Merging the Pathophysiology and Pharmacotherapy of Tics

Augustine, Farhan; Singer, Harvey S.

doi:10.7916/d8h14jtx

Cited by 18 publications

(8 citation statements)

References 149 publications

(118 reference statements)

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“…For these agents, we reviewed the English-language literature since 2011 in PubMed using the agent’s name in combination with “tics”, “tic disorder”, or “Tourette Syndrome”, including children, adolescents, and adults as search string. In addition, we checked the references since 2011 of other systematic reviews/meta-analyses [ 5 – 9 ], existing guidelines [ 3 , 4 , 10 – 12 ], non-systematic reviews on TS with statements about pharmacological treatment, i.e., dealing with various agents [ 13 – 38 ] or mentioning treatment in their title [ 39 – 64 ]. In addition, we had a look into the references of agent-specific reviews and meta-analyses of (in alphabetical order) aripiprazole [ 65 – 72 ], atypical antipsychotics [ 73 ], botulinum toxin [ 74 – 85 ], cannabis [ 86 – 88 ], clonidine [ 89 , 90 ], complementary alternative medicine [ 91 ], deutetrabenazine [ 92 ], non-dopaminergic agents [ 93 ], traditional Chinese medicine [ 94 ], and topiramate [ 95 , 96 ].…”

Section: Methodology Of Selection Of Agents and Literature Search Str...mentioning

confidence: 99%

“…TS has been associated with a dysfunction of many neurotransmitter systems, especially the dopaminergic system [ 39 , 112 ]. Based on findings from nuclear imaging studies, four hypotheses on dopamine dysfunction in TS have been postulated: (1) dopamine hyper-innervation within the striatum; (2) supersensitive postsynaptic striatal dopamine receptors; (3) presynaptic dopamine abnormality in dopa carboxylase; and (4) elevated intrasynaptic dopamine release as a result of an imbalance between tonic and phasic dopamine levels [ 112 ].…”

Section: Methodology Of Selection Of Agents and Literature Search Str...mentioning

confidence: 99%

“…Based on findings from nuclear imaging studies, four hypotheses on dopamine dysfunction in TS have been postulated: (1) dopamine hyper-innervation within the striatum; (2) supersensitive postsynaptic striatal dopamine receptors; (3) presynaptic dopamine abnormality in dopa carboxylase; and (4) elevated intrasynaptic dopamine release as a result of an imbalance between tonic and phasic dopamine levels [ 112 ]. Besides a dysfunction in the dopaminergic system, imbalances in other neurotransmitter systems have been suggested including serotonergic, noradrenergic, glutamatergic, GABAergic, cholinergic, histaminergic, endocannabinoid, and opioid systems [ 34 , 39 ]. These findings give some rationale to use substances other than dopamine blocking drugs particularly for the treatment of tics resistant to dopamine-modulating agents.…”

Section: Methodology Of Selection Of Agents and Literature Search Str...mentioning

confidence: 99%

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European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part III: pharmacological treatment

Roessner

Eichele

Stern

et al. 2021

Eur Child Adolesc Psychiatry

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In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients’ self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient’s needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician’s preferences, experience, and local regulatory requirements.

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Section: Methodology Of Selection Of Agents and Literature Search Str...mentioning

confidence: 99%

Section: Methodology Of Selection Of Agents and Literature Search Str...mentioning

confidence: 99%

Section: Methodology Of Selection Of Agents and Literature Search Str...mentioning

confidence: 99%

See 1 more Smart Citation

European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part III: pharmacological treatment

Roessner

Eichele

Stern

et al. 2021

Eur Child Adolesc Psychiatry

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“…Although tic disorders are a prevalent developmental disease in children, the etiology and pathogenesis of tic disorders are still unclear. The central hypothesis of its pathogenesis is the cortico-striatal-thalamo-cortical (CSTC) abnormal anatomical pathways and alterations in the neurotransmitters located within these circuits ( Augustine and Singer, 2018 ). Among the possible pathogenic mechanisms of TS, the evidence supporting dopaminergic abnormalities in TS is extensive, including the recognition that the most effective inhibitory drugs are DA receptor antagonists, such as Hal, which are widely used in the treatment of TS ( Augustine and Singer, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…The central hypothesis of its pathogenesis is the cortico-striatal-thalamo-cortical (CSTC) abnormal anatomical pathways and alterations in the neurotransmitters located within these circuits ( Augustine and Singer, 2018 ). Among the possible pathogenic mechanisms of TS, the evidence supporting dopaminergic abnormalities in TS is extensive, including the recognition that the most effective inhibitory drugs are DA receptor antagonists, such as Hal, which are widely used in the treatment of TS ( Augustine and Singer, 2018 ). In recent decades, there were growing evidence of immunity involvement to TS, but the mechanism is still not clear ( Hsu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation in a Rat Model of Tourette Syndrome

Zhang

Chen

et al. 2022

Front. Behav. Neurosci.

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ObjectiveTourette syndrome (TS) is a group of childhood-onset chronic neuropsychiatric disorders characterized by tics, i.e., repetitive, sudden, and involuntary movements or vocalizations, which is often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders and have a worse prognosis. The mechanism of TS is still not clear. The relationship between immune activation, neuroinflammation, and neuropsychiatric disorders has attracted much attention in the past two decades. To explore the underlying mechanism in TS, the relationship between neuroinflammation and behavioral alterations in TS rats was investigated in this study.MethodsA total of 36 Sprague-Dawley male rats were divided into three groups randomly as follows: the TS, control (CON), and drug intervention groups. The TS rat group was treated with haloperidol (Hal) (the TS + Hal group). The TS rat model was established using 3,3-iminodipropionitrile (IDPN), which is a well-known animal model of TS. The behavioral syndromes, brain tissue cytokines, like interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), and microglial activation of the three groups were assessed.ResultsThe behavioral scores of rats in the TS group and the TS + Hal group were higher than those in the CON group (P < 0.05), but the scores of behavioral tests in the TS + Hal group were lower than those in the TS group (P < 0.05). The levels of IL-6 and TNF-α in the rat brain tissue were significantly higher in the TS group than in the CON group (P < 0.05), while no significant differences were found between the CON group and the TS + Hal group (P > 0.05). The microglia was significantly activated in the TS group and slightly activated in the TS + Hal group, which was considerably less than that in the TS group.ConclusionThe IDPN-induced TS rats had significant neuroinflammation in the brain, and the interaction between dopamine (DA) dysregulation and immune dysfunction may play a vital role in the pathogenic mechanisms of TS.

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