Antidepressants SNRIs

The SNRIs have relatively fewer CYP450 interactions than the SSRIs. Venlafaxine is a substrate but not an inhibitor of CYP2D6 or other isoenzymes, whereas desvenlafaxine is a minor substrate for CYP3A4. Duloxetine is a moderate inhibitor of CYP2D6 and so may elevate TCA and other CYP2D6 substrate levels. Like all serotonergic antidepressants, SNRIs are contraindicated in combination with MAOIs. 

Venlafaxine Antidepressant, SNRI mdrla, MDRl KO mice [142] O... 

Selective noradrenaline reuptake inhibitors (SNRIs) are a group of drugs, which act as antidepressants by the selective inhibition of the reuptake of noradrenaline from the synaptic cleft via the selective blockade of the noradrenaline-specific neurontransmitter transporter (e.g. reboxetine). 

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. 

Each antidepressant has a response rate of approximately 60% to 80%, and no antidepressant medication or class has been reliably shown to be more efficacious than another 22 MAOIs may be the most effective therapy for atypical depression, but MAOI use continues to wane because of problematic adverse effects, dietary restrictions, and possibility of fatal drug interactions.22,28 There is some evidence that dual-action antidepressants, such as TCAs and SNRIs, may be more effective for inpatients with severe depression than are the single-action drugs such as SSRIs,22,28 but the more general assertion that multiple mechanisms of action confer efficacy advantages is quite controversial.33... 

The clinician should bear in mind the toxic potential for the various antidepressant medications when patients already have or develop suicidality. The TCAs and MAOIs have narrow therapeutic indices, whereas the SSRIs, SNRIs, nefa-zodone, and mirtazapine have wide therapeutic indices.22... 

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

PD may be treated successfully with TCAs, SSRIs, SNRIs, or MAO Is, as well as benzodiazepines51,52 (Table 37-6). While all these agents are similarly effective, SSRIs have become the treatment of choice in PD. Benzodiazepines often are used concomitantly with antidepressants, especially early in treatment,... 

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. 

Switching non-responsive patients from an SSRI to an SNRI led 25 per cent of them to get better. Change from an SSRI to bupropion produced virtually the same remission rate (26 per cent). But what of the patients who were not switched to a different class of antidepressant, but instead were simply given another SSRI Twenty-seven per cent of these patients also got better - a remission rate that is virtually identical to that produced by changing to a different type of medication. In other words, the rate of improvement did not depend on the kind of drug to which the patient had been switched. Simply changing from one SSRI to another was as effective as changing to a completely... 

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],... 

Another SNRI, bicifadine (20), formerly under clinical development for chronic low back pain, is now being developed for neuropathic pain [65,66]. Flufenoxine, also known as F-98214-TA (21), was reported to display greater potency than several reference antidepressants in animal models predictive of antidepressant and anxiolytic activities [67]. SEP-227162 (structure undisclosed) is another SNRI reportedly undergoing clinical development [68]. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

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),... 

Newer Generation Antidepressants. All SSRIs have been shown effective in the treatment of panic disorder. Of these, flnoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft), as well as the SNRI venlafaxine ER (Effexor XR), have received FDA approval for the treatment of panic disorder. Because they are safer and easier to tolerate, SSRls/SNRls have largely supplanted the MAOIs and TCAs as standard treatments (along with benzodiazepines) for panic disorder. 

SSRls and SNRIs. The SSRl antidepressants, together with venlafaxine, have replaced the benzodiazepines as treatments of choice for GAD. Paroxetine and escitalopram are FDA approved for GAD, though it is generally believed that all SSRls and SNRIs are effective for GAD. Similar to the TCAs, SSRIs/SNRIs appear to be most effective for the intrapsychic symptoms of GAD but less effective than benzodiazepines for the somatic manifestations of the disorder. 

Generalized Sociai Anxiety Disorder, Treatment Resistance. A significant minority of patients will not experience a satisfactory treatment response to antidepressant therapy, even after a trial of adequate duration at full strength doses. For those with comorbid depression who are experiencing no benefit from SSRI treatment for either the anxiety or depression, then switching treatment is advisable. The options include switching to another SSRI, a SNRI (venlafaxine or perhaps dulox-etine), or, when other alternatives fail, phenelzine. 

Neuroanatomically both the locus coeruleus and the raphe nuclei project to the spinal cord where they gate sensory pathways from the skeletomuscular areas. As there is evidence that both noradrenaline and 5-HT are dysfunctional in depression, it is perhaps not surprising to find that the pain threshold is often reduced in patients with depression. Conversely, different types of antidepressants have been shown to have an antinociceptive effect in both rodent models of neuropathic pain, and clinically in fibromyalgia, chronic fatigue syndrome, postherpetic neuralgia and diabetic neuropathy. In general, it would appear that the dual action antidepressants (such as the TCAs and SNRIs) are more effective than the SSRIs. 

Antidepressants MAOIs, TCAs, SSRIs, SNRIs, mirtazapine, venlafaxine Amphetamines, phentermine, methylphenidate, sibutramine... 

Many antidepressant drugs have pronounced effects on sleep. Several tricyclic compounds (amitriptyline and others) have sedative actions while others (imipramine and others) are less sedative or even stimulant. Monoamine oxidase inhibitors (MAOIs) have central stimulant effects and may cause insomnia. Specific serotonin reuptake inhibitors (SSRls) and combined serotonin, noradrenaline reuptake inhibitors (SNRIs) can also cause insomnia. 

Stahl, S. M., Grady, M. M., Moret, C., and Briley, M. (2005). SNRIs Their Pharmacology, Clinical Efficacy, and Tolerability in Comparison with Other Classes of Antidepressants, CNS Spectrums, 10 732-747. 

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