Norepinephrine-reuptake inhibitors side effects

Side effects, mainly due to serotonin reuptake inhibition include G1 upset, nervousness, and sexual dysfunction. SSRls are associated with an increased risk of falls. Hyponatraemia due to SIADH is an uncommon, but important side effect in elderly patients. Selective serotonin and norepinephrine reuptake inhibitors (S SNRls) such as venlafaxine and duloxetine are also useful in older patients. Other heterocyclic antidepressants of importance in older patients because of relative safety include bupro-prion and mirtazepine. They are reserved for patients with resistance to or intolerance of SSRls. Currently, trazodone is used mostly for sleep disturbance in depression in doses of 50-100 mg at bedtime. The monoamine oxidase inhibitors phenelzine. 

Switching from or addition of ofher norepinephrine reuptake inhibitors should be done with caution, as the additive pro-noradrenergic effects may enhance therapeutic actions in depression, but also enhance noradrenergically-mediated side effects... 

Venlafaxine (Effexor) is a new antidepressant that has been studied in the treatment of people who did not benefit from other antidepressants ("treatment-resistant") where it was often foimd to be effective. It is an effective first-line agent, and is the first of the newer antidepressants to be both a potent serotonin and norepinephrine reuptake inhibitor. Some studies suggest that it can produce benefits more quickly. Other than a tendency to produce a mild elevation of diastolic blood pressure, it has side effects similar to those of the SSRIs. Usual side effects from venlafaxine are nausea, anxiety, sedation, dizziness, blurred vision, and dry mouth. 

Nefazodone (Serzone), like venlafaxine, is a new antidepressant that affects multiple neurotransmitter systems. Like trazodone, nefazodone is a potent 5-HT2A receptor blocker. In addition, it is both a serotonin and norepinephrine reuptake inhibitor. The most common side effects are nausea, headache, anxiety, sedation, and dizziness. Its use is contraindicated with Seldane, Hismanal, and Propulsid, and there is a warning regarding its use with Xanax. 

Serotonin and norepinephrine reuptake inhibitors. The only member of this class which has received regulatory approval is venlafaxine (Effexor). Venlafaxine is a phenethylamine bicyclic derivative, chemically unrelated to tricyclic, tetracyclic or other available antidepressant agents. In a retrospective review of 35 consecutively treated overweight or obese outpatients with BED, venlafaxine 75-300 mg daily given for 1 to 43 weeks appeared to reduce the frequency of binge eating and to lower body weight (Malhotra et al. 2002). Reported side effects included dry mouth, sexual dysfunction, insomnia and nausea As there have thus far been no published randomised controlled trials, its place in the treatment of BED must remain uncertain. 

Legend s Major capacity for inducing side-effect Moderate capacity for inducing side-effect NARI Seiective noradrenaiine (norepinephrine) reuptake inhibitor... 

The selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of depression in the elderly. Compared with tricyciic antidepressants (TCAs), they are much safer in overdose and, for the most part, their side-effects are better tolerated. The antidepressants that have been shown, in controlled studies, to be effective in geriatric major depression are the SSRIs fluoxetine, paroxetine, and sertraline, the TCAs clomipramine and nortriptyline, and the serotonin and norepinephrine reuptake inhibitor (SNRi) venlafaxine. Given that most antidepressants are effective in the elderly, the choice of drug is based on its side-effect profile and its potential to interact with other medications. 

Until then, identifying the right drug for someone isn t about which drug will be most effective, but rather which side effect profile the person will best tolerate. The SSRIs in general have fewer side effects than the norepinephrine reuptake inhibitors. People often start with them. But most of the SSRIs are associated with impairment of sexual fiinction. So if that will be a major impediment to your life and relationships, then you might want to choose from another class of antidepressants. 

Serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g. duloxetine, venlafaxine and desvenlafax-ine) inhibit the reuptake of both serotonin and norepinephrine and are referred to as dual inhibitors or selective serotonin norepinephrine inhibitors . The SNRIs lack of anticholinergic side effects results in a distinct advantage over traditional TCAs [13,77,78]. For example, duloxetine is a potent, balanced inhibitor of serotonin and norepinephrine reuptake [79]. Venlafaxine inhibits serotonin reuptake at lower dosages and inhibits both serotonin and norepinephrine reuptake at higher dosages [70,80]. 

As we move forward with our discussion, we ll devote a section of this chapter to each of the key neurotransmitter systems that psychotropic medications interact with. We will discuss the following systems norepinephrine, dopamine, serotonin, GABA, acetylcholine, and histamine. Within each of the sections is a description of the effects that can be anticipated when a medication enhances the activity of that transmitter (reuptake inhibitors or agonists), and the effects to expect when a medication interferes (receptor antagonists) with the activity of that same transmitter. We will then describe strategies that can be implemented to help minimize and/or manage these side effects. 

Many inhibitors of the amine transporters for norepinephrine, dopamine, and serotonin are used clinically. Although specificity is not absolute, some are highly selective for one of the transporters. Many antidepressants, particularly the older tricyclic antidepressants can inhibit norepinephrine and serotonin reuptake to different degrees. This may lead to orthostatic tachycardia as a side effect. Some antidepressants of this class, particularly imipramine, can induce orthostatic hypotension presumably by their clonidine-like effect or by blocking 04 receptors, but the mechanism remains unclear. 

Reboxetine. Reboxetine (21) is a norepinephrine-selective reuptake inhibitor that lacks affinity for most of the monoamine receptors. It thus does not exhibit the typical side-effect profile of the tricyclics. Nevertheless, side effects include increased sweating, postural hypotension (leading to dizziness), dry mouth, constipation, blurred vision, impotence, and dysuria. Tachycardia and urinary retention have also been reported (59). There is no evidence of cardiotoxicity and sexual dysfunction seems to be rare. In contrast to some of the earlier tricyclics that are sedative, reboxetine is nonsedating and can cause insomnia (60,61).. 

This diverse collection has been grouped together mostly because they do not operate as selective serotonin reuptake inhibitors. Instead, each one interacts differently with neurotransmitters that are tied to depression serotonin, norepinephrine, or dopamine. For instance, one of the more popular non-SSRIs, Effexor (venlafaxine), selectively inhibits the uptake of serotonin and norepinephrine, acting on the same molecular machinery as tricyclic antidepressants (TCAs). But, in contrast to TCAs, Effexor shows no affinity for other neurotransmitter receptors and thus has far fewer side effects than the... 

As of yet, the pharmacological actions of Serzone and Desyrel are not completely understood. Like SSRIs they inhibit serotonin uptake. There is also evidence that they antagonize 5-HT2 serotonin receptors. Because of these two functions, Serzone and Desyrel are often referred to as SARIs (serotonin antagonists/reuptake inhibitors). Serzone also inhibits norepinephrine reuptake while Desyrel slightly stimulates alpha-adrenergic receptors. These small differences in pharmacological action can cause widely varying side effects, which will be discussed later on. 

Tricyclics modify peripheral sympathetic effects in two ways through blockade of norepinephrine reuptake at neuroeffector junctions and through alpha adrenoceptor blockade. Sedation and atropine-like side effects are common with tricyclics, especially amitriptyline. In contrast to sedative-hypnotics, tricyclics lower the threshold to seizures. The answer is (B). Selective serotonin reuptake inhibitors cause sexual dysfunction in some patients, with changes in libido, erectile dysfunction, and anorgasmia. Tricyclic antidepressants may also decrease libido or prevent ejaculation. Of the heterocyclic antidepressants bupropion is the least likely to affect sexual performance. The drug is also used in withdrawal from nicotine dependence. The answer is (B). 

Effexor is an inhibitor of the reuptake of both norepinephrine and 5-HT. Michael Thase of the University of Pittsburg found that Efforex caused a 45% remission rate in patients with depression compared with the SSRl rate of 35% and placebo of 25%. Subsequent studies showed less striking results, and hypertension was an occasional side effect. 

D. Selective norepinephrine and serotonin reuptake inhibitors. Both Venlafaxine and Duloxetine have shown significant higher effect than placebo in the treatment of pain in diabetic patients and both compounds are being used with increasing frequency in these patients. Duloxetine is a more potent inhibitor than Venlafaxine and seems from clinical studies to be more efficacious. Doses tested in trials are 60 and 120 mg/day and side effects include nausea, somnolence, dizziness, dry mouth and decreased appetite. 

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