Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

Pharmacological and neurosurgical interventions for individuals with cerebral palsy and dystonia: a systematic review update and meta-analysis.

AIM: To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia. METHOD: Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE. RESULTS: Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis. INTERPRETATION: Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.

Trihexyphenidyl induced malignant hyperthermia in a patient with Parkinson's disease complicated with pneumonia: A case report.

INTRODUCTION: Drug-induced fever is easy to overlook in respiratory departments. High fever is a rare side effect of trihexyphenidyl, which can be used clinically to treat Parkinson's disease. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a group of clinical syndromes caused by various diseases, resulting in water retention and refractory hyponatremia. However, pneumonia combined with malignant hyperthermia and SIADH has rarely been reported. We describe an unusual case of malignant hyperthermia and refractory hyponatremia due to trihexyphenidyl adverse reaction. PATIENT CONCERNS: Fifty-five-year-old male with pneumonia presented with malignant hyperthermia and refractory hyponatremia has a history of Parkinson's disease. DIAGNOSIS: Early considerations related the described hyperthermia findings to the manifestations of pneumonia. However, the last findings were due to trihexyphenidyl adverse reaction. INTERVENTIONS: Broad-spectrum antibiotics, oral and intravenous supplement of concentrated sodium chloride, drug, and physical cooling. OUTCOMES: The patient survived. During the 3-month follow up, the patient was no recurrence of fever or hyponatremia. CONCLUSION: High fever and SIADH can be a rare adverse reaction to trihexyphenidyl. Therefore, possible drug factors should be considered in the case. Consideration of other possible causes can improve early diagnosis and treatment of patients with fever of unknown origins.

Waddling Gait: A complication of valproate therapy and a thought beyond vitamin D deficiency.

Proximal muscle weakness is a common presentation in paediatric-orthopaedic clinics and is frequently paired with a vitamin D deficiency diagnosis. Recently, side effects of the extensive use of antiepileptic and antipsychotic drugs such as sodium valproate in childhood disorders are being documented. Sodium valproate causes a time-dependent, drug-induced proximal myopathy. We report a 13-year-old female patient who presented at the Orthopaedic Outpatient Department at Lady Hardinge Medical College, New Delhi, India, in 2019 with an abnormal gait. The patient was taking a combination therapy of sodium valproate, risperidone and trihexyphenidyl for absence seizures and a mood disorder. Following clinical investigations, the patient was diagnosed with proximal myopathy. As a result of elevated serum alkaline phosphatase and creatine kinase myocardial band levels, sodium valproate was replaced with ethosuximide and a carnitine supplementation was prescribed. The patient fully recovered and regained full mobility. Proximal myopathy had been incorrectly managed and assumed to be caused by a vitamin D deficiency.

Misuse of Trihexyphenidyl (Artane) on Réunion Island.

BACKGROUND: Trihexyphenidyl (THP) is an anticholinergic drug misused to procure hallucination, sedation, and anxiolysis. The aim of this cohort was to show and describe, within a public health risk management policy, the risks of a long-standing but relatively unknown addiction: THP addiction. METHODS: On Réunion island, a cohort with systematic data collection has been set up by addictologists working in the Centres for Addiction Prevention and Treatment, in the university hospital, and in general practices who have active lists of patients misusing THP. Data collection included socioeconomic data and clinical data concerning addiction. RESULTS: This cohort included 69 patients during November 2016. The average age of the patients was 36 years; 97% were men; 93% had living accommodation but only 32 % were employed. In this cohort drug administration was exclusively oral. The most common reasons for use were anxiolytic (46%), stimulation (26%), and sedation (10%), the main effects described were dyskinesia and behavioral disorders. Over half (61%) of the patients reported a coaddiction, mainly to benzodiazepines, cannabis, tobacco, alcohol, and buprenorphine. CONCLUSIONS: This cohort describing the clinical characteristics of 69 patients is the largest cohort studied for THP addiction. Patients from the Centres for Addiction Prevention and Treatment were the youngest and most recently addicted, whereas general practice patients had been addicted for longer and were more socially integrated. This clinical description of THP addiction therefore enables us to identify the patients who are the most at risk, to set up an adapted care protocol.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

[A differential approach to the improvement of prevention and correction of neuroleptic side extrapyramidal disorders with pantogam activ in patients with schizophrenia]. / Differentsirovannyi podkhod k usovershenstvovaniyu metodov preduprezhdeniya i korrektsii neirolepticheskikh pobochnykh ekstrapiramidnykh rasstroistv preparatom pantogam aktiv u bol'nykh shizofreniei.

AIM: To assess the efficacy and safety of pantogam active (PA) in prevention and correction of neurological side-effects during the course neuroleptic treatment of acute endogenous psychoses. MATERIAL AND METHODS: Eighty schizophrenic patients (mean age 33 years) with acute psychosis were examined. All patients received 28-day course treatment with typical and atypical neuroleptics. Two equal groups were studied: patients of the first group were treated with trihexyphenidyl (THP) in dose of 0,002-0,012 mg and patients of the second group received in addition PA in dose 0,9 mg/day. Clinical-observation, psychometric scales (PANSS, CGI-S, UKU) were administered at baseline and in 1st,3rd,7th, 14th, 21st, 28st day. RESULTS: PA in the combination with THP improved tolerability to neuroleptic therapy in whole and exerted the better correction effect on neuroleptic extrapyramidal disorders (EPD) compared to THP monotherapy. The number of patients with ERD was reduced by 1.5 times and prevention of EPD was observed 3 times more frequent in the group treated with PA. In the THP group, other adverse effects (AE) were 1,7 times more frequent and the total AE score was 2,5 times greater compared to the PA group (131 vs 50). Correction and preventive effects of the combined treatment on the clinically severe symptoms of EPD (akathisia, muscle dystonia) were more frequent in patients treated with typical neuroleptics. A less amount of THP (by 1,2 times) was used to stop EPD in the PA group. CONCLUSION: PA in the combination with THP has demonstrated the clear neuroprotective effect on the development, frequency and clinical presentations of neurological side-effects. The РА can be recommended as a drug of choice for correction and prevention of neuroleptic side-effects, it promotes their tolerability and improves quality of life during the course treatment.

Heat stroke during treatment with olanzapine, trihexyphenidyl, and trazodone in a patient with schizophrenia.

OBJECTIVE: Heat stroke is a medical emergency. Psychiatric patients are particularly susceptible to heat stroke. Therefore, awareness and preventive measures of heat stroke are important for both clinicians and patients. Case description A 49-year-old man with schizophrenia, who was under maintenance treatment with olanzapine 20 mg/day, trihexyphenidyl 4 mg/day, and trazodone 50 mg/day, suffered from heat stroke in a heat wave and required intensive care. He recovered with the medical treatment provided. Discussion Several factors could have contributed to the impaired thermoregulation and the occurrence of heat stroke in this case: schizophrenia, the psychotropic regimen, and lack of preventive measures. Possible differential diagnoses of heat stroke in this case include infection, neuroleptic malignant syndrome, and serotonin syndrome. CONCLUSION: Heat stroke can occur during the maintenance treatment of olanzapine, trihexyphenidyl, and trazodone for schizophrenia. Clinicians should be proactive to reduce the risk of heat stroke in psychiatric patients.

Acute colonic pseudo-obstruction in a child taking trihexyphenidyl for drooling: Prescribers beware.

Colonic pseudo-obstruction (Ogilvie's Syndrome) in children is relatively uncommon. We report an unusual case of colonic pseudo-obstruction in an 8-year-old child with cerebral palsy and long-term hypomotility issues being treated for drooling with the anticholinergic medication trihexyphenidyl. He presented as an emergency with severe abdominal distension, abdominal tenderness and vomiting. An emergency laparotomy revealed colonic dilatation and a defunctioning ileostomy was created. To our knowledge, this is the first case reporting colonic pseudo-obstruction as a possible complication of treatment with trihexyphenidyl. We suggest prescribers should exercise caution when prescribing trihexyphenidyl in patients with long-term intestinal hypomotility issues.

Multidrug overdose-induced myoclonus complicated by rhabdomyolysis: possible role and mechanism of muscle toxicity of risperidone.

WHAT IS KNOWN AND OBJECTIVE: Atypical antipsychotics are considered safe for treating schizophrenia and are rarely reported to induce rhabdomyolysis. CASE SUMMARY: Here is a case of a woman with schizophrenia who developed rhabdomyolysis following overdose of risperidone, trihexyphenidyl and benzodiazepines. There was no recurrence of rhabdomyolysis when above medication was resumed with therapeutic dose. WHAT IS NEW AND CONCLUSION: Multidrug overdose are common but are rarely reported to induce rhabdomyolysis. Overdose risperidone may increase the risk of rhabdomyolysis and need to be kept in mind.

Neuroleptic malignant syndrome masked by cerebral malaria.

A 38-year-old man with an underlying psychiatric illness presented with altered sensorium and abnormal behaviour. He was febrile at 38°C and weak looking; otherwise no other abnormalities were detected. A blood film conducted for malarial parasite (BFMP) revealed Plasmodium falciparum; hence a diagnosis of cerebral malaria was made. He was treated with antimalarial drugs for 2 days prior to being transferred out to the ward following clinical improvement. He subsequently developed episodes of stupor and refusal of feeding. Following an evaluation by the psychiatrist, a diagnosis of catatonic schizophrenia was made and he was started on oral sulpiride and benhexol. Unfortunately, he developed high-grade fever at 40°C with muscle rigidity and fasciculation. The diagnosis of neuroleptic malignant syndrome (NMS) was clinched and the antipsychotics were discontinued. However he succumbed to NMS several days later due to multiorgan failure.

Cervical dystonia: from pathophysiology to pharmacotherapy.

BACKGROUND: Dystonia is a chronic disorder characterised by an aberration in the control of movement. Sustained co-contraction of opposing agonist and antagonist muscles can cause repetitive and twisting movements, or abnormal postures. Cervical dystonia (CD), often referred to as spasmodic torticollis, is a type of focal dystonia involving the muscles of the neck and sometimes the shoulders. METHODS: This systematic review collates the available evidence regarding the safety and efficacy of a range of treatments for CD, focusing on their effectiveness as shown by double-blinded, randomised controlled trials. RESULTS: Our review suggests that botulinum toxin type A (BTA), botulinum toxin type B (BTB) and trihexyphenidyl are safe and efficacious treatments for CD. Evidence shows that botulinum toxin therapies are more reliable for symptomatic relief and have fewer adverse effects than trihexyphenidyl. When comparing BTA to BTB, both are found to have similar clinical benefits, with BTA possibly having a longer duration of action and a marginally better side effect profile. BTB is also safe and probably just as efficacious a treatment in those patients who are unresponsive or have become resistant to BTA. DISCUSSION: The current evidence shows that the pharmacological management of CD relies on BTA and BTB, two agents with established efficacy and tolerability profiles.

Colonic architectural change on colonoscopy in patients taking psychotropic medications.

BACKGROUND: Patients on psychotropic medications have been clinically observed to have higher rates of abnormal colonic architecture resulting in difficult colonoscopies. This study aims to determine if a correlation between use of psychotropic medications and colonic architectural change seen on colonoscopy exists. METHODS: A retrospective case-control study was undertaken with 252 adults selected from the hospital endoscopy database between January 2006 and July 2008. Cases were selected if they had 'capacious', 'megacolon', 'redundant' and/or 'featureless' colonic architecture reported in their first completed colonoscopy (n = 63). Demographic information and medication records were collected for both cases and controls. Logistic regression analysis was performed for each of the medication groups. RESULTS: Medication groups associated with increased incidence for colonic architectural changes observed during colonoscopy include: antipsychotic medications [odds ratio (OR) 7.79, confidence interval (CI) 2.59-23.41], benzhexol (OR 23.50, CI 2.83-195.08) and iron tablets (OR 2.97, CI 1.39-6.33). Antidepressants, laxatives, benzodiazepines, gastroprotective medications and antihypertensive medications were not found to have any significant effect on changes to colonic architecture. CONCLUSIONS: Use of antipsychotic medications is associated with changes to colonic architecture. This could predispose such a patient to difficult colonoscopy and therefore increase colonoscopy-associated risks. Medication history should be elicited prior to colonoscopy.

Trihexyphenidyl improves motor function in children with dystonic cerebral palsy: a retrospective analysis.

There are conflicting reports regarding the efficacy of trihexyphenidyl, an anticholinergic drug, for treatment of dystonia in cerebral palsy. The author hypothesized that trihexyphenidyl may be more effective in specific subgroups and performed a retrospective analysis of 31 children (8.2 ± 5.8 years) with dystonia following treatment with high-dose trihexyphenidyl (>0.5 mg/kg/day). Main outcome measure was extent of motor improvement calculated according to the body areas affected. Most (21/31) caregivers reported improvement in 1 or more areas, mainly arm, hand, and oromotor function. Improvement was greater in children without spasticity (P = .02) and in those with higher cognitive function (P = .02). While a third of caregivers (10/31) reported tone reduction, and half (15/31) noted overall functional improvement. Side effects were transient, with the exception of hyperopia (n = 1), and occurred less frequently in children with a history of prematurity (P = .02). In summary, trihexyphenidyl is effective particularly in absence of spasticity and in children with higher cognitive abilities.

Multicenter clinical study on the treatment of children's tic disorder with Qufeng Zhidong Recipe.

OBJECTIVE: To assess the effect and adverse reaction of Qufeng Zhidong Recipe (QZR) in treating children's tic disorder (TD). METHODS: With multicenter randomized parallel open-controlled method adopted, the patients enrolled were assigned to two groups, 41 cases in the Chinese medicine (CM) group and 40 in the Western medicine (WM) group. They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course. In total, two courses of treatment were given. The curative effect and adverse reactions were evaluated by scoring with Yale Global Tic Severity Scale (YGTSS), Traditional Chinese Medicine Syndrome Scale (TCMSS), and Treatment Emergent Symptom Scale (TESS), as well as results of laboratory examinations. RESULTS: After one course of treatment, the markedly effective rate in the CM and the WM group was 14.6% and 17.5%, respectively, and the total effective rate 43.9% and 47.5%, respectively, which showed insignificant difference between groups (P>0.05). However, after two courses of treatment, markedly effective rate in them was 73.2% and 7.5%, and the total effective rate was 100.0% and 57.5%, both showing significant differences between groups (P<0.05). Besides, the adverse reactions occurred in the CM group was less than that in the WM group obviously. CONCLUSION: QZR has definite curative effect with no apparent adverse reaction in treating TD, and it can obviously improve the symptoms and signs and upgrade the quality of life and learning capacities in such patients.

Pilot study on trihexyphenidyl in the treatment of dystonia in children with cerebral palsy.

The aim of this study was to assess trihexyphenidyl in reducing overall dystonia, improving upper limb function, and achieving goals in children with dystonic cerebral palsy. A randomized, double-blinded, placebo-controlled, crossover trial was conducted with 16 participants at a tertiary children's hospital. Assessments were performed at baseline, week 12, and week 28. The primary outcome measure was the Barry-Albright Dystonia scale for global assessment of dystonia. Secondary measures included the Quality of Upper Extremity Skills Test, Canadian Occupational Performance Measure, and Goal Attainment Scale. A total of 14 children (88%) completed the study. Mean baseline Barry-Albright Dystonia score was 18.4 (95% confidence interval, 15.5-21.2). There were no significant treatment effects as measured by change in outcome scores. There were significant order effects for both the Goal Attainment Scale and performance aspect of the Canadian Occupational Performance Measure. Side effects were common. Larger experimental trials with more narrowly defined functional levels are indicated.