Naltrexone is an opiate antagonist that is used for the treatment of alcohol dependence. Research shows that it is particularly useful in decreasing heavy drinking. It is found to be more helpful in people who are still drinking versus people who are abstaining already from alcohol. It works to extinguish drinking by removing the positive reinforcement effects to alcohol on the brain. Multiple studies have demonstrated its efficacy in reducing the frequency and severity of relapses. The multi-center COMBINE study showed the usefulness of naltrexone in the primary care setting.

A typical dose of oral naltrexone is 50mg/day (dosed qday or bid). A once-monthly, extended-release injectable formulation (Vivitrol) is available as well and is typically dosed at 380 mg qmonth. Common side effects include diarrhea and abdominal cramping. There is an FDA black box warning about the potential for liver damage, but further research has shown that this is a rare side effect and occurred only in patients who were given a higher-than-recommended dose. Still, some physicians elect to check baseline LFTs and monitor them periodically. It is important to avoid using opiate medications while taking naltrexone.

Acamprosate (Campral) is approved by the FDA for treatment for alcohol dependence with other supportive therapies. Studies have shown it to be helpful in both reduced consumption of as well as maintaining abstinence from alcohol. Its mechanism of action is still under study. Common side effects include diarrhea, headaches, insomnia and impotence. Less common but more serious side effects include irregular heart rate and effects on blood pressure. Acamprosate is cleared through the kidneys, so kidney function should be assessed prior to using the medication.

Disulfiram (Antabuse) works by producing an acute sensitivity to alcohol consumption by inhibiting acetaldehyde dehydrogenase. With disulfiram on board, 5-10 minutes after alcohol consumption, the patient will experience “hangover” symptoms for the next 30 minutes-several hours. These symptoms include flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, headache and mental confusion.

Typically the regimen is initiated by prescribing 500mg qday x 1-2weeks then the maintenance dose is 125-500mg qday until the patient has fully abstained from alcohol. There is no tolerance to disulfiram – the longer it is taken, the stronger its effects. The main drawback is that the patient has to be motivated to take the medication consistently.

This medication does not decrease craving for alcohol, so it is important that it be used in conjunction with supportive therapy and motivational interviewing. Common side effects include headache and metallic taste in mouth. It should not be taken within 12 hours of drinking alcohol and its effects can last for up to 2 weeks.

Gabapentin (Neurontin) was discussed in part 1 of this series as a treatment for prevention of withdrawal seizures but can also be used to maintain abstinence and prevent relapse.

All these medications work best in the context of psychosocial treatment.  At least three forms of psychosocial therapy have been shown to be effective at treating alcoholism, with roughly similar success rates. These include:

• Cognitive behavioral therapy, a form of psychotherapy focusing on identifying and modifying negative thoughts and thought patterns.

• 12-step facilitation, in which patients are encouraged to enter 12-step programs such as, Alcoholics Anonymous.
• Motivational enhancement therapy, a patient-centered approach in which counselors try to get patients to think about and express their motivations for change and to develop a personal plan that can help them make the necessary changes.

Patients with mild or moderate alcohol withdrawal syndrome can be treated as outpatients, which minimize expense and allows for less interruption of work and family life. Patients with severe symptoms or who are at high risk of complications should receive inpatient treatment.

Important Considerations:

• Blood and breath alcohol concentration levels correlates more accurately to cognitive impairment than urine concentration levels
• Intoxication itself is not a reason for psychiatric admission, but strongly consider it if the patient has other risk factors (current SI, no social contacts, history of depression, history of suicide attempts)
• Consider medical admission if history of complicated withdrawal (i.e. seizures, DTs)

Withdrawal Symptoms: generally peak at 24-36 hours

1. tremors
2. nausea/vomiting
3. anxiety/agitation
4. tachycardia/hypertension
5. diaphoresis
6. insomnia
7. hallucinations (in 5-10% of patients)
8. grand mal seizures (less than 5% of patients, peaks 24-48 hours)
   1. highest risk: length of alcohol dependence, history of withdrawal seizures
9. delirium tremens (less than 5% of patients, peaks 2-5 days)
   1. symptoms: disorientation, confusion, autonomic hyperactivity, can be lethal

Assessment: use a rating scale to help inform treatment: CIWA scale (link included)

http://www.ci2i.research.va.gov/paws/pdfs/ciwa-ar.pdf

Treatment:

1. Include thiamine 100 mg qday, folate 1 mg qday, multivitamin qday to prevent Wernicke’s encephalopathy (triad: confusion, ataxia, opthalmoplegia)

Give thiamine before patient eats or receives an IV

2. Include gabapentin 400mg tid for seizure prevention (as long as kidney function is fine). Also helpful for abstinence and relapse prevention, can be used past the acute phase of withdrawal
3. Can provide benzodiazepine taper to minimize discomfort of alcohol withdrawal

Use Librium as default, but use Ativan if liver function is compromised (ALT/AST over 300) or if patient is over 60yo.

–Librium sample taper:

Day 1: 50mg q4hr x 6 doses

Day 2: 50mg q6hr x 4 doses

Day 3: 50mg q8hr x 3 doses

Day 4: 25mg q6hr x 4 doses

Day 5: 25mg q12hr x 2 doses

Day 6: 25 mg x 1 dose then DC

–Ativan sample taper:

Day 1: 2mg q6hr x 4 doses

Day 2: 2mg q8hr x 3 doses

Day 3: 1mg q6hr x 4 doses

Day 4: 1mg q8hr x 3 doses

Day 5: 0.5mg q6hr x 4 doses

Day 6: 0.5mg q8hr x 3 doses

Ideally have patient return to clinic daily for benzodiazepine prescription and to check vitals and breathalyzer. The patient should have a reliable family member or friend who can check on them daily or stay with them during the first 3-5 days of treatment.

Successful treatment of AWS is the initial step toward long-term abstinence. Abstinence is unlikely if the patient does not enroll in a long-term treatment program

Next week’s e-weekly will address on-going management of alcohol addiction and treatment.