AMOXAPINE

brands

Class

• Neuroscience-based Nomenclature: norepinephrine, serotonin reuptake inhibitor (SN-RI)
• Tricyclic antidepressant (TCA), sometimes classified as a tetracyclic antidepressant
• Norepinephrine reuptake inhibitor
• Serotonin 2A antagonist
• Parent drug and especially an active metabolite are dopamine 2 antagonists

AMOXAPINE commonly prescribed for

(Bold for FDA approved)

How AMOXAPINE works

• Boosts neurotransmitter norepinephrine

• Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission

• Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, amoxapine can thus increase dopamine neurotransmission in this part of the brain

• A more potent inhibitor of norepinephrine reuptake pump than serotonin reuptake pump (serotonin transporter)

• At high doses may also boost neurotransmitter serotonin and presumably increase serotonergic neurotransmission

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

How long until AMOXAPINE works

• Onset of therapeutic actions usually not immediate, but often delayed 2–4 weeks

• If it is not working within 6–8 weeks for depression, it may require a dosage increase or it may not work at all

• May continue to work for many years to prevent relapse of symptoms

Notable Side Effects

• Blurred vision, constipation, urinary retention, increased appetite, dry mouth, nausea, diarrhea, heartburn, unusual taste in mouth, weight gain

• Fatigue, weakness, dizziness, sedation, headache, anxiety, nervousness, restlessness

• Sexual dysfunction, sweating

• Can cause drug-induced parkinsonism, akathisia, and theoretically, tardive dyskinesia

Life Threatening Side Effects

• Paralytic ileus, hyperthermia (TCAs/ tetracyclics + anticholinergic agents)

• Lowered seizure threshold and rare seizures

• Orthostatic hypotension, sudden death, arrhythmias, tachycardia

• QTc prolongation

• Hepatic failure, drug-induced parkinsonism

• Increased intraocular pressure

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

weight gain

common

sedation

common

What to do about AMOXAPINE side effects

• Wait

• Wait

• Lower the dose

• Switch to an SSRI or newer antidepressant

usual dosage range

• 200–300 mg/day

Dosage Forms

• Tablet 25 mg, 50 mg, 100 mg, 150 mg

long term use

• Generally safe

• Some patients may develop withdrawal dyskinesias when discontinuing amoxapine after long-term use

habit forming

• Some patients may develop tolerance

Renal Impairment

• Use with caution – may require lower than usual adult dose

Hepatic Impairment

• Use with caution – may require lower than usual adult dose

Cardiac Impairment

• Baseline ECG is recommended

• TCAs/tetracyclics have been reported to cause arrhythmias, prolongation of conduction time, orthostatic hypotension, sinus tachycardia, and heart failure, especially in the diseased heart

• Myocardial infarction and stroke have been reported with TCAs/tetracyclics

• TCAs/tetracyclics produce QTc prolongation, which may be enhanced by the existence of bradycardia, hypokalemia, congenital or acquired long QTc interval, which should be evaluated prior to administering amoxapine

• Use with caution if treating concomitantly with a medication likely to produce prolonged bradycardia, hypokalemia, slowing of intracardiac conduction, or prolongation of the QTc interval

• Avoid TCAs/tetracyclics in patients with a known history of QTc prolongation, recent acute myocardial infarction, and uncompensated heart failure

Elderly

• Baseline ECG is recommended for patients over age 50

• May be more sensitive to anticholinergic, cardiovascular, hypotensive, and sedative effects

• Initial dose 25 mg/day at bedtime; increase by 25 mg/day each week; maximum dose 300 mg/day

Children and Adolescents

• Use with caution, observing for activation of known or unknown bipolar disorder and/ or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Not generally recommended for use under age 16

• Several studies show lack of efficacy of TCAs/tetracyclics for depression

• May be used to treat enuresis or hyperactive/impulsive behaviors

• Some cases of sudden death have occurred in children taking TCAs/tetracyclics

• Adolescents: initial 25–50 mg/day; increase gradually to 100 mg/day in divided doses or single dose at bedtime

Pregnancy

• Controlled studies have not been conducted in pregnant women

• Some animal studies show adverse effects

• Amoxapine crosses the placenta

• Adverse effects have been reported in infants whose mothers took a TCA (lethargy, withdrawal symptoms, fetal malformations)

• Evaluate for treatment with an antidepressant with a better risk/benefit ratio

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or bottle feed

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Evaluate for treatment with an antidepressant with a better risk/benefit ratio