How to manage anxiety in a patient with long-term opioid use?

Managing Anxiety in Patients with Long-Term Opioid Use

Anxiety in patients on long-term opioids should be managed primarily through non-benzodiazepine approaches, including optimizing treatment for underlying anxiety disorders with SSRIs or SNRIs, implementing cognitive-behavioral therapy, and carefully evaluating whether the anxiety is related to inadequate pain control, opioid-induced effects, or an independent anxiety disorder. 1

Initial Assessment and Differential Diagnosis

When evaluating anxiety in a patient on chronic opioids, you must distinguish between several distinct entities:

• Therapeutic dependence/drug-seeking from inadequate pain control: Patients may exhibit anxiety-like behaviors because they fear pain recurrence or withdrawal symptoms, not true anxiety disorder 1
• Opioid-induced effects: Long-term opioid use can cause cognitive symptoms (reduced focus, memory problems) that may manifest as or worsen anxiety 1
• Withdrawal-related anxiety: If opioids are being tapered, anxiety is a cardinal withdrawal symptom that peaks at 48-72 hours and resolves within 7-14 days 1
• Independent anxiety disorder: Pre-existing or comorbid generalized anxiety disorder, panic disorder, social anxiety, or PTSD 1

Primary Treatment Approach

Optimize Anxiety Disorder Treatment (First-Line)

• Use SSRIs or SNRIs as first-line pharmacotherapy for anxiety disorders in this population, as they provide both anxiolytic and potential analgesic effects without respiratory depression risk 1
• Implement evidence-based psychotherapy, particularly cognitive-behavioral therapy (CBT), which has demonstrated efficacy for anxiety in patients on opioids 2
• Screen for anxiety using validated instruments (GAD-7, PHQ-4) to establish baseline severity and monitor response 1

Address Pain Management

• Reassess whether current opioid therapy is providing meaningful benefit for pain and function, as inadequate pain control can manifest as anxiety and drug-seeking behaviors 1
• If pain is inadequately controlled, optimize non-opioid analgesics and non-pharmacologic pain treatments rather than escalating opioid doses 1
• Discuss the pain management plan in a nonjudgmental manner to relieve patient anxiety about potential inadequate treatment 1

Critical Medication Safety Considerations

Avoid Benzodiazepines

Benzodiazepines should be avoided in patients on long-term opioids due to profound risk of respiratory depression, coma, and death. 3 The FDA explicitly warns that concomitant use increases drug-related mortality compared to opioids alone 3. If a patient is already taking both:

• Taper benzodiazepines first before considering opioid reduction, as benzodiazepine withdrawal carries higher risks including seizures and death 4
• Use a gradual benzodiazepine taper of 25% of the initial dose every 1-2 weeks, or slower (10% per month for long-term users) 4
• Monitor closely for withdrawal symptoms: anxiety, tremor, insomnia, sweating, tachycardia, and potentially seizures 4
• Consider adjunctive medications during benzodiazepine taper: gabapentin (100-300 mg titrated cautiously), carbamazepine, or pregabalin 4

Monitor for Opioid Use Disorder

• Patients with anxiety disorders have increased risk for developing opioid use disorder 1, 5
• Screen for signs of opioid misuse, particularly in patients with comorbid anxiety and depression, as emotion dysregulation may link these conditions to opioid-related problems 6
• If opioid use disorder is suspected, offer or arrange medication-assisted treatment with buprenorphine or methadone 4

Special Considerations During Opioid Tapering

If opioid tapering is being considered or implemented:

• Expect anxiety to emerge or worsen during tapering, as this is a common withdrawal symptom and may also reflect unmasking of underlying anxiety disorders 1
• Use a slow taper (10% of original dose per week as starting point, individualized based on tolerance) to minimize withdrawal-related anxiety 1
• Provide psychosocial support and optimize anxiety treatment before and during the taper through collaboration with mental health providers 1
• Monitor closely for anxiety, depression, and suicidal ideation during tapering 4
• Distinguish between time-limited withdrawal anxiety (resolves in 7-14 days) versus persistent anxiety disorder requiring ongoing treatment 1

Evidence on Buprenorphine for Comorbid Conditions

• For patients with opioid use disorder and generalized anxiety disorder, buprenorphine maintenance therapy may provide rapid anxiety reduction, though evidence is limited to small studies 7
• Methadone tapering may be superior to buprenorphine for managing anxiety and social functioning deficits during opioid withdrawal in preclinical models 8

Prognostic Considerations

• Patients with anxiety and chronic pain who are taking opioids show similar improvement rates with anxiety treatment (CBT and/or medication) compared to those not on opioids, but have lower overall response and remission rates at 18 months 2
• Among patients with comorbid pain and anxiety, those using opioids may show reduced sustained anxiety treatment response 2
• The comorbidity of opioid use disorder and anxiety disorders is associated with more severe clinical presentation and poorer prognosis 5