Tricyclic Antidepressant

Amoxapine

Amoxapine is a tricyclic antidepressant with unique dopamine-blocking properties, making it structurally and pharmacologically similar to antipsychotics. It is indicated for depression, particularly in patients with psychotic features, but carries increased risk of extrapyramidal side effects and tardive dyskinesia compared to other tricyclics.

Clinical Overview

Primary Clinical Applications

Amoxapine is indicated for depression and may be particularly useful for patients with depression accompanied by psychotic features or severe agitation. Its dopamine-blocking activity provides some antipsychotic effects, making it potentially valuable for psychotic depression when combination therapy is not feasible.

Mechanism and Clinical Profile

Like other tricyclics, amoxapine blocks norepinephrine and serotonin reuptake, but it also has significant dopamine D2 receptor blocking activity. This unique profile provides antidepressant effects with some antipsychotic activity, but also increases the risk of movement disorders typically associated with antipsychotics.

Safety Considerations

Amoxapine carries a higher risk of extrapyramidal side effects and tardive dyskinesia compared to other tricyclics due to its dopamine-blocking activity. It also has the typical tricyclic risks of cardiotoxicity and anticholinergic effects, making it a less favorable choice compared to newer antidepressants for most patients.

Key Clinical Points

A tricyclic with antipsychotic activity

Amoxapine blocks dopamine D2 receptors in addition to inhibiting norepinephrine and serotonin reuptake. This makes it unusual among tricyclics and potentially useful in depression with psychotic features when combination therapy is not feasible.

Movement disorder risk unique among tricyclics

Dopamine blockade brings extrapyramidal symptoms, tardive dyskinesia, and rare neuroleptic malignant syndrome into the risk profile. These are not concerns with other tricyclics and should inform the choice between agents.

Boxed warning in patients under 25

Carries the antidepressant class boxed warning for increased suicidal thinking and behaviour in patients under 25 years, requiring closer monitoring during initiation and dose adjustment.

Antagonises dopaminergic medication

Dopamine blockade means amoxapine will oppose the action of dopaminergic drugs. Contraindicated within fourteen days of an MAOI, and with linezolid or intravenous methylene blue.

Tardive dyskinesia counselling is advised

Where chronic use is contemplated, patients should be informed of tardive dyskinesia risk before starting, and monitored for emergent movement abnormalities throughout treatment.

Prescribing Information

Dosing & Administration

Depression – Adults:

Initial: 50 mg 2-3 times daily
Titration: May increase to 100 mg 2-3 times daily by end of first week
Range: 200-300 mg daily in divided doses
Maximum: 400 mg daily (outpatients), 600 mg daily (hospitalized patients)

Elderly:

Initial: 25 mg 2-3 times daily
Maintenance: Usually 50-150 mg daily
Maximum: 300 mg daily

Administration:

Divide daily dose into 2-3 administrations
May give largest portion at bedtime if sedation is desired
Take with food to reduce GI upset

Indications

Treatment of depression
May be particularly useful for depression with psychotic features

Contraindications

Hypersensitivity to tricyclic antidepressants
Use within 14 days of MAOI therapy
Acute recovery period following myocardial infarction
Concurrent use with linezolid or IV methylene blue

Warnings & Precautions

Boxed Warning: Increased risk of suicidal thoughts and behavior in patients under 25 years
Extrapyramidal symptoms: Higher risk than other tricyclics due to dopamine blockade
Tardive dyskinesia: Risk with long-term use, unique among tricyclics
Neuroleptic malignant syndrome: Rare but possible due to dopamine blockade
Cardiovascular effects: Monitor ECG in patients with cardiac disease
Anticholinergic effects: Dry mouth, constipation, urinary retention

Drug Interactions

MAOIs: Contraindicated – risk of serotonin syndrome
CNS depressants: Enhanced sedation
Anticholinergic drugs: Additive anticholinergic effects
CYP2D6 inhibitors: Increase amoxapine levels
Dopaminergic drugs: Antagonized by amoxapine’s dopamine blockade

Adverse Reactions

Common:

Drowsiness, dry mouth, constipation, blurred vision
Dizziness, tremor, confusion

Unique to amoxapine:

Extrapyramidal symptoms (akathisia, dystonia, parkinsonism)
Tardive dyskinesia with chronic use

Serious:

Cardiac arrhythmias, seizures, neuroleptic malignant syndrome

Special Populations

Elderly: Higher risk of anticholinergic and extrapyramidal effects
Cardiac Disease: Requires careful monitoring due to cardiotoxic potential
Pregnancy: Category C – use only if benefits outweigh risks
Movement disorder risk: Monitor for extrapyramidal symptoms and tardive dyskinesia

Frequently Asked Questions

What is Amoxapine used for?

What class of drug is Amoxapine?

Amoxapine is classified as: Tricyclic Antidepressant.

A tricyclic with antipsychotic activity?

Movement disorder risk unique among tricyclics?

Boxed warning in patients under 25?

Carries the antidepressant class boxed warning for increased suicidal thinking and behaviour in patients under 25 years, requiring closer monitoring during initiation and dose adjustment.

Antagonises dopaminergic medication?

Dopamine blockade means amoxapine will oppose the action of dopaminergic drugs. Contraindicated within fourteen days of an MAOI, and with linezolid or intravenous methylene blue.

Source: FDA prescribing information (DailyMed)

Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.