“Alcohol addiction is a disease that, too often, is criminalised instead of hospitalised,” says Dr Leverne Mountany, a psychiatrist that specialises in addiction at Riverfield Lodge in Gauteng, as well as a member of the South African Addiction Medicine Society (SAAMS), “This has a direct impact on social welfare with people suffering from the disease ending-up in prison, instead of treatment facilities.”
According to the South African Addiction Medicine Society Guidelines for the pharmalogical management of alcohol use disorder, “The disease burden attributable to alcohol consumption is significant and represents a substantial health, social and economic burden worldwide.
“It is an international priority area. Globally, harmful use of alcohol is estimated to result in 3.3 million deaths each year, which is 5.9% of all deaths and 5.1% of the global burden of disease. It is estimated that 320 000 young people between the age of 15 and 29 die annually from alcohol-related causes, resulting in 9% of all deaths in that age group.”
The incidence and prevalence in South Africa is above the world and region average, with per capita alcohol consumption among the highest in the world.
A South African perspective
According to a statistical update from the World Health Organization (WHO), tracking alcohol consumption per capita, across 194 countries, South Africa’s alcohol consumption rate has climbed, with the country now ranked as one of the top 20 biggest drinking nations in the world.
The data shows that in 2015, pure alcohol consumption (per litre) in South Africa was at 11.5 litres per capita per year – up from 11.0 litres in 2014.
This pushes South Africa up to the third biggest drinking nation in Africa, and the 19th biggest drinking nation in the world, tied with Poland.
South Africa has among the highest abstention rates in the world (72.9%) and the prevalence of heavy drinking episodes or ‘binges’, is above the world and regional average (45.4%), placing South Africans amongst the riskiest drinkers in the world. In fact, South Africa rates among the top five risky drinking countries in the world with a WHO ‘Pattern of Drinking Score’ of four out of a potential five. The higher this score, the larger the alcohol-attributable burden of disease for a country.
Schneider et al estimated the deaths in South Africa due to alcohol to be at 7.1% (6.6-7.5%) and the years lost due to disability and early death due to alcohol at 7% (6.6-7.4%).
Alcohol use disorder and diagnostic criteria
The ICD 10 definition is as follows: “A cluster of behavioural, cognitive and physiological phenomena that develop after repeated alcohol use and that typically include a strong desire to consume, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to alcohol use than to other activities and obligations, increased tolerance and sometimes a physical withdrawal state.”
The DSM V criteria involves having a number of manifestations, a minimum of two, in a 12 month period that are associated with a pattern of alcohol abuse that has led to dysfunction.
According to Mountany, these include, “Physiological manifestations, convulsions, hallucinations, sweating, diarrhoea, vomiting and tremors. Alcohol withdrawal can further mimic and/or exacerbate anxiety problems.
“Tolerance, loss of control and compulsive use despite negative consequences and dysfunctions within the workplace, relationships and finances, are further evidence of alcohol use disorder.”
A brief description of the neurobiological components of alcohol use disorder is necessary to improve the understanding of described treatment options.
Treatment options are based on targeting GABA pathways. Benzodiazepines are the primary treatment option for alcohol withdrawal and act by enhancing inhibitory GABA action.
Pharmacological management of alcohol withdrawal syndrome
Benzodiazepines are first-line treatment for the management of the alcohol withdrawal syndrome and are shown to reduce the severity of withdrawal including reducing the risk of seizures, delirium tremens and death. Different benzodiazepines have been shown to be equally effective in the management of alcohol withdrawal.
The choice of benzodiazepine is determined by the half-life. Shorter-acting benzodiazepines (e.g. Oxazepam, Lorazepam) may result in greater discomfort as the withdrawal symptoms tend to recur when the serum benzodiazepine levels decline. The shorter acting benzodiazepines work better in
fixed dose regimens and have the advantage of being safer in patients that have significant liver dysfunction. Longer acting benzodiazepines (e.g. Diazepam, Chlordiazepoxide, Clonazepam) may be associated with a ‘smoother’ withdrawal and less breakthrough withdrawal features. These may also be associated with better seizure control and effectiveness in delirium tremens. However, these
agents may lead to excessive accumulation, with drowsiness in patients with hepatic dysfunction and the elderly.
The duration of pharmacological management for alcohol withdrawal should be individualised and on average, lasts about seven days. Benzodiazepines can be used as a fixed dose regimen, a symptom triggered regimen or using a frontloading regimen.
A fixed dose benzodiazepine regimen implies that a predetermined fixed dose with fixed intervals is used and additional medication may be used to ‘top-up’ according to clinical need.
When symptom triggered regimes are used, benzodiazepine doses are determined by the presence of objective withdrawal features. Although the use of this regimen has shown to use less medication, it requires inpatient care and adequately trained staff.
The CIWA-Ar scale can be used as an objective assessment of the withdrawal features when using a symptom triggered withdrawal regime. It is suggested that if this approach is used, that monitoring takes place six hourly for mild
withdrawal features, four hourly for moderate withdrawal features and two hourly or less for severe withdrawal features.
Clinical observation should always include vital signs (blood pressure, pulse rate, respiratory rate).
Front-loading detoxification implies that high doses of long-acting benzodiazepines are administered early in the withdrawal phase and the long duration of action then results in a ‘self-tapering’ effect. This is usually followed by a symptom triggered dosing method.
Treating alcohol withdrawal with chlordiazepoxide
According to the American Academy of Family Physicians (AAFP), “Several detoxification medication regimens are appropriate for use in alcohol withdrawal. Chlordiazepoxide, one of the most frequently used medications, has a well-documented efficacy profile. This drug has a wide therapeutic window and is “self-tapering” because of its long half-life. Thus, chlordiazepoxide is an ideal drug for use in outpatient detoxification. One treatment option is to “front load” the patient to provide adequate sedation. Then small amounts of the drug are added as needed during the detoxification period.”
|SCHEDULE||DAY 1||DAY 2||DAY 3||DAY 4|
|Rigid||50 to 100 mg four times daily||50 to 100 mg three times daily||50 to 100 mg twice daily||50 to 100 mg at bedtime|
|Flexible||50 to 100 mg every 4 to 6 hours as needed based on symptoms*||50 to 100 mg every 6 to 8 hours as needed||50 to 100 mg every 12 hours as needed||50 to 100 mg at bedtime as needed|
|Front loading†||100 to 200 mg every 2 to 4 hours until sedation is achieved; then 50 to 100 mg every 4 to 6 hours as needed||50 to 100 mg every 4 to 6 hours as needed||50 to 100 mg every 4 to 6 hours as needed||None|
*—These symptoms include pulse rate greater than 90 per minute, diastolic blood pressure greater than 90 mm Hg or signs of withdrawal.
†—Frequently, very little additional medication is necessary after initial loading.
Please note: The above regimes are merely examples and that the doses of benzodiazepines should be commenced and adjusted according to individual patient clinical requirements and clinical response.
It is important to note that benzodiazepines may cause sedation and respiratory suppression in overdose. Patients therefore require supervision and monitoring during detoxification. Extreme caution is advised with the concomitant use of other central nervous system depressants as these drugs may have a cumulative effect. Withdrawal from more than one CNS depressant requires expert care.
Other medication that can be used for alcohol withdrawal features:
Gabapentin is used as adjunct therapy for partial seizures and monotherapy for nonepileptic conditions such as management of certain pain related conditions, movement disorders, bipolar disorder and social phobia. Some recent studies have shown positive results in the management of alcohol withdrawal features.
Carbamazepine has shown to be effective in the treatment of the alcohol withdrawal syndrome.
c) Valproic acid and Divelproax:
May be effective, but are limited by side-effects.
Importantly, if a patient is on a regular anticonvulsant prescription, these need to be continued and levels monitored. If these are stopped the risk of withdrawal seizures are greater.
Other medication like alpha-adrenergic agonists (Clonidine), B-blockers and Calcium Channel Blockers should not be considered as monotherapy options for the management of alcohol withdrawal syndrome.
Thiamine (Vitamin B1) is necessary for several biochemical pathways in the brain, such as intermediate carbohydrate metabolism (for energy production), lipid metabolism (for production and maintenance of the myelin sheath) and production of amino acids and glucose derived neurotransmitters.
Those who misuse alcohol are at risk of thiamine deficiency due to associated factors such as self-neglect, malnutrition, low content of vitamins and minerals in alcoholic beverages, decreased transport of thiamine across intestinal mucosa, low capacity of the liver to store the vitamins and the impaired conversion of thiamine to the active compound thiamine pyrophosphate.
Thiamine deficiency may lead to Wernicke’s encephalopathy (WE), an acute neuropsychiatric syndrome, which is characterised by nystagmus, opthalmoplegia, mental state changes and ataxia of the gait or limbs. This triad is, however, only seen in 16% of patients.
The impact of complications of alcohol withdrawal on outcomes can be significant. The incidence of alcohol withdrawal seizures (AWS) is 4-6% and for delirium tremens (DT) 4-15%. Delirium tremens is the harshest consequence of alcohol withdrawal syndrome. The patient presents with a sudden alteration of awareness, attention and cognition (sometimes with hallucinations) and can fluctuate significantly.
Due to the significant associated morbidity and mortality, as well as the burden that these can create on medical services, strategies to predict risk for AWS and DT are important for appropriate and prompt management. Treatment of patients presenting with alcohol withdrawal seizures or delirium tremens should ideally be managed in a high care or intensive care setting.
Pharmacotherapy should primarily be the use of benzodiazepines (e.g. diazepam). Administered intravenously, the benzodiazepines should be given at a rate that reduces the alcohol withdrawal features and imparts slight drowsiness but the patient should still be arousable. Appropriate doses of benzodiazepines and continuous monitoring should be implemented concurrently until the delirium improves. Adjunct medication in the form of antipsychotics can be used to treat agitation and hallucinations, which are difficult to control with benzodiazepines alone. However, it is important to note that antipsychotics can alter QT intervals which can potentially aggravate seizure threshold.
Evidence has highlighted that medication and detoxification alone does not improve outcomes. The combination with psychosocial interventions has shown to be effective regarding positive outcomes. This is the ‘umbrella’ of holistic, multidisciplinary care.
These interventions can include individual therapy and group therapy including:
- ‘Self-help’ groups (Alcoholics Anonymous)
- Social skills
- Family and caregiver support
- Education and relapse prevention.
Alcohol use disorder is a chronic condition and therefore maintaining sobriety is a continuous process. “It is important to note that these strategies are not ‘stand-alone’ and have to be part of a comprehensive relapse prevention model, which includes an individualised psychosocial treatment plan,” states the guidelines.
Disulfiram acts as a psychological deterrent for alcohol use in motivated clients who struggle with sobriety. Acetaldehyde is generated in the liver during the metabolic breakdown of alcohol. Normally, the enzyme aldehyde dehydrogenase is responsible for converting acetaldehyde to acetate. Disulfiram is an inhibitor of aldehyde dehydrogenase and when alcohol is consumed while taking disulfiram the build-up of acetaldehyde leads to an aversive and potentially dangerous reaction, which includes tachycardia, flushing, nausea and vomiting, headaches, seizures and in severe cases death. The use of disulfiram thus requires informed consent from the patient.
The guideline states:
“Use disulfiram with caution if the patient has:
- Heart problems
- History of psychosis
- Kidney disease
Avoid in pregnancy and during breastfeeding. Also note possible drug interactions may occur with certain psychiatric medications, tuberculosis treatments and metronidazole.”
“Disulfiram should only be commenced 12 to 24 hours after the last alcohol intake and patients should also be advised to wait at least seven days after stopping the medication, should they decide to consume alcohol again.”
“Acamprosate is thought to act by normalising the NMDA-mediated glutaminergic neurotransmission, by reducing NMDA receptor transmission and enhancing GABA receptor transmission. It adds a modest effect in improving relapse to alcohol by reducing cravings for alcohol, thereby maintaining abstinence superior to placebo when used in conjunction with a psychosocial treatment intervention,” states the guidelines.
Acamprosate seems to be well tolerated with only occasional gastrointestinal side effects. Contraindications include pregnancy or breastfeeding, severe renal (creatinine clearance <30ml/min) and hepatic dysfunction. It can be started as soon as the patient is detoxified from alcohol or five days after last drink.
“Opioid antagonists, like Naltrexone, decrease the reinforcing effects of alcohol, which can result in a reduction in harmful drinking. Although Naltrexone is licensed in some countries for the treatment of alcohol use disorder (FDA approved Naltrexone for the treatment of alcohol use disorders); it is currently used off-label for this indication in South Africa,” says Mountany.
Naltrexone has been shown to have benefit in alcohol use disorder particularly in achieving outcomes like:
- Relapse rate
- Time to first drink
- Reduction in the number of drinking days
- Reduction in craving
- Improved GGT
The dose of naltrexone is 50mg daily, taken orally.
Other treatments that show promise:
“Emerging evidence is showing promising results for the use of Topirimate and Gabapentin, certain antipsychotics, Baclofen (muscle relaxant), sodium oxybate and ondansetron as medication options in relapse prevention,” states SAAMS.
References are available on request.