| Objective: To explore the effect of combined use of beta-blockers metoprolol and propranolol on the steady-state plasma concentration of atypical antipsychotic drugs risperidone,quetiapine,olanzapine and clozapine in middle-aged and elderly patients with schizophrenia,In order to provide a theoretical reference for the formulation of individualized drug regimen and the reduction of ADR risk..Methods: Retrospective,observational case-control study.The clinical data of middle-aged and elderly patients with schizophrenia who met the inclusion criteria and exclusion criteria from August 2021 to February 2023 in the Department of Psychiatry,Anning First People ’s Hospital Affiliated to Kunming University of Science and Technology were collected.The results of the steady-state blood concentration of atypical antipsychotic drugs and their active metabolites were finally included in 185 patients,aged 45-94 years.According to the atypical antipsychotic drugs used by patients,the patients were divided into risperidone control group and observation group.Quetiapine control group,observation group;olanzapine control group,observation group;clozapine control group,observation group.There were 21 cases in risperidone control group,22 cases in observation group,23 cases in quetiapine control group,19 cases in observation group,28 cases in olanzapine control group,22 cases in observation group,27 cases in clozapine control group and 23 cases in observation group.STATA 16.0 software and SPSS 26.0 software were used for statistical analysis.The effects of beta-blockers metoprolol and propranolol on the steady-state plasma concentration and active metabolite concentration of atypical antipsychotics were analyzed.Main outcome measures : The differences of steady-state blood concentration/ dose(C / D)and active metabolite / parent drug(metabolic ratio)of parent drug,active metabolite and total active substance between each drug control group and observation group.Results :1.According to statistical analysis,it was found that the blood concentration of risperidone in the risperidone observation group was significantly increased after the use of beta blocker metoprolol and propranolol,and the difference was statistically significant compared with the control group,p < 0.01.There was no significant difference in the blood concentration of quetiapine,olanzapine and clozapine between the control group and the observation group(p > 0.05).2.The blood concentration of the active metabolite N-dealkyl quetiapine in the quetiapine observation group was significantly increased,and the difference was statistically significant compared with the control group,and p < 0.01.There was no significant difference in the blood concentration of 9-OH risperidone between the risperidone control group and the observation group(p > 0.05).3.The blood concentration of the total active ingredient in the quetiapine observation group was significantly higher than that in the control group(p <0.05).There was no significant difference in the blood concentration of the total active ingredient between the risperidone control group and the observation group(p > 0.05).4.The metabolic ratio of the risperidone observation group was significantly lower than that of the control group(p < 0.01),there was no significant difference in metabolic ratio between quetiapine control group and observation group.Conclusion : Our results suggest that there are pharmacokinetic drug-drug interactions between atypical antipsychotics risperidone,quetiapine and beta-blockers metoprolol and propranolol,metoprolol and propranolol can inhibit the activity of CYP2D6,which affects the blood concentration of risperidone and N-dealkyl quetiapine,the active metabolite of quetiapine.There may be no pharmacokinetic drug-drug interaction between olanzapine,clozapine and metoprolol,propranolol.It is suggested that we may need to adjust the dose of risperidone and quetiapine when applying metoprolol and propranolol to middle-aged and elderly schizophrenic patients with hypertension.It is suggested that clinicians should pay attention to the individualized medication of atypical antipsychotic drugs.In particular,middle-aged and elderly patients with weakened metabolism and excretion ability and simultaneous use of multiple drugs should pay attention to the occurrence of ADR,appropriately increase the frequency of TDM,closely monitor the blood concentration of atypical antipsychotic drugs,and formulate individualized medication plans to reduce the risk of ADR. |
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