Mining and analysis of risperidone adverse event signals based on FAERS database / 中国药房

OBJECTIVE To provide reference for safe use of risperidone in clinic. METHODS Data mining and analysis of risperidone-related adverse drug event （ADE） reports from the first quarter of 2017 to the third quarter of 2021 in the United States FAERS database were carried out using reported odds ratio and composite criteria methods from Medicines and Healthcare Products Regulatory Agency. RESULTS There were 101 181 ADE reports with risperidone as the primary suspect drug，involving a total of 33 179 patients. Among those reports，the male-to-female ratio was about 6.21 to 1； most of them were ＜18 years old （15.01%）； ADE was mainly reported by consumers （69.74%） and mainly reported by the United States （79.72%）； oral dosage form was the most used，accounting for 83.71%. A total of 409 ADE signals were obtained，including male breast development， pseudogynecomastia，abnormal increase in body mass，hyperprolactinemia and Wellens syndrome，etc. Twenty-six systems and organs were involved，mainly including reproductive system and breast diseases，various injuries，poisoning and operational complications， mental diseases，metabolic and nutritional diseases，and various nervous system diseases，etc. CONCLUSIONS The common ADE signals of risperidone and the system involved are consistent with the instructions，but we should also be alert to the ADE not recorded in the instruction，such as Wellens syndrome，fibroproliferative endocarditis，cavernous degeneration of portal vein，rabbit syndrome，etc.

Therapeutic effects of risperidone combined with olanzapine on first-episode schizophrenia in 30 patients / 中国基层医药

Objective:To investigate the clinical efficacy of risperidone combined with olanzapine in the treatment of first-episode schizophrenia and its effects on serum homocysteine level and cognitive function.Methods:Sixty patients with first-episode schizophrenia who received treatment in Yiwu Mental Health Center from May 2017 to May 2018 were included in this study. They were randomly assigned to receive either olanzapine (control group, n = 30) or olanzapine and risperidone (observation group, n = 30) treatment. All patients received 4 weeks of treatment. We compared serum homocysteine level, cognitive function, and clinical efficacy between the two groups. Results:There was no significant difference in serum homocysteine level pre-treatment between the two groups ( P > 0.05). Serum homocysteine level post-treatment was significantly lower in the observation group than in the control group [(13.59 ± 2.61) mmol/L vs. (15.83 ± 2.58) mmol/L, t = 3.34, P < 0.05). There were no significant differences in the scores of each cognitive function item pre-treatment between the two groups (all P > 0.05). The scores of each cognitive function item post-treatment in the observation group was (15.06 ± 2.28) points, (21.18 ± 3.26) points, (44.39 ± 4.42) points, (40.63 ± 6.27) points, which were significantly superior to those in the control group [(13.31 ± 2.04) points, (19.26 ± 3.07) points, (42.43 ± 2.07) points, (44.19 ± 5.86) points, t = 3.13, 2.34, 2.12, 2.27, all P < 0.05]. The total improvement rate was significantly higher in the observation group than in the control group [93.33% (28/30) vs. 70.00% (21/30), χ2 = 5.45, P < 0.05). Conclusion:Risperidone combined with olanzapine is highly effective on first-episode schizophrenia. The combined therapy can reduce serum homocysteine level and improve cognitive function.

Risperidone combined with diazepam for the treatment of alcohol-induced mental and behavioral disorders / 中国基层医药

Objective:To investigate the clinical efficacy of risperidone combined with diazepam in the treatment of alcohol-induced mental and behavioral disorders.Methods:Sixty patients with alcohol-induced mental and behavioral disorders admitted to Huainan Psychiatric Hospital from January 2018 to January 2022 were included in this study. They were randomly assigned to undergo either diazepam alone (control group, n = 30) or risperidone combined with diazepam (study group, n = 30). Clinical efficacy, Positive and Negative Syndrome Scale (PANSS) score, incidence of adverse reactions, quality of life, treatment satisfaction were compared between the two groups. Results:Total response rate differed significantly between the two groups ( Z = 6.25, P < 0.05). In the control group, PANSS scores measured before and after treatment were as follows: positive symptoms: (26.07 ± 3.70) points vs. (16.38 ± 2.04) points; negative symptoms: (24.04 ± 2.98) points vs. (13.86 ± 1.84) points; psychopathological symptoms: (44.06 ± 5.28) points vs. (31.83 ± 4.04) points; general score: (91.84 ± 9.76) points vs. (40.84 ± 6.26) points. In the study group, PANSS scores measured before and after treatment were as follows: positive symptoms: (25.84 ± 3.82) points vs. (10.30 ± 1.17) points; negative symptoms: (24.48 ± 3.26) points vs. (7.48 ± 0.82) points; psychopathological symptoms: (43.28 ± 5.21) points vs. (21.06 ± 3.72) points; general score: (92.06 ± 9.85) points vs. (68.27 ± 7.02) points. There were no significant differences in above indices measured before treatment between the two groups (all P > 0.05). After treatment, scores of positive, negative, psychopathological symptoms and general scores in the study group were significantly lower than those in the control group ( t = 14.16, 17.34, 10.74, 15.97, all P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Before and after treatment, the quality of life scores (physiological, psychological, social and environmental scores) of the control group were (12.64 ± 2.50) points vs. (13.87 ± 2.16) points; (12.47 ± 2.12) points vs. (13.28 ± 2.18) points; (9.54 ± 2.16) points vs. (14.20 ± 1.27) points; (10.97 ± 1.84) points vs. (12.78 ± 2.42) points. Before and after treatment, the quality of life scores (physiological, psychological, social and environmental scores) of the study group were (12.68 ± 2.53) points vs. (15.37 ± 2.07) points; (12.49 ± 2.14) points vs. (14.90 ± 2.20) points; (9.37 ± 2.14) points vs. (15.03 ± 1.27) points; (10.94 ± 1.81) points vs. (13.86 ± 2.18) points. After treatment, physiological, psychological, social and environmental scores in the study group were significantly higher than those in the control group ( t = 2.74, 2.86, 2.50, 2.81, all P < 0.001). There was significant difference in treatment satisfaction between the two groups ( χ2 =5.19, P = 0.022). Conclusion:Risperidone combined with diazepam can help improve the clinical symptoms of patients with alcohol-caused mental and behavioral disorders, further improves the treatment effect and quality of life, and is safe.

Formulation development and pharmacokinetic studies of long acting in situ depot injection of risperidone

Abstract Risperidone is an atypical antipsychotic drug widely prescribed all over the world due to its clinical advantages. The currently available long acting marketed depot formulation of risperidone is a microsphere based preparation using poly-[lactide-co-glycolide] (PLGA) as drug release barrier. It is however, a cold chain product due to thermal instability of PLGA at room temperature. After beginning the depot injection therapy it is administered every two weeks but associated with another drawback of about 3 weeks lag time due to which its tablets are also administered for three weeks so as to attain and maintain therapeutic drug concentration in the body. The present work attempts to develop a long acting depot delivery system of risperidone for once a month administration based on the combination of sucrose acetate isobutyrate and polycaprolactone dissolved in benzyl benzoate to provide an effective drug release barrier for one month without any lag time and which can be stored at room temperature precluding the requirement of cold supply chain. The developed depot formulation showed a sustained in vitro drug release profile with 88.95% cumulative drug release in 30 days with little burst release. The in vivo pharmacokinetic studies of the developed formulation conducted on rats showed attainment of mean peak plasma drug concentration of 459.7 ng/mL in 3 days with a mean residence time of 31.2 days, terminal half-life of 20.6 days, terminal elimination rate constant of 0.0336 per day, and a good in vitro- in vivo correlation.

Associations of white matter microstructural abnormalities with clinical symptoms, cognitive impairment and clinical outcomes in the early course of first-episode schizophrenia / 中华行为医学与脑科学杂志

Objective:To investigate the associations of brain white matter integrity deficits, and to explore the association of fractional anisotropy (FA) abnormality with clinical symptoms and cognitive impairments, as well as the prediction effect of the FA alterations on symptoms and cognitive function outcomes in the acute stage of schizophrenia from the whole brain level based on magnetic resonance diffusion tensor imaging (DTI).Methods:From November 2019 to December 2020, thirty-eight patients with first-episode schizophrenia and 38 healthy controls were recruited in this study. Wisconsin card classification test (WCST), digit span test (DST forward/backward), verbal fluency test, Stroop (A/B/C), trail making test (TMT-A/B), as well as positive and negative syndrome scale (PANSS) were utilized to evaluate patients' cognitive function and clinical symptoms both before and after 8 weeks of risperidone monotherapy. T1-weighted images and DTI data of all the subjects were collected . FSL and SPM8 were used to preprocess MRI data and compare the between-group differences of FA. Support vector machine (SVM) analysis was used to evaluate the accuracy of abnormal FA values in differentiating schizophrenic patients from healthy controls. Finally, stepwise multiple regression analysis or generalized linear models were used to explore the associations between white matter integrity and symptoms or cognition.Results:Before treatment, patients' FA values of right medial temporal lobe (mTL), cuneus, anterior cingulate gyrus (ACG) and inferior parietal lobe (IPL) were significantly lower than those in healthy controls ( P<0.01, GRF corrected), and patients' FA values of bilateral middle cingulate gyrus (mCG) were significantly higher than those in the control group ( P<0.01, GRF corrected). SVM analysis showed that four combinations could distinguish the patients from the control with the most accurate rate of 89.47%. Patients' baseline decreased FA values in the right IPL were positively associated with their increased total response time in WCST ( β=0.489, P=0.003, FDR corrected), correct response time in WCST ( β=0.450, P=0.008, FDR corrected), error response time in WCST ( β=0.435, P=0.008, FDR corrected), TMT-B ( β=0.296, P=0.042, FDR corrected), Stroop-C ( β=0.345, P=0.035, FDR corrected), and PANSS-P ( β=0.321, P=0.042, FDR corrected). Reduced FA values in the right mTL in patient group were significantly negatively related to the total time spent on the TMT-A ( β=-0.425, P=0.009, FDR corrected) and TMT-B ( β=-0.325, P=0.026 with FDR correction). Increased FA values in right mCG in patient group demonstrated positive associations with total response time in the WCST ( β=0.585, P=0.002, FDR corrected), correct response time in WCST ( β=0.524, P=0.003, FDR corrected), error response time in WCST ( β=0.536, P=0.003, FDR corrected) and total time consuming in TMT-B ( β=0.484, P=0.004, FDR corrected), as well as negative associations with DST-forward ( β=-0.319, P=0.042, FDR corrected). After treatment, patients' percentage changes in total response time of WCST ( β=0.715, P<0.001, FDR corrected), correct response time of WCST ( β=0.752, P<0.001, FDR corrected), as well as total time-consuming of TMT-A ( β=1.333, P=0.001, FDR corrected) showed positive correlations with baseline increased FA values in the left mCG. Percentage alteration of Stroop-B was negatively correlated with baseline FA values in the right cuneus ( β=-0.745, P=0.015, FDR corrected). Conclusions:The combination of abnormal FA values in multiple brain regions may be potential biomarkers to distinguish schizophrenic patients from healthy volunteers. There was regional dependence in the associations of the impairment of white matter integrity with the cognitive impairment, the severity of psychopathological symptoms as well as the prognosis of patients in the acute stage.

Preliminary screening of therapeutic drugs for phenylalanine hydroxylase deficiency / 中国基层医药

Objective:To screen new drugs for treatment of phenylalanine hydroxylase deficiency.Methods:From October 2019 to October 2020, virtual drug screening was performed in Center of Genetic Medicine, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University computer according to the characteristics of the binding ability of phenylalanine hydroxylase to drug spatial structure. Ten candidate drugs were screened from the FDA drug library (including 2 697 kinds of active pharmaceutical ingredients). A eukaryotic expression system was used to determine the effects of drugs on the activity of phenylalanine hydroxylase at the molecular level. Drug-sensitive mutants were screened.Results:Among the 10 candidate drugs, neoplasm hydrochloride, fluocinonide acetate and risperidone increased 23% [ t = 18.21, P < 0.001, vs. non-drug-treated phenylalanine hydroxylase group (i.e., only solvent and no drug added to the reaction system)], 21% ( t = 3.44, P < 0.05, vs. non-drug-treated phenylalanine hydroxylase group), 31% ( t = 19.57, P < 0.001, vs. non-drug-treated phenylalanine hydroxylase group) of the activity of phenylalanine hydroxylase. The remaining drugs exhibited weak even inhibitory effects on the activity of phenylalanine hydroxylase. 25% of p.D101N mutant could be activated by risperidone ( t = 15.86, P < 0.001, vs. non-drug-treated p.D101N mutant group). Conclusion:Neoplasm hydrochloride, fluocinonide acetate and risperidone can be used as potential therapeutic drugs for phenylalanine hydroxylase deficiency, and p.D101N mutant can be used as the drug-sensitive mutation site.

Effects of olanzapine versus risperidone on cognitive function and serum complement and high-sensitivity C-reactive protein levels in patients with schizophrenia / 中国基层医药

Objective:To investigate the effects of olanzapine versus risperidone on cognitive function, serum complement C3 and C4 levels and high sensitivity C-reactive protein (hs-CRP) level in patients with schizophrenia. Methods:Eighty patients with schizophrenia who received treatment in Lishui Second People's Hospital, China between September 2018 and September 2019 were included in this study. They were randomly assigned to receive treatment either with olanzapine (olanzapine group, n = 40) or risperidone (risperidone group, n = 40). Before and after treatment, the Positive and Negative Syndrome Scale (PANSS) score and the Wisconsin Card Sorting Test score were evaluated in each group. Before and after treatment, serum levels of dopamine, serotonin, norepinephrine, complement C3 and C4 and hs-CRP levels were compared between the olanzapine and risperidone groups. Results:Before treatment, there were no significant differences in PANSS and WCST scores between the two groups (both P > 0.05). After treatment, PANSS score, the number of perseverative errors and the number of random errors in each group were significantly decreased compared with before treatment [olanzapine group: (56.23 ± 9.37) points, (13.06 ± 6.26) points, (16.23 ± 6.35) points, t = 12.334, 5.885, 3.840, all P < 0.05; risperidone group: (55.98 ± 10.21) points, (13.97 ± 6.54) points, (16.31 ± 6.32) points, t = 12.044, 6.213, 3.321, all P < 0.05]. After treatment, the number of correct sorts and the number of categories in each group were significantly increased compared with before treatment [olanzapine group: (29.21 ± 2.24) points, (3.79 ± 1.12) points, t = 3.323, 2.087, both P < 0.05; risperidone group: (29.33 ± 2.35) points, (3.81 ± 1.15) points, t =2.750, 2.085, both P < 0.05]. After treatment, there were significant differences in these indexes between the two groups (all P > 0.05). Before treatment, there were no significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups (all P > 0.05). After treatment, serum levels of dopamine, serotonin and norepinephrine in each group were significantly decreased compared with before treatment [olanzapine group: (5.02 ± 0.13) μg/L, (66.24 ± 6.05) μg/L, (27.32 ± 4.05) μg/L, t = 67.800, 9.977, 5.082, all P < 0.05; risperidone group: (4.18 ± 0.12) μg/L, (63.12 ± 6.21) μg/L, (24.81 ± 4.13) μg/L, t = 99.761, 12.296, 6.882, all P < 0.05]. After treatment, there were significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups ( t = 30.029, 2.276, 6.882, all P < 0.05). Before treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups (all P > 0.05). After treatment, complement C3 and C4 and hs-CRP levels in each group were significantly increased compared with before treatment [olanzapine group: (1.12 ± 0.18) g/L, (0.24 ± 0.06) g/L, (1.09 ± 0.11) mg/L, t = 5.129, 4.049, 32.452, all P < 0.05; risperidone group: (1.13 ± 0.17) g/L, (0.25 ± 0.07) g/L, (1.10 ± 0.12) mg/L, t = 5.147, 5.164, 29.227, all P < 0.05]. After treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups ( t = 0.255, 0.686, 0.389, all P > 0.05). Conclusion:Olanzapine and risperidone have the same effects on improving the mental symptoms and cognitive function of patients with schizophrenia, but risperidone has more obvious effects on improving the body function than olanzapine.

MECT combined with risperidone in the treatment of schizophrenia complicating 12-month stupor： a case report / 四川精神卫生

The report elaborated a case of a 52-year-old female patients with over 10 years of schizophrenia complicating 12 months of stupor. After a course of modified electroconvulsive therapy（MECT） combined with risperidone oral solution， the patient gradually became active and functionally recovered， and remained stable. This case suggests that MECT combined with risperidone may allow schizophrenia patients in a state of prolonged stupor to obtain clinical rehabilitation and effectively stabilize psychotic symptoms. The discussion is based on this case with a view to providing references for clinical treatment.

High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers / Dos pacientes que tomaban inductores necesitaron dosis altas de medicamentos metabolizados en gran medida por el CYP3A4 para alcanzar concentraciones terapéuticas

ABSTRACT Introduction: In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations. Methods: The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4. Results: Case 1 was characterized by a history of high carbamazepine doses (up to 2,000 mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning. The high activity of the CYP3A4 isoenzyme was manifested by fast metabolism for quetiapine and diazepam, which took more than 1 year to normalize after the inducer, phenytoin, was stopped. Case 2 was also very sensitive to CYP3A4 inducers as indicated by very low C/D ratios for carbamazepine, risperidone and paliperidone. The carbamazepine (2,800 mg/day) and risperidone (20 mg/day) dosages for this second patient are the highest doses ever seen for these drugs by the senior author. Risperidone induction appeared to last for many months and metabolism was definitively normal 3 years after stopping carbamazepine. On the other hand, olanzapine C/D ratios were normal for induction. Conclusions: The literature has never described similar cases of very high doses of drugs metabolized by CYP3A4. We speculate that these 2 patients may have unusual genetic profiles at the nuclear receptor levels; these receptors regulate induction of drugs.

RESUMEN Introducción: Durante sus últimos 20 años de práctica, el último autor ha identificado estos 2 infrecuentes casos que necesitaban dosis extremadamente altas de medicaciones metabolizadas por el CYP3A4 para alcanzar y mantener concentraciones séricas terapéuticas. Métodos: La gran capacidad metabólica de estos 2 pacientes se demostró por los bajos cocientes entre concentración y dosis (C/D) de varias medicaciones metabolizadas por el CYP3A4. Resultados: El caso 1 se caracterizaba por una historia de altas dosis de carbamazepina (1.500 mg/día) y la necesidad de tomar 170 mg de diazepam en 2 días para facilitar una limpieza dental. La gran actividad de la isoenzima CYP3A4 se manifestó por una gran capacidad metabólica de quetiapina y diazepam, cuya normalización tardó más de 1 año tras la toma de un inductor, fenitoína. El caso 2 tambien era muy sensible a la inducción, lo cual se demuestra por los bajos cocientes C/D de carbamazepina, risperidona y paliperidona. Las dosis de carbamazepina (2.800 mg/día) y risperidona (20 mg/día) de este segundo paciente son las más altas nunca vistas por el último autor. La inducción de risperidona duró muchos meses y su metabolismo era normal 3 años después de interrumpir la carbamazepina. El cociente C/D de olanzapina era normal para la inducción. Conclusiones: Nunca se habían descrito casos similares de dosis tan altas de medicaciones metabolizadas por el CYP3A4. Se especula con que estos pacientes podrían tener unos perfiles genéticos inusuales en los receptores nucleares que regulan la inducción de medicamentos.

Dopaminergic drugs alter beta coherence during motor imagery and motor execution in healthy adults / Drogas dopaminérgicas alteram a coerência beta durante a imagética motora e a execução motora em adultos saudáveis

Abstract Background: Motor Imagery (MI) represents the cognitive component of the movement and recruits dopaminergic systems. Objective: To investigate the role of dopaminergic system through the action of methylphenidate and risperidone over beta coherence during execution, action observation and motor imagery. Methods: Electroencephalography (EEG) data were recorded before and after the substance intake. For statistical analysis, a three-way ANOVA was used to identify changes in beta coherence induced by the group, task and the moment variables. Statistical significance was set at p≤0.007. Results: We found a main effect for group for C3/CZ, and a main effect for task for CZ/C4 pairs of electrodes. Furthermore, significant differences were found in the post-drug administration between groups for C3/CZ pair of electrodes, and between task for C4/CZ pair of electrodes. Conclusion: The administration of methylphenidate and risperidone was able to produce electrocortical changes of the cortical central regions, even when featuring antagonistic effects on the dopaminergic pathways. Moreover, the execution task allowed beta-band modulation increase.

Resumo Introdução: A imagética motora (IM) representa o componente cognitivo do movimento e recruta os sistemas dopaminérgicos. Objetivo: Investigar o papel do sistema dopaminérgico por meio da ação do metilfenidato e da risperidona sobre a coerência em beta durante a execução, observação de ação e imagética motora. Métodos: Os dados de eletroencefalografia (EEG) foram registrados antes e depois da ingestão das substâncias. Para a análise estatística, uma ANOVA de três vias foi utilizada para identificar mudanças na coerência beta induzidas pelas variáveis grupo, tarefa e momento. A significância estatística foi estabelecida em p≤0,007. Resultados: Encontramos um efeito principal para o grupo C3/CZ e um efeito principal para a tarefa nos pares de eletrodos CZ/C4. Além disso, diferenças significativas foram encontradas após a administração da droga entre os grupos para o par de eletrodos C3/CZ e entre tarefa para o par de eletrodos C4/CZ. Conclusão: A administração de metilfenidato e risperidona foi capaz de produzir alterações eletrocorticais das regiões somatomotoras, mesmo apresentando efeitos antagônicos nas vias dopaminérgicas. Além disso, a tarefa de execução provocou maior modulação da banda beta.

A study on haloperidol and risperidone induced metabolic derangements in patients with newly diagnosed schizophrenia

Background: The occurrence of metabolic abnormalities in schizophrenic patients has been increased with the rampant use of second-generation antipsychotics. The aim and objective of this study is to compare the metabolic derangements induced by a typical antipsychotic: haloperidol and an atypical antipsychotic, risperidone in patients with newly diagnosed schizophrenia in a tertiary care hospital.Methods: Out of 60 newly diagnosed schizophrenic patients, 30 patients received tablet haloperidol and the remaining 30 patients received tablet risperidone orally. The anthropometric measurements like height, weight, waist circumference was measured and blood investigations like fasting blood glucose level and fasting lipid profile were taken at baseline and at the end of 3 and 6 months of drug therapy. The metabolic derangements induced by the two antipsychotics were compared and analyzed at end of 3rd and 6th month using SPSS software version 16.Results: At the end of 6th month statistically significant differences (p<0.05) were observed in weight, waist circumference, fasting blood sugar, fasting triglyceride and high-density lipoprotein level between the haloperidol and risperidone group on following the International Diabetic Federation (IDF) criteria of metabolic syndrome. Risperidone caused metabolic abnormalities in 13.3%, 4 patients whereas none of the patients in haloperidol group developed metabolic syndrome.Conclusions: Hence it is concluded that the atypical antipsychotic risperidone has been associated with an increased risk of causing metabolic abnormalities than the typical antipsychotic haloperidol. Regular and periodic monitoring of the anthropometric and metabolic parameters in schizophrenic patients on antipsychotics especially the atypical antipsychotics is mandatory to prevent further complications.

Changes in serum thyroid hormone levels in psychiatric patients after risperidone monotherapy or polytherapy treatment / 中国临床药理学与治疗学

AIM: To investigate changes in serum thyroid hormone levels in psychiatric patients after risperidone monotherapy or polytherapy treatment. METHODS: Twenty-nine in-patients who received risperidone monotherapy treatment and 25 in-patients who received polytherapy treatment of risperidone and other second-generation antipsychotics were included. Changes in thyroid hormone levels after treatment were retrospectively analyzed. RESULTS: After risperidone monotherapy treatment, serum levels of free thyroxine (FT4) and total thyroxine (TT4) significantly decreased, and serum TSH levels significantly increased (changes from baseline: FT4: median -2.52 pmol/L, P<0.001; TT4: -21.17 nmol/L, P=0.012; TSH: median 0.49 mIU/L, P=0.001). After risperidone polytherapy treatment, serum levels of free triiodothyronine (FT3), total triiodothyronine (TT3) and FT4 significantly decreased, and serum TSH levels significantly increased (changes from baseline: FT3: median -0.37 pmol/L, P=0.001; TT3: median -0.17 nmol/L, P=0.008; FT4: median -2.25 pmol/L, P<0.001; TSH: median 0.97 mIU/L, P=0.029). After risperidone monotherapy treatment, moderately positive relation was found between changes in serum TT4 levels and average daily dose of risperidone. No statistical difference was found on the incidence of subclinical thyroid dysfunction between the two therapeutic regimen (6.9% vs. 12.0%, P=0.862). CONCLUSION: To avoid other disease caused by abnormal thyroid hormone levels, changes in serum thyroid hormone levels should be noticed after risperidone treatment.

Relationship of leptin and ghrelin gene polymorphisms with metabolic changes induced by risperidone in patients with schizophrenia / 西安交通大学学报(医学版)

Objective To investigate the changes of body weight and metabolism related indexes after risperidone treatment in schizophrenia and to analyze the relationship of leptin gene 2548G/A polymorphism and polymorphism of ghrelin gene leucine 72 methionine (Leu72Met) with changes in body weight and metabolism related indicators. Methods Sixty-eight patients with schizophrenia were treated with risperidone monotherapy for 10 weeks. The metabolic indexes including body mass index (BMI), waist circumference, fasting blood glucose and blood lipid levels were measured at 4 and 10 weeks after treatment. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphisms of leptin gene and ghrelin gene. Results The patients' body weight, blood glucose and blood lipids were significantly increased during treatment (P 0.05). Conclusion During the acute phase of risperidone treatment, patients may have different levels of body weight, blood glucose and blood lipid. The ghrelin gene Leu72 allele may be a risk factor for hyperglycemia in patients with schizophrenia treated with risperidone.

Efficacy of risperidone and haloperidol in treatment of schizophrenia in tertiary care hospital

Background: Schizophrenia is a chronic debilitating disease with significant morbidity and mortality that often requires either typical or atypical antipsychotic pharmacotherapy. Atypical antipsychotic drugs are preferred over typical because of lower risk of extra pyramidal side effects. As there is paucity of data in Indian population, the present study was taken up to evaluate the efficacy of haloperidol and risperidone in the treatment of schizophrenia.Methods: It was a comparative study conducted on 60 patients of Schizophrenia for one year in a tertiary care hospital. The study subjects were randomly assigned into 2 groups of 30 patients each, where group 1 were treated with atypical antipsychotic drug risperidone and group 2 with typical antipsychotic drug Haloperidol and both groups received the treatment for one year. Efficacy was measured using positive and negative syndrome scale (PANSS), clinical global impression - severity of illness (CGI-S), clinical global impression - improvement (CGI-I) scales.Results: Both haloperidol and risperidone were associated with comparable baseline to endpoint reduction in symptom severity. However, risperidone treated subjects had significantly greater decrease in symptom severity as measured by PANSS score and total score, CGI-S scale. However, there is no significant difference between two groups in terms of CGI-S score.Conclusions: The reduction in positive, negative and general scores in risperidone treated patients were significant with that of haloperidol treated patients.

A comparative study of metabolic side effects of risperidone and olanzapine in the treatment of schizophrenia

ABSTRACTBackground: Schizophrenia is one of most serious chronic psychiatric disorder, which affects about 1% of population. Treatment of schizophrenia comprises of typical antipsychotics and or atypical antipsychotics. Typical antipsychotics like haloperidol have extrapyramidal side effects which limit their use in chronic cases. Atypical antipsychotics though have better treatment response, they have metabolic side effects like hypercholesteremia, hypertriglyceridemia and hyperglycaemia. As there is paucity of data in Indian population the present study has been taken up to compare the metabolic side effects of risperidone and olanzapine in the treatment of schizophrenic patients in a tertiary care hospital.Methods: It was a comparative study conducted on 60 patients of Schizophrenia for one year in a tertiary care hospital. The study subjects were randomly assigned into 2 groups of 30 patients each, where group 1 were treated with atypical antipsychotic drug risperidone and group 2 with Olanzapine and both groups received the treatment for one year. Metabolic side effects like hypercholesteremia, hypertriglyceridemia and hyperglycaemia were evaluated and compared over a period of one year.Results: Both risperidone and olanzapine were associated with comparable baseline to endpoint increase in metabolic side effects. However, risperidone treated subjects had significantly less metabolic side effects compared to olanzapine.Conclusions: Apart from total cholesterol and triglycerides, other metabolic side effects were less in risperidone treated patients than olanzapine treated patients.

Síndrome neuroléptico maligno inducido por risperidona y facilitado por sepsis de origen urinario: clínica y fisiopatología / Malignant neuroleptic syndrome induced by risperidone and facilitated by sepsis of urinary origin: clinical aspects and physiopathology

La risperidona es un antagonista selectivo monoaminérgico, con una elevada afinidad por receptores dopaminérgicos, que puede producir síndrome neuroléptico maligno (SNM), considerado una emergencia médica con alto riesgo de muerte. Tiene una incidencia de hasta el 3% y su mortalidad está entre el 10 y 20%. Se reporta el caso de una paciente de 56 años, que reunía los criterios clínicos del SNM, inducido por el uso de risperidona y facilitado por una sepsis de origen urinario. El tratamiento se condujo con un agente agonista dopaminérgico y cambio del antipsicótico, procedimientos que resultaron en una adecuada evolución clínica. El SNM es una entidad de baja prevalencia, para la cual existen criterios diagnósticos con especificidad y sensibilidad mayor del 90%, por lo que debe diferenciarse claramente de otras patologías. Se discute el mecanismo mediante el cual la infección urinaria facilitaría la ocurrencia de esta enfermedad. El diagnóstico precoz mejora la respuesta al manejo adecuado que se establezca en cada caso.

Risperidone is a selective monoaminergic antagonist with a high affinity for dopamine receptors that can cause neuroleptic malignant syndrome (NMS), considered a life-threatening medical emergency. It has an incidence of up to 3% and its mortality is between 10 and 20%. The case of a 56-year-old female who met the clinical criteria of NMS, induced by the use of risperidone and facilitated by a sepsis of urinary origin, is reported. It was managed with a dopamine agonist and the change of antipsychotic, which resulted in a favorable clinical course. The NMS is a low-prevalence entity whose diagnosis has specificity and sensitivity greater than 90%, reason for which must be clearly differentiated from other pathologies. The mechanism by which urinary infection could facilitate the occurrence of this disease is discussed. Early diagnosis improves the response to an adequate management to be established in each case.

Delusional Parasitosis: An Analysis of 177 Cases from a Tertiary General Hospital.

Introduction: Delusional parasitosis (DP) is a form ofmonohypochondriacalpsychosis characterized by a feelingthat there are parasites crawling beneath the skin and is seen inrarely in psychiatric or primary carepractice. The disorder haspoor prognosis with a varied course and multiple relapses. Thepresent paper reports an analysis of 177 cases of delusionalparasitosis seen in a tertiary general hospital over the last 11years.Material and methods: The present study is an analysis of177 cases of DP that presented to the psychiatry departmentof a tertiary general hospital over the past 11 years and thedata has been analyzed using a semi-structured proforma anddescriptive statistics.Results: The mean age of the sample was 34.6 ± 21.3 yearsand the mean age of onset of the disorder was 28.3 ± 17.1years. The mean duration of illness of the sample was 3.9 ±10.3 years. 103 (58.19%) had a magnetic resonance imagingof the brain done which was within normal limits. 56(31.63%) patients had repeated neuroimaging investigationslike EEG, MRI and CT Scans done which were also all withinnormal limits. Most patients were treated with Risperidoneand Aripiprazole while few were treated with Pimozide,Haloperidol and Amisulpride. 43 (24.29%) patients received acourse of electroconvulsive therapy (ECT) as well in additionto medications.Conclusion: DP though rare is seen in clinical practice andfurther longitudinal studies are needed to establish withgreater certainty facts about the course and prognosis of thedisorder

Cervical lympahadenitis with risperidone induced cervical dystonia

Abiogeniccervical dystonia, the most ordinary form of adult-onset focal dystonia, is elucidated as reflex muscle contractions. Idiopathic cervical dystonia is also called as spasmodic torticollis. The most habitually obliging medications were tetrabenazine (68% ofpatients upgraded) and anticholinergics (39% upgraded). Clinical manifestations include spinal curvature, local pain, muscle spasm, head-neck tremor and tremor in additional body regions. Antipsychotic drugs induce persistent dystonia. Lymphadenitis particularly refers to lymphadenopathies that are kindled by inflammatory processes. Treatment for lymphadenitis is complete antibiotic course of 10-14 days. A female patient of 14 years oldpresented with altered sensorium and neck tightness. She was diagnosedwith cervical lymphadenopathy with risperidoneinduced cervical dystonia. She was treated with antibioticsand the patient was relieved from her symptoms by stopping the intake of risperidonefor about 2 days.

Metabolic dysregulation in early onset psychiatric disorder before and after exposure to antipsychotic drugs

Antipsychotic Drugs (APDs) are being widely prescribed to treat various disorders, including schizophrenia and bipolar disorder; however, abnormal glucose metabolism and weight gain have been reported with Atypical Anti-Psychotic drugs (AAPDs) that can lead to insulin-resistance and type 2 diabetes mellitus. The study was designed to assess various biochemical parameters including insulin and blood sugar before and after exposure to APDs in order to exclude the involvement of psychiatric disorders and certain other factors in metabolic dysregulations. Fifty seven APDs-naïve patients with first episode psychosis were divided into six groups who received olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or combination of olanzapine with escitalopram and haloperidol. The serum samples were taken before the intake of the first dose and then on follow-up. Decrease in the level of elevated insulin and glucose was observed post-treatment in some patients, while others were observed whose insulin and glucose levels increased post-treatment, yet some patients did not show any disturbance in the insulin and glucose levels. It is concluded that psychiatric disorders by itself, narcotics, cigarette smoking and use of oral snuff may be also be implicated in metabolic dysregulations. The effects of APDs on insulin and glucose in healthy volunteers might be different than in patients with psychiatric disorders.

Psychotic Symptoms of Hashimoto's Encephalopathy: A Diagnostic Challenge

Hashimoto's encephalopathy (HE) is a rare and underdiagnosed neuropsychiatric illness. We present the case of a 17-year-old girl who was admitted to a tertiary-care psychiatric center with acute onset psychosis and fever. Her psychotic symptoms were characterized by persecutory and referential delusions, as well as tactile and visual hallucinations. Her acute behavioral disturbance warranted admission and treatment in a psychiatric setting (risperidone tablets, 3 mg/day). She had experienced an episode of fever with a unilateral visual acuity defect approximately 3 years before admission, which was resolved with treatment. Focused clinical examination revealed an enlarged thyroid, and baseline blood investigations, including thyroid function test results were normal. Abnormal laboratory investigations revealed elevated anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels (anti-TPO of 480 IU/mL; anti-TG of 287 IU/mL). Results of other investigations for infection, including cerebrospinal fluid examination, electroencephalography, and brain magnetic resonance imaging were normal. She was diagnosed with HE and was treated with intravenous corticosteroids (methylprednisolone up to 1 g/day; tapered and discontinued after a month). The patient achieved complete remission of psychotic symptoms and normalization of the anti-thyroid antibody titers. Currently, at the seventh month of follow-up, the patient is doing well. This case highlights the fact that in the absence of well-defined clinical diagnostic criteria, a high index of suspicion is required for early diagnosis of HE. Psychiatrists need to explore for organic etiologies when dealing with acute psychiatric symptoms in a younger age group.