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For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).
To compare the switch between the TCA nortriptyline and the SSRI escitalopram.
Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery–Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs.
Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = −0.38, 95% CI −0.51 to −0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = −0.34, 95% CI −0.41 to −0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions.
These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.
Declarations of interest
K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.
This chapter discusses evidence concerning the efficacy of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in treatment-resistant depression. It examines the variety of options available for managing non-responders to these medications. The difference between non-response and intolerance due to side effects has clinically significant implications. A patient who does not respond to an adequate trial of an antidepressant should usually next be treated with an antidepressant from a different class. There is no lack of treatment options for the depressed patient unresponsive to medication. The problem lies in the very profusion of options: how to choose between them, when and how to combine them, and what order in which to employ them. One way to simplify and categorize the options is wait, change, augment, or combine. Antidepressants are often helpful in syndromes other than depression.
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