In Memoriam: Professor Joseph Biederman's Contributions to Child and Adolescent Psychiatry.

OBJECTIVE: To provide an overview of Joe Biederman's contributions to child and adolescent psychiatry. METHOD: Nine colleagues described his contributions to: psychopharmacology, comorbidity and genetics, pediatric bipolar disorder, autism spectrum disorders, Tourette's and tic disorders, clinical and neuro biomarkers for pediatric mood disorders, executive functioning, and adult ADHD. RESULTS: Joe Biederman left us with many concrete indicators of his contributions to child and adolescent psychiatry. He set up the world's first pediatric psychopharmacology clinic and clinical research program in child adolescent psychiatry. As a young faculty member he began a research program that led to many awards and eventual promotion to full professor at Harvard Medical School. He was for many years the most highly cited researcher in ADHD. He achieved this while maintaining a full clinical load and was widely respected for his clinical acumen. CONCLUSION: The world is a better place because Joe Biederman was here.

Safety and Efficacy of Long-Term Deutetrabenazine Use in Children and Adolescents with Tics Associated with Tourette Syndrome: An Open-Label Extension Study.

Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics. Objective: To assess the safety and efficacy of deutetrabenazine (Teva Neuroscience, Inc, Parsippany, NJ), a vesicular monoamine transporter 2 inhibitor, in children and adolescents with TS. Methods: Alternatives for Reducing Tics in TS (ARTISTS) open-label extension (OLE) (NCT03567291) was a 54-week, global, phase 3, open-label extension study of deutetrabenazine (6-48 mg daily) conducted May 28, 2018 to April 3, 2020 with a 2-week randomized withdrawal period. Participants (6-16 years of age) had TS and active tics causing distress or impairment. Safety (primary outcome) was assessed by treatment-emergent adverse events (TEAEs) and clinical laboratory testing. Efficacy was measured by the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS). Results: The intent-to-treat population (228 participants; mean age, 12.0 years; 79.8% male; 86.4% white) had a median (range) duration of exposure of 28.4 (0.3-52.9) weeks. Of 227 participants in the safety analysis, 161 (70.9%) reported ≥1 TEAE (exposure-adjusted incidence rate, 2.77/patient-year), of which 95 (41.9%) were treatment related. The most frequently reported TEAEs were headaches, somnolence, nasopharyngitis, weight increases, and anxiety. No additional safety signals were observed. Worsening of YGTSS-TTS after the 2-week randomized withdrawal was not statistically significant (least squares mean difference, -0.4; P = 0.78). Several exploratory measures showed sustained improvement throughout the treatment periods. Conclusions: In this long-term, open-label trial, deutetrabenazine was well tolerated with low frequency of TEAEs. There was no significant difference in tics between treatment arms during the 2-week randomized withdrawal period, however, descriptive statistics and comparison with baseline showed a numeric improvement in tics, quality of life, and other measures.

Diagnosis and Management of Functional Tic-Like Phenomena.

Over the past 3 years, a global phenomenon has emerged characterized by the sudden onset and frequently rapid escalation of tics and tic-like movements and phonations. These symptoms have occurred not only in youth known to have tics or Tourette syndrome (TS), but also, and more notably, in youth with no prior history of tics. The Tourette Association of America (TAA) convened an international, multidisciplinary working group to better understand this apparent presentation of functional neurological disorder (FND) and its relationship to TS. Here, we review and summarize the literature relevant to distinguish the two, with recommendations to clinicians for diagnosis and management. Finally, we highlight areas for future emphasis and research.

Pharmacologic Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Tourette and Tic Disorders.

A complete and comprehensive medical and psychiatric evaluation is necessary to delineate tic symptoms from attention-deficit/hyperactivity disorder, and to prioritize the most problematic symptoms for intervention. Stimulants are the recommended first-line pharmacotherapy to treat attention-deficit/hyperactivity disorder symptoms in patients with tic disorders. Comprehensive behavioral intervention for tics is an effective behavioral therapy that is generally considered the first-line treatment of persistent tic disorders. α-Agonists can be added to stimulants if tics increase or be used as monotherapy to target attention-deficit/hyperactivity disorder and tics. Atomoxetine is also an excellent option to treat attention-deficit/hyperactivity disorder and tics.