Amoxapine

Mechanism-of-action classes: Dopamine Antagonists; Monoamine Oxidase Inhibitors; Norepinephrine Uptake Inhibitors; Serotonin Uptake Inhibitors.

• Amoxapine is indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. It is indicated for depression accompanied by anxiety or agitation.

• Amoxapine is contraindicated in patients who have shown prior hypersensitivity to dibenzoxazepine compounds. It should not be given concomitantly with monoamine oxidase inhibitors.contraindicated

Effective dosage of amoxapine may vary from one patient to another. Usual effective dosage is 200 to 300 mg daily. Three weeks constitutes an adequate period of trial providing dosage has reached 300 mg daily (or lower level of tolerance) for at least two weeks. If no response is seen at 300 mg, dosage may be increased, depending upon tolerance, up to 400 mg daily. Hospitalized patients who have been refractory to antidepressant therapy and who have no history of convulsive seizures may have dosage raised cautiously up to 600 mg daily in divided doses. Amoxapine may be given in a single daily dose, not to exceed 300 mg, preferably at bedtime. If the total daily dosage exceeds 300 mg, it should be given in divided doses. Initial Dosage for Adults Usual starting dosage is 50 mg two or three times daily. Depending upon tolerance, dosage may be increased to 100 mg two or three times daily by the end of the first week. (Initial dosage of 300 mg daily may be given, but notable sedation may occur in some patients during the first few days of therapy at this level.) Increases above 300 mg daily should be made only if 300 mg daily has been ineffective during a trial period of at least two weeks. When effective dosage is established, the drug may be given in a single dose (not to exceed 300 mg) at bedtime. Elderly Patients In general, lower dosages are recommended for these patients. Recommended starting dosage of amoxapine is 25 mg two or three times daily. If no intolerance is observed, dosage may be increased by the end of the first week to 50 mg two or three times daily.

Clinical Worsening and Suicide Risk Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients.

Adverse reactions reported in controlled studies in the United States are categorized with respect to incidence below. Following this is a listing of reactions known to occur with other antidepressant drugs of this class. Incidence Greater Than 1% The most frequent types of adverse reactions occurring with amoxapine in controlled clinical trials were sedative and anticholinergic: these included drowsiness (14%), dry mouth (14%), constipation (12%), and blurred vision (7%). Less frequently reported reactions are: CNS and Neuromuscular: anxiety, insomnia, restlessness, nervousness, palpitations, tremors, confusion, excitement, nightmares, ataxia, alterations in EEG patterns. Allergic: edema, skin rash. Endocrine: elevation of prolactin levels. Gastrointestinal: nausea. Other: dizziness, headache, fatigue, weakness, excessive appetite, increased perspiration. Incidence Less Than 1% Anticholinergic: disturbances of accommodation, mydriasis, delayed micturition, urinary retention, nasal stuffiness. Cardiovascular: hypotension, hypertension, syncope, tachycardia. Allergic: drug fever, urticaria, photosensitization, pruritus, vasculitis, hepatitis. CNS and Neuromuscular: tingling, paresthesias of the extremities, tinnitus, disorientation, seizures, hypomania, numbness, incoordination, disturbed concentration, hyperthermia, extrapyramidal symptoms, including, tardive dyskinesia. Neuroleptic malignant syndrome has been reported. (See WARNINGS .) Hematologic: leukopenia, agranulocytosis.

Pregnancy Studies performed in mice, rats, and rabbits have demonstrated no evidence of teratogenic effect due to amoxapine. Embryotoxicity was seen in rats and rabbits given oral doses approximating the human dose. Fetotoxic effects (intrauterine death, stillbirth, decreased birth weight) were seen in animals studied at oral doses 3 to 10 times the human dose. Decreased postnatal survival (between days 0 to 4) was demonstrated in the offspring of rats at 5 to 10 times the human dose. There are no adequate and well-controlled studies in pregnant women. Amoxapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Signs and Symptoms Toxic manifestations of amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects - particularly grand mal convulsions - occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Fatal overdoses with amoxapine have occurred. Renal failure may develop two to five days after toxic overdosage in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomyolysis and myoglobinuria is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures. Treatment Treatment of amoxapine overdosage should be symptomatic and supportive, but with special attention to prevention or control of seizures.

• Jun 28, 1991ANDAANDA072879Chartwell Rx
• Aug 28, 1992ANDAANDA072691Watson Labs

1. 1Poisoning408.4%
2. 2Drug Abuse377.8%
3. 3Drug Ineffective285.9%
4. 4Toxicity To Various Agents285.9%
5. 5Completed Suicide275.7%
6. 6Somnolence265.5%
7. 7Depression224.6%
8. 8Pyrexia214.4%
9. 9Asphyxia204.2%
10. 10Overdose204.2%
11. 11Tachycardia183.8%
12. 12Suicide Attempt173.6%
13. 13Death163.4%
14. 14Diarrhoea163.4%
15. 15Insomnia163.4%

Recent PubMed references pinned to Amoxapine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Evaluation of toxicokinetic interactions mediated by plasma protein binding during amoxapine intoxication.
  The Journal of toxicological sciences · 2026 · Okamoto A, Yamazaki Y, Hattori-Usami N, et al.
  PMID 41500576DOI 10.2131/jts.51.31
• Inhibitory Actions of Antidepressants, Hypnotics, and Anxiolytics on Recombinant Human Acetylcholinesterase Activity.
  Biological & pharmaceutical bulletin · 2024 · Obara K, Mori H, Ihara S, et al.
  PMID 38296462DOI 10.1248/bpb.b23-00719
• Preparation and characterization of amoxapine- and naringin-loaded solid lipid nanoparticles: drug-release and molecular-docking studies.
  Nanomedicine (London, England) · 2022 · Jat S, Bhatt M, Roychowdhury S, et al.
  PMID 36786368DOI 10.2217/nnm-2022-0167
• Successful Treatment of Amoxapine-Induced Intractable Seizures With Intravenous Lipid Emulsion.
  The Journal of emergency medicine · 2023 · Matsuoka M, Imai T, Iwabuchi S, et al.
  PMID 36450616DOI 10.1016/j.jemermed.2022.10.016
• FDA-Approved Amoxapine Effectively Promotes Macrophage Control of Mycobacteria by Inducing Autophagy.
  Microbiology spectrum · 2022 · Wang J, Sha J, Strong E, et al.
  PMID 36129262DOI 10.1128/spectrum.02509-22
• Over-Expression of GUSB Leads to Primary Resistance of Anti-PD1 Therapy in Hepatocellular Carcinoma.
  Frontiers in immunology · 2022 · Kong X, Zheng Z, Song G, et al.
  PMID 35812439DOI 10.3389/fimmu.2022.876048
• Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish.
  Cells · 2021 · Suryanto ME, Audira G, Uapipatanakul B, et al.
  PMID 33810553DOI 10.3390/cells10040738
• Elucidation of Degradation Behavior of Tricyclic Antidepressant Amoxapine in Artificial Gastric Juice.
  Chemical & pharmaceutical bulletin · 2020 · Saito K, Hagiwara N, Sakamoto M, et al.
  PMID 32879225DOI 10.1248/cpb.c20-00313

The 1 most recently updated of 1 ClinicalTrials.gov registrations naming Amoxapine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism
  Completed · Phase 4 · Interventional · 27 enrolled · University of Ottawa
  NCT00704860updated 2011-01-19

CPIC-curated drug–gene pairs for Amoxapine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP2D6CPIC B/C (provisional)FDA label: Informative PGx

Frequently asked questions

How does Amoxapine work?

Mechanism-of-action classes: Dopamine Antagonists; Monoamine Oxidase Inhibitors; Norepinephrine Uptake Inhibitors; Serotonin Uptake Inhibitors.

What is Amoxapine used for?

According to FDA labeling, Amoxapine carries indications including: Amoxapine is indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. It is indicated for depression accompanied by anxiety or agitation.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Amoxapine?

Amoxapine is classified as Non-selective monoamine reuptake inhibitors, Tricyclic Antidepressant, Dopamine Antagonists, Monoamine Oxidase Inhibitors, Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors, Decreased Serotonin Degradation, Increased Central Nervous System Norepinephrine Activity.

What are the contraindications for Amoxapine?

Amoxapine labeling lists contraindications including: Amoxapine is contraindicated in patients who have shown prior hypersensitivity to dibenzoxazepine compounds. It should not be given concomitantly with monoamine oxidase inhibitors.. Always consult the full prescribing information and a clinician.