Clinical Pharmacology of Dopamine-Modulating Agents in Tourette’s Syndrome

Mogwitz, Sabine; Buse, Judith; Ehrlich, Stefan; Roessner, Veit

doi:10.1016/b978-0-12-411546-0.00010-x

Cited by 52 publications

(39 citation statements)

References 250 publications

(363 reference statements)

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“…However, solid evidence for their therapeutic benefit is often limited or not available. Although double‐blind, placebo‐controlled trials found that haloperidol and pimozide were effective in reducing tic frequency and intensity, there are many reasons why these drugs should be avoided . For example, these and other typical neuroleptics carry the risk of adverse effects, such as metabolic syndrome, prolonged QT interval, and torsades de pointes.…”

Section: New Treatments and Discoveriesmentioning

confidence: 99%

Therapeutic Developments for Tics and Myoclonus

Jankovic

2015

Movement Disorders

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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.

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Section: New Treatments and Discoveriesmentioning

confidence: 99%

Therapeutic Developments for Tics and Myoclonus

Jankovic

2015

Movement Disorders

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“…In contrast with this progress, the pharmacotherapy of tic disorders is still often based on the employment of antipsychotic agents (which block dopamine receptors). Indeed, haloperidol and pimozide remain the best-validated drugs to reduce tic severity and frequency in the majority of TS patients with medium and severe TS, but their use often results in poor therapeutic compliance, due to their potentially serious side effects (Silva et al, 1996; Mogwitz et al, 2013; Egolf and Coffey, 2014). …”

Section: Introductionmentioning

confidence: 99%

Animal models of tic disorders: A translational perspective

Godar

Mosher

Giovanni

et al. 2014

Journal of Neuroscience Methods

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Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders.

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“…The efficacy of pimozide and haloperidol in treating tics compared with placebo has been documented by 6 and 3 randomized controlled trials (RCTs) of fair quality, respectively. [75][76][77] Direct comparison between the 2 agents did not show any significant difference in total tic scores, with a worse tolerability profile for haloperidol due to higher rates of sedation, lethargy, and, in particular, extrapyramidal symptoms. The use of fluphenazine is supported by open-label studies, 78 retrospective case series, 79 and one single-blind, placebo-controlled crossover study 75 ; there is moderate evidence that fluphenazine has fewer adverse effects than haloperidol.…”

Section: Box 1 Secondary Causes Of Ticsmentioning

confidence: 91%