The new paradigm for the treatment of major depressive disorder (MDD) is to “make patients feel well and do well.” Feeling well and doing well lead to being well. Treatment therefore needs to address the cognitive symptoms that have a negative impact on workplace performance. However, antidepressant efficacy has traditionally been assessed using tools that evaluate emotional symptoms rather than cognition. In a fascinating symposium at ECNP 2018, experts from the USA, Canada and Spain highlighted the need for a different approach to treatment and appropriate tools to measure outcomes to address the multiple circuitry systems involved in MDD, cognition, and workplace performance. They also discussed the link between cognitive measures and workplace performance and the importance of real-world data for evaluating the long-term effectiveness of antidepressants for patients.
The multidimensionality of depression is more than the sum of the emotional, cognitive and physical symptoms because the symptoms impact psychosocial function including workplace function, said Andrew Cutler, Chief Medical Officer of Meridien Research, Tampa, FL.
Four cognitive domains impacting workplace function
Cognitive symptoms can be categorized into four domains, explained Professor Cutler; each has a different impact on workplace performance and all these symptoms may be part of depressive symptomatology:
- Impaired executive function due to indecisiveness, worrying and inability to adapt leads to an inability to organize and multi-task, poor decision making, and procrastination
- Impaired attention due to loss of concentration and train of thought and distractability, leads to an inability to converse and follow through and poor-quality work
- Impaired memory due to loss of focus, forgetfulness, and aloofness leads to missed appointments, errors, and limited activities
- Impaired processing (psychomotor) speed due to low energy and slowness of thought leads to a slowness in initiating and completing tasks and a failure to meet deadlines.
A more complex approach to treatment is needed to address the multiple circuitry systems
The definition of treatment success is a full functional recovery
Professor Cutler highlighted the multiple circuitry systems associated with MDD in which the neurotransmitters dopamine, serotonin, and noradrenaline act on a variety of structures in the brain. A more complex approach to treatment is needed to address these systems, he said.
Iria Grande, Associate Professor of Psychiatry, University of Barcelona, Spain, considered whether the “traditional efficacy” of antidepressants is reflected in long-term treatment goals. The definition of treatment success in depression has evolved, she explained. In the 1980s it was defined as a response with many residual symptoms;1 now it is defined as a full functional recovery.2
Real-world data reveal the effectiveness of therapy for patients
Dr Grande highlighted how determining the long-term effectiveness of antidepressant therapy for patients is also an important aspect of understanding how antidepressants work.
Tools traditionally used to evaluate efficacy do not fully assess cognition
In a 2018 systematic review and network meta-analysis of the efficacy and acceptability of 21 antidepressant drugs for MDD,3 all antidepressants were found to be more effective than placebo for MDD. There were relatively small differences between individual antidepressants in traditional placebo-controlled studies.
However, the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) were used to determine efficacy, commented Dr Grande. These scales have been used traditionally to measure antidepressant efficacy but were not designed to measure cognition and patient functioning.4
Improved cognition is significantly associated with improved workplace productivity
Patients with depression often experience cognitive symptoms,5,6 and cognitive functioning is a key outcome,7 said Dr Grande. A study of 535 patients showed that over 70% want a return to their usual level of function at work, home, or socially.8
Patients want a full functional recovery — a return to their pre-depression function at work, home, and socially
Improvements in patient-reported cognitive dysfunction correlate with improvements in workplace productivity for patients treated for MDD, said Pratap Chokka, Clinical Professor of Psychiatry, University of Alberta, Canada.
This has been demonstrated by the Assessment in Work productivity and the Relationship with Cognitive symptoms in patients participating in the so-called “AtWoRC” study. This study involved 26 sites across Canada and 196 patients treated for MDD who had cognitive symptoms and were “gainfully employed.”9 Workplace productivity was evaluated using the 20-item Perceived Deficits Questionnaire (PDQ-D-20) and Work Limitations Questionnaire (WLQ).9
Both after 12 weeks, as well as after 52 weeks, improvements in cognitive symptoms were significantly correlated with improvements in workplace productivity (p<0.001),10 highlighting the importance of addressing cognitive symptoms to restore patient functioning in MDD.
Educational financial support provided by H. Lundbeck A/S