Issue Date: July-August 2011, Posted On: 5/15/2011
Professional Insights

Medications in the Treatment of Substance Use Disorders
It's Time to Overcome Pessimism About Successfully Treating Addictive Disorders

by Christina M. Delos Reyes, MD

I. Introduction

A. SUDs as medical illnesses


Christina M. Delos Reyes, MD
Christina M. Delos Reyes, MD

Alcohol and other substance use disorders have been recognized by the American Medical Association (AMA) as diseases since the mid-1960s. Despite this fact, the treatment of substance use disorders has remained largely segregated to free-standing substance abuse treatment centers, which rarely employ physicians and other medical staff. At the same time, physicians in hospitals and outpatient settings have found it difficult to treat patients with substance use disorders because of a lack of knowledge, a lack of skills, and a lack of effective medications to treat this population. For example, prior to 1984, only two medications were approved for the treatment of any substance use disorders (methadone for opiate dependence in 1947 and disulfiram for alcohol dependence in 1951). Since 1984, several more medications have been approved for the treatment of addictive disorders.


Segregation of addiction treatment from mainstream medicine has had other negative effects. Doctors tend to treat only the medical and psychiatric consequences of substance use disorders instead of focusing on the primary illness of addiction. Likewise, many providers of primary chemical dependency treatment mistrust the medical establishment and are very skeptical about the role of medications to treat addictive disorders. Not surprisingly, doctors and chemical dependency providers have developed a pervasive therapeutic pessimism about successfully treating addictive disorders.

B. Bringing medication-assisted treatment into the addiction field

Now is the time to integrate medication-assisted treatment into the chemical dependency field. In the most recent decade, numerous medications have been developed to treat the primary signs and symptoms of addictive disorders. This paper will review the medications most commonly used in the treatment of addictive disorders. Medications are currently used for two broad purposes in the treatment of substance use disorders. The first reason to use medications is to treat the symptoms of withdrawal during the process of detoxification. The second reason to use medications is to prevent relapse and to enhance long-term recovery from substance use disorders.

C. Medications during detoxification-treating symptoms of withdrawal

Not all drugs of abuse require medication treatment of withdrawal. Medications are most often used for the treatment of alcohol withdrawal, opiate withdrawal, and nicotine withdrawal. During the process of alcohol withdrawal, a cross-tolerant medication such as a benzodiazepine or phenobarbital is used to prevent seizures and delirium tremens. During the process of opiate withdrawal, medications such as clonidine, methadone, buprenorphine, or tramadol can be used to lessen the acute symptoms of opiate withdrawal, including but not limited to agitation, anxiety, muscle aches, sweats, chills, nausea, vomiting and diarrhea. During the process of nicotine withdrawal, nicotine replacement therapy is helpful in decreasing the acute signs and symptoms that may be present.

D. Medications during rehabilitation-enhancing relapse prevention

Medications can be used to prevent relapse to alcohol and other drug use. The Food and Drug Administration (FDA) has approved medications to treat alcohol, opiate, and nicotine dependence. At the present time, there are no FDA-approved medications to treat stimulant, marijuana, or hallucinogen dependence.

II. Medications for alcohol dependence

Disulfiram (Antabuse) is an oral medication that works by blocking the enzyme that breaks down alcohol. Therefore, toxic metabolites such as acetaldehyde accumulate in the body, causing very unpleasant symptoms such as severe nausea and vomiting and facial flushing. Disulfiram works as a deterrent to drinking alcohol and is most successful if patients are motivated to use it, or are closely observed taking it on a regular basis.

Naltrexone (Revia or Trexan) is an oral medication that works by blocking the opiate receptor. It was initially approved for the treatment of opiate dependence, but was later found to be useful in decreasing cravings for alcohol and in reducing the severity of alcohol relapses. Naltrexone also comes in the form of a monthly injection (Vivitrol) that helps to increase treatment adherence.

Acamprosate (Campral) is an oral medication that works by stabilizing the glutamate and GABA neurotransmitter systems in the brain. It helps to decrease cravings for alcohol and it increases periods of complete abstinence from alcohol. Acamprosate must be taken two to three times per day and is metabolized by the kidneys.

Other medications such as topiramate, baclofen, and ondansetron are currently being studied for their usefulness in treating alcohol dependence, but they are not yet FDA-approved for this indication.

III. Medications for opiate dependence

Naltrexone (Revia or Trexan) is an oral medication that blocks the opiate receptor. Patients that are taking opiates will not feel the rewarding effects of the opiates as long as they are taking naltrexone. However, its usefulness is limited by non-adherence to the treatment regimen. Recently, the FDA approved injectable naltrexone (Vivitrol) for the treatment of opiate dependence.

Methadone is an oral medication usually given in liquid form when used for the maintenance treatment of opiate dependence. Methadone is a full opiate agonist, which blocks cravings for opiates such as heroin without causing euphoria, sedation, or an analgesic effect. It allows individuals addicted to opiates to maintain abstinence and return to a productive life. At the present time, methadone for the maintenance treatment of opiate addiction is only available at federally licensed opiate treatment programs.

Buprenorphine is an oral medication that must be dissolved under the tongue; it currently comes in a tablet form or in the form of a thin film. It is a partial opiate agonist that is useful in both opiate detoxification and opiate maintenance treatment. Buprenorphine is safer than methadone in overdose situations. Unlike methadone, it can be prescribed directly from a qualified physician's office-based practice. Qualified physicians must complete special training and obtain a second DEA number in order to prescribe buprenorphine, and may treat only up to 100 patients with this medication at any given time. This medication comes in two forms-buprenorphine alone (known as Subutex) or buprenorphine combined with naloxone (known as Suboxone).

IV. Medications for nicotine dependence

There are three main classes of medications to treat nicotine dependence: nicotine replacement therapy (NRT), bupropion, and varenicline. Nicotine replacement therapy comes in five different forms. Three of these forms are available over-the-counter without a doctor's prescription-the nicotine patch, nicotine gum, and nicotine lozenges. The other two forms require a doctor's prescription and include the nicotine inhaler and nicotine nasal spray. All five types of NRT work by reducing the symptoms of nicotine withdrawal and nicotine cravings, thus allowing patients to achieve long-term abstinence from nicotine dependence.

Bupropion (Wellbutrin or Zyban) is an antidepressant medication taken orally that decreases nicotine withdrawal and nicotine cravings. It has effects on norepinephrine, dopamine, and acetylcholine receptors in the brain. Bupropion can be safely used in combination with NRT, and in fact these combinations appear to work better than NRT alone.

Varenicline (Chantix) is the first medication to specifically target the neurobiology of nicotine addiction. It is an oral medication that acts as a partial agonist at the nicotinic acetylcholine receptors in the brain. It reduces nicotine withdrawal, reduces craving, and results in a less satisfying smoking experience overall. In general, varenicline should not be combined with NRT. Varenicline must be used with caution in patients with psychiatric illness, because of recent case reports describing depressed mood, suicidal ideation, suicide, agitation and behavior changes in individuals attempting to quit smoking while taking this medication.

V. Medications for other drugs of abuse

There are currently no FDA-approved medications for the treatment of stimulant (i.e., cocaine or methamphetamine) dependence. Several medications which have been studied in this area include disulfiram, amantadine, bupropion, and desipramine, but results have been mixed. Research is currently being conducted on a cocaine vaccine, which would alter and possibly inactivate the effects of cocaine and other stimulants.

There are currently no FDA-approved medications for the treatment of marijuana dependence. Rimonabant (Acomplia) is a cannabinoid receptor blocker that is currently available in Europe for the treatment of obesity and nicotine addiction-it is unclear whether this medication will have any role in treating marijuana dependence in the future.

Research is very limited in the area of medications to treat hallucinogen, inhalant and Ecstasy dependence. There are currently no FDA-approved medications for these indications.

VI. Special issues in the use of medications in individuals with co-occurring disorders

There are several issues to consider when using psychotropic medications in persons with co-occurring mental illness and substance use disorders. The first issue is whether or not to prescribe psychotropic medication to an individual who is actively using or abusing alcohol, nicotine, or other drugs. Many physicians and prescribers have been uncomfortable with this situation, and some have even indicated to patients that they “will not prescribe psychotropic medications” as long as the person is still drinking or using drugs. Current evidence-based practices (such integrated dual disorders treatment or IDDT) clearly support the opposite position; that is, the simultaneous treatment of both mental illness and addictive disorders, including the use of psychotropic medications even in the presence of active addiction. To be sure, extra caution must be exercised in these situations, as noted below, but patients with dual disorders certainly deserve an integrated, balanced, and coordinated approach to medications and psychosocial treatments.

A second issue is the risk of interactions between psychiatric medications and substances of abuse. The metabolism of many psychiatric medications is affected by cigarette smoking. Smoking may decrease blood levels of certain medications, leading to the need to prescribe higher doses of medications to get the same blood levels as in a non-smoker. Alcohol may have a similar effect on the metabolism of psychotropic medications, and it also potentiates the effects of benzodiazepines, barbiturates, sleep aids, and other sedatives. Opiates, like alcohol, are central nervous system depressants, and will also potentiate the effects of sedative medications. Cocaine and amphetamines may exacerbate the risk of seizures, abnormal heart rhythms, and high blood pressure when mixed with specific psychotropic medications. Discussion and documentation of the risks of these substance and medication interactions are essential in the ongoing care of patients with dual disorders.

A third issue is the risk of cross-tolerance and cross-addiction, especially in the case of controlled substances such as benzodiazepines and stimulants. In patients with severe anxiety or mood disorders, benzodiazepines are commonly used medications with proven efficacy. Likewise, stimulants are sometimes used quite successfully to treat severe depressive disorders. However, in patients who also have an underlying addictive disorder, extreme caution must be used when prescribing controlled substances, because they may trigger a relapse of the addictive disorder, or they may pose a risk of creating a new addictive disorder in a vulnerable individual.

A fourth issue that may arise is that individuals with co-occurring mental illness and addictive disorders may misuse or abuse even non-controlled psychiatric medications. For example, patients may abuse diphenhydramine, benztropine, or trihexyphenidyl, which are commonly used to treat the side effects of antipsychotic medications. There have also been case reports of patients abusing quetiapine by crushing and snorting it. Clinician awareness and a high index of suspicion can help to uncover this issue in particular patients.

VII. Summary

Medications are just one part of a biopsychosocial approach to the treatment of dual disorders. Research continues to reveal new ways to approach these illnesses from a biological standpoint. Medication-assisted treatment of substance use disorders is slowly being incorporated into primary addiction treatment settings as well as primary psychiatric treatment settings. Integrating the medication treatment of both mental illness and addictive disorders is vital to the overall recovery of many individuals who continue to struggle with these illnesses.

Christina M. Delos Reyes, MD, is a medical consultant at the Center for Evidence-Based Practices at Case Western Reserve University and the Center's Ohio SAMI CCOE initiative. Dr. Delos Reyes is among the first physicians in the United States to be certified in Addiction Medicine by the American Board of Addiction Medicine (ABAM). She is board certified in adult and addiction psychiatry, maintains a clinical practice in Cleveland and teaches at the School of Medicine, Case Western Reserve University. Dr. Delos Reyes was selected as the recipient of the Woodruff Foundation Emerging Practitioner Leader award in 2009.
Addiction Professional 2011 July-August;9(4):N3