Opioid Dependence

There has been a constant struggle to define the role of opioids in medical therapy, due to their potential for misuse, overuse, and addiction since pain is a completely subjective sensation, not amenable to objective measurement, and is intimately tied to emotion and the patient’s psychological well-being. Thus the medical decision to administer an opioid analgesic is an attempt to balance the potential for pain relief, and the reliability of the patient’s reporting, against the potential for harm. The decision-making process is less complicated when dealing with acute traumatic injury or surgical trauma. However, with many chronic pain conditions, the etiology or severity of the patient’s pain is less obvious. In the majority of situations, a physician does not initiate opioid therapy with the intention of continuing it for months or years, but many patients will continue to seek opioids for relief of pain which becomes chronic.

Until 1990, chronic use of opioid analgesics was widely discouraged, with most physicians trained to taper their patients off opioid medication after an acute treatment trial. The paradigm began to shift as the movement to improve cancer pain treatment became successful with aggressive opioid prescribing. The success of aggressive opioid therapy for cancer pain treatment led to a spill over into chronic non-cancer pain treatment. As high-dose opioids became more available in the community, it was accompanied by a pattern of escalating drug diversion, opioid misuse, accidental opioid overdose, and deaths that continued to climb through the past decade.

Prevalence of chronic opioid therapy in the UK

According to NHS statistics compiled by Dr Cathy Stannard, author of Opioids in Chronic Pain, the number of prescriptions for opioids dispensed in England from 1999 to 2008 increased from 6.2 million to 14.8 million. And research for this article has revealed that prescriptions for the strongest compounds – morphine, oxycodone, fentanyl and buprenorphine – rose from one million to 4.1 million.

In the United States, the number of prescriptions written for opioids increased by 300% between 1991 and 2009. In Canada, the number of prescriptions written for oxycodone increased by 850% between 1991 and 2007.

Fatalities related to opioid consumption

The rates of fatal overdose increased concomitant with an increase in the number of patients on long-term opioid therapy. Patients who receive higher doses of prescribed opioids are at increased risk for overdose. In study of 9,940 adults receiving long-term opioid therapy for CNCP, those who received 100 mg/d or more of morphine equivalent had an 8.9 fold increase in overdose risk (95% confidence interval [CI 4.0-19.7). Moreover, prescription opioid misuse is associated with high and increasing mortality.

In Scotland, methadone-related deaths increased from 71 in 2001 to 275 in 2011  and they currently represent over half of all reported opioid-related deaths. Tramadol presents interesting data in the UK; in 1996, England and Wales reported one death with the drug mentioned, but by 2011 there were 154 deaths.

Risk factors for opioid abuse and misuse

A critical issue in pain management is the ability of the clinician to identify patients who are most “at-risk” for developing prescription drug abuse. Several risk factors have been described and include sociodemographic factors, pain and drug-related factors, genetics and environment, psychosocial and family history, psychopathology. and alcohol and substance use disorders. However none of these factors by themselves will increase the risk of drug abuse in a given individual. It is suggested that the risk of prescription drug abuse is greatest when risk factors in 3 categories, (i.e., psychosocial factors, drug related factors, and genetic factors) occur in the same individual. In the absence of psychosocial comorbidities and genetic predisposition, pain patients on stable doses of opioids in a controlled setting are unlikely to abuse opioids or develop addiction. On the other hand, patients with a personal or family history of substance abuse, and psychosocial comorbidity, are at increased risk, especially if treatment with opioids is not carefully structured and monitored.

In a study of primary care patients with high levels of pain disability, unemployment, and psychosocial stressors, prescription drug use disorder was concentrated among those with a family history of substance use disorder, those who have spent time in prison, are current cigarette smokers, are male, white, and those with pain-related functional limitations and posttraumatic stress disorder. The vast majority had co-occurring substance use disorder.

Opioid assessment screening tools

Although several formal screening instruments that identify aberrant drug-related behaviors in patients on opioid therapy have been described, there is no well-tested, reliable, and easily administered screening tool to detect drug seeking behaviors in primary care patients taking long-term opioids or being considered for such therapy.

In terms of tools for screening patients before initiating COT, a tool which has been described to have a reasonably high-quality deviation which may be used in conjunction with clinical assessment is the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R).

Atluri and Sudarshan  developed a tool to detect the risk of inappropriate use of prescription opioids in chronic pain patients. The tool was developed for use in interventional pain management settings. Six clinical criteria were identified to predict opioid abuse:

  • Focus on opioids
  • Opioid overuse
  • Other substance abuse
  • Low functional status
  • Unclear etiology of pain
  • Exaggeration of pain.

The score is derived by counting the number of positive criteria. The total score can range from 0 to 6; a cutoff score of 3 and above predicts abuse. Patients who misused opioids scored above the cutoff of 3. In a retrospective study of CNCP patients receiving opioids, a score of 3 or above indicated abuse. Manchikanti et al used these criteria in a prospective study of 500 patients in an interventional pain management setting and found that 100 out of 500 patients had a history of drug abuse. The authors concluded that this was a cost-effective and reliable tool for screening drug abuse potential in an interventional pain management setting.

It predicted substance abuse but did not identify illicit drug use.

Tackling opioid abuse and diversion

Effective strategies are needed to reduce diversion of opioids for nonmedical use. These strategies should be combined with education, behavioral interventions, and monitoring. A concerted effort to improve education and research about the rational management of chronic pain is needed to preserve the right of patients with chronic pain while reducing the catastrophic effects of opioid misuse, abuse, and overdose. Novel opioid formulations designed to reduce nonmedical use are being marketed to deter abuse. Future studies will demonstrate if these formulations play a vital role in limiting abuse and diversion.

Educating Patients and Providers

Patients need to be educated in the areas of safeguarding medications, disposing unused medications, and understanding the consequences of manipulating physicians and selling their medications.

Physician education should be focused on considering a patient’s risk for opioid misuse before initiating opioid therapy; recognizing that a patient is misusing and/or diverting prescribed medications; and understanding the variation in the abuse potential of different opioid medications currently on the market. Other strategies for providers include changing behavior and practice patterns, saying “no” to unreasonable patient demands, and adopting a universal precaution approach toward all patients prescribed drugs of addiction.

Behavioural interventions

Behavioural interventions with close monitoring and cognitive behavioral substance misuse counseling could increase overall compliance with opioids in noncompliant chronic pain patients.

Managing pain in patients with substance abuse

Interdisciplinary pain management, the use of universal precautions in all patients, and special attention to the structure of care in those at higher risk for opioid misuse may improve outcomes in this population.

Abuse deterrent formulations

Opioid formulations designed to deter and resist abuse address some, but not all, aspects of inappropriate opioid use. By incorporating physical and pharmacological barriers to contain the euphoric effects of opioids, these novel formulations make the drug less convenient or less desirable to abusers and may curb problematic opioid use.

While these drugs hold promise, it remains unproven if they can truly curb abuse. It is possible that abuse-deterring formulations may divert drug abusing individuals to find other drugs that are easier to compromise.

Substitution therapy and detoxification

Use of substitute medication is an important element in the treatment of opioid dependent patients and their medically assisted recovery (MAR). Both Methadone and buprenorphine are effective evidence-based medications used in the treatment of opioid dependence.  Both are effective support agents in detoxification.

The primary function is to reduce (and eventually replace) illicit opioid use and in so doing reduce harm and improve the health and psychological well-being of the patient. Both are more effective as part of a package of care that includes psychosocial support.

Choosing between maintenance and detoxification regimes can and should occur at many points during treatment, starting at the first assessment and then at various points, as appropriate.

Maintenance therapy

Methadone is still considered the gold standard substitute medication for long-term opioid dependence. However, buprenorphine is also effective.

Optimal daily dose for maintenance is usually between 60 and 120 mg for methadone and 12 and 32 mg for buprenorphine. Some people need larger doses, and some smaller.

Methadone is usually prescribed in an oral liquid formulation 1 mg/ml. Buprenorphine is prescribed as sublingual tablets of 0.4 mg, 2 mg or 8 mg; or in a buprenorphine/naloxone combination as 2 mg/0.5 mg and 8 mg/2 mg tablets.

Summary

Two major public health hazards are undertreatment of pain and prescription drug misuse/abuse. The widespread use of prescription opioids in recent decades has been associated with a steady increase in prescription drug abuse and an increase in opioid-related deaths. Multiple approaches to identify and manage at-risk patients have been proposed. Experts recommend combining several different strategies to identify at-risk patients, including examining the underlying origins or implications of aberrant behaviors, and tailoring treatments accordingly. Chronic pain treatments must be multimodal and combined with non-opioid medications. There should also be cognitive, behavioral, and interventional techniques to optimize outcomes, particularly for those who are unable to safely take their opioids in a structured fashion.

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