How long does it take for mirtazapine to start working for akathisia?

Mirtazapine for Akathisia: Onset of Action

Low-dose mirtazapine (15 mg/day) typically begins working for akathisia within 3-5 days of treatment initiation. 1

Mechanism and Effectiveness

Mirtazapine works against akathisia primarily through its potent serotonin 5-HT2A/2C receptor antagonism. This pharmacological property makes it particularly effective for treating antipsychotic-induced akathisia, even when other treatments have failed.

• In a double-blind randomized placebo-controlled study, significant improvements in akathisia symptoms were observed by day 3 of treatment with 15 mg/day of mirtazapine 1
• By day 5 of treatment, 53.8% of patients showed a clinically significant response (defined as a reduction of at least two points on the Barnes Akathisia Scale global subscale) 1

Dosing Considerations

For akathisia treatment:

• Starting dose: 15 mg once daily
• Duration: Improvement typically begins within 3-5 days
• Administration: Usually given at bedtime due to sedative effects

Unlike its use for depression where doses typically range from 15-45 mg/day, lower doses (15 mg) appear to be sufficient for akathisia treatment. This is important because at this dose, mirtazapine predominantly acts as a 5-HT2A/2C antagonist while minimizing other receptor effects.

Evidence for Different Types of Akathisia

Mirtazapine has shown effectiveness for akathisia induced by:

• Traditional neuroleptics 1
• Atypical antipsychotics including aripiprazole 2

In a study specifically examining aripiprazole-induced akathisia, mirtazapine (15 mg/day) produced significant improvement in subjective, distress, and global akathisia symptoms after a mean treatment duration of 8.5 days 2.

Advantages Over Other Treatments

Mirtazapine offers several advantages over traditional akathisia treatments:

• Well-tolerated with minimal side effects (mild sedation being the most common) 1, 2
• No cardiovascular side effects like those seen with propranolol
• May simultaneously help with insomnia, which often accompanies akathisia
• Can be beneficial for patients with comorbid depression

Potential Side Effects

The most common side effect of mirtazapine when used for akathisia is mild sedation, which is typically transient 2. This sedative effect can actually be beneficial when akathisia causes significant distress and sleep disturbance.

Clinical Pearls

• While mirtazapine is typically used as an antidepressant, it has emerged as an effective treatment for akathisia due to its specific receptor profile
• Paradoxically, there have been rare case reports of mirtazapine itself causing akathisia after prolonged use 3, though this is uncommon
• The anti-akathisia effect appears to be most pronounced at lower doses (15 mg) rather than higher antidepressant doses

For optimal results, monitor response at days 3 and 5 after initiation, as significant improvement should be evident by this time if the medication is going to be effective for akathisia.