Back To Search Results

Amoxapine

Editor: Raman Marwaha Updated: 11/18/2023 10:41:12 AM

Indications

FDA-Approved Indications

Amoxapine is classified as a second-generation tricyclic dibenzoxazepine antidepressant approved by the U.S. Food and Drug Administration (FDA). This medication is typically used as a second- or third-line treatment option when selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) have failed to control depression. Thus, amoxapine is indicated for managing treatment-resistant depression when the first- and second-line medications have proven ineffective in alleviating symptoms. Amoxapine is indicated for use in cases of depression accompanied by other psychiatric issues such as anxiety, agitation, psychosis, neurosis, or recurrent depression.[1][2]

Off-Label Uses

Research conducted in mice has shown that amoxapine can reduce the production of amyloid-beta chains associated with Alzheimer disease by targeting the serotonin-6 (HTR-6, 5-HT-6) receptor.[3] Multiple studies have shown that amoxapine can reduce the incidence of diarrhea in patients undergoing chemotherapy, particularly when used in conjunction with irinotecan.[4][5] Furthermore, research has highlighted amoxapine's effectiveness in the management of neuropathic pain.[6]

Mechanism of Action

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Mechanism of Action

Amoxapine, a second-generation tricyclic dibenzoxazepine antidepressant, primarily functions by inhibiting the reuptake of norepinephrine in neuronal synapses. The drug exhibits minimal effect on the histamine H1 receptor and serotonin receptors, except for the serotonin-6 receptor (HTR-6, 5-HT-6).[7][8][9] Furthermore, amoxapine also acts as a dopamine (DA) receptor antagonist, specifically targeting D2 and D4 receptors.[10]

Pharmacokinetics

Absorption: Amoxapine is rapidly absorbed in the body after oral administration. The time to peak plasma concentration for amoxapine is approximately 90 minutes.

Distribution: Amoxapine exhibits a high plasma protein binding of approximately 90%.

Metabolism: Amoxapine undergoes hepatic metabolism primarily via the CYP2D6 enzyme, leading to the formation of 2 active metabolites—7-hydroxy-amoxapine and 8-hydroxy-amoxapine. These active metabolites have been shown to reduce the incidence of diarrhea in patients after administering irinotecan chemotherapy. Research findings demonstrated that these metabolites effectively reduced tumor growth in patients.[5][11]

Elimination: Research indicates that the active metabolite, 8-hydroxy-amoxapine, has a half-life of 30 hours, whereas the drug has a half-life of 8 hours. The primary route of drug elimination from the body is through urine, with a minor fraction excreted in the feces.[2]

Administration

Available Dosage Forms and Strengths

Amoxapine is available in oral tablet formulations, with strengths of 25 mg, 50 mg, 100 mg, and 150 mg doses.

Adult Dosage

Amoxapine is typically administered orally at a starting dose of 100 mg, with the option to increase the dosage up to a maximum of 300 mg. The normal therapeutic dose for depression is between 200 and 300 mg, usually taken orally at bedtime.[12][13][14] Amoxapine can be administered daily to patients either as a single dose or 2 equally divided doses.[15] However, due to the prolonged half-life of the active drug metabolites, a single daily dose of amoxapine is often preferred over divided doses for more effective treatment. Antidepressant benefits from amoxapine may become noticeable within just 7 days, and more than 80% of patients experience significant improvement within 2 weeks.[7] The maximum recommended dosage of amoxapine for outpatient settings is 400 mg daily, whereas, for hospitalized patients with no history of seizures, it is 600 mg daily.

Maintenance Dosage

The recommended maintenance dose for amoxapine is the minimum effective dose needed to maintain remission. If symptoms reappear, the dosage should be increased to the previous level until they are under control. Notably, it is recommended to take a single dose of ≤300 mg at bedtime for maintenance therapy.

Specific Patient Populations

Hepatic impairment: The product labeling does not specify dosage adjustments for hepatic impairment. However, it is advisable to exercise caution when administering amoxapine to these patients, considering its liver-dependent metabolism.[11]

Renal impairment: The product labeling does not contain specific guidance on dosage adjustments for renal impairment. Thus, it is crucial to exercise caution when prescribing amoxapine to patients with renal impairment, as its primary elimination route is through the kidneys.

Pregnancy considerations: Amoxapine was previously classified by the FDA as a pregnancy category C drug. Studies on animals revealed fetotoxic effects, including intrauterine death, decreased birth weight, and stillbirth, occurring at oral doses 3 to 10 times higher than the human dose. There is limited availability of well-controlled studies involving pregnant women. Consequently, amoxapine use during pregnancy should be approached cautiously. Decisions regarding medication use in pregnant women should be made judiciously, taking into account a careful assessment of the potential benefits and risks to the fetus.[16]

Breastfeeding considerations: Limited published data exist on amoxapine use during breastfeeding. Cases of galactorrhea have been observed in non-breastfeeding women using amoxapine. When nursing a newborn or preterm infant, it is advisable to explore alternative agents, such as sertraline, due to its more established safety profile in this context.[17]

Pediatric patients: Amoxapine lacks FDA approval for use in pediatric patients.

Older patients: Clinical studies of amoxapine in individuals 65 and older did not establish whether they exhibit different responses compared to younger subjects. As amoxapine is metabolized by the liver and excreted by the kidney, healthcare providers should exercise caution when prescribing the medication to older patients, considering potential hepatic and renal impairments. According to the American Geriatrics Society (AGS) Beers Criteria, amoxapine is noted for its potent anticholinergic properties. Therefore, its use should be considered only after a meticulous risk-benefit assessment.[18]

Adverse Effects

The common adverse effects of amoxapine therapy include, but are not limited to, insomnia, palpitations, tachycardia, hypotension, and constipation.[19][20][2] Furthermore, research has indicated that amoxapine may trigger hypomanic states in individuals with underlying bipolar disorder.[19] Amoxapine has been observed to induce noradrenaline-mediated contraction of the urethra in guinea pigs and rats in various laboratory studies, leading to elevated urethral resistance.[21][22] In addition, the drug has been associated with instances of painful ejaculations relieved by the administration of tamsulosin.[23] Notably, tricyclic antidepressants (TCAs), including amoxapine, are correlated with an increased risk of seizures, especially in older patients and those with epilepsy.[24][25] Therefore, it is recommended to use SSRIs or SNRIs in patients with a history of epilepsy and seizures.

Amoxapine's anticholinergic properties can result in adverse effects such as sedation, dry mouth, delirium, and drug-induced Parkinsonism, particularly among older patients.[26] In a few cases, amoxapine has been associated with QTc interval prolongation.[27] Notably, as amoxapine may lead to urinary retention, it is important to exercise caution when prescribing the drug for patients with bladder outlet obstruction.[28]

Drug-Drug Interactions

  • Amoxapine has the potential to enhance central nervous system depression caused by barbiturates and alcohol. Therefore, concurrent use of the drug with barbiturates and alcohol should be avoided.[29]
  • In a subset of the Caucasian population who are poor metabolizers with reduced CYP2D6 activity, TCAs, such as amoxapine, have increased plasma concentrations.
  • Dose reduction may be necessary when TCAs, such as amoxapine, are combined with CYP2D6-inhibiting drugs, including quinidine, cimetidine, phenothiazines, propafenone, and flecainide.[30]
  • All SSRIs exhibit varying degrees of CYP2D6 inhibition. Therefore, clinicians should exercise caution when combining TCAs with SSRIs or making transitions between these 2 classes of medications. In addition, when switching from fluoxetine to amoxapine, a substantial time interval is necessary due to the extended half-life of fluoxetine, which is at least 5 weeks. This precaution helps prevent potential interactions and ensures the safe use of medications.[31]

Contraindications

Amoxapine is contraindicated in patients with a known hypersensitivity to dibenzoxazepine compounds. The primary mechanism of action of amoxapine involves inhibiting the presynaptic reuptake of norepinephrine. Therefore, patients are advised against taking amoxapine concurrently with other antidepressants or medications, such as monoamine oxidase inhibitors (MAOIs), that produce similar effects. Patients should avoid taking the drug within a 14-day window of taking other antidepressants. This period allows the prior antidepressant to be eliminated from the system before initiating amoxapine or any other TCA. Furthermore, due to amoxapine's potential for QTc prolongation, it is not prescribed to patients with extended QTc intervals or those experiencing acute myocardial infarction, as it may worsen their symptoms.[27]

Box Warning

Amoxapine has an FDA black box warning for increased suicidality risk in individuals aged 24 and younger and aged 65 and older. Amoxapine is not recommended for the treatment of pediatric depression.[32]

Warnings and Precautions

Although amoxapine is effective for certain conditions, it demands vigilant consideration of particular concerns to mitigate potential risks and adhere to essential safety measures associated with its usage.

Extrapyramidal adverse effects: Amoxapine's ability to block dopamine receptors increases the risk of experiencing extrapyramidal adverse effects and tardive dyskinesia.

Angle-closure glaucoma: Amoxapine's potential for inducing pupillary dilation is a crucial concern, especially for patients with anatomically narrow angles, as it heightens the risk of angle-closure glaucoma.

Seizures: TCAs are also contraindicated in patients with a history of epilepsy or seizures. Instead, individuals who are at risk of seizures should consider taking SSRIs or SNRIs instead of amoxapine, as research indicates that amoxapine may slightly increase the risk of seizures.[25]

Hepatic impairment: As amoxapine is metabolized in the liver, it is imperative to exercise extreme caution when prescribing this medication to patients with hepatic impairment or active liver disease.[11]

Electroconvulsive therapy: The concurrent administration of amoxapine and electroshock therapy may heighten the associated risks of electroconvulsive therapy. 

Neuroleptic malignant syndrome (NMS): NMS can arise as a result of antipsychotic drugs, including amoxapine. Clinical manifestations of NMS encompass hyperpyrexia, muscle rigidity, altered mental status, and signs of autonomic instability, such as irregular pulse or labile blood pressure, diaphoresis, and cardiac dysrhythmias. The management of NMS entails the immediate discontinuation of causative medications, including amoxapine, along with vigilant medical supervision and the prompt implementation of supportive care measures.[33][34]

Bipolar disorder: The initial manifestation of bipolar disorder can often resemble a major depressive episode. However, a concern prevails that using antidepressant monotherapy, such as amoxapine, can trigger a manic episode in individuals with a predisposition to bipolar disorder. Therefore, it is essential to conduct a thorough assessment of the patient's personal and family history of bipolar disorder and suicide before initiating antidepressant treatment.[35][36]

Monitoring

Patients taking amoxapine should undergo regular monitoring for resolution or reduction of symptoms, withdrawal symptoms from abrupt discontinuation, changes in body weight and BMI, blood pressure and blood glucose levels, worsening of depression, the emergence of suicidal thoughts, or unusual behavior at the onset of therapy or during dose adjustments. Older individuals and those with preexisting cardiac disease or hyperthyroidism should undergo a 12-lead electrocardiogram as part of their evaluation. As the older population faces an elevated risk of hyponatremia, necessitating electrolyte monitoring in patients 65 and older is important.[37] Clinicians can monitor patient responses using validated questionnaires such as the patient health questionnaire (PHQ-9) and the Hamilton Rating Scale for Depression. Furthermore, it is crucial to remain vigilant for signs of suicidal ideation.[38][39]

Toxicity

Signs and Symptoms of Overdose

The primary concern for TCA toxicity is the potential development of serotonin syndrome, particularly when the medication is combined with other antidepressants such as SSRIs or SNRIs. Serotonin syndrome is characterized by symptoms such as hyperthermia, hypertension, muscle rigidity, and delirium. 

Management of Overdose

In case of TCA or amoxapine overdose, there is no particular antidote available. The primary concern in cases of TCA overdose is ensuring proper respiration and delivering cardiovascular support to patients. Research has demonstrated that, in certain instances, sodium bicarbonate can reduce the incidence of QRS widening.[40] This treatment requires vigilant monitoring of sodium plasma concentrations, as there is a possibility of hypernatremia in patients receiving sodium bicarbonate. However, in the absence of immediate electrolyte changes, the standard protocol involves close monitoring of the patient in the intensive care unit to detect any cardiac abnormalities and ensure adequate hydration to facilitate drug elimination from the system. Analysis of U.S. Poison Control Center data from 2000 to 2014 reveals that amoxapine toxicity may lead to severe complications, including cardiac arrest, renal failure, and intractable seizures.[41] 

In a recent case report, intractable seizures were observed following an amoxapine overdose resulting from a suicide attempt involving the consumption of 3 g of the drug. Despite the administration of intravenous diazepam, levetiracetam, and phenobarbital, the seizures remained uncontrolled. However, the seizures ceased just within 2 minutes of initiating intravenous lipid emulsion (ILE). Although a seizure recurrence occurred 30 minutes after the initial ILE treatment, these seizures were effectively managed through the re-administration of ILE. Therefore, ILE should be considered as a potential intervention for managing severe amoxapine overdose.[42] The prevailing mechanism of lipid emulsion treatment as adjunctive therapy in cases of drug toxicity is based on the hypothesis of lipid shuttling. ILE administration establishes a substantial lipid compartment that efficiently absorbs highly lipid-soluble drugs such as amoxapine, aiding in their removal from the system.[43]

Enhancing Healthcare Team Outcomes

As TCAs, such as amoxapine, are typically reserved as third-line treatments for depression, patients who receive them or are being considered for their use typically exhibit recurrent or reactive depression. This suggests that other medication and treatment approaches have proven ineffective in managing the symptoms of these patients. Consequently, these patients are at an elevated risk of engaging in self-harming and suicidal behaviors. To address these concerns effectively, it is imperative to assemble a cohesive interprofessional healthcare team to oversee their treatment. This team should encompass regular coordination between the patient's primary physician, psychiatrist, and counselors, ensuring adherence to the medication regimen and monitoring the response to treatment. At every office visit, comprehensive assessments for suicidal ideations, plans, or tendencies should be conducted. Appropriate overdose precautions should be initiated if there is any indication that patients pose a risk to themselves or others.[44]

Treatment with amoxapine and other antidepressant medications is most effective when managed by an interprofessional healthcare team responsible for all aspects of the patient's case. This team comprises physicians who prescribe and make regimen-related decisions, specialists who provide in-depth condition-specific expertise, specialized nursing staff who oversee care, ensure patient adherence, and assist with monitoring patient symptoms, and pharmacists who conduct medication reconciliation and dosage verification. A retrospective analysis of data from hospitalized patients with poisoning indicates significant reductions in hospitalization duration, healthcare costs, and mortality rates when medical toxicologists actively participate in patient care.[45] All interprofessional team members, including clinicians (MD, DO, NP, and PA), nurses, specialists, toxicologists, and pharmacists, should collaborate and maintain open communication to ensure optimal care and outcomes related to amoxapine therapy.

References


[1]

Cugurra F. [Drug therapy and affective disorders: state of the art]. La Clinica terapeutica. 1995 Oct:146(10):577-85     [PubMed PMID: 8590559]


[2]

Kinney JL, Evans RL Jr. Evaluation of amoxapine. Clinical pharmacy. 1982 Sep-Oct:1(5):417-24     [PubMed PMID: 6764165]

Level 3 (low-level) evidence

[3]

Li X, Wang Q, Hu T, Wang Y, Zhao J, Lu J, Pei G. A tricyclic antidepressant, amoxapine, reduces amyloid-β generation through multiple serotonin receptor 6-mediated targets. Scientific reports. 2017 Jul 10:7(1):4983. doi: 10.1038/s41598-017-04144-3. Epub 2017 Jul 10     [PubMed PMID: 28694424]


[4]

Ahmad S, Hughes MA, Yeh LA, Scott JE. Potential repurposing of known drugs as potent bacterial β-glucuronidase inhibitors. Journal of biomolecular screening. 2012 Aug:17(7):957-65. doi: 10.1177/1087057112444927. Epub 2012 Apr 24     [PubMed PMID: 22535688]


[5]

Kong R, Liu T, Zhu X, Ahmad S, Williams AL, Phan AT, Zhao H, Scott JE, Yeh LA, Wong ST. Old drug new use--amoxapine and its metabolites as potent bacterial β-glucuronidase inhibitors for alleviating cancer drug toxicity. Clinical cancer research : an official journal of the American Association for Cancer Research. 2014 Jul 1:20(13):3521-30. doi: 10.1158/1078-0432.CCR-14-0395. Epub 2014 Apr 29     [PubMed PMID: 24780296]

Level 3 (low-level) evidence

[6]

Mika J, Zychowska M, Makuch W, Rojewska E, Przewlocka B. Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies. Pharmacological reports : PR. 2013:65(6):1611-21     [PubMed PMID: 24553009]

Level 3 (low-level) evidence

[7]

van Wyk EM, Louw DA. Amoxapine in the treatment of depression. A clinical evaluation in ambulant patients. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 1982 Jun 12:61(24):908-11     [PubMed PMID: 7046092]


[8]

Kapoor R, Peyear TA, Koeppe RE 2nd, Andersen OS. Antidepressants are modifiers of lipid bilayer properties. The Journal of general physiology. 2019 Mar 4:151(3):342-356. doi: 10.1085/jgp.201812263. Epub 2019 Feb 22     [PubMed PMID: 30796095]


[9]

Richelson E, Nelson A. Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. The Journal of pharmacology and experimental therapeutics. 1984 Jul:230(1):94-102     [PubMed PMID: 6086881]


[10]

Reeves KC, Virk S, Niedermier J, Duchemin AM. Addition of amoxapine improves positive and negative symptoms in a patient with schizophrenia. Therapeutic advances in psychopharmacology. 2013 Dec:3(6):340-2. doi: 10.1177/2045125313499363. Epub     [PubMed PMID: 24294487]

Level 3 (low-level) evidence

[11]

. Amoxapine. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012:():     [PubMed PMID: 31643838]


[12]

Ban TA, Fujimori M, Petrie WM, Ragheb M, Wilson WH. Systematic studies with amoxapine, a new antidepressant. International pharmacopsychiatry. 1982:17(1):18-27     [PubMed PMID: 7045016]

Level 1 (high-level) evidence

[13]

Apiquian R, Fresan A, Ulloa RE, de la Fuente-Sandoval C, Herrera-Estrella M, Vazquez A, Nicolini H, Kapur S. Amoxapine as an atypical antipsychotic: a comparative study vs risperidone. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2005 Dec:30(12):2236-44     [PubMed PMID: 15956984]

Level 1 (high-level) evidence

[14]

Ban TA, Wilson WH, McEvoy JP. Amoxapine: a review of literature. International pharmacopsychiatry. 1980:15(3):166-70     [PubMed PMID: 7016801]

Level 3 (low-level) evidence

[15]

Ragheb M, Wilson WH, Ban TA, Brannen JO. Amoxapine: once versus divided daily doses in neurotic and endogenous depression. The Journal of clinical psychiatry. 1981 Aug:42(8):318-21     [PubMed PMID: 7019201]

Level 1 (high-level) evidence

[16]

ACOG Committee on Practice Bulletins--Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstetrics and gynecology. 2008 Apr:111(4):1001-20. doi: 10.1097/AOG.0b013e31816fd910. Epub     [PubMed PMID: 18378767]


[17]

. Amoxapine. Drugs and Lactation Database (LactMed®). 2006:():     [PubMed PMID: 30000242]


[18]

By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023 Jul:71(7):2052-2081. doi: 10.1111/jgs.18372. Epub 2023 May 4     [PubMed PMID: 37139824]


[19]

Aono T, Kaneko M, Numata Y, Takahashi Y, Yamamoto T, Kumashiro H. Effects of amoxapine, a new antidepressant, on pseudoneurotic schizophrenia. Folia psychiatrica et neurologica japonica. 1981:35(2):115-21     [PubMed PMID: 7026396]


[20]

Hekimian LJ, Weise CC, Friedhoff AJ. Onset of action of amoxapine and doxepin in outpatients with "mixed anxiety/depression". The Journal of clinical psychiatry. 1983 Jul:44(7):248-52     [PubMed PMID: 6863224]

Level 1 (high-level) evidence

[21]

Obara K, Imanaka S, Fukuhara H, Yamaki F, Matsuo K, Yoshio T, Tanaka Y. Evaluation of the potentiating effects of antidepressants on the contractile response to noradrenaline in guinea pig urethra smooth muscles. Clinical and experimental pharmacology & physiology. 2019 May:46(5):444-455. doi: 10.1111/1440-1681.13072. Epub 2019 Mar 7     [PubMed PMID: 30737814]


[22]

Obara K, Michino M, Ito M, Ao L, Sawada A, Yamaki F, Matsuo K, Yoshio T, Tanaka Y. Evaluation of Antidepressant Effects on Recovery of Electrical Field Stimulation-Induced Contractions that have been Suppressed by Clonidine in Isolated Rat Vas Deferens. Pharmacology. 2019:103(3-4):189-201. doi: 10.1159/000495616. Epub 2019 Jan 29     [PubMed PMID: 30695779]


[23]

Demyttenaere K, Huygens R. Painful ejaculation and urinary hesitancy in association with antidepressant therapy: relief with tamsulosin. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2002 Aug:12(4):337-41     [PubMed PMID: 12126873]

Level 3 (low-level) evidence

[24]

Johannessen Landmark C, Henning O, Johannessen SI. Proconvulsant effects of antidepressants - What is the current evidence? Epilepsy & behavior : E&B. 2016 Aug:61():287-291. doi: 10.1016/j.yebeh.2016.01.029. Epub 2016 Feb 24     [PubMed PMID: 26926001]


[25]

Górska N, Słupski J, Cubała WJ, Wiglusz MS, Gałuszko-Węgielnik M. Antidepressants in epilepsy. Neurologia i neurochirurgia polska. 2018 Nov-Dec:52(6):657-661. doi: 10.1016/j.pjnns.2018.07.005. Epub 2018 Aug 11     [PubMed PMID: 30131174]


[26]

Farzam K, Sabir S, O'Rourke MC. Antihistamines. StatPearls. 2024 Jan:():     [PubMed PMID: 30844215]


[27]

Obers S, Staudacher I, Ficker E, Dennis A, Koschny R, Erdal H, Bloehs R, Kisselbach J, Karle CA, Schweizer PA, Katus HA, Thomas D. Multiple mechanisms of hERG liability: K+ current inhibition, disruption of protein trafficking, and apoptosis induced by amoxapine. Naunyn-Schmiedeberg's archives of pharmacology. 2010 May:381(5):385-400. doi: 10.1007/s00210-010-0496-7. Epub 2010 Mar 13     [PubMed PMID: 20229012]

Level 3 (low-level) evidence

[28]

Serlin DC, Heidelbaugh JJ, Stoffel JT. Urinary Retention in Adults: Evaluation and Initial Management. American family physician. 2018 Oct 15:98(8):496-503     [PubMed PMID: 30277739]


[29]

Dai Z, Abate MA, Long DL, Smith GS, Halki TM, Kraner JC, Mock AR. Quantifying enhanced risk from alcohol and other factors in polysubstance-related deaths. Forensic science international. 2020 Aug:313():110352. doi: 10.1016/j.forsciint.2020.110352. Epub 2020 May 31     [PubMed PMID: 32590196]


[30]

Poh BH, Lee JH, Abdul Haium AA, Choo TLJ. Complete Heart Block Secondary to Flecainide Toxicity: Is It Time for CYP2D6 Genotype Testing? Pediatrics. 2020 Jul:146(1):. pii: e20192608. doi: 10.1542/peds.2019-2608. Epub 2020 Jun 19     [PubMed PMID: 32561613]


[31]

. Drug interactions with selective serotonin reuptake inhibitors, especially with other psychotropics. Prescrire international. 2001 Feb:10(51):25-31     [PubMed PMID: 11503857]


[32]

Revet A, Montastruc F, Roussin A, Raynaud JP, Lapeyre-Mestre M, Nguyen TTH. Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database. BMC psychiatry. 2020 Jun 16:20(1):308. doi: 10.1186/s12888-020-02711-z. Epub 2020 Jun 16     [PubMed PMID: 32546134]


[33]

Oruch R, Pryme IF, Engelsen BA, Lund A. Neuroleptic malignant syndrome: an easily overlooked neurologic emergency. Neuropsychiatric disease and treatment. 2017:13():161-175. doi: 10.2147/NDT.S118438. Epub 2017 Jan 16     [PubMed PMID: 28144147]


[34]

Janati AB, Alghasab N, Osman A. Neuroleptic malignant syndrome caused by a combination of carbamazepine and amitriptyline. Case reports in neurological medicine. 2012:2012():183252. doi: 10.1155/2012/183252. Epub 2012 Jul 24     [PubMed PMID: 22953086]

Level 3 (low-level) evidence

[35]

Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, Sharma V, Goldstein BI, Rej S, Beaulieu S, Alda M, MacQueen G, Milev RV, Ravindran A, O'Donovan C, McIntosh D, Lam RW, Vazquez G, Kapczinski F, McIntyre RS, Kozicky J, Kanba S, Lafer B, Suppes T, Calabrese JR, Vieta E, Malhi G, Post RM, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar disorders. 2018 Mar:20(2):97-170. doi: 10.1111/bdi.12609. Epub 2018 Mar 14     [PubMed PMID: 29536616]


[36]

Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Azorin JM, Yatham L, Mosolov S, Möller HJ, Kasper S, Members of the WFSBP Task Force on Bipolar Affective Disorders Working on this topic. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 2018 Feb:19(1):2-58. doi: 10.1080/15622975.2017.1384850. Epub 2017 Nov 3     [PubMed PMID: 29098925]


[37]

Rochoy M, Zakhem-Stachera C, Béné J, Berkhout C, Gautier S, Réseau français des Centres Régionaux de Pharmacovigilance. [Antidepressive agents and hyponatremia: A literature review and a case/non-case study in the French Pharmacovigilance database]. Therapie. 2018 Oct:73(5):389-398. doi: 10.1016/j.therap.2018.02.006. Epub 2018 Mar 1     [PubMed PMID: 29773358]

Level 3 (low-level) evidence

[38]

Trivedi MH. Tools and strategies for ongoing assessment of depression: a measurement-based approach to remission. The Journal of clinical psychiatry. 2009:70 Suppl 6():26-31. doi: 10.4088/JCP.8133su1c.04. Epub     [PubMed PMID: 19922741]


[39]

Stone MB, Yaseen ZS, Miller BJ, Richardville K, Kalaria SN, Kirsch I. Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis. BMJ (Clinical research ed.). 2022 Aug 2:378():e067606. doi: 10.1136/bmj-2021-067606. Epub 2022 Aug 2     [PubMed PMID: 35918097]

Level 1 (high-level) evidence

[40]

Kassim T, Mahfood Haddad T, Rakhra A, Kabach A, Qurie A, Selim M, Nayfeh AS, Aly A, Holmberg MJ. A Case of Amitriptyline-induced Myocarditis. Cureus. 2018 Jun 19:10(6):e2840. doi: 10.7759/cureus.2840. Epub 2018 Jun 19     [PubMed PMID: 30430045]

Level 3 (low-level) evidence

[41]

Nelson JC, Spyker DA. Morbidity and Mortality Associated With Medications Used in the Treatment of Depression: An Analysis of Cases Reported to U.S. Poison Control Centers, 2000-2014. The American journal of psychiatry. 2017 May 1:174(5):438-450. doi: 10.1176/appi.ajp.2016.16050523. Epub 2017 Jan 31     [PubMed PMID: 28135844]

Level 3 (low-level) evidence

[42]

Matsuoka M, Imai T, Iwabuchi S, Kinoshita K. Successful Treatment of Amoxapine-Induced Intractable Seizures With Intravenous Lipid Emulsion. The Journal of emergency medicine. 2023 Jan:64(1):62-66. doi: 10.1016/j.jemermed.2022.10.016. Epub 2022 Nov 28     [PubMed PMID: 36450616]


[43]

Sohn JT. Half-Life of Lipid Emulsions Used in Lipid Emulsion Treatment for Drug Toxicity. The Journal of emergency medicine. 2023 Feb:64(2):253-254. doi: 10.1016/j.jemermed.2022.12.032. Epub     [PubMed PMID: 36906377]


[44]

Buckley NA, McManus PR. Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug safety. 1998 May:18(5):369-81     [PubMed PMID: 9589848]

Level 3 (low-level) evidence

[45]

Curry SC, Brooks DE, Skolnik AB, Gerkin RD, Glenn S. Effect of a medical toxicology admitting service on length of stay, cost, and mortality among inpatients discharged with poisoning-related diagnoses. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2015 Mar:11(1):65-72. doi: 10.1007/s13181-014-0418-z. Epub     [PubMed PMID: 25127915]

Level 2 (mid-level) evidence