Mirtazapine SSRIs

The starting dose is the usual therapeutic dose for most of the SSRIs, duloxetine, and mirtazapine, whereas there is usually need for at least some upward titration of venlafaxine, bupropion,... 

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... 

Lee etal. (2005) 5-HT6 (C267T) SSRIs, SNRIs, mirtazapine nefazodone, TCAs... 

Fluvoxamine SSRIs, SNRIs, mirtazapine, nefazodone, TCAs Milnacipran... 

Mirtazapine (Remeron) is a newer antidepressant that also blocks 5-HT reuptake, but additionally has antagonistic effects at adrenergic o2, 5-HT2, and 5-HT3 receptors (Stahl 1998). Mirtazapine appears to have indirect agonistic effects on 5-HTlA receptors, which may contribute to its antidepressant effect (Berendsen and Broekkamp 1997). Nefazodone, as well, has SSRI and 5-HT2 antagonist effects. The 5-HT2 antagonist effects of these antidepressants is believed to be responsible for their lower incidence of sexual side effects (Nutt 1997). 

Many commonly used medications also contain substances that are eliminated by the MAOIs and must not be taken by these patients. The list of medications to be avoided inclndes the narcotic pain reliever meperidine (Demerol), and many over-the-connter cold remedies containing dextromethorphan or pseudoephedrine. Finally, patients taking MAOIs must also avoid medications that elevate serotonin levels. This inclndes certain appetite snppressants and antidepressants including the SSRIs, venlafaxine, duloxetine, mirtazapine, nefazodone, and trazodone. Medications that interact with the MAOIs cannot be taken until at least 2 weeks after the MAOI has been stopped. 

Atypical Antidepressants. The atypical antidepressants are not a true class in the same sense as SSRIs or TCAs. There is no unifying property to these antidepressants. Each of these antidepressants is actually a class unto itself that is structurally and functionally different from all other antidepressants. The atypical antidepressants include trazodone (Desyrel), bupropion (Wellbutrin), venlafaxine (Effexor), duloxetine (Cymbalta), nefazodone (Serzone), and mirtazapine (Remeron). 

Dementia SSRIs Bupropion Duloxetine Mirtazapine Nefazodone Trazodone Venlafaxine TCAs... 

Depression SSRIs SNRIs Mirtazapine Bupropion Nortriptyline Desipramine ... 

Serotonin-Boosting Antidepressants. The SSRIs have also been studied in the treatment of generalized social anxiety disorder, and paroxetine, sertraline, and venlafaxine are effective. Preliminary data suggests that the serotonin-boosting atypical antidepressants (mirtazapine and nefazodone) may also be helpful. Like the MAOIs, they appear to be effective at doses comparable to those used to treat depression. They may help avoidant patients to gradually increase their social interaction and become more assertive. 

Antidepressants. The most widely used psychiatric medicines with the broadest range of application in TBI patients are undoubtedly the SSRI antidepressants. They are well tolerated, unlikely to worsen any of the preexisting deficits associated with TBI, and offer relief from not only depression but also impulsivity and virtually all variants of anxiety in these patients. As such, SSRIs are the preferred first-line treatment for all anxiety disorders after TBI. Other newer antidepressants that also work (at least in part) by boosting serotonin activity, namely, mirtazapine (Remeron), nefazodone (Serzone), venlafaxine (Effexor XR), and duloxetine (Cymbalta) can also be considered, but they have not been well studied in patients with TBI. In... 

Fenfluramine Dextromethorphan Meperidine Methylene dioxymethamphetamine Meta-chlorophenylpiperazine (mCPP) Trazodone (mCPP) Selegiline Nefazodone Trazodone Pethidine Tramadol Mirtazapine TCA medications Venlafaxine SSRI agents... 

Currently, the antidepressants of choice are the SSRIs because they have been shown to be efficacious and safe for the treatment of children and adolescents with MDD, but further research on the other new antidepressants (e.g., bupropion, venlafaxine, nefazodone, mirtazapine) is needed. Patients should be treated with adequate doses for at least 6 weeks before declaring lack of response to treatment (treatment of nonresponders is described below) (AACAP, 1998 Hughes et ah, 1999 Fig. 36.1). 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

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),... 

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. 

With this caveat in mind, each side of the debate has evidence to support its position. The evidence is first summarized supporting the position that SSRIs are less effective than are some other antidepressants (particularly those with dual effects on both serotonin and NE CNS systems) in patients with more severe depression or who are hospitalized. Danish investigators in two double-blind, active-controlled studies found that clomipramine produced a superior response with either paroxetine or citalopram in the treatment of patients hospitalized for major depression (116, 117). Two double-blind studies also have shown that venlafaxine and mirtazapine were more effective than fluoxetine in patients hospitalized with depression ( 114,118). Finally, there are studies showing that the addition of desipramine (one of the most selective NE reuptake inhibitors) to an SSRI can convert nonresponders or pamal responders to full response ( 119, 119a, 120). 

No comparable long-term studies have been done with the SSRIs, bupropion, nefazodone, venlafaxine, or mirtazapine. 

Fava M, Dunner D, Griest J, et al. An open-label study with mirtazapine in depressed patients who are SSRI treatment failures. New Research Program Abstracts, 152nd Annual Meeting of the American Psychiatric Association, Chicago, 2000 186(abst). 

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