Identifying and achieving treatment goals in MDD: What matters most to patients?

A large proportion of patients with MDD fail to show adequate response to first-line antidepressants. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) randomized trial, only 36.8% of patients achieved complete remission with the first course of antibiotics, with the likelihood of remission decreasing with subsequent lines of antidepressant medications.1 To reduce the burden of this problem, treatment decisions for MDD should consider a number of factors.  

For patients newly diagnosed with MDD, the selection process of an antidepressant medication should consider both patient factors and medication factors. Patient factors include clinical features and history, comorbidities, and patient preference; while medication factors include comparative efficacy and tolerability of the drug, possible drug-drug interactions, simplicity of use and dosing strategy, in addition to cost and availability.2


When considering comparative efficacy, drugs should not only be compared based on their ability to reduce the common symptoms of depression (i.e. continuous low mood and hopelessness), but should also take into consideration other emotional symptoms (such as emotional blunting, anhedonia, and lack of motivation), cognitive symptoms, and physical symptoms in an attempt to achieve full functional recovery of patients.3


In a large network meta-analysis that included 522 trials and 116,477 patients, and compared 21 antidepressants in the acute treatment of MDD, multimodal antidepressant was found to have similar efficacy (in terms of response rate) and acceptability/tolerability (in terms of treatment discontinuation due to any cause) to most other antidepressants.4


When it comes to its adverse events’ (AEs) profile, multimodal antidepressant was found to induce a prevalence of 0% to 9% in all its reported AEs except nausea (23%). This is considered relatively very safe compared to all new antidepressants.2 


Because many patients with MDD receive other medications besides their antidepressants, the possibility of drug-drug interactions should be carefully accounted for.2 While selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake Inhibitors (SNRIs) can affect the pharmacokinetics and/or pharmacodynamics of other medications, multimodal antidepressant tends to have a low to moderate potential for drug-drug interactions; hence, can be concomitantly used with many common drugs.2,5–8


Furthermore, findings from three clinical trials have proven that multimodal antidepressant helps in improving aspects of cognitive performance in patients with MDD. Interestingly enough, cognitive improvement was not mediated solely through its alleviation of depressive symptoms.9 Additionally, everyday functioning (as measured by the  University of California San Diego Performance-based Skills Assessment [UPSA] was also significantly improved compared to placebo after 8 weeks of treatment in the CONNECT study.10


In general, antidepressants should be continued for 6 to 9 months and longer for those at risk of recurrence.2 However, a lack of response (defined as 20% to 30% reduction from baseline depression) in 2 to 4 weeks is a predictor of non-response or non-remission.2,11 Incomplete recovery from a depressive episode and the subsequent lingering of residual symptoms raise the probability of relapse or recurrence of depression, possibly turning an acute problem into a more severe and chronic condition.12


In addition to a number of possible management strategies in case of a lack of response to initial treatment, switching to another antidepressant from a different class is a viable option.11,13

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


1.        Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. Am J Psychiatry. 2006;163(11):1905-1917. doi:10.1176/ajp.2006.163.11.1905

2.        Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. Can J Psychiatry. 2016;61(9):540-560. doi:10.1177/0706743716659417

3.        American Psychiatric Association. Diagnostical and Statistical Manual for Mental Disorders - Fifth Edition (DSM-5).; 2013.

4.        Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357-1366. doi:10.1016/S0140-6736(17)32802-7

5.        Brintellix® (Vortioxetine) Summary of Product Characteristics.; 2020.

6.        Chen G, Zhang W, Serenko M. Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin. J Clin Pharmacol. 2015;55(6):671-679. doi:10.1002/jcph.456

7.        Chen G, Nomikos GG, Affinito J, Zhao Z. Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium. Clin Pharmacokinet. 2016;55(9):1115-1127. doi:10.1007/s40262-016-0389-0

8.        Chen G, Højer A-M, Areberg J, Nomikos G. Vortioxetine: Clinical Pharmacokinetics and Drug Interactions. Clin Pharmacokinet. 2018;57(6):673-686. doi:10.1007/s40262-017-0612-7

9.        McIntyre R, Harrison J, Loft H, Jacobson W, Olsen C. The Effects of Vortioxetine on Cognitive Function in Patients with Major Depressive Disorder: A Meta-Analysis of Three Randomized Controlled Trials. Int J Neuropsychopharmacol. 2016;19(10):pyw055. doi:10.1093/ijnp/pyw055

10.      Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RS. A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder. Neuropsychopharmacology. 2015;40(8):2025-2037. doi:10.1038/npp.2015.52

11.      Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Möller H-J. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013;14(5):334-385. doi:10.3109/15622975.2013.804195

12.      Judd LL, Paulus MJ, Schettler PJ, et al. Does Incomplete Recovery From First Lifetime Major Depressive Episode Herald a Chronic Course of Illness? Am J Psychiatry. 2000;157(9):1501-1504. doi:10.1176/appi.ajp.157.9.1501

13.      Kudlow PA, McIntyre RS, Lam RW. Early Switching Strategies in Antidepressant Non-Responders: Current Evidence and Future Research Directions. CNS Drugs. 2014;28(7):601-609. doi:10.1007/s40263-014-0171-5