Therapeutic Developments for Tics and Myoclonus

Abstract

Tics and myoclonus are phenomenologically similar given that both are jerk-like movements, but, in contrast to myoclonus, tics are often preceded by premonitory sensations and are typically associated with a variety of behavioral comorbidities, including attention deficit and obsessive-compulsive disorder. There are many other clinical features that help differentiate these two hyperkinetic disorders. Whereas behavioral and antidopaminergic therapies are most effective in the management of tics, clonazepam, other anticonvulsants, and serotonergic drugs are often used to control myoclonic movements. Botulinum toxin may also be helpful in focal tics and in segmental forms of myoclonus. DBS plays an increasingly important role in the treatment of these disorders, particularly when they are generalized and are disabling despite optimal medical therapy.

Deutetrabenazine in Tics Associated with Tourette Syndrome

“…The results from our study are similar to the treatment effects demonstrated with tetrabenazine,7–9, fluphenazine,29 topiramate,30 aripiprazole,31 and other drugs used to treat TS 1,4,32. Deutetrabenazine was well tolerated (the most common AEs were fatigue, headache, and irritability) and there were no serious AEs, such as depression.…”

“…The pharmacological treatment of TS consists of antidopaminergic agents and a wide array of other psychotropic medications, and tolerability to these treatments is often compromised by the frequent occurrence of adverse effects (AEs) 3,4. Furthermore, a sizeable number of patients fail to obtain satisfactory relief with conventional medications, and some experience severe disabling tics requiring surgical intervention 5,6.…”

Significant Improvement of Metabolic Characteristics and Bioactivities of Clopidogrel and Analogs by Selective Deuteration

“…The subtle, but sometimes powerful, effect of deuteration has the potential to positively affect the safety, efficacy, and/or tolerability of drugs [17,19]. For example, SD-809, an analog of tetrabenazine with deuterated methoxy groups, forms an active metabolite that undergoes CYP2D6-mediated O-dealkylation at almost half the rate of the active metabolite of tetrabenazine, itself [20]. This provides a superior pharmacokinetic profile which has led to a New Drug Application (NDA) for SD-809 to the FDA for the treatment of chorea associated with Huntington's disease.…”

Clinical and scientific perspectives on movement disorders: Stanley Fahn's contributions

“…Dr. Fahn helped to develop the Unified Myoclonus Rating Scale, still the only quantitative rating scale for this symptom . Depending on the cause or type of myoclonus, many treatments can ameliorate myoclonus, including clonazepam and other anticonvulsants, tetrabenazine, sodium oxybate, and botulinum toxin for segmental myoclonus …”

“…Despite numerous genetic studies, no gene or genes responsible for Tourette syndrome and its behavioral co‐morbidities, particularly attention‐deficit hyperactivity disorder and obsessive‐compulsive behavior, have been identified . The treatment of Tourette syndrome must be tailored to the specific needs of the patient and includes behavioral therapy, presynaptic α 2 ‐adrenergic agonists, such as clonidine and guanfacine, anti‐dopaminergic drugs, such as tetrabenazine and fluphenazine, botulinum toxin injections, and deep brain stimulation …”