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
• The effect of emotional blunting on decision making  can reduce adherence and so compromise efficacy.⁴ In a recent study, 35% of patients discontinued treatment because of it.⁵

Central dopaminergic, mesolimbic and mesocortical reward pathways are implicated in anhedonia,² and emotional numbing may relate to reduced dopamine or glutamatergic activity⁶

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

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.^7,8

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.

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.⁹ After eight weeks of treatment, 50% of patients reported no blunting.

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).⁹ 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 trauma¹⁶

Childhood trauma can increase the risk of early-onset major depression, and is associated with a relapsing and chronic course.¹⁰

The many adults who have a history of childhood trauma are significantly less likely than others to benefit from commonly used treatments.¹¹

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.¹¹

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.^12-15

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.¹⁶

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.¹⁶

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.