Mirtazapine Dosing for Weight Gain
For weight gain purposes, start mirtazapine at 7.5 mg at bedtime and titrate up to a maximum of 30 mg at bedtime, as this dosing range optimally promotes sleep, appetite, and weight gain. 1
Recommended Dosing Strategy
Initial dose: Begin with 7.5 mg at bedtime 1
Target dose: Increase to 15-30 mg at bedtime as tolerated 1, 2
Maximum dose for weight gain: 30 mg at bedtime 1
The lower end of the therapeutic range (7.5-30 mg) is specifically noted in clinical guidelines for its ability to promote appetite and weight gain, while higher doses used for depression (up to 45 mg) may paradoxically have less weight-promoting effects due to increased noradrenergic activity 1, 2, 3.
Mechanism Supporting Weight Gain
Mirtazapine promotes weight gain through multiple mechanisms 3, 4:
- Histamine H1 receptor antagonism - produces sedation and increased appetite 3, 5
- 5-HT2C receptor blockade - removes serotonergic inhibition of appetite 3, 4
- 5-HT3 receptor antagonism - provides anti-emetic effects that may improve food tolerance 4, 6
Dose Titration Schedule
Week 1: Start 7.5 mg at bedtime 1
Week 2-3: Increase to 15 mg at bedtime if tolerated 2
Week 4+: May increase to 30 mg at bedtime for maximum weight gain effect 1, 2
Do not make dose changes more frequently than every 1-2 weeks to allow adequate assessment of response 2.
Clinical Evidence for Weight Gain
In depression treatment trials, mirtazapine consistently produced weight gain as a side effect, with 10% of patients experiencing clinically significant weight gain compared to 1% with placebo 1. The drug increases appetite in 11% versus 2% with placebo 1.
A small open-label trial in cancer-related cachexia using 15-30 mg daily showed 24% of patients gained ≥1 kg at 4 weeks, with 24% reporting improved appetite 7. One retrospective study in dementia patients using 30 mg daily reported mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with approximately 80% experiencing weight gain 1.
Important Clinical Considerations
Common side effects at these doses include: 1, 5, 4
- Sedation (19-23% vs 5-14% placebo) - dose at bedtime to minimize daytime impairment
- Increased appetite (11% vs 2% placebo)
- Dry mouth (25% vs 16% placebo)
- Dizziness
Contraindications and cautions: 2, 5
- Screen for bipolar disorder before initiating (risk of manic switch)
- Avoid within 14 days of MAOI use
- Monitor for rare agranulocytosis (obtain baseline CBC, monitor if fever/infection develops)
- Use caution with strong CYP3A4 inhibitors or inducers (may require dose adjustment)
Monitoring parameters:
- Weight weekly for first month, then monthly 7
- Appetite and food intake
- Sedation level (may decrease over 1-2 weeks)
- CBC if signs of infection develop 3, 5
Context: When NOT to Use for Weight Gain
Current guidelines explicitly recommend against using appetite stimulants, including mirtazapine, for weight gain in persons with dementia, as evidence is very limited and side effects must be balanced against uncertain benefits 1. The exception would be dementia patients who also have depression requiring antidepressant treatment, where mirtazapine could serve dual purposes 1.
For general obesity management, mirtazapine is listed among antidepressants that cause weight gain and should be avoided when possible 1.
Discontinuation
When stopping mirtazapine, taper gradually rather than stopping abruptly to minimize withdrawal symptoms 2. A reasonable taper would be reducing by 7.5-15 mg every 1-2 weeks.