Change in cognitive functioning in depressed older adults following treatment with sertraline or nortriptyline

Cognitive impairment is common in geriatric depression. Cognitive domains reported to be affected include memory (Gallassi, et al. 2006; Kramer-Ginsberg, et al. 1999; Salloway, et al. 1996), visuospatial functioning (Butters, et al. 2004; Kramer-Ginsberg et al. 1999), information processing speed (Lesser, et al. 1996; Nebes, et al. 2000), and executive functioning (Lesser et al. 1996; Lockwood, et al. 2002). The conversion rate of late-life depression into dementia among those with cognitive impairment is much higher than those without cognitive impairment (Modrego and Ferrandez 2004). Antidepressant medication is the first line of treatment for depression, particularly in the older adult community where primary care doctors provide the majority of treatment. Therefore, it is important to understand the effects of antidepressant medication on cognition among the depressed elderly, a cognitively vulnerable population. When examining the effect of antidepressant medication on cognition in depressed older adults, two interrelated sets of questions arise. The first set of questions focuses on within-treatment changes in cognitive functioning: a) does cognitive functioning change from pre- to post-treatment? and b) is there a differential impact of medication on cognition depending on whether or not the patient responds? Within the second set of questions, the focus is on between-treatment changes in cognitive functioning: a) is there a differential impact of antidepressant medication on cognitive functioning depending on medication class (e.g., SSRIs, SNRIs, TCAs, MAOs)? b) does change in cognitive functioning between treatment conditions depend on responder status? Of course, the concept of cognitive functioning is broad and consists of a number of functions including but not limited to memory, attention, processing speed, executive functioning, and visuospatial/visuoconstructional skills. Therefore, it is important to examine each of the above questions within the context of a multi-domain assessment to address how antidepressant medication (including whether or not the patient responds) differentially affects each of these cognitive domains. A number of studies have examined the impact of antidepressant medication on cognition but have not fully addressed the two interrelated sets of questions we have outlined (Bhalla, et al. 2006; Bondareff, et al. 2000; Butters, et al. 2000; Doraiswamy, et al. 2003; Gallassi et al. 2006; Nebes, et al. 2003; Raskin, et al. 2007). For example, some studies did not address whether change in cognition depends on response to treatment (Bondareff et al. 2000; Raskin et al. 2007). Other studies included only responders in their analyses rather than comparing change in cognition among responders and non-responders, which would have helped to differentiate the impact of medication versus response on change in cognitive functioning (Bhalla et al. 2006; Butters et al. 2000; Gallassi et al. 2006; Nebes et al. 2003). Finally, another study used a composite cognitive score in its analyses and thus did not address the differential impact of medication on different cognitive domains (Doraiswamy et al. 2003). To our knowledge, few studies have fully tested the impact of medication on cognitive function in depressed older adults. For example, in an 8-week randomized placebo-controlled trial of citalopram (Culang, et al. 2009), antidepressant non-response was associated with cognitive decline in verbal learning and psychomotor speed. Although responders on medication improved on some domains (psychomotor speed and visuospatial functioning), their improvement did not exceed the expected practice effect observed among patients randomized to placebo. This study, therefore, shows decline in some domains and improvement in other domains, and is an example of a differential impact of medication on cognition. In another study, nortriptyline and phenelzine produced no change in any cognitive domain assessed (verbal learning, psychomotor speed, visual memory) in depressed older adults when compared to placebo, and this effect did not depend on responder status (Georgotas, et al. 1989). In a third study, an uncontrolled trial in depressed older adults showed no change in any cognitive domain assessed (processing speed, executive functioning, verbal and visual memory, visuoperceptive functioning, and attention) over 12 months of treatment when compared to age-matched controls (Portella, et al. 2003). Furthermore, there were no differences in change among remitted and non-remitted patients. The purpose of this study was to examine the impact of a TCA and SSRI on cognition and to determine whether change in cognition depends on response to treatment and cognitive domain. To accomplish this aim, we used pre-post neuropsychological data on global cognitive functioning, verbal learning, attention, psychomotor speed, and executive functioning (the switching and response inhibition components), collected as part of a 12-week, randomized, double-blind, parallel-group design comparing sertraline and nortriptyline in the treatment of depressed older adults. In the context of this multi-domain assessment, we addressed the two sets of questions outlined above: 1.a) whether there were pre- to post-treatment changes in cognitive functioning within the sertraline and nortriptyline conditions, 1.b) whether change in cognitive functioning within each treatment condition depended on responder status, 2.a) whether there were differences in change in cognitive functioning between the nortriptyline and sertraline conditions, and 2.b) whether change in cognitive functioning between treatment conditions depended on responder status.