Selective norepinephrine reuptake inhibitors depression

Scates, A. C. Doraiswamy, P. M. (2000). Reboxetine a selective norepinephrine reuptake inhibitor for the treatment of depression. Ann. Pharmacother., 34, 1302-12. 

Altered removal of a neurotransmitter from the synaptic cleft. The third mechanism by which drugs may alter synaptic activity involves changes in neurotransmitter reuptake or degradation. A very well known example of a drug in this category is Prozac (fluoxetine), which is used to treat depression. The complete etiology is unknown, but it is widely accepted that depression involves a deficiency of monoamine neurotransmitters (e.g., norepinephrine and serotonin) in the CNS. Prozac, a selective serotonin reuptake inhibitor, prevents removal of serotonin from the synaptic cleft. As a result, the concentration and activity of serotonin are enhanced. 

Side effects, mainly due to serotonin reuptake inhibition include G1 upset, nervousness, and sexual dysfunction. SSRls are associated with an increased risk of falls. Hyponatraemia due to SIADH is an uncommon, but important side effect in elderly patients. Selective serotonin and norepinephrine reuptake inhibitors (S SNRls) such as venlafaxine and duloxetine are also useful in older patients. Other heterocyclic antidepressants of importance in older patients because of relative safety include bupro-prion and mirtazepine. They are reserved for patients with resistance to or intolerance of SSRls. Currently, trazodone is used mostly for sleep disturbance in depression in doses of 50-100 mg at bedtime. The monoamine oxidase inhibitors phenelzine. 

Venlafaxine is one of the first selective serotonin and norepinephrine reuptake inhibitors developed for the treatment of depression. It was originally released in the United States in 1994. 

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). 

Fluoxetine (Prozac /Lilly), paroxetine (Paxil /GlaxoSmithKilne), and sertraline (Zoloft /Pfizer) are selective serotonin reuptake inhibitors (SSRIs) and are useful in the treatment of depression. These agents potentiate the pharmacological actions of the neurotransmitter serotonin by preventing its reuptake at presynaptic neuronal membranes. In addition to its SSRI properties, venlafaxine (EfFexor /Wyeth-Ayerst) also appears to be a potent inhibitor of neuronal norepinephrine reuptake and a weak inhibitor of dopamine reuptake thereby enhancing the actions of these neurotransmitters as well. Venlafaxine is indicated for use in anxiety and depression. 

This herb is also known as St. Joan s wort, klamath weed, and goatweed. It has historically been used for many purposes, but most recently it is marketed as an antidepressant. In fact, it outsells all conventional antidepressants in Germany. The active constituent is hypericin that seems to act as a weak monoamine oxidase MAO inhibitor and a selective serotonin reuptake inhibitor (SSRI). Dopamine and norepinephrine uptakes are also mildly inhibited. St. John s wort is available in many forms, as a tablet, tea, tincture, and the raw dried herb. For best results, a tablet standardized to contain 0.3% hypericin should be taken Kira by Lichtwer Pharma is the most extensively studied. Randomized, placebo-controlled trials using 300 mg of St. John s Wort three times daily have found it to be superior to placebo in mild to moderate depression. Response rates are generally regarded as inferior to conventional antidepressants, including... 

Chronic pain patients tend to have concurrent depression however, the antidepressants chosen may not have any pain-relieving properties. Antidepressants that affect one neurotransmitter in the brain, such as selective serotonin reuptake inhibitors have not appeared to be effective in the management of pain in clinical trials. Antidepressants that affect multiple neurotransmitters— namely, serotonin and norepinephrine—have been shown to be effective pain relievers.Two published metaanalyses have shown that tricyclic antidepressants amitriptyline, desipramine, imipramine, and nortriptyline are the most effective treatment for the management of neuropathic pain. ° These publications review the published clinical trial data for all agents available for the management of neuropathic pain. 

This diverse collection has been grouped together mostly because they do not operate as selective serotonin reuptake inhibitors. Instead, each one interacts differently with neurotransmitters that are tied to depression serotonin, norepinephrine, or dopamine. For instance, one of the more popular non-SSRIs, Effexor (venlafaxine), selectively inhibits the uptake of serotonin and norepinephrine, acting on the same molecular machinery as tricyclic antidepressants (TCAs). But, in contrast to TCAs, Effexor shows no affinity for other neurotransmitter receptors and thus has far fewer side effects than the... 

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. 

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. 

The selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of depression in the elderly. Compared with tricyciic antidepressants (TCAs), they are much safer in overdose and, for the most part, their side-effects are better tolerated. The antidepressants that have been shown, in controlled studies, to be effective in geriatric major depression are the SSRIs fluoxetine, paroxetine, and sertraline, the TCAs clomipramine and nortriptyline, and the serotonin and norepinephrine reuptake inhibitor (SNRi) venlafaxine. Given that most antidepressants are effective in the elderly, the choice of drug is based on its side-effect profile and its potential to interact with other medications. 

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