Co-administration Of Risperidone Research Articles

Integrating machine learning with electronic health record data to facilitate detection of prolactin level and pharmacovigilance signals in olanzapine-treated patients.

Background and aimAvailable evidence suggests elevated serum prolactin (PRL) levels in olanzapine (OLZ)-treated patients with schizophrenia. However, machine learning (ML)-based comprehensive evaluations of the influence of pathophysiological and pharmacological factors on PRL levels in OLZ-treated patients are rare. We aimed to forecast the PRL level in OLZ-treated patients and mine pharmacovigilance information on PRL-related adverse events by integrating ML and electronic health record (EHR) data.MethodsData were extracted from an EHR system to construct an ML dataset in 672×384 matrix format after preprocessing, which was subsequently randomly divided into a derivation cohort for model development and a validation cohort for model validation (8:2). The eXtreme gradient boosting (XGBoost) algorithm was used to build the ML models, the importance of the features and predictive behaviors of which were illustrated by SHapley Additive exPlanations (SHAP)-based analyses. The sequential forward feature selection approach was used to generate the optimal feature subset. The co-administered drugs that might have influenced PRL levels during OLZ treatment as identified by SHAP analyses were then compared with evidence from disproportionality analyses by using OpenVigil FDA.ResultsThe 15 features that made the greatest contributions, as ranked by the mean (|SHAP value|), were identified as the optimal feature subset. The features were gender_male, co-administration of risperidone, age, co-administration of aripiprazole, concentration of aripiprazole, concentration of OLZ, progesterone, co-administration of sulpiride, creatine kinase, serum sodium, serum phosphorus, testosterone, platelet distribution width, α-L-fucosidase, and lipoprotein (a). The XGBoost model after feature selection delivered good performance on the validation cohort with a mean absolute error of 0.046, mean squared error of 0.0036, root-mean-squared error of 0.060, and mean relative error of 11%. Risperidone and aripiprazole exhibited the strongest associations with hyperprolactinemia and decreased blood PRL according to the disproportionality analyses, and both were identified as co-administered drugs that influenced PRL levels during OLZ treatment by SHAP analyses.ConclusionsMultiple pathophysiological and pharmacological confounders influence PRL levels associated with effective treatment and PRL-related side-effects in OLZ-treated patients. Our study highlights the feasibility of integration of ML and EHR data to facilitate the detection of PRL levels and pharmacovigilance signals in OLZ-treated patients.

Risperidone and escitalopram co-administration: A potential treatment of schizophrenia symptoms with less side effects.

Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms often accompanied by depression and cognitive deficits. Positive symptoms, like delusions and hallucinations are caused by an excess of dopamine (DA) signaling and are treated with the second generation antipsychotic drugs. Negative symptoms of schizophrenia are represented by social withdrawal, apathy and blunted emotional response. It was demonstrated that co-administration of risperidone and selective serotonin reuptake inhibitors alleviated depressive symptoms and cognitive dysfunction in animal models of schizophrenia. Moreover, combination of fluoxetine or mirtazapine with risperidone increased DA and 5-hydroxytryptamine (5-HT) release in the rat frontal cortex more potently than either drug given separately. The present study aimed to investigate whether combination of risperidone and escitalopram is effective in increasing DA and 5-HT release. The extracellular level of neurotransmitters in the rat frontal cortex and nucleus accumbens was examined using microdialysis in freely moving animals. The dialysate concentration of DA and 5-HT was assayed by HPLC. It was found that risperidone (0.2 and 1mg/kg) and escitalopram (5 and 10mg/kg) given together significantly increased cortical DA and 5-HT levels and were more efficient in enhancing neurotransmitter concentrations than any single-drug treatment. A similar effect on DA and 5-HT release was observed in the nucleus accumbens after administration of risperidone (1mg/kg) and escitalopram (5mg/kg). The present study demonstrates that co-administration of risperidone and escitalopram may be used to treat positive and negative symptoms of schizophrenia and will allow to minimize the drugs' side effects.

Co-Administration of Risperidone and Sodium Valproate Causing Bilateral Chronic Exertional Lower Leg Compartment Syndrome

We present the case of a 24-year-old man, who was a keen runner, developing chronic bilateral lower leg compartment syndrome following co-administration of Risperidone and Sodium Valproate. Having had failed medical and physical therapies, he underwent surgical decompression of his more problematic left lower leg compartments. In the interval between sequential fasciotomies, control of his psychiatric symptoms allowed the dose of his Risperidone to be reduced, resulting in a greater exercise tolerance. Ultimately he no longer required the contra-lateral lower leg compartments to be decompressed surgically. He had returned to his original level of activity with no further psychotic episodes.

Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats.

RationaleSome novel antipsychotics manifest antagonistic activity at serotonin-6 receptors; however, little is known about the role of 5-HT6 receptors in ameliorating sensory gating deficits.ObjectiveWe evaluated the effects of the combined administration of the 5-HT6 receptor antagonist SB 271046 with clozapine and haloperidol, as well as the co-administration of SB 271046 or SB 399885 with risperidone and the 5-HT2A antagonist M100907, to overcome the deficits induced by MK-801 in the prepulse inhibition (PPI) test.ResultsMK-801 (0.1 mg/kg) produced reliable PPI deficits. Administration of SB 271046 (6 and 9 mg/kg), SB 399885 (3 and 6 mg/kg), clozapine (2.5 mg/kg), haloperidol (0.1 and 0.2 mg/kg), risperidone (0.25–1 mg/kg), and M100907 (0.5 and 1 mg/kg) did not affect the MK-801-induced deficits, but the administration of clozapine (5 mg/kg) did reverse the effects of MK-801. In MK-801-treated rats, the co-administration of inactive doses of clozapine (2.5 mg/kg) and SB 271046 (6 mg/kg) reversed the PPI impairments compared to animals that were administered inactive doses of either clozapine or SB 271046 alone. Co-administration of risperidone (1 mg/kg) or M100907 (0.5 mg/kg) with SB 271046 (6 mg/kg) or SB 399885 (3 mg/kg) also attenuated the MK-801-induced PPI deficits. In contrast, joint administration of haloperidol and SB 271046 had no effect on the PPI deficit.ConclusionThe present results suggest that the 5-HT6 receptors may play adjunctive roles in antipsychotic drug action, and that the combination of 5-HT2A and 5-HT6 antagonism may represent an important element in the pharmacological profile of antipsychotic drugs.

Case Report of Valproate-Induced Hypothermia in a Patient With Schizoaffective Disorder

Case Report of Valproate-Induced Hypothermia in a Patient With Schizoaffective Disorder

Rifampin, a cytochrome P450 3A inducer, decreases plasma concentrations of antipsychotic risperidone in healthy volunteers

Although cytochrome P450 (CYP) 2D6 is often thought to be the only CYP responsible for the metabolism of risperidone, many reports suggest that CYP3A may be involved too. Rifampin, a potent CYP3A inducer, has been known to markedly decrease plasma concentrations of various drugs, which are concomitantly administered during treatment. To examine the effect of rifampin on plasma concentrations of a single oral dose of risperidone in healthy Thai male volunteers. In an open, randomized two-phase crossover study, separated by a 2-week period, 10 healthy Thai male volunteers received a single oral dose of 4-mg risperidone alone or with 600 mg rifampin, orally once daily for 5 days. Serial blood samples were collected at specific time points for a 48-h period. Risperidone was measured in plasma using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined by using non-compartmental analysis. Co-administration with 600-mg rifampin once daily for 5 days was associated with a significant decrease in risperidone area under the curve (AUC(0-48)) and maximal concentration (C(max)) by 72% (157 x 49 +/- 48 x 80 vs. 42 x 66 +/- 7 x 81 ng/L/h; P<0 x 01) and 50% (32 x 44 +/- 6 x 05 vs. 16 x 16 +/- 2 x 73 ng/mL; P<0 x 05), respectively when compared with risperidone alone. Rifampin when used concurrently with risperidone significantly decreases the plasma concentration of risperidone. Our results provide in vivo evidence of the involvement of CYP3A in the metabolism of risperidone, in addition to CYP2D6. Thus, co-administration of risperidone with CYP3A inducer(s), including rifampin should be recognized or avoided in clinical practice.

Coadministration of risperidone and donepezil is not associated with any clinically significant drug interactions,

Coadministration of risperidone and donepezil is not associated with any clinically significant drug interactions,

Decrease in plasma zonisamide concentrations after coadministration of risperidone in a patient with schizophrenia receiving zonisamide therapy

Decrease in plasma zonisamide concentrations after coadministration of risperidone in a patient with schizophrenia receiving zonisamide therapy