What are the psychiatric effects of long-term opioid use?

Psychiatric Effects of Long-Term Opioid Use

Long-term opioid therapy significantly increases the risk of opioid use disorder, major depression, and psychological distress, with prevalence of opioid dependence ranging from 3% to 26% in primary care settings and depression risk increasing in a dose-dependent manner. 1

Primary Psychiatric Risks

Opioid Use Disorder (OUD)

• Long-term opioid therapy is associated with increased risk of opioid abuse or dependence diagnosis compared to no opioid prescription. 1
• The prevalence of opioid dependence (DSM-IV criteria) in primary care settings ranges from 3% to 26%, representing a substantial psychiatric burden. 1
• OUD manifests as unsuccessful efforts to reduce or control use, use resulting in social problems, and failure to fulfill major role obligations at work, school, or home—distinct from tolerance and physical dependence. 1

Risk Factors for Psychiatric Complications

Specific patient characteristics dramatically increase psychiatric risk:

• History of substance use disorder 1
• Younger age 1
• Major depression (doubles the risk of transitioning to long-term use) 2
• Use of psychotropic medications 1

Depression and Bidirectional Relationship

• Long-term opioid therapy increases the risk of incident, recurrent, and treatment-resistant depression when controlling for confounding factors. 2
• Depressed patients are twice as likely to transition from short-term to long-term opioid use, representing adverse selection of high-risk patients. 2
• Depressed patients continue opioid use at lower pain intensity levels and higher levels of physical function than nondepressed patients, suggesting use for mood regulation rather than analgesia. 2
• Depression increases the risk of nonmedical opioid use among both adults and adolescents, which may be the pathway through which depression increases opioid use disorder risk. 2

Additional Psychiatric and Neuropsychiatric Effects

Cognitive and Mood Disturbances

• Sedation, decreased concentration and memory, drowsiness, and changes in mood are common adverse effects that limit treatment tolerability. 1
• Mental cloudiness and other changes in mental status, including mood effects and memory problems, occur with long-term use. 1
• Increased risk of falls in the elderly is associated with these cognitive effects. 1

Withdrawal-Related Psychiatric Symptoms

• Anxiety, restlessness, and psychological distress are cardinal features of opioid withdrawal syndrome. 1, 3
• Abrupt reduction or discontinuation has been associated with serious psychological distress and suicidality. 1
• Withdrawal symptoms begin 2-3 half-lives after the last dose, peak at 48-72 hours, and typically resolve within 7-14 days. 3

Clinical Implications for Monitoring

Clinicians must assess for psychiatric effects at specific intervals:

• Within 1-4 weeks of starting long-term opioid therapy or dose escalation, assess for early warning signs of opioid use disorder (craving, wanting to take opioids in greater quantities or more frequently than prescribed, difficulty controlling use). 1
• At least every 3 months for all patients on long-term therapy, evaluating for signs of opioid use disorder and depression. 1
• More frequently than every 3 months for patients with depression or other mental health conditions, as they represent higher-risk populations. 1

Evidence Quality Context

The evidence base for long-term opioid therapy remains limited, with no studies evaluating outcomes ≥1 year for pain, function, or quality of life. 1 Most evidence comes from observational studies or randomized trials with notable limitations (evidence type 3 or 4). 1 Despite limited evidence for long-term benefits, the psychiatric harms are well-documented and dose-dependent. 1

A critical caveat: While some older literature suggests opioids may have antidepressant properties in select populations, 4 the preponderance of higher-quality evidence demonstrates that long-term opioid therapy increases depression risk and worsens psychiatric outcomes in chronic pain populations. 2 The potential for short-term mood elevation should not be confused with long-term psychiatric safety.