Kaplan + Sadock's Synopsis of Psychiatry, 11e

997

29.23 Nefazodone and Trazodone

Table 29.22-3 Typical Dosage Forms and Recommended Dosages for Currently Available Monoamine Oxidase Inhibitors

Frampton JE, Plosker GL, Masand PS. Selegiline transdermal system in the treat- ment of major depressive disorder. Drugs. 2007;67:257. Goldberg JF, Thase ME. Monoamine oxidase inhibitors revisited: What you should know. J Clin Psychiatry. 2013;74(2):189–191. Holt A, Berry MD, Boulton AA. On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site, and effects thereby elicited. Neurotoxicology. 2004;25:251. Kennedy SH, Holt A, Baker GB. Monoamine oxidase inhibitors. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan & Sadock’s Comprehensive Textbook of Psychia- try. 9th edition. Vol. 2. Philadelphia: Lippincott Williams &Wilkins: 2009:3154. Maruyama W, Naoi M. “70th birthday professor riederer” induction of glial cell line-derived and brain-derived neurotrophic factors by rasagiline and (-)depre- nyl: A way to a disease-modifying therapy? J Neural Transm. 2013;120(1):83– 89. McGrath PJ, Stewart JW, Fava M, Trivedi MH, Wisniewski SR. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medi- cation trials for depression:A STAR*D report. Am J Psychiatry. 2006;163:1531. Nolen WA, Kupka RW, Hellemann G, Frye MA, Altshuler LL. Tranylcypromine vs. lamotrigine in the treatment of refractory bipolar depression: A failed but clinically useful study. Acta Psychiatr Scand. 2007;115:360. Salsali M, Holt A, Baker GB. Inhibitory effects of the monoamine oxidase inhibi- tor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C6, and CYP2D6. Cell Mol Neurobiol. 2004;24:63. Stahl SM, Felker A. Monoamine oxidase inhibitors: a modern guide to an unre- quited class of antidepressants. CNS Spectr. 2008;13:855. Tulen JH, Volkers AC, van den Broek WW, Bruijn JA. Sustained effects of phenel- zine and tranylcypromine on orthostatic challenge in antidepressant-refractory depression. J Clin Psychopharmacol. 2006;26:542. Verena H, Mergl R, Allgaier AK, Kohnen R, Möller HJ. Treatment of depression with atypical features: A meta-analytic approach. Psychiatry Res. 2006;141:89. Wood PL, Khan MA, Moskal JR, Todd KG, Tanay VAMI. Aldehyde load in ischemia-reperfusion injury: Neuroprotection by neutralization of reactive aldehydes with phenelzine. Brain Res. 2006;184. Nefazodone (Serzone) and Trazodone (Desyrel, Oleptro) are mechanistically and structurally related drugs approved as treat- ments for depression. Nefazodone (Serzone) is an analog of tra- zodone. When nefazodone was introduced in 1995, there were expectations that it would become widely used because it did not cause the sexual side effects and sleep disruption associated with the selective SSRIs. Although it was devoid of these side effects, it was nevertheless found to produce problematic seda- tion, nausea, dizziness, and visual disturbances. Consequently, nefazodone was never extensively adopted in clinical practice. This fact, as well as reports of rare cases of sometimes fatal hepatotoxicity, led the original manufacturer to discontinue pro- duction of branded nefazodone in 2004. Generic nefazodone remains available in the United States. Trazodone received Food and Drug Administration (FDA) approval in 1981 as a treatment for major depressive disorder (MDD). Its novel triazolopyridine chemical structure distin- guished it from the TCAs, and clinical trials suggested improved safety and tolerability compared with TCAs. There were high expectations that it would replace the older drugs as a mainstay of treatment for depression. However, the extreme sedation asso- ciated with trazodone, even at subtherapeutic doses, limited the clinical effectiveness of the drug. However, its soporific proper- ties made trazodone a favorite alternative to standard hypnotics as a sleep-inducing agent. Unlike conventional sleeping pills, trazodone is not a controlled substance. In 2010, the FDA approved an extended-release, once-daily formulation (Oleptro) as a treatment for MDD in adults. In the ▲▲ 29.23 Nefazodone and Trazodone

Maximum Dose (mg/day)

Usual Dose (mg/day)

Dosage (Oral) Formulation

Drug

Isocarboxazid (Marplan)

20–40

60

10-mg tablets

Phenelzine (Nardil)

30–60

90

15-mg tablets

Tranylcypromine (Parnate)

20–60

60

10-mg tablets

Rasagiline

0.5–1.0

1.0

0.5- or 1.0-mg tablets 5-mg tablets

Selegiline

10

30

(Eldepryl)

Moclobemide (Manerix)

300–600 600

100- or 150-mg tablets

and typical dosages. Phenelzine use should begin with a test dose of 15 mg on the first day. The dosage can be increased to 15 mg three times daily during the first week and increased by 15 mg a day each week thereafter until the dosage of 90 mg a day, in divided doses, is reached by the end of the fourth week. Tranylcypromine and isocarboxazid use should begin with a test dosage of 10 mg and may be increased to 10 mg three times daily by the end of the first week. Many clinicians and research- ers have recommended upper limits of 50 mg a day for isocar- boxazid and 40 mg a day for tranylcypromine. Administration of tranylcypromine in multiple small daily doses may reduce its hypotensive effects. Even though coadministration of MAOIs with TCAs, SSRIs, or lithium is generally contraindicated, these combinations have been used successfully and safely to treat patients with refractory depression. However, they should be used with extreme caution. Hepatic transaminase serum concentrations should be moni- tored periodically because of the potential for hepatotoxicity, especially with phenelzine and isocarboxazid. Elderly persons may be more sensitive to MAOI adverse effects than are younger adults. MAO activity increases with age, so MAOI dosages for elderly persons are the same as those required for younger adults. The use of MAOIs for children has had minimal study. Studies have suggested that transdermal selegiline has anti- depressant properties. Although selegiline is a type B inhibitor at low doses, it becomes less selective as the dose is increased. R eferences Adli M, Pilhatsch M, Bauer M, Köberle U, Ricken R, Janssen G, Ulrich S, Bschor T. Safety of high-intensity treatment with the irreversible monoamine oxidase inhibitor tranylcypromine in patients with treatment-resistant depression. Phar- macopsychiatry. 2008;41:252. Amsterdam JD, Bodkin JA. Selegiline transdermal system in the prevention of relapse of major depressive disorder: A 52-week, double-blind, placebo-substitution, parallel-group clinical trial. J Clin Psychopharmacol. 2006;26:579. Balu DT, Hoshaw BA, Malberg JE. Differential regulation of central BDNF pro- tein levels by antidepressant and non-antidepressant drug treatments. Brain Res. 2008;1211:37. Baker GB, Sowa S, Todd KG. Amine oxidases and their inhibitors: What can they tell us about neuroprotection and the development of drugs for neuropsychiatric disorders? J Psychiatr Neurosci. 2007;32:313. Elmer LW, Bertoni JM. The increasing role of monoamine oxidase type B inhibi- tors in Parkinson’s disease therapy. Expert Opin Pharmacother. 2008;9:2759.