Bupropion-Related Exacerbation of Tic Disorder in an Adult: A Case Report.

Bupropion is antidepressant and a smoking cessation aid medication related to dopaminergic activity. We report for the first time a case of an older adult with a known tic disorder, which was in remission but exacerbated during treatment with bupropion. It has been reported that other dopaminergic compounds such as methylphenidate can exacerbate tic disorder. Clinicians should be aware of this potential adverse effect when prescribing bupropion to adults with tic and other motor disorders.

Setting the record straight: The nosology of tardive syndromes.

We propose the use of the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements and the analogous repetitive movements of the limbs, trunk, or pelvis. The term tardive syndrome is an umbrella term to be used to refer to the spectrum of all persistent hyperkinetic, hypokinetic, and sensory phenomenologies resulting from chronic dopamine receptor blocking agent (DRBA) exposure. TD is a type of TS. The term tardive dystonia (TDyst) should be used when dystonia is the main feature of TS. Retrocollis and oromandibular dystonia appear to be the most common form of Tdyst. Tardive akathisia refers to the inability to remain still with an urge to move, giving the appearance of restlessness. In tardive tourettism, the patient has complex motor and phonic tics associated with premonitory urge and relief of tension after performing the tic behavior, thus resembling Tourette's syndrome. Tardive tremor is composed of mainly postural and kinetic tremors. It differs from the resting tremor seen in drug-induced parkinsonism. Tardive pain occurs in association with chronic use of DRBAs and involves the mouth, tongue, and genital region with no physical findings. In tardive parkinsonism, the patient has persistent parkinsonism even after discontinuation of the DRBA although this diagnosis is in question and may represent DRBA-uncovered idiopathic Parkinson's disease or coincident development of Parkinson's disease while taking DRBAs.

Tic Symptoms Induced by Atomoxetine in Treatment of ADHD: A Case Report and Literature Review.

OBJECTIVE: Patients with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for tic disorders. Atomoxetine (ATX) has been accepted as an alternative medication for patients with ADHD and a comorbid tic disorder. It is rarely reported that tic symptoms are induced by ATX. METHODS: This present report described a boy with ADHD who developed tic symptoms during ATX initiation. We used an ABAB trial to confirm the tics were related to ATX administration. In addition, we reviewed the published literature of patients whose tic symptoms were confirmed or suspected of relating to ATX usage. RESULTS: This present case with an ABAB design showed on-off control of tics with or without ATX, which allowed us to make a strong conclusion that the tics were related to ATX administration. Literature review also indicated that ATX might induce tic symptoms in children with ADHD, especially in those being boys and having a history of tics. The time from starting ATX to tics symptoms appearing was approximately 19 days. The most common tic symptoms were eye blinking, vocal tics, or throat clearing, and neck movements. These tics symptoms in most cases could be resolved after discontinuing ATX without further pharmacotherapy. CONCLUSION: Pediatricians and child psychiatrists should be well aware of this potential adverse effect in children with ADHD receiving ATX.

A dose-response relationship between organic mercury exposure from thimerosal-containing vaccines and neurodevelopmental disorders.

A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg) exposure from thimerosal-containing (49.55% Hg by weight) vaccines on the risk of neurodevelopmental disorders (NDs). Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991-2000) in the Vaccine Safety Datalink (VSD) project. ND cases were diagnosed with pervasive developmental disorder (PDD), specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV) administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR) = 1.054), specific developmental delay (OR = 1.035), tic disorder (OR = 1.034) and hyperkinetic syndrome of childhood (OR = 1.05) cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.

Managing the risks of ADHD treatments.

Pharmacotherapy of attention deficit-hyperactivity disorder (ADHD) is a well-established and effective treatment modality. However, ADHD medications are not without side effects. Understanding the prevalence of adverse events and effective management of risks associated with stimulants and other medications used to treat ADHD is central to broad applicability and effective treatment. This review discusses the literature on the prevalence of adverse events and management strategies employed. We searched online MEDLINE/PubMed and Cochrane databases for articles using several keywords relating to adverse events associated with ADHD medication management. We discuss the relevant data on the significance and prevalence of side effects and adverse events, highlight recent updates in the field, and suggest approaches to clinical management.

Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents.

BACKGROUND: Medication is an important element of therapeutic strategies for ADHD. While medications for ADHD are generally well-tolerated, there are common, although less severe, as well as rare but severe adverse events AEs during treatment with ADHD drugs. The aim of this review is to provide evidence- and expert-based guidance concerning the management of (AEs) with medications for ADHD. METHODS: For ease of use by practitioners and clinicians, the article is organized in a simple question and answer format regarding the prevalence and management of the most common AEs. Answers were based on empirical evidence from studies (preferably meta-analyses or systematic reviews) retrieved in PubMed, Ovid, EMBASE and Web of Knowledge through 30 June 2012. When no empirical evidence was available, expert consensus of the members of the European ADHD Guidelines Group is provided. The evidence-level of the management recommendations was based on the SIGN grading system. RESULTS: The review covers monitoring and management strategies of loss of appetite and growth delay, cardiovascular risks, sleep disturbance, tics, substance misuse/abuse, seizures, suicidal thoughts/behaviours and psychotic symptoms. CONCLUSION: Most AEs during treatment with drugs for ADHD are manageable and most of the times it is not necessary to stop medication, so that patients with ADHD may continue to benefit from the effectiveness of pharmacological treatment.

Stimulant side effects and inverted-U: implications for ADHD guidelines.

OBJECTIVE: To review literature relevant to a possible prediction of stimulant side effects in attention deficit hyperactivity disorder (ADHD), with implications for guidelines. METHOD: Recent literature on inverted-U effects of dopamine in the prefrontal cortex (PFC), default mode processing, and motor circuits relevant to stimulant side effects is reviewed. RESULTS: The literature on inverted-U effects in the PFC suggests that catechol-O-methyltransferase (COMT) Met versus Val polymorphisms may predict excess dopaminergic effects, including headache and introversion in Met/Met subjects, but therapeutic effects in Val/Val subjects, while dopamine transporter polymorphisms may predict motor side effects. In particular, an understanding of 'inverted-U' effects helps to explain why some children may experience side effects while others show improvements at similar dose ranges. CONCLUSION: Genetic prediction of stimulant side effects should be investigated, particularly given recent controversies in relation to National Health and Medical Research Council guidelines for stimulant use. A better understanding of treatment-emergent effects will also provide a better understanding of therapeutic effects.

Spatial and temporal properties of tic-related neuronal activity in the cortico-basal ganglia loop.

Motor tics are involuntary brief muscle contractions that interfere with ongoing behavior and appear as a symptom in several human disorders. While the pathophysiology of tics is still largely unknown, multiple lines of evidence suggest the involvement of the corticobasal ganglia loop in tic disorders. We administered local microinjections of bicuculline into the putamen of Macaca fascicularis monkeys to induce motor tics, while simultaneously recording neuronal activity from the primary motor cortex, putamen, and globus pallidus. These data were used to explore the spatial and temporal properties of tic-related neuronal activity within the cortico-basal ganglia system. In the putamen, tics were associated with brief bursts of activity of phasically active neurons (presumably the projection neurons) and complex excitation-inhibition patterns of tonically active neurons. Tic-related activity within the putamen was spatially focused and somatotopically organized. In the globus pallidus, tic-related activity was diffusely distributed throughout the motor territory. Tic-related activity in the putamen usually preceded the tic-related activations in the cortex, but in the globus pallidus, tic-related activity was mostly later than the cortex. These findings shed new light on the role of the different basal ganglia nuclei in the generation of motor tics. Despite the early and somatotopically focused nature of tic-related activity in the input stage of the basal ganglia, tic-related activity in the output nucleus is temporally late and diffusely distributed, making it incompatible with a role in tic initiation. Instead, abnormal basal ganglia activity may serve to modulate motor patterns or activate learning mechanisms, thus augmenting further tic expression.

The neurophysiological correlates of motor tics following focal striatal disinhibition.

The cortico-basal ganglia pathway is involved in normal motor control and implicated in multiple movement disorders. Brief repetitive muscle contractions known as motor tics are a common symptom in several basal ganglia related motor disorders. We used focal micro-injections of the GABA-A antagonist bicuculline to the sensorimotor putamen of behaving primates to induce stereotyped tics similar to those observed in human disorders. This focal disruption of GABA transmission in the putamen led to motor tics confined to a single or a few muscles. The temporal and structural properties of the tics were identified using electromyogram and frame-by-frame analysis of multi-camera video recordings. During experimental sessions the tics would wax and wane, but their size and shape remained highly stereotyped within the session. Neuronal spiking activity and local field potentials were recorded simultaneously from multiple locations along the cortico-basal ganglia pathway: motor cortex, putamen and globus pallidus external and internal segments. The local field potentials displayed stereotyped tic-related voltage transients lasting several hundred milliseconds. These 'local field potential spikes', which appeared throughout the cortico-basal ganglia pathway, were consistently observed in close temporal association to the motor tics. During tic expression, neuronal activity was altered in most of the recorded neurons in a temporally focal manner, displaying phasic firing rate modulations time locked to the tics. Consistent with theoretical models of tic generation, transient inhibition of the basal ganglia output nucleus prior to and during tic expression was observed. The phasic reduction of basal ganglia output was correlated with a disinhibition of cortical activity, manifesting as short bursts of activity in motor cortex. The results demonstrate that the basal ganglia provide a finely timed disinhibition in the output nuclei of the basal ganglia. However, a large fraction of the neurons were simultaneously inhibited during tics, although tics were only manifested in a small confined muscle group. This suggests that rather than representing a specific action within the basal ganglia itself, these nuclei provide a temporally exact but spatially distributed release signal. The tics induced by striatal disinhibition bear a striking resemblance to motor tics recognized in human pathologies associated with basal ganglia dysfunction. The neuronal changes observed during tic formation may provide valuable insights into the underlying mechanism of tic disorders, as well as into basic information processing in the cortico-basal ganglia loop.

Development of tics in a thirteen-year-old male following atomoxetine use.

Tics and Tourette syndrome are common comorbidities of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD). One of the mainstay pharmacologic therapies for ADHD has been stimulants. However, this class of drugs has been associated with tic exacerbations, thus limiting their utility in this patients subgroup. Atomoxetine has been explored as an alternative treatment as one of the few non-stimulants available to treat ADHD. Early data identifies atomoxetine's influence on Tourette symptomatology to be not merely equivocal but potentially suppressive in the manifestation of tics. There are, however, case studies describing patients experiencing recurrences of tics following treatment with atomoxetine. We present a unique case of a patient, without any prior history of a movement disorder, who developed tics following a single dose of atomoxetine that did not improve until interventional therapy was initiated.

Drug and non-drug treatments of children with ADHD and tic disorders.

OBJECTIVE: To review the treatment of ADHD in children with chronic tic disorders. BACKGROUND: Tic disorders are relatively common in school-age children and range from mild to severe. Children with mild tics may not require medication for the treatment of tics. The co-occurrence of attention deficit hyperactivity disorder (ADHD) and disruptive behavior are common in children with tic disorders and may be associated with significant morbidity. METHODS: We conducted a literature search to identify reports of tics as an adverse effect to stimulant medication, the treatment of children with ADHD and tics as well as novel treatments that have been proposed for the treatment of ADHD in children with tic disorders. RESULTS: The preponderance of evidence suggests that stimulant medications are safe and effective in the treatment of children with ADHD and tic disorders. A minority of children with tic disorders may show a worsening of tics or not tolerate stimulants for other reasons. The growing list of non-stimulants provides options for clinicians and parents of these children. CONCLUSIONS: Treatment planning for children with ADHD and tic disorders involves careful discussion with parents on choosing the best course of action. Stimulants should be part of this discussion. More study is needed on non-pharmacological approaches to the treatment of tics and ADHD in this population.

First-onset tics in patients with attention-deficit-hyperactivity disorder: impact of stimulants.

First-onset tics during stimulant treatment of attention-deficit-hyperactivity disorder (ADHD) are clinically relevant and remain a matter of scientific debate. Because there are limited clinical trials analyzing the risk of first-onset tics in stimulant-treated ADHD, a comprehensive evaluation is required for evidence-based clinical recommendations. An analysis of studies with high methodological quality (i.e. double-blind placebo-controlled) on first-onset tics during stimulant treatment of ADHD revealed that there seems to be no elevated risk of first-onset tics in children undergoing this treatment. Although a close temporal relationship might be seen in a few patients, the role of treatment duration, dose of stimulant, genetic vulnerability, and developmental aspects need to be further explored to clarify possible pathophysiological mechanisms of tic emergence under stimulant treatment. The results of high quality studies, in addition to specialized studies with methodological limitations, suggest that stimulants are the criterion standard for the safe and successful treatment of ADHD.

Amisulpride-induced tardive motor and phonic tics.

OBJECTIVE: To report a patient with tardive tics possibly induced by the atypical neuroleptic drug amisulpride. CASE REPORT: A 55-year-old woman developed motor and phonic tics after a prolonged treatment with amisulpride. Tics improved and finally disappeared after amisulpride withdrawal. CONCLUSIONS: Tardive motor and phonic tics should be considered as a possible adverse effect of amisulpride.

Amisulpride related tic-like symptoms in an adolescent schizophrenic.

Tic disorders can be effectively treated by atypical antipsychotics such as risperidone, olanzapine and ziprasidone. However, there are two case reports that show tic-like symptoms, including motor and phonic variants, occurring during treatment with quetiapine or clozapine. We present a 15-year-old girl schizophrenic who developed frequent involuntary eye-blinking movements after 5 months of amisulpride treatment (1000 mg per day). The tic-like symptoms resolved completely after we reduced the dose of amisulpride down to 800 mg per day. However, her psychosis recurred after the dose reduction. We then placed her on an additional 100 mg per day of quetiapine. She has been in complete remission under the combined medications for more than one year and maintains a fair role function. No more tic-like symptoms or other side effects have been reported. Together with previously reported cases, our patient suggests that tic-like symptoms might occur in certain vulnerable individuals during treatment with atypical antipsychotics such as quetiapine, clozapine, or amisulpride.