'''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.
'''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.
−
−
The abbreviation "SNRI" should not be used for "[[norepinephrine reuptake inhibitor|'selective' norepinephrine reuptake inhibitor]]s".
==Mode of action==
==Mode of action==
Line 9:
Line 9:
Depression is thought to be caused by a lack of information flow between [[neuron]]s in certain parts of the brain. Neurons pass information to each other by means of chemicals known as neurotransmitters, which shoot across the tiny [[synapse]]s between the cells. After firing, most of the neurotransmitter is reabsorbed by the presynaptic cell in a process called [[reuptake]].
Depression is thought to be caused by a lack of information flow between [[neuron]]s in certain parts of the brain. Neurons pass information to each other by means of chemicals known as neurotransmitters, which shoot across the tiny [[synapse]]s between the cells. After firing, most of the neurotransmitter is reabsorbed by the presynaptic cell in a process called [[reuptake]].
−
Antidepressants work by increasing the amount of neurotransmitters active in the synapse, thereby enhancing neuronal activity and increasing the responsiveness of mood. Modern antidepressants usually achieve this effect by blocking the [[Monoamine transporter|transporter proteins]] that reabsorb certain neurotranmitters, hence the name "reuptake inhibitors".
+
Antidepressants work by increasing the number of neurotransmitters active in the synapse, thereby enhancing neuronal activity and increasing the responsiveness of mood. Modern antidepressants usually achieve this effect by blocking the [[Monoamine transporter|transporter proteins]] that reabsorb certain neurotransmitters, hence the name "reuptake inhibitors".
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.
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.
==Adverse effects==
==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.
+
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 on increasing Norepinephrine synaptic acitivity, these drugs are [[contraindicated]] in patients with hypertension, heart disease, or risk of stroke.
==SNRIs currently available==
==SNRIs currently available==
−
*'''[[venlafaxine]]''' (tradenames '''Effexor®''', '''Efexor®''') 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.
+
*'''[[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.
−
*'''[[nefazodone]]''' (tradename '''Serzone®''') is an antidepressant with efficacy similar to SSRIs, but without the sexualsideeffects.Infact,Serzone at times may act similar to 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 06). However, the liverfailure is rare, and a simple blood test every 6 months to assess liver enzyme levels is sufficient. Nefazodonehasanactivemetabolitewhichat higher doses (> 250mg/day)canincreaseanxiety.
+
*'''[[desvenlafaxine]]''' (tradename '''Pristiq®''') is the activemetaboliteofvenlafaxineandisbelieved to work in the samemanner. ItwillbeintroducedbyWyethinlate2007-early2008.
+
+
*'''[[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 06). 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 (> 250mg/day) can increase anxiety. One of the benefits [[nefazodone]] has over '''Effexor®''' and '''Cymbalta®''' is its enhanced sedation when taken at bedtime.
*'''[[milnacipran]]''' (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.
*'''[[milnacipran]]''' (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.
Line 25:
Line 25:
*'''[[desipramine]]''' (tradenames '''Norpramine®''', '''Pertofraneis®''') is technically a [[tricyclic antidepressant]], and is usually categorized as such. It works, however, on both serotonin and norepinephrine, so it can also be considered an SNRI.
*'''[[desipramine]]''' (tradenames '''Norpramine®''', '''Pertofraneis®''') is technically a [[tricyclic antidepressant]], and is usually categorized as such. It works, however, on both serotonin and norepinephrine, so it can also be considered an SNRI.
−
*'''[[duloxetine]]''' (tradename '''Cymbalta®''') by Eli Lilly and Company, also inhibits serotonin and has been approved for the treatment of depression and neuropathic pain in August of 2004.
+
*'''[[duloxetine]]''' (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.
−
−
Effexor is the "newer" version of Serzone, while Cymbalta is the "newer" version of Effexor. These drugs have been considered a second tier drug for treating less severe adult ADHD, because they combine the serotonin reuptake inhibition (successful in treating some anxiety/depression and obsessive-compulsive disorder), and/or the "ruminating" done in ADHD patients with norepinephrine's stimulant effect.
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.
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.
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.
Depression is thought to be caused by a lack of information flow between neurons in certain parts of the brain. Neurons pass information to each other by means of chemicals known as neurotransmitters, which shoot across the tiny synapses between the cells. After firing, most of the neurotransmitter is reabsorbed by the presynaptic cell in a process called reuptake.
Antidepressants work by increasing the number of neurotransmitters active in the synapse, thereby enhancing neuronal activity and increasing the responsiveness of mood. Modern antidepressants usually achieve this effect by blocking the transporter proteins that reabsorb certain neurotransmitters, hence the name "reuptake inhibitors".
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.
As with the SSRIs, abrupt discontinuation of SNRI-medication usually leads to a 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 on increasing Norepinephrine synaptic acitivity, these drugs are contraindicated in patients with hypertension, heart disease, or risk of stroke.
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 (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.
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 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 06). 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 (> 250mg/day) can increase anxiety. One of the benefits nefazodone has over Effexor® and Cymbalta® is its enhanced sedation when taken at bedtime.
milnacipran (tradename Dalcipran®/ Portugal; Ixel®/ France) has shown to be significantly effective in the treatment of depression and 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. It works, however, on both serotonin and norepinephrine, so it can also be considered an SNRI.
duloxetine (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.
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.
Added by Dr Joe Kiff
Edit