amoxapine

Amoxapine is a tricyclic-like antidepressant in the dibenzoxazepine class. It is structurally related to the phenothiazines and was introduced in the 1960s for major depressive disorder. Today it is less commonly used, largely because of its side effect profile and the availability of newer antidepressants.

Pharmacology is characterized by inhibition of norepinephrine reuptake and, to a lesser extent, serotonin reuptake. Its active metabolite, 7-hydroxyamoxapine, has potent antagonism at dopamine D2 receptors, which can contribute antipsychotic-like effects and an increased risk of extrapyramidal symptoms. The drug also exhibits anticholinergic and sedative properties typical of agents in this class.

Indications for amoxapine focus on major depressive disorder. It may be considered in cases of treatment-resistant depression or where a patient’s symptoms might benefit from some dopamine antagonism, but its use is limited by tolerability concerns compared with more modern antidepressants.

Common adverse effects include anticholinergic symptoms (dry mouth, constipation, blurred vision), dizziness or orthostatic hypotension, and sedation. Extrapyramidal symptoms, tardive dyskinesia, and a lowering of seizure threshold are additional safety considerations, especially at higher doses or with prolonged use. Cardiac effects such as tachycardia and potential arrhythmias can occur. It can interact with alcohol and other central nervous system depressants and should not be used with monoamine oxidase inhibitors.

Contraindications include recent use of MAO inhibitors, glaucoma with narrow angles, urinary retention, seizure disorders, and significant cardiovascular disease. As with other antidepressants, monitoring for suicidality is advised, particularly in younger patients.