Serotonin-norepinephrine reuptake inhibitor 625632 223903450 2008-07-06T12:44:09Z It Is Me Here 2552569 Replaced PNG with SVG [[Image:Serotonin (5-HT).svg|thumb|[[Serotonin]]]] [[Image:Norepinephrine structure.png|thumb|[[Norepinephrine]]]] {{Citecheck|date=November 2007}} '''Serotonin-norepinephrine reuptake inhibitors (SNRIs)''' are a class of [[antidepressant]] used in the treatment of [[clinical depression]] and other affective disorders. They are also sometimes used to treat [[anxiety disorder]]s, [[obsessive-compulsive disorder]], [[attention deficit hyperactivity disorder]] (ADHD) and chronic [[neuropathic pain]]. They act upon two [[neurotransmitter]]s in the [[brain]] that are known to play an important part in mood, namely, [[serotonin]] and [[norepinephrine]]. This can be contrasted with the more widely-used [[selective serotonin reuptake inhibitor]]s (SSRIs), which act only on serotonin. ==Mode of action== Activity on [[norepinephrine]] reuptake is thought necessary for an antidepressant to be effective on neuropathic pain, a property shared with the older [[tricyclic antidepressants]] but not with the SSRIs. {{Fact|date=November 2007}} One feature common to all types of depression is a reduction in communication and connectivity between [[neuron]]s in [[Hippocampus]]. Neurons pass information to each other by means of [[neurotransmitters|neurotransmitter]], which pass across the narrow [[synapse]]s between the cells. After firing, most of the neurotransmitter is reabsorbed by the presynaptic cell in a process called [[reuptake]]. Antidepressants increase the number of neurotransmitters active in the synapse, thereby enhancing neuronal activity downstream. Via an effect on [[NMDA]] receptors, this causes neuronal growth and synapse formation which have been shown in animal models to correlate with depression.<ref name="pmid11282807">{{cite journal |author=Reid IC, Stewart CA |title=How antidepressants work: new perspectives on the pathophysiology of depressive disorder |journal=The [[British Journal of Psychiatry]]: the journal of mental science |volume=178 |issue= |pages=299–303 |year=2001 |pmid=11282807|doi= 10.1192/bjp.178.4.299}}</ref> Modern antidepressants usually achieve this effect by blocking the [[Monoamine transporter|transporter proteins]] that reabsorb certain neurotransmitters, hence the name "reuptake inhibitors". The result being that more of the neurotransmitter is left in the synaptic cleft, so it has a greater effect on the target neuron. SNRIs were developed more recently than SSRIs, and there are relatively few of them. Their efficacy as well as their tolerability appears to be somewhat better than the SSRIs, owing to their compound effect. {{Fact|date=November 2007}} ==Adverse effects== As with the SSRIs, abrupt discontinuation of SNRI-medication usually leads to a [[SSRI discontinuation syndrome|discontinuation syndrome]] which could include states of [[anxiety]] and further symptoms. It is therefore recommended to slowly taper down the dose under the supervision of a psychopharmacologist when discontinuing SNRIs. Due to the effects of increased norepinephrine synaptic activity, these drugs are [[contraindication|contraindicated]] in patients with hypertension, heart disease, or risk of stroke. {{Fact|date=November 2007}} ==Side effects and drug interactions== Because one of the actions of the SNRIs is to block the reuptake of serotonin as the SSRIs do, it has many of the same side effects. The most common include nausea, drowsiness, headache, changes in appetite, vivid dreams, and sexual side effects. There are two common sexual side effects: diminished interest in sex (libido) and difficulty reaching climax (orgasm). These drugs typically do not cause problems with erection, but the sexual side effects are the most common reason people stop taking this type of antidepressant even if it is working well. Activity at the norepinephrine transporter can sometimes cause anxiety, activation, and elevated blood pressure, leading to the recommendation that everyone who takes these medications should have their blood pressure monitored. SNRIs should be taken with caution when using [[St John's wort]].<ref>{{cite book | title=2006 Lippincott's Nursing Drug Guide |last=Karch |first=Amy |year= 2006 |publisher=Lippincott Williams & Wilkins |location=Philadephia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo |isbn= 1-58255-436-6 }}</ref>, and should never be taken with MAOI antidepressants. ==SNRIs currently available== *'''[[venlafaxine]]''' (tradenames '''Effexor XR''', '''Effexor''') is the first and most commonly used SNRI. Although it also works on [[dopamine]] somewhat at high dosages, the majority of its effect is on serotonin and norepinephrine. *'''[[desvenlafaxine]]'''<ref name="pmid16675639">{{cite journal |author=Deecher DC, Beyer CE, Johnston G, ''et al'' |title=Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor |journal=J. Pharmacol. Exp. Ther. |volume=318 |issue=2 |pages=657–65 |year=2006 |month=August |pmid=16675639 |doi=10.1124/jpet.106.103382 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16675639}}</ref> (tradename '''Pristiq''') is the active metabolite of venlafaxine and is believed to work in the same manner. It will be introduced by Wyeth in late 2007-early 2008. *'''[[sibutramine]]''' (tradenames '''Meridia''', '''Reductil''') is an SNRI which failed to show antidepressant activity in animal tests, but instead has been widely marketed as an [[appetite suppressant]] drug for weight loss. *'''[[nefazodone]]''' (tradename '''Serzone''') is an antidepressant with efficacy similar to SSRIs, but without the sexual side effects. In fact, Serzone at times may act similarly to [[bupropion|Wellbutrin]] in its neutral or at times positive effect on function. It has been discontinued in several countries due to rare cases of [[liver]] failure. The tradename "Serzone" has been discontinued, however generic nefazodone is currently available ([[May 6]]). However, the liver failure is rare, and a simple blood test every 6 months to assess liver enzyme levels is sufficient. Nefazodone has an active metabolite which at higher doses (> 250 mg/day) can increase anxiety. One of the benefits [[nefazodone]] has over '''Effexor''' and '''Cymbalta''' is its enhanced sedation when taken at bedtime.{{Verify source|date=November 2007}} *'''[[milnacipran]]'''<ref name="pmid17218444">{{cite journal |author=Nonogaki K, Nozue K, Kuboki T, Oka Y |title=Milnacipran, a serotonin and norepinephrine reuptake inhibitor, induces appetite-suppressing effects without inducing hypothalamic stress responses in mice |journal=Am. J. Physiol. Regul. Integr. Comp. Physiol. |volume=292 |issue=5 |pages=R1775–81 |year=2007 |month=May |pmid=17218444 |doi=10.1152/ajpregu.00527.2006 |url=http://ajpregu.physiology.org/cgi/pmidlookup?view=long&pmid=17218444}}</ref> (tradename '''Dalcipran/ Portugal'''; '''Ixel/ France''') has shown to be significantly effective in the treatment of depression and [[Fibromyalgia|Fibromyalgia syndrome]] (FMS). Although it has not yet been approved by the [[Food and Drug Administration]] (FDA) for use in the United States, it has been commercially available in Europe and Asia for several years. *'''[[desipramine]]''' (tradenames '''Norpramine''', '''Pertofraneis''') is technically a [[tricyclic antidepressant]], and is usually categorized as such. Like an SNRI it works on both serotonin and norepinephrine transporters, but because it also interacts with cholinergic and histamine receptors, leading to the characteristic side effects associated with blockade of these receptors, it lacks the specificity that the serotonin norepinephrine specific reuptake inhibitors have. *'''[[duloxetine]]'''<ref name="pmid15254142">{{cite journal |author=Iyengar S, Webster AA, Hemrick-Luecke SK, Xu JY, Simmons RM |title=Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine reuptake inhibitor in persistent pain models in rats |journal=J. Pharmacol. Exp. Ther. |volume=311 |issue=2 |pages=576–84 |year=2004 |month=November |pmid=15254142 |doi=10.1124/jpet.104.070656 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15254142}}</ref> (tradename '''Cymbalta''') by Eli Lilly and Company, also inhibits serotonin reuptake and has been approved for the treatment of depression and neuropathic pain in August of 2004. *'''[[bicifadine]]''' by DOV Pharmaceutical inhibits the reuptake of serotonin and norepinephrine (and dopamine to a lesser extent) but rather than being developed for the already crowded antidepressant market, it is being researched as a non-opioid, non-NSAID [[analgesic]] drug. Please note that some of the above medications may not be considered "true" SNRIs; refer to specific peer-reviewed scientific journals for more in-depth coverage on classifications and pharmaco-kinetics. ==See also== *[[Serotonin-noradrenaline-dopamine reuptake inhibitor]] *[[Noradrenergic and specific serotonergic antidepressant]] ==References== {{reflist}} {{Antidepressants}} [[Category:Serotonin-norepinephrine reuptake inhibitors| ]] [[de:Serotonin-Noradrenalin-Wiederaufnahmehemmer]] [[es:Inhibidor de la recaptura de la serotonina-noradrenalina]] [[fr:Inhibiteur de la recapture de la sérotonine-noradrénaline]] [[he:SNRI]] [[ja:SNRI]] [[pl:SNRI]] [[pt:ISRSN]]