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Fluvoxamine

Clinical data
Trade names	Luvox, others
AHFS/Drugs.com	Monograph
MedlinePlus	a695004
License data	US DailyMed: Fluvoxamine
Pregnancy category	AU: C
Routes of administration	By mouth
Drug class	Selective serotonin reuptake inhibitor (SSRI)
ATC code	N06AB08 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class C1 (Other controlled substances) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	53% (90% confidence interval: 44–62%)
Protein binding	77–80%
Metabolism	Liver (primarily O-demethylation) Major: CYP2D6 or CYP1A2 Minor: CYP3A4, CYP2C19, and/or CYP1A2
Elimination half-life	12–13 hours (single dose), 22 hours (repeated dosing)
Excretion	Kidney (98%; 94% as metabolites, 4% as unchanged drug)
Identifiers
IUPAC name 2-{ pentylidene}amino]oxy}ethanamine
CAS Number	54739-18-3
PubChem CID	5324346
IUPHAR/BPS	7189
DrugBank	DB00176
ChemSpider	4481878
UNII	O4L1XPO44W
KEGG	D07984
ChEBI	CHEBI:5138
ChEMBL	ChEMBL814
CompTox Dashboard (EPA)	DTXSID2044002
ECHA InfoCard	100.125.476
Chemical and physical data
Formula	C15H21F3N2O2
Molar mass	318.340 g·mol
3D model (JSmol)	Interactive image
SMILES FC(F)(F)c1ccc(\C(=N\OCCN)CCCCOC)cc1
InChI InChI=1S/C15H21F3N2O2/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18/h5-8H,2-4,9-11,19H2,1H3/b20-14+ Key:CJOFXWAVKWHTFT-XSFVSMFZSA-N
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Fluvoxamine, sold under the brand name Luvox among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and, perhaps more-especially, obsessive–compulsive disorder (OCD), but is also used to treat anxiety disorders such as panic disorder, social anxiety disorder, and post-traumatic stress disorder.

Fluvoxamine's side-effect profile is similar to that of other SSRIs. Common adverse effects include constipation, gastrointestinal problems, headache, anxiety, irritation, sexual problems, dry mouth, sleep problems and an increased risk of suicide at the start of treatment. These effects appear to be significantly weaker than with other SSRIs, with the exception of gastrointestinal side-effects.

Fluvoxamine appears to be more tolerable than other SSRIs, particularly with respect to cardiovascular complications. Compared to escitalopram and sertraline, fluvoxamine's gastrointestinal profile may be less intense, often being limited to nausea. Mosapride has demonstrated efficacy in treating fluvoxamine-induced nausea. It is also advised practice to divide total daily doses of fluvoxamine greater than 100 milligrams, with the higher fraction being taken in the evening (e.g., 50 mg at the beginning of the waking day and 200 mg at bedtime). In any case, high starting daily doses of fluvoxamine rather than the recommended gradual titration (starting at 50 milligrams and gradually titrating, up to 300 if necessary) may increase the likelihood of nausea.

It is on the World Health Organization's List of Essential Medicines.

Medical uses

In many countries (e.g., Australia, the United Kingdom, and Russia) it is commonly used for major depressive disorder. Fluvoxamine is also approved in the United States for obsessive–compulsive disorder (OCD), and social anxiety disorder. In Japan, it is also approved to treat OCD, social anxiety disorder and major depressive disorder. Fluvoxamine is indicated for children and adolescents with OCD. The NICE guidelines in the United Kingdom have, as of 2005, authorized its use for obsessive-compulsive disorder in adults and adolescents of any age and children over the age of 7.

There is evidence that fluvoxamine is effective for generalised social anxiety in adults, although, as with other SSRIs, some of the results may be compromised by having been funded by pharmaceutical companies. Of the SSRIs, however, fluvoxamine, paroxetine and sertraline do appear consistent as viable treatments for generalised social anxiety. Phenelzine, brofaromine, venlafaxine, gabapentin, pregabalin and clonazepam represent other viable options for the pharmacological treatment of generalised social anxiety.

Fluvoxamine is also effective for treating a range of anxiety disorders in children and adolescents, including generalized anxiety disorder, social anxiety disorder, panic disorder and separation anxiety disorder.

The drug works long-term, and retains its therapeutic efficacy for at least one year.

The average therapeutic dose for fluvoxamine is 100 to 300 mg/day, with 300 mg being the upper daily limit normally recommended. Obsessive-compulsive disorder, however, often requires higher doses; doses of up to 450 mg/day may be prescribed in this case.The (off-label) upper daily limits for other serotonin-reuptake inhibitors used in the treatment of obsessive-compulsive disorder, by analogy, are 400mg for sertraline, 100 mg for paroxetine, 120 mg for both fluoxetine and citalopram, 60 mg for escitalopram and 300 mg for clomipramine.

In any case with fluvoxamine, treatment is generally begun at 50 mg and increased in 50 mg increments every 4 to 7 days until a therapeutic optimum is reached.

Adverse effects

Fluvoxamine's side-effect profile is very similar to other SSRIs. Gastrointestinal side effects are characteristic of those receiving treatment with fluvoxamine.

Common

Common side effects occurring with 1–10% incidence:

• Abdominal pain
• Agitation
• Anxiety
• Asthenia (weakness)
• Constipation
• Diarrhea
• Dizziness
• Dyspepsia (indigestion)
• Headache
• Hyperhidrosis (excess sweating)
• Insomnia
• Loss of appetite
• Malaise
• Nausea
• Nervousness
• Palpitations
• Restlessness
• Sexual dysfunction (including delayed ejaculation, erectile dysfunction, decreased libido, etc.)
• Somnolence (drowsiness)
• Tachycardia (high heart rate)
• Tremor
• Vomiting
• Weight loss
• Xerostomia (dry mouth)
• Yawning

Uncommon

Uncommon side effects occurring with 0.1–1% incidence:

• Arthralgia
• Confusional state
• Cutaneous hypersensitivity reactions (e.g. oedema , rash, pruritus)
• Extrapyramidal side effects (e.g. dystonia, parkinsonism, tremor, etc.)
• Hallucination
• Orthostatic hypotension

Rare

Rare side effects occurring with 0.01–0.1% incidence:

• Abnormal hepatic (liver) function
• Galactorrhoea (expulsion of breast milk unrelated to pregnancy or breastfeeding)
• Mania
• Photosensitivity (being abnormally sensitive to light)
• Seizures

Unknown frequency

• Akathisia – a sense of inner restlessness that presents itself with the inability to stay still
• Bed-wetting
• Bone fractures
• Dysgeusia
• Ecchymoses
• Glaucoma
• Haemorrhage
• Hyperprolactinaemia (elevated plasma prolactin levels leading to galactorrhoea, amenorrhoea , etc.)
• Hyponatraemia
• Mydriasis
• Neuroleptic malignant syndrome – practically identical presentation to serotonin syndrome except with a more prolonged onset
• Paraesthesia
• Serotonin syndrome – a potentially fatal condition characterised by abrupt onset muscle rigidity, hyperthermia (elevated body temperature), rhabdomyolysis, mental status changes (e.g. coma, hallucinations, agitation), etc.
• Suicidal ideation and behaviour
• Syndrome of inappropriate antidiuretic hormone secretion
• Urinary incontinence
• Urinary retention
• Violence towards others
• Weight changes
• Withdrawal symptoms

Interactions

Fluvoxamine inhibits the following cytochrome P450 enzymes:

• CYP1A2 (strongly) which metabolizes agomelatine, amitriptyline, caffeine, clomipramine, clozapine, duloxetine, haloperidol, imipramine, phenacetin, tacrine, tamoxifen, theophylline, olanzapine, etc.
• CYP3A4 (moderately) which metabolizes alprazolam, aripiprazole, clozapine, haloperidol, quetiapine, pimozide, ziprasidone, etc.
• CYP2D6 (weakly) which metabolizes aripiprazole, chlorpromazine, clozapine, codeine, fluoxetine, haloperidol, olanzapine, oxycodone, paroxetine, perphenazine, pethidine, risperidone, sertraline, thioridazine, zuclopenthixol, etc.
• CYP2C9 (moderately) which metabolizes nonsteroidal anti-inflammatory drugs, phenytoin, sulfonylureas, etc.
• CYP2C19 (strongly) which metabolizes clonazepam, diazepam, phenytoin, etc.
• CYP2B6 (weakly) which metabolizes bupropion, cyclophosphamide, sertraline, tamoxifen, valproate, etc.

By so doing, fluvoxamine can increase serum concentration of the substrates of these enzymes.

Fluvoxamine may also elevate plasma levels of olanzapine by approximately two times. Combined olanzapine and fluvoxamine, which may cause increased sedation, should be used cautiously and controlled clinically and by therapeutic drug monitoring to avoid olanzapine induced adverse effects and/or intoxication.

The plasma levels of oxidatively metabolized benzodiazepines (e.g., triazolam, midazolam, alprazolam and diazepam) are likely to be increased when co-administered with fluvoxamine. However, the clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam; oxazepam, which is coincidentally a metabolite of diazepam; temazepam) are not affected by fluvoxamine and may be safely taken alongside fluvoxamine should concurrent treatment with a benzodiazepine be necessary. Additionally, it appears that benzodiazepines metabolized by nitro-reduction (clonazepam, nitrazepam) may also, in a somewhat similar vein, be unlikely to be affected by fluvoxamine.

Using fluvoxamine and alprazolam together can increase alprazolam plasma concentrations. If alprazolam is coadministered with fluvoxamine, the initial alprazolam dose should be reduced to the lowest effective dose.

Fluvoxamine and ramelteon coadministration is not indicated.

Fluvoxamine has been observed to increase serum concentrations of mirtazapine, which is mainly metabolized by CYP1A2, CYP2D6, and CYP3A4, by three- to four-fold in humans. Caution and adjustment of dosage as necessary are warranted when combining fluvoxamine and mirtazapine.

Fluvoxamine seriously affects the pharmacokinetics of tizanidine and increases the intensity and duration of its effects. Because of the potentially hazardous consequences, the concomitant use of tizanidine with fluvoxamine, or other potent inhibitors of CYP1A2, should be avoided.

When a beta-blocker is required, atenolol, pindolol and, possibly, metoprolol may be safer choices than propranolol, as the latter's metabolism is seriously, potentially dangerously, inhibited by fluvoxamine. Indeed, fluvoxamine may increase propranolol blood-levels by five-fold.

Clomipramine increases fluvoxamine levels and, conversely-likewise, fluvoxamine increases clomipramine levels (thereby its serotoninergic potential) and inhibits its metabolism to its strongly-noradrenergic metabolite, norclomipramine.

Pharmacology

Pharmacodynamics

Fluvoxamine is a potent selective serotonin reuptake inhibitor with around 100-fold affinity for the serotonin transporter over the norepinephrine transporter. It has negligible affinity for the dopamine transporter or any other site, with the sole exception of the σ₁ receptor. It behaves as a potent agonist at this receptor and has the highest affinity (36 nM) of any SSRI for doing so. This may contribute to its antidepressant and anxiolytic effects and may also afford it some efficacy in treating the cognitive symptoms of depression. It increases concentrations of the neurosteroid allopregnanolone, which may also contribute to its anxiolytic effects. Unlike some other SSRIs, fluvoxamine's metabolites are pharmacologically neutral.

Pharmacokinetics

Literature reviews have stated that fluvoxamine is metabolized primarily by CYP2D6 and to a minor extent by CYP1A2. However, CYP2D6 poor metabolizers do not have considerably higher fluvoxamine levels than extensive metabolizers. The Australian Therapeutic Goods Administration (TGA) label (last revised 2023) states that the specific enzymes involved in fluvoxamine are not definitively known and that in vitro data suggest that it is mainly metabolized by CYP1A2 and may also be metabolized by CYP3A4 and CYP2C19 to a much lesser extent.

History

Fluvoxamine was developed by Kali-Duphar, part of Solvay Pharmaceuticals, Belgium, now Abbott Laboratories, and introduced as Floxyfral in Switzerland in 1983. It was approved by the U.S. Food and Drug Administration (FDA) in 1994, and introduced as Luvox in the US. In India, it is available, among several other brands, as Uvox by Abbott. It was one of the first SSRI antidepressants to be launched, and is prescribed in many countries to patients with major depression. It was the first SSRI, a non-TCA drug, approved by the U.S. FDA specifically for the treatment of OCD. At the end of 1995, more than ten million patients worldwide had been treated with fluvoxamine. Fluvoxamine was the first SSRI to be registered for the treatment of obsessive compulsive disorder in children by the FDA in 1997. In Japan, fluvoxamine was the first SSRI to be approved for the treatment of depression in 1999 and was later in 2005 the first drug to be approved for the treatment of social anxiety disorder. Fluvoxamine was the first SSRI approved for clinical use in the United Kingdom. Manufacturers include BayPharma, Synthon, and Teva, among others.

Research directions

While early studies have suggested potential benefits for fluvoxamine as an anti-inflammatory agent and a possible impact on reducing cytokine storms, further studies did not confirm this expected benefit on COVID-19 patients. A cytokine storm refers to an excessive immune response characterized by a release of large amounts of pro-inflammatory cytokines.

In May 2022, based on a review of available scientific evidence, the U.S. Food and Drug Administration (FDA) chose not to issue an emergency use authorization covering the use of fluvoxamine to treat COVID-19, saying that, at the time, the data was not sufficient to conclude that fluvoxamine may be effective in treating non-hospitalized people with COVID-19 to prevent serious illness or hospitalization. The agency stated that study results suggest that further clinical trials may be warranted.

A large double-blind randomized controlled trial called ACTIV-6, published in 2023 in JAMA, revealed that taking 200 mg of fluvoxamine every day for about two weeks was not significantly better than placebo at shortening the duration of mild or moderate COVID-19 symptoms.

There is tentative evidence that fluvoxamine may reduce the overall morbidity of COVID-19 and complications thereof.

Environment

Fluvoxamine is a common finding in waters near human settlement. Christensen et al. 2007 finds it is "very toxic to aquatic organisms" by European Union standards.

References

1. Use During Pregnancy and Breastfeeding
2. Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
3. ^ "Product Information Luvox". TGA eBusiness Services. Abbott Australasia Pty Ltd. 15 January 2013. Archived from the original on 9 October 2017. Retrieved 21 October 2013.
4. van Harten J (March 1993). "Clinical pharmacokinetics of selective serotonin reuptake inhibitors". Clinical Pharmacokinetics. 24 (3): 203–220. doi:10.2165/00003088-199324030-00003. PMID 8384945. S2CID 84636672.
5. ^ Altamura AC, Caldiroli A, Buoli M (April 2015). "Pharmacokinetic evaluation of fluvoxamine for the treatment of anxiety disorders". Expert Opin Drug Metab Toxicol. 11 (4): 649–660. doi:10.1517/17425255.2015.1021331. PMID 25728382.
6. ^ Wyska E (October 2019). "Pharmacokinetic considerations for current state-of-the-art antidepressants". Expert Opin Drug Metab Toxicol. 15 (10): 831–847. doi:10.1080/17425255.2019.1669560. PMID 31526279.
7. "Luvox". ChemSpider. Royal Society of Chemistry. Archived from the original on 15 November 2013. Retrieved 21 October 2013.
8. "Fluvoxamine Maleate Information". U.S. Food and Drug Administration (FDA). 15 July 2015. Archived from the original on 29 November 2019. Retrieved 28 November 2019.
9. ^ McCain JA (July 2009). "Antidepressants and suicide in adolescents and adults: a public health experiment with unintended consequences?". P & T. 34 (7): 355–378. PMC 2799109. PMID 20140100.
10. "Fluvoxamine for the treatment of anxiety disorders in children and adolescents. The Research Unit on Pediatric Psychopharmacology Anxiety Study Group". The New England Journal of Medicine. 344 (17): 1279–1285. April 2001. doi:10.1056/NEJM200104263441703. PMID 11323729.
11. Figgitt DP, McClellan KJ (October 2000). "Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders". Drugs. 60 (4): 925–954. doi:10.2165/00003495-200060040-00006. PMID 11085201. S2CID 265712201.
12. ^ Irons J (December 2005). "Fluvoxamine in the treatment of anxiety disorders". Neuropsychiatric Disease and Treatment. 1 (4): 289–299. PMC 2424117. PMID 18568110.
13. Asnis GM, Hameedi FA, Goddard AW, Potkin SG, Black D, Jameel M, et al. (August 2001). "Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients". Psychiatry Research. 103 (1): 1–14. doi:10.1016/S0165-1781(01)00265-7. PMID 11472786. S2CID 40412606.
14. Vezmar, S. et al., « Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression », J Pharmacol Sci, vol. 110, no 1, 2009, p. 98 – 104 (ISSN 1347-8648)
15. ^ Westenberg HG, Sandner C (April 2006). "Tolerability and safety of fluvoxamine and other antidepressants". International Journal of Clinical Practice. 60 (4): 482–491. doi:10.1111/j.1368-5031.2006.00865.x. PMC 1448696. PMID 16620364.
16. Oliva V, Lippi M, Paci R, Del Fabro L, Delvecchio G, Brambilla P, et al. (July 2021). "Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 109. Elsevier BV: 110266. doi:10.1016/j.pnpbp.2021.110266. PMID 33549697. S2CID 231809760.
17. Ueda N, Yoshimura R, Shinkai K, Terao T, Nakamura J (November 2001). "Characteristics of fluvoxamine-induced nausea". Psychiatry Research. 104 (3). Elsevier BV: 259–264. doi:10.1016/s0165-1781(01)00320-1. PMID 11728615. S2CID 38761139.
18. Ware MR (1 March 1997). "Fluvoxamine: A Review of the Controlled Trials in Depression". The Journal of Clinical Psychiatry. 58 (suppl 5). Physicians Postgraduate Press, Inc.: 15–23. ISSN 0160-6689. PMID 9184623. Archived from the original on 6 December 2022. Retrieved 1 December 2023.
19. World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
20. ^ Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
21. "Luvox Tablets". NPS MedicineWise. Archived from the original on 22 October 2018. Retrieved 22 October 2018.
22. ^ Joint Formulary Committee (2013). British National Formulary (BNF) (65th ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
23. "Summary of Full Prescribing Information: Fluvoxamine". Drug Registry of Russia (RLS) Drug Compendium (in Russian). Archived from the original on 2 April 2015. Retrieved 21 March 2015.
24. ^ "Fluvoxamine Maleate tablet, coated prescribing information". DailyMed. U.S. National Library of Medicine. 14 December 2018. Archived from the original on 19 October 2020. Retrieved 28 November 2019.
25. "Luvox CR approved for OCD and SAD". MPR. 29 February 2008. Archived from the original on 28 August 2021. Retrieved 2 March 2019.
26. "2005 News Releases". Astellas Pharma. Archived from the original on 16 September 2018. Retrieved 16 September 2018.
27. "International Approvals: Ebixa, Depromel/Luvox, M-Vax". www.medscape.com. Archived from the original on 29 October 2020. Retrieved 16 September 2018.
28. "Fluvoxamine Product Insert" (PDF). Jazz Pharmaceuticals, Inc. U.S. Food and Drug Administration. March 2005. Archived (PDF) from the original on 4 November 2022. Retrieved 4 November 2022.
29. Williams T, Hattingh CJ, Kariuki CM, Tromp SA, van Balkom AJ, Ipser JC, et al. (October 2017). "Pharmacotherapy for social anxiety disorder (SAnD)". The Cochrane Database of Systematic Reviews. 10 (10): CD001206. doi:10.1002/14651858.CD001206.pub3. PMC 6360927. PMID 29048739.
30. Liu X, Li X, Zhang C, Sun M, Sun Z, Xu Y, et al. (July 2018). "Efficacy and tolerability of fluvoxamine in adults with social anxiety disorder: A meta-analysis". Medicine (Baltimore). 97 (28): e11547. doi:10.1097/MD.0000000000011547. PMC 6076099. PMID 29995828.
31. Williams, T., McCaul, M., Schwarzer, G., Cipriani, A., Stein, D. J., & Ipser, J. (2020). Pharmacological treatments for social anxiety disorder in adults: a systematic review and network meta-analysis. Acta neuropsychiatrica, 32(4), 169–176. https://doi.org/10.1017/neu.2020.6 Archived 7 September 2024 at the Wayback Machine
32. Davidson J. R. (2003). Pharmacotherapy of social phobia. Acta psychiatrica Scandinavica. Supplementum, (417), 65–71. https://doi.org/10.1034/j.1600-0447.108.s417.7.x Archived 7 September 2024 at the Wayback Machine
33. Tancer, M. E., & Uhde, T. W. (1997). Role of serotonin drugs in the treatment of social phobia. The Journal of clinical psychiatry, 58 Suppl 5, 50–54.
34. Aarre T. F. (2003). Phenelzine efficacy in refractory social anxiety disorder: a case series. Nordic journal of psychiatry, 57(4), 313–315. https://doi.org/10.1080/08039480310002110
35. Blanco C, Antia SX, Liebowitz MR. Pharmacotherapy of social anxiety disorder. Biol Psychiatry. 2002 Jan 1;51(1):109-20. doi: 10.1016/s0006-3223(01)01294-x. PMID 11801236.
36. Westenberg HG. Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb;14(2 Suppl 3):24-33. doi: 10.1017/s1092852900027267. PMID 19238127.
37. Davis ML, Smits JA, Hofmann SG. Update on the efficacy of pharmacotherapy for social anxiety disorder: a meta-analysis. Expert Opin Pharmacother. 2014 Nov;15(16):2281-91. doi: 10.1517/14656566.2014.955472. Epub 2014 Oct 5. PMID 25284086.
38. "Antidepressants for children and teenagers: what works for anxiety and depression?". NIHR Evidence (Plain English summary). National Institute for Health and Care Research. 3 November 2022. doi:10.3310/nihrevidence_53342. S2CID 253347210. Archived from the original on 5 November 2022. Retrieved 7 November 2022.
39. Boaden K, Tomlinson A, Cortese S, Cipriani A (2 September 2020). "Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment". Frontiers in Psychiatry. 11: 717. doi:10.3389/fpsyt.2020.00717. PMC 7493620. PMID 32982805.
40. Correll CU, Cortese S, Croatto G, Monaco F, Krinitski D, Arrondo G, et al. (June 2021). "Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review". World Psychiatry. 20 (2): 244–275. doi:10.1002/wps.20881. PMC 8129843. PMID 34002501.
41. Wilde MI, Plosker GL, Benfield P (November 1993). "Fluvoxamine. An updated review of its pharmacology, and therapeutic use in depressive illness". Drugs. 46 (5): 895–924. doi:10.2165/00003495-199346050-00008. PMID 7507038. S2CID 195691900.
42. Seibell PJ, Hamblin RJ, Hollander E. Obsessive-compulsive disorder: Overview and standard treatment strategies. Psychiatric Annals. 2015 Jun 1;45(6):297-302.
43. Rivas-Vazquez, R.A. and Blais, M.A., 1997. Selective serotonin reuptake inhibitors and atypical antidepressants: A review and update for psychologists. Professional Psychology: Research and Practice, 28(6), p.526.
44. Middleton, R., Wheaton, M.G., Kayser, R. and Simpson, H.B., 2019. Treatment resistance in obsessive-compulsive disorder. Treatment resistance in psychiatry: risk factors, biology, and management, pp.165-177.
45. Ninan PT, Koran LM, Kiev A, Davidson JR, Rasmussen SA, Zajecka JM, Robinson DG, Crits-Christoph P, Mandel FS, Austin C. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial. J Clin Psychiatry. 2006 Jan;67(1):15-22. doi: 10.4088/jcp.v67n0103. PMID 16426083.
46. "Psychopharmacology Institute". psychopharmacologyinstitute.com.
47. Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007 Jul;164(7 Suppl):5-53. PMID 17849776.
48. Figgitt, D.P. and McClellan, K.J., 2000. Fluvoxamine: an updated review of its use in the management of adults with anxiety disorders. Drugs, 60, pp.925-954.
49. Taylor D, Paton C, Shitij K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.
50. "Faverin 100 mg film-coated tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Abbott Healthcare Products Limited. 14 May 2013. Archived from the original on 21 October 2013. Retrieved 21 October 2013.
51. Szalavitz M (7 January 2011). "Top Ten Legal Drugs Linked to Violence". Time. Archived from the original on 21 September 2014. Retrieved 10 September 2014.
52. ^ Ciraulo DA, Shader RI (2011). Ciraulo DA, Shader RI (eds.). Pharmacotherapy of Depression (2nd ed.). Springer. p. 49. doi:10.1007/978-1-60327-435-7. ISBN 978-1-60327-435-7.
53. ^ Brunton L, Chabner B, Knollman B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
54. Baumann P (December 1996). "Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors". Clinical Pharmacokinetics. 31 (6): 444–469. doi:10.2165/00003088-199631060-00004. PMID 8968657. S2CID 31923953.
55. DeVane CL, Gill HS (1997). "Clinical pharmacokinetics of fluvoxamine: applications to dosage regimen design". The Journal of Clinical Psychiatry. 58 (Suppl 5): 7–14. PMID 9184622.
56. DeVane CL (1998). "Translational pharmacokinetics: current issues with newer antidepressants". Depression and Anxiety. 8 (Suppl 1): 64–70. doi:10.1002/(SICI)1520-6394(1998)8:1+<64::AID-DA10>3.0.CO;2-S. PMID 9809216. S2CID 22297498.
57. Bondy B, Spellmann I (March 2007). "Pharmacogenetics of antipsychotics: useful for the clinician?". Current Opinion in Psychiatry. 20 (2): 126–130. doi:10.1097/YCO.0b013e328017f69f. PMID 17278909. S2CID 23859992.
58. Kroon LA (September 2007). "Drug interactions with smoking". American Journal of Health-System Pharmacy. 64 (18): 1917–1921. doi:10.2146/ajhp060414. PMID 17823102.
59. Waknine Y (13 April 2007). "Prescribers Warned of Tizanidine Drug Interactions". Medscape News. Medscape. Archived from the original on 21 February 2013. Retrieved 1 February 2008.
60. "Fluvoxamine (Oral Route) Precautions". Mayo Clinic. Archived from the original on 6 March 2019. Retrieved 2 November 2018.
61. ^ Hemeryck A, Belpaire FM (February 2002). "Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update". Current Drug Metabolism. 3 (1): 13–37. doi:10.2174/1389200023338017. PMID 11876575.
62. "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". FDA. 26 May 2021. Archived from the original on 4 November 2020. Retrieved 25 December 2020.
63. Spina E, de Leon J (January 2007). "Metabolic drug interactions with newer antipsychotics: a comparative review". Basic & Clinical Pharmacology & Toxicology. 100 (1): 4–22. doi:10.1111/j.1742-7843.2007.00017.x. PMID 17214606.
64. Bogetto F, Bellino S, Vaschetto P, Ziero S (October 2000). "Olanzapine augmentation of fluvoxamine-refractory obsessive-compulsive disorder (OCD): a 12-week open trial". Psychiatry Research. 96 (2): 91–98. doi:10.1016/s0165-1781(00)00203-1. PMID 11063782. S2CID 43395897.
65. Hiemke C, Peled A, Jabarin M, Hadjez J, Weigmann H, Härtter S, et al. (October 2002). "Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects". Journal of Clinical Psychopharmacology. 22 (5): 502–506. doi:10.1097/00004714-200210000-00010. PMID 12352274. S2CID 38073367.
66. "Movox". NPS MedicineWise. 23 November 2020. Archived from the original on 4 November 2022. Retrieved 4 November 2022.
67. Dinis-Oliveira RJ (November 2017). "Metabolic profile of oxazepam and related benzodiazepines: clinical and forensic aspects". Drug Metabolism Reviews. 49 (4): 451–463. doi:10.1080/03602532.2017.1377223. PMID 28903606. S2CID 4528255.
68. Raouf M (2016). Fudin J (ed.). "Benzodiazepine Metabolism and Pharmacokinetics" (PDF). Archived (PDF) from the original on 12 July 2018. Retrieved 16 September 2018.
69. Peppers MP (1996). "Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease". Pharmacotherapy. 16 (1): 49–57. doi:10.1002/j.1875-9114.1996.tb02915.x. PMID 8700792. S2CID 1389910.
70. "fluvoxamine maleate: PRODUCT MONOGRAPH" (PDF). 2016. Archived (PDF) from the original on 16 September 2018. Retrieved 16 September 2018.
71. "Luvox Data Sheet" (PDF). Medsafe, New Zealand. 2017. Archived from the original (PDF) on 29 March 2018. Retrieved 16 September 2018.
72. "Faverin Tablets". NPS MedicineWise. July 2022. Archived from the original on 4 November 2022. Retrieved 4 November 2022.
73. Suzuki Y, Shioiri T, Muratake T, Kawashima Y, Sato S, Hagiwara M, et al. (April 2003). "Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles". European Journal of Clinical Pharmacology. 58 (12): 829–833. doi:10.1007/s00228-003-0563-9. PMID 12698310. S2CID 32559753.
74. Gerlach M, Warnke A, Greenhill L (2014). Psychiatric Drugs in Children and Adolescents: Basic Pharmacology and Practical Applications. Springer-Verlag Wien. p. 131. ISBN 978-3-7091-1500-8. Archived from the original on 10 January 2023. Retrieved 21 May 2020.
75. Fleishaker JC, Hulst LK (1994). "A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine". European Journal of Clinical Pharmacology. 46 (1): 35–39. doi:10.1007/bf00195913. PMID 8005185. S2CID 2161450.
76. Obach RS, Ryder TF (August 2010). "Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics". Drug Metabolism and Disposition. 38 (8): 1381–1391. doi:10.1124/dmd.110.034009. PMID 20478852. S2CID 8421997.
77. Pandi-Perumal SR, Spence DW, Verster JC, Srinivasan V, Brown GM, Cardinali DP, et al. (12 April 2011). "Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications". Journal of Central Nervous System Disease. 3: 51–65. doi:10.4137/JCNSD.S1611. PMC 3663615. PMID 23861638.
78. ^ Anttila AK, Rasanen L, Leinonen EV (October 2001). "Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold". The Annals of Pharmacotherapy. 35 (10): 1221–1223. doi:10.1345/aph.1A014. PMID 11675851. S2CID 44807359.
79. Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ (April 2004). "Fluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction". Clinical Pharmacology and Therapeutics. 75 (4): 331–341. doi:10.1016/j.clpt.2003.12.005. PMID 15060511. S2CID 25781307.
80. Perucca E, Gatti G, Spina E (September 1994). "Clinical pharmacokinetics of fluvoxamine". Clinical Pharmacokinetics. 27 (3): 175–190. doi:10.2165/00003088-199427030-00002. PMID 7988100. S2CID 22472247.
81. Zanardi R, Serretti A, Rossini D, Franchini L, Cusin C, Lattuada E, et al. (September 2001). "Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression". Biological Psychiatry. 50 (5): 323–330. doi:10.1016/s0006-3223(01)01118-0. PMID 11543734. S2CID 22692759.
82. Sluzewska A, Szczawinska K (May 1996). "The effects of pindolol addition to fluvoxamine and buspirone in chronic mild stress model of depression". Behavioural Pharmacology. 7: 105.
83. Mundo E, Guglielmo E, Bellodi L (September 1998). "Effect of adjuvant pindolol on the antiobsessional response to fluvoxamine: a double-blind, placebo-controlled study". International Clinical Psychopharmacology. 13 (5): 219–224. doi:10.1097/00004850-199809000-00005. PMID 9817627. S2CID 23946424.
84. Belpaire FM, Wijnant P, Temmerman A, Rasmussen BB, Brøsen K (May 1998). "The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors". European Journal of Clinical Pharmacology. 54 (3): 261–264. doi:10.1007/s002280050456. PMID 9681670. S2CID 28105445.
85. Xu ZH, Xie HG, Zhou HH (October 1996). "In vivo inhibition of CYP2C19 but not CYP2D6 by fluvoxamine". British Journal of Clinical Pharmacology. 42 (4): 518–521. doi:10.1046/j.1365-2125.1996.45319.x. PMC 2042705. PMID 8904628.
86. Belpaire FM, Wijnant P, Tammerman A, Bogaert M, Rasmussen B, Brosen K (1997). "Inhibition of the oxidative metabolism of metoprolol by selective serotonin reuptake inhibitors in human liver microsomes". Fundamental and Clinical Pharmacology. 2 (11): 147.
87. van Harten J (1995). "Overview of the pharmacokinetics of fluvoxamine". Clinical Pharmacokinetics. 29 (Suppl 1): 1–9. doi:10.2165/00003088-199500291-00003. PMID 8846617. S2CID 71812133.
88. Muscatello MR, Spina E, Bandelow B, Baldwin DS (May 2012). "Clinically relevant drug interactions in anxiety disorders". Human Psychopharmacology. 27 (3): 239–253. doi:10.1002/hup.2217. PMID 22311403. S2CID 11592004.
89. Szegedi A, Wetzel H, Leal M, Härtter S, Hiemke C (June 1996). "Combination treatment with clomipramine and fluvoxamine: drug monitoring, safety, and tolerability data". The Journal of Clinical Psychiatry. 57 (6): 257–264. PMID 8666564.
90. Hardy NE, Walkup JT (November 2021). "Clomipramine in Combination with Fluvoxamine: A Potent Medication Combination for Severe or Refractory Pediatric OCD". Journal of the Canadian Academy of Child and Adolescent Psychiatry. 30 (4): 273–277. PMC 8561855. PMID 34777510.
91. Ishikawa M, Ishiwata K, Ishii K, Kimura Y, Sakata M, Naganawa M, et al. (October 2007). "High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using SA4503". Biological Psychiatry. 62 (8): 878–883. doi:10.1016/j.biopsych.2007.04.001. PMID 17662961. S2CID 728565.
92. Schatzberg AF, Nemeroff CB (2009). The American Psychiatric Publishing textbook of psychopharmacology (4th ed.). Arlington, VA: American Psychiatric Pub. p. 354. ISBN 978-1-585-62386-0. OCLC 320111564.
93. Yahata M, Chiba K, Watanabe T, Sugiyama Y (September 2017). "Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma Concentration of Unbound Drugs, and Their Profiles for Substrates of Transporters". Journal of Pharmaceutical Sciences. 106 (9): 2345–2356. doi:10.1016/j.xphs.2017.05.007. PMID 28501470.
94. ^ Hashimoto K (September 2009). "Sigma-1 receptors and selective serotonin reuptake inhibitors: clinical implications of their relationship". Central Nervous System Agents in Medicinal Chemistry. 9 (3): 197–204. doi:10.2174/1871524910909030197. PMID 20021354.
95. Hindmarch I, Hashimoto K (April 2010). "Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered". Human Psychopharmacology. 25 (3): 193–200. doi:10.1002/hup.1106. PMID 20373470. S2CID 26491662.
96. Uzunova V (17 March 1998). "Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine". Proceedings of the National Academy of Sciences of the United States of America. 95 (6): 3239–3244. Bibcode:1998PNAS...95.3239U. doi:10.1073/pnas.95.6.3239. PMC 19726. PMID 9501247.
97. Hrdina PD (July 1991). "Pharmacology of serotonin uptake inhibitors: focus on fluvoxamine". Journal of Psychiatry & Neuroscience. 16 (2 Suppl 1): 10–18. PMC 1188307. PMID 1931931.
98. ^ Sittig's Pharmaceutical Manufacturing Encyclopedia (PDF) (3rd ed.). William Andrew. 2008. p. 1699. ISBN 978-0-8155-1526-5. Archived from the original (PDF) on 14 October 2013. Retrieved 17 October 2013.
99. Leslie LK, Newman TB, Chesney PJ, Perrin JM (July 2005). "The Food and Drug Administration's deliberations on antidepressant use in pediatric patients". Pediatrics. 116 (1): 195–204. doi:10.1542/peds.2005-0074. PMC 1550709. PMID 15995053.
100. "Brand Index―Fluvoxamine India". Archived from the original on 19 October 2013. Retrieved 18 October 2013.
101. Omori IM, Watanabe N, Nakagawa A, Cipriani A, Barbui C, McGuire H, et al. (March 2010). "Fluvoxamine versus other anti-depressive agents for depression". The Cochrane Database of Systematic Reviews. 2013 (3): CD006114. doi:10.1002/14651858.CD006114.pub2. PMC 4171125. PMID 20238342.
102. "OCD Medication". Archived from the original on 14 October 2013. Retrieved 17 October 2013.
103. "Fluvoxamine Product Monograph" (PDF). 1999. Archived (PDF) from the original on 27 October 2020. Retrieved 15 September 2018.
104. "Luvox Approved For Obsessive Compulsive Disorder in Children and Teens". Archived from the original on 16 January 2009. Retrieved 8 February 2014.
105. Higuchi T, Briley M (February 2007). "Japanese experience with milnacipran, the first serotonin and norepinephrine reuptake inhibitor in Japan". Neuropsychiatric Disease and Treatment. 3 (1): 41–58. doi:10.2147/nedt.2007.3.1.41. PMC 2654524. PMID 19300537.
106. Wishart DS, Guo AC, Oler E, Wang F, Anjum A, Peters H, et al. "Showing metabocard for Fluvoxamine (HMDB0014322)". Human Metabolome Database, HMDB. 5.0.
107. "Solvay's Fluvoxamine maleate is first drug approved for the treatment of social anxiety disorder in Japan". Archived from the original on 15 September 2018. Retrieved 15 September 2018.
108. Walker R, Whittlesea C, eds. (2007) . Clinical Pharmacy and Therapeutics (4th ed.). Edinburgh: Churchill Livingstone Elsevier. ISBN 978-0-7020-4293-5.
109. "Fluvoxamine". www.drugbank.ca. Archived from the original on 4 November 2019. Retrieved 22 October 2019.
110. Bhuta S, Khokher W, Kesireddy N, Iftikhar S, Beran A, Mhanna M, et al. (2022). "Fluvoxamine in Nonhospitalized Patients With Acute COVID-19 Infection and the Lack of Efficacy in Reducing Rates of Hospitalization, Mechanical Ventilation, and Mortality in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis". American Journal of Therapeutics. 29 (3): e298 – e304. doi:10.1097/MJT.0000000000001496. PMID 35383578. S2CID 247978477.
111. Asadi Anar M, Foroughi E, Sohrabi E, Peiravi S, Tavakoli Y, Kameli Khouzani M, et al. (2022). "Selective serotonin reuptake inhibitors: New hope in the fight against COVID-19". Frontiers in Pharmacology. 13: 1036093. doi:10.3389/fphar.2022.1036093. PMC 9748354. PMID 36532776.
112. Hu B, Huang S, Yin L (January 2021). "The cytokine storm and COVID-19". Journal of Medical Virology. 93 (1): 250–256. doi:10.1002/jmv.26232. PMC 7361342. PMID 32592501.
113. "FDA declines to authorize common antidepressant as COVID treatment". Reuters. 16 May 2022. Archived from the original on 17 May 2022. Retrieved 18 May 2022.
114. Memorandum Explaining Basis for Declining Request for Emergency Use Authorization of Fluvoxamine Maleate (PDF) (Memorandum). Food and Drug Administration. 16 May 2022. 4975580. Archived (PDF) from the original on 17 May 2022. This article incorporates text from this source, which is in the public domain.
115. Ingram I (17 November 2023). "Higher-Dose Fluvoxamine Fails for COVID Outpatients". MedPage Today. Archived from the original on 17 November 2023. Retrieved 4 December 2023.
116. Nyirenda JL, Sofroniou M, Toews I, Mikolajewska A, Lehane C, Monsef I, et al. (September 2022). "Fluvoxamine for the treatment of COVID-19". The Cochrane Database of Systematic Reviews (Systematic review). 2022 (9): CD015391. doi:10.1002/14651858.CD015391. PMC 9473347. PMID 36103313.
117. Wannigama DL, Hurst C, Phattharapornjaroen P, Hongsing P, Sirichumroonwit N, Chanpiwat K, et al. (April 2024). "Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial". eClinicalMedicine. 70: 102517. doi:10.1016/j.eclinm.2024.102517. PMC 10955208. PMID 38516100.
118. ^
     •  • Chia MA, Lorenzi AS, Ameh I, Dauda S, Cordeiro-Araújo MK, Agee JT, et al. (May 2021). "Susceptibility of phytoplankton to the increasing presence of active pharmaceutical ingredients (APIs) in the aquatic environment: A review". Aquatic Toxicology. 234. Elsevier: 105809. Bibcode:2021AqTox.23405809C. doi:10.1016/j.aquatox.2021.105809. PMID 33780670. S2CID 232419482.
     •  • Christensen AM, Faaborg-Andersen S, Ingerslev F, Baun A (January 2007). "Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans". Environmental Toxicology and Chemistry. 26 (1). John Wiley & Sons, Inc. (Society of Environmental Toxicology and Chemistry (SETAC)): 85–91. doi:10.1897/06-219R.1. PMID 17269464. S2CID 6562531.

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