Serotonin and norepinephrine reuptake inhibitors SNRIs

Reuptake inhibitors, which include the tricyclic and tetracyclic antidepressants (TCAs and TeCAs),the SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), the serotonin and norepinephrine reuptake inhibitors (SNRIs duloxetine, milnacipran, and venlafaxine), and the norepinephrine and dopamine reuptake inhibitor (bupropion). 

Sibutramlne is a serotonin and norepinephrine reuptake inhibitor (SNRI)... 

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. 

MAOI, monoamine oxidase inhibitor SARI, serotonin antagonist and reuptake inhibitor SNRI, serotonin and norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

FIGURE 38-1. Primary assessment and initial treatment for complaint of excessive daytime sleepiness. RLS, restless-legs syndrome NPSG, nocturnal polysomnography OSA, obstructive sleep apnea DA, dopamine agonist MSLT, multiple sleep latency test BZDRA, benzodiazepine receptor agonist SNRI, serotonin and norepinephrine reuptake inhibitor TCA, tricyclic antidepressant CPAP, continuous positive airway pressure. 

Two classes of antidepressants act as combined serotonin and norepinephrine reuptake inhibitors selective serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). 

SNRI (dual serotonin and norepinephrine reuptake inhibitor) may be classified as an antidepressant, but it is not just an antidepressant... 

The serotonin and norepinephrine reuptake inhibitors, or SNRIs, have both serotonin and norepinephrine inhibition, and are less selective than the SSRls. They also have nausea as a common adverse event on initiation, and can have dizziness, drowsiness, sweating, and dry mouth, as well as sexual dysfunction, as occur with the SSRI and have been associated with serotonin syndrome. 

There are three approved drugs, venlafaxine (16), duloxetine (17) and milnacipran (18), in the serotonin-norepinephrine reuptake inhibitor (SNRI) class. Whereas milnacipran blocks 5-HT and NE reuptake with almost equal potency, venlafaxine and duloxetine block 5-HT reuptake preferentially [39-41]. Clinical evidence shows that SNRIs have comparable efficacy in the treatment of MDD compared with antidepressants in the SSRI class. An advantage with SNRIs appears to be the ability of alleviating chronic pain associated with, and independent of depression [42-44],... 

In the past decade, other antidepressants have been introduced. Many of these act, at least in part, via serotonin-mediated mechanisms and, as such, have been tested in the treatment of one or more anxiety disorders. These additional antidepressants include two dual serotonin-norepinephrine reuptake inhibitors (SNRIs),... 

Although the SSRIs provided a tremendous advantage over the TCAs in terms of tolerability, an effect on norepinephrine also has some theoretical advantages. For example, some authors have suggested that dual reuptake inhibitors may be more likely to lead to remission (Thase et al. 2001). As the name of the class implies, these agents affect the reuptake of both serotonin and norepinephrine, while having very little effect on muscarinic, histaminic or Hj, or aj-adrenergic receptors. Hence these medications share many of the tolerability and safety benefits of the SSRIs. Currently, two serotonin-norepinephrine reuptake inhibitors (SNRIs) are available in the United States venlafaxine and duloxetine. 

Similar observations can be made with regard to the antidepressants introduced in the last 15 years or so. Both SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) represent some quantitative progress from the earlier antidepressants in that they are less toxic, cause fewer medically significant adverse events and support treatment compliance. As is the case for antipsychotics and schizophrenia, the development of these newer antidepressants was not based on fundamentally new insights into the pathophysiology of affective disorders. 

Noradrenaline (norepinephrine) reuptake inhibitors (NARIs) Serotonin and noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) Atypical... 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

The serotonin-norepinephrine reuptake inhibitors (SNRIs) block reabsorption of both 5-HT and NE. Examples of this class of antidepressant include venlafaxine (Effexor, A.62) and duloxetine (Cymbalta, A.63) (Figure A.19). 

Venlafaxine extended-release, a serotonin-norepinephrine reuptake inhibitor (SNRI), alleviates anxiety in patients with and without co-morbid depression. The reduction in psychic symptoms of anxiety and tension is not accompanied by significant reductions in somatic symptoms. Venlafaxine (dosed once daily) was effective at doses of 150 and 225 mg for 2 months in patients with GAD, and efficacy was maintained for an additional 6 months of therapy." Paroxetine was significantly more effective than placebo at achieving response in 62% and 68% of patients at 20 and 40 mg daily, respectively, after 2 months. Remission occurred in 30% and 36% of patients taking 20 and 40 mg of paroxetine, respectively." Escitalopram was more efficacious than placebo in three 8-week trials in patients with GAD. In a four paraUel-group comparison, diazepam and trazodone were found to be equivalent in anxiolytic activity (remission rates of 66% and 69%, respectively) compared with placebo (47% remission rate), but rmipramine s rate of remission (73%) exceeded that of the other three treatments. ... 

Duloxetine is the most potent inhibitor of the reuptake of serotonin and norepinephrine (among the SNRIs). It is a little more potent at blocking the reuptake of serotonin, although at higher doses (within the therapeutic range) it is... 

The importance and versatility of the Friedel-Crafts reaction in thiophene chemistry can be seen in the following examples of duloxetine synthesis involving Friedel-Crafts acylations. Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor (SNRI) known for its use as an antidepressant. 

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