Selective serotonin reuptake inhibitors trazodone

Antidepressants Trazodone, mirtazapine, paroxetine, other selective serotonin reuptake inhibitors venlafaxine... 

Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. 

Trazodone, 25 to 100 mg, is often used for insomnia induced by selective serotonin reuptake inhibitors or bupropion. Side effects include serotonin syndrome (when used with other serotonergic drugs), oversedation, a-adrenergic blockade, dizziness, and rarely priapism. 

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. 

This case report (Figures 6-4Ato 6-4C) (McDermut et al. 1995) of selective response to dihydropyridine CCBs but not a phenylalkylamine CCB is of considerable interest in relationship to the patient s history of nonre-sponsivity to multiple tricyclic antidepressants, the selective serotonin reuptake inhibitors, lithium, carbamazepine (the patient developed drug-induced hepatitis on carbamazepine and was unable to be evaluated), alprazolam, trazodone, and phenelzine. This suggests that patients with refractory mood disorders may have differential responses to various CCBs and that nonresponse to one CCB does not preclude response to another CCB, particularly if the other CCB is from a different category (Table 6-3). 

It is thus understandable why some earlier authors previously doubted the efficacy of antidepressants in general (Weiner et al.. 1980) or the advantages of newer antidepressants compared with classical products (Song et al., 1993). However, the great majority of doctors and scientific authors consider that the efficacy of first-generation antidepressants (imipramine, amitriptyline, nortriptyline) has been proved beyond any reasonable doubt, and that efficacy also has been demonstrated for newer products such as trazodone, the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake... 

Insomnia caused by major psychiatric illnesses often responds to specific pharmacological treatment for that illness. In major depressive episodes with insomnia, for example, the selective serotonin reuptake inhibitors, which may cause insomnia as a side effect, usually will result in improved sleep because they treat the depressive syndrome. In patients whose depression is responding to the serotonin reuptake inhibitor but who have persistent insomnia as a side effect of the medication, judicious use of evening trazodone may improve sleep, as well as augment the antidepressant effect of the reuptake inhibitor. However, the patient should be monitored for priapism, orthostatic hypotension, and arrhythmias. 

Most prominent among the psychotropics that enhance serotonergic transmission are the selective serotonin reuptake inhibitors (SSRIs), which may induce sexual dysfunction in as many as 50-75% of patients, in part by activation of central 5-HT2 receptors. Antidepressants that antagonize the 5-HT2 receptor, such as mirtazapine and trazodone, cause fewer sexual side-effects compared with the SSRIs. Stimulation of the 5-HTia receptor facilitates sexual functioning, while activation of the 5-HTib,id and 5-HTic receptors inhibits... 

Phenytoin, a liver enzyme inducer, decreases serum levels of TCAs (especially desipramine and clomipramine). An increase in serum levels of nortriptyline and trazodone has also been reported. In these cases, the net effect of enzyme induction (by phenytoin) and enzyme inhibition (by TCAs) seem to be in favor of the inhibitory effects. Carbamazepine also induces liver enzymes, with a consequent reduction in serum levels of TCAs (amitriptyline, desipramine, doxepin, and nortriptyline). These effects of carbamazepine have not been observed with clomipramine, but have been reported with selective serotonin reuptake inhibitors (SSRIs). 

C. Serotonin uptake inhibitors (often called selective serotonin reuptake inhibitors or SSRIs) such as fluoxetine, citalopram, sertraline, paroxetine, flu-voxamine, venlafaxine, and trazodone may interact with each other or with chronic use of an MAO inhibitor (see p 269) to produce the serotonin syndrome (see below and p 21). 

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. 

The older tricyclic agents show less than a ten-fold selectivity in inhibiting noradrenaline over that for 5-HT (e.g. desipramine, imipramine, nortriptyline) through amitryptyline. which shows virtually no selectivity, to trazodone, zimelidine and clomipramine, which are somewhat 5-HT selective. The newer Serotonin-Selective Reuptake Inhibitors (SSRIs) show a higher selectivity for inhibition of 5-HT reuptake in the brain, and have a different pharmacology. Examples clinically used include citalopram, fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline, trazodone and venlafaxine. Experimental agents include 6-nitroquipazine, alaproclate, litoxetine, indatraline and p-CIT. 

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