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Pharmacotherapy for Tics and Comorbidities

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Pharmacotherapy for Tics and Comorbidities Noa Benaroya Milshtein, M.D., Ph.D Matta and Harry Freund Neuropsychiatric tic Clinic SCMCI Diagnosis Neurodevelopmental Aspect Comorbidities Etiology, Biology Environment Interaction DD Treatment Principles History: Georges Gilles de la Tourette Gaspard Itard, 1825 French neurologist, student of Charcot Interest in hysteria, hypnotism 1885 published paper describing maladie des tics • Study of 9 patients, including Marquise de Dampierre • Patients characterized by convulsive tics, obscene utterances, repetition of others’ words • Charcot renamed it “Gilles de la Tourette Syndrome” DSM 5 DSM-5 neurodevelopmental disorders: Motor Disorders Developmental Coordination Disorder Stereotypic Movement Disorder Tourette’s Disorder Persistent Motor or Vocal Tic Disorder Provisional Tic Disorder Other Specified/Unspecified Tic Disorder Neurodevelopmental Aspects Tics severity fluctuates Premonitory urge Premonitory Urge (PU): Disturbing sensory- physical sensations that create the urge to produce a tic PU is identified by children from the age of 10 years (Woods et al, 2005, Steinberg et al, 2010) Comorbid conditions (90%) Robertson, British Journal of Hospital Medicine, 2011 Developmental Delays ADHD >50% OCD/OCB and anxiety >50% Roessner et al., Eur Child Adolesc Psychiatry, 2007 ASD (echolalia, palilalia) Petek E, et al. Mol Genet Genomics, 2007 Berkson’s Bias, tertiary clinics Age of Onset Comorbidity Hirschtritt et al, JAMA, 2015 Fig. 3 Genetic correlations across neurological and psychiatric phenotypes. The Brainstorm Consortium et al. Science 2018;360:eaap8757 Published by AAAS Why is immunity explored in GTS? GROUP A STREPTOCOCCUS and PANDAS PANDAS is defined as tics and/or obsessive-compulsive symptoms with very abrupt onset and an episodic course in temporal association with anti-streptococcal immune response. The proposed mechanism is similar to the one suggested for Sydenham’s chorea and rheumatic fever The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n°278367 RHEUMATIC FEVER Chorea Obsessive-compulsive symptoms Emotional lability Separation anxiety Regressive/oppositional behavior Hyperactivity Deteriorated handwriting & school performance PANDAS The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n°278367 Pathophysiology Robertson et al, Nature Reviews, 2017 Pathophysiology Biology Environment Interaction What I can control and what I can’t Differential Diagnosis No lab test or imaging Easy to make diagnosis DD Epilepsy, Chorea, Tardive Dyskinesia Compulsions Functional Tics Stereotypic movements Tics Stereotypies Mean onset 5-7 y Onset typically: 3y enjoyable, fun, Distressing Lack of premonitory urge Migration of tics over Typically remains relatively months or years stable Common location: eyes, Frequently involve: hand ,arm or entire face, head, shoulders body Tic related OCD Symmetry, ordering and exactness, intrusive aggressive, sexual or religious images TS-related compulsions are often driven by physical sensation or drive - “just right” Earlier age of onset, predominantly affects males, poorer response to SSRI Tx ? AAN Guidelines,2019 • Psycho- education and reassurance followed by a watch and wait strategy • Impairment evaluation Psychological Interventions (Level B, Should) HRT and ERP Training patients to monitor their tics and premonitory sensations ERP - Exposure and Response Prevention (Level C) HRT – Habit Reversal Therapy A voluntary behavior that is physically incompatible with the tics (Level B) TS Triad, Kurlan, NEJM, 2010 ADHD+TS Aggression, Behavioral Disorders, Low Frustration threshold Social problems, Family Conflicts Dysfunction Problems “Are Stimulants Safe?” Tics and ADHD Clonidine Clonidine plus Methylphenidate Methylphenidate Guanfacine Reduce tic severity and reduce ADHD symptoms (EVID) Review, Pringsheim T., et al. Neurology, 2019 Atomoxetine - selective noradrenergic reuptake inhibitor Treatment of ADHD Target dosage for ADHD 1.2 mg/kg (start from 0.5 mg/kg) Max 1.4 mg/kg body weight Capsules and Oral Sol. SE Liver injury - rare No worsening of tics (Review, Pringsheim T., et al. Neurology, 2019) Indications for Pharmacological Treatment Social impairment Low self-esteem, reactive depression Subjective discomfort (e.g. pain or injury) Impaired academic achievements (Roessner et al.,2007) Tics severity fluctuates Pharmacological Prescribing 24 AUG 2015 400 consecutive TS patients seen over a 10-year period 255/400 (64%) were prescribed medication The most commonly prescribed medications were aripiprazole (64%), clonidine (40%), risperidone (30%) and sulpiride (29%) The number of different drugs: one (n = 155), two (n = 69), three (n = 36), four (n = 14), five (n = 15), six (n = 5), seven (n = 2) and eight (n = 1) Medication Groups α2 - Agonists Tics and ADHD (Level B) Tics (Level B) Monitor HT and BP (Level A) Consider sedation Gradually tapering avoid rebound HT Guanfacine (QT interval) Starting dose: 0.025 mg at bed time Maximum dose: 0.3-0.4 mg/day, 2/d Antipsychotics Physicians may prescribe antipsychotics for the treatment of tics when the benefits of treatment outweigh the risks (May, Level C) Haloperidol, risperidone, aripiprazole, and tiapride (more likely, EVID) Pimozide, ziprasidone, and metoclopramide (Possibly more likely, EVID) Antipsychotics Frequent side effects of all antipsychotic sedation Increased appetite, weight gain, metabolic syndrome Extrapyramidal Symptoms QT prolongation Hyperprolactinemia Tetrabenazine Tetrabenazine is a drug that depletes presynaptic dopamine Blocking vesicular monoamine transporter type 2 (VMAT2) No RCTs, Off Lable Side effects: sedation, parkinsonism, and depression Topiramate Level B, should AE: Cognitive and language problems AE: Somnolence, weight loss, and an increased risk of renal stones 25–150 mg/day Botulinum Toxin Local intramuscular injection of botulinum toxin is a therapeutic option (older adolesc Level C) Eye blinking, neck, shoulder tics The benefits are temporary, lasting 3 to 6 months SE, Hypophonia Delta 9-THC Tetrahydrocannabinol Cannabis-based medications should be avoided in children and adolescents Paucity of evidence Association between cannabis exposure in adolescence and potentially harmful cognitive and affective outcomes Positive effects on tic severity and tic frequency, in treatment resistance Adults (Level C) Other Therapies DBS Physicians may consider DBS for severe, self- injurious tics, such as severe cervical tics that result in spinal injury (Level C) TMS ? Neurodevelopmental Disorder Biology Environment Interaction Comorbidities play a major role Psycho Education Behavioral treatments Pharmacological treatments Take Home Message Acknowledgements Alan Apter Silvana Fennig Tamar Steinberg Tourette clinic team, SCMCI.
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