Usage
Amoxapine is primarily prescribed for the treatment of major depressive disorder. It is classified as a tricyclic antidepressant (TCA) with additional antipsychotic properties due to its metabolite, 7-hydroxyamoxapine. Its mechanism of action involves inhibiting the reuptake of norepinephrine and serotonin, two key neurotransmitters in the brain, thereby increasing their availability in the synaptic cleft. It also blocks dopamine, histamine, and muscarinic receptors.
Alternate Names
While amoxapine is the generic name, it is marketed under various brand names, most notably Asendin.
How It Works
Pharmacodynamics: Amoxapine exerts its antidepressant effect by increasing the synaptic concentrations of norepinephrine and serotonin. The 7-hydroxyamoxapine metabolite contributes to its antipsychotic properties through dopamine receptor antagonism. The blockade of histamine and muscarinic receptors can lead to side effects such as sedation and dry mouth.
Pharmacokinetics: Amoxapine is well-absorbed after oral administration. It is extensively metabolized in the liver, primarily by CYP2D6, to its active metabolite, 7-hydroxyamoxapine. Elimination occurs mainly through renal excretion.
Mode of Action: Amoxapine inhibits the presynaptic reuptake pumps for norepinephrine and serotonin, leading to increased levels of these neurotransmitters in the synaptic cleft. 7-Hydroxyamoxapine blocks dopamine D2 receptors.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Amoxapine inhibits norepinephrine and serotonin reuptake pumps. 7-Hydroxyamoxapine blocks dopamine D2 receptors. It also interacts with histamine H1 and muscarinic M1 receptors.
Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
Initial: 50 mg two or three times daily. The dose may be increased to 100 mg two or three times daily by the end of the first week. If no response at 300 mg/day after two weeks, it can be increased up to 400 mg/day for outpatients. Single bedtime doses up to 300 mg can be used. Doses above 300 mg should be divided.
Children:
Not recommended.
Special Cases:
- Elderly Patients: Initial: 25 mg two to three times daily. Increase cautiously if needed, generally not exceeding 150-300 mg daily, especially in those sensitive to anticholinergic effects.
- Patients with Renal Impairment: Caution advised; dosage adjustment may be needed. No specific guidelines are available.
- Patients with Hepatic Dysfunction: Caution is advised; dosage adjustment may be needed.
- Patients with Comorbid Conditions: Individualized dosing based on specific conditions is necessary.
Clinical Use Cases
Amoxapine is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency scenarios like status epilepticus or cardiac arrest.
Dosage Adjustments
Dose adjustments should be individualized based on patient response and tolerability. Consider reducing the dose in patients with renal or hepatic impairment.
Side Effects
Common Side Effects
Drowsiness, dry mouth, constipation, blurred vision, dizziness, weight changes, nausea.
Rare but Serious Side Effects
Neuroleptic malignant syndrome (NMS), tardive dyskinesia, seizures, severe allergic reactions, cardiac arrhythmias (including QT prolongation), serotonin syndrome.
Long-Term Effects
Tardive dyskinesia can persist even after discontinuation.
Adverse Drug Reactions (ADR)
NMS, severe allergic reactions, serotonin syndrome, cardiac arrhythmias.
Contraindications
Hypersensitivity to amoxapine, recent myocardial infarction, concomitant or recent (within 14 days) use of MAOIs.
Drug Interactions
MAOIs, alcohol, CNS depressants, anticholinergic drugs, CYP2D6 inhibitors or inducers (e.g., fluoxetine, paroxetine), QT prolonging agents.
Pregnancy and Breastfeeding
Not recommended during pregnancy or breastfeeding due to potential risks to the fetus/infant.
Drug Profile Summary
- Mechanism of Action: Inhibits norepinephrine and serotonin reuptake; metabolite blocks dopamine receptors.
- Side Effects: Drowsiness, dry mouth, constipation, NMS, tardive dyskinesia, seizures.
- Contraindications: Hypersensitivity, recent MI, concurrent MAOI use.
- Drug Interactions: MAOIs, alcohol, CNS depressants.
- Pregnancy & Breastfeeding: Avoid.
- Dosage: Adults: Initial 50 mg BID/TID, up to 400mg/day; Elderly: Initial 25 mg BID/TID, max 300 mg/day.
- Monitoring Parameters: ECG, mental status, weight, blood glucose.
Popular Combinations
Generally not combined with other antidepressants.
Precautions
Monitor for suicidal ideation, cardiac function (especially in elderly), and neurological side effects. Avoid alcohol. Use cautiously in patients with seizure disorders, urinary retention, and cardiovascular disease.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amoxapine?
A: Adults: Initial 50 mg BID/TID, titrated up to 400 mg/day; elderly: 25 mg BID/TID initially, max 300 mg/day.
Q2: What are the common side effects of Amoxapine?
A: Drowsiness, dry mouth, constipation, blurred vision, dizziness.
Q3: What are the serious side effects of Amoxapine?
A: Neuroleptic malignant syndrome, tardive dyskinesia, seizures, cardiac arrhythmias.
Q4: What are the contraindications for Amoxapine?
A: Hypersensitivity, recent myocardial infarction, concurrent MAOI use.
Q5: Can Amoxapine be used during pregnancy?
A: It is generally avoided due to potential risks to the fetus.
Q6: What are the potential drug interactions with Amoxapine?
A: MAOIs, alcohol, CNS depressants, CYP2D6 inhibitors/inducers, QT prolonging agents.
Q7: How does Amoxapine work?
A: It inhibits norepinephrine and serotonin reuptake, and its metabolite blocks dopamine receptors.
Q8: What should be monitored in patients taking Amoxapine?
A: Cardiac function (ECG), mental status changes, neurological side effects, weight, and blood glucose.
Q9: What is the maximum recommended dosage for Amoxapine?
A: 400 mg/day for outpatients, and up to 600 mg/day for hospitalized patients with no history of seizures.
Q10: Can Amoxapine be used in children?
A: No, it is not recommended for use in children.
