe, would manifest as opioid craving. If the value of the reward system induced by sweets doesn’t meet the threshold invoked by the opioid stimulation, this “withdrawal” may lead to further sugar cravings in an attempt to reach the same reward level. In animals, certain foods and drugs share the same neurological pathway involved in the “reward system” potentially explaining why opioids influence food palatability in humans (Pelchat, 2002).
Alternatively, it is possible that buprenorphine induces hypoglycemia at high doses (Bullingham et al., 1981) such that hypoglycemia may paradoxically act to enhance sugar craving similar to the Somogyi effect in insulin dependent diabetics. Another possible mechanism of action is that since buprenorphine acts to decrease glucose metabolism in the brain (Walsh et al., 1994), this may lead to a neural compensatory response by increasing sugar access to the brain behaviorally via glycolimiaand somatically reducing insulin release, thus explaining the high hemoglobin A1c observed in opioid addicts (Giugliano, 1984). Given the above presentation, complaints of sugar craving may indicate consideration to increase buprenorphine dosing and trial of this in those with glycolimia without opioid dependence may be warranted.
Funding AcknowledgementsNo funding.
188 Buspirone-Induced Somnambulism
- Sulekho Egal, Alan R Hirsch
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- Published online by Cambridge University Press:
- 15 June 2018, pp. 107-108
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Objective
Buspirone has not heretofore been reported to trigger somnambulism. Such a case is described.
BackgroundBuspirone is a partial 5HT1A agonist, which acts to suppress REM sleep and increase sleep fragmentation (Ware, 1994).
Design/MethodsA 36-year old right handed woman presented with one-year of constant anxiety and panic attacks with epochs of dyspnea, tachycardia, diaphoresis,paresthesias of both hands, and out of body sensations. She affirmed déjà vu and PM insomnia, and vivid dreams. When in high school she had one sleepwalking event, without recurrence. The patient was begun on buspirone, initially 2.5 mg and raised to 5 mg QHS. Within a day of increasing the dose, she experienced an episode whereby in the early hours in the morning, she removed her pajamas, folded them neatly into a stack next to the bed, and returned to bed, sans clothes. She was amnestic for this event, but based this history on her husband’s report. She discontinued the buspironeand for over 1 year, there has been no recurrence of such events.
ResultsAbnormalities in her neurological examination: Mental Status
ExaminationAnxious. Memory: immediate recall: 7 digits forwards and 4 digits backwards: Cranial Nerve Examination: Cranial Nerve I: Alcohol Sniff Test: 8 cm (hyposmia), Reflexes: 3+ throughout. Neuropsychiatric testing: Clock Drawing test: 4 (Normal). Animal Fluency test: 20 (normal).
ConclusionsBuspirone induced somnambulism may relate directly to its mechanism of action, as a 5HT1A partial agonist. Since other 5HT1A agonists, to cause noctambulism (Raja2012). Buspirone increases sleep fragmentation (Wilson, 2005), and thus may act to disrupt slow wave sleep, promoting susceptibility to somnambulism. Alternatively, her somnambulism may be a nocturnal variant of Buspirone induced dissociative state (Bystritsky, 2013). Given the above, it is worthwhile to query those who are undergoing therapy with buspirone for the development of somnambulism.
Funding AcknowledgementsNo funding.
189 Emetophobia: The Specific Phobia of Vomiting: 2 Case Studies With 1-Year Follow-up
- Sultana Jahan, Sailaja Bysani
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- Published online by Cambridge University Press:
- 15 June 2018, p. 108
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EDUCATIONAL OBJECTIVES
At the conclusion of the session, the participant should be able: 1) To recognize emetophobia & how it can lead to significant impairment & reduce quality of life; 2) To appreciate the prevalence of emetophobia among the general population, 3) To learn that the selective serotonin reuptake inhibitor sertraline can be effective for emetophobia; 4)Need for more research.
INTRODUCTIONEmetophobia is an intense, irrational fear of vomiting. The prevalence rate of emetophobia in a community sample has been estimated to 8.8 % with a female to male ratio 4:1: It can occur at any age and can have a chronic course affecting one’s academic/career, family, and social life.
METHODSCase 1: B. was a 7 year old female referred by her pediatrician for psychiatric evaluation for her intense fear ofvomiting. Mother shared that B’s overwhelming fear of vomiting started when she was 6 years old and it may have stemmed from an incident when one of B’s cousins threw up inside their van. At school, B constantly monitored whether or not anybody was getting sick around her. If she found out, someone was sick she began screaming and crying. B’s academic performance was negatively affected due to her intense irrational fear.
Case 2: P was a 12 year male patient referred by his pediatrician for psychiatric evaluation after receiving 4 days inpatient treatment on the pediatric unit for dehydration. Patient reported that he was afraid of vomiting and gradually stopped eating and drinking & became so dehydrated that he was hospitalized. Several months prior to his hospitalization he had suffered from theflu & during that time he had intense vomiting and since then he has been fearful of a recurrence of the vomiting.
After a complete psychiatric evaluation, a diagnosis of emetophobia was established for each patient. Both patients were treated with sertraline.
RESULTSB and P both started with initial dose of sertraline 12.5mg daily and then increased gradually over a period of next few months. They responded well with sertraline. B and P continued sertraline 50mg daily and 25mg daily as a maintenance treatment respectively. At 1 year follow up visit both of them were symptoms free.
CONCLUSIONSEmetophobia is a common and chronic debilitating mental illness. Still there are no treatment protocols and randomized controlled trials for the treatment of emetophobia. CBT/Exposure-based therapies are the most commonly used approaches for emetophobia per literature. More studies are needed for a better understanding of eremophobia, which is relatively deserted illness although it can cause as much suffering as other major psychiatric disorders do and any patient presenting with these symptoms deserve to be evaluated an managed with scientific understanding and guideline.
Funding AcknowledgementsNo funding.
191 Multi-Watt Near Infrared Phototherapy as a Treatment for Traumatic Brain Injury
- Theodore Henderson, Larry D. Morries
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- Published online by Cambridge University Press:
- 15 June 2018, p. 109
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Background
Depression treatment is hampered by low efficacy of antidepressant medications and concerns about alternative modalities. Animal studies of treatment with low-level (0.5 Watt or less) near infrared (NIR) light from diodes has shown some benefit in models of traumatic brain injury (TBI) with evidence of reduced lesion size, increased neurotrophin production, synaptogenesis, fewer apoptotic cells, and improved neurological function. Two small case series have demonstrated transient clinical improvement with low-level NIR treatment given on a daily basis over several weeks. We have previously shown marked and persistent clinical improvement in a case series of patients with chronic mild-to-moderate (m-MTBI) after treatmentwith NIR at a power of 9 Watts or greater. We also have published a review of the potential for application of NIR for the treatment of depression. The current study explores NIR efficacy in a proof-of-concept study as a treatment for depression.
MethodsThirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton Depression Rating Scale. Each completed the Quick Inventory of Depression Symptomatology-Self Reports (QIDS) before and after treatment. Patients received transcranial multi-Watt near-infrared light treatment (NILT) using near-infrared lasers (810/980 nm at 8-15 Watts) applied to forehead and temporal regions bilaterally for 9-12 minutes to each area.
ResultsFor 36 of the 39 patients, after 16.82 + 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by > 50%). For 32 of 39 patients post-treatment QIDS scores indicated a remission from depression (decrease of QIDS total score < 5). Overall, the QIDS score fell from 14.10 + 3.39 to 3.44 + 3.39 SD (p=6.29 X 10-19). With 12 or fewer treatments, QIDS score dropped from 14.83 + 2.55 to 4.17 + 3.93. Patients receiving 13 or more treatments showed a change in QIDS score from 13.67 + 3.64 to 3.11 + 3.14. Those (N=15) who received the entire treatment course within 8 weeks or less (5.33 + 1.72 weeks) showed a change in QIDS score from 13.86 + 3.14 to 4.5 + 3.94. Suicidal ideation resolved in all, but two patients. The non-responsive patients are described in detail. Patients remained in remission for up to 55 months after a single course of treatment.
ConclusionThis is the first report of high-powered NILT showing efficacy for depression. Patients saw benefit often within 4 treatments and some had resolution of depressive symptoms in as little as 4 weeks. These data raise an intriguing possibility – that NILT may be a safe, effective, and rapid treatment for depression. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.
Funding AcknowledgementsNeuro-Laser Foundation
192 Multi-Watt Near Infrared Phototherapy is an Effective Treatment for Depression
- Theodore Henderson, Larry D. Morries
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- Published online by Cambridge University Press:
- 15 June 2018, pp. 109-110
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Background
Depression treatment is hampered by low efficacy of antidepressant medications and concerns about alternative modalities. Animal studies of treatment with low-level (0.5 Watt or less) near infrared (NIR) light from diodes has shown some benefit in models of traumatic brain injury (TBI) with evidence of reduced lesion size, increased neurotrophin production, synaptogenesis, fewer apoptotic cells, and improved neurological function. Two small case series have demonstrated transient clinical improvement with low-level NIR treatment given on a daily basis over several weeks. We have previously shown marked and persistent clinical improvement in a case series of patients with chronic mild-to-moderate (m-MTBI) after treatmentwith NIR at a power of 9 Watts or greater. We also have published a review of the potential for application of NIR for the treatment of depression. The current study explores NIR efficacy in a proof-of-concept study as a treatment for depression.
MethodsThirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton Depression Rating Scale. Each completed the Quick Inventory of Depression Symptomatology-Self Reports (QIDS) before and after treatment. Patients received transcranial multi-Watt near-infrared light treatment (NILT) using near-infrared lasers (810/980 nm at 8-15 Watts) applied to forehead and temporal regions bilaterally for 9-12 minutes to each area.
ResultsFor 36 of the 39 patients, after 16.82 + 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by > 50%). For 32 of 39 patients post-treatment QIDS scores indicated a remission from depression (decrease of QIDS total score < 5). Overall, the QIDS score fell from 14.10 + 3.39 to 3.44 + 3.39 SD (p=6.29 X 10-19). With 12 or fewer treatments, QIDS score dropped from 14.83 + 2.55 to 4.17 + 3.93. Patients receiving 13 or more treatments showed a change in QIDS score from 13.67 + 3.64 to 3.11 + 3.14. Those (N=15) who received the entire treatment course within 8 weeks or less (5.33 + 1.72 weeks) showed a change in QIDS score from 13.86 + 3.14 to 4.5 + 3.94. Suicidal ideation resolved in all, but two patients. The non-responsive patients are described in detail. Patients remained in remission for up to 55 months after a single course of treatment.
ConclusionThis is the first report of high-powered NILT showing efficacy for depression. Patients saw benefit often within 4 treatments and some had resolution of depressive symptoms in as little as 4 weeks. These data raise an intriguing possibility – that NILT may be a safe, effective, and rapid treatment for depression. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.
Funding AcknowledgementsNeuro-Laser Foundation
193 A New Syndrome: Phantogeusia-Induced Phantosmia
- Umar Ahmad, Alan R. Hirsch
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- Published online by Cambridge University Press:
- 15 June 2018, p. 110
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Case Objective
While phantosmia-induced phantogeusia has been described (Ahmed, 20173), the reverse, phantogeusia-induced phantosmia, has not heretofore been described. Such a case is presented.
MethodsCase Study: A 39-yr-old left-handed (pathological) male, six years prior to presentation, noted a sudden onset of phantogeusia of roast cooking, pizza, fruit, strawberries, or a sour taste, and shortly thereafter he would develop unpleasant phantosmias which would sometimes combine with the ambient aroma. These would occur 3-10 times per week and would last for the duration of the phantogeusia, for as long as 1-2 hours. Occasionally the phantosmia would occur first and then induce the phantogeusia of asour taste.
ResultsAbnormalities in Neurologic examination: Mental status examination: Immediate recall: Digit span: 6 digits forward and 3 digits backwards. CN XI, X: Decreased gag bilaterally. Motor Examination: Drift: left pronator drift with right abductor digiti minimi sign and right cerebellar spooning. Gait Examination: Tandem Gait: unstable. Cerebellar Examination: Holmes Rebound Phenomena: bilaterally positive, left greater than the right. Sensory Examination: Ipswich Touch Test: decreased in left lower extremity. Temperature: decreased in left lower extremity. Rydel-Seiffer Vibratory Test: bilateral upper extremities 5, bilateral lower extremities 3. Reflexes: upper extremities 1+, absent lower extremities. Neuropsychiatric Examination: Go-No-Go Test: 6/6 (normal). Animal Fluency Test: 15 (normal). Clock Drawing Test: 3 (abnormal). Center for Neurologic Study Lability Scale: 16 (Pseudobulbar affect).
ConclusionClose connection of the tertiary smell and taste integration areas, where smell and taste converge, in the posterior orbitofrontal cortex, anterior to the insular taste cortex, and posterior to the granular orbitofrontal cortex may have allowed activation of memory engrams connecting these two (Rolls, 19944). Alternatively, electrical discharge from the primary taste area may have spread to involve the cortical representation of smell. Since the cortical area involved in the interpretation and hedonics of taste co-localize with the area involving olfactory hedonics, spread from one area to the other area may occur. As a result of electrical discharge (from an epileptiform focus) or as a result of well-connected and developed memory engrams with associated hedonics, phantom tastes may induce phantom smells. Alternatively, this may represent a distorted retronasal smell whereby the olfactory component of the gustatory hallucination causes a discharge of the olfactory epithelium (a pseudoretronasal smell).
Given the above, treatment of those with both phantosmia and phantogeusia may respond to treatment of phantogeusia alone. Under this construct, the phantosmia is the slave of the phantogeusia whereby management of the taste hallucination will thus eliminate the smell hallucination.
Funding AcknowledgementsSmell and Taste Treatment and Research Foundation.
195 Current Use and Trends in the Management of Tardive Dyskinesia: Role of VMAT2 Inhibitors
- Venkatesh Sreeram, Shanila Shagufta, Faisal Kagadkar, Mustafa Qureshi
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- Published online by Cambridge University Press:
- 15 June 2018, p. 111
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Objectives
Tardive Dyskinesia (TD) is a debilitating condition that requires prompt care and intervention. Studies demonstrated the probable role of Vesicular Monoamine Transport 2 (VMAT2) in the pathogenesis of TD and use of VMAT2inhibitors in managing TD. Our aim is to provide available data on the management of TD and to determine the efficacy ofvarious VMAT2 inhibitors for independent use. Also, to identify their use in combination and assess if there, any change inoutcome with early intervention.
MethodsWe did a pivotal search of the scientific literature by querying PubMed and Google Scholar for studies on treatment modalities of TD including atypical antipsychotics and VMAT2 inhibitors. Also, references from publications were accessed for review.
ResultsEarly detection and prevention are of paramount importance in managing TD. Cessate the antipsychotic been using andother dopamine blocking agents that probably implicated in causing the symptoms. Certain studies showed the use of new atypical antipsychotics like Paliperidone, Quetiapine in small titrated dose resolving the symptoms. According to the available data, using benzodiazepines, botulinum toxin injections and VMAT2 inhibitors like Valbenazine, Tetrabenazine, andDeutetrabenazine also managed TD with efficacy. Valbenazine has breakthrough global approval in resolving the symptoms. Although other VMAT2 inhibitors were used for TD earlier and showed to be effective in managing TD, larger trials are required showing their safety and reliability in efficacy.
ConclusionsVMAT2 inhibitors were tested as efficacious in managing TD. Valbenazine and recently deutetrabenazine has been approved by US Food and Drug Administration (FDA) to treat TD. However, Tetrabenazine is yet to be approved by FDA. More clinical trials are required exploring their efficacy by comparing them or using them in combination. Our review also suggests timely detection and earlier intervening, especially if witnessed in children and adolescents would differ the outcome of TD.
Funding AcknowledgementsNo funding.