Schedule H

Oral

• Tablets: 25 mg, 50 mg, 100 mg (immediate-release)

Note: Extended-release formulations are NOT AVAILABLE in India.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD)

Used particularly when a sedating antidepressant is preferred or when insomnia is a prominent symptom.

Parameter Recommendation

Starting dose 50–100 mg orally at bedtime

Titration Increase by 50 mg every 3–4 days based on response and tolerability

Usual maintenance dose 150–300 mg/day in divided doses (if >150 mg/day, divide into 2–3 doses)

Maximum dose 400 mg/day (outpatient); 600 mg/day (hospitalised patients under specialist supervision)

Clinical Notes:

• Administer at bedtime or after meals to minimise sedation and orthostatic hypotension

• Therapeutic antidepressant effect typically requires 2–4 weeks at adequate doses

• Higher doses (>150 mg/day) should be divided to reduce peak-related adverse effects

• Lower doses (25–100 mg) are primarily sedating; antidepressant efficacy requires higher doses

1. Depression with Associated Insomnia

Low-dose use leveraging sedative properties alongside antidepressant effect.

Parameter Recommendation

Starting dose 25–50 mg orally at bedtime

Titration May increase to 100 mg at bedtime if needed

Usual maintenance dose 50–100 mg at bedtime

Maximum dose 100 mg at bedtime (when used primarily for sleep in depression)

Clinical Notes:

• At these doses, sedative effect predominates; full antidepressant effect requires higher doses

• Commonly used as adjunct to other antidepressants for sleep enhancement

• Particularly useful in elderly patients with depression and insomnia

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Insomnia (Primary, without depression) 25–50 mg at bedtime; Maximum: 100 mg Short-term (2–4 weeks) or intermittent use OFF-LABEL; Common in Indian practice; Lower abuse potential than benzodiazepines; Evidence: Clinical experience; Not approved for primary insomnia

Generalised Anxiety Disorder 75–150 mg/day in divided doses 6–12 weeks trial OFF-LABEL; Specialist only; Evidence: Limited comparator trials; Clinical experience

Fibromyalgia-Related Sleep Disturbance 25–50 mg at bedtime Intermittent or long-term OFF-LABEL; Specialist only; Evidence: Limited RCTs; Indian practice-based use

SSRI/SNRI-Induced Insomnia (Adjunct) 25–50 mg at bedtime Ongoing with primary antidepressant OFF-LABEL; Common adjunctive use; Monitor for serotonin syndrome

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for routine use in children and adolescents below 18 years in India.

• Safety and efficacy not established in paediatric population

• Risk of suicidal ideation may be increased in younger patients

Secondary Indications – Paediatrics (Off-label, if any)

Indication Age Dose Notes

Major Depressive Disorder (Refractory) 12–17 years Starting: 1–1.5 mg/kg/day in 1–2 divided doses; Titration: Increase by 0.5–1 mg/kg every 3–5 days; Usual range: 2–3 mg/kg/day; Maximum: 6 mg/kg/day or 300 mg/day (whichever lower) OFF-LABEL; Specialist only (Child Psychiatry); Evidence: Limited; Used when SSRIs inadequate

Safety Monitoring in Paediatric Use:

• Suicidal ideation — close monitoring, especially first 4 weeks

• Sedation and orthostatic hypotension

• ECG if cardiac concerns

• Growth and development

Not recommended below 12 years of age under any circumstances. Use above 12 years only under specialist child psychiatry supervision.

Mild to moderate impairment No dose adjustment required

• Known hypersensitivity to trazodone or any excipient

• Concurrent use with monoamine oxidase inhibitors (MAOIs) or use within 14 days of MAOI discontinuation

• Recent acute myocardial infarction

• Known QT prolongation or congenital long QT syndrome

• Concurrent use with other QT-prolonging drugs in patients with risk factors

• Suicidal ideation and behaviour — especially in patients under 25 years; close monitoring required in early treatment

• Cardiovascular disease — risk of orthostatic hypotension and arrhythmias

• Elderly patients — increased susceptibility to orthostatic hypotension, sedation, and falls

• Volume depletion or concurrent antihypertensives — increased hypotension risk

• Priapism risk — rare but serious; counsel male patients to report prolonged erections (>4 hours)

• Hepatic or renal impairment — dose adjustment may be required

• Seizure disorders — may lower seizure threshold

• Concurrent serotonergic drugs — risk of serotonin syndrome

• Bipolar disorder — may precipitate mania; screen before initiation

• Bleeding disorders or concurrent anticoagulants/antiplatelets — may increase bleeding risk

• Driving or operating machinery — sedation may impair alertness

Parameter Details

Risk Category Limited human data; animal studies show some developmental effects at high doses

Recommendation Avoid if possible, especially in first trimester; use only if potential benefit clearly outweighs risk

Preferred Alternatives SSRIs (sertraline preferred) have more pregnancy safety data; consider only if sedating antidepressant specifically needed

When May Be Used When SSRIs are ineffective/not tolerated and sedation is therapeutically desirable; requires specialist psychiatric and obstetric input

Monitoring Maternal sedation, orthostatic hypotension; fetal growth surveillance; neonatal observation for sedation and withdrawal if used near term

Parameter Details

Compatibility Probably compatible at low doses; limited data but low milk transfer expected

Drug Levels in Milk Low; relative infant dose estimated <1%

Preferred Alternatives Sertraline, paroxetine (more lactation safety data)

Infant Monitoring Sedation, feeding difficulties, irritability, adequate weight gain

Recommendation If used, prefer lowest effective dose (25–50 mg at bedtime); monitor infant closely

Parameter Recommendation

Starting dose 25–50 mg orally at bedtime

Titration Slower titration — every 5–7 days; increase by 25 mg increments

Maximum dose Generally ≤200 mg/day unless under specialist supervision

Special Risks Orthostatic hypotension (leading to falls), excessive sedation, confusion, hyponatraemia (SIADH), urinary retention

Monitoring Blood pressure (including orthostatic), falls risk assessment, electrolytes, cognitive function

Note: Trazodone is often preferred over benzodiazepines for insomnia in elderly due to lower dependence potential.

Interacting Drug Mechanism / Effect Recommendation

MAO Inhibitors (phenelzine, tranylcypromine, selegiline, moclobemide, linezolid, methylene blue IV) Serotonin syndrome risk Contraindicated — do not use within 14 days of MAOI

QT-Prolonging Drugs (haloperidol, amiodarone, sotalol, moxifloxacin, ondansetron, methadone) Additive QT prolongation; risk of torsades de pointes Avoid combination if possible; if essential, ECG monitoring mandatory

Strong CYP3A4 Inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) Markedly increased trazodone levels Reduce trazodone dose; monitor for toxicity

CNS Depressants (benzodiazepines, opioids, alcohol, sedating antihistamines) Additive CNS depression; respiratory depression risk with opioids Use with caution; reduce doses; avoid alcohol

Antihypertensives (especially alpha-blockers, prazosin) Potentiation of hypotensive effect Monitor blood pressure; dose adjustment may be needed

Interacting Drug Mechanism / Effect Recommendation

SSRIs/SNRIs (fluoxetine, sertraline, venlafaxine) Serotonin syndrome risk; CYP2D6 inhibition by some SSRIs increases trazodone levels Common combination for sleep but monitor closely for serotonin syndrome; lower trazodone dose may be needed

Triptans (sumatriptan) Potential additive serotonergic effect Use with caution; monitor for serotonin syndrome

Carbamazepine CYP3A4 induction reduces trazodone levels May need to increase trazodone dose; monitor efficacy

Phenytoin CYP3A4 induction; possible increased phenytoin levels Monitor phenytoin levels; may need dose adjustment

Digoxin Trazodone may increase digoxin levels Monitor digoxin levels and clinical response

Warfarin Occasional INR increases reported Monitor INR when starting or stopping trazodone

Tramadol Additive serotonergic effect; seizure risk Use with caution; monitor for serotonin syndrome

Alcohol Additive CNS depression Advise avoidance

• Drowsiness / Sedation (most common)

• Dizziness / Light-headedness

• Orthostatic hypotension

• Dry mouth

• Blurred vision

• Nausea

• Constipation

• Headache

• Fatigue / Asthenia

• Confusion (especially in elderly)

• Nasal congestion

• Weight changes (usually minimal)

Note: Sedation is more prominent at lower doses; may diminish with continued use or higher antidepressant doses.

Adverse Effect Clinical Action

Priapism (prolonged painful erection >4 hours) Medical emergency; discontinue immediately; urological referral; failure to treat may cause permanent damage

QT Prolongation / Torsades de Pointes Discontinue; ECG monitoring; correct electrolytes; cardiology referral

Serotonin Syndrome (when combined with serotonergic drugs) — hyperthermia, rigidity, myoclonus, autonomic instability Discontinue all serotonergic drugs immediately; supportive care; may require hospitalisation

Suicidal Ideation / Behaviour (especially in patients <25 years) Close monitoring; psychiatric evaluation; may require discontinuation

Orthostatic Hypotension with Syncope Reduce dose; ensure hydration; falls precautions

Hyponatraemia (SIADH-like effect, especially in elderly) Check electrolytes; discontinue or reduce dose; may require specialist management

Hepatotoxicity (rare) Monitor LFTs if symptoms; discontinue if significant elevation

Cardiac Arrhythmias ECG; cardiology referral; discontinue if significant

Seizures (rare, dose-related) Discontinue; neurological evaluation

First 4 weeks Weekly assessment of suicidal ideation (especially in patients <25 years); blood pressure monitoring; assess sedation and tolerability

After dose changes Blood pressure; sedation level; efficacy assessment

Long-term Periodic electrolytes (especially in elderly or on diuretics); LFTs if symptoms suggest hepatic dysfunction; ECG if dose >200 mg/day or on other QT-prolonging drugs; falls risk assessment in elderly

• Trazalon (Intas)

• Trazonil (Sun Pharma)

• Trazodep (Torrent)

• Trazodone (Various generic manufacturers)

• Desyrel (Limited availability)

Note: FDCs are not commonly available for trazodone in India.

• Not included in NLEM 2022; pricing not NPPA-controlled

• May be available free in psychiatry OPDs of government tertiary hospitals

• Generic versions significantly cheaper than branded products

• Paradoxically, lower doses (25–50 mg) are often more sedating than higher doses — this makes low-dose trazodone ideal for insomnia but inadequate for antidepressant effect; antidepressant efficacy requires 150–300 mg/day

• Administer at bedtime due to prominent sedation — advise patients to rise slowly from bed to prevent orthostatic hypotension-related falls

• Priapism is rare but potentially devastating — counsel ALL male patients to seek immediate medical attention for erections lasting >4 hours; avoid in patients with history of priapism or penile conditions predisposing to priapism

• Preferred sedating antidepressant in patients who cannot tolerate tricyclic antidepressants or benzodiazepines — lower anticholinergic burden than TCAs; no dependence potential unlike benzodiazepines

• Commonly used as adjunct to SSRIs/SNRIs for sleep — but monitor for serotonin syndrome; keep doses low (25–50 mg)

• Baseline ECG recommended in elderly patients and those with cardiac history before using doses >100 mg/day

Trazodone; depression; insomnia; SARI; sedating antidepressant; serotonin antagonist; priapism risk; QT prolongation; elderly-caution; orthostatic hypotension; serotonin syndrome; Schedule H

RxIndia v1.0 — 25 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• NLEM 2022 (referenced for exclusion status)

• API Textbook of Medicine — Psychiatry chapter

• AIIMS Psychiatry Department Treatment Protocols

• Indian Psychiatric Society Clinical Practice Guidelines

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian hospital protocols for insomnia/depression management