Kaplan + Sadock's Synopsis of Psychiatry, 11e

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29.23 Nefazodone and Trazodone

Erectile Disorder.  Trazodone is associated with an increased risk of priapism. Trazodone can potentiate erections resulting from sexual stimulation. It has thus been used to prolong erectile time and turgidity in some men with erectile disorder. The dosage for this indication is 150 to 200 mg a day. Trazodone-triggered priapism (an erection lasting more than 3 hours with pain) is a medical emergency. The use of trazodone for treatment of male erectile dysfunction has diminished considerably since the intro- duction of phosphodiesterase (PDE)-5 agents (see Chapter 25). Other Indications.  Trazodone may be useful in low dos- ages (50 mg a day) for controlling severe agitation in chil- dren with developmental disabilities and elderly persons with dementia. At dosages above 250 mg a day, trazodone reduces the tension and apprehension associated with generalized anx- iety disorder. It has been used to treat depression in patients with schizophrenia. Trazodone may have a beneficial effect on insomnia and nightmares in persons with PTSD. Precautions and Adverse Reactions The most common adverse effects associated with trazodone are sedation, orthostatic hypotension, dizziness, headache, and nau- sea. Some persons experience dry mouth or gastric irritation. The drug is not associated with anticholinergic adverse effects, such as urinary retention, weight gain, and constipation. A few case reports have noted an association between trazodone and arrhythmias in persons with preexisting premature ventricular contractions or mitral valve prolapse. Neutropenia, usually not of clinical significance, may develop, which should be consid- ered if persons have fever or sore throat. Trazodone may cause significant orthostatic hypotension 4 to 6 hours after a dose is taken, especially if taken concurrently with antihypertensive agents or if a large dose is taken without food. Administration of trazodone with food slows absorption and reduces the peak plasma concentration, thus reducing the risk of orthostatic hypotension. Because suicide attempts often involve ingestion of sleeping pills, it is important to be familiar with the symptoms and treat- ment of trazodone overdose. Patients have survived trazodone overdoses of more than 9 g. Symptoms of overdose include lethargy, vomiting, drowsiness, headache, orthostasis, dizzi- ness, dyspnea, tinnitus, myalgias, tachycardia, incontinence, shivering, and coma. Treatment consists of emesis or lavage and supportive care. Forced diuresis may enhance elimination. Treat hypotension and sedation as appropriate. Trazodone causes priapism, prolonged erection in the absence of sexual stimuli, in one of every 10,000 men. Trazo- done-induced priapism usually appears in the first 4 weeks of treatment but may occur as late as 18 months into treatment. It can appear at any dose. In such cases, trazodone use should be discontinued, and another antidepressant should be used. Pain- ful erections or erections lasting more than 1 hour are warning signs that warrant immediate discontinuation of the drug and medical evaluation. The first step in the emergency management of priapism is intracavernosal injection of an a 1 -adrenergic ago- nist pressor agent, such as metaraminol (Aramine) or epineph- rine. In about one-third of reported cases, surgical intervention was required. In some cases, permanent impairment of erectile function or impotence resulted.

both medications. Nefazodone also slows the metabolism of haloperidol (Haldol) so that the dosage of haloperidol should be reduced in persons taking both medications. Addition of nefazodone may also exacerbate the adverse effects of lithium carbonate (Eskalith). There are no known laboratory interferences associated with nefazodone. Dosage and Clinical Guidelines Nefazodone is available in 50-, 200-, and 250-mg unscored tablets and 100- and 150-mg scored tablets. The recommended starting dosage of nefazodone is 100 mg twice a day, but 50 mg twice a day may be better tolerated, especially by elderly per- sons. To limit the development of adverse effects, the dosage should be slowly raised in increments of 100 to 200 mg a day at intervals of no less than 1 week per increase. The optimal dos- age is 300 to 600 mg daily in two divided doses. However, some studies report that nefazodone is effective when taken once a day, especially at bedtime. Geriatric persons should receive dos- ages about two-thirds of the usual nongeriatric dosages, with a maximum of 400 mg a day. Similar to other antidepressants, clinical benefit of nefazodone usually appears after 2 to 4 weeks of treatment. Patients with premenstrual syndrome are treated with a flexible dosage that averages about 250 mg a day. Trazodone is readily absorbed from the GI tract and reaches peak plasma levels in about 1 hour. It has a half-life of 5 to 9 hours. Trazodone is metabolized in the liver, and 75 percent of its metabolites are excreted in the urine. Trazodone is a weak inhibitor of serotonin reuptake and a potent antagonist of serotonin 5-HT 2A and 5-HT 2C receptors. The active metabolite of trazodone is mCPP, which is an ago- nist at 5-HT 2C receptors and has a half-life of 14 hours. mCPP has been associated with migraine, anxiety, and weight loss. The adverse effects of trazodone are partially mediated by a 1 Therapeutic Indications Depressive Disorders.  The main indication for the use of trazodone is MDD. There is a clear dose–response relation- ship, with dosages of 250 to 600 mg a day being necessary for trazodone to have therapeutic benefit. Trazodone increases total sleep time, decreases the number and the duration of nighttime awakenings, and decreases the amount of REM sleep. Unlike tricyclic drugs, trazodone does not decrease stage 4 sleep. Tra- zodone is thus useful for depressed persons with anxiety and insomnia. Insomnia.  Trazodone is a first-line agent for the treatment of insomnia because of its marked sedative qualities and favor- able effects on sleep architecture (see above) combined with its lack of anticholinergic effects. Trazodone is effective for insom- nia caused by depression or use of drugs. When used as a hyp- notic, the usual initial dosage is 25 to 100 mg at bedtime. Trazodone Pharmacologic Actions

-adrenergic receptor antagonism.