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Post-COVID-19 depression responds well to SSRIs

Presented by
Dr Mario Mazza , San Raffaele University, Italy
ECNP 2021

Antidepressants typically have a moderate response rate of 40–60%, but this rate seems to be higher in post-COVID-19 depression. In a pilot study, a rapid response to first-line antidepressants was observed in over 90% of patients, irrespective of clinical variables [1].

Considering the possible anti-inflammatory and antiviral properties of selective serotonin reuptake inhibitors (SSRIs), post-COVID-19 depression triggered by infection and sustained by infection-related systemic inflammation could particularly benefit from antidepressant treatment, explained Dr Mario Mazza (San Raffaele University, Italy).

The study included 56 adult patients with depressive episodes in the 6 months following a SARS-CoV-2 infection. The severity of depression was rated at baseline and 4 weeks into treatment using the Hamilton Depression Rating Scale (HDRS). Response was defined as a 50% reduction in HDRS score. Patients were treated with sertraline (n=26), citalopram (n=18), paroxetine (n=8), fluvoxamine (n=4), and fluoxetine (n=2).

Of the 56 participants, 53 (91%) were clinical responders to SSRI treatment. Age, sex, mood disorder history, or hospitalisation for COVID-19 did not affect response. HDRS score significantly decreased (F=618.90, P<0.001), irrespective of sex (F=0.28; P=0.599), mood disorder history (F=0.04; P=0.834), and SSRI used (F=1.47; P=0.239).

The authors remarked that mounting evidence suggests antidepressants may:

  • decrease markers of inflammation;
  • inhibit acid sphingomyelinase, preventing the infection of epithelial cells with SARS-CoV-2;
  • prevent the COVID-19-related cytokine storm by stimulating the σ-1 receptor;
  • exert antiviral effects via lysosomotropic properties; and
  • inhibit platelet activation [2].

  1. Mazza MG, et al. Rapid antidepressant response to first-line selective serotonin reuptake inhibitors in post-COVID-19 depression. P.0404, ECNP 2021 Congress, 2–5 October.
  2. Hoertel N, et al. Mol Psychiatry 2021:1–14.

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