Adam Bisaga, MD

Over the past 10 years, the prevalence of heroin and prescription opioid misuse has significantly increased, in large part because of the increased prescribing of opioid analgesics in the US. As a result, there has been an unparalleled rise in the number of people affected with opioid use disorders and great concerns about the associated morbidity and mortality-including opioid-related overdoses and deaths in conjunction with the spread of infectious diseases, such as HIV infection and hepatitis C.

In this environment, it is imperative that physicians, particularly psychiatrists, are able to identify opioid use disorders; provide education and strategies for harm reduction; and offer effective, evidence-based treatments.

In this brief overview, we provide a step-by-step process for clinical decision making with 2 common-scenario case vignettes.

Mr Gordon is a 45-year-old construction worker who had been injured a year earlier when picking up a heavy piece of equipment. His primary care physician (PCP) prescribed oxycodone for the pain. After 3 months, the original dose prescribed no longer controlled his pain, and Mr Gordon began gradually increasing the dose and subsequently running out of his medication earlier than anticipated. After multiple discussions about his increasing use of oxycodone and his failed attempts to cut down on his use, Mr Gordon’s PCP stopped prescribing the medication.

After using the last dose of oxycodone, Mr Gordon woke up sweating profusely, with diarrhea, nausea, bone aches and pains, and anxiety. The next morning, he experienced very strong urges to use oxycodone, and he made 3 appointments with different physicians and managed to obtain prescriptions from each of them. In addition, he began buying “blue roxies” (colloquial term for oxycodone 30-mg tablets) from a neighbor, and learned to crush and use 5 to 8 tablets intranasally daily, noting a faster onset of effect.

In a short time, Mr Gordon found himself frequently calling in sick to work so he could continue using the pain-killers. He felt sick on the mornings when he did not have enough pills. He also became depressed and uninterested in socializing, and he had poor appetite and no sex drive. He stopped going to the gym, which had previously been his passion.

After missing work for the third time in a week, he was fired. Out of work and with only a few tablets of oxycodone left, Mr Gordon feels that his use of oxycodone is out of control and that he has become “a different person.”

In DSM-5, opioid use disorders, like all substance use disorders, have been redefined as a spectrum of pathology and impairment. The criteria for an opioid use disorder are generally the same as in DSM-IV. The diagnostic criteria for DSM-IV abuse and dependence were combined in DSM-5 except for 2 changes: (1) the criterion for recurrent legal problems has been removed and (2) a new criterion for craving, or a strong desire or urge, to use opioids has been added (see 

In DSM-5, the two disorders of opioid abuse and opioid dependence are replaced by a category of opioid use disorder. A patient must meet at least 2 diagnostic criteria to qualify as having an opioid use disorder. Severity is characterized as “mild” if 2 or 3 criteria are met, “moderate” if 4 or 5 criteria are met, and “severe” if 6 or more criteria are met.

Mr Gordon meets 7 criteria, which qualifies him for a severe opioid use disorder. He demonstrates tolerance to oxycodone; is using more and for longer than intended; has had multiple failed attempts to decrease his use, withdrawal, and craving; has increased time spent obtaining opioids; and has failed to fulfill work obligations.

Mr Gordon also meets criteria for a DSM-5 category of opioid-induced depressive disorder. For that diagnosis, the onset of depressive disorder needs to be temporally connected with the substance use (ie, within 1 month as opposed to before the initiation of substance use or during a prolonged period of abstinence). Moreover, the opioids need to be capable of producing the specific syndrome, which is certainly the case with the depressive disorder.

"While opioid dependence is among the most severe and lethal of addictions, it also has the most effective medication treatments."

In the US, there are 3 FDA-approved medication treatments for opioid use disorders, all of which engage the Î¼-opioid receptor: methadone, a full agonist; buprenorphine, a partial agonist; and naltrexone, an antagonist. 

 compares the different properties of each medication. While methadone is an effective pharmacological option, because of federal regulations, it is only available at designated methadone administration sites (methadone maintenance treatment programs) and is not available for the treatment of opioid use disorders by prescription.

Patients who desire office-based treatment for opioid use disorders have the 2 remaining options: buprenorphine and naltrexone. When selecting which medication is best suited for your patient, there are several factors to consider, includ-ing clinical history, treatment preferences, available support system, and access to resources. Each of these pharmacotherapies has a potential to decrease or eliminate craving for heroin or a prescription opioid, which helps the patient engage and benefit from a behavioral, abstinence-oriented treatment to achieve recovery-a voluntarily maintained lifestyle characterized by sobriety with care for personal health and relationships.

Buprenorphine partially activates the Î¼-opioid receptor, at approximately 50% the maximum effect produced by an agonist. At lower doses (16 mg or less), its agonist effect is directly correlated with the dose; however, at higher doses (more than 16 mg), its pharmacological and clinical effects decrease and plateau, with the increasing dose reaching a ceiling above which no further agonist effect is possible. The agonist effects of buprenorphine prevent opioid withdrawal and reduce or eliminate the craving for opioids. In addition to its agonist properties, bupre-norphine has a higher affinity for the Î¼-opioid receptor than commonly used opioids. As a result, buprenorphine functionally acts as an antagonist, preventing other opioids from binding to the receptor.

Buprenorphine is available in 2 sublingual formulations-as pure buprenorphine (Subutex) and as a buprenorphine/naloxone combination (Suboxone, Zubsolv)-and in a buccal film formulation (Bunavail).

Naloxone is a short-acting opioid antagonist, which is mostly inactive by the sublingual route. The addition of naloxone to the formulation is designed to deter misuse of the medication, since naloxone becomes active and exerts antagonist effects when used intravenously.

Physicians who are interested in using buprenorphine to treat patients with opioid use disorders can obtain a DATA 2000 (Drug Addiction Treatment Act of 2000) waiver by completing training and submitting their waiver of intent as outlined by the Substance Abuse and Mental Health Services Administration (SAMHSA). Training can be completed in person or online (pcssmat.org). The Drug Enforcement Administration will subsequently provide the physician with a separate license number (X-number) to be used when writing buprenorphine prescriptions.

Naltrexone binds to the Î¼-opioid receptor with a high affinity but does not exert any activity; rather, it prevents binding of agonists or displaces agonists at the receptor. Naltrexone can be administered after detoxification to prevent relapse, when it provides a complete blockade of opioid effects.

Naltrexone is available in an oral tablet formulation that requires daily administration or a once-monthly, long-acting intramuscular injection (Vivitrol) to bypass the difficulties with adherence to daily medication that many patients have at treatment outset. No additional training or licensure is required to prescribe naltrexone for opioid use disorders, but training materials are available (pcssmat.org).

All 3 of these medications should be considered in Mr Gordon’s treatment.

After the benefits and limitations of different medication options are explained to Mr Gordon, a decision is made for outpatient buprenorphine induction and maintenance treatment. This choice of treatment is made on the basis of his unwillingness to go through the detoxification and his preference for office-based treatment.

During the first month of treatment, he is maintained on buprenorphine 12 mg/d: he has no cravings and maintains abstinence from opioids as confirmed with weekly urine drug screens. After 2 months of treatment, he requests a dose decrease and the medication is gradually tapered to 4 mg/d. After 1 month of stabilization with buprenorphine, he reports that his depressed mood is resolved, his appetite is improved, and he is going to the gym daily. He is hired by another construction company; he goes to work every day, reengages with his friends, and resumes dating.

He feels that he is “cured” and decides to stop coming to treatment; he self-tapers off buprenorphine and notes minimal withdrawal symptoms. After about 6 months, he begins to casually use oxycodone again because he thinks that he is now able to control use, which he does in the first few weeks. However, his use gradually escalates and after 2 months of using, he admits that he needs help and reengages in treatment.

Given that he had an excellent response with buprenorphine, treatment is re-induced at a dosage of 8 mg/d, which, over 2 to 3 months, is gradually tapered to 4 mg/d. At this point, he has been stable and in recovery from opioids for 3 years. He plans to continue on buprenorphine maintenance indefinitely. He has no mood problems and is very happy with his current health and life situation.

Mr Gordon’s case highlights the chronic and potentially exacerbating nature of opioid use disorders, which is similar to other chronic psychiatric disorders, such as bipolar disorder. A long-term focus on medication adherence is needed as well as regular office visits to monitor stability, work on relapse prevention strategies, recognizing destabilizing events, and developing other health-promoting activities.

Ms Derbin is a 26-year-old bartender who self-presents for outpatient treatment after injecting heroin for the past month. She first used nonprescribed oxycodone at age 19, when someone introduced her to snorting it at a party. Initially, she used it 1 or 2 times a week, usually on weekends; but over the next 2 years, her use progressed to daily snorting. She is no longer experiencing euphoria with use and is now using primarily to avoid withdrawal symptoms.

When oxycodone became increasingly more difficult to obtain, a boyfriend introduced her to injecting heroin to reduce daily expense and to have greater and faster euphoric effects. In addition to using opioids, Ms Derbin has been a daily marijuana smoker for 10 years and regularly uses intranasal cocaine (14 of the past 30 days), alcohol (weekend binge drinking), and benzodiazepines (mainly alprazolam for 5 of the past 30 days). She also reports a history of ADHD, for which she took stimulant medication from age 13 through 19.

She reports that this is not her first time coming to treatment for opioid use. At age 22, she had an inpatient methadone-assisted detox from opioids; treatment was tapered and discontinued before discharge. She remembers “not feeling well” following her discharge and relapsing 2 days after leaving the facility.

She went to her second detox 6 months later, and this time was discharged to a residential treatment center that followed a therapeutic community model. She stayed there for 3 months and was instructed to “become personally responsible for her behavior to be drug-free.” Medication-assisted treatment was not offered, but she was instructed to seek out Alcoholics Anonymous to maintain sobriety.

After her discharge and a total of 6 months abstaining from opioids, she relapsed with oxycodone and benzodiazepines-she notes that she felt “bored” at work and was seeking excitement. She overdosed during the first week, and a friend called an ambulance after she became nonresponsive.

This overdose prompted Ms Derbin to seek treatment again-this time as an outpatient with buprenorphine induction and maintenance. She did well for 2 months while taking buprenorphine, using heroin only occasionally, but she continued to use cocaine and alprazolam. Eventually she began diverting the buprenorphine and attempting to inject it. After 1 month, she stopped injecting buprenorphine and resumed daily injections of heroin. She presents to you with concerns about her injection use. She wants to be detoxified because she does not want to be “dependent on any substance ever again.”

Ms Derbin’s previous experience with multiple and varied treatment settings is quite common for many patients struggling with opioid use disorders. Her first two experiences of detoxification without the offer of medication-assisted treatment to prevent relapse is still the most frequently used strategy. However, as demonstrated in this case, patients whose detoxification is not followed by relapse-prevention treatment are at high risk for relapse. As many as 90% of such patients relapse, usually in 1 to 2 months, and unfortunately many will overdose given that they no longer have physiological tolerance to opioids once detoxified.

Detoxified individuals are at greater risk for overdose than those who avoid treatment and continue to use opioids regularly. Individuals who use opioids in the context of sedative and alcohol use are at the highest risk for respiratory suppression and overdose. All opioid users, especially those who decline further treatment following detoxification, should be counseled about the high risk of overdose with relapse and provided with a naloxone rescue kit. Their friends and family need to be educated about how to obtain a rescue kit (SAMHSA Opioid Overdose Toolkit; projectlazarus.org) and about how to administer the naloxone in the event of an overdose. Patients who inject opioids should also be informed about clean needle exchanges.

Ms Derbin’s history indicates a past trial of buprenorphine maintenance with a poor treatment response. While many patients do well with agonist or partial agonist maintenance treatment for opioid use disorder, others do not respond and continue to have cravings and illicit opioid use. Others, such as those engaged in recovery in the 12-step community, find it difficult to accept the idea of being “dependent” on another type of drug/opioid. Given Ms Derbin’s personal preference and interest, a trial of antagonist treatment with naltrexone in conjunction with relapse-prevention therapy and psychosocial interventions was agreed on, and her parents were brought in to be a part of treatment.

To transition to antagonist treatment, the patient must first go through detoxification. One of 3 detox strategies can be used: agonist-assisted detoxification, symptomatic treatment only with non-opioid medication, or antagonist-assisted detoxification with symptomatic treatment. The main difference between agonist-assisted detoxification and the other two strategies is that withdrawal symptoms tend to be more severe toward the later part of treatment with agonists, while withdrawal symptoms are more severe earlier in treatment with the other two methods. Also, agonist detoxification requires a 7- to 10-day washout period before administration of naltrexone to prevent precipitated withdrawal. Because of this prolonged detoxification period and delay in starting naltrexone, some patients may drop out of treatment and relapse.

Once a patient completes detoxification, a urine drug screen should be obtained to confirm abstinence from all opioids (including buprenorphine). Administering naltrexone to a patient who is still physically dependent on opioids will precipitate a severe withdrawal reaction. If long-acting injectable naltrexone is selected, a trial of oral naltrexone may be given first to ensure that the patient tolerates the medication and withdrawal is not precipitated. If the patient has been abstinent (eg, in residential treatment), naltrexone injection can be given at treatment outset. Monthly injection of a long-acting intramuscular naltrexone is generally preferable to a daily oral administration, especially at treatment outset, because rates of treatment response tend to be twice as high with the long-acting prepa-ration (for more information, see pcssmat.org or SAMHSA’s 

Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorders: A Brief Guide

Often the psychiatrist is the only health care professional who has regular contact with a patient who has an opioid use disorder. This should be seen as an opportunity to provide prevention strategies, screening, counseling, and possible referrals for co-occurring medical problems commonly seen in this patient population. Given Ms Derbin’s recent injection drug use, HIV and hepatitis C and B status should be obtained with routine blood work in addition to referral for hepatitis B vaccinations if she has not already received them.

Ms Derbin was successfully detoxified with small ascending doses of oral naltrexone and supportive medications, including clonidine, zolpidem, and clonazepam. Subsequently, monthly injections of a long-acting intramuscular naltrexone were started. Her parents were instrumental early in treatment in reminding her of and bringing her to appointments and arranging for her to meet with a physician to better understand the nature of her condition and the role that medication plays in recovery.

As she became more engaged in the relapse-prevention behavioral therapy over time, she lost cravings for the drugs and now only uses marijuana with decreased frequency (from daily use down to 4 times a week). She has been abstinent from opioids for 18 months with ongoing monthly injections of naltrexone. At present, Ms Derbin reports much greater stability than with previous treatment attempts. When she started working, her PCP prescribed extended-release stimulants to treat symptoms of her ADHD. Ms Derbin reports improvement in work and life satisfaction. She broke up with the heroin-using boyfriend and began attending regular Narcotics Anonymous meetings, at which she has found a community of people she identifies with in recovery.

Many advances have been made in the treatment of opioid use disorders over the past decade. While opioid dependence is among the most severe and lethal of addictions, it also has the most effective medication treatments. Treatment is the most important strategy to reduce death due to opioid overdose-pharmacological treatments reduce the risk by 90%. The challenge now comes with implementing medication-assisted treatment into a widespread community practice to allow easier access to evidence-based care for patients. The medication-free approach cannot be justified as the only treatment for opioid addiction: overwhelming evidence exists to support the greater success of a medication-assisted approach.

Psychiatrists are in a prime position to launch a campaign in their communities to inform those seeking help and their families about the gap between what is being offered to patients and what is actually known to be effective at preventing relapse and death. Patients deserve the opportunity to make a well-informed choice about which path they take to recovery.

We should shift the focus away from discussing the superiority of one medication approach over another toward having thoughtful, tailored discussions to better understand which medication treatment option can best match an individual patient’s needs. Ultimately, as more evidence-based medication treatments are provided to patients with opioid use disorders, overdose deaths and other significant morbidity can be decreased.

Dr Brezing is a Fellow in Addiction Psychiatry at the New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons in New York. Dr Bisaga is a Professor of Psychiatry at Columbia University College of Physicians and Surgeons and a Chair of the mentoring program “Physicians’ Clinical Support Service for Medication-Assisted Treatment.” (PCSS-MAT). The authors report no conflicts of interest concerning the subject matter of this article.

The PCSS-MAT is a national training and mentoring project developed in response to the prescription opioid misuse epidemic and the availability of newer pharmacotherapies to address opioid dependence. The overarching goal of PCSS-MAT is to make available the most effective evidence-based education and training resources about medication-assisted treatments to serve patients in a variety of settings, including primary care, psychiatry, and pain management. The PCSS-MAT mentors are a national network of trained providers with expertise in medication-assisted treatment and who are skilled in clinical education. The PCSS-MAT mentoring program is available at no cost to providers. Funding for this initiative was made possible by a grant from SAMHSA (Substance Abuse and Mental Health Services Administration).

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While opioid dependence is among the most severe and lethal of addictions, it also has the most effective medication treatments. The authors provide 2 case vignettes and a step-by-step process for clinical decision making.

Adam Bisaga, MD

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