What is the recommended treatment approach for patients with Chronic Regional Pain Syndrome (CRPS) experiencing severe depression and anxiety?

Treatment of Severe Depression and Anxiety in Chronic Regional Pain Syndrome (CRPS)

For CRPS patients with severe depression and anxiety, initiate treatment with a serotonin-norepinephrine reuptake inhibitor (SNRI), specifically duloxetine, combined with cognitive behavioral therapy (CBT), as this addresses both the neuropathic pain component and psychiatric symptoms simultaneously. 1

Pharmacological Management

First-Line Antidepressant Selection

• Duloxetine is the preferred first-line agent because it functions as both an adjuvant analgesic for neuropathic pain and treats depression/anxiety, providing dual benefit in CRPS 1, 2
• Alternative SNRIs include venlafaxine, which also addresses both pain and mood symptoms effectively 1, 2
• If SNRIs are contraindicated or not tolerated, use secondary amine tricyclic antidepressants (desipramine or nortriptyline) rather than tertiary amines, as they have better tolerability profiles in older adults and chronic pain populations 1
• Avoid benzodiazepines despite anxiety symptoms, as evidence is equivocal for chronic pain benefit and they carry significant dependence risk 1

Dosing and Monitoring Strategy

• Start duloxetine at low doses (20-30mg daily) and titrate slowly over 2-4 weeks to therapeutic range (60-120mg daily) 1
• Assess treatment response at 4 weeks and 8 weeks using standardized instruments like the PHQ-9 for depression (scores ≥10 require psychiatric referral) 1, 3
• If symptoms remain stable or worsen after 8 weeks despite good adherence, adjust the regimen by either switching medications or adding psychotherapy 1

Psychological Interventions

Cognitive Behavioral Therapy

• CBT should be initiated concurrently with pharmacotherapy, not sequentially, as it has comparable efficacy to antidepressants and addresses pain catastrophizing specific to CRPS 1, 3
• Individual CBT sessions are preferred over group therapy for anxiety disorders 3
• When both depression and anxiety are present, prioritize treating depressive symptoms first, or use a unified protocol combining CBT approaches for both conditions 1

Additional Psychological Support

• Biofeedback and relaxation training provide pain relief and should be incorporated into the treatment plan 1
• Regular assessment by mental health professionals is essential, with evaluations at pretreatment, 4 weeks, 8 weeks, and end of treatment 1, 3

Adjuvant Pain Management

Neuropathic Pain Targeting

• Add gabapentinoids (gabapentin or pregabalin) to the SNRI regimen, as anticonvulsants are recommended as part of multimodal strategy for neuropathic pain in CRPS 1
• Consider topical agents (lidocaine patches or capsaicin) for focal pain, as they provide additional benefit without systemic side effects 1

Avoid Ineffective Agents

• Do not prescribe skeletal muscle relaxants for chronic CRPS pain, as evidence is insufficient and they are not preferred for chronic conditions 1
• Selective serotonin reuptake inhibitors (SSRIs) alone provide less analgesic benefit than SNRIs or tricyclics for pain syndromes 2

Interdisciplinary Team Approach

• Establish care with an interdisciplinary team including pain medicine, psychiatry, physical therapy, and occupational therapy, as CRPS requires coordinated management 1, 4
• Physical and restorative therapy should be used as part of the multimodal strategy to restore function 1
• Consultation-liaison psychiatry involvement is critical, as CRPS patients show higher prevalence of depressive symptoms than general chronic pain populations and carry increased suicide risk 5

Critical Screening Requirements

Baseline Mental Health Assessment

• Screen all CRPS patients for depression using the two-question screen: "During the past 2 weeks have you often been bothered by feeling down, depressed, or hopeless?" and "During the past 2 weeks have you been bothered by little interest or pleasure in doing things?" 1
• If either answer is affirmative, ask: "Is this something with which you would like help?" 1
• Use PHQ-9 for quantitative assessment in settings without immediate psychiatric access (scores ≥10 have 88% sensitivity and specificity for major depression) 1

Assess Modifiable Risk Factors

• Evaluate self-esteem, coping skills, recent major losses, substance use history, domestic safety, and suicidal ideation before initiating treatment 1
• Screen for neurocognitive disorders prior to long-term opioid therapy if being considered 1

Treatment Resistance Management

• If no response after 8 weeks of combined SNRI and CBT, switch to a different antidepressant class (tricyclic) or add augmentation with gabapentinoids 1
• Consider referral to specialized pain psychiatry for refractory cases, as CRPS patients frequently require individualized strategies beyond standard protocols 5, 4, 6
• Monitor for suicidal ideation closely, as CRPS patients with depression have elevated suicide risk compared to general chronic pain populations 5

Common Pitfalls to Avoid

• Do not treat anxiety with benzodiazepines as monotherapy, as this fails to address underlying pain mechanisms and creates dependence risk 1
• Avoid using SSRIs alone when neuropathic pain is prominent, as they lack the noradrenergic component necessary for pain modulation 1, 2
• Do not delay psychiatric referral when PHQ-9 scores are ≥10 or suicidal ideation is present 1
• Never prescribe antidepressants without establishing a monitoring strategy for side effects, adverse events, and compliance 1