Desipramine side effects profile

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

The SSRIs, due to their superior tolerability and side-effect profile, are currently considered the first-line treatment for the long-term treatment of dysthymic disorder. In the case of failure or intolerance to SSRIs, the TCAs amitriptyline, desipramine, and imipramine or the reversible MAOl moclobemide should be tried. The reversible MAOl phenelzine has shown superior effectiveness to imipramine in one double-blind study. However, it should be reserved as third-line therapy due to its less-favorable side-effect profile and dietary restrictions. 

Alternative choices for TCAs include amitriptyline, nortriptyline, or desipramine. All of these agents have been shown to be effective in the treatment of neuropathic pain. Consequently, the choice is based on the drug s side-effect profile. In this regard, desipramine is not associated with sedation, as it lacks antihistaminic effects. Moreover, the incidence of anticholinergic effects is lower when compared to amitriptyline. Alternatively, nortriptyline may be used if lack of... 

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... 

---