Early intervention and treatment adjustment as necessary to provide complete symptomatic relief and restore full functional recovery are essential to ensure long term remission from a major depressive episode. The good news is that while the challenges of treating patients with major depressive disorder (MDD) are real, they may not be insurmountable. There are treatment adjustment strategies that physicians can adopt to optimize pharmacotherapy in patients with MDD and a partial or no response to initial antidepressant treatment.
Unmet needs in MDD
The unmet needs in treatment of patients with MDD are substantial. Studies show that eight out of ten patients treated for MDD do not receive minimally adequate treatment of pharmacotherapy or psychotherapy.1† Furthermore, half of patients with MDD do not respond adequately to initial antidepressant pharmacotherapy,2 and half of patients prematurely discontinue antidepressant medications within 6 months.3
Not responding adequately to initial pharmacotherapy implies residual symptoms that can include: anxiety, depressed mood, emotional blunting/anhedonia, cognitive and psychomotor problems, eating and sleeping problems, impaired work and interests, fatigue or lack of energy, sexual symptoms, feelings of worthlessness and/or guilt, suicidal ideations, and lack of motivation.4,5 The Collaborative Depression Study showed that lingering residual symptoms contribute towards a more severe, relapsing, and chronic future course of depression.6,7
While the initial focus of management is typically to prevent a relapse and eliminate any residual symptoms, a key goal set out in treatment guidelines is to restore the patient’s prior level of functioning.8-11 Both patients with MDD and physicians define functional goals as important for treatment success,12 as patients who do not achieve substantial functional recovery at remission are more likely to relapse.13
A key goal of antidepressant treatment is to restore the patient’s prior level of functioning
Early intervention and assessment of treatment response is critical
Early treatment optimization offers patients the greatest opportunity for full functional recovery, which in turn increases the likelihood of sustained treatment response and remission. Studies show that 70% of patients treated early (within 1 month of onset of depressive symptoms) achieve remission and 70% of patients who display sustained early improvement in the first 2 weeks of treatment become sustained responders, thus underscoring the urgency of early effective treatment.14-16
The main focus of antidepressant treatment should be to restore the patient’s sense of wellbeing
How best to manage partial and inadequate response?
Clinical guidelines, including those from the Canadian Network for Mood and Anxiety Treatments (CANMAT) and the UK National Institute for Health and Care Excellence (NICE), recommend adjusting pharmacotherapy after 2–4 weeks if patients with MDD respond inadequately to initial treatment, and some recommend increasing the antidepressant dose for non-improvers as early as week 2.11, 17-20 Treatment adjustment strategies include: titrate the dose, combine with another antidepressant, switch to another antidepressant, or augment with other treatments.
Dose titration as a strategy to optimizing treatment is recommended in clinical guidelines.11,17-20 When patients with MDD do not respond to an initial selective serotonin reuptake inhibitor (SSRI), dose escalation may not be beneficial. Increasing doses of SSRIs and serotonin-noradrenaline reuptake inhibitors (SNRIs) can be associated with an increase in some side effects, and often with little evidence for an increase in efficacy.21-24
Asking the patient which symptoms trouble them the most can help to guide treatment decisions and improve outcomes
An alternative treatment adjustment strategy is to switch to another antidepressant, particularly if it is the first antidepressant trial, the first antidepressant is poorly tolerated, there is no or partial response to the initial antidepressant, or the patient prefers to switch.11,17,25-27 Early switching in patients with MDD who do not respond to initial treatment can increase the chances of response and remission,28 and switching to a different class of antidepressant can increase the rate of remission compared with a within-class switch.29
When deciding on a treatment adjustment strategy, patient treatment history should be evaluated, and consideration of patient preference included.30,31 Asking the patient what their goals of treatment are and which symptoms trouble them the most can help to guide treatment decisions and improve outcomes. When patients are involved in the decision-making process for the treatment of MDD they are more likely to adhere to treatment.32-34
When patients are involved in decision-making, they are more likely to adhere to treatment
Strategies for maintaining a treatment response and preventing relapse
In the long term, guidelines recommend that sustained MDD management involving continuous treatment optimization using a stepwise approach is needed to achieve and maintain treatment response and prevent relapse.17
†Data based on adults with major depressive disorder from 23 World Health Organization World Mental Health community epidemiological surveys across 21 countries. Minimally adequate treatment was defined using evidence-based guidelines and consisted of receiving pharmacotherapy (≥1 month of a medication, plus ≥4 visits to any type of medical doctor) or psychotherapy (≥8 visits with any professional).
MDD : Major Depressive Disorder
CANMAT : Canadian Network for Mood and Anxiety Treatments
NICE : National Institute for Health and Care Excellence
SSRI : selective serotoninreuptake inhibitor
SNRI : serotonin-noradrenaline reuptake inhibitor
BE-NOTPR-0228, approval date : 03.2023
