Trimipramine – Surmontil®-Trimip®-Tripramine®

• Surmontil®
• Trimip®
• Tripramine®

• Tricyclic Antidepressant

• • Trimipramine Tablets BP: 12.5 mg, 25 mg, 50 mg and 100 mg Trimipramine (as maleate)
  • Trimipramine Capsules: 75 mg Trimipramine (as maleate)

• Depressive Illness
• Endogenous Depression

Mechanism of action:

• Tricyclic anti-depressant with sedative properties
• Anti-cholinergic effects
• Potentiates sympathetic responses by blocking the re-uptake of noradrenaline which has been released by the presynaptic neurones.
• Quinidine-like effect on the heart and produces ECG and EEG changes.

• Absorption: GI
• Metabolism: Hepatic
• Distribution:
  • Half-Life: 16-40 hr
  • Peak plasma time: 2 hr
  • Bioavailability: 18-63%
  • Protein Binding: 95%
• Excretion: Urine

Initial Dosage:

• Adults:
  • Initial dose: 75 mg/day in two or three divided doses.
  • Increase in dosage by 25 mg by adding to the late afternoon doses.
  • Optimal dose: 150 mg/day
• Severely Depressed Patients:
  • Initial dose: 100 mg/day in two or three divided doses
  • Optimal dose:150 to 200 mg/day
  • Max dose: 300 mg/day
• Elderly or debilitated patients:
  • Test dose: Give 12.5 to 25 mg of the drug and examine the patient sitting and standing to check for orthostatic hypotension after 45 minutes.
  • Initial doses: not more than 50 mg/day in divided doses
  • weekly increase: not more than 25 mg/week
  • Therapeutic dose: 50 to 150 mg/day.
  • Blood pressure and cardiac rhythm must be checked frequently (particularly in patients who have unstable cardiovascular function)

 Maintenance Dosage:

• Once a satisfactory response has been obtained >>> the dosage should be adjusted to the lowest level required
• Medication should be continued for the expected duration of the depressive episode in order to minimize the possibility of relapse following clinical improvement.
• When a maintenance dosage has been established as described above, trimipramine may be administered in a single dose before bedtime provided such a dosage regimen is well tolerated.

Behavioural:

• Drowsiness (mainly during initial therapy), fatigue, excitement, agitation, restlessness, insomnia, shifts to hypomania or mania, activation of latent psychosis, disorientation, confusion, hallucinations, delusions, nightmares, jitteriness, anxiety, giddiness.

Neurological:

• Seizures, incoordination, ataxia, tremors, dystonia, extrapyramidal symptoms, numbness, tingling, paresthesia of the limbs, peripheral neuropathy, headache, alteration in EEG patterns, tinnitus, slurred speech.

Autonomic:

• Dry mouth, urinary retention, constipation, paralytic ileus, disturbance of accommodation, blurred vision, precipitation of latent and aggravation of existing glaucoma, mydriasis, vertigo, syncope.

Cardiovascular:

• Hypotension, hypertension, palpitations, tachycardia, arrhythmias, prolonged conduction time and asystole, heart block, fibrillation, myocardial infarction, stroke and sudden death in patients with cardiovascular disorders. The ECG changes include flattening or inversion of T-waves, depressed S-T segment and bundle branch block.

Endocrine:

• Changes in libido, weight gain or loss, testicular swelling, gynecomastia and impotence in the male, breast enlargement and galactorrhea in the female, elevation or lowering of blood sugar levels.

Allergic:

• Skin rash, edema, urticaria, pruritus, and photosensitivity.

Hematologic:

• Bone marrow depression, including agranulocytosis, leukopenia, eosinophilia, purpura and thrombocytopenia.

Gastrointestinal:

• Nausea, epigastric distress, heartburn, vomiting, anorexia or increased appetite, stomatitis, peculiar taste, diarrhea.

Miscellaneous:

• Obstructive jaundice, weakness, urinary frequency, increased perspiration, alopecia, parotid swelling, black tongue.

Withdrawal Symptoms:

• Abrupt cessation of treatment after prolonged administration may produce nausea, headache, and malaise. These symptoms are not indicative of addiction.

1. Hypersensitivity
2. Concomitant use with MAO inhibitors
3. Narrow Angle Glaucoma
4. Prostatic Hypertrophy
5. Myocardial Infarction: during the acute recovery phase
6. Acute congestive heart failure.

• Pregnancy: Category C
• Breast Feeding: Not recommended in nursing mothers

1. Concomitant use with MAOIs:
   1. Should not be administered concomitantly or within 2 weeks of treatment with an MAO inhibitor.
   2. Hyper pyretic crises, severe convulsions and death have occurred in patients receiving MAO inhibitors and tricyclic antidepressants.
2. Cardiac problems:
   1. Tricyclic antidepressants in high doses, have been reported to produce arrhythmias, sinus tachycardia, and prolongation of conduction time, unexpected death in patients with cardiovascular disorders.
3. Myocardial infarction and stroke:
   1. Drug should be administered with caution to patients with a history of cardiovascular disease, those with circulatory lability and elderly patients.
4. Usage in patients receiving thyroid drugs:
   1. Close supervision is required because of the possibility of cardiovascular toxicity.
5. Usage in daily activity:
   1. Patients should be advised against driving or engaging in activities requiring mental alertness and physical coordination until their response to the drug has been well established.
6. Usage with Alcohol:
   1. Response to alcohol might be potentiated.
7. Usage in children:
   1. not recommended for use in children
8. Usage in seriously depressed patients:
   1. Possibility of Suicide in seriously depressed patients:
      1. Remains until significant remission occurs.
      2. Patients should be closely supervised throughout therapy.

• Patient should not have access to large quantities of trimipramine.

9. Usage in patients with psychiatric disorders:
   1. Precipitate psychotic manifestations in schizophrenic patients and hypomanic or manic episodes in manic-depressive patients.
   2. Reduction or discontinuation of the drug, and/or administration of an antipsychotic agent is needed.
10. Usage in convulsive disorders:
    1. Trimipramine reduces seizure threshold >>> should be administered with caution in patients with a history of convulsive disorders.
    2. Caution in concurrent administration of ECT with trimipramine.
11. Possibility of Paralytic ileus:
    1. Particularly in the elderly and in hospitalized patients.
12. Caution in combined usage with:
    1. Drugs acting on the central nervous system
    2. Alcohol
    3. Barbiturates
    4. CNS depressants
13. Concomitant usage with anticholinergic agents or sympathomimetic drugs:
    1. Block the antihypertensive effects of guanethidine
    2. Careful supervision and adjustment of dosages are required.
14. Usage in patients with liver diseases:
    1. Caution of usage in patients with impaired liver function or history of hepatic damage or blood dyscrasias.
    2. Periodic blood counts and liver function test should be performed.
15. Therapeutic response lag:
    1. Occurs at the onset of therapy and last from several days to a few weeks.
    2. Increasing the dosage does not shorten latent period.
16. Over dose:
    1. Symptoms: Drowsiness, mydriasis, dysarthria, general weakness, excitement, agitation, hyperactive reflexes, muscle spasms and rigidity, hypothermia, hyperpyrexia, vomiting, perspiration, rapid thready pulse, convulsions, severe hypotension, hypertension, tachycardia, disturbances of cardiac conduction, arrhythmia, congestive heart failure, circulatory collapse, respiratory depression and coma.
    2. Treatment: treatment is essentially symptomatic and supportive.