Kaplan + Sadock's Synopsis of Psychiatry, 11e

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Chapter 29: Psychopharmacological Treatment

The use of trazodone is contraindicated in pregnant and nursing women. Trazodone should be used with caution in per- sons with hepatic and renal diseases. Drug Interactions Trazodone potentiates the CNS depressant effects of other cen- trally acting drugs and alcohol. Concurrent use of trazodone and antihypertensives may cause hypotension. No cases of hyper- tensive crisis have been reported when trazodone has been used to treat MAOI-associated insomnia. Trazodone can increase levels of digoxin and phenytoin. Trazodone should be used with caution in combination with warfarin. Drugs that inhibit CYP3A4 can increase levels of trazodone’s major metabolite, mCPP, leading to an increase in side effects. Laboratory Interferences No known laboratory interferences are associated with the administration of trazodone. Dosage and Clinical Guidelines Trazodone is available in 50-, 100-, 150-, and 300-mg tablets. Once-a-day dosing is as effective as divided dosing and reduces daytime sedation. The usual starting dose is 50 mg before sleep. The dosage can be increased in increments of 50 mg every 3 days if sedation or orthostatic hypotension does not become a problem. The therapeutic range for trazodone is 200 to 600 mg a day in divided doses. Some reports indicate that dosages of 400 to 600 mg a day are required for maximal therapeutic effects; other reports indicate that 250 to 400 mg a day is sufficient. The dosage may be titrated up to 300 mg a day; then the per- son can be evaluated for the need for further dosage increases on the basis of the presence or the absence of signs of clinical improvement. Once-daily trazodone is available as bisectable tablets of 150 mg or 300 mg. The starting dosage of the extended-release formulation is 150 mg once daily. It may be increased by 75 mg per day every 3 days. The maximum dosage is 375 mg per day. Dosing should be at the same time every day in the late evening, preferably at bedtime, on an empty stomach. Tablets should be swallowed whole or broken in half along the score line. R eferences Ciraulo DA, Knapp C, Rotrosen J, Sarid-Segal O, Seliger C. Nefazodone treat- ment of cocaine dependence with comorbid depressive symptoms. Addiction. 2005;100(Suppl 1):23. DeSanty KP, Amabile CM. Antidepressant-induced liver injury. Ann Pharmaco- ther. 2007;41(7):1201. Dykens JA, Jamieson JD, Marroquin LD, Nadanaciva S, Xu JJ, Dunn MC, Smith AR, Will Y. In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone, and buspirone. Toxicol Sci. 2008;103(2):335. Goldberg JF. A preliminary open trial of nefazodone added to mood stabilizers for bipolar depression. J Affect Disord. 2013;144(1–2):176–178. Hettema JM, Kornstein SG. Trazodone. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Vol. 2. Philadelphia: Lippincott Williams & Wilkins: 2009:3253. Khan AA, Kornstein SG. Nefazodone. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Vol. 2. Philadelphia: Lippincott Williams & Wilkins: 2009:3164. Kocsis JH, Leon AC, Markowitz JC, Manber R, Arnow B, Klein DN, Thase ME. Patient preference as a moderator of outcome for chronic forms of major depressive disorder treated with nefazodone, cognitive behavioral analysis sys- tem of psychotherapy, or their combination. J Clin Psychiatry. 2009;e1–e8, pii.

Kostrubsky SE, Strom SC, Kalgutkar AS, Kulkarni S, Atherton J. Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. Toxicol Sci. 2006;90(2):451. Owens MJ, Dole KC, Knight DL, Nemeroff CB. Preclinical evaluation of the puta- tive antidepressant nefazodone. Depression. 2008;1(6):315. Papakostas GI, Fava M. A meta-analysis of clinical trials comparing the serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with selective sero- tonin reuptake inhibitors for the treatment of major depressive disorder. Eur Psychiatry. 2007;22(7):444. Passos SR, Camacho LA, Lopes CS, dos Santos MA. Nefazodone in out-patient treatment of inhaled cocaine dependence: A randomized double-blind placebo- controlled trial. Addiction. 2005;100(4):489. Sasada K, Iwamoto K, Kawano N, et al. Effects of repeated dosing with mirtazap- ine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers. Human Psychopharmacology: Clinical and Experimental. 2013;28(3):281–286. Schatzberg AF, Rush AJ, Arnow BA, Banks PL, Blalock JA. Chronic depression: Medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not. Arch Gen Psychiatry. 2005;62(5):513. Schatzberg AF, Prather MR, Keller MB, Rush AJ, Laird LK. Clinical use of nefazodone in major depression: A 6-year perspective. J Clin Psychiatry. 2002; 63(1):18. Tanimukai H, Murai T, Okazaki N, et al. An observational study of insomnia and nightmare treated with trazodone in patients with advanced cancer. Am J Hosp Palliat Care. 2013;30(4):359–362. VanAmeringen M, Mancini C, Oakman J. Nefazodone in the treatment of general- ized social phobia: A randomized, placebo-controlled trial. J Clin Psychiatry. 2007;68(2):288. Xu JJ, Henstock PV, Dunn MC, SmithAR, Chabot JR, de Graaf D. Cellular imaging predictions of clinical drug-induced liver injury. Toxicol Sci. 2008;105(1):97. Opioid receptor agonists are a structurally diverse group of compounds that are used for pain management. These drugs are also called narcotics. Although highly effective as analge- sics, they often cause dependence and are frequently diverted for recreational use. Commonly used opioid agonists for pain relief include morphine, hydromorphone (Dilaudid), codeine, meperidine (Demerol), oxycodone (OxyContin), buprenorphine (Buprenex), hydrocodone (Robidone), tramadol (Ultram), and fentanyl (Durogesic). Heroin is used as a street drug. Metha- done is used both for pain management and for treatment of opiate addiction. This chapter focuses on the m -opioid receptor agonists that are most likely to be used in the treatment of psy- chiatric disorders instead of pain management. It is now recognized that the pharmacology of the opioid sys- tem is complex. There are multiple types of opioid receptors, with m - and k -opioid receptors representing functionally oppos- ing endogenous systems (Table 29.24-1). All of the compounds above, which represent the most extensively used narcotic anal- gesics, are agonists at m -opioid receptors. However, analgesic effects also result from antagonist effects on the k -opioid recep- tor. Buprenorphine has mixed receptor effects, being primarily a m -opioid receptor agonist as well as a k -opioid antagonist. There is growing interest in the use of some drugs that act on opioid receptors as alternative treatments for a subpopulation of patients with refractory depression, as well as treatment for cut- ting behavior in patients with borderline personality disorder. Consideration of such off-label use is tempered by the well- known fact that ongoing, regular use of opioids produces depen- dence and tolerance and may lead to maladaptive use, functional impairment, and withdrawal symptoms. The prevalence of ▲▲ 29.24 Opioid Receptor Agonists