The guideline reviews the rationale for use and possible side effects for 5 medications that have been shown to be effective for the treatment of AUD: naltrexone, acamprosate, disulfiram, gapapentin, and topiramate. These treatments are meant as part of an interdisciplinary approach to the treatment of substance abuse, not as a substitute.

Naltrexone is an opioid antagonist. It is found to be more helpful in people who are still drinking versus people who are already abstaining from alcohol. It works to extinguish drinking by removing the positive reinforcement effects to alcohol on the brain. Studies have shown that it can help prevent the development of severe alcohol use disorder. It does not necessarily help on its own to achieve abstinence from alcohol, but even reduction of heavy drinking can reduce some of the major negative effects of alcohol use, including medical and occupational effects. Studies have shown that it is effective in reducing and preventing relapses into heavy drinking. It can be particularly helpful in people who have high cravings for alcohol. A typical dose of oral naltrexone is 25 mg 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 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 renally so it should be avoided in patients with significant renal impairment.

Disulfiram 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. The 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.

Naltrexone and acamprosate have the best evidence backing their use in treating AUD. Disulfiram can be helpful if a patient is seeking abstinence and is motivated. Topiramate and gabapentin can be considered as treatment options once naltrexone and/or acamprosate have been tried first. More studies need to be conducted to assess their effectiveness in AUD, but generally the concern is that there is a higher risk of problematic side effects with these two medications compared to naltrexone and acamprosate. Patients taking topiramate are at an increased risk of cognitive dysfunction, dizziness and loss of appetite, whereas patients taking gabapentin may experience fatigue, insomnia, and headache.

The full practice guideline is included here as a reference for those who are interested in more detailed information.

https://psychiatryonline.org/doi/pdf/10.1176/appi.books.9781615371969

Pharmacological treatment is an important part of the interdisciplinary approach to effectively treating AUD and reducing its negative outcomes.

Some experts in the field of substance abuse are arguing for a change in the thinking of how to treat Alcohol Use Disorder (AUD). Most clinicians, with the focus being on sobriety, refer patients to detoxification and substance abuse programs, which is appropriate. Many clinicians do not consider treatment options to reduce alcohol use as a treatment goal. It has been shown that even avoidance of heavy drinking can reduce some of the major negative effects of alcohol use, including medical and occupational effects.

Naltrexone is a medication that blocks opioid receptors. It works by removing the positive reinforcement of drinking on the brain. Studies have shown that it can help prevent the development of severe alcohol use disorder. It does not necessarily help on its own to achieve abstinence from alcohol, but even reduction of heavy drinking can have improvements in outcomes. Studies have shown that it is effective in reducing and preventing relapses into heavy drinking. It can be particularly helpful in people who have high cravings for alcohol. There is a common belief that if someone has a propensity towards addiction, that they should avoid any exposure to a substance. A medication like this could change that way of thinking, that even eliminating heavy drinking and limiting the euphoric effects of alcohol to reduce the amount of alcohol consumed can make a real difference in measurable health and lifestyle outcomes.

Please see the e-Weekly newsletter dated August 25, 2016 for more details on dosing naltrexone and the side effects to monitor for. The newsletter also discusses other medications that can be useful for treating alcohol abuse.

Traditionally different aspects of substance abuse treatment and related mental health concerns have remained separate – separate detoxification centers, separate mental health therapy and psychiatry, separate substance abuse therapy programs. In an effort to integrate substance abuse treatment, more and more, alcohol treatment programs are starting to offer medication augmentation to therapy. This integrative approach will hopefully lead to better success, both in terms of achieving and maintaining sobriety, for patients.

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.