Reboxetine adverse effects

Reboxetine is generally well tolerated. Compared to placebo, most frequently reported adverse effects in the reboxetine group are dry mouth and insomnia (Versi-ani et ah, 2000). There are also reports of tremor, hypertension, and somnolence in association with reboxetine use. Reboxetine has a wide therapeutic index and does not appear to increase the QTc or alter cardiac conduction. 

As a results of these studies, clinicians have proposed that switching to reboxetine or bupropion might a useful strategy given that these antidepressants share the ability with desipramine and imipramine to block NE uptake. Nevertheless, only one small open label study has been done to test this possibility ( 365). If bupropion is to be used in patients switched from an ineffective trial of fluoxetine, the dose should be kept low for several weeks to allow for the clearance of fluoxetine and norfluoxetine. Case reports indicate that fluoxetine can elevate levels of the active metabolites of bupropion, which, in turn, could mediate an increase risk of adverse effects (366). 

As with most data for reboxetine, this information primarily comes from summary papers rather than primary sources (473, 474). With this caveat, the adverse-effect profile of reboxetine is consistent with its pharmacology as an NSRI. Thus, it is similar to that of desipramine and maprotiline but without the risk of serious CNS (i.e., seizures, delirium) or cardiac (i.e., conduction disturbances) toxicity. The most common adverse effects of reboxetine are dry mouth, constipation, urinary hesitancy, increased sweating, insomnia, tachycardia, and vertigo. Whereas the first three adverse effects are commonly called anticholinergic, they are well known to occur with sympathomimetic drugs as well. In other words, these effects can be either the result of decreased cholinergic tone or increased sympathetic tone, although they tend to be more severe with the former than the latter. In contrast to TCAs, reboxetine does not directly interfere with intracardiac conduction. The tachycardia produced by reboxetine, however, can be associated with occasional atrial or ventricular ectopic beats in elderly patients. 

In terms of comparative adverse effects, imipramine produces more dry mouth than reboxetine probably because imipramine blocks muscarinic cholinergic receptors as well as inhibiting NE uptake (47,5). Imipramine also produces more tremulousness and hypotension than reboxetine. Consistent with their pharmacology, fluoxetine produces more serotonin-mediated adverse effects than does reboxetine (i.e., nausea, loose stools, and somnolence), whereas reboxetine causes more sympathomimetic adverse effects (476). To date, reboxetine has not been reported to cause an increased incidence of laboratory abnormalities. 

The loss of weight in this patient did not seem to be due her to psychiatric condition. The authors speculated that reboxetine might have some serotonergic activity, which could have accounted for a reduction in appetite and concomitant weight loss. However, drugs that potentiate noradrenaline activity can also reduce hunger, so this adverse effect could be due to the well characterized noradrenergic effects of reboxetine. 

One of the adverse effects of reboxetine is difficulty in passing urine (SEDA-21,13). Eight patients taking reboxetine (4-8 mg/day) had troublesome urinary hesitancy (5). They were successfully treated with tamsulosin (0.4 mg/day), and in two patients tamsulosin was withdrawn after 2 weeks without recurrence of the urinary symptoms. Reboxetine is a selective noradrenaline reuptake inhibitor and may therefore produce urinary symptoms by activating i-adrenoceptors in the bladder, which tamsulosin would be expected to reverse. However, tamsulosin is also effective for urinary symptoms caused by other mechanisms, for example benign prostatic hyperplasia. Whether its apparent effectiveness in reboxetine -induced dysuria represents specific pharmacological antagonism is therefore uncertain. 

Reboxetine is metabolized by CYP3A4. In 11 healthy volunteers ketoconazole, an inhibitor of CYP3A4, increased the plasma AUC of reboxetine by about 50% and prolonged the half-life (7). The adverse effects profile of reboxetine was not altered by ketoconazole, but the... 

Reboxetine is a nontricyclic SNRI in which the propylamine side chain of the TCAs is constrained into a morpholine ring (Fig. 21.8). It is a potent and selective ligand for the NET, with a mechanism of action is similar to that of desipramine. Reboxetine is used for the treatment of major depressive disorders. It is a chiral compound that is marketed as a racemic mixture of R,R- and S,S-reboxetine. The antidepressant activity for reboxetine appears to reside with the S,S-(+)-enantiomer, which has approximately twofold the inhibition potency of the R,R-enantiomer (42). It is well tolerated, with different adverse-event profiles, and it appears to be at least as effective as the SSRIs in the treatment of depressive illness. Currently, it is available only in Europe and is under U.S. FDA review. It preferentially inhibits the reuptake of NE (5-FIT NE ratio, 8). Reboxetine is not metabolized by the polymorphic isoforms, CYP2D6 or CYP2C19, and may offer a valuable alternative to the secondary amine TCAs in the treatment of major depression. Reboxetine is likely to become a promising alternative for patients who have failed treatment with or do not tolerate serotonergic antidepressants. Reboxetine has been shown to be effective and well tolerated in the treatment of panic... 

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