Serotonin and norepinephrine reuptake inhibitors

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. 

DUAL SELECTIVE SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SSNRIs)... 

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. 

Post-2000 Renal rhabdomyolysis with the statin, cerivastin cardio-toxicity with the COX-2 inhibitor, rofecoxib and liver damage with the selective serotonin and norepinephrine reuptake inhibitor, atomoxetine. 

Venlafaxine is one of the first selective serotonin and norepinephrine reuptake inhibitors developed for the treatment of depression. It was originally released in the United States in 1994. 

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

Additional dual 5HT-NE reuptake inhibitors include sibutramine, which is approved for the treatment of obesity but not depression. Tramadol is a kappa opiate agonist approved for the treatment of pain, but it also has serotonin and norepinephrine reuptake inhibitor properties. Dual reuptake inhibitors in clinical testing as antidepressants include milnacipran and duloxetine. 

Nefazodone is the prototypical member of the SARI class of antidepressants. It is a powerful serotonin 2A antagonist with secondary actions as a serotonin and norepinephrine reuptake inhibitor (Figs. 7—14 and 7—15). Nefazodone also blocks alpha 1 receptors, but the clinical consequences of this are generally not important, perhaps because its norepinephrine reuptake inhibition reduces this action in vivo. 

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

SNRI dual serotonin and norepinephrine reuptake inhibitor... 

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. 

Venlafaxine is a serotonin and norepinephrine reuptake inhibitor that potentiates norepinephrine, serotonin, and dopamine neurotransmitter activity in the CNS by inhibiting their neuronal reuptake. Effexor, Effexor XR are used in treatment of major depressive disorder. Effexor XR is used in treatment of generalized anxiety disorder and treatment of social anxiety disorder. 

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). 

Mirtazapine is primarily metabolized by CYP450 2D6, 1A2, and 3A4. Mirtazapine is at least as effective as the tricyciic antidepressants and trazodone in a wide range of patient subgroups, including in- and outpatients with moderate to severe depression. It also appears to be at least as effective as the serotonin and norepinephrine reuptake inhibitor venlafaxine in the treatment of severely depressed melancholic patients. 

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. 

Treat with serotonin and norepinephrine reuptake inhibitor (duloxetine, venlafaxine) or alternatively with serotonin reuptake inhibitors, (citalopram, paraoxetine). 

Thiophene seems to be very popular in Li Lilly drugs. Its dual selective serotonin and norepinephrine reuptake inhibitor (SSNRI) for depression, duloxetine (Cymbalta), contains a thiophene. And its atypical antipsychotic drug olanzapine (Zyprexa) has a fused thiophene as its core structure. 

In the 1980s the Boots company developed the serotonin- and norepinephrine-reuptake inhibitor sibutramine for reduction of severe overweight. [242, 244] Sibutramine has a dual function to increase the feeling of satiety and to enhance metabolism. In 1997, the drug was launched under the trade name Meridia , however after an unfavourable risk/benefit assessment and the consequent ban by the European Medicines Agency (EM A) and the FDA, it was ultimately suspended by Abbott in 2010. 

One of the main issues related to tramadol is the fact that it blocks serotonin reuptake and may cause serotonin syndrome in susceptible patients. Serotonin syndrome is characterized by neurological and cardiovascular stimulation, and can lead to seizures and death. Risks of developing serotonin syndrome are increased in patients treated with selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. 

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. 

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