mirtazapine

General Information

Mirtazapine (Remeron) is a noradrenergic and specific serotonergic antidepressant (NaSSA) approved for major depressive disorder and frequently chosen for patients needing sedation, appetite stimulation, or an augmentation option with low sexual side-effect burden.

Despite advantages for insomnia or cachexia, weight gain and metabolic monitoring are central considerations when selecting mirtazapine as monotherapy or adjunct therapy.

The compare tool can help contrast sedation, weight change, and activation strategies, and mirtazapine evidence summaries can support review when adjusting augmentation plans.

For bipolar-spectrum augmentation or insomnia management, follow-up can be coordinated with the bipolar disorder hub, and counselling materials from the mirtazapine print view can support monitoring expectations.

Sedation and weight gain make metabolic monitoring standard; rare agranulocytosis makes infection-symptom counseling important.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Antagonizes central α2 autoreceptors and heteroreceptors, increasing norepinephrine and serotonin release, and blocks 5-HT2 and 5-HT3 receptors while enhancing 5-HT1A transmission.

Potent H1 antagonism explains strong sedative and appetite-stimulating effects.

• α2 antagonist; 5-HT2/5-HT3 antagonist; potent H1 antagonist.

Metabolism and Pharmacokinetics

• Peak ~2 h; half-life 20–40 h.
• Metabolized via CYP1A2, CYP2D6, CYP3A4 to inactive metabolites; eliminated renally and via feces.

Dosing and Administration

• Typical adult initiation: 15 mg at bedtime; increase to 30 mg after 1–2 weeks based on response; usual maintenance 15–45 mg nightly.
• Lower doses (7.5–15 mg) can cause more prominent sedation; doses ≥30 mg often provide stronger antidepressant effects with relatively less sedation.
• Older adults or patients with renal/hepatic impairment often start 7.5–15 mg nightly with cautious titration; doses may be limited to 30 mg/day in moderate impairment.
• Tapering is typically gradual over weeks to avoid cholinergic rebound and discontinuation symptoms.

Monitoring & Labs

• Weight and appetite changes, plus fasting lipids and glucose at baseline and periodically, given weight gain and dyslipidemia risk.
• Daytime sedation and falls risk, especially in older adults and when other sedatives are co-prescribed.
• Infection symptoms (fever, sore throat) given rare neutropenia; prompt evaluation is appropriate when symptoms arise.
• Mood elevation or agitation in bipolar-spectrum illness; coordinate prevention plans via the bipolar disorder hub.

Mirtazapine is often chosen for insomnia and poor appetite; metabolic monitoring and anticipatory counseling on weight gain are key to sustained adherence. Sedation precautions and infection symptom reporting are commonly revisited throughout treatment.

Adverse Effects

Interactions

• Contraindicated with MAOIs; a 14-day washout is typically used to avoid hypertensive crisis or serotonin syndrome.
• Additive sedation with alcohol, benzodiazepines, opioids, or other CNS depressants—driving and machinery precautions are commonly discussed.
• CYP1A2/2D6/3A4 inhibitors (fluvoxamine, paroxetine, ketoconazole) increase levels; inducers (carbamazepine, phenytoin) lower exposure—dose adjustments are guided by clinical response.
• Combined serotonergic agents (SSRIs, SNRIs, linezolid, triptans, tramadol) increase serotonin syndrome risk; combinations are often avoided or monitored closely.

Other Useful Information

• Good option for depression with insomnia, poor appetite, or sexual dysfunction intolerance; lifestyle strategies to counter metabolic effects are often discussed.
• Weight/BMI, blood pressure, and fasting lipids/glucose are typically monitored at baseline and periodically during therapy.
• Education often covers agranulocytosis warning signs (fever, sore throat) and that these symptoms warrant prompt evaluation.
• Pregnancy planning and breastfeeding are typically discussed; obstetrics coordination is common to weigh benefits versus potential risks.
• In bipolar depression augmentation, monitoring for emergent mania/hypomania can be coordinated with the bipolar disorder hub.
• Dosing time matters: bedtime dosing is typical for sedation; if daytime fatigue persists, dose, other sedatives, and sleep disorders are often reassessed.

References

1. Remeron (mirtazapine) prescribing information — DailyMed (2025)
2. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
3. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)
4. Comparative efficacy and acceptability of 21 antidepressant drugs for major depressive disorder — The Lancet (2018)Meta-analysisdepressionefficacy