Mirtazapine for Akathisia
Yes, low-dose mirtazapine (7.5-15 mg daily) is an effective treatment option for antipsychotic-induced akathisia and should be considered when first-line treatments fail or are contraindicated.
Treatment Algorithm for Akathisia
First-Line Approach
- Reduce antipsychotic dose if clinically feasible, or switch to quetiapine or olanzapine which have lower akathisia risk 1
- Propranolol (10-30 mg, two to three times daily) remains the traditional first-line pharmacological treatment 1
- Benzodiazepines provide symptomatic relief but are not consistently effective 1
When First-Line Options Fail or Are Contraindicated
Mirtazapine emerges as a compelling alternative, particularly when:
- Propranolol is contraindicated (asthma, bradycardia, orthostatic hypotension) 2
- Beta-blockers have failed to provide adequate relief 2
- The patient is on aripiprazole, where mirtazapine shows particularly strong efficacy 3, 4
Mirtazapine Dosing and Evidence
Recommended Dosing
- Start with 7.5 mg once daily at bedtime 3
- Can increase to 15 mg daily if needed 2, 4
- Treatment duration: typically 8-10 days shows significant improvement 3, 4
Efficacy Data
- 41.6% response rate (≥2-point reduction on Barnes Akathisia Rating Scale global subscale) with 7.5 mg dose 3
- 62.5% response rate with 15 mg dose 4
- Significant reductions in subjective distress and global akathisia scores (P<0.01 to P<0.001) 3, 4
- Particularly effective for aripiprazole-induced akathisia 3, 4
Mechanism of Action
Mirtazapine's anti-akathisia properties stem from its marked postsynaptic serotonin 5-HT2a receptor antagonism, representing a mechanistically distinct approach from beta-blockers 2
Side Effect Profile
Expected Side Effects
- Mild, transient sedation (most common, resolves quickly) 4
- Generally well-tolerated at low doses (7.5-15 mg) 3, 4
- At higher antidepressant doses (not used for akathisia), mirtazapine causes sedation (
23%), increased appetite (11%), weight gain (10%), and dry mouth (25%) 5
Critical Caveat
Paradoxical akathisia induction is extremely rare but documented - one case report describes akathisia developing after 20 years of continuous mirtazapine treatment 6. However, this should not deter use at low doses for acute akathisia treatment, as the evidence overwhelmingly supports its anti-akathisia properties 2, 3, 4.
Practical Implementation
The "B-CALM" mnemonic helps recall akathisia treatment options: Beta-blockers, Clonazepam, Anticholinergics, cLonidine, and Mirtazapine 7. Current evidence best supports propranolol and mirtazapine as the most effective options 7.
Monitoring
- Assess Barnes Akathisia Rating Scale scores at baseline and after 7-10 days 3, 4
- Watch for treatment-emergent sedation (usually mild and transient) 4
- Monitor for any worsening of akathisia symptoms, though this is exceedingly rare 6