Comorbid Substance Use Disorders: Primer for Pain Management

Patients who misuse opioids may be recreational users, patients with the disease of addiction, patients who suffer from pain seeking more relief, and/or patients escaping emotional pain.

By David Cosio, PhD and Erica H. Lin, PharmD, BCACP

The topic of opioid misuse and abuse (and the rising heroin epidemic) has dominated headlines lately, but what does this really mean for chronic pain specialists. How does one balance the needs of the legitimate pain patient, with those of society as a whole?

Recent data suggests that chronic pain and addiction can go hand and hand. But what is the real incidence? A small-scale trial from 2005 (before the current opioid-epidemic) indicated that approximately one-third (32%) of chronic pain patients may have comorbid substance use disorders (SUD’s).¹However, a 2011 review of the literature found that anywhere from 4% [primary care setting] to 48% [AIDS clinic] of patients with chronic pain have a current SUD.²

In addition, among 5,814 patients with chronic pain who were also prescribed chronic opioid therapy, 19.5% had a current SUD diagnosis documented in their medical record.³The wide range in prevalence rates reflected in these studies makes it difficult to know what the true incidence of SUD is among chronic pain patients.

This is not a purely academic question, however. Patients with SUD’s have been found to be at greater risk for aberrant medication-related behaviors—for example, if prescribed an opioid, there is an increased risk for prescription opioid misuse and abuse.² Patients with a comorbid SUD (past and present) are also potentially more difficult to treat and are at higher risk for comorbidities (depression, anxiety, sleep disturbances, etc).²

In the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the revised chapter of “Substance-Related and Addictive Disorders” includes substantive changes to the disorders. According to the new definition, a patient is diagnosed with a SUD if he/she exhibits a maladaptive pattern of substance use leading to clinically significant impairment or distress.⁴ Table 1 lists clinical features designed to help differentiate patients with pain from those who may misuse or abuse opioids.⁵

In the 2008 Morasco study, the substances most often used included: cannabis (16%), prescription and/or illicit opioids (15%), and stimulants (cocaine 11% and amphetamines 8%). Although legal, alcohol was found to be the most used substance (73%).³More than half of the U.S. population has been identified as drinkers, designating alcohol the number one used substance in America.⁶

How Other Mood-Altering Substances Affect Pain

Alcohol

People have used alcohol to relieve pain since ancient times. However, the greatest pain-reducing effects occur when alcohol is consumed at doses exceeding guidelines for moderate daily alcohol use.⁷

Withdrawal from chronic alcohol use often increases pain sensitivity, which could lead to additional drinking to reverse withdrawal-related increases in pain. Prolonged, excessive alcohol exposure can also generate painful, small-fiber peripheral neuropathies. Abrupt withdrawal from chronic alcohol use can lead to seizures and death, so it is recommended that patients be detoxed under physician supervision.⁷

Using alcohol with other substances to alleviate pain places people at risk for a number of harmful health consequences, including acute liver failure (with acetaminophen), gastric bleeding (with aspirin or non-steroidal anti-inflammatory drugs), and potential overdose (with opiates).⁷

Marijuana

Another commonly used substance is marijuana, or cannabis. In 2012, cannabis was the most commonly used federally banned drug, with more than 18 million users.⁶ Marijuana use disorder is now estimated to affect 6.3% of adults at some point in their lives (see Marijuana Use Disorder is Common and Often Untreated).

More recently, the use of cannabis to manage chronic pain has caused national ethical and legal discourse (see Legal Status of Medical Marijuana). Given the interplay of federal and state laws, an individual could be legally using cannabis under state law but still be in violation of federal criminal law. Thus, as a matter of federal law, providers are discouraged from prescribing cannabis or complete state medical marijuana forms.⁸

When it comes to cannabis, practitioners must exercise caution. Providers should remain aware that there is a distinction between medicinal cannabis and recreational marijuana. Knowing the potential harms of cannabis use and its negative interactive effects with concurrent use of opioids can also help guide practitioners in their clinical decision-making. Research with cannabis does demonstrate its efficacy in treating anorexia, vomiting from cancer chemotherapy, HIV/AIDS, and other debilitating medical disorders. There are also studies that document cannabis’ therapeutic potential in pain management.⁹

“A strong evidence base supporting the use of cannabis to treat chronic pain, particularly neuropathic pain, already exists in the peer-reviewed literature,” explained Gregory T. Carter, MD, MS.¹⁰ “Medical marijuana works very well for patients with fibromyalgia, degenerative arthritis, spinal cord injury, neuromuscular disorders such as amyotrophic lateral sclerosis and multiple sclerosis, among other conditions.”

However, Dr. Carter cautioned that “cannabis is not for everyone. I would not recommend it for patients with a history of psychiatric disorders, such as schizophrenia.” It is clear from the literature that even low doses of tetrahydrocannabinol (THC) may, in susceptible individuals, cause mental status changes, perceptual distortions, and impaired judgment.⁸In addition to significant mental status changes,¹¹ marijuana increases driving accidents,¹² adds risks in the workplace and other activities of daily living, and leads to possible substance abuse.¹³

Therefore, many pain practitioners do not recommend its use, especially in patients with a history of SUD. In the event that a drug screen is positive for marijuana or any other illicit/illegal substance, Gerald Arnoff, MD, noted that: “I will not write for a prescription for any controlled substance—meaning that if the patient is receiving an opioid analgesic for pain from another prescriber, a new prescription will not be written.”¹⁴

How Opioid Misuse Affects Pain?

The vast majority of people prescribed opioid medications for pain take their medications responsibly and without incidence. That being said, the diversion of prescription opioids for non-medical uses has become a public health crisis.¹⁵ In 2012, more than 2 million people used prescription drugs non-medically for the first time in the U.S.⁶ Among pain patients, opioid misuse is defined as:

Negative urine drug screen (UDS) for prescribed opioids
Positive UDS for opioids or controlled substances not prescribed by the provider
Positive UDS for stimulants (cocaine or amphetamines-not prescribed by the provider)
Evidence of procurement of opioids from multiple providers through state prescription monitoring
Illegal distribution, including diversion of opioids and prescription forgery.

Patients who misuse opioids may be recreational users, patients with the disease of addiction, patients who suffer from pain who are seeking more relief, and/or patients escaping emotional pain. Past research has found that 29% to 60% of people with opioid addiction report chronic pain.^16-19

Providers are, therefore, charged with the daunting task of screening patients for SUD through careful history taking and assessment before prescribing opioid therapy.⁵ Then deciphering the results and prescribing an appropriate care plan.

In addition, it is important for providers to understand that despite the widely held perception that opioids are the most potent medications available for the treatment of pain, there is little evidence that they are more effective than other therapies.²⁰

At this juncture, it is important to remind readers of the World Health Organization 3-Step Ladder.²¹ It is not a specific opioid guideline but a template that provides a practical roadmap for pain treatment. Forest Tennant, MD, wrote that “the ladder views opioids as secondary to non-opioid measures, which are grouped into 2 categories: non-opioid pharmaceuticals and adjuvant therapies, which include non-pharmacologic measures.”

Fundamentally, it calls for a multifaceted approach to pain treatment in which opioids are the second and third rung of the ladder, and not the primary or first step. “Opioids are not to be restricted but rather to be used when necessary,” noted Dr. Tennant.²¹ Prior to beginning a patient on opioids, the clinician must weigh the risks (physical dependence, potential addiction, drowsiness, constipation, respiratory depression) versus the benefits, and have a rational exit strategy for when to wean a patient off therapy.

Other Commonly Abused Medications

Other medications that are co-administered with opiates are stimulants. Research studies have shown that amphetamines may provide an analgesic effect and enhance the analgesic effects of opioids, thus potentially reducing the dose of opioids (opioid-sparing).²²Prescription stimulates, however, are the third most abused prescription medication. There were more than 1 million users of stimulants for non-medical purposes identified in 2012.⁶

Stimulant drugs are typically prescribed for attention deficit hyperactivity disorder (ADHD) and narcolepsy, and include: methylphenidate (Ritalin, Concerta, others), dextroamphetamine (Dexedrine, others), and combinations of amphetamine and dextroamphetamine (Adderall, others). Physicians traditionally have been reluctant to prescribe stimulants to pain patients for fear of abuse or addiction, as well as concerns that high blood pressure and tachycardia may result.

Street amphetamine abuse, such as cocaine and crystal meth, come with additional risks, including weight loss, aggression, damage to organs (nasal tissue, lung function, and heart), depletion of vitamins and minerals in the body, as well as dependence and overdose. In 2012, nearly 2 million people in America were current cocaine users, and over 400,000 people were using methamphetamine.⁶

Furthermore, in cases in which multiple medications are prescribed, providers should assess the risks versus benefits of each medication. Benzodiazepines should raise red flags in patients already prescribed or taking opioids, as the combination may contribute to respiratory depression and overdose. Note that 2 million non-medical, prescription drug users surveyed in 2012 were identified as non-medical users of benzodiazepines.^6,23

What Treatment Options Are Available for Addiction?

Medication and psychotherapy (especially when combined) are important elements of an overall therapeutic process that often begins with detoxification, followed by treatment, and relapse prevention.²⁴ The most widely used self-help programs are based on the Alcoholic Anonymous 12-Step model. These independent, self-helps groups are a wonderful resource for patients coping with re-integration into the community and for preventing relapse.

In terms of medication management, methadone, buprenorphine, and naltrexone are effective medications for the treatment of opiate addiction. Naltrexone, acamprosate, and disulfiram have been FDA-approved for treating alcohol addiction; while topiramate has shown encouraging results in clinical trials (Table 3).

Acting on the same targets in the brain as heroin and morphine, methadone and buprenorphine suppress withdrawal symptoms and relieve cravings. Naltrexone blocks the effects of opioids at their receptor sites in the brain and should be used only in patients who have already been detoxified. The recently released guidelines from American Society of Addiction Medicine (ASAM)25 noted that:

Methadone is recommended for patients who are physiologically dependent on opioids, able to give informed consent, and who have no specific contraindications for agonist treatment when it is administered in the context of an appropriate plan that includes psychosocial intervention.
Switching from methadone to another medication may be appropriate if the patient experiences intolerable side effects or is not able to go daily to a methadone maintenance program.
Buprenorphine is a partial opioid agonist. Opioid-dependent patients should wait until they are experiencing mild to moderate opioid withdrawal before taking the first dose of buprenorphine to reduce the risk of precipitated withdrawal.
Patients who discontinue agonist therapy and resume opioid use should be made aware of the risks associated with an opioid overdose, and especially the increased risk of death.
Naltrexone is a recommended treatment in preventing relapse in opioid use disorder. Oral formula naltrexone may be considered for patients in whom adherence can be supervised. Extended-release injectable naltrexone may be more suitable for patients who have issues with adherence.

Psychotherapy can enhance the effectiveness of medications and help people stay in treatment longer. Treatment for addiction can be delivered in many different settings using a variety of behavioral approaches. Outpatient treatment programs offer several forms of behavioral treatment, such as:

Cognitive Behavioral Therapy, which helps patients recognize, avoid, and cope with the situations in which they are most likely to abuse substances.
Multi-dimensional Family Therapy, which addresses a range of influences on substance abuse patterns and is designed to improve overall family functioning.
Motivational Interviewing, which capitalizes on the readiness of individuals to change their behavior and enter treatment.
Contingency Management, which uses positive reinforcement to encourage abstinence from substances.²⁴

Residential treatment programs are highly structured programs in which patients remain at a residence, typically for 6 to 12 months. The focus of residential treatment programs is on the re-socialization of the patient to a substance-free lifestyle.

In addition, the ASAM guidelines recognized the role of the rapid-acting opioid blocker naloxone (Evzio, Narcan), which plays a critical role in reversing opioid overdose.²⁵

The Dangers of Smoking: How Tobacco Affects Pain

In 2012, an estimated 69 million Americans over age 12 were current users of a tobacco product.³ According to a recent study, 14 million major medical conditions have been attributable to smoking.²⁶Smoking remains the leading preventable cause of premature death in the U.S., with more than 20 million premature deaths since the release of the first Surgeon General’s report in 1964.²⁷

Tobacco use is 2 times higher among patients with chronic pain. Furthermore, smokers are more likely to develop chronic low back pain than nonsmokers.²⁸Nicotine has analgesic properties that, at first, can help relieve acute pain. However, over time, nicotine can alter pain processing and contribute to the development of chronic pain and greater pain intensity. This paradox is an important aspect of both acute and chronic pain management for patients who use tobacco products.²⁹

In addition, smoking is also common among people with SUD. A seminal 11-year, retrospective cohort study of 845 people who had been in addiction treatment found that 51% of deaths were the result of tobacco-related causes.³⁰Therefore, addressing patients’ smoking habits and encouraging them to quit smoking is an integral part of a pain management program.³¹

Treatment Options for Tobacco Cessation

The U.S. Preventative Services Task Force recommends a counseling strategy employs the “5-As”:

Ask about tobacco use
Advise to quit through clear
personalized messages
Assess willingness to quit
Assist to quit
Arrange follow-up and support

Counseling can be brief and occur one-time or consist of longer or multiple sessions, with the latter being more effective. Also, it is more effective to combine counseling with medication than either component alone.³¹ Counseling can include developing strategies individualized for the patient that can increase the chance for a successful attempt to quit including:

Helping the patient identify personal motivations for quitting
Monitoring smoking habits to determine smoking triggers
Creating an action plan to cope with triggers and stress
Gradual reduction of smoking
Setting a quit date
Using social supports and celebrating successes.

The available FDA-approved pharmacotherapy for tobacco cessation includes nicotine replacement therapy (NRT), sustained-release bupropion (Zyban), and varenicline (Chantix). NRT comes in various formulations for patient convenience and preference, with the gum, lozenge, and transdermal patch available without a prescription (Table 3, above).

The starting strength of the formulation is dependent on how soon the first cigarette is smoked after waking (gum and lozenge) or the total number of cigarettes smoked in a day (patch) then gradually tapered for up to 12 weeks. Patients should be counseled on the appropriate “chew and park” method for the NRT gum to ensure proper absorption of the nicotine and to avoid food or drinks 15 minutes before or during use with either the gum or lozenge. The patch may be removed at bedtime to minimize sleep disturbances.

Other formulations, such as the nasal spray or oral inhaler, require a prescription, with duration of therapy lasting between 3 to 6 months.

Precautions with using NRT formulations include recent myocardial infarction, serious underlying arrhythmias, serious angina pectoris, pregnancy, and breastfeeding.³²

The antidepressant bupropion SR was the first prescription medication approved for tobacco cessation. Therapy should begin 1 to 2 weeks prior to the patient’s established quit date, with the duration of 7 to 12 weeks and up to 6 months in certain patients.³² The starting dose is 150 mg every morning for 3 days then titrated to 150 mg twice a day.

Bupropion SR is contraindicated in patients with a seizure disorder as it can lower the seizure threshold, patients with a current or prior diagnosis of bulimia or anorexia nervosa, simultaneous abrupt discontinuation of alcohol or sedatives or benzodiazepines, and in patients who have used MAO inhibitors within the past 14 days prior to therapy initiation.³²

Varenicline is a partial nicotine agonist also approved for tobacco cessation. Therapy is initiated 1 week prior to the patient’s established quit date, with the duration of 12 weeks and up to an additional 12 weeks, if needed.³² The starting dose is 0.5 mg every morning for the first 3 days, then titrated to 0.5 mg twice a day thereafter. The dose must be adjusted for patients with severe renal impairment.

Both varenicline and bupropion SR have black box warnings regarding the risk of neuropsychiatric symptoms, including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide.³² Patients should be routinely monitored while on therapy and advised to contact their provider immediately if experiencing these symptoms.

Electronic cigarettes, which mimic the look and feel of regular cigarettes, are also available and can be very addictive. They consist of a nicotine cartridge, inhaler, battery, and heating element that converts the liquid nicotine into vapor to be inhaled. Since e-cigarettes are not regulated by the FDA, manufacturers of e-cigarettes are not required to submit complete information on chemicals used, emissions, and safety. In fact, a FDA lab study in 2009 found that e-cigarettes can expose users to the same harmful chemicals found in cigarettes.³³ The World Health Organization and FDA do not recommend use of e-cigarettes as tobacco cessation aids, and the sales, marketing, and import have been banned in several countries.³³

Facilities may have tobacco cessation clinics where patients may either be referred or walk-in for appointments based on availability. These clinics can provide counseling, initiate medication, and monitor patients’ progress towards becoming smoke free. Subsequent visits may be conducted via telephone or face-to-face. Tobacco cessation groups run by psychologists, pharmacists, or social workers are also available. There are also national (1-877-44U-QUIT) and state tobacco quit lines (1-800-QUITNOW) as well as text messaging programs available like smokefreeTXT (Table 4).

There are several resources available to patients interested in tobacco cessation.^34,35 Providers may also want to highlight the health benefits of quitting tobacco with their chronic pain patients.³⁶

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