Promising data in depression associated with emotional blunting or trauma

While anhedonia is the reduced ability to experience and anticipate pleasure, emotional blunting can be described as reduced emotional responsiveness – either positive and negative.^1,2 Both impose burdens on patients with major depressive disorder (MDD), and both are common.

• Franken et al found around 75% of patients with MDD reported anhedonia¹
• Guy Goodwin and colleagues in Oxford found emotional blunting in 46% of treated MDD patients²
• In a survey of patients in New  Zealand, around 60% of those taking a range of different antidepressants – both SSRIs and an SNRI -- reported feeling emotionally numb³

Central dopaminergic, mesolimbic and mesocortical reward pathways are implicated in anhedonia,² and emotional numbing may relate to reduced dopamine or glutamatergic activity⁴

In the COMPLETE study, use of a multimodal antidepressant was associated with reduced emotional blunting and improved functioning^5,6,7

Promising new data in emotional blunting

So there is great interest in the results of the recent COMPLETE study involving an antidepressant that combines modulation of activity at a range of serotonin receptor subtypes with inhibition of the serotonin transporter and a positive effect on downstream dopamine.^5,6

The study involved patients with only a partial response to an SSRI or SNRI who experienced emotional blunting on treatment and who wanted to switch agent.⁷

Presenting the data at EPA 2021 Virtual, Andrea Fagiolini (University of Siena, Italy) reported that the multimodal antidepressant significantly improved emotional blunting as measured by the Oxford Depression Questionnaire.⁷ After eight weeks of treatment, 50% of patients reported no blunting.⁷

Improvement in emotional blunting was accompanied by improvement in overall functioning (and in work, family and social domains) and greater motivation and energy (mental, social and physical).⁷ Ongoing studies are assessing the role of this agent in patients with anhedonia.

Prospects also enhanced in trauma-related MDD

The multimodal agent improved symptoms and functioning in MDD patients reporting childhood or recent trauma¹⁴

Childhood trauma can increase the risk of early-onset major depression, and is associated with a relapsing and chronic course.⁸

The many adults who have a history of childhood trauma are significantly less likely than others to benefit from commonly used treatments.⁹

According to the international Study to Predict Optimized Treatment for Depression (iSPOT-D), patients with MDD who had been abused when aged 4-7 years were 1.6 times less likely than non-abused people to achieve response or remission when taking an SSRI or SNRI.⁹

Lower risk of relapse over 24 weeks

Professor Fagiolini described a series of studies in patients with MDD who had reported either childhood or recent trauma using an antidepressant with multimodal effects on neural pathways including enhanced glutamate signaling.^10-13

Meta-analysis of the short-term studies showed the multimodal agent significantly improved short and long-term symptoms, including anxiety and well as depression, both in patients with childhood trauma and in those with recent trauma.¹⁴

In a long-term study, use of the multimodal agent was associated with improved symptoms and better overall functioning and health-related quality of life when baseline values were compared with those at week 48, and with a significantly lower risk of depression relapse within 24 weeks.¹⁴

Educational financial support for the symposium was provided by H. Lundbeck A/S, who also funded the studies reported in patients with depression associated with emotional blunting and childhood trauma.

EPA: European Psychiatric Association

MDD: Major depressive disorder

SSRI : selective serotonin reuptake inhibitor

SNRI : Serotonin and Noradrenalin Reuptake Inhibitor

BE-NOTPR-0077; approval date 10/2021