ATrain Education

 

Continuing Education for Health Professionals

Alcohol Use Disorders and Opioid Dependence Treated in Primary Care

Module 3

Pharmacotherapies for Substance-Related and Addictive Disorders

The role of medication assisted treatment, the provision of medications as part of comprehensive care, varies according to the needs and goals of the patient [28, 29]. Reduction in substance use, overdose prevention, withdrawal from dependence, relapse prevention, and maintenance are all legitimate goals potentially served by Food and Drug Administration (FDA) approved medications. Only pharmacotherapies indicated for use in addictive disorders are presented in Table 1. Off-label use of medications without an FDA approved indication for addictive disorders and the role of pharmacotherapy for cooccurring psychiatric and medical disorders associated with relapse are beyond the scope of this paper.

 

Note. This table highlights some of the properties of each medication. It does not provide complete information and is not intended as a substitute for the package inserts or other drug reference sources used by clinicians. For patient information about these and other drugs, the National Library of Medicine provides MedlinePlus (http://medlineplus.gov/). Adapted from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Helping Patients Who Drink Too Much: A Clinician’s Guide. Updated 2005 Edition (NIH Publication number 07-3769). Bethesda, MD: NIAAA, National Institutes of Health, 2007; Substance Abuse and Mental Health Services Administration. 2013; and Alkermes, Inc. Medication Guide. Revised November 2010 (VIV993B). Waltham, MA: Author, 2010a (Accessed at http://www.vivitrol.com/Content/pdf/medication guide.pdf).

Pharmacotherapies in the Treatment of Substance Use Disorders

Medication

Dosage Form

Mechanism of Action

DEA Schedule

Application in Primary Care

Methadone

Tablet: 5mg, 10mg

Tablet for suspension: 40mg

Oral concentrate: 10 mg/mL

Oral solution: 5 mg/5 mL, 10 mg/5 mL

Injection: 10 mg/mL

Mu agonist at the mu opioid receptor and also possible antagonist at the N-methyl-D-aspartate receptor

CII

Based on federal regulations primary care integration into/or linkage with Opioid Treatment Programs is required

Buprenorphine-naloxone

Sublingual film:buprenorphine/
  naloxone 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg, and 12 mg/3 mg

Sublingual tablet: buprenorphine/
  naloxone 1.4 mg/0.36 mg, 2 mg/0.5 mg, 5.7 mg/1.4 mg, and 8 mg/2 mg

Buprenorphine: Partial mu agonist at the mu opioid receptor and an antagonist at the kappa opioid receptor

Naloxone: antagonist at mu opioid receptor and produces withdrawal signs/symptoms

CIII

To prescribe buprenorphine in a primary care setting, a physician must obtain a waiver from SAMHSA and be issued an additional registration number by the DEA (see http://www.dpt.samhsa.gov/ for details)

Buprenorphine

 

Partial mu agonist at the mu opioid receptor and an antagonist at the CIII kappa opioid receptor

CIII

Buprenorphine without naloxone products are indicated only for patients with documented hypersensitivity to naloxone

Naltrexone

Tablets: 25 mg, 50 mg, and 100 mg

Extended-release injectable suspension: 380 mg/vial

Opioid antagonist with highest affinity for the mu opioid receptor

Little or no opioid agonist activity

Produces some pupillary constriction by an unknown mechanism

n/a

Provided by prescription; naltrexone provides a blockade of opioid receptors, reduces cravings, and diminishes the rewarding effects of alcohol and opioids

Extended-release injectable naltrexone is indicated for the prevention of relapse to opioids or alcohol

Acamprosate

Delayed-release tablet: 333 mg

Mechanism not completely understood; studies suggest that acamprosate may interact with glutamate and GABA neurotransmitter systems centrally

n/a

Provided by prescription; acamprosate reduces symptoms of protracted abstinence associated with chronic alcohol exposure and alcohol withdrawal

Disulfiram

Tablet: 250 mg, 500 mg

Blocks oxidation of alcohol at the acetaldehyde stage

n/a

When taken in combination with alcohol, disulfiram causes severe physical reactions, including nausea, flushing, and heart palpitations

The knowledge that such a reaction is likely if alcohol is consumed acts as a deterrent to drinking

Naloxone

Injection: 0.4 mg/mL, 1 mg/mL, and 0.4 mg/0.4 mg

Opioid antagonist; in vitro studies suggest that it antagonizes opioid effects by competing for the mu, kappa, and sigma opiate receptor sites in the CNS, with the greatest affinity for the mu receptor

n/a

Naloxone is the antidote to opioid toxicity

It reverses the respiratory depression induced by opioids

It has no psychoactive properties and no abuse potential

To be effective naloxone should be administered as soon as possible when opioid overdose is suspected, usually prior to transport to an emergency department

Because of this naloxone should be prescribed to persons at risk of opioid overdose for emergency administration

Education and training should be provided to the patient and family members on how to reduce risk, recognize, and respond to overdose appropriately

Naloxone is typically dispensed in an injectable form and may require prescription of syringes

 

Medically Managed Withdrawal (Detoxification)

Medically managed withdrawal or detoxification may be a necessary first step in recovery for patients, who are physically dependent on alcohol, opioids, or sedative/hypnotics. Medically managed withdrawal serves to palliate otherwise intolerable withdrawal symptoms and reduce the risk of serious medical consequences. Inpatient medically managed withdrawal is appropriate for patients at risk for severe withdrawal, delirium tremens, or with significant medical and psychiatric comorbidities [3, 12, 30]. Institutional protocols can be developed to assist in determining inpatient versus outpatient detoxification [12, 30, 31]. Regardless of the setting, medically managed withdrawal is not by itself addiction treatment but rather a bridge to treatment. Relapse and even death from overdose are not uncommon for those patients who do not successfully transition to treatment and/or support program to address chronic relapse to drug and/or alcohol use or abuse.

Pharmacotherapy for Alcohol Use Disorders

Patients who report one or more heavy drinking days in the past year or who have, for example, an AUDIT score greater than 8 should receive further assessment beyond a screening in primary care [2, 10, 32, 33]. In determining the need for pharmacotherapy, consideration should be given to

  1. the factors motivating a patient toward treatment,
  2. the patient’s stage of change,
  3. the potential for relapse,
  4. the severity of any concomitant medical and psychiatric problems,
  5. the patient’s ability to tolerate medications, and
  6. whether the patient is pregnant.

If a patient engages in heavy drinking but does not meet the criteria for an alcohol use disorder, or meets only the criteria for mild alcohol use disorder, the clinician should use his or her professional judgment in helping the patient decide whether reducing or abstaining from alcohol is the more appropriate goal, based on factors such as a family history of alcohol problems and the patient’s age or history of traumatic injuries related to drinking [33]. Information from family members and significant others can provide useful perspectives on the patient’s status, as can communication with or records from clinicians who treated the patient in the past [16, 34]. The provider and patient should mutually agree on an initial goal and be willing to refine and revise that goal as treatment progresses [2]. For example, in working with a patient who is unwilling to set a goal of complete abstinence, the clinician should support the patient in reducing his or her drinking as an interim goal, while maintaining that complete abstinence is the safer strategy, with a greater chance of long-term success [10, 16, 35].

Disulfiram

Disulfiram, the initial medication approved by the FDA for the treatment of alcohol dependence, is an alcohol aversive or alcohol sensitizing agent [5]. As such, disulfiram causes an acutely toxic physical reaction approximately 10–30 minutes after ingestion of alcohol. The reaction to alcohol can be multisystem comprising warmth and flushing of the upper chest and face, hyperventilation, blurred vision, chest pain, tachycardia, vertigo, marked confusion, and weakness. The reaction is usually proportional to the amount of alcohol and disulfiram ingested. Disulfiram does not reduce the urge to consume alcohol but does provide motivation to not use alcohol.

Patients who are good candidates for treatment with disulfiram include those who are motivated for treatment and want to achieve abstinence, those who are medically appropriate, those who can receive supervised dosing, and those who are capable of understanding the consequences of drinking alcohol while taking disulfiram. It also may be an appropriate short-term therapy for a patient in recovery who anticipates being in a situation that may trigger craving for alcohol (such as a family holiday visit) and who requests an additional incentive to remain abstinent [2, 36, 37]. Steps in initiating treatment with disulfiram are as follows [2, 36, 37].

  1. Wait until the patient has abstained from alcohol for at least 12 hours and/or until the breath or blood alcohol level is zero.
  2. Perform an electrocardiogram if clinically indicated (as in a patient with a history of heart disease).
  3. Confirm the absence of allergy to disulfiram. Monitoring should include confirmation of abstinence with breath or blood alcohol tests if needed, liver function, and other tests as clinically indicated. Patient education and ongoing supervision, as well as contingency management intervention, promote the efficacy of disulfiram.

Naltrexone

The low rate of retention and adherence encountered with oral naltrexone led to the development of the extended-released injectable formulation, which was approved by FDA for the treatment of alcohol use disorders in 2006 [2, 38]. Oral naltrexone is most effective when prescribed for patients who are highly motivated and/or supported with observed daily dosing [39, 40]. Either form of naltrexone appears to be effective in the following patient populations: patients who have a history of opioid use disorder and who are seeking treatment for alcohol use disorder because naltrexone will reduce the reinforcing effects of and curb cravings for both opioids and alcohol; patients with intense craving for alcohol during treatment because they may experience greater medication benefit than patients with low levels of craving for alcohol; patients who have a family history of alcohol use disorders [38–41], both laboratory studies and clinical trials suggest that patients with a family history of alcohol problems may benefit more from treatment with naltrexone than patients who do not have such a history [42]; and patients with the Asp40 allele of the gene encoding the mu opioid receptor (OPRM1) [43]. Extended-release injectable naltrexone should be considered for patients who have problems with treatment adherence or do not have adequate support to comply with daily dosing [38].

Although patients may experience fewer medication side effects if they are abstinent from alcohol when they begin treatment with naltrexone, it is safe for patients to begin taking the medication during medically supervised withdrawal or if they are actively drinking [2, 44].

Acamprosate

Acamprosate is an FDA approved medication for use in postwithdrawal maintenance of alcohol abstinence. Acamprosate normalizes the alcohol-related changes in the brain due to chronic alcohol consumption and reduces the symptoms of withdrawal, thereby reducing the potential to relapse to alcohol consumption [5]. A recent Cochrane review of 24 studies showed that acamprosate had a moderate effect on preventing a return to drinking and on increasing the number of days being abstinent [45]. Acamprosate appears to be most effective for patients who are motivated with a goal of complete abstinence as opposed to reduced consumption [46]. Thus, acamprosate can be utilized as a component of a treatment paradigm with the goal of maintenance of abstinence for individuals who are alcohol-dependent. Acamprosate typically is initiated five days after the cessation of alcohol use. However, it can be used safely in combination with alcohol (and benzodiazepines) and thus can be started during medically supervised withdrawal. The drug typically reaches full effectiveness in 5 to 8 days [2, 5, 36]. Acamprosate therapy should be continued even if a patient relapses to alcohol use [5]. Patients who may be particularly suited to treatment with acamprosate are those with hepatic disease; those who are being treated with opioids for pain or addiction because acamprosate is eliminated renally and does not affect endogenous or exogenous opioids; and those who are coping with multiple medical issues and who are taking many other medications because there are no clinically significant drug interactions with acamprosate.

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