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.