The Need for Psychosocial Interventions to Facilitate the Transition to Extended-Release Naltrexone (XR-NTX) Treatment for Opioid Dependence: A Concise Review of the Literature

Introduction

Improving treatment for opioid dependence is increasingly important as rates of abuse and dependence have risen over the past decades, largely due to increased prescription opioid abuse. ¹ The costs of opioid dependence to the individual and society are significant, including numerous negative medical consequences, overdose, health care and law enforcement costs, and damage to family and social relationships.^2,3 In the U.S., in 2011, 426,000 individuals were diagnosed with heroin abuse or dependence, and another 1,768,000 were dependent on or abused prescription opioid pain relievers. The number of persons with nonmedical pain reliever dependence increased 50% from 2002 to 1.4 million in 2011, but only 51% of those individuals received adequate addiction treatment. Rates of emergency department visits associated with pharmaceutical misuse or abuse increased 114% between 2004 and 2011, with over 420,000 involving opioid analgesics in 2011 alone. ⁴ Between 1999 and 2010, more than 125,000 people in the U.S. died from an overdose involving an opioid analgesic, which outnumbers overdose deaths involving all illicit drugs combined. ⁵ It is estimated that prescription opioid abuse cost the U.S. $55.7 billion in 2007 alone. ⁶ Opioid analgesics were involved in 30% of drug overdose deaths in 1999, compared to nearly 60% in 2010.

Achieving successful remission from opioid dependence is difficult. Individuals seeking to become opioid free have very low success rates without the assistance of medications that mitigate or block the reinforcing effects of opioids. Opioid agonist agents, otherwise known as opioid replacement agents, attach to the opioid receptors. At low doses, opioid agonists prevent withdrawal symptoms, and, at higher doses, they block the euphoric effects of any opioids that might be self-administered. In contrast, opioid antagonists attach to the opioid receptors but do not activate the receptors, and they prevent opioids from attaching to the receptors. Opioid antagonists are effective and are preferred by some individuals seeking treatment for opioid dependence. ⁷ While there are limited data regarding the percentage of those seeking treatment for opioid dependence who prefer antagonist therapy, two recent studies have found that this percentage may be as high as 32%–52%.^8,9 However, in order to transition from opioid use or opioid replacement therapy to opioid antagonist therapy, one must first withdraw from all opioid agonists in order to avoid the sudden onset of potentially severe opioid withdrawal. Withdrawal symptoms are extremely unpleasant, even with comfort medications. Symptoms include vomiting, tremors, aches, fatigue, weakness, restlessness, and insomnia as well as the psychological symptoms of intense depression and anxiety. ¹⁰ Many opioid users expend great energy obtaining opioids to avoid withdrawal. In addition, prolonged use of opioids can cause hypersensitivity to the unpleasant physical and mental symptoms of withdrawal. ¹¹ Tolerating the symptoms of withdrawal is one of the earliest barriers that treatment-seeking individuals must confront and is thought to be one of the primary reasons for detoxification dropout.^12–14

Transitioning to xr-NTX

Once detoxification has occurred, extended-release injectable naltrexone (XR-NTX), a long-acting opioid antagonist, is an effective means of preventing relapse. The Food and Drug Administration approved XR-NTX in October 2010 to treat opioid dependence. The extended-release injectable form lasts 30 days, preventing patients from impulsively discontinuing the medication. XR-NTX provides opioid-dependent patients the opportunity to take effective medication monthly, as opposed to the daily dosing required by other opioid dependence medications (ie, methadone, buprenorphine, oral naltrexone). Although the evidence-base is less extensive than for agonist therapy, XR-NTX is an effective, evidence-based practice for opioid dependence.^7,15,16

Before patients can initiate XR-NTX, they must first completely detoxify from opioids. Chronic opioid-dependent individuals tend to have maladaptive coping behaviors and often cannot tolerate the high levels of physical and mental discomfort from withdrawal.^10,11 Physical and psychological withdrawal symptoms may be more extreme for chronically opioid-dependent individuals. ¹¹ Chronic opioid use can result in hypersensitivity to physical pain, ¹⁷ as well as greater fear of anxiety and anxiety-related sensations. ¹⁸

Opioid detoxification has high rates of dropout and relapse to opioid abuse.^19,20 While rates of success vary widely between programs, studies have found that an average of 30% or fewer patients are abstinent at the end of detoxification.^21,22 A multisite study of outpatient Suboxone detoxification found that only 29% of participants were opioid free at the end of treatment. ²³ Briefer detoxification programs have reported lower success rates ranging from 9% ²⁴ to 21%. ²⁵ In a review of 28 buprenorphine detoxification studies, the range of patients who successfully completed treatment was from 22% to 51%. ²¹ These low rates of successful detoxification, which itself is only the first step in recovery from opioid dependence, indicate that improvements to the detoxification process are needed. Programs that incorporate psychosocial interventions into detoxification protocols have improved program completion and opioid abuse rates. ²⁶ However, few of these interventions have focused on tolerance and acceptance of the withdrawal symptoms as their primary therapeutic target.

Acceptance and Commitment Therapy May Assist with Transition to xr-NTX

A relatively recent innovation in cognitive behavioral therapy is the development of theoretical and clinical approaches to experiential acceptance. ²⁷ Hayes et al. developed a specific treatment approach, Acceptance and Commitment Therapy (ACT), ²⁸ to produce acceptance behaviors aimed at private events that have interfered with accomplishing life goals, such as the symptoms of nicotine withdrawal preventing an individual from quitting smoking. The interest in acceptance stems from literature supporting interventions that disrupt experiential avoidance of negative sensations. ²⁹ This paradigm, which is a departure from traditional cognitive behavioral therapies focused on controlling thoughts and feelings, is highly suited to the acceptance and tolerance of aversive symptoms associated with opioid withdrawal.

Acceptance can be defined as the act of approaching psychologically aversive or troubling internal stimuli while behaving adaptively; ³⁰ it involves actively engaging in the process of experiencing feelings, thoughts, and sensations without attempting to avoid or change the experiences and without allowing them to influence one's behavior in negative ways. ²⁸ One key ACT concept is that a reliance on avoidance and control coping strategies produces psychological inflexibility, which manifests as constrained behavioral repertoires in response to negative internal stimuli. ²⁸ The problematic consequence of these avoidance and coping strategies is that they can interfere with more goal-directed, adaptive behaviors. Hence, the negative internal stimuli are not a problem in and of themselves; they become problematic when they result in destructive, values-inconsistent behaviors. ³¹ This process is evident in substance dependence where drugs are used to avoid unpleasant internal stimuli and then become the source of unpleasant stimuli through withdrawal and other problems associated with opioid dependence. ³² Acceptance interventions acknowledge the impossibility of completely preventing negative thoughts, feelings, and sensations. Treatment components from ACT that have been developed to facilitate adaptive responses to negative affect and other negative internal stimuli include acceptance, defusion, values clarification, commitment, self-as-context, and willingness. ²⁸ ACT is particularly apt to address withdrawal as opioid-dependent patients are more likely to engage in avoidance-based coping through drug use ³² and have heightened sensitivity to physical and psychological discomfort.^10,11,17,18

ACT has been found to be an effective treatment for many common clinical disorders, including substance dependence, in which recovery requires learning adaptive ways to adjust to uncomfortable symptoms.^32,33 Studies have successfully used ACT for smoking cessation,^34–37 alcohol dependence, ³⁸ and methadone maintenance.^32,39 Hayes et al. ³¹ conducted the first study examining the efficacy of ACT for substance use. They compared ACT with a time-matched Twelve-Step Facilitation intervention and a treatment as usual control condition among polydrug-abusing methadone clinic patients. Those assigned to the ACT condition had lower rates of objectively measured opioid use and total drug use and lower subjective measures of total drug use compared to control participants. The Twelve-Step Facilitation participants had results similar to the ACT participants; however, intention-to-treat analyses of the objective total drug use measure supported the superiority of ACT over control but not the superiority of Twelve-Step Facilitation over control. In addition, ACT has been used successfully to treat disorders with symptoms that overlap with opioid withdrawal, including affective and anxiety disorders ⁴⁰ and chronic pain.^41–43 In one study ⁴⁴ examining the efficacy of ACT for chronic pain, ACT was found to result in significant improvements not only in the area of pain but also in depression, pain-related anxiety, disability, medical visits, work status, and physical functioning; effect sizes for all domains were in the medium to large range. Intense physical discomfort and symptoms of depression and anxiety are among the typical symptoms of opioid detoxification.

An intensive ACT-based program has been developed to facilitate methadone dose reduction during methadone maintenance treatment. ³⁹ This intervention consists of 24 weekly sessions over the course of 6 months while participants taper their methadone. The ACT intervention was modified to address issues specific to methadone treatment and was compared to a drug counseling (DC) protocol that encouraged abstinence without addressing coping skills. Although this small study (n = 56) did not detect statistically significant differences between the conditions, 60% of the individuals who received ACT completed treatment compared to 46.2% in the DC condition. In addition, 36.7% of the ACT group was considered successful compared to 19.2% of the DC group, with treatment success defined as having an opioid-negative urine drug screen at the end of treatment without having reenrolled in methadone treatment. ACT also reduced fear of detoxification compared to the DC condition. Rates of opioid use during detoxification were similar across conditions. This study demonstrates the potential of ACT-based interventions to target the physical discomfort associated with opioid withdrawal, as well as the accompanying negative mood symptoms.

Conclusions

XR-NTX is an effective treatment for opioid dependence. However, before treatment with XR-NTX can be initiated, patients must completely detoxify from opioids. The physical and mental discomfort experienced during the withdrawal process causes many patients to relapse to opioid use prior to completing the detoxification process. The incorporation of psychosocial interventions into detoxification protocols has been found to improve outcomes. Interventions rooted in ACT have shown promise in the treatment of other clinical disorders characterized by the presence of uncomfortable symptoms. The use of ACT-based interventions to facilitate the transition to XR-NTX treatment warrants investigation; the contribution of this type of intervention to the XR-NTX transition process is currently unknown.

Author Contributions

Wrote the first draft of the manuscript: SR, DR, RH, PF. Contributed to the writing of the manuscript: SR, DR, RH, TWP, EA, VN, PF. Agree with manuscript results and conclusions: SR, DR, RH, TWP, EA, VN, PF. Jointly developed the structure and arguments for the paper: SR, DR, RH, PF. Made critical revisions and approved final version: SR, DR, RH, TWP, EA, VN, PF. All authors reviewed and approved of the final manuscript.