Mirtazapine Dosing for Neuropathic Pain
Mirtazapine is not a first-line agent for neuropathic pain and lacks robust clinical evidence for this indication—you should use duloxetine, gabapentin, or pregabalin instead. 1
Why Mirtazapine Is Not Recommended for Neuropathic Pain
The most recent and highest-quality guideline evidence does not support mirtazapine for neuropathic pain management:
The 2020 ESMO-EONS-EANO guidelines for chemotherapy-induced peripheral neuropathy make no mention of mirtazapine as a treatment option, instead recommending duloxetine (Level I, Grade B evidence) as the only antidepressant with proven efficacy 1
The 2011 consensus recommendations for painful diabetic peripheral neuropathy similarly omit mirtazapine from treatment algorithms, recommending duloxetine 60-120 mg/day and venlafaxine 150-225 mg/day as the evidence-based antidepressant options 1
The 2010 NCCN cancer pain guidelines list tricyclic antidepressants (amitriptyline, nortriptyline, desipramine), duloxetine, venlafaxine, and bupropion as antidepressant coanalgesics for neuropathic pain, but do not include mirtazapine 1
What the Limited Evidence Shows
While mirtazapine is mentioned in one older guideline for Alzheimer's disease management, this reference is for treating depression—not neuropathic pain—with dosing of 7.5 mg at bedtime titrated to 30 mg at bedtime 1. This context is entirely different from neuropathic pain management.
The only relevant research is a 2008 animal study showing that mirtazapine 20-30 mg/kg in rats reduced neuropathic pain through anti-inflammatory mechanisms 2. However, animal data cannot be extrapolated to clinical practice, and no human trials have validated mirtazapine for neuropathic pain.
Recommended First-Line Agents Instead
For neuropathic pain, use these evidence-based options:
Duloxetine: Start 30 mg daily for 1 week, then increase to 60 mg daily (the only antidepressant with Level I, Grade B evidence for neuropathic pain) 1
Gabapentin: Start 100-300 mg at bedtime, titrate to 900-3600 mg/day in divided doses over 3-8 weeks 3, 4
Pregabalin: Start 50 mg three times daily, increase to 100 mg three times daily, maximum 600 mg/day 1
Tricyclic antidepressants (if duloxetine fails): Nortriptyline or desipramine 10-25 mg nightly, increase to 50-150 mg nightly (better tolerated than amitriptyline) 1
Critical Clinical Pitfall
Do not use mirtazapine as a primary treatment for neuropathic pain. While it has sedating properties that might help with sleep disturbances in depressed patients 1, 5, this does not translate to analgesic efficacy for neuropathic pain. The drug's mechanism—enhancing noradrenergic and serotonergic neurotransmission via α2-adrenoceptor blockade 6, 7—differs fundamentally from the dual serotonin-norepinephrine reuptake inhibition of duloxetine, which has proven neuropathic pain efficacy 1.
If Mirtazapine Must Be Used (Off-Label)
If you are considering mirtazapine despite lack of evidence (perhaps for comorbid depression with insomnia and poor appetite), the standard antidepressant dosing would be: Start 7.5-15 mg at bedtime, increase to 30-45 mg at bedtime 1, 5, 7. However, this remains an off-label use without supporting evidence for neuropathic pain, and the animal study suggesting benefit used much higher weight-adjusted doses (20-30 mg/kg) than are feasible in humans 2.
The evidence strongly favors duloxetine, gabapentin, or pregabalin as your first choice for neuropathic pain. 1