Trazodone monoamine oxidase

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... 

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. 

Although trazodone is related to nefazodone it probably potentiates 5-HT neurotransmission less. Trazodone is often added to monoamine oxidase inhibitors and serotonin re-uptake inhibitors at low doses (50-150 mg/day) as a hypnotic. In one case the combination of trazodone with nefazodone provoked the serotonin syndrome (37). 

Adverse interactions of lithium with tricyclic antidepressants, SSRIs, and monoamine oxidase inhibitors have been reviewed (581). In reviews of antidepressants and the serotonin syndrome, a possible contributory role has been suggested for lithium, based on case reports with tricyclic antidepressants, SSRIs, trazodone, and venlafax-ine (204,582). 

Antidepressant drugs A major class of psychotropic drugs with diverse chemical configurations including the monoamine oxidase inhibitors (MAOIs), the heterocyclic drugs (composed of mono-, di-, tri-, and hetero-cyclics), the serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, trazodone, and venlafaxine), and bupropion are more recent innovations. Antidepressants usually must be taken for several weeks to have the desired effect and they often have a low therapeutic index, so they must be closely monitored. 

Antidepressants are divided into the following classes the dibenzapine derivatives are called tricyclic antidepressants and include imipramine (Tofranil), desipramine (Norpramin), amitriptyline (Elavil), nortriptyline (Aventyl), protriptyline (Vivactil), and doxepin (Adapin). The monoamine oxidase inhibitors are nsed occasionally to treat depression. The hydrazine derivatives consist of isocarboxazid (Marplan) and phenelzine sulfate (Nardil). The nonhydrazine derivatives inclnde tranylcypromine (Parnate). L-Tryptophan is the only member of the monoamine precnrsors nsed to treat depression. The newer and second-generation antidepressants inclnde amoxapine, doxepin, flnoxetine, maprotiline, trazodone, mianserin, alprazolam, and bnpropion (see also Tables 5 throngh 7). 

Trimipramine is contraindicated in patients with known hypersensitivity to tricyclic antidepressants, trazodone, and related compounds in the acute recovery phase of myocardial infarction (MI), because the drug depresses cardiac function and causes dysrhythmia in patients in coma or severe respiratory depression (additive CNS and respiratory depression) and during or within 14 days of therapy with monoamine oxidase inhibitors. 

Many noncyclic antidepressants are now available, including trazodone (Desyrel l), nefazodone (Serzone ), fluoxetine (Prozac ), sertraline (Zolotf ), citalopram (Celexa ), escitalopram (Lexapro ), paroxetine (Paxil ), tluvoxamine (Luvox ), venlafaxine (Effexor ), and bupropion (Wellbutrin ). Bupropion is also marketed under the brand name Zyban tor smoking cessation. Mirtazapine (Remeron ), a tetracyclic antidepressant, has recently become available. In general, these drugs are much less toxic than the tricyclic antidepressants (see p 90) and the monoamine oxidase (MAO) inhibitors (p 269), although serious effects such as seizures and hypotension occasionally occur. Noncyclic and tricyclic antidepressants are described in Table 11-7. 

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