Impact of placebo assignment in clinical trials of tic disorders

Cubo, Esther; González, Miguel; Singer, Harvey S.; Mahone, E. Mark; Scahill, Lawrence; Müller‐Vahl, Kirsten; Fuente‐Fernández, Raúl de la; Armesto, Diana; Kompoliti, Katie

doi:10.1002/mds.25365

Cited by 37 publications

(13 citation statements)

References 18 publications

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“…There is one systematic review in tic disorders that only evaluated the placebo response and not the nocebo response . This study included six placebo‐controlled RCTs (parallel and cross‐over study designs), assessing medical interventions for tic disorders (literature search from 1990 until 2008) in a total of 91 patients included in placebo arms.…”

Section: Resultsmentioning

confidence: 99%

Placebo and nocebo responses in other movement disorders besides Parkinson's disease: How much do we know?

2018

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Among movement disorders and medicine in general, PD is one of the conditions for which there is a greater knowledge of the placebo and nocebo responses. In other movement disorders, the knowledge of placebo and nocebo responses is less. An advance in this field is expected to contribute to a better understanding of the nature of a therapeutic benefit in clinical research and clinical practice, and mechanisms of placebo and nocebo. We conducted a review on placebo and nocebo responses in other movement disorders besides PD by primarily examining meta-analyses of clinical trials assessing specifically the placebo and/or nocebo responses. Second, we examined both efficacy and safety results of a placebo arm in pivotal placebo-controlled trials for the different movement disorders. RLS is the movement disorder for which the most data exist, followed by tic disorders and Huntington's disease. Data available in other conditions document a placebo response in a varied phenomenology. We found different placebo responses according to clinical domains assessed, type of outcomes used for the same clinical domain, and modes of treatment administration, including rehabilitation and surgical interventions. Data on the nocebo response were very scarce. Although the data available are limited, RLS has the better documentation of placebo and nocebo responses. In contrast, atypical parkinsonisms are the group of movement disorders with the least knowledge. The clinical entities with a more robust placebo response are those that have the most beneficial available symptomatic treatments. © 2018 International Parkinson and Movement Disorder Society.

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Section: Resultsmentioning

confidence: 99%

Placebo and nocebo responses in other movement disorders besides Parkinson's disease: How much do we know?

2018

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“…Marked reductions in Unified Parkinson Disease Rating Scale scores can be seen up to 6 months from the application of placebo . As a result of these studies, a cutoff of 50% improvement in symptoms has been regarded as the standard for placebo response in other movement disorders, including progressive supranuclear palsy, Huntington's disease (HD), and tic disorders . FXTAS includes parkinsonism as a motor feature and could reasonably be added to the list of movement disorders to hold to this standard.…”

Section: Discussionmentioning

confidence: 99%

“…15 As a result of these studies, a cutoff of 50% improvement in symptoms has been regarded as the standard for placebo response in other movement disorders, including progressive supranuclear palsy, 16 Huntington's disease (HD), 18 and tic disorders. 19 FXTAS includes parkinsonism as a motor feature and could reasonably be added to the list of movement disorders to hold to this standard. However, the neuropsychiatric profiles of PD and FXTAS are quite different, with cognitive impairment occurring earlier in the disease course and characterized by more prominent executive dysfunction in FXTAS than in PD.…”

Section: Discussionmentioning

confidence: 99%

Placebo Response in Fragile X‐associated Tremor/Ataxia Syndrome

Hill

Goetz

Stebbins

et al. 2020

Movement Disord Clin Pract

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Background Fragile X‐associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder characterized by intention tremor, cerebellar ataxia, and executive dysfunction in carriers of a CGG repeat expansion premutation (55–200 repeats) in the fragile X mental retardation 1 (FMR1) gene. Given reports of poor insight in FXTAS, we postulated that patients with FXTAS would be less likely to exhibit placebo response. Objective To analyze placebo response from the first randomized controlled trial in FXTAS that evaluated cognitive and motor outcomes after 1 year of treatment with memantine. Methods Data from the placebo arm of the first randomized controlled trial in FXTAS were analyzed. There were 2 coprimary outcomes. Based on studies in Parkinson's disease, placebo responders were defined as individuals with an improvement of at least 50% in the coprimary outcomes. Improvements of 20% and 30% served as secondary cutoff values based on the suggested magnitude of placebo response in other movement disorders. Results A total of 36 participants in the placebo group completed baseline and follow‐up evaluations. The average age was 66 ± 7 years, and 60% were men. Average CGG repeat size was 86 ± 18. A total of 19 participants had stage 3 disease. Only 1 patient showed 50% improvement in both coprimary outcomes. At 30% and 20% improvement, there were 2 and 3 patients showing placebo response in the coprimary outcomes, respectively. Conclusions Patients with FXTAS exhibited low rates of placebo response in a randomized controlled trial. Further studies on the relationship between baseline insight and placebo responsivity are applicable to FXTAS and other disorders exhibiting cognitive impairment.

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“…al, who demonstrated that the magnitude of improvement resulting from placebo effect was relatively small (0.16 for all participants, 0.18 for children), but clinically relevant. 42 The etiology of this effect remains unclear; with suggestions including observer bias, inaccuracy of self-assessment of tic severity, or the fluctuating nature of tics. The magnitude of improvement seen in our small placebo group was larger than that typically described.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind, Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome

Lemmon

Grados

Kline

et al. 2015

Pediatric Neurology

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Background It has been hypothesized that glutamatergic transmission may be altered in Tourette syndrome (TS). In this study, we explored the efficacy of a glutamate agonist (D-serine) and antagonist (riluzole) as tic-suppressing agents in children with TS. Methods We performed a parallel 3-arm, 8-week, double-blind, randomized placebo-controlled treatment study in children with TS. Each child received 6 weeks of treatment with D-serine (maximum dose 30 mg/kg/day), riluzole (maximum dose 200 mg/day), or placebo, followed by a 2-week taper. The primary outcome measure was effective tic suppression as determined by the differences in the Yale Global Tic Severity Scale score (YGTSS); specifically, the Total Tic score (TTS) and the combined score (TTS + global impairment) between treatment arms after 6 weeks of treatment. Mann-Whitney U tests were performed to analyze differences between each group and the placebo group. Results Twenty-four patients (males = 21, ages 9-18) enrolled in the study and one patient dropped out prior to completion. Combined YGTSS and TTS scores improved in all groups. The 6-week mean percent improvement of the riluzole (n=10), D-serine (n=9), and placebo (n=5) groups in the combined YGTSS were 43.7, 39.5, and 30.2 percent and for TTS were 38.0, 25.0, and 34.0 percent, respectively. There were no significant differences in YGTSS or TTS, respectively, between the riluzole and placebo (p = 0.35, 0.85) or D-serine and placebo (p = 0.50, 0.69) groups. Conclusion Tics diminished by comparable percentages in the riluzole, D-serine, and placebo groups. These preliminary data suggest that D-serine and riluzole are not effective in tic suppression.

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Impact of placebo assignment in clinical trials of tic disorders

Abstract: The magnitude of the placebo effect in tic disorders appeared to be small. Further longitudinal studies using objective assessments for tic disorders are warranted to confirm the current results. © 2013 Movement Disorder Society.

Cited by 37 publications

References 18 publications

Placebo and nocebo responses in other movement disorders besides Parkinson's disease: How much do we know?

Placebo and nocebo responses in other movement disorders besides Parkinson's disease: How much do we know?

Placebo Response in Fragile X‐associated Tremor/Ataxia Syndrome

Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind, Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome

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