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amoxapine

Adjunctive therapy

Brand: Asendin

Published 2026-03-24 · Last reviewed 2026-03-31 · 4 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: Label dosing is individualized. A common initiation is 50 mg two or three times daily with gradual increases based on response and tolerability (label).·Half-life: Single-dose mean 8 h·LAI available: No

Class: Adjunctive therapy
Typical dose: Label dosing is individualized. A common initiation is 50 mg two or three times daily with gradual increases based on response and tolerability (label).
Half-life: Single-dose mean 8 h
LAI available: No

Quick answers

What is amoxapine?: Amoxapine (brand Asendin; generics) is an older antidepressant indicated for depression, including depression accompanied by anxiety or agitation (label). It is structurally distinct from TCAs but shares many TCA-like safety considerations.
What is Asendin?: Asendin is a brand name for amoxapine.
What is Asendin (amoxapine) used for?: Label indications include: Depression, including depression with anxiety or agitation (label).
What drug class is Asendin (amoxapine)?: Tricyclic Antidepressant.
What is the mechanism of action of Asendin (amoxapine)?: Dibenzoxazepine antidepressant with norepinephrine/serotonin reuptake inhibition and clinically meaningful dopamine receptor blockade (EPS/TD risk).
What strengths does Asendin (amoxapine) come in?: Oral tablets (label): 25 mg, 50 mg, 100 mg, 150 mg.

General information

Amoxapine (brand Asendin; generics) is an older antidepressant indicated for the relief of symptoms of depression, including depression with anxiety or agitation (label).

A key differentiator is clinically meaningful dopamine receptor blocking activity. This can produce extrapyramidal symptoms (EPS) and is associated with a warning about Tardive dyskinesia—a profile that overlaps with antipsychotic monitoring concerns (label).

Because of anticholinergic burden, orthostasis, seizure risk at higher doses, and the possibility of movement disorders, amoxapine is generally used selectively rather than as a first-line depression option (clinical).

Label pharmacokinetics report a parent half-life of ~8 hours and a major metabolite (8-hydroxy-amoxapine) with a longer ~30-hour half-life, which can extend both benefits and adverse effects (label).

The compare view, amoxapine evidence feed, and amoxapine print page support counseling and documentation when a tricyclic-like antidepressant is being weighed in the context of psychosis risk or prior antipsychotic exposure.

U.S. approvals

Depression

Formulations & strengths

Oral tablets (label): 25 mg, 50 mg, 100 mg, 150 mg.

Generic availability

Generic tablets available from multiple manufacturers.

Amoxapine is used infrequently in modern practice because safer options exist for most patients. When it is selected, monitoring focuses on movement disorders (EPS/TD), seizure risk at higher doses, and typical tricyclic-like tolerability issues (orthostasis and anticholinergic effects).

View labelExact

Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Amoxapine inhibits norepinephrine and serotonin uptake and has dopamine receptor blocking activity; the dopamine-blocking component explains its uncommon antidepressant association with EPS and tardive dyskinesia (label/mechanism).

Antagonism at histamine H1, muscarinic, and α1-adrenergic receptors contributes to sedation, constipation/urinary retention, and Orthostatic hypotension (class effects).

Tricyclic-like antidepressant with dopamine-blocking activity (EPS/TD risk).

Metabolism & pharmacokinetics

Rapidly absorbed; label describes peak blood levels around 90 minutes after ingestion (label).
Extensively metabolized. Parent half-life is ~8 hours; major metabolite 8-hydroxy-amoxapine has a biologic half-life of ~30 hours (label).
Metabolites are excreted in urine in conjugated form as glucuronides (label).

Dosing & administration

Label dosing is individualized. A common initiation is 50 mg two or three times daily with gradual increases based on response and tolerability (label).
Some patients transition to 100 mg two or three times daily; labeling notes that if 300 mg/day is ineffective after 2 weeks, higher doses may be required in select patients (label).
Label allows single-bedtime dosing when total daily dose does not exceed 300 mg; higher doses are divided (label).
Hospitalized, treatment-refractory patients without seizure history may require higher doses (up to 600 mg/day in labeling), with close monitoring for seizures, orthostasis, and movement disorders (label/clinical).
Gradual tapering is commonly used when discontinuing after longer courses to reduce withdrawal symptoms and to distinguish withdrawal from relapse (clinical).

Monitoring & labs

Movement-disorder screening for EPS (rigidity, tremor, akathisia) and abnormal movements concerning for tardive dyskinesia, especially during titration and at higher doses (label/clinical).
Seizure risk review (history, co-medications) and reassessment when dose escalation is considered (label/clinical).
Orthostatic vitals, falls risk, and anticholinergic burden (bowel and bladder symptoms, cognition), especially in older adults (clinical).
ECG planning in patients with cardiac history, older age, electrolyte disturbance risk, or multiple QT-active drugs (clinical).
Suicidality and mood switching surveillance early in treatment and after dose changes (label/clinical).

Monitoring for amoxapine blends antidepressant follow-up with antipsychotic-like movement-disorder screening because of dopamine-blocking activity.

Adverse effects

FDA boxed warnings

Boxed warning: antidepressants increase the risk of suicidal thoughts/behaviors in children, adolescents, and young adults.

Common side effects (≥10%)

Sedation and daytime impairment: Sedation can occur and is often dose limiting, especially with polypharmacy (label/clinical).
Anticholinergic effects: Anticholinergic side effects (constipation, urinary retention, blurry vision, cognitive slowing) are common limiting adverse effects (label/clinical).
Orthostasis: Orthostatic hypotension and dizziness can occur during titration and with polypharmacy; falls risk is a common follow-up topic (label/clinical).
Weight and appetite change: Weight gain can occur; monitoring is individualized to baseline risk (clinical).

Other notable effects

Dopamine-blocking activity can cause EPS and is associated with a warning about Tardive dyskinesia; monitoring resembles antipsychotic movement screening in higher-risk patients (label/clinical).
Seizure threshold reduction can occur, particularly at higher doses or in patients with predisposing risk factors (label).
Cardiac conduction changes and arrhythmias are class risks for tricyclic-like agents; ECG monitoring is often used when baseline risk is elevated (clinical).
Mood switching can occur in bipolar-spectrum illness; monitoring for Mania/Hypomania is commonly coordinated when treating depressive episodes (clinical).
Serotonin syndrome can occur with serotonergic combinations (label/class).

Interactions

MAOIs are contraindicated; washout periods are used to reduce risk of severe reactions (label).
Additive CNS depression can occur with alcohol, benzodiazepines, opioids, and other sedatives; functional safety is a common review topic (label/clinical).
CYP2D6 inhibition (fluoxetine, paroxetine, quinidine) can increase exposure of tricyclic-like antidepressants; medication reconciliation is commonly used to anticipate toxicity risk (clinical).
Other anticholinergic medications (some antipsychotics, antihistamines) can compound constipation, urinary retention, and delirium risk (clinical).

Other useful information

Amoxapine is generally positioned after SSRIs/SNRIs in depression guidelines because safer alternatives exist for most patients (APA/CANMAT/clinical).
If abnormal movements, rigidity, restlessness, or Akathisia emerge, clinicians commonly reassess the medication choice and consider switching to a non–dopamine-blocking antidepressant (label/clinical).
When depressive symptoms occur in bipolar disorder, antidepressants are commonly paired with a mood stabilizer and monitored for mood switching; see the bipolar disorder hub for longitudinal care pathways.
For older adults, medication review that reduces additive anticholinergic and sedative burden is often higher yield than adding multiple “side-effect” medications (clinical).

References

Related hubs:SMI toolkit·Support resources