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Clinical data
Trade namesDavedax, Edronax, Narebox, Prolift, Solvex, Yeluoshu, Zuolexin
Routes of
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Protein binding97-98%[1][2]
MetabolismHepatic, CYP3A4-mediated[1]
Elimination half-life12-12.5 hours[1][2]
ExcretionRenal (78%; 9-10% unchanged)[1][2]
CAS Number
PubChem CID
E number{{#property:P628}}
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Chemical and physical data
Molar mass313.391 g/mol
3D model (JSmol)
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Reboxetine (brand names: Edronax (AU, IE, IL, NZ, ZA, UK), Prolift (AR,† BR, CL, VE†))[3] is a drug of the norepinephrine reuptake inhibitor class, marketed as an antidepressant by Pfizer for use in the treatment of unipolar depression, although it has also been used off-label for panic disorder and ADHD. It is approved for use in many countries worldwide, but has not been approved for use in the United States. Although its efficacy as an antidepressant has been challenged in multiple published reports, its popularity has continued to increase.[4]

Medical uses

Major depressive disorder

There has been much debate as to whether reboxetine is more efficacious than placebo into the treatment of depression. According to a 2009 meta-analysis of 12 second-generation antidepressants, reboxetine was no more effective than placebo, and was "significantly less" effective, and less acceptable, than the other drugs in treating the acute-phase of adults with unipolar major depression.[5]

The British MHRA said in September 2011 that the study had several limitations, and that "Overall the balance of benefits and risks for reboxetine remains positive in its authorised indication."[6] A UK and Europe-wide review of available efficacy and safety data has confirmed that reboxetine has benefit over placebo in its authorised indication. Efficacy was clearly shown in patients with severe or very severe depression.[6]

According to a systematic review and meta-analysis by IQWiG, including unpublished data, published data on reboxetine overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also underestimated harm, concluding that reboxetine was an ineffective and potentially harmful antidepressant. The study also showed that nearly three quarters of the data on patients who took part in trials of reboxetine were not published by Pfizer until now.[4]

Panic disorder

In a randomised double-blind placebo-controlled trial reboxetine significantly improved the symptoms of panic disorder.[7] Another randomised controlled trial that compared paroxetine to reboxetine found that paroxetine significantly outperformed reboxetine as a treatment for panic disorder.[8] Despite this discouraging finding an open-label trial examining the efficacy of reboxetine in SSRI-resistant panic disorder demonstrated significant benefit from reboxetine treatment.[9]

Attention deficit hyperactivity disorder

Numerous clinical trials have provided support for the efficacy of reboxetine in the treatment of attention deficit hyperactivity disorder (ADHD) in both the short[10][11][12][13] and long-term[14][15] and in both children/adolescents[11][12][14][15] and adults.[10][13]

Other uses

A case series and open-label pilot study have demonstrated the efficacy of reboxetine in treating bulimia nervosa.[16][17] Reboxetine's efficacy in treating therapy-resistant paediatric nocturnal enuresis.[18] A pilot study demonstrated the efficacy of reboxetine in the treatment of narcolepsy.[19] Reboxetine may also attenuate olanzapine-induced weight gain.[20]

Adverse effects

Incidence of adverse effects[21][22]

Very common (>10% incidence) adverse effects include:

  • Insomnia
  • Nausea
  • Excessive sweating
  • Dry mouth
  • Constipation

Common (1-10%) adverse effects include:

Uncommon (0.1-1%) adverse effects include:

Rare (<0.1%) adverse effects include:

Unknown frequency adverse effects include:

  • Hyponatraemia (low blood sodium)
  • Aggressive behaviour
  • Hallucination
  • Suicidal Ideation/behaviour
  • Increased intraocular pressure
  • Peripheral coldness
  • Raynaud`s phenomenon
  • Allergic dermatitis
  • Testicular pain
  • Irritability

Overall in the aforementioned 2009 meta-analysis reboxetine was significantly less well-tolerated than the other 11 second-generation antidepressants compared in the analysis.[5]


Reboxetine is contraindicated in narrow-angle glaucoma, cardiovascular disease, epilepsy, bipolar disorder, urinary retention, prostatic hypertrophy, patients concomitantly on MAOIs and those hypersensitive to reboxetine or any of its excipients.[1][23]


Because of its reliance on CYP3A4, reboxetine O-desethylation is markedly inhibited by papaverine and ketoconazole.[24] It weakly inhibits CYP2D6 and CYP3A4.[21] Reboxetine is an intermediate-level inhibitor of P-glycoprotein, which gives it the potential to interact with ciclosporin, tacrolimus, paroxetine, sertraline, quinidine, fluoxetine, fluvoxamine.[25]


Reboxetine is considered a relatively low-risk antidepressant in overdose.[26] The symptoms are as follows:[26]

  • Sweating
  • Tachycardia
  • Changes in blood pressure



Reboxetine is a fairly selective norepinephrine reuptake inhibitor (NRI) with approximately 20.4x selectivity for the norepinephrine transporter over the serotonin transporter.[27] Despite this selectivity reboxetine does slightly inhibit the reuptake of serotonin at therapeutic doses.[22]

Reboxetine has been found to inhibit both brain and cardiac GIRKs, a characteristic it shares with the norepinephrine reuptake inhibitor atomoxetine.[28]

Binding profile[29][30]

Protein Ki (nM)
SERT 273.5
NET 13.4
DAT 11500
5-HT1A >10000
5-HT1B >10000
5-HT1D >10000
5-HT2A >10000
5-HT2C 457
α1A 11900
α2A >10000
D2 >10000
D3 >10000
mAChRs 6700
H1 312


Both the (R,R)-(–) and (S,S)-(+)-enantiomers of reboxetine are predominantly metabolized by the CYP3A4 isoenzyme.[24] The primary metabolite of reboxetine is O-desethylreboxetine, and there are also three minor metabolites—Phenol A, Phenol B, and UK1, Phenol B being the most minor.[24]


Reboxetine has two chiral centers. Thus, four stereoisomers may exist, the (R,R)-, (S,S)-, (R,S)-, and (S,R)-isomers. The active ingredient of reboxetine is a racemic mixture of two enantiomers, the (R,R)-(–)- and (S,S)-(+)-isomer.[31]


Society and culture

Brand names

Edronax is the brand name of reboxetine in every English-speaking country that has approved it for clinical use. Brand names include (where † denotes a product that is no longer marketed):[3]

  • Norebox (ES)
  • Solvex (DE)
  • Yeluoshu (CN)
  • Zuolexin (CN)

See also

Notes and references

  1. 1.0 1.1 1.2 1.3 1.4 1.5 "PRODUCT INFORMATION EDRONAX® Reboxetine mesilate" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 17 October 2012. Retrieved 10 November 2013.
  2. 2.0 2.1 2.2 2.3 Holm, KJ; Spencer, CM (July 1999). "Reboxetine". CNS Drugs. 12 (1): 65–83. doi:10.2165/00023210-199912010-00006.
  3. 3.0 3.1 Reboxetine Mesilate. Martindale: The Complete Drug Reference. The Royal Pharmaceutical Society of Great Britain. 8 November 2011. Retrieved 10 November 2013.
  4. 4.0 4.1 Eyding, D; Lelgemann, M; Grouven, U, Härter, M; Kromp, M; Kaiser, T; Kerekes, MF; Gerken, M; Wieseler, B (October 2010). "Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials". BMJ. 341: c4737. doi:10.1136/bmj.c4737. PMC 2954275. PMID 20940209.
  5. 5.0 5.1 PMID 19185342 (PMID 19185342)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  6. 6.0 6.1 "Reboxetine: benefit-risk balance reviewed". Drug Safety Update. Medicines and Healthcare products Regulatory Agency. September 2011. Retrieved 10 November 2013.
  7. Versiani, M; Cassano, G; Perugi, G; Benedetti, A; Mastalli, L; Nardi, A; Savino, M (January 2002). "Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder". The Journal of Clinical Psychiatry. 63 (1): 31–37. doi:10.4088/JCP.v63n0107. PMID 11838623.
  8. Bertani, A; Perna, G; Migliarese, G; Di Pasquale, D; Cucchi, M; Caldirola, D; Bellodi, L (September 2004). "Comparison of the treatment with paroxetine and reboxetine in panic disorder: A randomized, single-blind study". Pharmacopsychiatry. 37 (5): 206–210. doi:10.1055/s-2004-832593.
  9. Dannon, PN; Iancu, I; Grunhaus, L (October 2002). "The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study". Human Psychopharmacology. 17 (7): 329–333. doi:10.1002/hup.421. PMID 12415550.
  10. 10.0 10.1 Hashemian, F; Mohammadian, S; Riahi, F; Ghaeli, P; Ghodsi, D (2011). "A comparison of the effects of reboxetine and placebo on reaction time in adults with Attention Deficit-Hyperactivity Disorder (ADHD)". Daru. 19 (3): 231–235. PMC 3232108. PMID 22615662.
  11. 11.0 11.1 Tehrani-Doost, M; Moallemi, S; Shahrivar, Z (April 2008). "An open-label trial of reboxetine in children and adolescents with attention-deficit/hyperactivity disorder". Journal of Child and Adolescent Psychopharmacology. 18 (2): 179–184. doi:10.1089/cap.2006.0034. PMID 18439114.
  12. 12.0 12.1 Ratner, S; Laor, N; Bronstein, Y; Weizman, A; Toren, P (May 2005). "Six-week open-label reboxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder". Journal of the American Academy of Child and Adolescent Psychiatry. 44 (5): 428–433. doi:10.1097/01.chi.0000155327.30017.8c. PMID 15843764.
  13. 13.0 13.1 Riahi, F; Tehrani-Doost, M; Shahrivar, Z; Alaghband-Rad, J (November 2010). "Efficacy of reboxetine in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled clinical trial". Human Psychopharmacology. 25 (7–8): 570–576. doi:10.1002/hup.1158. PMID 21312292.
  14. 14.0 14.1 Toren, P; Ratner, S; Weizman, A; Lask, M; Ben-Amitay, G; Laor, N (December 2007). "Reboxetine maintenance treatment in children with attention-deficit/hyperactivity disorder: a long-term follow-up study". Journal of Child and Adolescent Psychopharmacology. 17 (6): 803–812. doi:10.1089/cap.2006.0145. PMID 18315452.
  15. 15.0 15.1 Quintero, J; López-Muñoz, F; Alamo, C; Loro, M; García-Campos, N (November 2010). "Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study". Attention Deficit and Hyperactivity Disorders. 2 (3): 107–113. doi:10.1007/s12402-010-0027-x. PMID 21432596.
  16. El-Giamal, N; de Zwaan, M; Bailer, U; Lennkh, C; Schüssler, P; Strnad, A; Kasper, S (November 2000). "Reboxetine in the treatment of bulimia nervosa: a report of seven cases". International Clinical Psychopharmacology. 15 (6): 351–6. doi:10.1097/00004850-200015060-00006. PMID 11110011.
  17. Fassino, S; Daga, GA; Boggio, S; Garzaro, L; Pierò, A (September 2004). "Use of reboxetine in bulimia nervosa: a pilot study". Journal of Psychopharmacology. 18 (3): 423–428. doi:10.1177/026988110401800314. PMID 15358988.
  18. Nevéus, T (2006). "Reboxetine in therapy-resistant enuresis: results and pathogenetic implications". Scandinavian Journal of Urology and Nephrology. 40 (1): 31–34. doi:10.1080/00365590500407803. PMID 16452053.
  19. Larrosa, O; de la Llave, Y; Bario, S; Granizo, JJ; Garcia-Borreguero, D (May 2001). "Stimulant and anticataplectic effects of reboxetine in patients with narcolepsy: a pilot study". Sleep. 24 (3): 282–285. PMID 11322710.
  20. Poyurovsky, M; Isaacs, I; Fuchs, C; Schneidman, M; Faragian, S; Weizman, R; Weizman, A (February 2003). "Attenuation of olanzapine- induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study" (PDF). The American Journal of Psychiatry. 160 (2): 297–302. doi:10.1176/appi.ajp.160.2.297. PMID 12562576.
  21. 21.0 21.1 "Edronax 4mg Tablets". electronic Medicines Compendium. Pfitzer Limited. 12 July 2013. Retrieved 10 November 2013.
  22. 22.0 22.1 Template:Cite isbn
  23. Template:Cite isbn
  24. 24.0 24.1 24.2 Wienkers LC, Allievi C, Hauer MJ, Wynalda MA. (1999). "Cytochrome P-450-Mediated Metabolism of the Individual Enantiomers of the Antidepressant Agent Reboxetine in Human Liver Microsomes". Drug Metabolism & Disposition. 27 (11): 1334–1340. PMID 10534319.
  25. Weiss, J; Dormann, SM; Martin-Facklam, M; Kerpen, CJ; Ketabi-Kiyanvash, N; Haefeli, WE (2003). "Inhibition of P-glycoprotein by newer antidepressants". Journal of Pharmacology & Experimental Therapeutics. 305 (1): 197–204. doi:10.1124/jpet.102.046532. PMID 12649369.
  26. 26.0 26.1 Template:Cite isbn
  27. Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 10 November 2013.
  28. Kobayashi, T; Washiyama, K; Ikeda, K (Jun 2010). "Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine". Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 35 (7): 1560–9. doi:10.1038/npp.2010.27. PMC 3055469. PMID 20393461.
  29. Template:Cite isbn
  30. Roth, BL; Driscol, J. "PDSD Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 2014-03-31.
  31. Melloni P, Della Torre A, Lazzari E, Mazzini G and Meroni M (1985). "Configuration studies on 2-[alpha -(2-ethoxyphenoxy)benzyl]-morpholine FCE 20124". Tetrahedron. 41 (1): 1393–1399. doi:10.1016/S0040-4020(01)96541-X.
  32. Brenner, Eric; Baldwin, Ronald M.; Tamagnan, Gilles (2005). "Asymmetric Synthesis of (+)-(S,S)-Reboxetine via a New (S)-2-(Hydroxymethyl)morpholine Preparation". Organic Letters. 7 (5): 937–9. doi:10.1021/ol050059g. PMID 15727479.

External links

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