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Amoxapine - a tricyclic antidepressant with antipsychotic effects

Amoxapine is a medication primarily used in the treatment of depression. It belongs to the class of drugs known as tricyclic antidepressants (TCAs). Like other TCAs, amoxapine works by increasing the levels of certain neurotransmitters in the brain, such as serotonin and norepinephrine, which are believed to be involved in regulating mood.

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

Amoxapine use in Major Unipolar depressive disorder:

Initial dose: 25 to 50 mg, 1 to 3 times daily.
Increase dose based on response and tolerability over 1 to 2 weeks.
Usual dose: 200 to 300 mg/day, divided into 2 to 3 doses.
If no response to 300 mg/day for 2 weeks, may increase to 400 mg/day.
In hospitalized patients refractory to antidepressant therapy, may cautiously increase to 600 mg/day.
Once effective dose reached, doses ≤300 mg may be given once daily at bedtime; doses >300 mg/day should be divided.
Maximum daily dose: 400 mg outpatient; 600 mg hospitalized patients.

Discontinuation of Therapy:

Gradually taper dose over 2 to 4 weeks to minimize withdrawal symptoms and detect reemerging symptoms.
Consider slower titration (over 4 weeks) for certain cases (eg, short half-life drugs, high doses, long-term treatment).
If intolerable withdrawal symptoms occur, resume previous dose and/or decrease dose more gradually.

Switching Antidepressants:

Strategies include cross-titration and direct switch.
Cross-titration standard for most switches but contraindicated with MAOIs.
Direct switch may be appropriate for same or similar class of antidepressants, short-term use, or adverse effects.
Consider discontinuation symptoms, drug interactions, antidepressant properties, and desired symptom control.

Switching to or from an MAOI:

Allow 14 days between discontinuing an MAOI and starting amoxapine.
Allow 14 days between discontinuing amoxapine and starting an MAOI.

Amoxapine Dose in Children

Not recommended

Pregnancy Risk Factor C

Tricyclic antidepressants like amoxapine are categorized as Pregnancy Risk Factor C, meaning adverse events were observed in some animal reproduction studies.
While they can help treat depression, there are potential risks, including irritability, jitteriness, and convulsions in newborns.
The American College of Obstetricians and Gynecologists (ACOG) advises individualized treatment plans for depression during pregnancy, involving input from mental health clinicians, obstetricians, primary healthcare providers, and pediatricians.
The American Psychiatric Association (APA) suggests weighing the risks of medication against untreated depression and considering restarting medication postpartum for those at high risk.
Treatment guidelines from ACOG and APA offer guidance for managing depression before and during pregnancy.
Pregnant women on antidepressants are encouraged to join the National Pregnancy Registry for Antidepressants (NPRAD) by calling 844-405-6185, ideally enrolling early in pregnancy.

Amoxapine use during breastfeeding:

Amoxapine can pass into breast milk, as indicated by a case report where low concentrations of both amoxapine and its active metabolite were found in the milk of a non-nursing woman who developed galactorrhea during treatment.
Therefore, caution is advised if prescribing amoxapine to a nursing mother, as recommended by the manufacturer.

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:

Amoxapine should not be used in individuals with a known hypersensitivity to amoxapine itself, any component of its formulation, or dibenzoxazepine compounds.
It's also contraindicated for use with or within 14 days of MAO inhibitors due to the risk of serious drug interactions.
Additionally, it should be avoided during the acute recovery phase following a myocardial infarction to prevent potential complications.

Warnings and Precautions

Suicidal thoughts/behaviour [US Boxed Warning]

Amoxapine, like many antidepressants, carries a US Boxed Warning due to the increased risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years) with major depressive disorder (MDD) and other psychiatric disorders.
Before prescribing amoxapine, it's crucial to assess this risk.
Short-term studies haven't shown an increased risk in patients over 24 years old and even demonstrated a decreased risk in those aged 65 and above.
However, all patients should be closely monitored for any signs of clinical worsening, suicidality, or unusual changes in behavior, especially during the initial 1 to 2 months of therapy or during dosage adjustments.
Patients' families or caregivers should be informed to watch for these signs and report them to the healthcare provider promptly.
Amoxapine is not FDA approved for use in pediatric patients, and a medication guide regarding antidepressant use should be dispensed with each prescription.

Anticholinergic effects

Amoxapine may lead to anticholinergic effects such as constipation, dry mouth (xerostomia), blurred vision, and urinary retention.
It's important to use caution when prescribing it to patients with conditions like decreased gastrointestinal motility, paralytic ileus, urinary retention, benign prostatic hyperplasia (BPH), dry mouth, or visual impairments.
Compared to other antidepressants, amoxapine tends to have a higher degree of anticholinergic blockade, which means these side effects may be more pronounced.

CNS depression:

Amoxapine can induce CNS depression, potentially impairing both physical and mental abilities.
Patients should be warned about engaging in activities requiring mental alertness, such as operating machinery or driving.
Compared to other antidepressants, the level of sedation associated with amoxapine is moderate.

Extrapyramidal symptoms:

Amoxapine may lead to extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia, although the risk of these reactions is low.
However, the risk of dystonia (and possibly other EPS) may increase with higher doses, use of conventional antipsychotics, male gender, and younger age.
Tardive dyskinesia, which can be potentially irreversible, is often associated with the total cumulative dose and duration of therapy, with an increased risk in elderly patients, particularly elderly women.
Antipsychotics may also mask signs and symptoms of tardive dyskinesia.
It's essential to discontinue therapy if signs or symptoms of tardive dyskinesia appear in any patient.

Fractures

Antidepressant treatment has been linked to bone fractures.
If a patient undergoing antidepressant therapy experiences unexplained bone pain, point tenderness, swelling, or bruising, it's crucial to consider the possibility of a fragility fracture.
This awareness can aid in prompt diagnosis and appropriate management.

Neuroleptic malignant syndrome (NMS):

Amoxapine use may be associated with neuroleptic malignant syndrome (NMS), a serious condition characterized by mental status changes, fever, muscle rigidity, and/or autonomic instability.

Ocular effects

Amoxapine may cause mild pupillary dilation, which in some individuals can trigger an episode of narrow-angle glaucoma.
Patients should be evaluated for risk factors of narrow-angle glaucoma, especially if they haven't undergone iridectomy.
This proactive approach can help prevent potential complications related to ocular effects.

Orthostatic hypotension

Amoxapine may induce orthostatic hypotension, with a risk level considered moderate compared to other antidepressants.
Caution should be exercised when prescribing it to patients at risk of this effect or those who may not tolerate transient hypotensive episodes.
This includes individuals with conditions such as cerebrovascular disease, cardiovascular disease, hypovolemia, or those taking medications that can predispose to hypotension or bradycardia.

Cardiovascular disease

Amoxapine should be used cautiously in patients with a history of cardiovascular disease, including previous myocardial infarction (MI), stroke, tachycardia, or conduction abnormalities.
The risk of conduction abnormalities associated with amoxapine is considered moderate compared to other antidepressants, according to the American Psychiatric Association (APA) guidelines from 2010.

Diabetes:

Amoxapine should be used cautiously in patients with diabetes mellitus, as it may affect glucose regulation.
This caution is in line with the guidelines provided by the American Psychiatric Association (APA) in 2010.
Regular monitoring of blood glucose levels is advisable for patients with diabetes who are taking amoxapine.

Hepatic impairment

Amoxapine should be used cautiously in patients with hepatic impairment.
Individuals with liver problems may metabolize the drug differently, potentially affecting its efficacy and safety.
Close monitoring and possible dose adjustments may be necessary in such patients.

Hypomania and mania:

Amoxapine may trigger a shift to mania or hypomania in individuals with bipolar disorder.
It's recommended to avoid using it as monotherapy in patients with bipolar disorder.
When treating patients with depressive symptoms, particularly those at risk for bipolar disorder, thorough screening is essential, including assessing family history of suicide, bipolar disorder, and depression.
Additionally, it's important to note that amoxapine is not FDA approved for the treatment of bipolar depression.

Renal impairment

Amoxapine should be used with caution in patients with renal impairment.
Individuals with compromised kidney function may experience altered metabolism and excretion of the drug, potentially leading to increased drug levels and a higher risk of adverse effects.
Close monitoring and possible dose adjustments may be necessary in patients with renal impairment.

Seizure disorder:

Amoxapine should be used cautiously in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications that may lower the seizure threshold.
It's important to consider the individual's seizure risk factors and weigh the potential benefits against the risks before prescribing amoxapine in such cases.
Close monitoring and appropriate precautions are advisable to minimize the risk of seizures.

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

Risk Factor C (Monitor therapy).
Acetylcholinesterase inhibitors	Anticholinergic Agents may have a decreased therapeutic effect. Anticholinergic Agents can decrease the therapeutic effects of Acetylcholinesterase inhibitors.
Ajmaline	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Alcohol (Ethyl)	CNS Depressants can increase the CNS depressant effects of Alcohol (Ethyl).
Alizapride	CNS Depressants may increase the CNS depressant effects.
Alpha1-Agonists	Tricyclic Antidepressants could decrease the therapeutic effects of Alpha1Agonists. Tricyclic Antidepressants could decrease the vasopressor effects of Alpha1Agonists. Tricyclic Antidepressants could enhance Alpha1-Agonists' therapeutic effects. Tricyclic Antidepressants could enhance Alpha1-Agonists' vasopressor effects.
Alpha2-Agonists (Ophthalmic).	Tricyclic Antidepressants could decrease the therapeutic effects of Alpha2-Agonists.
Altretamine	May increase the orthostatic hypotensive effects of Tricyclic Antidepressants.
Amantadine	Anticholinergic Agents may have an enhanced anticholinergic effect.
Amezinium	Might increase the toxic/adverse effects of Tricyclic Antidepressants.
Amifampridine	Agents with Seizure Threshold Lower Potential can enhance the neuroexcitatory or seizure-potentiating effects of Amifampridine.
Amphetamines	Tricyclic Antidepressants can enhance Amphetamines' stimulatory effects. Tricyclic Antidepressants can also increase the cardiovascular effects of Amphetamines.
Anticholinergic Agents	Other Anticholinergic Agents may have an adverse/toxic effect.
Antiemetics (5HT3 Antagonists)	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Antipsychotic Agents	Antipsychotic Agents may have a greater adverse/toxic effect if they are regulated with serotonin modulators. Serotonin modulators can increase dopamine blockade and, therefore, may increase the risk of developing the neuroleptic malignant syndrome. Serotonin modulators may have a serotonergic effect that is enhanced by antipsychotic agents. This could lead to serotonin syndrome.
Beta2-Agonists	Tricyclic Antidepressants can increase the toxic/adverse effect of Beta2Agonists.
Botulinum Toxin-Containing Products	Anticholinergic Agents may have an enhanced anticholinergic effect.
Brexanolone	CNS Depressants can increase the CNS depressant effects of Brexanolone.
Brimonidine (Topical)	CNS Depressants may increase the CNS depressant effects.
Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Cannabis	CNS Depressants may increase the CNS depressant effects.
CarBAMazepine	Might decrease serum Tricyclic Antidepressants.
Chloral Betaine	Anticholinergic Agents may have an adverse/toxic effect.
Chlorphenesin Carbamate	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Cimetidine	May reduce the metabolism of Tricyclic Antidepressants.
CloBAZam	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
CNS Depressants	Can increase the toxic/adverse effects of CNS Depressants.
Cobicistat	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Moderate CYP2D6 inhibitors	Might decrease the metabolism of CYP2D6 substrates (High Risk with Inhibitors).
Darunavir	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Desmopressin	Tricyclic Antidepressants can increase the toxic/adverse effects of Desmopressin.
Dexmethylphenidate	Might increase the toxic/adverse effects of Tricyclic Antidepressants. The serum concentrations of Tricyclic Antidepressants may be increased by Dexmethylphenidate.
Dimethindene (Topical).	CNS Depressants may increase the CNS depressant effects.
Doxylamine	CNS Depressants may have a greater depressant effect on the brain. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	CNS Depressants may increase the CNS depressant effects.
DULoxetine	This may increase the serotonergic effects of Tricyclic Antidepressants. This could lead to serotonin syndrome. DULoxetine could decrease the metabolism of Tricyclic Antidepressants.
Esketamine	CNS Depressants may increase the CNS depressant effects.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents can reduce the therapeutic effects of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic agents may increase the toxic/adverse effects of Glucagon. Particularly, there may be an increase in the likelihood of gastrointestinal adverse reactions.
Guanethidine	Tricyclic Antidepressants can reduce the therapeutic effects of Guanethidine.
HydrOXYzine	CNS Depressants may increase the CNS depressant effects.
Imatinib	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Ioflupane I 123	Amoxapine can decrease the diagnostic effectiveness of Ioflupane I123.
Itopride	Itopride's therapeutic effects may be diminished by anticholinergic agents.
Kava Kava	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Lumefantrine	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Magnesium Sulfate	CNS Depressants may increase the CNS depressant effects.
Metaxalone	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Methylphenidate	May increase the toxic/adverse effects of Tricyclic Antidepressants. The serum concentrations of Tricyclic Antidepressants may be increased by Methylphenidate.
Methylphenidate	Can increase the toxic/adverse effects of Serotonin-Modulators. In particular, there may be an increase in the risk of serotonin syndrome and serotonin toxicities.
MetyroSINE	MetyroSINE may have a sedative effect that can be enhanced by CNS depressants.
MetyroSINE	Might increase the toxic/adverse effects of Tricyclic Antidepressants.
Mianserin	Anticholinergic Agents may have an enhanced anticholinergic effect.
Minocycline	CNS Depressants may increase the CNS depressant effects.
Mirabegron	Anticholinergic agents may increase the toxic/adverse effects of Mirabegron.
Mirtazapine	CNS Depressants can increase the CNS depressant effects of Mirtazapine.
Nabilone	CNS Depressants may increase the CNS depressant effects.
Nicorandil	Tricyclic Antidepressants can increase the hypotensive effects of Nicorandil.
Nitroglycerin	The absorption of Nitroglycerin may be decreased by anticholinergic agents. Anticholinergic Agents may reduce the dissolution of sublingual nitroglycerin tablet, which could impair or slow down nitroglycerin absorption.
Panobinostat	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Peginterferon Alfa-2b	High risk with inhibitors. May lower the serum concentration of CYP2D6 substrates. Peginterferon Alf-2b could increase serum concentrations of CYP2D6 Substrates.
Perhexiline	Perhexiline may be increased by CYP2D6 Substrates. Perhexiline can increase serum concentrations of CYP2D6 substrates (High Risk with Inhibitors).
Piribedil	CNS Depressants could increase the CNS depressant effects of Piribedil.
Pitolisant	Tricyclic Antidepressants can reduce the therapeutic effects of Pitolisant.
Pramipexole	Pramipexole may have a greater sedative effect if it is combined with CNS depressants.
Protease inhibitors	May increase serum Tricyclic Antidepressants.
QuiNINE	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Ramosetron	Ramosetron's constipating effects may be enhanced by anticholinergic agents.
ROPINIRole	CNS Depressants can increase the sedative effects of ROPINIRole.
Rotigotine	CNS Depressants can increase the sedative effects of Rotigotine.
Rufinamide	CNS Depressants may have an adverse/toxic effect that can be exacerbated by this. Particularly, dizziness and sleepiness may be increased.
Selective Serotonin Reuptake inhibitors	CNS Depressants can increase the toxic/adverse effects of Selective Serotonin Reuptake Inhibitors. Particularly, psychomotor impairment could be increased.
Serotonin Modulators	This may increase the toxic/adverse effects of other Serotonin Activators. Serotonin syndrome can develop. Exceptions: Nicergoline; Tedizolid.
Sodium Phosphates	Tricyclic Antidepressants can increase the toxic/adverse effects of Sodium Phosphates. Patients with severe sodium phosphate-induced fluid/electrolyte abnormalities may have a higher risk of losing consciousness and having seizure.
Sulfonylureas	Cyclic Antidepressants can increase the hypoglycemic effects of Sulfonylureas.
Tedizolid	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Tetrahydrocannabinol	CNS Depressants may increase the CNS depressant effects.
Tetrahydrocannabinol, and Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Thiazide and Thiazide -Like Diuretics	Anticholinergic Agents can increase serum Thiazide or Thiazide-Like Diuretics.
Thyroid Products	May increase the arrhythmogenic effects of Tricyclic Antidepressants. Thyroid Products can increase the stimulatory effects of Tricyclic Antidepressants.
Topiramate	Topiramate's toxic/adverse effects may be exacerbated by anticholinergic agents.
Trimeprazine	CNS Depressants may increase the CNS depressant effects.
Valproate Products	May increase serum Tricyclic Antidepressants.
Vitamin K antagonists (eg warfarin)	Tricyclic Antidepressants can increase the anticoagulant effects of Vitamin K Antagonists.
Yohimbine	Tricyclic Antidepressants can increase Yohimbine's serum concentration.
Risk Factor D (Consider therapy modifications)
Abiraterone Acetate	High risk of Inhibitors causing an increase in serum concentrations of CYP2D6 substrates. When possible, avoid concurrent use of abiraterone and CYP2D6 Substrates with a narrow therapeutic index. If concurrent use cannot be avoided, closely monitor patients for signs/symptoms and treatment.
Direct-Acting Alpha-/Beta Agonists	Tricyclic Antidepressants can increase the vasopressor effects of Alpha/Beta-Agonists (Direct Acting). Patients on tricyclic antidepressants should avoid direct-acting alpha/beta-agonists. Monitor for increased pressure effects when combined and reduce the initial doses of alpha/beta-agonists.
Alpha2-Agonists	Tricyclic Antidepressants can reduce the antihypertensive effects of Alpha2Agonists. Management: Avoid this combination. Monitor for decreased alpha2-agonist effects if the combination is used. If you are discontinuing the use of an alpha2-agonist for a patient who is on a TCA, be careful. Lofexidine, Brimonidine (Ophthalmic), and Apraclonidine are exceptions.
Asunaprevir	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Barbiturates	May increase the metabolism of Tricyclic Antidepressants.
Blonanserin	CNS Depressants can increase the CNS depressant effects of Blonanserin.
Buprenorphine	CNS Depressants can increase the CNS depressant effects of buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Buprenorphine patches (Butrans) should be initiated at 5 mg/hr for adults when taken with other CNS depression drugs.
Chlormethiazole	CNS Depressants may increase the CNS depressant effects. Monitoring: Look out for signs of CNS depression. If a combination of chlormethiazole and other drugs is required, a reduced dose should be used.
Cinacalcet	It may increase serum levels of Tricyclic Antidepressants. Management: Look for alternatives whenever possible. These combinations should be monitored closely to ensure that there are no increased effects/toxicity or elevated serum levels (if testing is possible) of the tricyclic antidepressant.
Citalopram	Tricyclic Antidepressants can increase the toxic/adverse effects of Citalopram. Tricyclic Antidepressants can increase Citalopram's serum concentration. Citalopram could increase serum levels of Tricyclic Depressants. Management: If possible, consider alternatives to this combination. When citalopram is used with a TCA, monitor for any adverse effects such as serotonin syndrome or QT-interval prolongation.
Strong CYP2D6 inhibitors	Might decrease the metabolism of CYP2D6 substrates (High Risk with Inhibitors).
Dacomitinib	High risk of Inhibitors causing an increase in serum concentrations of CYP2D6 substrates. Management: Do not use dacomitinib concurrently with CYP2D6 Substrates that have a narrow therapeutic Index.
Droperidol	CNS Depressants may increase the CNS depressant effects. Management: Droperidol and other CNS agents, such as opioids, may be reduced or used in combination with droperidol. Separate drug interaction monographs provide more detail on exceptions to this monograph.
Escitalopram	Tricyclic Antidepressants can increase the toxic/adverse effects of Escitalopram. The serum concentrations of Tricyclic Antidepressants may be increased by Escitalopram. Management: If possible, consider alternatives to this combination. When a TCA is used with escitalopram, monitor for any adverse effects such as serotonin syndrome or QT-interval prolongation.
Flunitrazepam	CNS Depressants can increase the CNS depressant effects of Flunitrazepam.
FLUoxetine	Might increase the toxic/adverse effects of Tricyclic Antidepressants. FLUoxetine can increase serum levels of Tricyclic Antidepressants. Management: If possible, consider alternatives to this combination. When fluoxetine is used with a TCA, monitor for any adverse effects such as serotonin syndrome or QT-interval prolongation.
FluvoxaMINE	Could increase the toxic/adverse effects of Tricyclic Antidepressants. FluvoxaMINE could increase serum levels of Tricyclic Antidepressants. Management: If possible, consider alternatives to this combination. When a TCA is used with fluvoxamine, monitor for any adverse effects such as serotonin syndrome or QT-interval prolongation.
HYDROcodone	CNS Depressants can increase the CNS depressant effects of HYDROcodone. When possible, avoid concomitant use with hydrocodone, benzodiazepines, or other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Iohexol	Agents with Seizure Threshold Lowering Potential can increase the toxic/adverse effects of Iohexol. The risk of seizures could be elevated. Management: Stop using agents that lower the seizure threshold 48 hrs before you start intrathecal iohexol. To resume these agents, wait at least 24 hours following the procedure. Consider using prophylactic anticonvulsants in non-elective procedures.
Iomeprol	Agents with Seizure Threshold Lowering Potential can increase the toxic/adverse effects of Iomeprol. The risk of seizures could be elevated. Management: Stop using agents that lower the seizure threshold 48 hrs before you start intrathecal iomeprol. To resume these agents, wait at least 24 hours following the procedure. Consider using prophylactic anticonvulsants in non-elective procedures.
Iopamidol	Agents with Seizure Threshold Lowering Potential can increase the toxic/adverse effects of Iopamidol. The risk of seizures could be elevated. Management: Stop using agents that lower the seizure threshold 48 hrs before you start intrathecal iopamidol. To resume these agents, wait at least 24 hours following the procedure. Consider using prophylactic anticonvulsants in non-elective procedures.
Linezolid	This may increase the serotonergic effects of Tricyclic Antidepressants. This could lead to serotonin syndrome. Management: If possible, consider other combinations. Linezolid should be initiated only if it is clinically approved.
Linezolid	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome. Management: Serotonin syndrome/serotonin toxaemia can occur if serotonin modulators are stopped 2 weeks before linezolid is administered. Stop using serotonin moderators immediately if you need to initiate linezolid immediately.
Lithium	May increase the neurotoxic effects of tricyclic antidepressants. You should exercise caution when using this combination. If combined treatment is clinically recommended, be sure to monitor for signs of serotonin toxicities/serotonin syndrome.
Lofexidine	Tricyclic Antidepressants can reduce the therapeutic effects of Lofexidine. This combination should be avoided. Monitor for any decreased alpha2-agonist effects if the combination is used. If you are discontinuing the use of an alpha2-agonist for a patient who is receiving a TCA, be careful.
Methotrimeprazine	Methotrimeprazine may have a higher CNS depressant activity than CNS Depressants. Methotrimeprazine can increase the CNS depressant effects of CNS Depressants. Management: Lower the adult dose of CNS Depressants by 50% and start concomitant methotrimeprazine treatment. After the clinically proven efficacy of methotrimeprazine, further CNS depressant dosage adjustments should only be made.
Metoclopramide	This may increase the toxic/adverse effects of Tricyclic Antidepressants. Management: If possible, seek alternatives to this combination. Patients receiving metoclopramide and tricyclic antidepressants should be monitored for extrapyramidal symptoms, neuroleptic malignant Syndrome, or serotonin syndrome.
Opioid Agonists	CNS Depressants can increase the CNS depressant effects of Opioid Aggonists. Management: When possible, avoid concomitant use of opioid agonists and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
OxyCODONE	CNS Depressants can increase OxyCODONE's CNS depressant effects. When possible, avoid the simultaneous use of oxycodone and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
PARoxetine	Could increase the toxic/adverse effects of Tricyclic Antidepressants. PARoxetine can increase serum levels of TricyclicAntidepressants. Management: If possible, consider alternatives to this combination. When a TCA is used with paroxetine, monitor for any adverse effects such as serotonin syndrome or QT-interval prolongation.
Perampanel	CNS Depressants may have a greater CNS depressant effect. Perampanel and any other CNS depressant drug should be used in combination. Patients who take perampanel together with any other drug should not engage in complex or high-risk activities until they have had experience with the combination.
Pramlintide	Anticholinergic Agents may have an enhanced anticholinergic effect. These effects are only for the GI tract.
QuiNIDine	Tricyclic Antidepressants could increase the QTc-prolonging effects of QuiNIDine. QuiNIDine could increase serum levels of Tricyclic Antidepressants. Management: The drug interactions monographs for drugs listed as an exception to this monograph will discuss the management of these drugs in greater detail.
Secretin	Secretin's therapeutic effects may be diminished by anticholinergic agents. Concomitant use: Secretin and anticholinergic agents should be avoided. Stop using anticholinergic drugs for at least five half-lives before administering secretin.
Sertraline	Could increase the toxic/adverse effects of Tricyclic Antidepressants. Sertraline can increase serum levels of Tricyclic Antidepressants. Management: If possible, consider alternatives to this combination. When sertraline is used with a tricyclic antidepressant (TCA), monitor for adverse effects, including serotonin syndrome or QT-interval prolongation.
Sodium Oxybate	CNS Depressants may have a greater depressant effect if taken in combination. Management: Look for alternatives to the combination use. If you must combine use, reduce the dose of any one or more drugs. It is not recommended to combine sodium oxybate and alcohol, or any sedative-hypnotics.
St John's Wort	May increase the metabolism of tricyclic antidepressants. The possibility of serotonin syndrome could theoretically increase.
Suvorexant	CNS Depressants can increase the CNS depressant effects of Suvorexant. Management: Suvorexant or any other CNS depression can be reduced in doses. Suvorexant should not be taken with alcohol. It is also not recommended to take suvorexant along with any other drugs for insomnia.
Tapentadol	CNS Depressants may increase the CNS depressant effects. Tapentadol, benzodiazepines and other CNS depressants should be avoided when possible. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Zolpidem	CNS Depressants can increase the CNS depressant effects of Zolpidem. Management: For men who also take CNS depressants, reduce the adult Intermezzo brand sublingual Zolpidem dose to 1.75mg. For women, no dose adjustment is advised. Avoid using CNS depressants at night; do not use alcohol.
Risk Factor X (Avoid Combination)
Aclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Azelastine (Nasal)	CNS Depressants could increase the CNS depressant effects of Azelastine.
Bromopride	Might increase the toxic/adverse effects of Tricyclic Antidepressants.
Bromperidol	CNS Depressants may increase the CNS depressant effects.
Cimetropium	Cimetropium may have an anticholinergic effect that can be enhanced by the use of anticholinergic agents.
Dapoxetine	Can increase the toxic/adverse effects of Serotonin Activators.
Dronedarone	Tricyclic Antidepressants can increase Dronedarone's arrhythmogenic effects. Management: The drug interactions monographs for drugs listed as an exception to this monograph provide more information.
Eluxadoline	Eluxadoline may cause constipation by using anticholinergic agents.
Glycopyrrolate (Oral Inhalation)	Anticholinergic agents may increase the anticholinergic effects of Glycopyrrolate (Oral inhalation).
Glycopyrronium (Topical)	Anticholinergic Agents may have an enhanced anticholinergic effect.
Iobenguane Radiopharmaceutical Products	Tricyclic Antidepressants can decrease the therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Stop using any drug that could inhibit or interfere with catecholamine transport and uptake for at most 5 biological half-lives prior to iobenguane Administration. These drugs should not be administered until 7 days following each iobenguane dosage.
Oral Inhalation with Ipratropium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Levosulpiride	Anticholinergic Agents can reduce the therapeutic effects of Levosulpiride.
Methylene Blue	Tricyclic Antidepressants could increase the serotonergic effects of Methylene Blue. This could lead to serotonin syndrome.
Methylene Blue	This may increase the serotonergic effects of Serotonin Activators. This could lead to serotonin syndrome.
Monoamine Oxidase Inhibitors	This may increase the serotonergic effects of Tricyclic Antidepressants. This could lead to serotonin syndrome. Although methylene blue is expected to interact with linezolid via this mechanism, management guidelines differ from those for other monoamine-oxidase inhibitors. For more information, refer to monographs pertaining to these agents. Exceptions: Linezolid; Methylene Blue; Tedizolid.
Orphenadrine	Orphenadrine may be more effective against CNS depression than other drugs.
Oxatomide	Anticholinergic Agents may have an enhanced anticholinergic effect.
Oxomemazine	CNS Depressants may increase the CNS depressant effects.
Paraldehyde	Paraldehyde may be enhanced by CNS depressants.
Potassium Chloride	Potassium Chloride may have an ulcerogenic effect that can be exacerbated by anticholinergic agents. Treatment: Patients taking drugs that have significant anticholinergic effects should not consume any oral dosage form of potassium chloride.
Potassium Citrate	Potassium Citrate may be more ulcerogenic if it is given to anticholinergic agents.
Revefenacin	Revefenacin may be enhanced by anticholinergic agents.
Thalidomide	CNS Depressants can increase Thalidomide's CNS depressant effects.
Tiotropium	Anticholinergic agents may increase the anticholinergic effects of Tiotropium.
Umeclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.

Monitoring Parameters:

Monitoring Considerations for Patients Taking Amoxapine

ECG (Electrocardiogram):
- For patients at increased risk of QT-prolonging effects due to certain conditions.
Serum Sodium:
- Monitor as clinically indicated, especially in at-risk populations.
Heart Rate and Blood Pressure:
- Regular monitoring of heart rate and blood pressure is important.
Blood Glucose:
- Check blood glucose levels periodically, particularly in patients with diabetes.
Weight and BMI (Body Mass Index):
- Monitor weight and BMI changes over time.
Mental Status:
- Assess mental status regularly for any changes.
Suicidal Ideation:
- Especially important to monitor at the beginning of therapy or when doses are adjusted.
Anxiety:
- Keep an eye on anxiety levels and report any significant changes.
Abnormal Involuntary Movements or Parkinsonian Signs:
- Watch for any signs of abnormal movements or Parkinsonian symptoms.
Tardive Dyskinesia:
- Be vigilant for any signs of tardive dyskinesia and address promptly.
Changes in Menstruation or Libido:
- Monitor for changes in menstrual patterns or libido.
Galactorrhea:
- Watch for the development of galactorrhea, especially in women.
Erectile or Ejaculatory Dysfunction:
- Keep an eye out for any issues related to erectile or ejaculatory function.

Regular monitoring of these parameters can help ensure the safe and effective use of amoxapine in patients.

How to Administer Amoxapine?

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

Mechanism of action of Amoxapine:

Amoxapine works by reducing the reuptake of serotonin and norepinephrine, two neurotransmitters involved in mood regulation.
Its metabolite, 7-OH-amoxapine, exhibits significant activity in blocking dopamine receptors, similar to antipsychotic medications.
This dual mechanism of action contributes to its antidepressant effects and may also influence its efficacy in certain psychiatric conditions.

Onset of Antidepressant Effect:

Typically occurs after 1 to 2 weeks of treatment, but may take 4 to 6 weeks for full efficacy.

Absorption:

Rapid and well absorbed by the body.

Distribution:

Volume of distribution (V): 0.9 to 1.2 L/kg.

Protein Binding:

Approximately 90% of the drug is bound to proteins in the bloodstream.

Metabolism:

Extensively metabolized in the liver.
Hepatic hydroxylation produces two active metabolites: 7 hydroxyamoxapine (7-OH-amoxapine) and 8-hydroxyamoxapine (8-OH-amoxapine).
Metabolites undergo conjugation to form glucuronides.

Half-Life Elimination: