Current Drug Therapy - Volume 15, Issue 2, 2020

Background: Tourette syndrome is reflectively and quite erroneously associated by many as a syndrome with tics and swearing. However, the syndrome is a complex neuropsychiatric disorder consisting of features known as Tourette syndrome combined with several serious comorbidities justifying the quite recent term of Tourette disorder rather than “syndrome”. Unfortunately, the published literature is mostly dedicated to tics, while mentioning the comorbidities only briefly. Objective: The study aimed to provide a brief description of the “many faces” of Tourette syndrome. Methods: This study included a summary of the relevant published literature. Results: The literature review provided indicates that this rare neuropsychiatric clinical syndrome is more a multidisciplinary “disorder” rather than a” syndrome”. Conclusion: Patients with Tourette disorder should be evaluated and treated by a multidisciplinary team.

Background: Tics, defined as quick, rapid, sudden, recurrent, non-rhythmic motor movements or vocalizations are required components of Tourette Syndrome (TS) - a complex disorder characterized by the presence of fluctuating, chronic motor and vocal tics, and the presence of co-existing neuropsychological problems. Despite many advances, the underlying pathophysiology of tics/TS remains unknown. Objective: To address a variety of controversies surrounding the pathophysiology of TS. More specifically: 1) the configuration of circuits likely involved; 2) the role of inhibitory influences on motor control; 3) the classification of tics as either goal-directed or habitual behaviors; 4) the potential anatomical site of origin, e.g. cortex, striatum, thalamus, cerebellum, or other(s); and 5) the role of specific neurotransmitters (dopamine, glutamate, GABA, and others) as possible mechanisms (Abstract figure). Methods: Existing evidence from current clinical, basic science, and animal model studies are reviewed to provide: 1) an expanded understanding of individual components and the complex integration of the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit - the pathway involved with motor control; and 2) scientific data directly addressing each of the aforementioned controversies regarding pathways, inhibition, classification, anatomy, and neurotransmitters. Conclusion: Until a definitive pathophysiological mechanism is identified, one functional approach is to consider that a disruption anywhere within CBGTC circuitry, or a brain region inputting to the motor circuit, can lead to an aberrant message arriving at the primary motor cortex and enabling a tic. Pharmacologic modulation may be therapeutically beneficial, even though it might not be directed toward the primary abnormality.

Background: Most of the patients with Tourette Syndrome (TS) present additional comorbidities. Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD) are the most common. Sleep Disorder has been suggested also as common comorbidity. Objective: To review the literature on sleep characteristics and sleep disorder in patients with Tourette Syndrome (TS), with emphasis on the contribution of specific co-morbidities to the severity of impaired sleep and life quality of the patients. Results: In general, sleep problems are not frequent at the age when tics appear which are estimated to affect about 10 % of these children. In severe cases, tics appear in all sleep stages. In a large study, the prevalence of sleep problems was 17.8% but was 12 % in “TS-only” (9.4% in children and 7.5 in adults) compared to 22% in children and 18% in adults with TS+ADHD. Unfortunately, in most of the studies, the characteristics of these “sleep problems” are not defined. In spite of the scarcity of data, the two main sleep disorders in TS patients are insomnia and parasomnias. Although much more data is needed, many TS subjects are sleep deprived (which exacerbate the tics) and may suffer from excessive daytime sleepiness, which negatively affects normal functioning. Conclusions: Although the literature is not conclusive, children and adolescents with TS appear to suffer more from sleep disturbances and sleep disorders than age-matched controls. Not all patients have tics during sleep, but in severe cases, tics may appear in all sleep stages. It is clear that when patients present both TS and ADHD, (a very common condition), the sleep difficulties are related mainly to ADHD. Much more research is warranted in all aspects of sleep and sleep disorders in TS.

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by multiple repetitive motor and vocal tics. In most patients, its clinical course has a waxing and waning nature and most patients, usually children, will benefit from tolerant environmental and psychoeducation. Patients with more complicated tics, in particular, those with significant comorbidities will require drug therapy. Objective: The present paper is a mini-review of the current therapeutic arsenal for TS with reference to drug and non-drug management approach. Methods: A systematic survey of medical literature regarding the treatment decision making and the reported clinical trials or accumulating experience with different medications or other therapeutic modalities which were proven beneficial over the years. Results: Reviewing the literature indicates that dopamine antagonists, such as haloperidol and pimozoide, are the most reliable agents in terms of treatment response. Due to numerous adverse effects, newer atypical anti-psychotic drugs have been shown effective. Other widely accepted medications include alpha-2 adrenergic agonists, benzamides, dopamine depleting agents, benzodiazepines and dopamine depleting agents. In more selective and intractable cases botulinum toxin, dopamine agonists and cannabinoids should be also considered. Non-pharmacologic therapies reported beneficial effects, which include on the one hand, non-invasive behavioral techniques, such as comprehensive behavior therapy for tics. While on the other hand, in cases with particular protracted pharmaco-resistant tics electric stimulation techniques, such as deep brain stimulation, have been shown to be successful. Conclusion: Currently, there are numerous multifarious options for treatment of tics and other comorbid symptoms of TS. Nevertheless, treatment options and decision-making algorithms are still a clinical challenge. Area Covered: A step by step decision-making and various drugs and non-pharmacologic modalities appropriate for the management of TS.

Background: Capsaicin is a pungent component of chili peppers that suppresses the growth of various cancer cell lines including breast cancer. However, it shows extremely low oral bioavailability due to its poor water solubility. Objective: The objective of the present work was to improve the solubility and dissolution rate of capsaicin. Methods: Solid dispersions were prepared by the solvent evaporation method using different molar ratios of capsaicin and urea (1:1, 1:2, and 1:3). Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) study were used to characterize the solid dispersion. Solid dispersions were evaluated for solubility, dissolution rate and in vitro cytotoxicity in breast cancer cell lines. Results: XRD and DSC studies exhibited the reduced crystallinity of a drug in solid dispersion. Phase solubility study shows that the drug solubility increased by increasing carrier concentration. In vitro release study of the solid dispersion showed the faster dissolution of a drug with increasing carrier concentration. Solid dispersion formulation effectively inhibited the growth of MCF-7 human breast cancer and MDA-MB-231 triple negative human breast cancer cells in an MTT assay that measures metabolic activity, but only slightly decreased cell viability when compared to capsaicin alone. Conclusion: The present study demonstrated that solid dispersion of capsaicin in PEG 6000 overcomes the problems related to the poor aqueous solubility of this drug and improving its dissolution rate.

Background: The present study deals with the formulation and optimization of piroxicam fast dissolving tablets and analyzes the impact of an independent variable while selecting the optimized formulation utilizing Quality by Design (QbD) and Box-Behnken Design (BBD). Method: Seventeen formulations were prepared by direct compression technique by altering the proportion of cross carmellose sodium, spray dried lactose and hydro propyl methyl cellulose (HPMC K4M). The BBD statistical technique was used to optimize formulations and correlate the relationship among all the variables. Also, the powder mixture characteristics and tablet physiochemical properties such as hardness, friability, drug content, Disintegration Time (DT) and dissolution test were determined using 900 ml of 0.1N HCl (pH-1.2) at 37 ± 0.5°C. Result: Significant quadratic model and second order polynomial equations were established using BBD. To find out the relationship between variables and responses, 3D response surface and 2D contour plot was plotted. A perturbation graph was also plotted to identify the deviation of the variables from the mean point. An optimized formula was prepared based on the predicted response and the resulting responses were observed to be close with the predicted value. Conclusion: The optimized formulation with the desired parameter and formulation with variables and responses can be obtained by BBD and could be used in the large experiment with the involvement of a large number of variables and responses.