How to manage pruritus and neuropathy in a patient with Generalized Anxiety Disorder (GAD) and bipolar disorder?

Management of Pruritus and Neuropathy in GAD and Bipolar Disorder

In a patient with GAD and bipolar disorder experiencing pruritus and neuropathy, first rule out medication-induced causes (especially mood stabilizers and antipsychotics), then treat the pruritus with emollients and topical therapies while using gabapentin or pregabalin for neuropathic symptoms, avoiding sedating antihistamines due to cognitive risks in psychiatric populations. 1, 2

Initial Diagnostic Approach

Critical first step: Evaluate whether current psychiatric medications are causing the symptoms. 2

• Conduct a medication review focusing on:
  • Lithium (can cause pruritus and tremor mimicking neuropathy) 2
  • Antipsychotics (especially quetiapine, which can cause metabolic changes leading to small fiber neuropathy) 1
  • Anticonvulsants used as mood stabilizers (may paradoxically cause neuropathy) 1
• If drug-induced pruritus is suspected and the risk-benefit ratio is acceptable, trial medication cessation or substitution 2
• Do not label as psychogenic pruritus until all organic causes are excluded - this is a critical pitfall 1

Evaluation for Neuropathic Pruritus

Neuropathic pruritus occurs from pathology anywhere along the afferent nervous system pathway and commonly presents with burning, paresthesia, stinging, and tingling. 1

• Screen for small fiber neuropathy causes relevant to psychiatric patients:
  • Metabolic syndrome (common with atypical antipsychotics) 1
  • Diabetes mellitus (increased risk with mood stabilizers) 1
  • Vitamin deficiencies (B12, folate) 1
• Consider skin biopsy if clinical suspicion is high, as small fiber neuropathy may not show electrophysiological changes 1

Psychological Factors Assessment

Pruritus can be triggered or worsened by stress, anxiety, and emotional factors - highly relevant in GAD and bipolar patients. 1

• Assess whether pruritus meets criteria for functional itch disorder:
  • Chronic pruritus >6 weeks with no somatic cause 1
  • Variations in intensity associated with stress 1
  • Predominance during rest or inaction 1
  • Pruritus worse at night 1
• Important caveat: The presence of psychiatric comorbidity does NOT mean the pruritus is psychogenic - thorough organic workup is mandatory 1, 3

Treatment Algorithm for Pruritus

First-Line Therapies

Start with emollients and topical agents regardless of etiology. 2

• Emollients applied liberally and frequently to maintain skin hydration 2
• Topical menthol preparations for symptomatic relief 2
• Topical clobetasone butyrate (mild corticosteroid) for localized areas 2
• Topical doxepin (if needed): Limited to 8 days maximum, ≤10% body surface area, ≤12g daily 2, 4

Second-Line Therapies

Non-sedating antihistamines are preferred in psychiatric populations. 2

• Fexofenadine 180 mg daily OR loratadine 10 mg daily 2
• Cetirizine 10 mg (mildly sedative) can be considered if non-sedating options fail 2
• Avoid hydroxyzine despite FDA approval for anxiety and pruritus - it causes QT prolongation, has significant drug interactions with psychiatric medications, and increases dementia risk in long-term use 5, 2

Third-Line Systemic Therapies

For refractory pruritus, consider agents that address both pruritus and psychiatric symptoms. 2

SSRIs/SNRIs (preferred in this population):

• Paroxetine or fluvoxamine - effective for both GAD and pruritus 2, 6, 7
• Sertraline - particularly useful if hepatic component suspected 1
• Advantage: Treats underlying anxiety while addressing pruritus 6, 7, 8

Mirtazapine:

• Effective for both anxiety and pruritus 2, 9
• Sedating properties may help with sleep disturbance from itching 9
• Caution: Weight gain and metabolic effects 9

Treatment of Neuropathic Component

Gabapentin or pregabalin are first-line for neuropathic pruritus and neuropathy. 2

• Gabapentin: Start low (100-300 mg at bedtime), titrate to effect (up to 1800-3600 mg/day divided) 2
• Pregabalin: 75-150 mg twice daily 2, 8
• Critical caveat: Avoid gabapentin if hepatic pruritus is present 2
• Advantage in psychiatric patients: Both agents have anxiolytic properties and can augment mood stabilization 8, 9

Behavioral and Psychological Interventions

Integrate behavioral strategies alongside pharmacotherapy. 1

• "Coping with Itch" program components:
  • Education on trigger avoidance 1
  • Relaxation techniques 1
  • Cognitive restructuring to reduce catastrophizing 1
  • Lifestyle modifications 1
• Evidence: Reduces frequency of itch and scratching, improves coping, decreases healthcare utilization 1
• Patient support groups can be beneficial 2

Critical Pitfalls to Avoid

Drug interactions with psychiatric medications:

• Hydroxyzine potentiates CNS depressants and prolongs QT interval - avoid with antipsychotics 5
• SSRIs for pruritus may interact with existing mood stabilizers - monitor serotonin syndrome risk 6
• Gabapentin/pregabalin can cause sedation when combined with benzodiazepines 2

Premature psychogenic diagnosis:

• Psychiatric comorbidity increases risk of dismissing organic causes 1, 3
• Small fiber neuropathy from metabolic syndrome (common with psychiatric medications) is easily missed 1

Long-term sedating antihistamine use:

• Increases dementia risk - particularly concerning in psychiatric populations 2, 10
• Should only be used in palliative care settings 2

Monitoring and Follow-up

• Reassess after 2-4 weeks of initial therapy 2
• If no improvement, advance to next treatment tier 2
• Monitor for medication interactions with psychiatric regimen 5
• Screen for metabolic complications of psychiatric medications that may worsen neuropathy 1
• Consider dermatology or neurology referral if refractory to initial management 4