Selective Serotonin-Norepinephrine Reuptake Inhibitors

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. 

Venlafaxine is approved by the U.S. Food and Drug Administration for the treatment of both major depression and generalized anxiety disorder. Preliminary data suggest that it might also have a role in the treatment of chronic pain conditions and perhaps other disorders against which SSRIs are effective. Serotonin reuptake inhibition is prominent at lower doses of venlafaxine at higher doses, inhibition of norepinephrine reuptake becomes more significant. 

The recommended dose range is 75-225 mg/day. The extended-release preparation, which allows for once-daily dosing in most pa- 

Unlike SSRIs, venlafaxine shows a positive dose-response relation patients with mild depression may respond to lower doses, whereas patients with more severe or recurrent depression may respond better to higher doses. 

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FDA, Combined Use of 5-Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors (SSRIs) or Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) May Result in Life-Threatening Serotonin Syndrome , FDA Public Health Advisory (2006) http //www.fda.gov/Cder/Drug/advisory/ S SRI S S200607.htm... 

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

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS Selective Serotonin-Norepinephrine Reuptake Inhibitors... 

SELECTIVE SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS AND TRICYCLIC ANTIDEPRESSANTS... 

Selective serotonin norepinephrine reuptake inhibitors (SSNRIs) The newest group of medicines that have successfully been used to treat emotional and behavioral problems such as depression, panic disorder, obsessive-compulsive disorder (OCD), similar to their counterparts, the SSRIs. Some examples of the SSNRIs include Effexor, Serzone, and Remeron. 

FIGURE 30-2. Pain algorithm. AED, antiepileptic drug APAP, acetaminophen NSAID, non-steroidal antiinflammatory drug SNRI, serotonin-norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

BiPAP bi-level positive airway pressure SNRI serotonin norepinephrine reuptake inhibitor SSRI selective serotonin reuptake inhibitor... 

SSRI = selective serotonin reuptake inhibitor SNRI = serotonin norepinephrine reuptake inhibitor ARB = angiotensin receptor blocker ACE = angiotensin converting enzyme COX-2 = cyclooxygenase 2 ADHD = attention deficit hyperactivity disorder. 

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). 

MAOIs, monoamine oxidase inhibitors ND, no data found SNRIs, serotonin-norepinephrine reuptake inhibitors SSRIs, selective serotonin reuptake inhibitors. 

Reuptake Norepinephrine transporter Tricyclic antidepressants (imipramine, f) Tricyclic norepinephrine reuptake inhibitors (desipiamine, ) Selective norepinephrine reuptake inhibitors (reboxetine, ) Dual serotonin/ norepinephrine reuptake inhibitors (venlafaxine, J.)... 

SCA Second-generation antipsychotic SNRI Serotonin-norepinephrine reuptake inhibitor SSRI Selective serotonin reuptake inhibitor TCA Tricyclic antidepressant TeCA Tetracyclic antidepressant... 

Name of modally J Some (less-estabHshed) efficacy 1H iHiHj ) Efficacy not well established If partial response SNRI SSRI Serotonin-norepinephrine reuptake inhibitor Selective serotonin reuptake inhibitor... 

Serotonin Norepinephrine Reuptake Inhibitor Selective Serotonin Reuptake Inhibitor Sales of Mevalotin (Daiichi Sankyo, 799M) not included Sales of Amlodin (Sumitomo, 506M) not included Note Salts have been omitted from structures. 

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]. 

Papakostas GI, Fava M. A meta-analysis of clinical trials comparing milnacipran, a serotonin -norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 2007 17(l) 32-36. 

SSRIs, selective serotonin reuptake inhibitors SNRIs, serotonin and norepinephrine reuptake inhibitors TCAs, tricyclic antidepressant... 

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