A Comparative Study On The Efficacy And Safety Of Gabapentin In The Maintenance Period Of Patients With Alcohol Dependence

BackgroundAlcohol dependence（AD）is a mental disorder,which is characterized by compulsive drinking behavior,loss of control over drinking,withdrawal symptoms when stopping use,and obvious impairment of social and occupational functions.The number of deaths caused by alcohol accounts for about 5.3% of the deaths in the world.Alcohol addiction seriously endangers individual physical and mental health,family happiness and social stability.The treatment of alcohol dependence can be divided into acute withdrawal treatment and maintenance treatment after abstinence.In the acute withdrawal period,benzodiazepines（BZD）have significant clinical efficacy.However,in the maintenance period after abstinence,there is no specific drug at present.A new generation of antipsychotics,selective serotonin reuptake inhibitor（SSRI）,valproate and so on are often selected in clinic.Studies have shown that gabapentin in the treatment of alcohol dependence can reduce the amount of alcohol consumption,delay the relapse of patients and improve the ethics rate of patients.This study intends to select two kinds of commonly used clinical drugs as a comparison,compare the efficacy difference between gabapentin and gabapentin,and explore the role of gabapentin in the treatment of alcohol dependent patients,so as to guide clinical treatment.Objective（1）To compare the efficacy and safety of gabapentin,valproate and SSRI antidepressants in patients with alcohol dependence.（2）To clarify the medium and long-term preventive effect of gabapentin on drinking again after abstinence in patients with alcohol dependence.MethodFrom September 2020 to September 2021,72 male patients with alcohol dependence were selected from the Fifth Department of psychiatry of our hospital.The patients were randomly divided into gabapentin group（1200-1800 mg）,valproate group（0.5-1.0g）and antidepressant group（SSRI drugs,equivalent to sertraline 50-100mg）.Two weeks after admission,all of the patients received scales assessment,including Clinical Alcohol Withdrawal Rating Scale（CIWA-Ar）,Pennsylvania Alcohol Craving Scale（PACS）,Epworth Sleepiness Scale（EPS）,Pittsburgh Sleep Scale（PSQI）,Mini Mental State Scale（MMSE）,Trail Making Test-B,（TMT-B）,Digital Span Test（DST）,Verbal Fluency Test（VFT）,Ho Pkins Verbal Learning Test Revised,（HVLT-R）,Hamilton Anxiety Scale（HAMA）and Hamilton Depression Scale（HAMD）,and these scales were evaluated again at weeks2 and 4.At the same time,the results of laboratory examination and ECG were recorded at baseline and week 4.At the 8th,16 th and 24 th weeks,the patients were followed up by telephone to record whether they drank again.For example,the time of drinking again was recorded,the withdrawal days were calculated,and the amount of drinking（g）and frequency of drinking（day / week）were asked.Results1.There was no significant difference in age,years of education,drinking time,addiction time and previous abstinence times among the three groups（P > 0.05）.2.Efficacy of gabapentin in maintenance period of patients with alcohol dependence.（1）In the baseline,there was no significant difference in the clinical alcohol withdrawal Rating Scale（CIWA AR）,Pennsylvania alcohol craving scale（PACS）,Epworth Sleepiness Scale（EPS）,Pittsburgh Sleep Scale（PSQI）,Mini Mental State Scale（MMSE）,connection test B（TMT-B）,digit span test（DST）,word fluency test（VFT）,Hopkins Word Learning Test revised（HVLT-R）,Hamilton Anxiety Scale（HAMA）and Hamilton Depression Scale（HAMD）among the three groups（P >0.05）.（2）At week 2,there was no significant difference in alcohol withdrawal Rating Scale（CIWA AR）and Epworth Sleepiness Scale（EPS）among three groups（P >0.05）.There was significant difference between the groups of Pennsylvania alcohol craving scale（PACS）（P < 0.05）.The pairwise comparison showed that compared with valproate group,the PACS score of SSRI group and gabapentin group decreased,and the difference was statistically significant（P < 0.05）,suggesting that SSRI drugs and gabapentin.may alleviate the craving degree of patients in the early stage than valproate.（3）At week 4,there was no significant difference in clinical alcohol withdrawal Rating Scale（CIWA-Ar）,Pennsylvania alcohol craving scale（PACS）,Pittsburgh Sleep Scale（PSQI）,Mini Mental State Scale（MMSE）,connection test B（TMT-B）,digit span test（DST）,word fluency test（VFT）,Hopkins Word Learning Test revised（HVLT-R）,Hamilton Anxiety Scale（HAMA）,and Hamilton Depression Scale（HAMD）（P > 0.05）.（4）At week 8,there were statistically significant differences in the rehydration rate,drinking frequency,amount of alcohol per drink and amount of alcohol per week among the three groups（all P < 0.05）.The pairwise comparison showed that the rehydration rate,drinking frequency,amount of alcohol per drink and amount of alcohol per week in gabapentin group were lower than those in valproate group and SSRI group.（5）At the 16 th week,the rehydration rate,drinking frequency and drinking volume of gabapentin group were less than those of the other two groups,but the difference was not statistically significant（P > 0.05）.（6）At the 24 th week after enrollment,the rehydration rate,drinking frequency and alcohol consumption of gabapentin group were also lower than those of the other two groups,but the difference was not statistically significant（P > 0.05）.（7）The withdrawal days of patients during the whole follow-up period were recorded and compared among the three groups.There was a significant difference in the withdrawal days among the three groups（P < 0.05）.The pairwise comparison showed that there was a significant difference between gabapentin group and SSRI group（P < 0.05）,suggesting that gabapentin group can maintain a longer withdrawal time compared with SSRI group.3.Safety of three groups of drugs in maintenance treatment of patients with alcohol dependence（1）At the 4th week,there was significant difference among the three groups in Epworth Sleepiness Scale（EPS）（P < 0.05）.The pairwise comparison showed that the EPS score of gabapentin group was higher than that of SSRI group（P < 0.05）.It is suggested that the degree of sleepiness in gabapentin group is higher than that in SSRI group.（2）At baseline,there was no significant difference in the results of laboratory examination and ECG among the three groups（P > 0.05）.（3）At the fourth week of enrollment,there was no significant difference in the results of laboratory examination and ECG among the three groups（P > 0.05）.（4）There was no significant difference in the results of laboratory examination and ECG before and after administration in gabapentin group（P > 0.05）.Conclusion（1）When gabapentin is used to treat patients with alcohol dependence,the improvement of withdrawal,sleep,emotion and cognitive symptoms is basically the same as that of valproate and SSRI drugs.（2）In the short-term treatment of alcohol dependent patients,gabapentin m ay better reduce the rehydration rate of patients than valproate drugs and SSRI drugs.（3）During the observation period of 24 weeks,gabapentin may maintain a longer withdrawal time and improve the ethics rate of alcohol dependent patien ts.（4）Gabapentin may make patients have higher drowsiness than SSRI drugs.Compared with valproate and SSRI drugs,gabapentin had no significant side effects on blood routine examination,liver and kidney function and ECG.