Why do antidepressants cause emotional blunting and what can be done to resolve it in clinical practice?

A negative impact on patient outcome

46% of patients on antidepressants report emotional blunting

Emotional blunting is a residual symptom of MDD, which is a symptom experienced by patients with MDD despite antidepressant therapy. Such patients are at risk of relapse.⁴

Emotional blunting can impact everyday patient function and prevent a full functional recovery.⁵ More severe emotional blunting is associated with a poorer quality of remission.⁶

Nearly half of patients on all types of monoaminergic antidepressants report emotional blunting,⁶ and it is associated with serotonin reuptake inhibitor (SSRI) therapy as follows:^2,5

• among 161 patients, 46% reported a narrowed range of affect, 21% reported an inability to cry, and 19% reported apathy⁷
• a cross-sectional study of 117 patients revealed that approximately 30% of patients reported some form of apathy⁸

What causes emotional blunting?

Higher doses of SSRI are more likely to cause emotional blunting^9,10

The primary effect of SSRIs is reduced processing of negative stimuli rather than increased positive stimuli.⁹

Emotional blunting is related to SSRI dose,^9,10 and possibly serotonergic effects on the frontal lobes and/or serotonergic modulation of midbrain dopaminergic systems projecting to the prefrontal cortex (PFC).¹⁰ By enhancing serotonergic transmission, SSRIs can activate GABA interneurons, thereby dampening the noradrenergic and dopaminergic input.¹¹

Dorsolateral PFC:

• is primarily associated with “cognitive” or “executive” functions¹²
• appears to play a role in regulating negative emotion through reappraisal/suppression strategies^13,14
• lesions are associated with significantly higher MDD scores than for head injuries not involving the PFC¹²
• is hypoactive at rest and increases in activity during symptom remission¹⁵

Dorsolateral PFC appears to play a critical role in MDD through a defect in regulation of negative affect

Ventromedial PFC:

• is largely ascribed “emotional” or “affective” functions¹²
• lesions are associated with significantly lower MDD scores than for brain injuries not involving the PFC¹²
• is hyperactive at rest and decreases in activity during symptom remission¹³

Imaging studies suggest a critical link between the automatic processing of emotional signals in the amygdala and the regulation of this activity in the frontal cortex.¹⁶

Lowering SSRI dose⁸ or changing antidepressant are therapeutic options

Options to resolve emotional blunting are therefore to:

• lower the dose and/or discontinue the SSRI⁸
• change the antidepressant to one with a different profile that might improve the patient’s emotional response¹⁷