NSRIs

Reboxetine is a norepinephrine selective reuptake inhibitor (NSRI). Based on in vitro studies, reboxetine does not block the reuptake of either dopamine or serotonin. 

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. 

This antidepressant can interact with other drugs via its two mechanisms of action serotonin and NE uptake inhibition. The former action means that the same pharmacodynamic interactions will occur with venlafaxine as with SSRIs, including the serotonin syndrome. At higher doses, venlafaxine is also prone to the same pharmacodynamic interactions as NSRIs such as secondary amine TCAs like desipramine and with newer NSRIs such reboxetine. Thus, the combination of high-dose venlafaxine plus an MAOl could produce a hypertensive crisis as well as the serotonin syndrome. 

Consistent with its most potent known mechanism of action, bupropion is an indirect dopamine agonist via its inhibition of the neuronal uptake pump for dopamine (503, 504). Hence, bupropion can potentiate the effects of other dopamine agonists. This interaction does not typically cause serious problems and may even be advantageous in specific instances such as patients with Parkinson s disease plus a depressive disorder. Because of its ability to inhibit NE uptake, bupropion would be prone to the same interactions as NSRIs such as desipramine and reboxetine. 

These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro see the appendix). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft. A number of other antidepressants are potent nonselective serotonin reuptake inhibitors (NSRIs). These include the atypical venlafaxine (Effexor) and the tricyclic clomipramine (Anafra-nil). Nefazodone (Serzone) has been withdrawn from the market due to liver damage. 

While usually examined as separate classes of antidepressants, the NSRIs like Effexor also share many characteristics with the SSRIs, including the capacity to induce stimulation, anxiety, agitation, and mania. 

Venlafaxine (Effexor), approved by the FDA in December 1993, was described in more detail early in this chapter. It is one of the newer antidepressants implicated in causing suicidality. It is a NSRI that also strongly inhibits the reuptake of epinephrine. Its profile is very similar to the SSRIs in producing stimulation, including anxiety, nervousness, insomnia, anorexia, and weight loss. It causes the various emotional and behavioral abnormalities that go along with stimulation, such as agitation and mania, and has been associated with hostility, paranoid reaction, psychotic depression, and psychosis. It can cause hypertension. 

Fourth, as an expert in criminal and civil cases, I have studied the lives of many individuals who—under the influence of psychoactive drugs such as SSRIs, nonselective serotonin reuptake inhibitors (NSRIs), and benzodiazepines—have committed acts of aggression that were wholly alien to their character and antithetical to their prior behavior. It is, of course, well known that the illegal use of stimulant drugs, such as meth-amphetamine and cocaine, can be associated with paranoid reactions and violence. 

NSRI Antidepressants. Nonselective serotonin reuptake inhibitors (NSRI)also block the reuptake of norepinephrine. Several of the old tricyclic antidepressants belong in this category. Imipramine and desipramine reduce REM sleep because of the increased norepinephrine levels at postsynaptic receptors caused by reduced reuptake of norepinephrine. 

Norepinephrine-selective reuptake inhibitors (NSRIs NaRIs) Reboxetine (21)... 

Figure 8. Structures of the SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), the NSRI reboxetine, and the SNRI venlafaxine.

Scientists at Lilly Research Laboratories synthesized more than 50 phenoxypropylamines derived from the antihistamine diphenhydramine (Benadryl) before discovering fluoxetine (21,22) (Fig. 21.2). The first of these compounds was nisoxetine, a potent SNRI (see Fig. 21.8) that was clinically developed but never marketed. Other derivatives that have since been marketed by Lilly include atomoxetine (a SNRI) and duloxetine (a NSRI). 

The following guidelines apply to all antidepressants, inoluding SSRIs, SNRIs, and NE/serotonin reuptake inhibitors (NSRIs) ... 

Nikkan Kogyo Shimbun (Business Technology Daily News) (13 Jan 2015). http //nsri. nssmc.eom/assets/files/japamnelal-20150113 01.pdf... 

Relative renal failure, hepatic failure, patients with seizure disorders, patients treated with SSRIs and NSRIs, patients taking coumadin or warfarin (dose reduction are required). 

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