Usage
Trimipramine is prescribed for the treatment of major depressive disorder. It is classified as a tricyclic antidepressant (TCA). Its mechanism of action involves inhibiting the reuptake of norepinephrine and serotonin, two neurotransmitters in the brain, thereby increasing their levels in the synaptic cleft and alleviating depressive symptoms. It also has a sedative effect.
Alternate Names
Trimipramine maleate is the chemical name. Brand names include Surmontil and Herphonal, among others.
How It Works
Pharmacodynamics: Trimipramine primarily affects the central nervous system by increasing the concentration of norepinephrine and serotonin in the synaptic cleft. This is achieved through the inhibition of their reuptake into the presynaptic neuron. The relative potency of Trimipramine on serotonin and norepinephrine are roughly equal. The increased levels of norepinephrine and serotonin can improve mood and reduce symptoms of depression. Its sedative effect is attributed to the antihistaminic properties of Trimipramine (H1 receptor antagonism).
Pharmacokinetics: Trimipramine is well-absorbed after oral administration. It is extensively metabolized in the liver, primarily by CYP2D6, CYP2C19, and CYP3A4 isoenzymes. The major active metabolite is desmethyltrimipramine, which also contributes to the antidepressant effects. Trimipramine is excreted primarily in the urine, with a half-life of approximately 24 hours (range: 7 to 30).
Mode of Action: Trimipramine binds to the presynaptic norepinephrine and serotonin transporters, blocking their reuptake. It also demonstrates antagonism at histamine H1 receptors, muscarinic acetylcholine receptors, and alpha-adrenergic receptors, which contributes to some of its side effects.
Elimination Pathways: Primarily hepatic metabolism followed by renal excretion. The contribution of CYP2D6 to trimipramine clearance can vary significantly based on individual genetic variations in CYP2D6 activity (e.g., poor metabolizers, intermediate metabolizers, extensive metabolizers, and ultrarapid metabolizers). This suggests that the elimination pathways of trimipramine may vary considerably from patient to patient.
Dosage
Standard Dosage
Adults:
Initial: 50-75 mg orally per day, in divided doses.
Maintenance: 50-150 mg orally per day (up to 200 mg/day if necessary). May be administered as a single dose at bedtime for convenience.
Children:
Not recommended for use in children under 12 years of age. Safety and efficacy have not been established in this population.
Adolescents (12 years and older): 50 mg orally per day initially, gradually increased to a maximum of 100 mg/day as needed and tolerated.
Special Cases:
- Elderly Patients: Initiate at a lower dose (e.g., 50 mg/day), with cautious and gradual titration based on response and tolerability. The maximum daily dose is generally not recommended to exceed 100 mg/day.
- Patients with Renal Impairment: Dose adjustment may be necessary. Start with a low dose and titrate carefully.
- Patients with Hepatic Dysfunction: Start with a low dose and titrate carefully. Monitor closely for adverse effects.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, glaucoma, urinary retention, or seizure disorders. Dosage adjustment may be required.
Clinical Use Cases
Trimipramine is not typically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is in the treatment of depression.
Dosage Adjustments
Dosage adjustments should be based on individual patient response and tolerance. Consider lower starting doses and slower titration in elderly patients, individuals with renal or hepatic impairment, and those with comorbid conditions.
Side Effects
Common Side Effects:
Drowsiness, dizziness, dry mouth, constipation, blurred vision, urinary retention, weight gain, tremor, changes in appetite, and sexual dysfunction.
Rare but Serious Side Effects:
Cardiac arrhythmias, myocardial infarction, stroke, seizures, severe allergic reactions (anaphylaxis), serotonin syndrome, and suicidal thoughts or behavior (especially in young adults).
Long-Term Effects:
Tardive dyskinesia (rare), weight gain, and sexual dysfunction.
Adverse Drug Reactions (ADR)
Agranulocytosis, neuroleptic malignant syndrome, and hepatitis (rare).
Contraindications
- Hypersensitivity to trimipramine or other TCAs.
- Recent myocardial infarction.
- Concomitant use of monoamine oxidase inhibitors (MAOIs).
- Severe hepatic impairment.
- Uncontrolled angle-closure glaucoma.
Drug Interactions
Trimipramine interacts with numerous medications, including:
- MAOIs: Concomitant use can lead to serotonin syndrome.
- CNS depressants (e.g., alcohol, benzodiazepines): Increased sedation and respiratory depression.
- Anticholinergic agents: Additive anticholinergic effects.
- CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): Increased trimipramine levels.
- CYP2D6 inducers (e.g., rifampin): Decreased trimipramine levels.
- Antihypertensives: May potentiate or antagonize their effects.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C (limited data available). Use only if potential benefits outweigh the risks to the fetus. Trimipramine has been associated with neonatal withdrawal symptoms.
Trimipramine is present in breast milk and may cause adverse effects in infants. Breastfeeding is generally not recommended while taking trimipramine.
Drug Profile Summary
- Mechanism of Action: Inhibits norepinephrine and serotonin reuptake.
- Side Effects: Drowsiness, dizziness, dry mouth, constipation, blurred vision, urinary retention, and potential for cardiac effects and seizures.
- Contraindications: Hypersensitivity, recent myocardial infarction, concomitant MAOI use, severe hepatic impairment.
- Drug Interactions: MAOIs, CNS depressants, anticholinergics, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution during pregnancy. Breastfeeding not recommended.
- Dosage: Adults: 50-150 mg/day; elderly: start lower, max 100mg/day.
- Monitoring Parameters: Blood pressure, heart rate, mental status, liver function tests.
Popular Combinations
Trimipramine is not typically used in combination with other antidepressants due to the increased risk of adverse effects. It may be prescribed along with short-term anxiolytics for initial anxiety relief.
Precautions
- Baseline ECG and monitoring are recommended, especially in patients with cardiovascular risk factors.
- Monitor for suicidal thoughts and behavior, especially in young adults.
- Caution in patients with glaucoma, urinary retention, prostatic hypertrophy, seizure disorders, and hepatic or renal impairment.
- Avoid alcohol consumption.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Trimipramine?
A: Adults: 50–150mg daily, up to 200 mg/day if necessary. Elderly: start low at 50mg with a maximum of 100mg. Not recommended for children under 12. Adolescents: 50mg increasing to a maximum of 100mg.
Q2: What is the mechanism of action of Trimipramine?
A: Trimipramine inhibits the reuptake of serotonin and norepinephrine, thereby increasing their concentrations in the synaptic cleft.
Q3: What are the common side effects of Trimipramine?
A: Drowsiness, dizziness, dry mouth, constipation, blurred vision, urinary retention.
Q4: What are the serious side effects of Trimipramine?
A: Cardiac arrhythmias, seizures, serotonin syndrome, suicidal thoughts.
Q5: What are the contraindications for Trimipramine?
A: Recent myocardial infarction, concomitant MAOI use, severe hepatic impairment, hypersensitivity to trimipramine.
Q6: How should Trimipramine be used in elderly patients?
A: Start with a lower dose (e.g., 50 mg/day) and titrate cautiously up to a maximum of 100mg/day, monitoring closely for adverse effects.
Q7: Does Trimipramine interact with other medications?
A: Yes, it interacts with numerous medications, including MAOIs, CNS depressants, and some antihypertensives.
Q8: Can Trimipramine be used during pregnancy and breastfeeding?
A: Use with caution during pregnancy only if the potential benefits outweigh the risks. Breastfeeding is generally not recommended due to the drug’s presence in breast milk.
Q9: What should patients be advised about lifestyle while taking Trimipramine?
A: Patients should avoid alcohol consumption and activities requiring alertness until their response to the medication is established.
Q10: How long does it take for Trimipramine to start working?
A: It may take 2–4 weeks, or even longer in some cases, to experience the full therapeutic effects of Trimipramine.
