Depression trazodone

The only examples of ring oxidation are the one-electron anodic oxidation of Nl-aryl[l,2,4]triazolo[4,3-a]pyridines such as compound 143 to give quaternary salts (88ZC187), and the voltammetric oxidation of the anti-depressant Trazodone (Section V.A) (87MI1). 

Antidepressant medications with sedating properties have been frequently used for insomnia. Although mirtazapine and nefazodone are still being used in patients with depression, trazodone is commonly used for the sole purpose of treating insomnia. Trazodone blocks serotonin 2A receptors and has significant sedating properties. The efficacy of trazodone as an antidepressant occurs at high doses but at lower doses it is safely used as a hypnotic. Mirtazapine and nefazodone also block serotonin 2A receptors and have occasionally been used as sedative-hypnotics. 

Trazodone (150 mg/day) is indicated in the treatment of depression. Trazodone selectively inhibits serotonin reuptake in the brain, causes beta-receptor subsensitivity, and induces significant changes in serotonin-receptor binding with only a slight effect on alpha-adrenergic receptors. Also, trazodone potentiates the action of 5-hydroxytryp-tophan, the precursor of serotonin (see also Tables 5 through 7). 

By far the most important compound covered by this chapter is trazodone (257) (Desyrel in the USA), a 1,2,4-triazolo [4,3-a] pyridin3(2//)-one marketed in a number of countries around the world as a treatment for depression. Trazodone blocks the re-uptake of 5-HT into serotoninergic neurons and is also a potent central antagonist of 5-HT <81LS2449>. Compound (258), a closely... 

Trazodone routinely causes sedation, which is why it is used far more often as an adjunct with other antidepressants for sleep than as a primary agent for the treatment of depression. Priapism is a rare but serious adverse effect in males who take trazodone. In addition, orthostatic hypotension and dizziness are more common with trazodone than with nefazodone because the latter agent has a weaker effect at a-adrenergic receptors and also has a balancing of adrenergic effects owing... 

It is not clear that inhibition of adenosine deaminase is the basis for the clinical efficacy of Trazodone for the treatment of depression. 

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... 

Trazodone (Desyrel). Trazodone was the first of the atypical antidepressants and was actually introduced prior to the SSRIs. It does not have the serious cardiac toxicity or anticholinergic side effects of the TCAs and was the most popular antidepressant until the arrival of the SSRIs. It is approved for the treatment of depression and is also commonly used in low doses to treat agitation in demented patients and insomnia. 

Antidepressants. In the early 1980s, the recognition that depression is a frequent comorbid feature of BN coupled with the observation that appetite changes are a common feature of depression led researchers to evaluate antidepressant treatment for BN. Since that time, a series of controlled studies have demonstrated efficacy for a wide assortment of antidepressants including the TCAs imipramine (Tofranil) and desipramine (Norpramin), the MAOl phenelzine (Nardil), the SSRl fluoxetine (Prozac), and the atypical antidepressants trazodone (Desyrel) and bupropion (Wellbutrin). Overall, approximately two-thirds of antidepressant-treated patients with bulimia experience symptomatic improvement while nearly one-third achieves complete remission of binging and purging. In addition, the improvement in the symptoms of BN is not dependent on the presence of comorbid depression. 

The antidepressant trazodone (Desyrel) is commonly used in low doses to treat agitation or insomnia in dementia patients. However, older patients often do not tolerate the higher doses of trazodone needed to treat depression. 

Trazodone Blocks histamine receptor KSerotonin Depression Insomnia... 

These include trazodone and a derivative of its metabolite nefazodone, both of which are strongly sedative, an effect which has been attributed to their potent alpha-1 receptor antagonism rather than to any antihistaminic effects. A main advantage of these drugs in the treatment of depression is that they appear to improve the sleep profile of the depressed patient. Their antidepressant activity is associated with their weak 5-HT reuptake inhibition and also a weak alpha-2 antagonism. However, unlike most of the second-generation antidepressants, neither drug is effective in the treatment of severely depressed patients. Furthermore, there is some evidence that trazodone can cause arrythmias, and priapism, in elderly patients. 

Suicidality in children and adolescents Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of trazodone or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Trazodone not approved for use in pediatric patients (see Clinical worsening and suicide risk and Children sections in Warnings). 

Drugs that may affect trazodone include carbamazepine, phenothiazines, and venlafaxine. Drugs that may be affected by trazodone include alcohol, barbiturates, CNS depressants, digoxin, MAOIs, phenytoin, and warfarin. 

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. 

HT2 antagonists like trazodone, nefazodone, clozapine and risperidone are used in the treatment of schizophrenia and depression. They block adrenoceptors and Hi-histamine-receptors as well. Hypotension, drowsiness and weight gain can occur. 

Haria, M., Fitton, A., and McTavish, D. (1994) Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging 4 331—355. 

Other new antidepressants, including bupropion, ven-lafaxine, nefazodone, and mirtazapine, have been found to be efficacious in the treatment of depressed adults, but only a few open-label studies have been carried out in children and adolescents (e.g., Daviss et ah, 2001). Bupropion and velanfaxine may be useful in treating youth with MDD and ADHD (Plizka, 2000 Daviss et ah, 2001). Because of the sedative effects of mirtazapine and trazodone, these medications have been used as adjunctive treatments for patients with severe insomnia. 

Venlafaxine, paroxetine, sertraline, imipramine, and trazodone have all proven effective in relieving symptoms of GAD. Venlafaxine, a combined serotonin and norepinephrine reuptake blocker, may be an exceptionally good choice for people who have other psychiatric illnesses in addition to GAD, or when it is not clear whether the patient has GAD or a depressive illness, or both. Although, to date, only certain SSRIs have been... 

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). 

Mouret J, Lemoine P, Minuit MP, et al Effects of trazodone on the sleep of depressed subjects, a polygraphic study. Psychopharmacology 95 (suppl) S37-S43, 1988... 

Nierenberg AA, Amsterdam JD Resistant depression definition and treatment approaches. J Chn Psychiatry 51 (suppl) 39-47, 1990 Nierenberg AA, Adler LA, Peselow E, et al Trazodone for antidepressant-associated insomnia. Am J Psychiatry 151 1069-1072, 1994a Nierenberg AA, Feighner JP, Rudolph R, et al Venlafaxine for treatment-resistant unipolar depression. J Chn Psychopharmacol 14 419-423, 1994b... 

Ware JC Increased deep sleep after trazodone use a double-blind placebo-controlled study in healthy young adults. J Clin Psychiatry 519 (suppl) 18-22, 1990 Ware JC, Brown FW, Morad PJ, et al Effects on sleep a double blind study comparing trimipramine to imipramine in depressed insomniac patients. Sleep 12 537-549, 1989... 

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