Adult: Initially, 75 mg daily. May be increased to 300 mg, if necessary.
Oral Depression, Major depressive disorder
Adult: Initially, 150 mg daily in divided doses or as a single dose at bedtime. Dose may be increased by 50 mg daily every 3-4 days. Max: 300-400 mg. Hospitalised patient with severe cases: Max: 600 mg daily. Elderly: Initially, 100 mg daily in divided doses or as a single dose at bedtime. Dose may be increased to 300 mg.
Administration
Should be taken with food. Take shortly after a meal or a light snack.
Contraindications
Acute MI. Concomitant use or within 14 days of discontinuing MAOI(s). Children. Concomitant use with linezolid or IV methylene blue.
Special Precautions
Patient with history of suicide related events; bipolar disorder, CV disease (e.g. previous MI, stroke, tachycardia, conduction abnormalities); risk factors for narrow-angle glaucoma; conditions which may predispose to priapism (e.g. sickle-cell anaemia, multiple myeloma, leukaemia); risk or history of seizures, head trauma, brain damage, alcoholism; hyperthyroidism, micturition disorder (e.g. prostate hypertrophy), hypokalaemia or hypomagnesaemia. Hepatic and renal impairment. Elderly. Pregnancy and lactation. Avoid abrupt withdrawal and dose reduction.
Adverse Reactions
Significant: Suicidal ideation and behaviour, cardiac arrhythmia (e.g. QT interval prolongation, ventricular tachycardia); increased risk of bleeding, CNS depression, fall, osteoporotic fracture, narrow-angle glaucoma, orthostatic hypotension, syncope, priapism, activation of mania/hypomania, withdrawal syndrome, hyponatraemia. Cardiac disorders: Palpitation, bradycardia, tachycardia. Ear and labyrinth disorders: Tinnitus. Eye disorders: Ocular pruritus, blurred vision. Gastrointestinal disorders: Dry mouth, taste changes, flatulence, nausea, vomiting, constipation, diarrhoea, dyspepsia, stomach pain, gastroenteritis. General disorders and administration site conditions: Perspiration, oedema, influenza-like symptoms. Metabolism and nutrition disorders: Weight gain, anorexia, increased hunger. Musculoskeletal and connective tissue disorders: Asthenia, limb pain, back pain. Nervous system disorders: Dizziness, drowsiness, headache, tremor. Psychiatric disorders: Nervousness, expressive aphasia, confusional state, disorientation, mania, agitation, aggressive reaction, hallucinations. Respiratory, thoracic and mediastinal disorders: Nasal/sinus congestion. Skin and subcutaneous tissue disorders: Skin rash, pruritus. Vascular disorders: Hypertension. Potentially Fatal: Haemorrhage, serotonin syndrome, severe hepatic failure.
This drug may cause drowsiness, sedation, dizziness, confusional states, and blurred vision, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor for clinical worsening, behavioural changes and emergence of suicidal thoughts. Monitor LFT prior to initiation of therapy and periodically thereafter.
Overdosage
Symptoms: Drowsiness, dizziness, nausea, vomiting, bradycardia, ECG changes, QT prolongation, torsade de pointes, tachycardia, hypotension, hyponatraemia, convulsions, seizures, priapism, respiratory failure, coma. Management: Administer activated charcoal or gastric lavage within 1 hour of ingestion. Give oxygen supply as needed. Correct acid-base and metabolic disturbances. May give IV diazepam or lorazepam, or an IV infusion of phenytoin for seizures. Monitor BP, pulse, and Glasgow Coma Scale. Symptomatic and supportive treatment for hypotension and excessive sedation. May give inotropes (e.g. dopamine, dobutamine) for severe hypotension.
Drug Interactions
Increased plasma concentration and increased risk of adverse effect with potent CYP3A4 inhibitor (e.g. itraconazole, clarithromycin). Increased risk of cardiac arrhythmia with drugs that can prolong QT interval (e.g. Class 1A/3 antiarrhythmics, chlorpromazine, gatifloxacin). Decreased concentration with CYP3A4 inducers (e.g. carbamazepine, phenytoin). Potentially Fatal: Increased risk of serotonin syndrome with MAOI(s), linezolid, IV methylene blue, TCA, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines. Increased risk of bleeding events with aspirin, NSAIDs, warfarin.
Food Interaction
Increased sedative effects with alcohol. Increased risk of serotonin syndrome with St John’s wort.
Lab Interference
May give false-positive result for amphetamine/methamphetamine urine test.
Action
Description: Trazodone, a triazolopyridine derivative, is both an SSRI and 5-HT2A/2C receptor antagonist. It inhibits serotonin reuptake at the presynaptic neuronal membrane, thereby causing adrenoreceptor subsensitivity. It also blocks histamine (H1) and α1-adrenergic receptors. Onset: Depression: Initial: Within 1-2 weeks of treatment, continued improvements through 4-6 weeks. Pharmacokinetics: Absorption: Readily absorbed from the gastrointestinal tract. Food increases absorption and decreases peak plasma concentration. Time to peak plasma concentration: Approx 1 hour. Distribution: Enters breast milk. Plasma protein binding: Approx 89-95%. Metabolism: Extensively metabolised in the liver by CYP3A4 via N-oxidation and hydroxylation into active metabolite, m-chlorophenylpiperazine. Excretion: Mainly via urine (74%, as metabolites; <1%, as unchanged drug); faeces (approx 21%). Elimination half-life: 5-9 hours.
Chemical Structure
Trazodone Source: National Center for Biotechnology Information. PubChem Database. Trazodone, CID=5533, https://pubchem.ncbi.nlm.nih.gov/compound/Trazodone (accessed on Jan. 23, 2020)
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