[Three oral Chinese patent medicines for children with tic disorder: a rapid health technology assessment].

This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.

[Comparison of tiapride and topiramate in the prophylactic treatment of chronic migraine: a randomised, double-blind, pilot study]. / Comparación de la tiaprida y el topiramato en el tratamiento profiláctico de la migraña crónica: estudio piloto, aleatorizado y doble ciego.

AIM: The aim of this study was to evaluate the efficacy and safety of tiapride compared to topiramate as a prophylactic in chronic migraine. PATIENTS AND METHODS: The study was conducted under randomised and double blind conditions. A total of 56 patients aged 18-65 years with chronic migraine were assigned to two treatment arms: tiapride, 100 mg twice daily, or topiramate, 25 mg twice daily, for 12 weeks. The primary endpoint was the change in the monthly average number of migraine days. In addition, measurements were performed to determine the change in the monthly number of headache days, the percentage of subjects with >50% and >75% decrease in their monthly migraine days, and the change in headache impact as measured by the Headache Impact Test-6. RESULTS: The intention-to-treat population included 39 subjects (tiapride = 21; topiramate = 18), 35 of whom (tiapride = 18; topiramate = 16) completed the trial. The tiapride group had a mean reduction of 7.2 ± 7.5 migraine days per month compared to 7.6 ± 5.8 for the topiramate group (p = 0.86). As with the other efficacy variables measured, no differences were found between the two groups. Adverse side effects were mild in both groups. CONCLUSION: In patients with chronic migraine, tiapride was found to be an effective, safe and well-tolerated prophylactic treatment when compared to topiramate.

TITLE: Comparación de la tiaprida y el topiramato en el tratamiento profiláctico de la migraña crónica: estudio piloto, aleatorizado y doble ciego.Objetivo. Evaluar la eficacia y la seguridad de la tiaprida en comparación con el topiramato en la profilaxis de la migraña crónica. Pacientes y métodos. Es un estudio aleatorizado y doble ciego. Un total de 56 pacientes de 18 a 65 años con migraña crónica fueron asignados a dos brazos de tratamiento: tiaprida, 100 mg dos veces al día, o topiramato, 25 mg dos veces al día, durante 12 semanas. El criterio de valoración principal fue el cambio en el promedio mensual de días de migraña. Además, se midió el cambio en el número mensual de días de cefalea, el porcentaje de sujetos con disminución > 50% y > 75% de sus días de migraña mensual, y el cambio del impacto de la cefalea medido por el Headache Impact Test-6. Resultados. La población por intención de tratar incluyó a 39 sujetos (tiaprida = 21; topiramato = 18) y completaron el ensayo 35 participantes (tiaprida = 18; topiramato = 16). El grupo con tiaprida tuvo una reducción media de 7,2 ± 7,5 días con migrañas por mes en comparación con 7,6 ± 5,8 para el grupo con topiramato (p = 0,86). Al igual que en las otras variables de eficacia medidas, no hubo diferencias significativas entre ambos grupos. Los efectos adversos fueron leves en ambos grupos. Conclusión. En pacientes con migraña crónica, la tiaprida demostró ser un tratamiento profiláctico eficaz, seguro y bien tolerado, al compararla con el topiramato.

Efficacy of tiapride in the treatment of psychiatric disorders: A systematic review.

BACKGROUND: Tiapride is an atypical antipsychotic used to treat alcohol withdrawal, aggressiveness and agitation, headache, dyskinesias, tic and Tourette's disorder. More recently, it has been proposed for the treatment of delirium and agitation in hospitalised patients with COVID-19. Although its safety profile makes it suitable for use in vulnerable populations, the use of tiapride for psychiatric disorders is limited. This work aims to systematically review the available evidence on the efficacy and tolerability of tiapride in individuals with a psychiatric disorder. METHODS: We searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey, and ProQuest up to March 2020 for randomised controlled trials focussing on the use of tiapride in the treatment of individuals with a psychiatric disorder (e.g., mood disorder, schizophrenia spectrum, substance use disorder). The Risk of Bias 2 was performed for the quality assessment of the included studies. RESULTS: We identified 579 records. Of them, six studies (published between 1982 and 2010) were included in the review. Four studies referred to alcohol withdrawal, and two to the management of agitation in elderly patients with dementia. None of the studies reported significant differences between tiapride and other active comparators in terms of efficacy and tolerability. The overall risk of bias was moderate to high. CONCLUSION: Tiapride may be considered as a relatively safe treatment option for selected patients with alcohol withdrawal or agitation in dementia. However, solid evidence of its efficacy in the scientific literature is lacking. High-quality trials remain necessary to fully sustain its use in clinical practice.

Estudio de utilización de psicofármacos en usuarios de la policlínica del Hospital Vilardebó con diagnóstico de esquizofrenia (años 2006 y 2016) / Study of the use of psychotropic drugs in users of the Vilardebó Hospital polyclinic with a diagnosis of schizophrenia (2006 and 2016)

El tratamiento farmacológico de demostrada eficacia en la esquizofrenia es el antipsicótico. Sin embargo, en muchas ocasiones se requiere medicación concomitante que depende de comorbilidades y efectos adversos. Se realizó un estudio cuantitativo, longitudinal, retrospectivo, considerando el año 2006 y 2016, en una población de usuarios con esquizofrenia de la Policlínica del Hospital Vilardebó, analizando los tratamientos con psicofármacos. Se diferenciaron los tratamientos según monoterapia antipsicótica y polifarmacia con 2 antipsicóticos, y polifarmacia con más de 2 antipsicóticos, antidepresivos, estabilizantes del humor, benzodiacepinas y anticolinérgicos. La población inicial en 2006 fue de 621 pacientes y 398 pacientes continuaban en tratamiento en 2016. Mantuvieron el trata-miento con antipsicóticos 377 pacientes; 184 mantuvieron benzodiacepinas; 59 se mantuvieron con anticolinérgicos; 49, con estabilizantes del humor y 47, con antidepresivos. La monoterapia antipsicótica se presentó en torno al 50 % de la población estudiada. Se deberían revisar aquellas prácticas que se infieren a partir de este estudio, como el uso prolongado de anticolinérgicos, benzodiacepinas, y polifarmacia con más de 2 antipsicóticos, que está extendida en los usuarios con esquizofrenia. El tratamiento con clozapina fue el más estable y no parece aumentar la mortalidad en estos pacientes

Antipsychotics are the proved effective therapy for schizophrenia. However, on many occasions, associated drugs are required depending on comorbidities and side effects. A retrospective longitudinal quantitative study of drug prescription for 2006 and 2016 in patients with schizophrenia diagnosis was carried out in an outpatient clinic at Hospital Vilardebó. Treatments were classified as antipsychotic monotherapy, two antipsychotic drugs polypharmacy and polypharmacy with two antipsychotic drugs, antidepressants, mood stabilizers, benzodiazepines and anticholinergic drugs. Initial population in 2006 included 621 patients, 398 were still being treated in 2016. Antipsychotic drugs were still being received in 377 patients, benzodiazepines in 184, anticholinergic drugs in 59, mood stabilizers in 49, and anti-depressants in 47. Antipsychotic monotherapy was 50% of the population. Those practices that can be inferred from this study, with lengthy use of anticholinergic drugs, benzodiazepines, and the use of more than 2 antipsychotic drugs in patients with schizophrenia diagnosis should be revised. Clozapine therapy was the most stable and does not seem to increase mortality.

Estimation of a preliminary therapeutic reference range for children and adolescents with tic disorders treated with tiapride.

PURPOSE: Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated. METHODS: Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures. RESULTS: In the 49 paediatric patients (83.7% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97-19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3% of the patients. 27.1% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs. CONCLUSIONS: This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).

The Efficacy of Tiapride and Carbamazepine Combination Therapy in Reducing Alcohol Withdrawal Symptoms: A Systematic Review and Meta-Analysis.

The combination of tiapride (TIA) and carbamazepine (CBZ) as an alternative treatment option to benzodiazepines and clomethiazole has been investigated by several investigations. We performed a systematic review and meta-analysis to further explore the efficacy of this combination in order to render more definite answers whether this combination can be recommendable in the clinical practice. We systematically searched electronic databases including PubMed (MEDLINE), EMBASE, OVID, Cochrane, Google Scholar, and Scopus for human studies. Statistical homogeneity was checked by χ2 test and I2 using Cochran heterogeneity statistic. Our analysis showed a significant efficacy of the combination of TIA and CBZ in reducing alcohol withdrawal syndrome (AWS) (p<0.0001, z-value: 4.07). The cumulative analysis illustrated that the favorable efficacy of this combination therapy has been consistent over time. Our study shows that the combination of TIA/CBZ is an effective treatment in management of AWS in patients with alcohol abstinence. However, the safety of this combination could not be proven, so we recommend its prescription after an informed consent.

Diagnosis and treatment of acute alcohol intoxication and alcohol withdrawal syndrome: position paper of the Italian Society on Alcohol.

The chronic use of alcohol can lead to the onset of an alcohol use disorder (AUD). About 50% of subjects with an AUD may develop alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption and, in 3-5% of them, convulsions and delirium tremens (DTs), representing life-threatening complications, may occur. Unfortunately, few physicians are adequately trained in identifying and treating AWS. The Italian Society on Alcohol has, therefore, implemented a task force of specialists to draw up recommendations for the treatment of AWS with the following main results: (1) while mild AWS may not require treatment, moderate and severe AWS need to be pharmacologically treated; (2) out-patient treatment is appropriate in patients with mild or moderate AWS, while patients with severe AWS need to be treated as in-patients; (3) benzodiazepines, BDZs are the "gold standard" for the treatment of AWS and DTs; (4) alpha-2-agonists, beta-blockers, and neuroleptics may be used in association when BDZs do not completely resolve specific persisting symptoms of AWS; (5) in the case of a refractory form of DTs, the use of anaesthetic drugs (propofol and phenobarbital) in an intensive care unit is appropriate; (6) alternatively to BDZs, sodium oxybate, clomethiazole, and tiapride approved in some European Countries for the treatment of AWS may be employed for the treatment of moderate AWS; (7) anti-convulsants are not sufficient to suppress AWS, and they may be used only in association with BDZs for the treatment of refractory forms of convulsions in the course of AWS.

Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease.

There are currently no effective pharmacological agents available to stop or prevent the progression of Huntington's disease (HD), a rare hereditary neurodegenerative disorder. In addition to psychiatric symptoms and cognitive impairments, HD causes progressive motor disturbances, in particular choreiform movements, which are characterized by unwanted contractions of the facial muscles, trunk and extremities. Management of choreiform movements is usually advised if chorea interferes with daily functioning, causes social isolation, gait instability, falls, or physical injury. Although drugs to reduce chorea are available, only few randomized controlled studies have assessed the efficacy of these drugs, resulting in a high variety of prescribed drugs in clinical practice. The current pharmacological treatment options to reduce chorea in HD are outlined in this review, including the latest results on deutetrabenazine, a newly developed pharmacological agent similar to tetrabenazine, but with suggested less peak dose side effects. A review of the existing literature was conducted using the PubMed, Cochrane and Medline databases. In conclusion, mainly tetrabenazine, tiapride (in European countries), olanzapine, and risperidone are the preferred first choice drugs to reduce chorea among HD experts. In the existing literature, these drugs also show a beneficial effect on motor symptom severity and improvement of psychiatric symptoms. Generally, it is recommended to start with a low dose and increase the dose with close monitoring of any adverse effects. New interesting agents, such as deutetrabenazine and pridopidine, are currently under development and more randomized controlled trials are warranted to assess the efficacy on chorea severity in HD.

Tiapride is more effective and causes fewer adverse effects than risperidone in the treatment of senile dementia.

OBJECTIVE: We wanted to compare the effects of tiapride and risperidone in treating behavioral and psychological symptoms of senile dementia. PATIENTS AND METHODS: 108 patients with senile dementia received respective treatments (54 patients per treatment, either with 100 mg/day risperidone or 2.0 mg tiapride/day) for 2 months. Outcomes included the positive and negative syndrome scale (PANSS) scores, the curative rate of senile dementia, and prevalence of adverse effects (somnolence, headache, loss of weight, extrapyramidal system response, irritation and insomnia). RESULTS: PANSS scores before treatment were comparable between treatment groups. On days 7, 15, 30, and 60 of the treatment, the differences between two treatment groups became evident. Thus, curative rates in patients treated with risperidone were 74.1% and in those treated with tiapride 88.9% (p < 0.05). Prevalence of adverse reactions was significantly lower in the latter group (9.3% vs. 25.9% in patients treated with risperidone; p < 0.05). CONCLUSIONS: Tiapride is more effective in improving clinical symptoms of senile dementia and causes fewer adverse effects.

Trends in psychopharmacologic treatment of tic disorders in children and adolescents in Germany.

Data on medical treatment of children and adolescents with tic disorders are scarce. This study examined the administrative prevalence of psychopharmacological prescriptions in this patient group in Germany. Data of the largest German health insurance fund were analysed. In outpatients aged 0-19 years with diagnosed tic disorder, psychotropic prescriptions were evaluated for the years 2006 and 2011. In 2011, the percentage of psychotropic prescriptions was slightly higher than in 2006 (21.2 vs. 18.6%). The highest prescription prevalence was found in Tourette syndrome (51.5 and 53.0%, respectively). ADHD drugs were most frequently prescribed, followed by antipsychotics. In 2011, prescriptions of second generation antipsychotics (SGA) were higher and prescriptions of first generation antipsychotics (FGA) lower than in 2006. Concerning prescribed antipsychotic substances, in 2011 risperidone prescriptions were higher and tiapride prescriptions lower. Paediatricians issued 37.4%, and child and adolescent psychiatrists issued 37.1% of psychotropic prescriptions. The FGA/SGA ratio was highest in GPs (1.25) and lowest in child and adolescent psychiatrists (0.96). From 2006 to 2011, there was only a slight increase in psychotropic prescriptions for children and adolescents with a diagnosis of tic disorder in Germany, which stands in contrast towards the significant increase in psychotropic prescriptions in other child and adolescent psychiatric disorders (e.g. ADHD). There were marked differences in treatment patterns by tic disorder subgroups, with Tourette syndrome patients receiving most frequently psychopharmacotherapy. Risperidone prescriptions increased, probably reflecting a switch in prescribing practice towards up-to-date treatment guidelines. In primary care physicians, dissemination of current tic disorder treatment guidelines might constitute an important educational goal.

[The White man's burden - a case study caught between bipolar affective disorder and Huntington's disease]. / White Man's Burden - Im Grenzgebiet zwischen bipolarer affektiver Störung und Huntington-Erkrankung.

We report upon a case of a 55 year old patient with a bipolar affective disorder, presenting herself with a depressive symptomatology in addition to a severe motor perturbation. The main emphasis upon admittance was perfecting and improving her latest medication. Four weeks prior to her stay at our clinic a thorough neurological examination had taken place in terms of an invalidity pension trial which did not result in any diagnostic findings. Therefore a neurological disease seemed at first highly unlikely. Even though the prior testing was negative, the ensuing neurological examination at our clinic resulted in movement disorders very much indicative of Huntington's Disease. A detailed investigation in regards to the particular family history of the patient was positive for Huntington's Disease. However, whether the patient's mother had also been a genetic carrier of Huntington's Disease was still unknown at the time the patient was admitted to our clinic. It was nevertheless discovered that her mother had also suffered from a bipolar affective disorder. A genetic testing that followed the neurological examination of the patient proved positive for Huntington's Disease. Neuro-imaging resulted in a bicaudate-index of 2.4 (the critical value is 1.8). In a clinical psychological test battery the ensuing results were highly uncommon for patients with solely a bipolar affective disorder people. Under the medical regimen of Quetiapine, Citalopram and Tiaprid the patient's mood could be stabilized and there was some improvement of her motor pertubation.

Pharmacological treatment of tic disorders and Tourette Syndrome.

The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug trials in TS patients fulfilling evidence based medicine standards are still scarce. Treatment decisions are often guided by individual needs and personal experience of treating clinicians. The present recommendations for pharmacological tic treatment are therefore based on both scientific evidence and expert opinion. As first-line treatment of tics risperidone (best evidence level for atypical antipsychotics) or tiapride (largest clinical experience in Europe and low rate of adverse reactions) are recommended. Aripiprazole (still limited but promising data with low risk for adverse reactions) and pimozide (best evidence of the typical antipsychotics) are agents of second choice. In TS patients with comorbid attention deficit hyperactivity disorder (ADHD) atomoxetine, stimulants or clonidine should be considered, or, if tics are severe, a combination of stimulants and risperidone. When mild to moderate tics are associated with obsessive-compulsive symptoms, depression or anxiety sulpiride monotherapy can be helpful. In more severe cases the combination of risperidone and a selective serotonin reuptake inhibitor should be given. In summary, further studies, particularly randomized, double-blind, placebo-controlled trials including larger and/or more homogenous patient groups over longer periods are urgently needed to enhance the scientific basis for drug treatment in tic disorders. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.

[Effects of Jing'an Oral Liquid on the central neurotransmitter of multiple tics children].

OBJECTIVE: To study the effects of Jing'an Oral Liquid (JOL) on the central neurotransmitters of multiple tics (MT) children. METHODS: Sixty MT children patients were randomly assigned to the treatment group and the control group, 30 cases in each group. Another 30 healthy children were recruited as the health group. JOL and Tiapride Tablet (TT) was respectively given to patients in the treatment group and the control group. The treatment course was 2 months. The levels of central neurotransmitters [dopamine (DA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), glutamic acid (GLU), aspartate (ASP), gamma-aminobutyric acid (GABA)] were measured using high performance liquid chromatography (HPLC) before and after treatment, and compared with the health group. RESULTS: Compared with the health group, the levels of 5-HT, HVA, GLU, and ASP significantly increased in the treatment group and the control group before treatment (P < 0.05), GABA significantly decreased (P < 0.05). Compared with before treatment in the same group, the levels 5-HT, HVA, and GLU significantly decreased in the treatment group (P < 0.05), while the levels of NE and GABA significantly increased (P < 0.05). The levels of DA, 5-HT, GLU, and ASP significantly decreased, while the levels of NE ang GABA significantly increased in the control group, showing statistical difference (P < 0.05). There was no statistical difference in each index between the treatment group and the control group before and after treatment (P > 0.05). CONCLUSIONS: (1) The imbalance of a variety of monoamines and amino acid neurotransmitters can lead to MT, especially in the changes of 5-HT, HVA, GLU, ASP, and GABA. (2) JOL can significantly reduce the levels of 5-HT, HVA, and GLU, and significantly increase the levels of NE and GABA, which might be its pharmacodynamic mechanisms for treating MT.