Venlafaxine Benzodiazepines

Tricyclic antidepressants are not licensed for use in the anxiety disorders, so in theory the SSRIs should not be compared with them in cost-effectiveness terms. The SSRIs and venlafaxine are supplanting benzodiazepines as the latter s long-term problems become more appreciated. The SSRIs will take an increasing proportion of the market. However, in comparison with the overall costs of the anxiety disorders, this drug expenditure can be justified. Further cost-offset and cost-effectiveness studies will help hammer this point home. 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

Generalized anxiety Duloxetine Escitalopram Paroxetine Venlafaxine XR Benzodiazepines Buspirone Imipramine Sertraline Hydroxyzine Pregabalin... 

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. 

Serotonin-boosting antidepressants or longer-acting benzodiazepines are also both suitable first-line treatments for APD. For APD patients who are also troubled by depression, an antidepressant is obviously preferable. We also prefer to use antidepressants rather than benzodiazepines to treat APD patients who have a history of substance abuse. The current data suggests that any of the SSRls as well as nefazodone, mirtazapine, and venlafaxine may be helpful. When these do not work, a MAOI is a reasonable alternative provided the patient is willing to commit to the dietary regimen. 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

Generalized anxiety disorder Buspirone, benzodiazepines, venlafaxine, SSRIs... 

Social phobia SSRIs, MAOIs, benzodiazepines, buspirone, venlafaxine... 

Generahzed anxiety disorder can be treated with benzodiazepines, buspirone, and certain antidepressants (e.g., venlafaxine, paroxetine, escitalopram). These agents are compared in Table 3-3. 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

We have discussed how various antidepressants, especially venlafaxine XR, are being used increasingly for the treatment of generalized anxiety disorder. Buspirone remains a first-line generalized anxiolytic for chronic anxiety, and benzodiazepines are used largely for short-term treatment of intermittent anxiety symptoms. 

FIGURE 9-6. Various treatments can be given in combination for panic disorder (i.e., panic combos). The basis of all many combination treatments is a serotonin selective reuptake inhibitor (SSRI). Other antidepressants such as venlafaxine, nefazodone, mirtazapine, tricyclic antidepressants, and monoamine oxidase inhibitors can all have antipanic actions, although they are second-line treatments, as are the benzodiazepines. On the other hand, benzodiazepines are often added to SSRIs, particularly at the initiation of an SSRI and intermittently when there is breakthrough panic. Cognitive and behavioral psychotherapies can also be added to any of these drug treatments. 

As social phobia is only recently becoming better recognized and researched, better documentation for the various treatments mentioned above is now evolving. This applies especially to the five SSRIs and to some of the newer antidepressants such as venlafaxine XR. Guidelines are emerging for the use of high-potency benzodiazepines, MAO inhibitors, RIMAs, beta blockers, and various drugs in combination as second- or third-line treatments for social phobia. 

Antidepressant drugs, however, might have direct anxiolytic effects. That is, certain antidepressants such as paroxetine (Paxil) or venlafaxine (Effexor) can help reduce anxiety independent of their effects on depression.1,47 These antidepressants have therefore been advocated as an alternative treatment for anxiety, especially for people who cannot tolerate the side effects of traditional anxiolytics, or who might be especially susceptible to the addictive properties of drugs like the benzodiazepines.1,9,46 Moreover, antidepressants such as paroxetine or venlafaxine are now considered effective as the primary treatment for several forms of anxiety, including generalized anxiety disorder, social phobia, and panic disorder.4,29,53 Antidepressants, either used alone or in combination with antianxiety drugs, have become an important component in the treatment of anxiety. 

A delayed response in GAD is not as critical as with acute situational anxiety. A sensible approach (especially in benzodiazepine naive patients) is to start with buspirone for 6-8 weeks, at least 30 mg day increasing over 2-3 weeks to minimise unwanted actions patients should be warned not to expect an immediate benefit. Those who do not respond should receive an antidepressant (SSRI or venlafaxine) for 6-8 weeks at full therapeutic dose. There remain some patients, including those with a... 

Benzodiazepines (low-potency), carbamazepine, inositol, mirtazapine, nefazodone, reboxetine, reversible inhibitors of MAO type A (RiMA), valproate, venlafaxine... 

For treatment-resistant patients who do not respond to SSRIs or TCAs, or to the combination of TCAs/SSRIs with benzodiazepines, other antidepressants have shown at least some beneficial effects in alleviating PD symptoms (e.g. mirtazapine, moclobemide, nefazodone, phenelzine, reboxetine, and venlafaxine). Other agents have also been reported to exert beneficial effects in PD, especially when combined with SSRIs/TCAs (lithium, pindolol, and propranolol). In cases where all treatments have failed, valproate or olanzapine should be considered.2 - ° In order to optimize treatment, patients should avoid or reduce the consumption of compounds that could potentially induce/exacerbate panic attacks (e.g. caffeine, alcohol, and nicotine) and should exercise regularly. i... 

Anxiolytic antidepressants (trazodone, venlafaxine), clonazepam (or other benzodiazepines note that, generally, benzodiazepines are not recommended for long-term use in SAD), gabapentin,... 

Fluvoxamine inhibits liver drug-metabolizing enzymes. Dosages of alprazolam, theophylline, and warfarin must be reduced if any of these drugs are given concomitantly with fluvoxamine. Nefazodone may also decrease the metabolism of benzodiazepines, and venlafaxine may inhibit haloperidol metabolism. The answer is (B). 

Venlafaxine a racemate has no appreciable affinity for muscarinic, alpha-adrenergic, beta-adrenergic, histamine-1, 5-HT-lA, 5-HT-2, dopamine-2, benzodiazepine, or opiate receptors [45] and thus is not expected to induce side-effects caused by interaction of venlafaxine itself with these receptors. However, the possibility remained that metabolites of venlafaxine could have affinity for the above mentioned neuroreceptors and thereby cause unwanted side-effects. 

However, a pharmacodynamic interaction may occur. Hallucinations have been seen with zolpidem alone, and they have also occurred, rarely, when zolpidem and some benzodiazepines were given with the SSRIs , (below), which are related to venlafaxine. However, adverse effects such as these seem rare and the concurrent use of these drugs need not be avoided, but bear this possible interaction in mind if hallucinations occur. 

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