| Objective: To compare the efficacy,safety and quality of life in patients with epilepsy of arotinolol hydrochloride and propranolol hydrochloride in the treatment of valproate-induced tremor using single-center randomized controlled trial.Methods: Patients with epilepsy due to tremor caused by valproate monotherapy at the epilepsy center of Sichuan Provincial People's Hospital from February 2018 to March 2019 who meet inclusion and exclusion criteria were continuously randomized.The patients were randomly divided into the arotinololol hydrochloride group(n = 28)and the propranolol hydrochloride group(n = 24)by the random number table method.On the basis of maintaining the original oral VPA dose,the two groups of patients were orally administered arotinolol hydrochloride tablets(trade name Almar,manufactured by Sumitomo Pharmaceutical Co.,Ltd.,10 mg each,sub-package approval number: National Drug Standard J20140161)5 mg bid and propranolol hydrochloride Tablets(produced by Changzhou Kangpu Pharmaceutical Co.,Ltd.,the specification is 10 mg per tablet,the approval number is Sinopharm H2021276)10 mg bid respectively,and observation period was 12 weeks.The severity of tremor(Clinical rating scale for tremor),the quality of life(Qualityof life in epilepsy—31 inventory scores),seizure frequency,blood pressure,heart rate,electrocardiogram before and after treatment were assessed,and adverse reactions during treatment were recorded.Results: Of the 189 patients with epilepsy treated with valproate monotherapy at the Epilepsy Center of Sichuan Provincial People's Hospital,33.9%(64 cases)of patients with epilepsy had adverse reactions to tremor.A total of 52 patients with epilepsy who met the inclusion and exclusion criteria for treatment of tremors were included in this study.During treatment,one patient was lost to follow-up,one patient was dropped off,and one patient withdrew from the test on his own.Eventually,49 patients completed the whole trial(27 in the arotinolol hydrochloride group,22 in the propranolol hydrochloride group).Among them,there were 24 males(49.0%)and 25females(51.0%),with an average age of 34.53 ± 10.78 years.The average time of taking valproate : 3.74 ± 2.71 years,the average dosage of valproate:1163.27 ± 296.88 mg,the average blood concentration of valproate: 86.08 ±15.33 ug / ml,the average tremor duration: 14.94 ± 11.86 months.For epileptic patients with valproate-induced tremor,tremors appear 2 months after regular valproate treatment.Tremor mainly presents postural tremor,predominantly in the upper limbs.There were 42 cases(80.7%)of tremor involving both upper limbs.Some patients have tremors in other parts of the body: head,tongue,lower limbs,trunk.Correlation analysis between valproate plasma concentration and CRST total score showed that there was no exact correlation between the plasma concentration of valproate and the severity oftremor(correlation coefficient r = 0.154,P> 0.05).At the end of the 12 th week of treatment,the tremor scores of the two groups of epilepsy patients were significantly lower than before treatment(arotinolol hydrochloride group :34.96±14.89 vs 17.89±10.05,P<0.01;propranolol hydrochloride group:34.14±13.18 vs 29.59±11.12,P<0.01),and the improvement of tremor was more obvious in the arotinolol hydrochloride group(17.89±10.05 vs29.59±11.12,P < 0.01).The total quality of life score of the arotinolol hydrochloride group was significantly higher than that before treatment(54.59±12.46 vs.57.73±10.89,P<0.05);but the total quality of life score of the propranolol hydrochloride group was improved compared with the previous one,there was no significant difference(50.82±11.27 vs 54.08±6.56,P>0.05).The arotinolol hydrochloride group showed significant improvement in medication effects and social function(39.48±20.15 vs 51.33±20.55,P <0.01;54.26±15.18 vs 58.48±15.62,P<0.05),but the propranolol group only improved in terms of medication effects(30.15±16.31 vs 40.15±16.64,P <0.05).The heart rate of the two groups was significantly lower than that before treatment(P<0.05),respectively changing(-6.68±5.31),(-4.51 ±5.51)times · min-1(both P <0.01),but the average heart rate was ?60 times/min,within a safe range.The systolic and diastolic blood pressures of propranolol hydrochloride group were significantly lower than those before treatment(P<0.05),respectively changing(systolic pressure:-4.81 ± 2.70),(diastolic pressure:-6.10±5.16)mmHg,but mean blood pressure was within safe range and no clinical symptoms.Blood pressure in the arotinololhydrochloride group was slightly lower than before treatment,respectively changing(systolic pressure:-2.19±7.20)and(diastolic pressure:-1.48±5.63)mmHg,but the difference was not significant(P>0.05).The electrocardiogram at the end of the observation period did not suggest abnormal changes such as atrioventricular block and so on.There was no significant difference in seizure frequency between the two groups compared with that before treatment(P>0.05).During the treatment period of the arotinolol hydrochloride group,one patient experienced burnout,and one patient consciously exacerbated the tremor after taking the drug and stopped the drug withdrawal.In the propranolol hydrochloride group,during the treatment period,2 patients felt dizzy,but the severity was mild,and the symptoms disappeared after continuing to take the drugs.There was no significant difference in the incidence of adverse reactions between the two groups(7% vs.9%,P>0.05).There were no abnormal changes in blood routine and biochemistry before and after treatment.Conclusion: For epileptic patients with valproate-induced tremor,tremor mainly presents postural tremor,predominantly in the upper limbs.The severity of tremor was not correlated with plasma concentration of valproate.Arotinolol hydrochloride and propranolol hydrochloride in the treatment of valproate-induced tremor did not reduce the frequency of seizures.Both arotinolol hydrochloride and propranolol hydrochloride can improve the tremor caused by sodium valproate,and arotinolol hydrochloride is more effective,and the improvement of tremor is more significant.It has a smaller effect on blood pressure,is safer,and can improve the quality of life of patients with epilepsy. |
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