Premonitory Urges Research Articles

The nosology of tardive syndromes

Since the original description of side effects of neuroleptics, different terminologies and definitions for tardive dyskinesia (TD) and tardive syndrome (TS) have been used by different authors, and often these two terms have been used interchangeably. This paper proposes a nosology designed to define and clarify various terms and phenomenologies within the TS spectrum.We propose to use the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements, as well as to the analogous repetitive movements that can appear in the limbs, trunk, or pelvis. The repetitive, relatively rhythmic nature of the movements is the common denominator of this phenomenologic category.The term tardive syndrome refers to the spectrum of all persistent hyperkinetic, hypokinetic and sensory phenomenologies resulting from chronic dopamine receptor blocking agents (DRBA) exposure. Thus, TS is an umbrella term.When dystonia is the main feature of TS it is considered to be tardive dystonia (TDyst). Retrocollis appears to be the predominant form of cervical dystonia in this condition. Cranial dystonias, particularly oromandibular dystonia, are also common forms of TDyst. Tardive akathisia refers to the inability to remain still with an urge to move, giving the appearance of restlessness. It is a sensory phenomenon and a common and disabling form of TS. Unlike acute akathisia, tardive akathisia tends to occur late and persists after the drug is withdrawn. In tardive tourettism, the patient exhibits the features of Tourette syndrome with complex motor and phonic tics associated with premonitory urge and relief of tension after performing the tic behavior. Tardive tremor differs from the resting tremor seen in drug-induced parkinsonism in that it is mainly a postural and kinetic greater than resting tremor. Tardive pain has been reported in association with chronic use of DRBA's. The pain involved the mouth, tongue and the genital region. The patients tended to obsess over the pain and usually had some other form of motor tardive syndrome, either tardive dyskinesia, tardive akathisia or tardive dystonia. The term tardive parkinsonism has been proposed for those drug induced parkinsonism patients who have persistent symptoms following discontinuation of the DRBA. However, there is a strong possibility that the DRBA may have simply unmasked subclinical parkinsonism or that there is coincident Parkinson disease developing during the period the patient is taking the DRBA.

Botulinum toxin for motor and phonic tics in Tourette's syndrome.

Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.

Neuroimaging Applications in Tourette's Syndrome.

Tics are neurodevelopmental hyperkinetic symptoms typically associated with unpleasant sensory experiences called premonitory urges. Tourette syndrome (TS) is the primary chronic tic disorder for which medical surveillance is most frequently required, and is associated with a complex phenotypical spectrum encompassing different types of abnormal behaviors. Animal models of tics support their link to phasic activity changes throughout the sensorimotor loop of the cortico-basal ganglia-thalamo-cortical network. Event-related functional magnetic resonance imaging (fMRI) studies on patients with TS showed that the supplementary motor area relays preparatory signals related to tics to the primary motor area and other cortical regions relevant to action monitoring, following which cortico-basal ganglia-thalamo-cortical activation leads to the manifestation of tics. Despite their methodological heterogeneity, structural MRI studies highlighted the existence of anatomical markers of distinct sub-phenotypes of the TS spectrum. Initial evidence suggests that combining MRI structural methods and functional intrinsic connectivity assessed during resting state could even discriminate between TS patients and control groups. MR-spectroscopy and positron emission tomography studies suggest that TS may be related to a complex interplay between different neurotransmitters (particularly dopamine, GABA and glutamate), but discrepancy across studies prevents firm conclusions. Recent volumetric, cortical thickness and fMRI studies results showed an association between premonitory urges and somatosensory and insular cortical regions, involved in the processing of interoceptive and enteroceptive stimuli and motor output modulation. Finally, both structural and functional MRI studies have provided important support to the subtyping of the TS spectrum with respect to behavioral co-morbidities, in line with a "dimensional approach" to the classification of neuropsychiatric disorders, which is based on the identification of neurocognitive endophenotypes and of their anatomical substrate.

The Role of Transcranial Direct Current Stimulation (tDCS) in Tourette Syndrome: A Review and Preliminary Findings.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is being investigated for a variety of neurological and psychiatric conditions. Preliminary evidence suggests that tDCS may be useful in the treatment of Tourette Syndrome (TS). This paper reviews the literature on the use of tDCS in commonly occurring comorbid conditions that are relevant to its proposed use in TS. We describe the protocol for a double-blind, crossover, sham-controlled trial of tDCS (Trial ID: ACTRN12615000592549, registered at www.anzctr.org.au) investigating the efficacy, feasibility, safety, and tolerability of tDCS in patients with TS aged 12 years and over. The intervention consists of cathodal tDCS positioned over the Supplementary Motor Area. Patients receive either sham tDCS for three weeks followed by six weeks of active tDCS (1.4 mA, 18 sessions over six weeks), or six weeks of active sessions followed by three weeks of sham sessions, with follow-up at three and six months. Pilot findings from two patients are presented. There was a reduction in the frequency and intensity of patients’ tics and premonitory urges, as well as evidence of improvements in inhibitory function, over the course of treatment. Larger scale studies are indicated to ascertain the maintenance of symptom improvement over time, as well as the long-term consequences of the repetitions of sessions.

Premonitory Urge for Tics Scale (PUTS): replication and extension of psychometric properties in youth with chronic tic disorders (CTDs).

Individuals with chronic tic disorders (CTDs) frequently describe aversive subjective sensory sensations that precede their tics. The first aim of the present study was to explore the psychometric properties of a standardized self-report measure to assess premonitory urges in CTDs, The Premonitory Urge for Tics Scale (PUTS), by replicating the analyses of Woods et al. (J Dev Behav Pediatr 26:397-403, 2005) using a sample twice the size of theirs. The second aim was to conduct an exploratory factor analysis of the PUTS. Eighty-four youth with CTDs, recruited from a pediatric OCD and tic specialty clinic, completed the PUTS while their caregivers completed The Parent Tic Questionnaire (PTQ) and a demographic measure. Consistent with (Woods et al. J Dev Behav Pediatr 26:397-403, 2005), the PUTS was found to be internally consistent (α=0.82) and significantly correlated with overall tic severity as measured by the PTQ (r=0.24, p<0.05) as well as the PTQ number (r=0.34, p<0.01) and intensity (r=0.24, p<0.05) subscales. A factor-analysis of the PUTS revealed a two-factor solution with one factor capturing the quality of premonitory sensations while the other factor assessed the overall intensity of the urges. These results support the use of the PUTS in reliably measuring premonitory urges, particularly in children over the age of 10years. Additionally, these findings highlight that urges are uniformly reported across gender and age and are more closely associated with number of tics than the frequency or intensity of tics.

4.34 The Premonitory Urge Revisited: An Individualized Premonitory Urge for Tics Scale

Premonitory urge ratings have advanced our understanding of urge phenomenology among individuals with tic disorders (TDs). However, these ratings have been limited by their reliance on a single global dimension of urge severity. This study examined the psychometric properties of a novel scale called the Individualized Premonitory Urge for Tics Scale (I-PUTS) that assesses urge severity across multiple dimensions (number, frequency, and intensity).

Premonitory urges and Touretting volcanoes

Abstract Causative meaning including, but not limited to, causation, prevention, and enabling is realized in language use through force construal. Force is explored in this article through consideration of narratives on Tourette Syndrome, a disorder that is largely characterized by its constitutive actions (vocal and motor tics). To account for force construal, the article proposes a merger of a vector model for the description of force in language and cognition and a lexical semantic model of ontologies and construals. Force is accounted for in terms of a number of configurations (cause, enable, prevent, withstand, and despite) that are realized through construal operations. This merger of explanatory models allows nuanced and flexible description of forceful meaning in actual language use.

Investigating Habituation to Premonitory Urges in Behavior Therapy for Tic Disorders

Behavior therapy is effective for Persistent Tic Disorders (PTDs), but behavioral processes facilitating tic reduction are not well understood. One process, habituation, is thought to create tic reduction through decreases in premonitory urge severity. The current study tested whether premonitory urges decreased in youth with PTDs (N = 126) and adults with PTDs (N = 122) who participated in parallel randomized clinical trials comparing behavior therapy to psychoeducation and supportive therapy (PST). Trends in premonitory urges, tic severity, and treatment outcome were analyzed according to the predictions of a habituation model, whereby urge severity would be expected to decrease in those who responded to behavior therapy. Although adults who responded to behavior therapy showed a significant trend of declining premonitory urge severity across treatment, results failed to demonstrate that behavior therapy specifically caused changes in premonitory urge severity. In addition, reductions in premonitory urge severity in those who responded to behavior therapy were significant greater than those who did not respond to behavior therapy but no different than those who responded or did not respond to PST. Children with PTDs failed to show any significant changes in premonitory urges. Reductions in premonitory urge severity did not mediate the relationship between treatment and outcome in either adults or children. These results cast doubt on the notion that habituation is the therapeutic process underlying the effectiveness of behavior therapy, which has immediate implications for the psychoeducation and therapeutic rationale presented in clinical practice. Moreover, there may be important developmental changes in premonitory urges in PTDs, and alternative models of therapeutic change warrant investigation.

Sensory pathways evaluation in children and adolescents with tic disorder

Background: Tic and Tourette disorders are not just movement disorders. Non-motor elements either sensory or cognitive are frequently associated with the expression of tics, commonly referred to as ‘premonitory urge’. Older children with tic disorder are able to describe their sensory sensitivity, but this may remain undetected and underestimated in toddlers and young children. Although an important element in the pathophysiology of tic disorder, sensory pathways have not been widely evaluated neither in the clinical nor in a research setting. Objective: To elucidate associated sensory symptoms in children presenting with tic disorder. Methods: We studied 81 children and adolescents with tics and Tourette syndrome, (N = 62 children with provisional tic disorder, Ν = 12 children with chronic motor tic disorder, Ν = 7 children with Tourette syndrome), aged 3,5 to 15,5 years. In order to assess their sensory symptoms, all subjects underwent evaluation through the following YGTSS (Yale Global Tic Severity Scale) for the assessment of tic severity, Premonitory Urge for Tics Scale (PUTS) for the assessment of premonitory urge and Sensory Profile (SPQ) for the assessment of sensory disorders. Additionally, sensory pathways were evaluated using sensory evoked potentials (SEPs). Results: A significant positive correlation was found between age and Total YGTSS score (rho = 0.335, p < 0.05), as well as a between age and PUTS (rho = 0.445, p < 0.05) and PUTS and Yale (rho = 0.482, p < 0.05). According the results of regression analysis, we conclude that PUTS can be used as a prediction of Yale with the aid of a specific mathematic formula. Yale = 1.389*PUTS + 4.836 No significant correlation was found in median nerve SEP cortical latencies between patients and age-matched controls. Conclusion: The evaluation of sensory symptoms in children with tic disorders could be of benefit in the design of individualized management and specific interventions and thus should be part of their routine assessment.

Tics, Tourette’s Syndrome, and Current Therapies Review—Current Pediatric Report

ᅟ Tourette syndrome and tic disorders are characterized by Tics—both motor and vocal. They are of childhood onset and considered to be neurodevelopmental disorders. Tics are preceded by premonitory urges with subsequent relief. These disorders often result in lower quality of life for patients, especially when presentation is severe.

Functional neuroimaging in Tourette syndrome: recent perspectives

Functional neuroimaging in Tourette syndrome: recent perspectives Nanette Mol Debes,&nbsp;Marie Pr&eacute;el,&nbsp;Liselotte Skov Pediatric Department, Tourette Clinic, Herlev University Hospital, Herlev, DenmarkAbstract: The most recent functional neuroimaging studies on Tourette syndrome (TS) are reviewed in this paper. Although it can be difficult to compare functional neuroimaging studies due to differences in methods, differences in age of the included subjects, and differences in the extent to which the presence of comorbidity, medical treatment, and severity of tics are considered in the various studies; most studies show that the cortico-striato-thalamo-cortical circuit seems to be involved in the generation of tics. Changes in this circuit seem to be correlated with tic severity. Correlations have been found between the presence of tics and hypermetabolism in various brain regions. Abnormalities of GABAergic, serotonergic, and dopaminergic neurotransmission in patients with TS have been suggested. During tic suppression, increased activity in the inferior frontal gyrus is seen. The premotor cortex might be involved in inhibition of motor control in subjects with TS. The right anterior insula is suggested to be a part of the urge&ndash;tic network. Several studies have shown altered motor network activations and sensorimotor gating deficits in subjects with TS. In future studies, inclusion of more well-defined subjects and further examination of premonitory urge and tic suppression is needed in order to increase the knowledge about the pathophysiology and treatment possibilities of TS. Keywords: functional neuroimaging, Tourette syndrome

Moderators and predictors of response to behavior therapy for tics in Tourette syndrome.

To examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders. Data from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9-69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression-Improvement score assessed by masked evaluators. The presence of tic medication significantly moderated response to CBIT vs PST (p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity (p = 0.005) and positive participant expectancy (p = 0.01) predicted greater tic improvement. Anxiety disorders (p = 0.042) and premonitory urge severity (p = 0.005) predicted lower tic reduction. Presence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication. The child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respectively). This study provides Class I evidence that CBIT is effective in reducing tic severity across subgroups of patients with chronic tic disorders, although the difference between treatments was smaller for participants on tic-suppressing medications, suggesting reduced efficacy in this subgroup.

Neurobiology of the Premonitory Urge in Tourette's Syndrome: Pathophysiology and Treatment Implications.

Motor and vocal tics are relatively common motor manifestations identified as the core features of Tourette's syndrome (TS). Although traditional descriptions have focused on objective phenomenological observations, such as anatomical location, number and frequency of tics, patients' first-person accounts have consistently reported characteristic subjective correlates. These sensory phenomena are often described as a feeling of mounting inner tension or urge to move ("premonitory urge"), which is transiently relieved by tic expression. This article reviews the existing literature on the clinical and neurobiological aspects of the premonitory urge in patients with TS, with focus on its pathophysiology and possible treatment implications.

Systematic review of severity scales and screening instruments for tics: Critique and recommendations.

Several clinician, informant, and self-report instruments for tics and associated phenomena have been developed that differ in construct, comprehensiveness, and ease of administration. A Movement Disorders Society subcommittee aimed to rate psychometric quality of severity and screening instruments for tics and related sensory phenomena. Following the methodology adopted by previous Movement Disorders Society subcommittee papers, a review of severity and screening instruments for tics was completed, applying a classification as "recommended," "suggested," or "listed" to each instrument. A total of 5 severity scales (Yale Global Tic Severity Scale, Tourette Syndrome Clinical Global Impression, Tourette's Disorder Scale, Shapiro Tourette syndrome Severity Scale, Premonitory Urges for Tics Scale) were "recommended," and 6 (Rush Video-Based Tic Rating Scale, Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey, Tourette Syndrome Global Scale, Global Tic Rating Scale, Parent Tic Questionnaire, Tourette Syndrome Symptom List) were "suggested." A total of 2 screening instruments (Motor tic, Obsession and compulsions, Vocal tic Evaluation Survey and Autism-Tics, Attention Deficit/Hyperactivity Disorder and Other Comorbidities Inventory) were "recommended," whereas 2 others (Apter 4-questions screening and Proxy Report Questionnaire for Parents and Teachers) were "suggested." Our review does not support the need for developing new tic severity or screening instruments. Potential objectives of future research include developing a rating instrument targeting the full spectrum of tic-related abnormal behaviors, assessing/screening malignant forms of tic disorders, and developing patient-reported outcome measures. © 2017 International Parkinson and Movement Disorder Society.

Non-Motor Aspects of Tic Disorders-New Developments.

The cardinal characteristics of tic-related disorders are stereotyped motor movements and vocalizations. However, they may be accompanied by non-motor features that appear sequentially during the course of the disorder and can sometimes be more disabling than the tics themselves. This review presents our perspectives on several non-motor aspects of Tourette syndrome based on the long experience of the Neuropsychiatric Tourette Clinic of a tertiary pediatric medical center. The effect of premonitory urges, sensory modulation disorder, tic-related cognitions, and environmental conditions on the expression and intensity of tics is elaborated, with suggestions for treatment approaches to each. We also describe the mediatory effect of parental attachment style on the link between maternal stress and ticcing intensity and the need to adjust psychotherapy interventions to account for the importance of this factor in emotion regulation. This review is intended to direct attention to the non-motor aspects of Tourette syndrome. An in-depth understanding of this complex and debilitating disorder will facilitate the formulation of innovative therapeutic protocols.

Tourette Syndrome and Chronic Tic Disorders: The Clinical Spectrum Beyond Tics.

The clinical surveillance and active management of Tourette syndrome (TS) and other primary chronic tic disorders cannot be limited to tics, as these patients manifest a spectrum of sensory-, behavioral-, cognitive-, and sleep-related problems that have a major impact on their functioning and quality of life, influencing enormously clinical decision making on a routine basis. The sensory phenomena of primary tic disorders consist of premonitory urges and heightened sensitivity to external somatosensory and interoceptive stimuli. Recent evidence suggests that raised interoceptive awareness may be related to the classical premonitory urges associated with tics. The burden of behavioral comorbidities is very important in determining the degree of disability of patients with primary tic disorders. Only 10%-15% of these patients presents exclusively with a tic disorder. Obsessive-compulsive disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. "Tic-related OCD" represents a phenomenologically characteristic subtype of OCD, also associated with "just right" phenomena. Probably the presence of comorbid attention deficit/hyperactivity disorder is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Mood and anxiety disorders, impulse control disorders, rage attacks, "impulsive" tic-like behaviors (e.g., nonobscene socially inappropriate behaviors, and self-injurious behaviors), and autism spectrum disorders complete the wide psychopathological spectrum of primary chronic tic disorders. Moreover, specific sleep abnormalities have been reported in TS patients, although more research is needed on this specific clinical problem. As in other areas of clinical neuroscience, a comprehensive approach to both motor and nonmotor aspects of this group of disorders will help personalizing treatment interventions and, ultimately, improve quality of care.

Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a hereditary, neuropsychiatric movement disorder with reported abnormalities in the neurotransmission of dopamine and γ-aminobutyric acid (GABA). Spatially focalized alterations in excitatory, inhibitory and modulatory neurochemical ratios within specific functional subdivisions of the basal ganglia, may lead to the expression of diverse motor and non-motor features as manifested in Gilles de la Tourette syndrome. Current treatment strategies are often unsatisfactory thus provoking the need for further elucidation of the underlying pathophysiology. In view of (i) the close spatio-temporal synergy exhibited between excitatory, inhibitory and modulatory neurotransmitter systems; (ii) the crucial role played by glutamate (Glu) in tonic/phasic dopaminergic signalling; and (iii) the interdependent metabolic relationship exhibited between Glu and GABA via glutamine (Gln); we postulated that glutamatergic signalling is related to the pathophysiology of Gilles de la Tourette syndrome. As such, we examined the neurochemical profile of three cortico-striato-thalamo-cortical regions in 37 well-characterized, drug-free adult patients and 36 age/gender-matched healthy control subjects via magnetic resonance spectroscopy at 3 T. To interrogate the influence of treatment on metabolite concentrations, spectral data were acquired from 15 patients undergoing a 4-week treatment with aripiprazole. Test-retest reliability measurements in 23 controls indicated high repeatability of voxel localization and metabolite quantitation. We report significant reductions in striatal concentrations of Gln, Glu + Gln (Glx) and the Gln:Glu ratio, and thalamic concentrations of Glx in Gilles de la Tourette syndrome in comparison to controls. ON-treatment patients exhibited no significant metabolite differences when compared to controls but significant increases in striatal Glu and Glx, and trends for increases in striatal Gln and thalamic Glx compared to baseline measurements. Multiple regression analysis revealed a significant negative correlation between (i) striatal Gln and actual tic severity; and (ii) thalamic Glu and premonitory urges. Our results indicate that patients with Gilles de la Tourette syndrome exhibit an abnormality in the flux of metabolites in the GABA-Glu-Gln cycle, thus implying perturbations in astrocytic-neuronal coupling systems that maintain the subtle balance between excitatory and inhibitory neurotransmission within subcortical nuclei.

The Current Understanding of Premonitory Urge Phenomena in Chronic Tic Disorders

Purpose of Review The goal of this review is to collect the progress made in the area of premonitory urge research in the areas of demographics, psychometrics, neurologic, psychopharmacology, and behavioral psychotherapy.

P.1.i.031 - Basal ganglia structure in Tourette’s disorder and attention deficit hyperactivity disorder: influence of comorbidity and medication use

Tourette syndrome is characterized by open motor behaviors — tics — but another crucial aspect of the disorder is the presence of premonitory urges: uncomfortable sensations that typically precede tics and are temporarily alleviated by tics. We review the evidence implicating the somatosensory cortices and the insula in premonitory urges and the motor cortico-basal ganglia-thalamo-cortical loop in tics. We consider how these regions interact during tic execution, suggesting that the insula plays an important role as a nexus linking the sensory and emotional character of premonitory urges with their translation into tics. We also consider how these regions interact during tic learning, integrating the neural evidence with a computational perspective on how premonitory-urge alleviation reinforces tics.

Aripiprazole Improves Associated Comorbid Conditions in Addition to Tics in Adult Patients with Gilles de la Tourette Syndrome.

Gilles de la Tourette Syndrome (GTS) is characterized by motor and vocal tics, as well as associated comorbid conditions including obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, and anxiety which are present in a substantial number of patients. Although randomized controlled trials including a large number of patients are still missing, aripiprazole is currently considered as a first choice drug for the treatment of tics. The aim of this study was to further investigate efficacy and safety of aripiprazole in a group of drug-free, adult patients. Specifically, we investigated the influence of aripiprazole on tic severity, comorbidities, premonitory urge (PU), and quality of life (QoL). Moreover, we were interested in the factors that influence a patient's decision in electing for-or against- pharmacological treatment. In this prospective uncontrolled open-label study, we included 44 patients and used a number of rating scales to assess tic severity, PU, comorbidities, and QoL at baseline and during treatment with aripiprazole. Eighteen out of fortyfour patients decided for undergoing treatment for their tics with aripiprazole and completed follow-up assessments after 4–6 weeks. Our major findings were (1) aripiprazole resulted in significant reduction of tics, but did not affect PU; (2) aripiprazole significantly improved OCD and showed a trend toward improvement of other comorbidities including depression, anxiety, and ADHD; (3) neither severity of tics, nor PU or QoL influenced patients' decisions for or against treatment of tics with aripiprazole; instead patients with comorbid OCD tended to decide in favor of, while patients with comorbid ADHD tended to decide against tic treatment; (4) most frequently reported adverse effects were sleeping problems; (5) patients' QoL was mostly impaired by comorbid depression. Our results suggest that aripiprazole may improve associated comorbid conditions in addition to tics in patients with GTS. It can be hypothesized that these beneficial effects are related to aripiprazole's adaptive pharmacological profile, which exhibits an influence on the dopaminergic as well as a number of other neurotransmitter systems. For the first time, our data provide evidence that patients' decision making process for or against medical treatment is influenced by other factors than tic severity and QoL.