Side Effects of amoxapine: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Findings

Amoxapine, an antidepressant, has been linked to several adverse effects, including cardiac arrhythmias, sudden death, and neuroleptic-like side effects. 7 The drug's mechanism of action involves inhibition of the hERG potassium channel, leading to prolonged repolarization and potentially apoptosis. 7 Additionally, amoxapine has been observed to disrupt hERG protein trafficking, further contributing to cardiac issues. 7 22 While primarily known for its antidepressant properties, amoxapine also exhibits antipsychotic effects, potentially leading to neuroleptic-like side effects in certain individuals. 11 4

Research using zebrafish larvae revealed that amoxapine can affect locomotor activity, with some individuals exhibiting increased activity during the light cycle. 5 However, the exact mechanism responsible for this biphasic response remains unclear and necessitates further investigation. 5 Amoxapine's ability to block GABAA receptors, potentially contributing to convulsant side effects, has also been reported. 20

Reasons for Side Effects

Amoxapine's side effects are primarily attributed to its pharmacological actions. The drug's ability to inhibit the hERG potassium channel in the heart, disrupt hERG protein trafficking, and block GABAA receptors contribute to the observed cardiac and neurologic adverse effects. 7 20 The drug's affinity for dopamine and serotonin receptors may also play a role in its antipsychotic effects and potential for neuroleptic-like side effects. 11 4

General Side Effects

Cardiac

Amoxapine can cause QT prolongation, a condition that increases the risk of cardiac arrhythmias and sudden death. 7 It can also lead to acute heart failure. 7

Neurologic

Amoxapine can induce neuroleptic-like side effects, including extrapyramidal symptoms (EPS), and may even lead to neuroleptic malignant syndrome. 4 18 The drug's blockade of GABAA receptors can potentially result in seizures, particularly in cases of overdose. 20

Other

Amoxapine can cause gastrointestinal side effects such as nausea, vomiting, and constipation. 22 It can also lead to drowsiness, dizziness, and a decrease in concentration. 22

Side Effect Management

Cardiac

Regular monitoring of heart health is crucial while taking amoxapine. 7 If any symptoms of cardiac arrhythmias or sudden death occur, immediate medical attention is necessary. 7

Neurologic

Consult a doctor if neuroleptic-like side effects arise. 4 18 Adjusting the dosage or switching medications may be required. 4 18

Other

Limit alcohol consumption while taking amoxapine. 22 Avoid driving or operating machinery. 22

Comparison Between Studies

Commonalities

The studies consistently show that amoxapine can cause cardiac and neurologic side effects. 7 22 4 18 It is also evident that the drug can interact with other medications. 22

Differences

The incidence and severity of side effects can vary depending on the study. 7 22 4 18 The types of depression for which amoxapine is effective may also differ across studies. 7 22 4 18

Real-life Application Note

It is essential to consult a doctor before taking amoxapine, especially considering its potential for cardiac and neurologic side effects. 7 22 4 18 Moreover, always inform your doctor about any other medications you are taking to avoid potential drug interactions. 22 Due to amoxapine's effects on the heart and nervous system, refrain from driving or operating machinery until you understand how it affects you. 22

Limitations of Current Research

Research on the side effects of amoxapine is still limited. 7 22 4 18 Specifically, long-term side effects remain poorly understood. 7 22 4 18 More research is needed to address these gaps in knowledge.

Future Research Directions

Further research on the long-term side effects of amoxapine is crucial. 7 22 4 18 Additional research is needed to investigate the specific types of depression for which amoxapine is most effective, the relationship between dosage and side effects, and the interactions with other medications. 7 22 4 18

Conclusion

Amoxapine is an antidepressant medication with potential benefits, but it also carries risks of cardiac and neurologic side effects. 7 22 4 18 Open and honest communication with your doctor is vital before starting treatment with amoxapine, ensuring a thorough understanding of its potential benefits and risks. 7 22 4 18 If you experience any side effects, seek medical attention promptly. 7 22 4 18

Literature analysis of 22 papers
Positive Content
13
Neutral Content
1
Negative Content
8
Article Type
4
1
0
6
22
1.

Tolerability of long-term treatment with lercanidipine versus amlodipine and lacidipine in elderly hypertensives.

Author: LeonettiGastone, MagnaniBruno, PessinaAchille Cesare, RappelliAlessandro, TrimarcoBruno, ZanchettiAlberto,

Hypertension control
Side effects

This trial compared the tolerability of lercanidipine, a calcium antagonist, to two other calcium antagonists (amlodipine and lacidipine) in elderly hypertensive patients. The study aimed to evaluate the side effects associated with these antihypertensive drugs.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Peripheral edema and headache associated with amlodipine treatment: a meta-analysis of randomized, placebo-controlled trials.

Author: VukadinovićDavor, ScholzSean S, MesserliFranz H, WeberMichael A, WilliamsBryan, BöhmMichael, MahfoudFelix

CAD treatment
Hypertension treatment
Headache
Peripheral edema

Amlodipine treatment was associated with a three-fold higher risk of peripheral edema compared to placebo.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

4.

Amoxapine and neuroleptic side effects: a case report.

Author: SunderlandT, OrsulakP J, CohenB M

Increased prolactin levels
Neuroleptic side effects

A depressed patient taking amoxapine alone developed neuroleptic-like side effects, despite therapeutic amoxapine levels. This was associated with an elevated prolactin level and significant neuroleptic activity.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish.

Author: SuryantoMichael Edbert, AudiraGilbert, UapipatanakulBoontida, HussainAkhlaq, SaputraFerry, SiregarPetrus, ChenKelvin H-C, HsiaoChung-Der

Sedative effects

This study assessed the potential adverse effects of 18 antidepressants on zebrafish larval locomotor activity performance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies.

Author: MikaJoanna, ZychowskaMagdalena, MakuchWioletta, RojewskaEwelina, PrzewlockaBarbara

Antidepressant efficacy
Chronic pain treatment
Antidepressant side effects

Tricyclic antidepressants (TCAs) are often used to treat chronic pain, but they can have significant side effects. This review examines the evidence for the efficacy and safety of various antidepressants, including TCAs, tetracyclic antidepressants (TeCAs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and atypical antidepressants, for the treatment of neuropathic pain.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Multiple mechanisms of hERG liability: K+ current inhibition, disruption of protein trafficking, and apoptosis induced by amoxapine.

Author: ObersSabrina, StaudacherIngo, FickerEckhard, DennisAdrienne, KoschnyRonald, ErdalHande, BloehsRamona, KisselbachJana, KarleChristoph A, SchweizerPatrick A, KatusHugo A, ThomasDierk

Heart failure
QT prolongation
Sudden death

Amoxapine, an antidepressant, can cause QT prolongation, heart failure, and death. This study found that amoxapine blocks hERG potassium channels, which are involved in heart rhythm regulation, and also disrupts hERG protein trafficking and induces apoptosis. These findings suggest multiple mechanisms by which amoxapine can harm the heart.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Amoxapine as an antipsychotic: comparative study versus haloperidol.

Author: ChaudhryImran B, HusainNusrat, KhanSalahuddin, BadshahSareer, DeakinBill, KapurShitij

Antipsychotic effect
Improved negative symptoms
Extrapyramidal side effects

Amoxapine, an antidepressant, showed similar antipsychotic effects as haloperidol in patients with schizophrenia. However, amoxapine did not demonstrate fewer extrapyramidal side effects than haloperidol.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Amoxapine as an atypical antipsychotic: a comparative study vs risperidone.

Author: ApiquianRogelio, FresanAna, UlloaRosa-Elena, de la Fuente-SandovalCamilo, Herrera-EstrellaMiguel, VazquezAlejandra, NicoliniHumberto, KapurShitij

Improved depressive symptoms
Improved negative symptoms
Improved positive symptoms
Less EPS
Less prolactin elevation
Low-cost alternative

Amoxapine and risperidone are both effective atypical antipsychotics for treating schizophrenia. Amoxapine is associated with less side effects, such as movement disorders and elevated prolactin levels, than risperidone. Amoxapine is an off-patent drug and may be a valuable, low-cost alternative for patients in low-income countries.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Challenges in the treatment of depression with psychotic features.

Author: RothschildAnthony J

Major depression with psychotic features

This study discusses the challenges of treating major depression with psychotic features (MDpsy), a disorder with high morbidity and mortality.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study.

Author: ApiquianRogelio, UlloaElena, FresanAna, LoyzagaCristina, NicoliniHumberto, KapurShitij

Antipsychotic effect
Side effects

Amoxapine, marketed as an antidepressant, shares similarities with atypical antipsychotics in terms of receptor occupancy and effects in pre-clinical models. This study investigated the antipsychotic and side effect profile of amoxapine in acutely psychotic patients with schizophrenia, suggesting that amoxapine might possess atypical antipsychotic effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Painful ejaculation and urinary hesitancy in association with antidepressant therapy: relief with tamsulosin.

Author: DemyttenaereKoen, HuygensRemko

Painful ejaculation

Tamsulosin has been shown to be effective in resolving painful ejaculation associated with reboxetine, a type of antidepressant.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Differential effects of the tricyclic antidepressant amoxapine on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters.

Author: NúñezE, López-CorcueraB, VázquezJ, GiménezC, AragónC

Improved glycine transporter pharmacology
Sedative and psychomotor side effects

Amoxapine, a tricyclic antidepressant, selectively inhibits the glycine transporter 2a (GLYT2a). This inhibition may contribute to the sedative and psychomotor side effects of amoxapine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Is amoxapine an atypical antipsychotic? Positron-emission tomography investigation of its dopamine2 and serotonin2 occupancy.

Author: KapurS, ChoR, JonesC, McKayG, ZipurskyR B

Extrapyramidal side effects

Atypical antipsychotics are commonly used to treat various mental health conditions. Amoxapine, an atypical antipsychotic, showed a high serotonin (5-HT)2 occupancy, greater 5-HT2 than dopamine (D)2 occupancy, and a higher incidence of extrapyramidal side effects when its D2 occupancy exceeded 80%.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Amoxapine versus amitriptyline for continuation therapy of depression.

Author: MasonB J, KocsisJ H, FrancesA J, MannJ J

Effective continuation therapy
Relapse
Side effects

Amoxapine, a relatively new antidepressant, was not found to offer any clear advantage over amitriptyline for continuation therapy in patients with major depressive disorder. In a double-blind controlled comparison study of 92 patients, amitriptyline was more effective in inducing full recovery, while amoxapine had a trend for higher relapse rates.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression.

Author: AntonR F, BurchE A

Reduced extrapyramidal side effects

Amoxapine and a combination of amitriptyline plus perphenazine were both effective in treating major depression with psychotic features. However, amoxapine was associated with significantly fewer extrapyramidal side effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Antidepressants, metabolites, and apparent drug resistance.

Author: PotterW Z, ManjiH K

Antidepressant effect
Drug resistance
Metabolic issues
Side effects

Antidepressant metabolites can have different properties than the parent drug, leading to drug resistance or intolerance. This article explores the pharmacodynamic consequences of metabolism and highlights the potential role of active metabolites in drug response.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

Amoxapine-induced neuroleptic malignant syndrome.

Author: MadakasiraS

Neuroleptic malignant syndrome

Amoxapine, an antidepressant, caused neuroleptic malignant syndrome in a patient, which resolved after the drug was discontinued. Older patients may be at higher risk for this adverse effect.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

19.

Treatment of affective illness in the elderly with drugs and electroconvulsive therapy.

Author: JenikeM A

Affective illness treatment
Post-stroke depression treatment
Anticholinergic effects
Lithium toxicity
Orthostatic hypotension
Tardive dyskinesia

Several medications and ECT are effective in treating affective illness in the elderly, with varying levels of effectiveness and side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

20.

Antidepressants and metabolites that block GABAA receptors coupled to 35S-t-butylbicyclophosphorothionate binding sites in rat brain.

Author: SquiresR F, SaederupE

Antidepressant action
Convulsions

Many clinically effective antidepressants were found to reverse the inhibitory action of GABA, suggesting that GABA antagonism may be involved in their antidepressant action and convulsant side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

21.

Adverse reactions to five new antidepressants.

Author: HayesP E, KristoffC A

Depression Treatment
Hemolytic Anemia
Hypersensitivity Reactions
Priapism
Seizures

Of the new antidepressants, only trazodone offers advantages over the tricyclic and tetracyclic agents in terms of side effects and toxicities.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

Antidepressant drug therapy in the elderly: enhancing safety and compliance.

Author: HalarisA

Enhanced compliance
Improved safety
Adverse reactions
Side effects

This review article focuses on the complex issues surrounding antidepressant drug usage in the elderly. It highlights the side effects and adverse reactions associated with tricyclic antidepressants and lithium, offering suggestions for improving safety and compliance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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