Relaxation therapy as a treatment for tics in patients with Tourette syndrome: a systematic literature review

Background Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple motor and phonic tics, often associated with co-morbid behavioural problems. Tics can be modulated by environmental factors and are characteristically exacerbated by psychological stress, among other factors. This observation has led to the development of specific behavioural treatment strategies, including relaxation therapy. Objective This review aimed to assess the efficacy of relaxation therapy to control or reduce tic symptoms in patients with TS. Methods We conducted a systematic literature review of original studies on the major scientific databases, including Medline, EMBASE, and PsycInfo, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes measures included both tic severity and tic frequency. Results Our literature search identified three controlled trials, with a total number of 40 participants (range: 6–18 participants). In all three studies, relaxation therapy decreased the severity and/or the frequency of tic symptoms. However, the only trial comparing relaxation therapy to two other behavioural techniques found relaxation therapy to be the least effective intervention, as it reduced the number of tics by 32% compared to 44% with self-monitoring and 55% with habit reversal. Discussion The results of this systematic literature review provide initial evidence for the use of relaxation therapy as a behavioural treatment intervention for tics in patients with TS. Caution is needed in the interpretation of these findings, because the reviewed trials had small sample sizes and there was high heterogeneity across the study protocols.


Introduction
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the chronic presence of motor and phonic tics. Tics are defined as sudden, involuntary, repetitive, nonrhythmic movements (motor tics) or vocalizations (phonic tics) [1,2]. Tics are preceded by sensory experiences referred to as 'premonitory urges' and are modulated by environmental factors [2,3]. Based on clinical observations, stress has long been associated with tic exacerbations, contributing to the characteristic 'waxing and waning' course of TS [4]. Specifically, the results of multiple studies have suggested the existence of a relationship between tic severity and both psychological stress [5,6] and physical stress [7,8]. Moreover, self-report measures of patients with TS have pointed towards a correlation between tic frequency and daily life stress [9]. From the neurobiological point of view, there is evidence of overactivation of the hypothalamic-pituitaryadrenal axis in patients with TS [10]. In consideration of these findings, a number of behavioural treatment interventions targeting patients' stress have been implemented in order to decrease tic severity and frequency [11]. We set out to conduct a systematic literature review on the effectiveness of relaxation therapy in controlling or reducing tics in patients with TS compared to other treatment types or no treatment. We aimed to fill an important gap in our knowledge about TS, as information about the effectiveness of relaxation therapy can inform clinicians about the choice of appropriate treatment interventions for patients with tics.

Methods
This systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [12], used in conjunction with the Explanation and Elaboration document [13]. We included in our review all studies using a form of relaxation therapy as the main treatment intervention for tics in patients with a diagnosis of TS or other persistent tic disorders. The relaxation therapies included were those in which individuals were taught a specific relaxation technique by a clinician or expert: relaxation training, hypnosis and/or relaxation with mental imagery, yoga, and mindfulness based stress reduction [14]. Studies using behavioural interventions that were not predominantly based on muscular relaxation were excluded, as well as studies that did not specify the details of the relaxation technique. Studies using Habit Reversal Training were also excluded, as relaxation training is not the core element of this behavioural technique for tic control. We included both studies using another form of behavioural therapy as comparator and studies using no comparator. The outcomes of interest were the severity and frequency of tics, assessed with validated measures.
The searches were conducted on five databases: MEDLINE, Embase, PsycInfo, and NCBI PubMed. The search terms were as follows: 'Tourette*' OR 'Tic*' AND 'Relaxation' OR 'Stress reduction' OR 'Stress relief'. For comprehensiveness, the reference lists of eligible articles were also screened to identify any relevant articles. Google scholar was used to search for the grey literature. Since a few of the reviewed studies were published in the same scientific journals, the contents of the 'Journal of Behavior Therapy and Experimental Psychiatry' and 'Behaviour Research and Therapy' were manually searched for any further relevant articles. We limited our search to articles published in English language, but there were no chronological, geographic, or demographic limitations to the inclusion of studies. Both qualitative and quantitative study designs were included for review. We excluded studies in which medications were used, including anti-anxiety agents, muscle relaxants, and alpha-2 adrenergic agonists, which modulate noradrenaline signalling, a neurotransmitter normally produced in response to stress [15][16][17]. The Crowe Critical Appraisal Tool (CCAT) was used to assess the quality of the selected studies, and any studies scoring less than 30% were excluded from the review [18,19].

Results
Our systematic literature search yielded a total of 53 articles, after removal of duplicates. Of these, 13 were considered relevant to the review and their full texts were inspected. A further two studies were excluded because the English full text was not available; one study was excluded because its participants did not have a formal diagnosis of TS or other persistent tic disorders [20]. One study retrieved by manually searching the contents of relevant journals was excluded as it focused on a different behavioural technique for tic control (massed practice) [21]. A total of 10 results met all the inclusion criteria. This methodology is displayed in the flow diagram (Fig. 1).
Three original studies on relaxation therapy as a treatment for tics were included in the present review (Table 1): a randomized controlled trial involving 16 participants with a diagnosis of TS in which relaxation training was compared to a control arm of relaxation involving music and sitting quietly [23]; a single arm study involving 18 participants on mindfulness-based stress reduction consisting of sitting meditation, walking meditation, yoga, and body scan [22]; a controlled trial in which 6 participants received three different behavioural interventions [24]. As the studies had different comparators and outcome measures, a meta-analysis could not be performed [25].
A further seven articles presenting individual case studies and case series were included in the review for separate qualitative analysis (Table 2).

Discussion
We conducted a systematic literature review on the effectiveness of relaxation therapy as a treatment for tics in patients with TS, retrieving three original studies that recruited a total of 40 participants. In each of the three controlled trials included in the present review, relaxation therapy decreased the severity and/or the frequency of tics in the study population, therefore supporting its use in patients with TS. However, the only trial comparing relaxation therapy to two other behavioural techniques for tic control found relaxation therapy to be the least effective intervention, as it reduced the number of tics by 32%, compared to 44% with self-monitoring and 55% with habit reversal [24]. Moreover, one of the reviewed trials did not show a statistical difference between the experttaught relaxation intervention arm and the control group [23]. In this study, both the intervention group and the control group received a form of relaxation training and both groups reported an improvement, although the participants in the control group were not taught a recognized technique for relaxation. The findings of the third study showed a significant improvement in tic severity, however in this trial there was no control group or comparator, resulting in increased risk of bias and decreased reliability [22].
Four of the seven single case studies and case series on the effectiveness of relaxation therapy supported its use for the treatment of tics. Specifically, 7 of the 12 cases (58%) individually described in the literature reported positive results.
One of the participants included in a case series dropped out before follow-up assessment; however, she had reported an initial improvement before she dropped out [33]. Overall, the reviewed case studies and case series supported the use of relaxation therapy, although the level of evidence was relatively low, leading to a large margin of error.
Relaxation therapy is currently used as a component of recommended behavioural treatments for tics, such as Habit Reversal Training and the wider Comprehensive Behavioral Intervention for Tics [30,34,35]. Although the exact effect of relaxation therapy in combination with other techniques is still unclear, our findings suggest that relaxation therapy might play an important role within multi-component treatment interventions. However, it is worthy of note that in one of the reviewed trials [23], the taught relaxation therapy had no statistical benefit over the control group, in which participants were simply told to relax. This could indicate that although relaxation is effective per se, it is not the expert-taught techniques or the hypnotherapy protocol which is beneficial, but simply taking the time to consciously relax the body on a regular basis. These observations could have practical clinical relevance, in consideration of the lack of trained therapists as a limiting factor for the implementation of behavioural treatment interventions on a larger scale [36].
As TS often presents with co-morbid conditions such as obsessive-compulsive disorder and attention-deficit and hyperactivity disorder [37,38], it would be important to assess the effectiveness of relaxation therapy as a possible treatment intervention for TS-related conditions. The presence of comorbid behavioural symptoms has been shown to have farreaching consequences in terms of patients' health-related quality of life [39,40]. The results of three recent randomized controlled trials have suggested that cognitive behavioural therapy is more effective than relaxation therapy for the treatment of both obsessive-compulsive disorder [41,42] and attention-deficit and hyperactivity disorder [43].
The present systematic literature review has limitations. The reviewed controlled trials had relatively small sample sizes, as well as heterogeneous study protocols, resulting in increased risk of bias and limited generalizability of the findings. Moreover, the majority of the studies included in the review were older, the oldest having been published in 1978, meaning there may be some discrepancy in validity between studies. The diagnostic criteria for TS have changed over time, raising the possibility that the results of some of the older studies might not be transferable or reproducible in patients who were diagnosed more recently [44]. Finally, the reviewed narrative case studies have a higher risk of both publication bias and sampling bias, because of the selective attention to patients who have proven unresponsive to other treatment interventions.
Further research is needed to establish whether relaxation therapy is an effective treatment intervention for tics in the  general population of patients with TS. Larger randomized controlled trial comparing relaxation therapy to a control of minimal treatment would be useful to understand whether relaxation therapy is an effective intervention either in isolation or in conjunction with other types of behavioural therapy currently in use. Other areas for future research include the evaluation of the efficacy of relaxation therapy in comparison to other behavioural treatments and the identification of patient groups who are most likely to benefit from relaxation therapy, based on age, tic severity, presence of co-morbid conditions, and other clinical parameters.
In summary, the results of this systematic literature review showed preliminary evidence for the safety and efficacy of relaxation therapy as a treatment for tics in patients with TS. As the available literature is limited, further research is needed to confirm our preliminary findings and reach more accurate conclusions. Specifically, it is still unclear how relaxation therapy compares to other behavioural treatment interventions for tic control, as well as its exact role within multi-component behavioural interventions for tic control such as the Comprehensive Behavioral Intervention for Tics. The ongoing search for more effective treatment strategies is a key component of clinical research aimed at improving healthrelated quality of life in patients with tic disorders.
Acknowledgements Gratitude is expressed to Tourettes Action UK and Tourette Association of America for their ongoing support.

Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
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