Tourette 1
Tourette 1
Tourette 1
https://doi.org/10.1007/s00702-019-02105-w
Received: 10 October 2019 / Accepted: 14 November 2019 / Published online: 18 January 2020
© Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract
Motor and phonic tics associated with Tourette syndrome (TS) can range in severity from barely perceptible to disabling and
most patients have a variety of behavioral co-morbidities, particularly, attention deficit disorder and obsessive compulsive
disorder. Therefore, therapy must be tailored to the individual needs of the patients. In addition to behavioral therapy, oral
medications such as alpha agonists, dopamine depletors, anti-psychotics, and topiramate are used to control the involuntary
movements and noises. Botulinum toxin injections are particularly effective in patients with troublesome focal motor and
phonic tics, including coprolalia. Deep brain stimulation may be considered for patients with “malignant” TS, that is, refrac-
tory to medical therapy. When appropriate therapy is selected and implemented, most patients with TS can achieve their full
potential and lead essentially normal life.
Keywords Tics · Tourette syndrome · Obsessive-compulsive disorder · Attention deficit disorder · Deutetrabenazine ·
Botulinum toxin
* Joseph Jankovic
Numerous studies have provided evidence that behavioral
[email protected] therapies are effective in patients with TS. In the abovemen-
https://www.jankovic.org tioned AAN guideline report (Pringsheim et al. 2019a, b)
1
there was high confidence that the Comprehensive Behav-
Department of Neurology, Parkinson’s Disease Center
and Movement Disorders Clinic, Baylor College
ioral Intervention for Tics (CBIT), including Habit Rever-
of Medicine, 7200 Cambridge, Suite 9A, Houston, sal Therapy (HRT), was more likely than psychoeducation
TX 77030‑4202, USA
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and supportive therapy to reduce tics. Although highly clonidine, it is often preferred, especially in the treatment
recommended CBIT is often difficult to access, because of of co-morbid ADHD and impulse control. Both alpha-2
lack of trained and certified psychologists or occupational agonists, however, have limited efficacy in the treatment of
therapists, poor insurance coverage, and high demands on tics. In one study, involving 34 children with chronic tic
patients and their parents to fully comply with the instruc- disorder, extended release of guanfacine did not exert a
tions. In this regard, an interactive online treatment pro- clinically meaningful effect, as determined by reduction in
gram, called “TicHelper” (https://www.tichelper.com) has Global Tic Severity Scale Total Tic Score (YGTSS-TTS)
been launched. In a direct comparison of pharmacotherapy and other scales, compared to placebo (Murphy et al. 2017).
with behavioral therapy in children and adolescents with TS, Besides sedation, other potential side effects of alpha-2
both approaches were effective in reducing tics and improv- agonists include fatigue, dry mouth, headaches, irritability,
ing quality of life, but only pharmacotherapy was effective bradycardia, and orthostatic hypotension. Because of some,
in reducing obsessive–compulsive symptoms (Rizzo et al. albeit modest, efficacy of alpha-2 agonists, these drugs may
2018). be helpful in patients with mild tics that are troublesome
enough to require pharmacologic therapy.
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Treatment of tics associated with Tourette syndrome 845
significantly different between the groups in favor of ari- pathway has been suggested to suppress tics (Godar et al.
piprazole (p = 0.0321). Side effects of aripiprazole included 2016; Santangelo et al. 2018). In this regard, ecopipam, a
significant increase in mean body weight, body mass index, selective D1 receptor antagonist, was evaluated in a 4-week
and waist circumference. These findings were confirmed by double-blind, placebo-controlled crossover study of 40 TS
a phase 3, randomized, double-blind, placebo-controlled patients, aged 7–17 years, randomized to either ecopipam
trial, which enrolled 133 patients (Sallee et al. 2017). At (50 mg/day for weight of < 34 kg, 100 mg/day for weight
week 8, the treatment difference in YGTSS-TTS vs. pla- of > 34 kg) or placebo for 30 days, followed by a 2-week
cebo was − 6.3 (p = 0.0020) and − 9.9 (< 0.0001), respec- washout and then crossed to the alternative treatment for
tively. Furthermore, 69% (29/42) of patients in the low-dose 30 days (Gilbert et al. 2018). The YGTSS-TTS decreased
(5–10 mg/day) and 74% (26/35) of patients in the high-dose more robustly in patients randomized to ecopipam rela-
aripiprazole (10–20 mg/day) groups indicated that they were tive to those exposed to placebo: from 32.8 to 27.2 (− 5.6)
much or very much improved. Although aripiprazole is mar- with ecopipam vs. from 33.7 to 30.3 (− 3.4) with placebo
keted as an atypical antipsychotic with low risk of tardive (p = 0.043). The study confirmed the findings from an ear-
dyskinesia, there have been many reports of this iatrogenic lier, smaller trial (Gilbert et al. 2014), but further studies are
side effect in patients treated with the drug (Peña et al. 2011; needed before the drug will be approved by the FDA for the
Carbon et al. 2018). treatment of TS.
Besides these three neuroleptics, there have been many
other dopamine receptor blocking drugs used in the treat- Dopamine‑depleting drugs
ment of TS such as risperidone and ziprasidone (Weisman
et al. 2013; Pandey and Dash 2019). Tiapride is one of the While dopamine receptor blocking drugs are generally quite
most frequently prescribed drugs for tics in Europe although effective in reducing tics, they are associated with a variety
double-blind, placebo-controlled trials are lacking (Roessner of potential serious and permanent complications such as
et al. 2013). Fluphenazine, a typical antipsychotic found to tardive dyskinesia. Dopamine-depleting drugs that act by
be effective for TS in small studies, has been also found inhibiting vesicular monoamine transporter 2 (VMAT2)
to be safe and effective in long-term observational stud- have been used in the treatment of a variety of hyperkinetic
ies. In a retrospective review of the use of fluphenazine for movement disorders, including tics, without causing tardive
the treatment of TS conducted at Baylor College of Medi- dyskinesia (Jankovic 2016).
cine, which included 268 patients treated for an average of Tetrabenazine, approved by the FDA for the treatment of
2.6 ± 3.2 years (range 0.01–16.8, 40 patients over 5 years and chorea associated with Huntington disease, has been shown
13 patients over 10 years), the response to fluphenazine was to be effective in several open-label trials for the treatment
rated as “moderate to marked” in 80.5% of patients at first of tics associated with TS (Kenney et al. 2007; Chen et al.
follow-up visit and 76% at last follow-up (Wijemanne et al. 2012). Although effective in the treatment of a variety of
2014). The mean dose at last follow-up was 3.2 ± 2.3 mg hyperkinetic movement disorders, tetrabenazine has been
(range 0.5–12 mg) per day. The most common side effects reported to be associated with various side effects, includ-
were drowsiness (26.1%), weight gain (11.6%), akathisia ing drowsiness, parkinsonism, depression, and akathisia. In
(8.5%), and acute dystonic reactions (7.0%), but there were the United States, tetrabenazine (now available as a generic
no cases of tardive dyskinesia. The low risk of tardive dys- drug) carries a black-box warning regarding the risk of
kinesia in this study is probably due to relatively young age depression and suicidality. A recent study of patients with
of the studied population, the mean age at initiation was Huntington disease, however, has suggested that patients
15.8 ± 10.8 years (range 4.1–70.2). taking tetrabenazine may actually have a lower risk of
While the benefits of dopamine receptor blocking drugs depression and suicidality than those not taking the drug
in reducing tics have been demonstrated in multiple trials, (Schultz et al. 2018).
their use is limited by short-term and long-term side effects, Other dopamine depletors currently investigated in the
including sedation, school phobia, weight gain, metabolic treatment of TS include deutetrabenazine (also known as
syndrome, hyperprolactinemia, acute dystonic reactions, SD-809 or TV50717) and valbenazine (also known as NBI-
Parkinsonism, tardive dyskinesia, and neuroleptic malignant 98854). In a pilot, open-label, study of deutetrabenazine, 23
syndrome (Mogwitz et al. 2013). adolescent patients (mean age 16 years; range: 12–18) with
In addition to the above anti-psychotics which block pre- moderate-to-severe tics associated with TS were titrated over
dominantly D2 dopamine receptors, there are novel, experi- a 6-week period and maintained for 2 weeks at a mean dose
mental, anti-dopaminergic drugs currently investigated in of 32.1 mg (range: 18–36 mg) of SD-809 (Jankovic et al.
the treatment of TS. Based on studies of animal models 2016). An independent blinded rater assessed tic severity
exhibiting tic-like behaviors, including the D1CT-7 mouse, using the YGTSS and tic impact by the TS-Clinical Global
blocking the direct, D1 receptor mediated, “net excitatory”, Impression (TS-CGI). The mean YGTSS Total Tic Score
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Treatment of tics associated with Tourette syndrome 847
with TS and obsessive compulsive disorder (Müller-Vahl tetrahydrocannabinol and palmitoylethanolamide are cur-
et al. 2019). Treatment with escitalopram, a serotonin re- rently ongoing.
uptake inhibitor of the patients, resulted in a significant ABX-1431 is a monoacylglycerol lipase, an enzyme that
reduction in serotonin transporter binding. Other serotonin regulates 2-arachidonoylglycerol, which is an endogenous
re-uptake inhibitors and drugs that modulate serotonergic agonist of cannabinoid CB1 and CB2 receptors. Inhibi-
activity have been found to be effective in treating tics, as tion of this enzyme has shown anti-nociceptive, anxiolytic,
well as the co-morbid obsessive compulsive behavior. Small, and anti-inflammatory effects, and exerted neuroprotective
open-label studies have shown some benefit in patients with effects in animal models of Parkinson’s disease and Alzhei-
TS treated with serotonin antagonists such as ketanserin and mer’s disease (Jiang and van der Stelt 2018). A double-blind
ondansetron (Toren et al. 2005). Clonazepam, a benzodiaz- crossover single-dose randomized clinical trials involving
epine which presumably acts predominantly on the seroto- 19 adult TS patients showed a modest (10%) but significant
nin system has been found effective in many patients with reduction in YGTSS-TTS at 8 h after dosing (Bellows and
TS, but its usefulness is limited by sedation and depression. Jankovic 2020). A phase 2 randomized clinical trial testing
Therefore, newer serotonergic agents are currently being two dose levels is currently underway in adult TS patients
explored in the management of TS. (NCT03625453).
Pimavanserin is a non-dopaminergic, potent, and selec- The AAN guideline report (Pringsheim et al. 2019a, b)
tive serotonin inverse agonist. It acts like an agonist in that found moderate confidence that haloperidol, risperidone,
it binds to the same receptor as serotonin, however, it pro- aripiprazole, tiapride, clonidine, onabotulinumtoxinA injec-
duces the opposite effect. While traditional antagonists block tions probably more likely reduce tics than placebo. There
the effects of binding agonists, inverse agonists inhibit the was low confidence that pimozide, ziprasidone, metoclo-
basal activity of the receptor. Pimavanserin has high affin- pramide, guanfacine, topiramate, and tetrahydrocannabinol
ity at the 5-HT2A receptor, but also has lower affinity at the were possibly more likely than placebo to reduce tics. Other
5-HT2C serotonin receptor (Sahli and Tarazi 2018). Cur- drugs occasionally prescribed for TS such as baclofen, lev-
rently approved by the FDA for treatment of psychosis in etiracetam, riluzole, pramipexole, flutamide, mecamylamine,
Parkinson’s disease, pimavanserin is currently studied in a and selegiline received “very low-level confidence” that they
pilot, open-label trial in adult patients with TS. reduced tic severity more likely than placebo.
There is a growing public interest in marijuana and can- Botulinum toxin injections have been used in the treatment
nabinoids for treatment of movement disorders, including TS of focal motor tics and in some simple and complex phonic
(Kluger et al. 2015; Lim et al. 2017). Patients often report tics (including coprolalia) for long time, but rigorous stud-
an improvement in tics with cannabis, but the response is ies are lacking (Scott et al. 1996; Lotia and Jankovic 2016;
usually quite non-specific and difficult to substantiate. In Jankovic 2018; Pandey et al. 2018; Pandey and Dash 2019).
two small controlled trials, an improvement in tics was dem- Open-label studies and cases series have demonstrated the
onstrated with delta-9-tetrahydrocannabinol without major benefits of botulinum toxin not only in reducing the inten-
side effects (Müller-Vahl 2013). According to a Cochrane sity and frequency of the tics, but also in ameliorating the
review on the efficacy of cannabinoids in TS, definite con- regional premonitory urge (Kwak et al. 2003). The effects
clusions about the safety and efficacy of cannabinoids in of botulinum toxin was also studied in an open-label, lon-
the treatment of TS cannot be drawn (Curtis et al. 2009). gitudinal study of 35 patients (30 male) treated with botuli-
Well-designed controlled studies with a large number of num toxin for problematic tics present for a mean duration
patients are needed to determine the efficacy and safety of 15.3 years (range 1–62 years) (Kwak et al. 2000). During a
cannabinoids for treatment of TS. A systematic review and mean follow-up of 21.2 months (range 5–84 months) and
meta-analysis found “little evidence for the effectiveness of 115 treatment sessions (mean number of visits 3.3), the mean
pharmaceutical CBD or medicinal cannabis” for the treat- peak effect response was 2.8 (0 = no response; 4 = marked
ment of various disorders, including TS (Black et al. 2019). improvement in both severity and function); the mean dura-
A preliminary report of finding of a phase IIa study at tion of benefit was 14.4 weeks (maximum, 45 weeks). Fur-
Yale University showed that THX-110, a combination drug thermore, 21 (84%) of 25 patients with premonitory sensa-
of dronabinol and palmitoylethanolamide, met its primary tions derived marked relief of these symptoms (mean benefit
endpoint and significantly improved symptoms in adult sub- 70.6%). Total mean dose of onabotulinumtoxinA per visit
jects with TS (https://clinicaltr ials.gov/ct2/show/NCT03 was 119.9 U (range 15–273 U). Sites of injections were as
651726). Further studies in TS using a combination of follows: cervical or upper thoracic area (17), upper face (14),
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848
lower face (7), vocal cords (4), upper back and/or shoulder on controlled trials and evidence-based data, should be bal-
(3), scalp (1), forearm (1), leg (1), and rectus abdominis anced against and coupled with a more pragmatic approach,
(1). Complications included neck weakness (4), dysphagia based on long-term experience and expert opinion. While
(2), ptosis (2), nausea (1), hypophonia (1), fatigue (1), and the AAN guidelines did not specifically differentiate which
generalized weakness (1), which were all mild and transient. therapeutic approaches may be more appropriate for children
In another study, involving 30 TS patients treated with botu- versus adults, most cited studies were performed in adult
linum toxin, improvement in phonic tics was reported by populations. Because the risk of tardive dyskinesia is much
93% of patients and 50% were reportedly free of phonic tics higher in adults than in children, we are less likely to use
after the botulinum toxin injection; premonitory sensation dopamine receptor blocking drugs in adults with TS. On the
and quality of life also improved. (Porta et al. 2004). The other hand, we tend to consider surgical intervention, such
most common side effect was hypophonia, noted in 80% as deep brain stimulation, more commonly in adults than in
of patients. A randomized, double-blind placebo-controlled children. This again highlights the importance of individual-
study of botulinum toxin for motor tics demonstrated a sig- ized approach to the treatment of TS.
nificant improvement in urge and tic frequency (Marras et al.
2001). There was 39% reduction in tics/min with botulinum
toxin vs. 6% increase with placebo (p = 0.004). Furthermore,
the urge score decreased by 0.46 with botulinum toxin and References
increased by 0.49 with placebo (p = 0.02). There was no sig-
Bellows S, Jankovic J (2020) Treatment of dystonia and tics. Clin Par-
nificant change in other measures such as severity score, tic
kinsonism Relat Disord 2:12–19
suppression, pain, and patient global impression, possibly Bashir H, Jankovic J (2018) Deutetrabenazine for the treatment of Hun-
because of its small sample size, relatively mild symptoms, tington’s chorea. Expert Rev Neurother 18(8):625–631
and a fixed treatment protocol. Black KJ, Jankovic J, Hershey T, McNaught KS, Mink JW, Walkup J
(2014) Progress in research on Tourette syndrome. J Obsessive
Botulinum toxin is clearly an effective treatment particu-
Compuls Relat Disord 3(4):359–362
larly in patients with bothersome tics that are refractory to Black N, Stockings E, Campbell G, Tran LT, Zagic D, Hall WD, Farrell
oral medications such as repetitive cervical extension (so M, Degenhardt L (2019) Cannabinoids for the treatment of mental
called “whiplash tics”) seen in some cases with “malignant” disorders and symptoms of mental disorders: a systematic review
and meta-analysis. Lancet Psychiat 6(12):995–1010
TS (Cheung et al. 2007). Botulinum toxin injections into the
Brander G, Isomura K, Chang Z, Kuja-Halkola R, Almqvist C, Larsson
extensor muscles of the neck have been reported to reverse H, Mataix-Cols D, Fernández de la Cruz L (2019) Association of
compressive cervical myelopathy as a complication of the Tourette syndrome and chronic tic disorder with metabolic and
“whiplash” tics (Krauss and Jankovic, 1996). Although focal cardiovascular disorders. JAMA Neurol 76(4):454–461
Carbon M, Kane JM, Leucht S, Correll CU (2018) Tardive dyskinesia
weakness can occur after botulinum toxin injection, this is
risk with first-and second-generation antipsychotics in compara-
rarely troublesome of disabling and it is always transient. tive randomized controlled trials: a meta-analysis. World Psychia-
try 17(3):330–340
Cavanna AE, Nani A (2013) Antiepileptic drugs and Tourette syn-
drome. Int Rev Neurobiol 112:373–389
Surgical therapy Chen JJ, Ondo WG, Dashtipour K, Swope DM (2012) Tetrabenazine
for the treatment of hyperkinetic movement disorders: a review
Deep brain stimulation targeting various subcortical struc- of the literature. Clin Ther 34(7):1487–1504
tures has been proposed as a treatment option for severe Cheung MY, Shahed J, Jankovic J (2007) Malignant Tourette syn-
drome. Mov Disord 22(12):1743–1750
TS, but only a few trials have provided data based on “con-
Coulombe MA, Elkaim LM, Alotaibi NM et al (2018) Deep brain
trolled” design (Viswanathan et al. 2012). In a randomized, stimulation for Gilles de la Tourette syndrome in children and
double-blind, crossover trial of deep brain stimulation of youth: a meta-analysis with individual participant data. J Neuro-
globus pallidus internus in 15 patients with medically intrac- surg Pediatr 23(2):236–246
Curtis A, Clarke CE, Rickards HE (2009) Cannabinoids for Tourette’s
table TS, there was 40.1% improvement in tics (Kefalopou-
syndrome. Cochrane Database Syst Rev 4:CD006565
lou et al. 2015). In an international deep brain stimulation Draper A, Stephenson MC, Jackson GM, Pépés S, Morgan PS, Morris
registry involving 185 patients treated with deep brain PG, Jackson SR (2014) Increased GABA contributes to enhanced
stimulation targeting centromedian thalamic region (57%), control over motor excitability in Tourette syndrome. Curr Biol
24(19):2343–2347
anterior globus pallidus (25%), and other areas the YGTSS
Du YS, Li HF, Vance A, Zhong YQ, Jiao FY, Wang HM, Wang MJ,
mean total score improved 45% (from 75.0 at baseline to Su LY, Yu DL, Ma SW, Wu JB (2008) Randomized double-blind
41.2) (Martinez-Ramirez et al. 2018). multicentre placebo-controlled clinical trial of the clonidine adhe-
The AAN guideline report (Pringsheim et al. 2019a, b) sive patch for the treatment of tic disorders. Aust N Z J Psychiatry
42(9):807–813
found low confidence that deep brain stimulation of the
Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin RE (2014) A
globus pallidus was possibly more likely than placebo to D1 receptor antagonist, ecopipam, for treatment of tics in Tourette
reduce tics. The conclusions from this report, which focused syndrome. Clin Neuropharmacol 37(1):26–30
13
Treatment of tics associated with Tourette syndrome 849
Gilbert DL, Murphy TK, Jankovic J, Budman CL, Black KJ, Kurlan Mogwitz S, Buse J, Ehrlich S, Roessner V (2013) Clinical pharmacol-
RM, Coffman KA, McCracken JT, Juncos J, Grant JE, Chipkin ogy of dopamine-modulating agents in Tourette’s syndrome. Int
RE (2018) Ecopipam, a D1 receptor antagonist, for treatment of Rev Neurobiol 112:281–349
tourette syndrome in children: a randomized, placebo-controlled Müller-Vahl KR (2013) Treatment of Tourette syndrome with cannabi-
crossover study. Mov Disord 33(8):1272–1280 noids. Behav Neurol 27(1):119–124
Godar SC, Mosher LJ, Strathman HJ et al (2016) The D1CT-7 Müller-Vahl KR, Szejko N, Wilke F, Jakubovski E, Geworski L, Bengel
mouse model of Tourette syndrome displays sensorimotor gat- F, Berding G (2019) Serotonin transporter binding is increased
ing deficits in response to spatial confinement. Br J Pharmacol in Tourette syndrome with Obsessive Compulsive Disorder. Sci
173(13):2111–2121 Rep 9(1):972
Hedderick EF, Morris CM, Singer HS (2009) Double-blind, crosso- Murphy TK, Fernandez TV, Coffey BJ, Rahman O, Gavaletz A, Hanks
ver study of clonidine and levetiracetam in Tourette syndrome. CE, Tillberg CS, Gomez LI, Sukhodolsky DG, Katsovich L, Sca-
Pediatr Neurol 40(6):420–425 hill L (2017) Extended-release guanfacine does not show a large
Jankovic J (2015) Therapeutic developments for tics and myoclonus. effect on tic severity in children with chronic tic disorders. J Child
Mov Disord 30(11):1566–1573 Adolesc Psychopharmacol 27(9):762–770
Jankovic J (2016) Dopamine depleters in the treatment of hyper- Niemann N, Jankovic J (2018) Treatment of tardive dyskinesia: a gen-
kinetic movement disorders. Expert Opin Pharmacother eral overview with focus on the vesicular monoamine transporter
17(18):2461–2470 2 inhibitors. Drugs 78(5):525–541
Jankovic J (2018) An update on new and unique uses of botulinum Pandey S, Dash D (2019) Progress in Pharmacological and surgical
toxin in movement disorders. Toxicon 1(147):84–88 management of Tourette syndrome and other chronic Tic disor-
Jankovic J, Jimenez-Shahed J, Brown LW (2010) A randomised, ders. Neurologist 24(3):93–108
double-blind, placebo-controlled study of topiramate in the Pandey S, Srivanitchapoom P, Kirubakaran R, Berman BD (2018)
treatment of Tourette syndrome. J Neurol Neurosurg Psychia- Botulinum toxin for motor and phonic tics in Tourette’s syndrome.
try 81(1):70–73 Cochrane Database Syst Rev 1:CD012285
Jankovic J, Jimenez-Shahed J, Budman C, Coffey B, Murphy T, Paschou P, Fernandez TV, Sharp F, Heiman GA, Hoekstra PJ (2013)
Shprecher D, Stamler D (2016) Deutetrabenazine in tics asso- Genetic susceptibility and neurotransmitters in Tourette syn-
ciated with Tourette syndrome. Tremor Other Hyperkinet Mov drome. Int Rev Neurobiol 112:155–177
(NY) 7(6):422 Peña MS, Yaltho TC, Jankovic J (2011) Tardive dyskinesia and other
Jiang M, van der Stelt M (2018) Activity-based protein profiling deliv- movement disorders secondary to aripiprazole. Mov Disord
ers selective drug candidate ABX-1431, a monoacylglycerol lipase 26(1):147–152
inhibitor, to control lipid metabolism in neurological disorders. J Porta M, Maggioni G, Ottaviani F, Schindler A (2004) Treatment of
Med Chem 61(20):9059–9061 phonic tics in patients with Tourette’s syndrome using botulinum
Kefalopoulou Z, Zrinzo L, Jahanshahi M et al (2015) Bilateral globus toxin type A. Neurol Sci 24(6):420–423
pallidus stimulation for severe Tourette’s syndrome: a double- Pringsheim T, Holler-Managan Y, Okun MS, Jankovic J, Piacentini J,
blind, randomised crossover trial. Lancet Neurol 14(6):595–605 Cavanna AE, Martino D, Müller-Vahl K, Woods DW, Robinson
Kenney C, Hunter C, Mejia N, Jankovic J (2007) Tetrabenazine in the M, Jarvie E, Roessner V, Oskoui M (2019a) Comprehensive sys-
treatment of Tourette syndrome. J Ped Neurol 5:9–13 tematic review summary: treatment of tics in people with Tourette
Kim DD, Barr AM, Chung Y et al (2018) Antipsychotic-associated syndrome and chronic tic disorders. Neurology 92(19):907–915
symptoms of Tourette syndrome: a systematic review. CNS Drugs Pringsheim T, Okun MS, Müller-Vahl K, Martino D, Jankovic J,
32(10):917–938 Cavanna AE, Woods DW, Robinson M, Jarvie E, Roessner V,
Kluger B, Triolo P, Jones W, Jankovic J (2015) The therapeutic Oskoui M, Holler-Managan Y, Piacentini J (2019b) Practice
potential of cannabinoids for movement disorders. Mov Disord guideline recommendations summary: treatment of tics in peo-
30(3):313–327 ple with Tourette syndrome and chronic tic disorders. Neurology
Krack P, Volkmann J, Tinkhauser G, Deuschl G (2019) Deep brain 92(19):896–906
stimulation in movement disorders: from experimental surgery to Quezada J, Coffman KA (2018) Current approaches and new develop-
evidence-based therapy. Mov Disord 34(12):1795–1810 ments in the pharmacological management of tourette syndrome.
Krauss JK, Jankovic J (1996) Severe motor tics causing cervical mye- CNS Drugs 32(1):33–45
lopathy in Tourette’s syndrome. Mov Disord 11(5):563–566 Rizzo R, Pellico A, Silvestri PR et al (2018) A randomized controlled
Kwak CH, Hanna PA, Jankovic J (2000) Botulinum toxin in the treat- trial comparing behavioral, educational, and pharmacological
ment of tics. Arch Neurol 57(8):1190–1193 treatments in youths with chronic Tic disorder or Tourette syn-
Kwak C, Dat Vuong K, Jankovic J (2003) Premonitory sensory phe- drome. Front Psychiatry 9:100
nomenon in Tourette’s syndrome. Mov Disord 18(12):1530–1533 Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou
Lerner A, Bagic A, Simmons JM et al (2012) Widespread abnormality P, Roessner V, Woods DW, Hariz M, Mathews CA, Črnčec R,
of the γ-aminobutyric acid-ergic system in Tourette syndrome. Leckman JF (2017) Gilles de la Tourette syndrome. Nat Rev Dis
Brain 135(Pt 6):1926–1936 Prime 3:16097
Lim K, See YM, Lee J (2017) A systematic review of the effectiveness Roessner V, Schoenefeld K, Buse J, Bender S, Ehrlich S, Münchau A
of medical cannabis for psychiatric, movement and neurodegen- (2013) Pharmacological treatment of tic disorders and Tourette
erative disorders. Clin Psychopharmacol Neurosci 15(4):301–312 Syndrome. Neuropharmacology 68:143–149
Lotia M, Jankovic J (2016) Botulinum Toxin for the Treatment of Sahli ZT, Tarazi FI (2018) Pimavanserin: novel pharmacotherapy
Tremor and Tics. Semin Neurol 36(1):54–63 for Parkinson’s disease psychosis. Expert Opin Drug Discov
Marras C, Andrews D, Sime E, Lang AE (2001) Botulinum toxin for 13:103–110
simple motor tics: a randomized, double-blind, controlled clinical Sallee F, Kohegyi E, Zhao J, McQuade R, Cox K, Sanchez R, van Beek
trial. Neurology 56(5):605–610 A, Nyilas M, Carson W, Kurlan R (2017) Randomized, double-
Martinez-Ramirez D, Jimenez-Shahed J, Leckman JF et al (2018) Effi- blind, placebo-controlled trial demonstrates the efficacy and
cacy and safety of deep brain stimulation in tourette syndrome: safety of oral aripiprazole for the treatment of Tourette’s disorder
the international tourette syndrome deep brain stimulation public in children and adolescents. J Child Adolesc Psychopharmacol
database and registry. JAMA Neurol 75(3):353–359 27(9):771–781
13
J. Jankovic
850
Santangelo A, Bortolato M, Mosher LJ, Crescimanno G, Di Giovanni Weisman H, Qureshi IA, Leckman JF, Scahill L, Bloch MH (2013)
G, Cassioli E, Ricca V, Casarrubea M (2018) Behavioral fragmen- Systematic review: pharmacological treatment of tic disorders–
tation in the D1CT-7 mouse model of Tourette’s syndrome. CNS efficacy of antipsychotic and alpha-2 adrenergic agonist agents.
Neurosci Ther 24(8):703–711 Neurosci Biobehav Rev 37(6):1162–1171
Schultz JL, Killoran A, Nopoulos PC, Chabal CC, Moser DJ, Kamholz Wijemanne S, Wu LJ, Jankovic J (2014) Long-term efficacy and safety
JA (2018) Evaluating depression and suicidality in tetrabenazine of fluphenazine in patients with Tourette syndrome. Mov Disord
users with Huntington disease. Neurology 91(3):e202–e207 29(1):126–130
Scott BL, Jankovic J, Donovan DT (1996) Botulinum toxin injection Yang CS, Zhang LL, Zeng LN, Huang L, Liu YT (2013) Topiramate
into vocal cord in the treatment of malignant coprolalia associated for Tourette’s syndrome in children: a meta-analysis. Pediatr Neu-
with Tourette’s syndrome. Mov Disord 11(4):431–433 rol 49(5):344–350
Thenganatt MA, Jankovic J (2016) Recent advances in understand- Yoo HK, Joung YS, Lee JS, Song DH, Lee YS, Kim JW, Kim BN,
ing and managing Tourette syndrome. F1000Res. https://doi. Cho SC (2013) A multicenter, randomized, double-blind, placebo-
org/10.12688/f1000research.7424.1 controlled study of aripiprazole in children and adolescents with
Toren P, Weizman A, Ratner S, Cohen D, Laor N (2005) Ondansetron Tourette’s disorder. J Clin Psychiatry 74(8):e772–e780
treatment in Tourette’s disorder: a 3-week, randomized, double-
blind, placebo-controlled study. J Clin Psychiatry 66(4):499–503 Publisher’s Note Springer Nature remains neutral with regard to
Tourette’s Syndrome Study Group (2002) Treatment of ADHD in jurisdictional claims in published maps and institutional affiliations.
children with tics: a randomized controlled trial. Neurology
58(4):527–536
Viswanathan A, Jimenez-Shahed J, Baizabal Carvallo JF, Jankovic J
(2012) Deep brain stimulation for Tourette syndrome: target selec-
tion. Stereotact Funct Neurosurg 90(4):213–224
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