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Tricyclic Antidepressant (TCA) Pregnancy: UK SPC §4.6, verbatim: 'There is no evidence of the safety of the drug in human pregnancy. There have been isolated reports of a possible connection between the use of tricyclic antidepressants and adverse effects (developmental disorders) on the foetus; treatment with Imipramine Hydrochloride should be avoided during pregnancy, unless the anticipated benefits justify the potential risk to the foetus. Neonates whose mothers had taken imipramine up until delivery have developed dyspnoea, lethargy, colic, irritability, hypotension or hypertension, tremor or spasms, during the first few hours or days. Imipramine Hydrochloride should if possible be gradually withdrawn at least 7 weeks before the calculated date of confinement.' Breast-feeding: 'The active substance of Imipramine hydrochloride, imipramine, and its metabolites, desmethylimipramine, pass into the breast milk in small quantities. Imipramine hydrochloride should be gradually withdrawn or the mother advised to cease breast-feeding.' The US label agrees: 'there have been clinical reports of congenital malformations associated with the use of the drug... imipramine hydrochloride should be used in women who are or might become pregnant only if the clinical condition clearly justifies potential risk to the fetus.'

Imipramine

Brand names: Tofranil

Imipramine is a tricyclic antidepressant used in the treatment of depression and also for nocturnal enuresis in children.

Adult dose

Dose: Depression: 25 mg up to three times daily initially, increased stepwise to 150–200 mg daily, which should be reached by the end of the first week; maintenance thereafter is individually determined by gradual reduction, usually to about 50–100 mg daily
Route: Oral. SPC §4.2 Method of administration, verbatim: 'For oral administration.' The source product is an oral solution containing 25 mg imipramine hydrochloride in 5 ml.
Frequency: Divided doses at initiation (25 mg up to three times daily), escalating to 150–200 mg daily by the end of the first week; hospitalised severe cases may go to 100 mg three times daily. Elderly patients over 60 years start at 10 mg daily.
Max: 300 mg daily, and only in hospitalised patients. UK SPC §4.2, verbatim: 'In patients in hospital, i.e. severe cases, the dose may be increased to 100mg three times daily until a distinct improvement is seen.' The US label sets the ceilings explicitly — hospitalised patients: 'If no response after two weeks, increase to 250 to 300 mg/day'; outpatients: 'Dosages over 200 mg/day are not recommended.'
SCOPE: this covers the page's PRIMARY indication and route only — depression, oral. The same SPC also licenses nocturnal enuresis in children; that is a different indication and its regimen is carried in paedDose (with its own scope note), never mixed into the adult depression figures above. || VERBATIM (UK SPC §4.2, Depression, Adults): '1 x 25mg up to three times daily, increasing stepwise to 150-200mg. This should be reached by the end of the first week and maintained until definite improvement has occurred. The subsequent maintenance dose should be individually determined by gradually reducing the dosage, usually to about 50-100mg daily. In patients in hospital, i.e. severe cases, the dose may be increased to 100mg three times daily until a distinct improvement is seen. Again the subsequent maintenance dose should be determined individually by reducing the dosage, usually to about 100mg daily.' || ELDERLY (UK SPC §4.2, verbatim): 'Patients over 60 years of age may respond to lower doses of Imipramine Hydrochloride than those recommended above. Treatment should be initiated with 10mg daily, gradually increasing to 30-50mg daily. The optimum dose should be reached after about 10 days and then continued until the end of treatment.' §4.8 adds that elderly patients 'are particularly sensitive to anticholinergic, neurological, psychiatric, or cardiovascular effects. Their ability to metabolise and eliminate drugs may be reduced, leading to a risk of elevated plasma concentrations at therapeutic doses.' || US LABEL (cross-check, DOSAGE AND ADMINISTRATION — Depression, verbatim): 'Hospitalized patients - Initially, 100 mg/day in divided doses gradually increased to 200 mg/day as required. If no response after two weeks, increase to 250 to 300 mg/day. Outpatients - Initially, 75 mg/day increased to 150 mg/day. Dosages over 200 mg/day are not recommended. Maintenance, 50 to 150 mg/day. Adolescent and Geriatric Patients - Initially, 30 to 40 mg/day; it is generally not necessary to exceed 100 mg/day.' It also states: 'Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients as compared to hospitalized patients who will be under close supervision. Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a longer period of time, at the lowest dose that will maintain remission.' || RESPONSE DELAY (§4.4, verbatim): 'As improvement in depression may not occur for the first two to four weeks' of treatment, patients should be closely monitored during this period.' || WITHDRAWAL: the SPC requires gradual withdrawal in the enuresis section; no separate adult tapering schedule is given in the fetched text. || NO FIGURE IN THE FETCHED SOURCES SUPPORTS a therapeutic plasma-level target, an ECG threshold dose, or a '75 mg once at night' starting regimen — none of those is asserted here.

Paediatric dose

Route: Oral, taken just before bedtime
Frequency: Once daily just before bedtime. UK SPC §4.2: 'The dose should be taken just before bedtime.' US label: 'Medication should be given one hour before bedtime'; and 'Evidence suggests that in early night bedwetters, the drug is more effective given earlier and in divided amounts, i.e., 25 mg in midafternoon, repeated at bedtime.'
Max: 75 mg daily. US label, verbatim: 'A daily dose greater than 75 mg does not enhance efficacy and tends to increase side effects.' The UK SPC's highest band (over 11 years, weight 35–54 kg) is 50–75mg daily. A separate weight-based ceiling also applies and is quoted in the notes below.
Concentration: 5 mg/ml
SCOPE — READ FIRST: THESE ARE NOCTURNAL ENURESIS DOSES, NOT PAEDIATRIC DEPRESSION DOSES. Imipramine is not licensed for depression in children; the US label states 'Safety and effectiveness in the pediatric population other than pediatric patients with nocturnal enuresis have not been established.' Do not apply the figures below to any other paediatric indication. || WHY dosePerKg IS NULL: the SPC doses by age and weight BAND, not per kilogram, so no single per-kg per-dose figure is valid across the paediatric range. || VERBATIM (UK SPC §4.2, Nocturnal Enuresis in Children): 'Not for use in children under 6 years. 6 - 7 years (weight 20-25kg or 44-55lbs) 8 - 11 years (weight 25-35kg or 55-77lbs) Over 11 years (weight 35-54kg or 77-119lbs) 25mg daily 25-50mg daily 50-75mg daily. A daily dose of 2.5mg/kg should not be exceeded in children. The dose should be taken just before bedtime. The maximum period of treatment should not exceed three months and withdrawal should be gradual. Should a relapse occur, a further course of treatment should not be started until a full physical examination has been made.' Read as three bands: 6–7 years (20–25 kg) 25 mg daily; 8–11 years (25–35 kg) 25–50 mg daily; over 11 years (35–54 kg) 50–75 mg daily. || WEIGHT-BASED CEILING (kept out of the maxDose field deliberately, because it is a per-kilogram value): 'A daily dose of 2.5mg/kg should not be exceeded in children' (UK SPC); the US label repeats 'A dose of 2.5 mg/kg/day should not be exceeded' and adds 'ECG changes of unknown significance have been reported in pediatric patients with doses twice this amount.' Apply this cap alongside the band above and use whichever is lower. || US LABEL (Childhood Enuresis, verbatim): 'Initially, an oral dose of 25 mg/day should be tried in children aged 6 and older. Medication should be given one hour before bedtime. If a satisfactory response does not occur within one week, increase the dose to 50 mg nightly in children under 12 years; children over 12 may receive up to 75 mg nightly. A daily dose greater than 75 mg does not enhance efficacy and tends to increase side effects... Consideration should be given to instituting a drug free period following an adequate therapeutic trial with a favorable response. Dosage should be tapered off gradually rather than abruptly discontinued; this may reduce the tendency to relapse. Children who relapse when the drug is discontinued do not always respond to a subsequent course of treatment.' || AGE FLOOR: 'Infants and children under 6 years old' is an absolute contraindication in UK SPC §4.3; both labels state that safety and effectiveness for enuresis under 6 years of age have not been established. || DURATION: UK — 'The maximum period of treatment should not exceed three months and withdrawal should be gradual.' US — the safety of long-term chronic use for enuresis in children 6 years and older has not been established. || CONCENTRATION: 5 mg/mL, from the source product name 'Imipramine Hydrochloride 25mg/5ml Oral Solution' (25 mg in 5 ml). Tablets of other strengths also exist — confirm the strength of the actual preparation before calculating a volume. || Verify any under-18 use against a children's formulary.

Dose adjustments

Renal

No dose adjustment figure is given in any fetched section. UK SPC §4.4, verbatim: 'Caution is called for when giving tricyclic antidepressants to patients with severe renal disease.' The US Geriatric Use section adds that dose selection should be cautious in older patients, 'reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.'

Hepatic

'Severe liver disease' is an absolute CONTRAINDICATION in UK SPC §4.3 — this is a contraindication, not a dose reduction. For lesser impairment, §4.4, verbatim: 'Periodic monitoring of hepatic enzymes levels is recommended in patients with liver disease.' No dose adjustment figure is given in any fetched section. §4.8 lists occasional elevated transaminases, rare impaired liver function and isolated cases of hepatitis with or without jaundice.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to imipramine, any of the excipients listed in section 6.1, or cross-sensitivity to other tricyclic antidepressants of the dibenzazepine group (SPC §4.3)
  • Recent myocardial infarction (SPC §4.3). US label: 'The drug is contraindicated during the acute recovery period after a myocardial infarction.'
  • Any degree of heart block or other cardiac arrhythmias (SPC §4.3)
  • Mania (SPC §4.3)
  • Severe liver disease (SPC §4.3)
  • Narrow angle glaucoma (SPC §4.3)
  • Infants and children under 6 years old (SPC §4.3)
  • Retention of urine (SPC §4.3)
  • Concurrent use in patients receiving, or within 3 weeks of cessation of therapy with, monoamine oxidase inhibitors (SPC §4.3). The US label requires 'a minimum of 14 days' and warns that 'Hyperpyretic crises or severe convulsive seizures may occur in patients receiving such combinations. The potentiation of adverse effects can be serious, or even fatal.'
  • Concomitant treatment with selective, reversible MAO-A inhibitors such as moclobemide (SPC §4.3)
  • Porphyria — SPC §4.3: 'Imipramine has been reported to be a porphyrinogenic agent and therefore should be avoided in patients with a known diagnosis or history of porphyria. Patients presenting with psychiatric symptoms in conjunction with gastrointestinal symptoms or dermatological conditions should be tested for porphyria prior to administration of imipramine.'

Side effects

  • Anticholinergic — frequently (>10%): dry mouth, sweating, constipation, disorders of visual accommodation, blurred vision, hot flushes; occasionally disturbances of micturition; isolated cases of mydriasis, glaucoma and paralytic ileus (SPC §4.8)
  • Cardiovascular — frequently: sinus tachycardia and clinically irrelevant ECG changes (T and ST changes) in patients of normal cardiac status, and postural hypotension, which 'are likely to occur with high dosage or in deliberate overdosage. They may also occur in patients with pre-existing heart disease taking normal dosage'; occasionally arrhythmias and conduction disorders (widening of QRS complex and PR interval, bundle-branch block), palpitations; isolated cases of increased blood pressure, cardiac decompensation and peripheral vasospastic reactions (SPC §4.8)
  • Neurological — frequently tremor; occasionally paraesthesia, headache, dizziness; rarely epileptic seizures; isolated cases of EEG changes, myoclonus, weakness, extrapyramidal symptoms, ataxia, speech disorder and drug fever (SPC §4.8). §4.4 notes 'It appears that the occurrence of seizures is dose dependent.'
  • Psychiatric — occasionally fatigue, drowsiness, restlessness, delirium, confusion, disorientation and hallucination (particularly in geriatric patients and those with Parkinson's disease), increased anxiety, agitation, sleep disturbances, swings from depression to hypomania or mania; rarely activation of psychotic symptoms; isolated cases of aggressiveness. 'Cases of suicidal ideation and suicidal behaviours have been reported during Imipramine therapy or early after treatment discontinuation' (SPC §4.8)
  • Metabolic/endocrine — frequently weight gain; occasionally disturbances of libido, impotency or abnormal ejaculation (SPC §4.8)
  • Gastrointestinal — occasionally nausea, vomiting, anorexia; isolated cases of stomatitis, tongue lesions and abdominal disorders. Hepatic: occasionally elevated transaminases, rarely impaired liver function, isolated cases of hepatitis with or without jaundice (SPC §4.8)
  • Skin — occasionally allergic skin reactions (rash, urticaria); isolated cases of oedema, photosensitivity, hyperpigmentation, pruritus, petechiae and hair loss (SPC §4.8).
  • Hyponatraemia — §4.4: 'Hyponatraemia (usually in the elderly) has been associated with all types of antidepressants and should be considered in all patients who develop symptoms such as drowsiness, confusion or convulsions.'
  • Serotonin syndrome — §4.4: concomitant administration with buprenorphine/opioids or other serotonergic agents 'may result in serotonin syndrome, a potentially life-threatening condition'; symptoms 'may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms'
  • US label additionally lists haematological reactions: 'Bone marrow depression including agranulocytosis; eosinophilia; purpura' (US ADVERSE REACTIONS, truncated at the source-fetch limit)
  • This side-effect list may be incomplete — check the full SPC.

Monitoring

  • Close monitoring during the first two to four weeks of treatment, because improvement in depression may not occur before then (SPC §4.4); watch for suicidal ideation and suicidal behaviour during therapy and early after discontinuation (SPC §4.8)
  • Check blood pressure before initiating treatment — §4.4, verbatim: 'Before initiating treatment it is advisable to check the patient's blood pressure, because individuals with hypotension or a labile circulation may react to the drug with a fall in blood pressure.'
  • Periodic full blood counts and watch for fever and sore throat — §4.4: 'Although changes in the white blood cell count have been reported with imipramine only in isolated cases, periodic blood cell counts and monitoring for symptoms such as fever and sore throat are called for, particularly during the first few months of therapy.'
  • Periodic monitoring of hepatic enzyme levels in patients with liver disease (§4.4)
  • Monitoring of cardiac function in elderly patients (§4.4 — the sentence is truncated at the source-fetch limit)
  • Consider hyponatraemia in any patient who develops drowsiness, confusion or convulsions (§4.4)
  • Observe for serotonin syndrome, particularly during treatment initiation and dose increases, when other serotonergic agents are co-prescribed (§4.4)
  • Extreme caution and seizure vigilance in epilepsy or other predisposing factors — brain damage of varying aetiology, concomitant neuroleptics, or withdrawal from alcohol or anticonvulsant drugs such as benzodiazepines (§4.4)
  • Watch for CYP2D6-mediated toxicity — US Drug Interactions: 'An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy', the inhibitors named being quinidine, cimetidine, other antidepressants including the SSRIs fluoxetine, sertraline and paroxetine, phenothiazines, propafenone and flecainide
  • Caution in hyperthyroidism or concomitant thyroid preparations (aggravation of unwanted cardiac effects) and in tumours of the adrenal medulla such as phaeochromocytoma and neuroblastoma, where TCAs 'may provoke hypertensive crises' (§4.4)

Clinical monograph

How it works

It inhibits the reuptake of noradrenaline and serotonin at the synaptic cleft and also has antimuscarinic, antihistaminic and alpha-adrenergic blocking actions.

Prescribing in practice

  • Tricyclic antidepressants are dangerous in overdose, causing cardiac arrhythmias, seizures and coma, so consider toxicity risk in patients at risk of self-harm and limit quantities supplied.
  • Antimuscarinic and cardiovascular effects make it unsuitable in recent myocardial infarction, arrhythmias and severe cardiac disease, and it should be used with caution in the elderly.
  • When used for enuresis in children, dosing must follow a children's formulary and avoid the doses used for depression.

Monitoring

Monitor mood, suicidal ideation (particularly early in treatment and in younger patients), cardiac status and antimuscarinic side effects.

Counselling the patient

  • Explain that full antidepressant benefit may take several weeks.
  • Do not stop the medicine abruptly, as withdrawal effects can occur.
  • Report worsening mood, suicidal thoughts, palpitations or difficulty passing urine.

Evidence & guidelines

Imipramine is one of the original tricyclic antidepressants with long-established efficacy in depression; NICE recommends caution owing to its toxicity in overdose relative to newer agents.

Reference: NICE CG111 (Nocturnal Enuresis); Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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