Amoxapine increases the synaptic concentration of serotonin and norepinephrine in the central nervous system by inhibiting their reuptake by the presynaptic neuronal membrane pump.

It is used to treat patients with unipolar major depression which may include depression with psychotic features.

Amoxapine Dose in Adults

Major Unipolar depressive disorder:

• 25 - 50 mg orally 1 - 3 times a day
• The dose may be increased over 1 -2 weeks to the usual dose of 200 - 300 mg/day in 2 - 3 divided doses if tolerated.
• The maximum daily dose for outpatients use is 400 mg per day and for hospitalized patients is 600 mg/day.
• Higher doses should be used with caution in patients with refractory depression with no history of seizures.
• Doses greater than 300 mg per day should be given in divided doses.

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• Discontinuation of therapy:

  • Discontinuation of therapy should be gradual over 2 - 4 weeks to minimize the incidence of withdrawal symptoms.
  • Patients who develop intolerable withdrawal symptoms should resume the previously prescribed dose and then titrate the drug more gradually.
  • Patients with a history of discontinuation syndrome may benefit from a more gradual tapering regimen over at least 3 months.

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• Switching antidepressants:

  • Although data regarding switching strategies from one antidepressant to another antidepressant is limited, some of the important points are listed here:
    • Cross-titration: This method is usually followed especially when amoxapine or another antidepressant has been used for more than 2 – 4 weeks. One drug is gradually tapered while the dose of the other drug is increased gradually at the same time.
    • Direct switch: Direct switch is the abrupt discontinuation of one drug and initiating the other drug at an equivalent dose. This method may be appropriate in cases where the drug has been used for less than 1 – 2 weeks or when the drug is discontinued because of the adverse effects.

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• Switching to or from an MAOI:

  • At least a 14 day drug-free interval should be allowed when switching from an MAOI to amoxapine and vice versa.
  • Cross-titration is contraindicated when switching from an MAOI to an SSRI and vice versa.

Amoxapine Dose in Children

 Not recommended

Pregnancy Risk Factor C

• The placenta is crossed by amoxapine. Some animal reproduction studies have shown adverse events.
• In case of reports, CNS effects, limb defects, and developmental delay were noted. However, no causal relationship has been established.
• Neonates may become irritable, and jittery, and may rarely develop seizures.
• Crying, constipation, urinary problems, and nausea may also occur in neonates exposed during pregnancy.
• Women who may be at a high risk of postpartum depression may restart the medicine following delivery.

Amoxapine use during breastfeeding:

• It can be excreted in breast milk so it should not be used by breastfeeding mothers.

Amoxapine Dose in Renal Disease:

• Adjustment in the dose has not been recommended. It should be avoided in severe renal impairment. 

Amoxapine Dose in Liver Disease:

• Adjustment in the dose has not been recommended. It should be avoided in severe hepatic impairment. 

Common Side Effects of Amoxapine Include:

• Central nervous system:
  • Drowsiness
• Gastrointestinal:
  • Xerostomia
  • Constipation

Less Common Side Effects of Amoxapine Include:

• Cardiovascular:
  • Edema
  • Palpitations
• Central nervous system:
  • Anxiety,
  • Ataxia,
  • Confusion,
  • Dizziness,
  • EEG pattern changes,
  • Excitement,
  • Fatigue,
  • Headache,
  • Insomnia,
  • Nervousness,
  • Nightmares,
  • Restlessness
• Dermatologic:
  • Diaphoresis,
  • Skin rash
• Endocrine & metabolic:
  • Increased serum prolactin
• Gastrointestinal:
  • Increased appetite,
  • Nausea
• Neuromuscular & skeletal:
  • Tremor,
  • Weakness
• Ophthalmic:
  • Blurred vision

Contraindications to Amoxapine Include:

• Allergy reactions to amoxapine or dibenzoxazepine compound, or any component of the formulation
• Within 14 days of MAOIs, coadministration
• Acute recovery phase following myocardial infarction

Warnings and Precautions

• Suicidal thoughts/behaviour [US Boxed Warning]
  • AmoxapineThis product is not FDA-approved for use in children.
  • Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders.
  • Families and caregivers should be informed to report any changes in behavior and watch for the following behaviors:
    • Anxiety
    • Agitation
    • Panic attacks
    • insomnia,
    • irritability,
    • Hostility
    • Impulsivity
    • Akathisia
    • Hypomania is a condition that causes depression.
    • mania.
  • For any clinical changes, behavior changes, or suicidality, the patient should be closely monitored during the first 1 - 2 months.
  • Stopping the medication should be done if you have suicidal thoughts or are experiencing worsening depression.
• Anticholinergic effects
  • You should use it with caution when treating the following patients:
    • Reduced gastrointestinal motility
    • Increased intraocular pressure
    • Narrow-angle glaucoma
    • Paralytic ileus
    • Urinary retention
    • Benign prostatic hyperplasia
    • xerostomia
    • Visual problems
  • It has a higher degree of an anticholinergic effect than other antidepressants.
• CNS depression:
  • CNS depression can result in mental or physical impairments from Amitriptyline. It is important to warn patients about tasks that require mental alertness.
  • It is mildly sedative compared to antidepressants.
• Extrapyramidal symptoms:
  • Extrapyramidal symptoms may occur, which could include the following:
    • Pseudoparkinsonism
    • Acute dystonic reactions
    • Akathisia
    • Tardive dyskinesia
  • Extrapyramidal symptoms are most likely to occur if you use high doses and frequent doses.
  • Tardive dyskinesia can be irreversible. Treatment must be stopped immediately.
  • The clinical signs of tardive dyskinesia may be masked by antipsychotics.
• Fractures
  • Undiagnosed bone pain, swelling, bruise, or tenderness after taking amitriptyline should prompt a physician to investigate for bone fractures.
  • TCAs have been linked to fragility fractures in the long term.
• Neuroleptic malignant syndrome (NMS):
  • Its use could be linked to neuroleptic malignant disorder.
  • Monitor the patient for changes in mental state, muscle rigidity, fever, or autonomic instability.
• Ocular effects
  • Because of pupillary dilation, it may worsen angle-closure glaucoma.
• Orthostatic hypotension
  • Patients with hypovolemia, cerebrovascular disease, and cardiovascular disease should be cautious.
• Cardiovascular disease
  • Patients with a previous myocardial infarction, stroke, tachycardia, or conduction abnormalities should be advised of the drug with caution.
• Diabetes:
  • It can alter glucose regulation. Patients with diabetes should use it with caution.
• Hepatic impairment
  • Patients with liver disease should be cautious.
• Hypomania and mania:
  • The treatment of bipolar disorder, is not FDA-approved. It is important to screen patients for signs of hypomania or mania and then treat them accordingly.
• Renal impairment
  • Patients suffering from kidney disease should be cautious.
• Seizure disorder:
  • Patients at high risk for seizures such as those with seizures due to head trauma, brain damage or alcoholism should be cautious.

Amoxapine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• Monitor serum sodium in at-risk populations as clinically indicated)
• Evaluate:
  • mental status,
  • suicidal thoughts and ideation especially at the beginning of therapy and after any dose adjustment,
  • anxiety,
  • social functioning,
  • mania,
  • panic attacks or other unusual changes in behavior.
• Monitor:
  • heart rate,
  • blood pressure and
  • ECG in older adults and patients with preexisting heart disease
  • electrolyte panel to assess the risk of conduction abnormalities
  • blood glucose
  • weight and BMI
  • Observe for involuntary movements and signs of Parkinson's disease
  • tardive dyskinesias
  • ejaculatory and erectile dysfunction
  • galactorrhea
  • changes in libido and menstruation

How to Administer Amoxapine?

• It should be taken with evening meals to reduce gastrointestinal side effects and sedation.

Mechanism of action of Amoxapine:

• Amoxapine increases synaptic serotonin levels and norepinephrine concentrations in the central nervous system by inhibiting their reuptake through the presynaptic neural membrane pump.
• Its metabolite 7OH-amoxapine is similar to antipsychotic drugs in that it has significant dopamine receptor-blocking ability.

The process takes between 1 and 2 weeks. the antidepressant effect may take up to 6 weeks for maximum results to be observed. It works well-absorbed, and Absorption is quick. 95% of the drug's active ingredient is protein-bound. It is widely used.

MetabolizedThrough hepatic hydrolysis.

 It contains two metabolites: 7-hydroxyamoxapine (7OH-amoxapine), and 8-hydroxyamoxapine (OH-amoxapine), which form glucuronides through the process of conjugation.

Thehalf-life eliminationIt takes 8 hours. The half-life of its metabolite 8 hydroxyamoxapine is 30 hours. The drug takes approximately 90 minutes to reach its destination. peak serum concentrationIt isexcretedIn the urine.

Amoxapine International Brands:

• Adisen
• Asendin
• Defanyl
• Demolox
• Oxcap

Amoxapine Brands in Pakistan:

No brands available in Pakistan.