Selective norepinephrine reuptake inhibitors efficacy

Preliminary studies and atomoxetine s known mechanism of action as a selective norepinephrine reuptake inhibitor suggest its efficacy as an antidepressant... 

Atomoxetine, a selective norepinephrine reuptake inhibitor, is the first nonstrmulant approved by the Food and Drug Administration (FDA) for the treatment of ADHD. In contrast to the stimulants, it has no apparent abuse potential and is not a controlled substance. Placebo-controlled, short-term trials (6 to 12 weeks) have shown that atomoxetine is effective in reducing ADHD symptoms in children, teens, and adults. It is not clear whether it is as effective as the stimulants, although one preliminary open study suggested comparable efficacy with methylphenidate. ... 

It is thus understandable why some earlier authors previously doubted the efficacy of antidepressants in general (Weiner et al.. 1980) or the advantages of newer antidepressants compared with classical products (Song et al., 1993). However, the great majority of doctors and scientific authors consider that the efficacy of first-generation antidepressants (imipramine, amitriptyline, nortriptyline) has been proved beyond any reasonable doubt, and that efficacy also has been demonstrated for newer products such as trazodone, the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake... 

It was initially believed that the antidepressant effectiveness of MAOIs was the direct result of MAO inhibition. This acute effect decreases degradation of monoamines (e.g., norepinephrine, serotonin, or dopamine) stored in presynaptic neurons, thereby resulting in an increased amount of these neurotransmitters available at the synapse. More recent research indicates that this model does not fully explain the mechanism of MAOIs efficacy. For example, the positive (h-) stereoisomer of tranylcypromine is a poor antidepressant despite inhibiting MAO. The main pharmacologic difference between the negative (-) and + isomers of tranylcypromine is that the former has much weaker effects as a norepinephrine reuptake inhibitor in relation to its potency as an MAOI. The other MAOIs may also block the reuptake of selected neurotransmitters. However, like the non-MAOI uptake inhibitors, these acute effects often precede clinical antidepressant effects by weeks. More consistent with the 2- to 4-week lag in therapeutic effect, chronic treatment with a diverse number of MAOIs has been shown to reduce the number of a2- and P-adrenergic and serotonin (5-HT2) postsynaptic binding sites in the brain. 

When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine may show an earlier onset of action (although data are currently not well established). Mirtazapine has also been found to be efficacious in the treatment of elderly patients with depression. Mirtazapine has been shown to be effective in the treatment of panic disorder, social phobia, and post-traumatic stress disorder. In one study, mirtazapine combined with citalopram in obsessive-compulsive patients induced an earlier response when compared with citalopram plus placebo. It was suggested that antagonism of presynaptic a2-adrenergic receptors does not enhance serotonin neurotransmission directly, but rather disinhibits the norepinephrine activation of serotonergic neurons and thereby increases serotonergic neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. 

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... 

D. Selective norepinephrine and serotonin reuptake inhibitors. Both Venlafaxine and Duloxetine have shown significant higher effect than placebo in the treatment of pain in diabetic patients and both compounds are being used with increasing frequency in these patients. Duloxetine is a more potent inhibitor than Venlafaxine and seems from clinical studies to be more efficacious. Doses tested in trials are 60 and 120 mg/day and side effects include nausea, somnolence, dizziness, dry mouth and decreased appetite. 

Atomoxetine is a selective inhibitor of norepinephrine presynaptic reuptake transporters that has been shown to increase extracellular norepinephrine and dopamine concentrations in the prefrontal cortex in rats (Bymaster et al. 2002), which may account for its clinical efficacy in the treatment of ADHD symptomatology. However, atomoxetine does not appear to affect dopamine levels in the striatum or nucleus accumbens and consequently is not thought to carry the abuse potential associated with stimulant medications. 

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