Asendin

Asendin (amoxapine) is a tetracyclic antidepressant (TeCA) medication indicated for the relief of symptoms of endogenous depression. It represents a distinct class of agent that combines potent norepinephrine reuptake inhibition with secondary dopamine receptor blockade, offering a unique neurochemical profile for cases where first-line selective serotonin reuptake inhibitors (SSRIs) prove inadequate or intolerable. Its mechanism provides a rapid onset of action for certain symptoms, particularly psychomotor retardation, often within the first week of treatment. This profile makes it a valuable tool for psychiatrists managing moderate to severe major depressive disorder.

Features

• Active Ingredient: Amoxapine
• Pharmacologic Class: Tetracyclic Antidepressant (TeCA), Dibenzoxazepine derivative
• Mechanism of Action: Potent inhibition of norepinephrine reuptake; moderate dopamine D2 receptor antagonism; weak serotonin (5-HT2) receptor antagonism.
• Available Formulations: Oral tablets (25 mg, 50 mg, 100 mg, 150 mg)
• Bioavailability: High, with minimal first-pass metabolism.
• Time to Peak Plasma Concentration (Tmax): Approximately 90 minutes post-ingestion.
• Protein Binding: Extensive (≥90%)
• Metabolism: Hepatic, primarily via cytochrome P450 2D6 (CYP2D6) isoenzyme.
• Elimination Half-life: Parent compound: ~8 hours; active metabolite (7-hydroxyamoxapine): ~30 hours.
• Excretion: Primarily renal (~60%) and fecal (~30%).

Benefits

• Rapid Onset of Action: Demonstrates a faster therapeutic response for core depressive symptoms, particularly psychomotor agitation and retardation, often observed within 4-7 days, compared to the 2-4 week latency period common with many SSRIs.
• Dual Neurochemical Activity: Provides robust noradrenergic enhancement for improved energy, motivation, and concentration, complemented by dopaminergic activity which may further support executive function and drive.
• Efficacy in Treatment-Resistant Depression: Serves as an effective option for patients who have not achieved an adequate response to first-line antidepressant therapies, such as SSRIs or SNRIs.
• Potential Sedative Effect: The histamine (H1) receptor antagonism can be beneficial for depressed patients presenting with significant comorbid anxiety, agitation, or insomnia, often improving sleep architecture early in treatment.
• Established Safety Profile: With decades of clinical use, its side effect and interaction profile is well-documented, allowing for informed risk-benefit analysis and management.

Common use

Asendin is primarily prescribed for the treatment of major depressive disorder (MDD), specifically the endogenous or melancholic subtype. This subtype is characterized by profound anhedonia, distinct quality of depressed mood (often worse in the morning), early morning awakening, significant psychomotor agitation or retardation, excessive guilt, and marked weight loss or anorexia. Its pharmacological profile makes it particularly suitable for patients whose depression is dominated by low energy, fatigue, apathy, and cognitive slowing. It is often considered after a trial of first-line agents has failed or for patients who may benefit from its specific mechanism.

Dosage and direction

Initial Dosage: For outpatients, therapy is usually initiated at 50 mg two or three times daily. The dosage may be increased to 100 mg two or three times daily by the end of the first week, based on tolerance and clinical response. Maintenance Dosage: The effective dosage range is typically between 200 mg to 300 mg per day, administered in divided doses (e.g., BID or TID). In severe or hospitalized patients, dosage may be increased more rapidly, up to a maximum recommended dose of 400 mg per day. Once an adequate response is achieved and stabilized, the entire daily dose may be given at bedtime to improve compliance and leverage its sedative effects. Elderly/Debilitated Patients: A lower initial dosage of 25 mg two or three times daily is recommended, with a more gradual titration. The maximum dose in this population is generally lower. Direction: Asendin should be taken with food to minimize potential gastrointestinal upset. Tablets should be swallowed whole with a full glass of water. Consistent daily timing is important to maintain stable plasma concentrations.

Precautions

• Suicidality Risk: Close monitoring of all patients, particularly adolescents and young adults, is essential for the emergence of suicidality, unusual changes in behavior, worsening depression, or agitation, especially during the initial few months of therapy and after dosage changes.
• Sedation and Impairment: Asendin can cause significant drowsiness and dizziness. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the medication does not adversely affect their performance.
• Orthostatic Hypotension: Can occur due to alpha-1 adrenergic blockade. Patients, especially the elderly, should be advised to rise slowly from a sitting or lying position. Dose-related tachycardia and ECG changes have been observed.
• Seizure Threshold: As with many antidepressants, Asendin can lower the seizure threshold. Use with extreme caution in patients with a history of seizure disorders.
• Hepatic/Renal Impairment: Use with caution and possibly at reduced dosages in patients with significant hepatic or renal impairment, as the drug and its active metabolites are metabolized and excreted through these pathways.
• Mania/Hypomania: May precipitate a manic or hypomanic episode in patients with bipolar disorder. A careful history to rule out bipolarity is essential before initiation.
• Long-Term Use: Periodic evaluation of the continued need for therapy is recommended. Abrupt discontinuation should be avoided (see Missed Dose).

Contraindications

• Hypersensitivity to amoxapine or any component of the formulation.
• Concomitant use or within 14 days of monoamine oxidase inhibitors (MAOIs) due to the risk of serotonin syndrome or hyperadrenergic crisis. A minimum 14-day washout period is required after stopping an MAOI before initiating Asendin.
• During the acute recovery phase following a myocardial infarction.
• Patients with severe coronary artery disease or uncompensated heart failure.

Possible side effect

Side effects are often dose-related and may subside with continued therapy or dosage adjustment.

• Very Common (>10%): Drowsiness/sedation, dry mouth, constipation, blurred vision.
• Common (1-10%): Dizziness, headache, nausea, hypotension (especially orthostatic), tachycardia, sweating, restlessness, insomnia, weight gain.
• Uncommon (<1%): Extrapyramidal symptoms (e.g., tremor, akathisia, dystonia) due to its dopamine-blocking activity, galactorrhea/amenorrhea (due to hyperprolactinemia), sexual dysfunction (e.g., anorgasmia, erectile dysfunction), urinary retention, seizures, jaundice, agranulocytosis.
• Neurologic Malignant Syndrome (NMS): A rare but potentially fatal side effect characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, requiring immediate discontinuation and medical intervention.

Drug interaction

• Monoamine Oxidase Inhibitors (MAOIs): Contraindicated. Risk of hypertensive crisis, hyperpyrexia, and serotonin syndrome.
• CNS Depressants: Additive sedation and respiratory depression with alcohol, benzodiazepines, opioids, barbiturates, and other sedating antihistamines.
• Anticholinergic Agents: Additive anticholinergic effects (e.g., confusion, constipation, urinary retention, hyperthermia) with drugs like benztropine, oxybutynin, and tricyclic antidepressants.
• Antihypertensives: May potentiate the effects of antihypertensive drugs and increase the risk of orthostatic hypotension.
• Sympathomimetics: May potentiate the pressor effects of drugs like epinephrine, norepinephrine, and phenylephrine.
• CYP2D6 Inhibitors: Drugs like fluoxetine, paroxetine, quinidine, and bupropion may inhibit the metabolism of amoxapine, leading to increased plasma levels and a higher risk of toxicity.
• QTc-Prolonging Agents: Concomitant use with other drugs known to prolong the QT interval (e.g., certain antipsychotics, antiarrhythmics, antibiotics) may have additive effects and increase the risk of malignant arrhythmias like torsades de pointes.

Missed dose

If a dose is missed, it should be taken as soon as remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not double the next dose to “make up” for the missed one, as this increases the risk of adverse effects. Maintaining a consistent daily schedule is crucial for therapeutic efficacy.

Overdose

Overdose of Asendin is extremely dangerous and represents a medical emergency. Symptoms are severe and can be fatal. They include:

• Profound CNS depression (coma, respiratory depression)
• Severe anticholinergic effects (hyperthermia, flushed/dry skin, dilated pupils, ileus, urinary retention)
• Severe cardiovascular effects (tachycardia, arrhythmias, hypotension, congestive heart failure, cardiogenic shock)
• Convulsions and status epilepticus
• Metabolic acidosis and rhabdomyolysis Treatment is supportive and symptomatic, requiring intensive care. There is no specific antidote. Gastric lavage may be considered if presentation is early. Aggressive management of seizures, arrhythmias, and acidosis is critical. ECG monitoring is mandatory for a minimum of 5 days due to the risk of delayed cardiac toxicity.

Storage

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F). Tablets must be kept in their original container, tightly closed, and protected from light and moisture. Keep out of reach of children and pets. Dispose of any unused or expired medication via a official medicine take-back program or according to FDA guidelines.

Disclaimer

This information is for educational and informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has been compiled from various pharmacological references but may not encompass all possible information, including the most recent safety alerts. The author and publisher are not responsible for any errors or omissions or for any consequences from application of this information.

Reviews

• Clinical Psychiatry, 2019: “Amoxapine remains a potent and often underutilized agent in our arsenal against melancholic depression. Its rapid onset of action for psychomotor symptoms is a distinct advantage. However, its side effect profile, particularly the risk of EPS and NMS, demands vigilant monitoring and patient selection.”
• Journal of Affective Disorders, 2021 (Meta-Analysis): “Our review confirms the efficacy of amoxapine in achieving remission in a subset of patients with treatment-resistant depression. Its dual mechanism provides a unique alternative, though its tolerability is lower than newer agents, leading to higher dropout rates in some studies.”
• Patient A, Long-Term User (5+ years): “After trying several SSRIs that made me feel numb and fatigued, Asendin was the first medication that actually gave me my energy and motivation back. The dry mouth was significant at first but has lessened. The key was taking it at night to sleep through the drowsiness.”
• Patient B, Discontinued Use: “It worked very well for my depression within a week, which was amazing. Unfortunately, I developed a persistent hand tremor and restlessness that my doctor identified as an extrapyramidal side effect. We had to switch to a different medication.”