Schedule H

Oral

Formulation Type Available Strengths

Film-coated tablets 7.5 mg, 15 mg, 30 mg, 45 mg

Orally disintegrating tablets (ODT) 15 mg, 30 mg, 45 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD) — Adults

Parameter Recommendation

Starting dose 15 mg once daily at bedtime

Titration Increase by 15 mg every 1–2 weeks based on response and tolerability

Usual maintenance dose 15–45 mg once daily

Maximum dose 45 mg/day

Clinical notes:

• Administer at bedtime due to sedating effect

• Paradoxically, lower doses (15 mg) are more sedating than higher doses (30–45 mg) due to dose-dependent noradrenergic activation

• Onset of antidepressant effect typically 1–2 weeks; full response may take 4–6 weeks

• Preferred in depressed patients with insomnia, poor appetite, or weight loss

• Avoid abrupt discontinuation — gradual taper required over 2–4 weeks

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes Evidence

Generalised Anxiety Disorder (GAD) Starting: 15 mg at bedtime; Maintenance: 15–30 mg/day 8–12 weeks trial OFF-LABEL; Specialist only Meta-analyses; Indian psychiatric practice

Insomnia associated with depression 7.5–15 mg at bedtime Short-term adjunct OFF-LABEL; Specialist only Low-dose sedative effect; widely used in Indian psychiatric settings

Appetite stimulation in anorexia/cachexia 15–30 mg at bedtime Variable OFF-LABEL; Specialist only Observational studies; palliative care practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable. Mirtazapine has no approved paediatric indications in India.

Secondary Indications — Paediatric (Off-label)

Indication Age Dose Notes Evidence

Major Depressive Disorder ≥12 years Starting: 15 mg once daily at bedtime OFF-LABEL; Specialist only Limited international data

Titration: Increase by 15 mg every 2 weeks if needed Child/adolescent psychiatrist supervision mandatory

Usual maintenance: 15–30 mg/day

Maximum: 45 mg/day

Safety Monitoring in Paediatrics:

• Monitor for suicidal ideation and behavioural changes — especially in first 1–2 months

• Assess weight gain, sedation, and academic performance regularly

• Baseline and periodic metabolic parameters (weight, lipids, glucose)

Important statements:

• Not recommended below 12 years of age under any circumstances

• Use in adolescents requires paediatric psychiatrist supervision

• Black box warning regarding increased suicidality in young patients applies

• Known hypersensitivity to mirtazapine or any excipient

• Concurrent use with MAO inhibitors — contraindicated during treatment and for at least 14 days after stopping MAOI; wait at least 14 days after stopping mirtazapine before starting MAOI

• Concurrent use with linezolid or intravenous methylene blue (MAOI activity)

• History of bipolar disorder — risk of inducing manic or hypomanic episode

• Suicidal ideation — particularly in first few weeks of treatment and in young adults

• Seizure disorders — may lower seizure threshold

• Elderly patients — increased risk of sedation, falls, and confusion

• Risk of hyponatraemia (SIADH) — especially in elderly or volume-depleted patients

• Pre-existing metabolic syndrome, obesity, or diabetes — mirtazapine causes weight gain

• Bone marrow suppression history — rare agranulocytosis reported

• Narrow-angle glaucoma — anticholinergic effects

• Urinary retention — use with caution in prostatic hypertrophy

• Discontinuation syndrome if stopped abruptly

Parameter Recommendation

Overall safety Limited human data; animal studies show some risk — use only if benefit clearly outweighs risk

Preferred alternative Sertraline (more safety data in pregnancy)

When may be used Only if essential; shared decision with psychiatrist and obstetrician; avoid in first trimester if possible

What to monitor Maternal weight gain (mirtazapine increases appetite); neonatal withdrawal symptoms if used late in pregnancy (respiratory distress, feeding difficulties, irritability)

Parameter Recommendation

Compatibility Compatible with breastfeeding; low levels in breast milk

Preferred alternative Sertraline, nortriptyline

Drug levels in milk Low

Infant monitoring Sedation, feeding difficulties, excessive weight gain

Parameter Recommendation

Starting dose 7.5–15 mg once daily at bedtime

Titration Slow titration — every 2–4 weeks

Special risks Sedation, dizziness, confusion, falls, orthostatic hypotension

Additional considerations Monitor closely for hyponatraemia (SIADH); consider ODT formulation if swallowing difficulties; increased sensitivity to anticholinergic effects

Interacting Drug Effect / Risk Recommendation

MAO inhibitors (phenelzine, selegiline, tranylcypromine) Serotonin syndrome — potentially fatal Contraindicated

Linezolid, IV methylene blue MAOI activity — serotonin syndrome risk Contraindicated

Clonidine, methyldopa Mirtazapine antagonises α2-adrenergic effects — may reduce antihypertensive efficacy Avoid combination if used for BP control

CNS depressants (benzodiazepines, opioids, alcohol) Additive sedation; respiratory depression risk Avoid or use with extreme caution; reduce doses

Carbamazepine, phenytoin CYP3A4 induction — reduced mirtazapine levels May need increased mirtazapine dose; monitor response

Interacting Drug Effect / Risk Recommendation

SSRIs, SNRIs Risk of serotonin syndrome Avoid combination or use with caution under specialist supervision

Tramadol Additive CNS depression; serotonin syndrome risk Use with caution; consider alternatives

Warfarin Possible minor increase in INR Monitor INR when initiating or stopping mirtazapine

Ketoconazole, itraconazole CYP3A4 inhibition — increased mirtazapine levels Monitor for increased sedation and adverse effects

Cimetidine Inhibits mirtazapine metabolism — increased levels Monitor for adverse effects; consider dose reduction

Rifampicin CYP3A4 induction — reduced mirtazapine efficacy May require increased mirtazapine dose

• Sedation and somnolence (very common, especially at lower doses)

• Increased appetite

• Weight gain

• Dry mouth

• Constipation

• Dizziness

• Peripheral oedema

• Vivid or abnormal dreams

• Fatigue

Adverse Effect Notes

Agranulocytosis / Neutropenia Rare; if unexplained fever, sore throat, or infection occurs — check CBC immediately; discontinue if confirmed

Seizures Rare; particularly at high doses or in predisposed patients

SIADH / Hyponatraemia Especially in elderly — monitor sodium; discontinue if symptomatic

Serotonin syndrome If combined with serotonergic drugs — agitation, hyperthermia, tremor; discontinue immediately

Suicidal ideation Especially in young adults — close monitoring in first 1–2 months

Hepatotoxicity Rare; monitor LFTs if symptoms of hepatic dysfunction appear

QT prolongation Rare; caution with other QT-prolonging drugs

Long-term Weight and BMI at each visit; fasting lipids and glucose every 6–12 months; CBC if unexplained fever/infection; serum sodium periodically in elderly

• Mirtaz (Sun Pharma)

• Mirnite / Mirnite Meltab (Intas)

• Mirt (Torrent)

• Zapiz M (Intas) — FDC with clonazepam

• Mirtagard (Micro Labs)

• Mirtazap (Cipla)

• Remeron (Organon — limited availability)

• Multiple generic brands available

Notes:

• Prices vary by brand and procurement source

• Not listed under NLEM 2022 — not price-controlled under NPPA

• Government supply availability is limited

1. Dose-dependent sedation paradox: Lower doses (7.5–15 mg) are more sedating than higher doses (30–45 mg) — at higher doses, noradrenergic activation counteracts histamine-mediated sedation; use this to tailor therapy

1. Ideal for depression with insomnia or weight loss: The sedating and appetite-stimulating properties make mirtazapine particularly suitable for depressed patients with prominent insomnia, anorexia, or weight loss

1. Useful after SSRI-induced sexual dysfunction: Mirtazapine has minimal sexual side effects compared to SSRIs — consider as alternative or augmentation

1. ODT formulation for elderly or dysphagic patients: Orally disintegrating tablets dissolve without water — useful for patients with swallowing difficulties

1. Always taper gradually: Reduce dose by 25–50% weekly over 2–4 weeks to avoid discontinuation symptoms (dizziness, nausea, paraesthesia, agitation)

1. Weight monitoring is essential: Significant weight gain is common — counsel patients about dietary measures from initiation; consider alternatives if weight gain exceeds 5% of baseline

mirtazapine; NaSSA; depression; MDD; sedating-antidepressant; appetite-stimulant; insomnia; weight-gain; elderly-caution; psychiatry

RxIndia v1.0 — 25 Apr 2025

• CDSCO-approved prescribing information

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Psychiatry protocols

• Indian Psychiatric Society clinical practice patterns

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th edition

• Meta-analyses (for off-label anxiety and insomnia indications — annotated as off-label)