Evidence-based review of pharmacotherapy for tics: New Canadian Guidelines

Abstract:

"This article seeks to provide the practising clinician with guidance on the pharmacological management of tic disorders in children and adults. We performed a systematic review of the literature on the treatment of tic disorders. A multi-institutional group of 14 experts in psychiatry, child psychiatry, neurology, pediatrics, and psychology engaged in a consensus meeting. The evidence was presented and discussed, and nominal group techniques were employed to arrive at consensus on recommendations. A strong recommendation is made when the benefits of treatment clearly outweigh the risks and burdens, and can apply to most patients in most circumstances without reservation. With a weak recommendation, the benefits, risks, and burdens are more closely balanced, and the best action may differ depending on the circumstances. Based on these principles, weak recommendations were made for the use of pimozide, haloperidol, fluphenazine, metoclopramide (children only), risperidone, aripiprazole, olanzapine, quetiapine, ziprasidone, topiramate, baclofen (children only), botulinum toxin injections, tetrabenazine, and cannabinoids (adults only). Strong recommendations were made for the use of clonidine and guanfacine (children only). While the evidence supports the efficacy of many of the antipsychotics for the treatment of tics, the high rates of side effects associated with these medications resulted in only weak recommendations for these drugs. In situations where tics are not severe or disabling, the use of a medication with only a weak recommendation is not warranted. However, when tics are more distressing and interfering, the need for tic suppression to improve quality of life is stronger, and patients and clinicians may be more willing to accept the risks of pharmacotherapy."

From: Pringsheim T, Doja A, Gorman D, McKinlay D, Day L, Billinghurst L, Carroll A, Dion Y, Luscombe S, Steeves T, Sandor P. Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy. Can J Psychiatry 2012 Mar; 57(3):133-43.

Tony Attwood talks about Asperger's

An interview with Prof. Tony Attwood, one of the world's leading experts on Asperger's Syndrome. (Asperger's is a 'disorder' that sometimes co-occurs in people with Tourette Syndrome and which has some shared symptom groups). An excellent overview and in depth insights into the nature Asperger's. New research on ASD in women and girls is discussed and how it is more prevalent than previously thought and how it often presents different challenges. 

>> Click here to listen (interview starts at 00:42)

Broadcast date: Thursday 2 February 2012 on ABC Radio Brisbane

Dr Duncan McKinley on the CoffeeKlatch discusses Tourette Syndrome

Listen to programme (1hr 4mins):

Listen to internet radio with The Coffee Klatch on Blog Talk Radio

Watch the documentary 'Life's a Twitch' featuring Duncan McKinley: Life's a Twitch

Intelligence can disguise disabilities and disabilities can disguise intelligence

The majority of people with Tourette Syndrome fall into the average to above average range of intelligence. A child with TS may appear bright and highly articulate. Most are early readers and develop impressive verbal skills and a substantial vocabulary. Herein lies a potential paradox. They may have non-verbal learning difficulties. Their reading (and writing) speed may be slow and assignments may take them considerably longer to do than other children/students and their performance in written assessments may poorly reflect their actual academic abilities. 


Concentration, attention span and listening ability can be impaired significantly and mean children with TS may have difficulties in following the content of lessons but may compensate in other ways as a consequence of high intelligence. Evidence suggests that children with Tourette's are often highly verbal. This is a possible unintentional compensating strategy for difficulties experienced in other communication modalities that are impaired by tics, hyperactivity, sensory processing difficulties, obsessive behaviours and thoughts and attention deficit. Conversely it often happens that individuals with overt tic behaviours (and complex ritualistic behaviours) are perceived, mistakenly, as being impaired intellectually and cognitively.


Many of the difficulties that educators have in evaluating individuals with TS and in determining appropriate educational provisions, accommodations and adjustments, arise from a misunderstanding of the disorder. It is essential that the often more profound, 'hidden' but central aspects of TS are understood. TS in most cases involves much more than the tics that are seen and heard (many tics are also not observable). In fact 'tics-only' TS is apparent in only 8 - 12% of recorded cases. In children, diagnosis tends to be more dependent on observable signs that are reported by parents or seen by a physician. Children are less able to articulate their symptoms (e.g. what they experience) as they do not know how to do so or have little basis for interpreting aspects of the disorder, with which they live daily, as anything unusual. TS is a complex disorder of 'central' neurological dysregulation/dysinhibition and overactivity, affecting cognitive, motor and somatosensory pathways and appears to involve a number of distinct areas of the brain including cortical, sub-cortical and cerebellar regions.


An excellent quotation that embraces the misconceptions that are commonly made about Tourette Syndrome is:

"Intelligence can disguise disabilities and disabilities can disguise intelligence" 


The original author of this quote is unknown but it was used recently at a conference, with good effect and insight, by specialist educator Kathy Giordano in relation to special educational provision for students with TS.

Out of Our Control: The Chronicled Lives of Tourette's Syndrome - Completed documentary

A documentary about Tourette Syndrome: young people with TS speak about their own challenges and symptoms. 
Created by Ruthie: @jspershing93  
Ruthie's Blog: http://alittlebitdiffrent.blogspot.com

Key discoveries and advances in the understanding of Tourette Syndrome

Historical Perspective:

The French neurologists, Georges Albert Édouard Brutus Gilles de la Tourette 1857–1904 (right) and Jean-Martin Charcot 1825–1893

Timeline from: Advances in understanding and treatment of Tourette syndrome. Nat Rev Neurol 2011 Dec; 7(12):667-76.

Neurological inhibitory dysfunction plays a central role in Tourette Syndrome

The Spectrum of Tourette Syndrome

Tourette Syndrome is expressed differently in different people. In some, certain symptoms will predominate which in others are not present. For some it is overt tics that are the greatest difficulty. For others it may be obsessive thinking, impulsive and compulsive behaviours that are their most significant challenge. In many anxiety and social 'stresses' are a very significant problem. 

No abrupt dividing lines can be defined between different 'aspects' of Tourette Syndrome. In most individuals, behaviours/impairments are complex, integrated and expressed as a seamless repertoire. Discrete 'fencing off' of symptoms/behaviours is subjective although some professionals tend to split symptoms into 'co-morbidities' by 'identifying' multiple single disorders. Such an approach is often seen as less representational of actual clinical phenotypes. Dysinhibition (impaired inhibition) and impaired selectivity are implicated in may aspects of TS especially tics, impulsivity, compulsions, obsessions and reactivity and also sensory hypersensitivity. Many symptoms are thought to be due to sensorimotor dysfunction and other structural/neuro-chemical developmental abnormalities in the basal ganglia, cortex, cerebellar and other regions of the brain.

It is difficult to be definitive about the causation of reading, writing and social communication difficulties, when present, due the complex influences involved. These present different difficulties according to the individual and their combination of symptoms. Reading and writing are often affected by obsessive and compulsive behaviours (OCB), simple or complex tics and may also be influenced by impaired attention/concentration (also affected by tics and OCB) and for many by sensory integration issues. Some vocal tics and motor tics are easily heard/seen by others although many are not, with only the person themselves being aware of them, and neural tic 'activity' does not appear to be limited to expressed vocal and motor impulses alone. Evidence suggests tic activity also influences sensory and cognitive processes. Tic behaviours often wax and wane and in many individuals become less problematic in adulthood or the individual becomes more adept at compensating and in suppressing them. Although tics may diminish with age in many, other aspects of TS may presist or become more problematic with time.

Low mood is a common aspect of TS and is a symptom recorded in up to 79% of individuals attending clinics. Evidence shows that, in TS, concentrations of the neurotransmitters, serotonin and nor-epinephrine (nor-adrenaline), in the brain, are low. Reduced serotonin and nor-epinephrine levels are known to be involved in low mood. The stresses and social stigma of living with TS are also likely to contribute greatly. Low serotonin is also thought to be involved in obsessive-compulsive behaviours in TS, although it is likely that neuroanatomical (structural) differences play an important role. TS-related OCBs show similarities to behaviours characteristic of classic psychiatric OCD however research indicates there are distinct and characteristic differences. TS-related OCB frequently proves highly resistant to standard pharmaceutical therapies, such as SSRIs, which are used to treat OCD in patients without TS. OCB in TS has a complex inter-relationship with tic behaviours, especially so-called 'complex tics' and reiterative and persistent thoughts. Many tics and OCBs have a strong 'just-right' aspect to them and may involve evening-up and symmetry and may have a numerical (or counting) component.

A comprehensive listing of peer-reviewed published research material/citations is available on this site for those who wish to read further. It must be borne in mind that TS is a 'complex' condition and distinct international differences of perspective are prevalent in the approach to research and interpretation of findings. Often diagnostic definitions influence research paradigms, data sampling and subsequent numerical analysis. Diagnostic definitions are also undoubtedly influenced by prevalent therapeutic regimes (especially pharmacotherapies) and the convenience of identifying treatable aspects of complex disorders such as TS. Much of the research to date has centered around tic behaviours and also symptom groups that are shared with other disorders such as obsessive behaviours, attention deficit and hyperactivity. There has been a recent increase in clinical research involving other non-tic symptomatologies of TS notably the social/language difficulties and cognitive and sensory dysinhibition/dysregulation.

Treatment strategies for tics in Tourette syndrome.

Clare M. Eddy, Hugh E. Rickards and Andrea E. Cavanna  Ther Adv Neurol Disord. 2011

Download full article in pdf format (free)

Probably the best current review of evidence-based pharmacological and other therapeutic approaches for tics in Tourette syndrome:

Abstract: "Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by tics: repetitive, involuntary movements and vocalizations. These symptoms can have a significant impact on patients’ daily functioning across many domains. Tics tend to be most severe in child and adolescent sufferers, so their presence has the potential to impact a period of life that is both critical for learning and is often associated with the experience of greater social tension and self-consciousness than adulthood. Furthermore, control over tics that lead to physical impairment or self-injurious behaviour is of vital importance in maintaining health and quality of life. There are numerous complicating factors in the prescription of treatment for tics, due to both the side effects associated with alleviating agents and patient characteristics, such as age and comorbid conditions. This review summarizes literature pertaining to the efficacy and safety of both traditionally prescribed and more modern medications. We also discuss the merits of behavioural and surgical techniques and highlight newer emerging treatments. Although treatment response is to some extent variable, there are a number of agents that are clearly useful as first-line treatments for TS. Other interventions may be of most benefit to patients exhibiting refractory tics or more specific symptom profiles."

Inclusive or reductionist approaches to 'spectrum' disorders?

There are many proponents for the breaking down of symptom and behaviour profiles of spectrum disorders, such as Tourette Syndrome and autism (ASD/Asperger's), into discrete 'comorbid' disorders. Despite this tendency, preferred by many psychiatrists/psychoanalysts and to a somewhat lesser extent, neurologists and neuroscientists, substantial evidence for the existence of multiple co-occuring comorbidity, in all cases, is yet to be established convincingly. Clearly comorbidity can and does occur between disorders but can be assumed too readily if definitions are not concise or substantiated.

Symptoms and signs do not directly equate to disorders (a symptom is what a patient experiences, a sign is what a physician observes/elicits). Attention deficit is a symptom but cannot be (definitively) said to represent, or belong exclusively to, Attention Deficit Disorder (ADD) as there are other possible neurological or psychological (and environmental) mechanisms by which attention deficit may occur. Many 'disorders' are 'diagnosed' in a relatively subjective manner, using behavioural checklists and sometimes almost arbitrary fencing off or 'recognition' of perceived symptom groupings. It may not seem important that a person is diagnosed with an inclusive disorder in which the symptoms and behaviours are all seen as a manifestation of that disorder or whether a core disorder is diagnosed along with other separate comorbid disorders. However this does matter in many ways to the patient, their family and especially in terms of medical and other provision they may require. Although a core neuro-developmental disorder has been diagnosed, invariably, and for many disconcertingly, the comorbid disorders are defined as psychiatric.

Non-medical professionals such as teachers, educational psychologists, speech and occupational therapists rely heavily on expert opinion and have built paradigms around specific 'disorders' and the assumed difficulties they represent and hence the ways in which they can be approached. Individuals, their parents and family want to be able to make sense of the diagnoses they have been given and increase their understanding also. Many find an 'alphabet soup' diagnosis of multiple disorders bewildering and confusing. Another concern, especially for Tourette Syndrome, is the disparity in clinical treatment response achieved when those comorbid disorders are treated (in isolation) compared to the responses expected in individuals without Tourette Syndrome with those disorders.

This diagnostic uncertainty and a paucity of underlying mechanisms to explain many of those 'disorders' also has profound consequences for research. Research involves establishing a model for a disorder and then designing data collection and analysis around already established diagnostic categories and criteria. Researchers work on the assumption that what they are looking for and quantifying is real. This breaks down when the diagnostic definitions and symptom-separation may be erroneous, artificial or poorly defined. If TS is perceived as an 'inclusive' spectrum disorder, symptoms, although variable and diverse, will mostly (excepting genuine comorbid symptomatology) be seen as intrinsic to that disorder and suggest appropriate directions for research and help in determining underlying mechanisms for a disorder of greater complexity. However if symptoms such as obsessive and compulsive thinking and behaviours are allocated to a separate disorder (OCD), attention deficit and hyperactivity are allocated to ADD/ADHD, low mood to an affective disorder (depression) or theory of mind difficulties to autism, then clearly the approach will differ markedly. There is much research on TS, OCD, ADD, SPD and ASD, however the boundaries are not as distinct as one might imagine and symptom patterns may be blurred as a number of characteristic symptoms are shared between disorders.

Whether an inclusive (spectrum) or comorbidity (reductive) approach is taken for defining and understanding the symptoms and behaviours of Tourette Syndrome, it is essential that an awareness is achieved of the full range and expression of possible symptoms and behaviours. Many parents of children with a diagnosis are often left without knowing what to expect or why certain behaviours are occurring or whether other children and parents have experienced those issues. In a nutshell, there needs to be an awareness and understanding of the full spectrum of Tourette Syndrome. Parents are frequently informed that one behaviour belongs to Tourette Syndrome but another does not, often without sufficient explanation or worse due to insufficient knowledge of the expert consulted. 

Not knowing the 'true' presentation of Tourette Syndrome is a common difficulty for many physicians, therapists, scientists and the public in general. There is some friction between those who have or live with the disorder and the professional 'experts' who differ widely in their understanding and interpretation. One thing that is certain is that people with TS rarely feel that experts fully understand what the disorder entails and fail to have sufficient insight into the existential nature of TS. It is often felt that simplistic and reductionistic explanations are given that do not concur with actual experience. Science and (medical practice) should always be evidence-based but concern is being expressed that too few professionals are familiar with the current available literature and thinking and that uncertainties and errors of definition (especially in diagnostic definition) are undermining the value of research. 

Tourette Syndrome is not a 'new' disorder and was described in detail more than a century ago. There is a substantial volume of scientific, clinical and biographical literature but what is lacking is a synthesis. This is, in part, due to a hiatus in objective study of TS during the rise (and subsequent decline) of the Freudian derived school of psychoanalysis/psychiatry which diverged from the neurological research and clinical approaches that once prevailed. This absence of objective research on Tourette Syndrome, during the first half of the 20th Century, was alleviated by the pioneering work of Dr Arthur Shapiro and others during the 1960s.