What are the side effects of chronic opioid (narcotic analgesic) use?

From the Guidelines

Chronic opioid use is associated with a high risk of side effects, including constipation, nausea, sedation, respiratory depression, and the development of tolerance and physical dependence, and therefore, should be prescribed with caution and careful monitoring, as recommended by the most recent study 1. The most common side effects of chronic opioid use include:

• Constipation, which affects nearly all chronic opioid users, and can be managed with a prophylactic bowel regimen, including stool softeners like docusate sodium (100mg twice daily) and stimulant laxatives such as senna (8.6mg daily to twice daily) 1
• Nausea, which often improves after 1-2 weeks of therapy, but can be managed with antiemetics like ondansetron (4mg every 6-8 hours as needed) or promethazine (12.5-25mg every 6 hours as needed) 1
• Sedation, which typically improves with continued use, but patients should avoid driving or operating machinery until effects are known 1
• Respiratory depression, which is most concerning in opioid-naïve patients or with dose increases, and patients should be monitored closely during these periods 1
• Long-term use leads to tolerance, requiring dose increases to maintain pain control, and physical dependence, necessitating gradual tapering (typically 10% reduction every 1-2 weeks) when discontinuing to avoid withdrawal symptoms 1 Other potential side effects include hormonal changes, immune suppression, hyperalgesia, and increased risk of falls 1. Regular assessment of benefits versus risks is essential, with consideration of opioid rotation or adjunctive non-opioid therapies if side effects become problematic, and the use of opioid risk prediction tools, such as the SOAPP, SOAPP-R, and ORT, can help identify patients at high risk of opioid-related harms 1. The decision to treat chronic pain with opioid analgesics should be made with caution, and patients should be closely monitored for signs of opioid-related harms, as recommended by the American Pain Society and the American Academy of Pain Medicine 1.

From the FDA Drug Label

The potential for these risks should not, however, prevent the prescribing of buprenorphine hydrochloride for the proper management of pain in any given patient Patients at increased risk may be prescribed opioids such as buprenorphine hydrochloride, but use in such patients necessitates intensive counseling about the risks and proper use of buprenorphine hydrochloride along with frequent reevaluation for signs of addiction, abuse, and misuse. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist

Chronic Opioid Use Side Effects:

• Respiratory Depression: Life-threatening respiratory depression can occur with opioid use, even at recommended doses.
• Sleep-Related Breathing Disorders: Opioids can cause central sleep apnea and sleep-related hypoxemia.
• Opioid-Induced Hyperalgesia: Opioids can increase pain or sensitivity to pain.
• Physical Dependence: Opioid use can lead to physical dependence, with withdrawal symptoms occurring after abrupt discontinuation.
• Addiction, Abuse, and Misuse: Opioids carry a risk of addiction, abuse, and misuse, particularly in patients at increased risk.

2

From the Research

Chronic Opioid Use and Side Effects

• Chronic opioid use can lead to opioid use disorder (OUD), a chronic, relapsing condition associated with various problems, including legal, interpersonal, and employment issues 3.
• Medications such as methadone, buprenorphine, and naltrexone are effective for treating OUD, but may have limitations, including poor adherence to treatment recommendations and high rates of relapse and overdose 3, 4, 5.
• Long-term opioid therapy (LTOT) is often used to control chronic pain, but its inefficacy and complications have led to more frequent opioid tapering, which can also have its own set of complications 6.
• Complex persistent opioid dependence (CPOD) is a clinically distinct but biologically similar state compared to OUD, and its treatment may involve buprenorphine, but more research and policy development are needed to clarify its definition, mechanisms, and treatment 6.

Treatment Options

• Methadone, buprenorphine, and naltrexone are the primary medications used to treat OUD, with methadone having the strongest evidence for effectiveness 3, 7.
• Buprenorphine is a partial opioid agonist that can be used to treat OUD, and its different formulations, including long-acting injectable formulations, may decrease the risk of diversion and improve adherence 4, 7.
• Naltrexone is an opioid antagonist that can be used to reverse opioid overdose, and take-home naloxone programs aim to prevent fatal overdose 3.

Challenges and Limitations

• OUD treatment is often limited by lack of access and stigma, and expanding access to approved treatments such as methadone may be the most useful approach to addressing the rising toll from OUD 3.
• The treatment of CPOD requires further clarification through research and policy development, and the increasing utilization of buprenorphine for both LTOT ineffectiveness and opioid tapering problems raises urgent needs for review of its clinical definition, mechanisms, and treatment 6.