In an adult without contraindications, which psychotropic agents can be used to reduce itching?

Psychotropic Agents for Reducing Itching

Yes, several psychotropic agents effectively reduce itching, with the strongest evidence supporting SSRIs (particularly sertraline and paroxetine), mirtazapine, and gabapentin/pregabalin, depending on the underlying cause of pruritus.

Evidence-Based Psychotropic Options

For Hepatic Pruritus

• Sertraline is recommended as third-line treatment after rifampicin and cholestyramine for hepatic pruritus 1
• This SSRI should be considered before opioid antagonists like naltrexone 1

For Generalized Pruritus of Unknown Origin (GPUO)

The British Association of Dermatologists guidelines recommend considering the following psychotropic agents 1:

• SSRIs: Paroxetine and fluvoxamine 1
• Tetracyclic antidepressant: Mirtazapine 1
• Anticonvulsants: Gabapentin and pregabalin 1
• Sedating antihistamines: Hydroxyzine (only for short-term or palliative settings) 1

For Opioid-Induced Pruritus

• Mirtazapine is listed as an alternative antipruritic agent when naltrexone cannot be used 1
• Gabapentin is also an option in this context 1

For Psychogenic Pruritus

Topical doxepin (a tricyclic antidepressant) can be prescribed, but treatment must be limited to 8 days, covering no more than 10% body surface area, with maximum 12g daily 1

Supporting Research Evidence

Mirtazapine shows particular promise: A 2019 systematic review found that all studies reported reduction in itch intensity following mirtazapine administration, suggesting it may be effective for chronic pruritus refractory to first-line treatments 2

Broader antidepressant evidence: A 2017 systematic review of oral antidepressants (fluoxetine, fluvoxamine, paroxetine, sertraline, amitriptyline, nortriptyline, doxepin, and mirtazapine) found that the majority of studies showed marked improvement of pruritus, particularly in uremic, cholestatic, and paraneoplastic pruritus 3

Mechanism considerations: Psychotropic drugs are utilized because the central nervous system plays a key role in pruritus development 4, 5. These agents can address both the sensory and emotional components of chronic itch 4

Clinical Algorithm for Selection

1. Identify the underlying cause of pruritus first 1

2. For hepatic pruritus: Use sertraline as third-line after rifampicin and cholestyramine 1

3. For GPUO or refractory pruritus:

   • Start with non-sedating antihistamines first 1
   • If ineffective, consider SSRIs (paroxetine or fluvoxamine) or mirtazapine 1
   • Gabapentin/pregabalin are alternatives 1

4. For elderly patients: Gabapentin may be beneficial, but avoid sedative antihistamines 1

5. Avoid gabapentin specifically in hepatic pruritus 1

Important Caveats

• Most recommendations are based on lower-quality evidence (Strength D), reflecting limited randomized controlled trials 1
• Sedating antihistamines like hydroxyzine should only be used short-term or in palliative settings, not as first-line therapy 1
• Psychosocial interventions should be considered alongside pharmacotherapy for patients with psychogenic pruritus, including behavioral interventions and referral to psychiatry when appropriate 1
• Topical doxepin has strict limitations due to potential systemic absorption and side effects 1