Alternative to benzodiazepines or clomethiazole in the treatment of alcohol withdrawal syndrome?
Alcohol withdrawal syndrome (AWS) is a potentially life-threatening condition. A meta-analysis published in the journal Pharmacopsychiatry in September 2019 examines the effect of the combination of tiapridal and carbamazepine in the treatment of AWS. Is this combination a viable alternative to benzodiazepines or clomethiazole?
Carbamazepine and tiapride
Carbamazepine is an anticonvulsant commonly used in the treatment of seizure states and neuropathic pain. Several studies have also demonstrated its effectiveness in the therapy of AWS. Tiapride is an antagonist of dopamine D2 and D3 receptors. It is used in the treatment of dyskinesias, negative symptoms of psychoses, agitation, and aggression in the elderly.
The combination of tiapride and carbamazepine effectively influences the symptoms of AWS without unwanted sedation. In this combination, tiapride acts as an anxiolytic, while carbamazepine works on hallucinations, delirium tremens, and epileptic seizures. Compared to commonly used benzodiazepines, there is no risk of misuse and dependence. The lack of evidence and the absence of a meta-analysis addressing this issue, however, leads to caution in using this combined therapy in clinical practice.
The presented work aims to map the data published so far and summarize the efficacy and safety of the combination of tiapride and carbamazepine in the therapy of AWS.
Evaluated studies
Studies published up to May 2018 were included. The authors used the databases PubMed, EMBASE, OVID, Cochrane, Google Scholar, and Scopus for the search. The keywords for the search were tiapride, carbamazepine, alcohol withdrawal, alcohol dependence and alcohol abuse. Based on these keywords, 290 articles were initially found. After excluding irrelevant works, 7 studies remained.
Most of the evaluated studies used the Clinical Institute Withdrawal Assessment (CIWA) or its revised version (CIWA-Ar) to assess the severity of withdrawal symptoms. This scale assesses 10 common withdrawal symptoms: nausea and vomiting, tremor, paroxysmal sweating, anxiety, agitation, sensory disturbances, auditory disturbances, visual disturbances, headaches, and orientation. Each item is rated independently (0−7 points, orientation is rated 0−4 points). The maximum score is 67. The total number of points corresponds to the severity of the withdrawal syndrome (mild < 15; moderate 16−20; severe > 20).
Results and discussion
The combination of tiapride and carbamazepine can effectively reduce withdrawal symptoms in alcohol-dependent patients (p < 0.0001). The beneficial effect of this therapy also persisted over time. Tiapride and carbamazepine potentiate each other in influencing the vegetative manifestations of AWS and reduce the risk of epileptic seizures. According to Franz et al., the mentioned combination could reduce the occurrence of secondary epileptic seizures in patients with AWS more effectively than clomethiazole. The effect is also achieved faster when using tiapride + carbamazepine than when administering clomethiazole.
Conclusion
According to this meta-analysis, the combination of tiapride and carbamazepine in the treatment of AWS is an effective alternative to benzodiazepines and clomethiazole. However, its safety needs to be verified in further studies.
(dos)
Sources:
1. Latifi S., Messer T. The efficacy of tiapride and carbamazepine combination therapy in reducing alcohol withdrawal symptoms: a systematic review and meta-analysis. Pharmacopsychiatry 2019 Sep; 52 (5): 209–216, doi: 10.1055/a-0795-3689.
2. Franz M., Dlabal H., Kunz S. et al. Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole. A pilot study. Eur Arch Psychiatry Clin Neurosci 2001; 251: 185–192, doi: 10.1007/s004060170039.
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