Venlafaxine side effects profile

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

The SSRIs are first-line pharmacotherapy for PTSD. Venlafaxine, the TCAs, and MAOIs may also be effective, but they have less favorable side-effect profiles. 

Nortriptyline (Pamelor). A recent study suggested that the tricyclic antidepressant nortriptyline, like bupropion, is effective in the treatment of smoking cessation. Nortriptyline does not have any significant effect on dopamine reuptake activity, but it does increase norepinephrine availability. Like bupropion, nortriptyline may therefore reduce the physical symptoms of nicotine withdrawal. Because nortriptyline carries the danger of lethality in overdose and has the unfavorable side effect profile of the tricyclics, we do not recommend its use for smoking cessation. However, it does raise the question as to whether other newer antidepressants that increase norepinephrine activity (e.g., venlafaxine, mirtazapine, duloxetine) may also prove to be effective treatments for nicotine withdrawal. 

Beyond their action upon SERT and NET, venlafaxine (1), milnacipran (2) and duloxetine (3) are remarkably selective molecules. All three of them have displayed very low in vitro affinity Ki > 3(X)0 nM) for ai- and a2-adrenergic, histamine Hj, muscarinic, and DA D2 receptors, consistent with favorable side-effect profiles. Venlafaxine (1) and duloxetine (3) also have low affinity for a number of serotonergic receptors, and do not inhibit monoamine oxidase A or B. An expanded in vitro receptor profile of >50 receptors and binding sites... 

Regarding side-effect profiles, all three SSNRIs are generally well tolerated, most adverse events occurring early in treatment, with a mild to moderate severity and a tendency to decrease or disappear with continued treatment. Venlafaxine (1) seems to be the least weU-toIerated SNRI, combining a higher level of serotonergic adverse events (nausea, sexual dysfunction, withdrawal problems) with dose-dependent hypertension. In contrast, milnacipran (2) and duloxetine (3) appear better tolerated and essentially devoid of cardiovascular toxicity. 

Newer antidepressants (such as the SSRIs, bupropion, and venlafaxine] probably achieved their impressive popularity primarily because their side-effect profiles were more favorable. Because dry mouth, blurry vision, tachycardia, lethargy, constipation, urinary hesitancy, and arrhythmias are deeply distressing to many, paucity of anticholinergic side effects from SSRIs was especially noteworthy. Convenience and simplicity of use are also favorable qualities for some newer agents. However, the decreased libido, anorgasmia, and erectile problems caused by SSRIs are of note and should be taken into consideration for long-term therapy. 

The side-effect profile of venlafaxine is similar to that of SSRIs and includes gastrointestinal symptoms, sexual dysfunction, and transient discontinuation symptoms. Like the SSRIs, venlafaxine does not affect cardiac conduction or lower the seizure threshold. In most patients, venlafaxine is not associated with sedation or weight gain. Side effects that differ from those of SSRIs are hypothesized to be related to the increased noradrenergic activity of this drug at higher doses these side effects are dose-dependent anxiety (in some patients) and dose-dependent hypertension. 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

The SSRIs, venlafaxine, or nefazodone may be reasonable alternatives to earlier generation antidepressants because of their less problematic side effect profiles (486). The propensity to increase activity, the lack of sedation, gastrointestinal symptoms, and alterations in blood pressure are potential complications, however. Given AIDS-induced altered metabolism, for many of these agents, TDM may be helpful in establishing an effective, nontoxic dose. 

When they occur, depressive symptoms should be treated actively using a combination of cognitive-behavioral therapy and an antidepressant drug. Of the available antidepressants, selective serotonin reuptake inhibitors (SSRIs) have the most favourable combination of efficacy and side-effect profile for the elderly, regardless of the presence of medical co-morbidities. Although the dual agent venlafaxine has been proposed as an alternative agent for older patients who are either non-responders or partial responders to SSRIs, the frail elderly may be particularly vulnerable to its side effects (Hayes 2004). 

Compared with other classes of antidepressants, SRIs have a more favorable side-effect profile and better efficacy data. A review of randomized, controlled trials with SRIs for the treatment of PMDD reported that the agents were well tolerated and effective in treating physical as well as behavioral symptoms with either intermittent or continuous dosing. Citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine all have been effective in PMDD placebo-controlled trials (60% to 90% efficacy rates with almost complete relief of symptoms). For fluvoxamine, there are mixed results because one controlled study reported that it had similar efficacy to placebo treatment in PMDD. Although antidepressants usually take... 

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. 

The traditional scheme is complicated by the fact that some antidepressants exhibit characteristics of more than one class. For example, clomipramine, a tricyclic antidepressant (TCA) with side effects and toxicity similar to other TCAs, works more like the selective serotonin reuptake inhibitors (SSRls). Similarly, venlafaxine and duloxetine, which are usually grouped with the atypical antidepressants, have a side effect and safety profile comparable to the SSRls. Although a classihcation system based on mechanism of action offers some advantage (see Table 3.7), even this scheme is limited by the fact that antidepressants that work in the same way may have widely divergent side effect and safety profiles. In the following discussion, the traditional classification system is adopted. Although fraught with problems and inconsistencies. 

Other antidepressant drugs that primarily affect serotonin reuptake include trazodone [TRAZ oh done], fluvoxamine [floo VOX a meen], nefazodone [ne FAZ oh don], paroxetine [pah ROX a teen], sertraline [SIR trah leen], and venlafaxine [vin lah FACKS in]. These SSRIs differ from fluoxetine in their relative effects on the reuptake of serotonin and norepinephrine. They do not seem to be more efficacious than fluoxetine, but their profiles of side effects are somewhat different. There is a high variability among patients in the rate of elimination of these drugs (including fluoxetine), and failure to tolerate one drug should not preclude a trial of another SSRI. 

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