Genetic screening for SSRI drug response among those with major depression: great promise and unseen perils

Abstract

This article examines evidence for the potential benefit of genetic testing for SSRI response, as well as potential ethical and practical implications of the implementation of this test into standard psychiatric practice. We reviewed three areas of the literature: the burden of treatment-resistant and treatment-intolerant major depressive disorders, the evidence for the value of genetic testing to predict drug response, and the ethical and practical issues of genetic testing in usual care. Treatment resistance and treatment intolerance are common for persons treated with selective serotonin reuptake inhibitors (SSRIs) and are associated with both financial and quality-of-life costs. There is strong evidence from association studies that some polymorphisms are associated with SSRI response. However, no randomized trials have yet tested the efficacy of genetic tests to improve outcome in those with treatment resistance or treatment intolerance to SSRIs. Given the nonspecific nature of the test proposed, several ethical concerns are also involved with administering the genetic tests to patients. A randomized trial comparing response in those treated with standard psychiatric care and in those treated with psychiatric care tailored as a result of genetic test results should be completed before the implementation of these tests can be considered. Additionally, the ethical and practical questions concerning the tests must be addressed now, so that the potential impact of these tests on patient care can be well understood prior to adoption in standard practice.

Pharmacogenetics in Psychiatry - A Useful Clinical Tool or Wishful Thinking for the Future?

“…As far as univariate relations between cause and effect are applied in pharmacogenetic research such as measuring drug response in dependence of a geno-type without assessing drug exposure, causal associations cannot be explored. Without results from an integrated approach accounting for all relevant knowledge on pharmacokinetics and pharmacodynamics, it can currently not be recommended to implement testing on these polymorphisms prior to antidepressive treatment for selection of type or dose of medication [40,41].…”

Psychomotor retardation in depression: Biological underpinnings, measurement, and treatment

“…This is a fairly effective method; nevertheless, only about 50% of patients respond to their first antidepressant treatment and less than 40% achieve remission (Gorlyn et al, 2008; Kemp et al, 2008; Trivedi et al, 2006). Treatment failures produce substantial financial and quality of life burdens for these individuals and society (Rasmussen-Torvik and McAlpine, 2007). …”

“…The SSRIs have been studied most frequently in patients with psychomotor retardation (1986; 1990; Amsterdam, 1998; Burns et al, 1995; Caligiuri et al, 2003; Flament et al, 1999; Gorlyn et al, 2008; Hegerl et al, 2001; Higuchi et al, 2008a; Joyce et al, 2002; Kemp et al, 2008; Mallinckrodt et al, 2007; McGrath et al, 2008; Mitchell Philip B., 1995; Mitchell P.B., 1997; Rasmussen-Torvik and McAlpine, 2007; Roose et al, 1994; Sabbe et al, 1997; Taylor et al, 2006; Yoshimura et al, 2004). Some studies made the argument that SSRIs would not work as well for patients with psychomotor retardation because it is likely these patients have a dopamine and/or norepinephrine imbalance in addition to or instead of a serotonin imbalance (Amsterdam, 1998; Caligiuri et al, 2003; Flament et al, 1999; Herrera-Guzman et al, 2008; Kemp et al, 2008; Taylor et al, 2006).…”

“…One major reason could be that the studies do not classify patients and psychomotor retardation in a uniform manner. Studies used a variety of different tools to determine if a patient has psychomotor retardation, some of which include: the CORE rating scale, MHPG levels, reaction time, speech measures, drawing tasks, actigraph, and specific parts of depression severity scales (1986; 1990; Aman and Turbott, 1991; Amsterdam, 1998; Brown, 2007; Burns et al, 1995; Caligiuri et al, 2003; Del Zompo et al, 1990; Flament et al, 1999; Gorlyn et al, 2008; Guiard et al, 2009; Hegerl et al, 2001; Herrera-Guzman et al, 2008; Higuchi et al, 2008a,b; Hordern et al, 1963, 1964; Joffe et al, 1987; Joyce et al, 2002; Kemp et al, 2008; Mallinckrodt et al, 2005, 2007; Mitchell Philip B., 1995; Mitchell P.B., 1997; Mulder et al, 2006; Ranelli and Miller, 1981; Raoux et al, 1994; Rasmussen-Torvik and McAlpine, 2007; Roose et al, 1994; Sabbe et al, 1997; Sobin and Sackeim, 1997; Taylor et al, 2006; Thase et al, 1995; White and White, 1986; Yoshimura et al, 2004; Zarate et al, 1996). Although all these measures are related to psychomotor retardation, they are considerably different, and could potentially lead researchers to study a heterogeneous group of patients.…”

“…If this occurred in any of the studies, then the potential efficacy of the drug may not have been shown. Genetic, neuroimaging, and transcranial magnetic stimulation studies may provide further data regarding this question in the future (Loo et al, 2008; Rasmussen-Torvik and McAlpine, 2007). …”