Escitalopram Treatment of Depression in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome A Randomized, Double-Blind, Placebo-Controlled Study Jacqueline Hoare, MD, FCPsych, Mphil,* Paul Carey, PhD,Þ John A. Joska, MMed, FCPsych,* Henri Carrara, MPH,þ Katherine Sorsdahl, PhD,* and Dan J. Stein, FCPsych, PhD* Abstract: Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syn- drome. Large randomized studies of newer selective serotonin reuptake in- hibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale ( p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered. Key Words: Randomized controlled study, depression, HIV (J Nerv Ment Dis 2014;202: 133Y137) D epression can be a chronic and impairing illness in people living with human immunodeficiency virus (HIV)/acquired immuno- deficiency syndrome (AIDS). Depression occurs in almost twice as many people with HIV when compared with the general population in the developed world (Ciesla and Roberts, 2001). In lower- and middle-income countries, indications are that depression affects up- ward of 30% of HIV clinic attendees (Olley et al., 2004). In a South African primary care context, identification of de- pression was generally poor (Carey et al., 2003) and perhaps even worse in clinics focused on chronic medical illnesses including HIV (Evans et al., 1996). Later in the illness, overlap with HIV symptoms (Jacobsberg and Perry, 1992) and side effects from antiretroviral treatment in more advanced disease may serve to complicate diag- nosis (Kalichman et al., 2000). There is little doubt that a significant proportion of patients with comorbid depression and HIV go unrecognized and untreated. Depression in HIV is associated with greater delays initiating antiretroviral treatment (Fairfield et al., 1999) and poorer adherence to antiretroviral medication (Gordillo et al., 1999). Depression is important not only because of its psychological impact but also be- cause of its impact on the course of HIV. Evidence suggests that depression accelerates HIV disease progression (Leserman et al., 1999) and is independently associated with increased HIV mortality and a more rapid decline in CD4 + lymphocyte counts (Ickovics et al., 2001). Compliant selective serotonin reuptake inhibitor (SSRI) use has been associated with improved antiretroviral adherence and lab- oratory parameters (Horberg et al., 2008). It is possible that early and effective treatment of depression in HIV may significantly improve quality of life and that longer-term use may have an influence on HIV disease progression and associated morbidity. Expert consensus suggests that selective SSRIs are first-line treatments of depression in HIV (Caballero and Nahata, 2004). SSRIs may be as effective as and better tolerated than tricyclic anti- depressants (TCAs) in HIV-positive adults (Caballero and Nahata, 2004). However, published controlled studies in this area are limited to trials with fluoxetine versus placebo (Rabkin et al., 1999) and paroxetine versus imipramine (Elliott et al., 1998), with comparable response rates as in depressed cohorts without HIV. A recent meta- analysis of the use of SSRIs for depression in HIV argued that the lack of data prevented conclusions being drawn on the most useful SSRIs in this context (Ferrando and Freyberg, 2008). Because of fluoxetine’s properties as an inhibitor of cytochrome P450 isoforms 2D6 and 3A4 and its long half-life, interactions with antiretrovirals may occur. Newer SSRIs such as citalopram and escitalopram offer a theoretically lower potential for drug-drug interactions, but large ran- domized studies examining comparative treatment efficacy and safety have yet to be done in HIV-positive patients. A recent meta-analysis of 12 new-generation antidepressant drugs in non-HIV cohorts in the treatment of depression found, for both efficacy and acceptability, in favor of escitalopram and sertraline (Cipriani et al., 2009). Escitalopram, the most selective SSRI available (Owens et al., 2001), may offer a particular advantage for treating depression in HIV. Aside from the established efficacy of escitalopram in non-HIV depression (Burke et al., 2002; Lepola et al., 2003; Wade et al., 2002), escitalopram mediates a more rapid and robust treatment re- sponse than its predecessor citalopram (Gorman et al., 2002) and has only weak or negligible effects on hepatic enzymes crucial to the metabolism of most medicines including those frequently used in highly active antiretroviral therapy (Brosen and Naranjo, 2001; Gutierrez et al., 2003; von Moltke et al., 2001). This drug-drug inter- action remains relevant in South Africa because patients are still pre- scribed protease inhibitors (PIs). The South African antiretroviral roll out programme consists of a nonnucleoside reverse transcriptase inhibitor (NNRTI) based first-line regimen and a ritonavir-boosted protease inhibitor (PI) containing second-line regimen. Ten milli- grams of escitalopram per day is effective and well tolerated in the treatment of depression in primary care (Burke et al., 2002). Therefore, the present study aimed to investigate the efficacy and tolerability of escitalopram for the treatment of Diagnostic and ORIGINAL ARTICLE The Journal of Nervous and Mental Disease & Volume 202, Number 2, February 2014 www.jonmd.com 133 *Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; †Department of Psychiatry, Faculty of Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa; and ‡School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. Send reprint requests to Jacqueline Hoare, MD, FCPsych, Mphil, Department of Psychiatry and Mental Health, University of Cape Town, Anzio Road Obser- vatory, 7925, Cape Town, South Africa. E-mail: hoare.jax@googlemail.com. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0022-3018/14/20202Y0133 DOI: 10.1097/NMD.0000000000000082 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.