From the Guidelines
Chronic opioid use can lead to severe side effects, including physical dependence, tolerance, and addiction, as well as increased risk for opioid use disorder, overdose, and death, particularly at higher dosages, as noted in the 2022 CDC clinical practice guideline for prescribing opioids for pain 1.
Severe Side Effects of Chronic Opioid Use
Some of the most severe side effects of chronic opioid use include:
- Physical dependence and addiction
- Respiratory depression, which can be fatal
- Hormonal imbalances, such as reduced testosterone in men and irregular menstruation in women
- Gastrointestinal problems, including severe constipation, bowel obstruction, hemorrhoids, and anal fissures
- Opioid-induced hyperalgesia, which increases pain sensitivity
- Immune system suppression, increasing susceptibility to infections
- Cognitive impairment, affecting memory, attention, and decision-making
- Sleep-disordered breathing, including sleep apnea
- Cardiovascular risks, including heart rhythm abnormalities and increased risk of heart attack
Medications Involved
Common medications involved in chronic opioid use include:
- Morphine
- Oxycodone (OxyContin)
- Hydrocodone (Vicodin)
- Fentanyl
- Methadone
Recommendations for Clinicians
Clinicians should exercise caution when prescribing opioids for chronic pain, considering the potential risks and benefits, and should prioritize non-opioid treatments and multimodal pain management approaches 1.
Key Considerations
- Opioid therapy should only be initiated with consideration of an exit strategy and careful monitoring of patients for signs of opioid use disorder and overdose
- Clinicians should discuss the risks and benefits of opioid therapy with patients, including the potential for physical dependence, addiction, and overdose
- Patients should be closely monitored for signs of opioid-related harms, and opioid doses should be tapered or discontinued if necessary to minimize risks
- Non-opioid treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and nonpharmacologic therapies, should be prioritized for chronic pain management whenever possible 1.
From the FDA Drug Label
The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3)] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5. 4)] Interactions with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions (5.5)] Adrenal Insufficiency [see Warnings and Precautions (5.8)] Severe Hypotension [see Warnings and Precautions (5.9)] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.11)] Seizures [see Warnings and Precautions (5.12)] Withdrawal [see Warnings and Precautions (5. 13)] Serious adverse reactions associated with morphine use included: respiratory depression, apnea, and to a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest. Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Androgen Deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12. 2)] .
The most severe side effects of chronic opioid use long term include:
- Life-threatening respiratory depression
- Addiction, abuse, and misuse
- Adrenal insufficiency
- Androgen deficiency
- Seizures
- Serotonin syndrome
- Severe hypotension
- Gastrointestinal adverse reactions
- Respiratory arrest, shock, and cardiac arrest 2
- Neonatal opioid withdrawal syndrome 2
From the Research
Severe Side Effects of Chronic Opioid Use
- Common side effects of opioid administration include:
- Sedation
- Dizziness
- Nausea
- Vomiting
- Constipation
- Physical dependence
- Tolerance
- Respiratory depression 3
- Less common side effects may include:
- Delayed gastric emptying
- Hyperalgesia
- Immunologic and hormonal dysfunction
- Muscle rigidity
- Myoclonus 3
- Long-term opioid use may have significant effects on various systems, including:
- Endocrine system
- Immune system
- Cardiovascular system
- Respiratory system
- Gastrointestinal system
- Neural system 4
- Increased risk of:
- Fractures
- Infections
- Cardiovascular complications
- Sleep-disordered breathing
- Bowel dysfunction
- Overdose
- Mortality 4
- Opioid use disorder (OUD) is a complex, primary, chronic, neurobiological disease rooted in genetic, environmental, and psychosocial factors 5
- Depression is closely linked to long-term opioid therapy, with depressed patients being twice as likely to transition to long-term use and at higher risk of opioid misuse and addiction 6
Management of Opioid-Related Side Effects
- Proper patient screening, education, and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events 3
- Switching opioids and/or routes of administration may provide benefits for patients 3
- Opioid-based medications and non-opioid drugs may be used to treat patients with OUD and alleviate opioid withdrawal symptoms 5
- Clinicians should be aware of the complications associated with prescribing opioids, discuss them with patients, prevent complications if possible, and diagnose them early and manage adequately 4