Reboxetine
Reboxetine (brand names: Edronax (AU, IE, IL, NZ, ZA, UK), Prolift (AR, BR, CL, VE)) 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.

# 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.
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." 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.
According to a systematic review and meta-analysis by IQWiG, including unpublished data, published data on reboxetine overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also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.

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

## 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 and long-term and in both children/adolescents and adults.

## Other uses
A case series and open-label pilot study have demonstrated the efficacy of reboxetine in treating bulimia nervosa. Reboxetine's efficacy in treating therapy-resistant paediatric nocturnal enuresis. A pilot study demonstrated the efficacy of reboxetine in the treatment of narcolepsy. Reboxetine may also attenuate olanzapine-induced weight gain.

# Adverse effects
Incidence of adverse effects
Very common (>10% incidence) adverse effects include:
- Insomnia
- Nausea
- Excessive sweating
- Dry mouth
- Constipation
Common (1-10%) adverse effects include:
- Appetite loss
- Agitation
- Anxiety
- Headache
- Dizziness
- Paraesthesia
- Akathisia
- Dysgeusia
- Accommodation disorder
- Tachycardia
- Palpitations
- Vasodilatation
- Hypotension (low blood pressure)
- Hypertension (high blood pressure)
- Vomiting
- Rash
- Sensation of incomplete bladder emptying
- Urinary tract infection
- Dysuria (painful or very difficult urination)
- Urinary retention
- Chills
- Erectile dysfunction
- Ejaculatory pain
- Ejaculatory delay
Uncommon (0.1-1%) adverse effects include:
- Mydriasis
- Vertigo
Rare (<0.1%) adverse effects include:
- Glaucoma
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.

## Contraindications
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.

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

## Overdose
Reboxetine is considered a relatively low-risk antidepressant in overdose. The symptoms are as follows:
- Sweating
- Tachycardia
- Changes in blood pressure

# Pharmacology
Pharmacodynamics
Reboxetine is a fairly selective norepinephrine reuptake inhibitor (NRI) with approximately 20.4x selectivity for the norepinephrine transporter over the serotonin transporter. Despite this selectivity reboxetine does slightly inhibit the reuptake of serotonin at therapeutic doses.
Reboxetine has been found to inhibit both brain and cardiac GIRKs, a characteristic it shares with the norepinephrine reuptake inhibitor atomoxetine.
Binding profile
Pharmacokinetics
Both the (R,R)-() and (S,S)-(+)-enantiomers of reboxetine are predominantly metabolized by the CYP3A4 isoenzyme.
The primary metabolite of reboxetine is O-desethylreboxetine, and there are also three minor metabolitesPhenol A, Phenol B, and UK1, Phenol B being the most minor.

# Chemistry
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.

# 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):
- Davedax (IT)
- Edronax (AU, AT, BE, CZ, DK, FI, DE, IE, IL, IT, MX, NZ, NO, PH, PL, PT, RU, ZA, SE, CH, TH, TR, UK)
- Irenor (ES)
- Norebox (ES)
- Prolift (AR, BR, CL, VE)
- Solvex (DE)
- Yeluoshu (CN)
- Zuolexin (CN)