Trazodone action

Atypical Antidepressants. StmcturaHy diverse dmgs such as the tetracyclic mianserin (46) and various bicyclic and tricyclic compounds such as trazodone (47), venlafaxine (48), nefazodone (49), and amfebutamone (50) are atypical antidepressants. The exact mechanism of action is unclear but probably... 

Two rather broad structural classes account for the large majority of drugs that have proven useful in the clinic for treating depression. Each of these has associated with it some clearly recognized side effects the monoamine oxidase inhibitors, most commonly derivatives of hydrazine, tend to have undesirable effects on blood pressure the tricyclic compounds on the other hand may cause undesirable changes in the heart. Considerable effort has thus been expended toward the development of antidepressants that fall outside those structural classes. An unstated assumption in this work is the belief that very different structures will be associated with a novel mechanism of action and a different set of ancillary activities. One such compound, trazodone... 

Hwang EC, Van Woert MH. 1979. Serotonin-norepinephrine interactions in the tremorolytic actions of phenoxybenzamine and trazodone. Pharmacol Biochem Behav 10(1) 27-29. 

The triazolopyridine trazodone does not have an appreciable effect on the re-uptake of the neurotrans-mittors dopamine or noradrenaline. It is a weak inhibitor of serotonin re-uptake but is a potent antagonist of the serotonin 5-HT2 receptor. Clinical experience has shown unpredictable efficacy. Trazodone has little antimuscarinic activity and has little if any action on cardiac conduction. Like mianserin it can therefore safely be used in patients for which anticholinergics are contraindicated and there are no absolute contraindications for patients with concomitant diseases of the cardiovascular system. 

Trazodone (Apothecon) is also classified as an antidepressant agent. It is a selective serotonin reuptake inhibitor (SSRI), partial agonist at postsynaptic 5-HTia receptors, and exhibits a-adrenoceptor blocking actions. 

Therapy with phentolamine may result in reflex tachycardia, arrhythmias, and hypotension the latter effect can be exacerbated by other vasodilatory drugs and by the simultaneous ingestion of ethanol. The pharmacological actions of trazodone can be reduced by paroxetine and possibly other SSRIs. 

On the basis of the large placebo-controlled studies, mirtazapine has undoubted antidepressant action and is licensed in both Europe and the United States [Claghorn and Lesem 1995 Sitsen et al. 1995). The evidence for superior efficacy is again limited by the failure to set up studies that were large enough to provide an adequate test of two active antidepressants. Nevertheless, mirtazapine has been shown to be more effective than trazodone in hospitalized patients with major depression (van Moffaert et al. 1995) and in a more recent study, mirtazapine was more effective than fluoxetine given in a dose of 20 mg [S. A. Montgomery 1996). 

Marek GJ, McDougle CJ, Price EH, et al A comparison of trazodone and fluoxetine implications for a serotonergic mechanism of antidepressant action. Psychopharmacology 109 2-11, 1992... 

Because nefazodone does inhibit the 5-HT uptake pump, it has the same class warning against combined use with an MAOl. Nevertheless, there are several reasons to suspect that there may be less risk of this interaction with nefazodone than other serotonin uptake pump inhibitors. First, trazodone, an analogue of nefazodone, is one of the few antidepressants that can be used in combination with an MOAI with minimal risk of an adverse interaction. Second, the most potent action of nefazodone is 5-HT2a receptor blockade, rather than 5-HT uptake inhibition. Nonetheless, we recommend the conservative approach of avoiding this combination, particularly when using high doses (i.e., > 450 mg per day), at which appreciable serotonin uptake inhibition is produced by nefazodone. 

Some of the same augmentation strategies discussed in detail in Chapter 7 for the treatment of depression, mentioned above for the treatment of OCD, can also be applied to the treatment of panic disorder. Thus, adding the 5HT2A antagonist trazodone to an SSRI can boost the actions of an SSRI, as possibly also could the... 

The newer agents that may have actions that are novel or atypical include maprotiline, amoxapine, fluoxetine, trazodone, bupropion, mianserin, and alprazolam. 

Three antidepressants—nefazodone, venlafaxine, and mirtazapine—are all related to earlier agents in either structure or mechanism of action. Nefazodone is closely related to trazodone but is less sedating. It produces fewer adverse sexual effects than the SSRIs but is a potent inhibitor of CYP3 A4. (Fluvoxamine causes the same inhibition of CYP3 A4.)... 

Although it is claimed to be relatively free of effects usually attributed to anticholinergic activity, trazodone does cause complaints of dry mouth and blurred vision, which may be mediated through its actions on alpha-adrenoceptors. Urinary retention has been reported in a 69-year-old woman taking a combination of trazodone and an anticholinergic drug (isopropamide iodide) (15). Cholinergic overactivity has also been described in two patients after withdrawal (16). 

Inhibition of ejaculation was reported in a middle-aged man 1 week after he started taking trazodone 100 mg at night (27). The symptoms abated 3 days after withdrawal and did not return when treatment was changed to dox-epin 50 mg/day. Because trazodone has relatively more alpha-adrenoceptor blocking action and less anticholinergic activity than doxepin, the author speculated that this was the mechanism. 

Trazodone can not only improve insomnia in depressed patients treated with antidepressants, but can also be an effective booster of antidepressant actions of other antidepressants (use combinations of antidepressants with caution as this may... 

An alternative categorisation of antidepressants is based solely on mechanism of action (Fig. 19.1). The majority of antidepressants, including TCAs, SSRIs and related compounds are reuptake inhibitors. Certain novel agents including trazodone and mirtazapine are receptor blockers while MAOIs are enzyme inhibitors. 

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