Stone EA, Lin Y, Quartermain D: A final common pathway for depression? Progress toward a general conceptual framework. Neurosci Biobehav Rev 2008;32:508.
Thase ME et al: A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults. Eur Neuropsychopharmacol 2016;26:979.
Tuccori M et al: Use of selective serotonin reuptake inhibitors during pregnancy and risk of major and cardiovascular malformations: An update. Postgrad Med 2010;122:49.
Warden D et al: The STAR *D Project results: A comprehensive review of findings. Curr Psychiatry Rep 2007;9:449.
Wheeler BW et al: The population impact on incidence of suicide and non-fatal self harm of regulatory action against the use of selective serotonin reuptake inhibitors in under 18s in the United Kingdom: Ecological study. Br Med J 2008;336(7643):542.
Wilson KL et al: Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol 2011;28:19.
Yu S, Holsboer F, Almeida OF: Neuronal actions of glucocorticoids: Focus on depression. J Steroid Biochem Mol Biol 2008;108:300.
The patient has previously responded to fluoxetine, so this drug is an obvious choice. However, she is taking other drugs and fluoxetine, the prototype SSRI, has a number of pharma-cokinetic and pharmacodynamic interactions. Fluoxetine is a CYP450 2D6 inhibitor and thus can inhibit the metabolism of 2D6 substrates such as propranolol and other β block-ers; tricyclic antidepressants; tramadol; opioids such as methadone, codeine, and oxycodone; antipsychotics such as haloperidol and thioridazine; and many other drugs. This inhibition of metabolism can result in significantly higher plasma levels of the concurrent drug, and this may lead to an increase in adverse reactions associated with that drug. As a potent inhibitor of the serotonin transporter, fluox-etine is associated with a number of pharmacodynamic interactions involving serotonergic neurotransmission. The combination of tramadol with fluoxetine has occasionally been associated with a serotonin syndrome, characterized by diaphoreses, autonomic instability, myoclonus, seizures, and coma. The combination of fluoxetine with an MAOI is contraindicated because of the risk of a fatal serotonin syndrome. In addition, meperidine is specifically contrain-dicated in combination with an MAOI. An interaction with hydrochlorothiazide is not likely.
Mark A. Schumacher, PhD, MD Allan I. Basbaum, PhD, & Ramana K. Naidu, MD
A 60-year-old man with a history of methamphetamine use and moderate chronic obstructive pulmonary disease presents in the emergency department with a broken femur suffered in an automobile accident. He complains of severe pain. What is the most appropriate immediate treatment for his pain? Are any special precautions needed?