Abstract
Aim : Affective disorders such as depression and anxiety are one
of the most prevalent symptoms observed in patients following
coronavirus disease 2019 (COVID-19). The aim of the TELESPHOR study was
to evaluate the antidepressant effectiveness and tolerability of
agomelatine therapy in daily clinical practice in patients with major
depressive episodes (MDE) post-COVID-19.
Methods : This multicenter, observational study enrolled
outpatients aged 18-65 years who experienced an MDE (17 item Hamilton
Rating Scale for Depression [HAMD-17] total score of 8-24) within 3
months of laboratory confirmed SARS-CoV-2 infection and who had
initiated treatment with agomelatine. Study visits occurred at weeks 2,
4 and 8. The primary outcome was the antidepressant effectiveness of
agomelatine assessed by change in HAMD-17 total score at week 8.
Secondary outcomes included changes in HAMD-17 item 10 (anxiety psychic)
and item 11 (anxiety somatic), the proportion of responders (≥50%
decrease in baseline HAMD-17) and remitters (HAMD-17 score ≤7 at week
8), and impact on quality of life (QoL) (Short Form Survey [SF-36]
questionnaire). Tolerability was assessed at each study visit.
Results : The full analysis set comprised 103 patients of whom
73 (70.9%) were women. Median age was 45 years, and in the past 3
months 81 (78.6%) had experienced mild and 22 (21.4%) moderate
COVID-19. The mean time from onset of infection to study inclusion was
2.1±0.7 months. At study entry, 55 (53.4%) had mild and 48 (46.6%) had
moderate MDE. Agomelatine was associated with a significant improvement
in depression severity with decreases in mean total HAMD-17 score
compared with baseline of 2.6±3.3, 6.7±5.3, and 10.9±4.9 at weeks 2, 4,
and 8, respectively (P<0.0001 for all). Significant reductions
in anxiety psychic and anxiety somatic were also observed. Mental and
physical components of SF-36 were significantly improved compared with
baseline (P<0.0001). The proportion of responders was 81.4%
and the proportion of remitters was 71.6%. Agomelatine was well
tolerated over the 8-week follow-up.
Conclusion : Treatment with agomelatine was associated with
rapid and significant antidepressive and anxiolytic effectiveness,
improved QoL, and good tolerability in the treatment of patients with an
MDE after COVID-19.
KEYWORDS: agomelatine, COVID-19, major depressive disorder,
routine clinical practice
INTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
is the causative agent of coronavirus disease 2019 (COVID-19), a disease
with a wide range of manifestations, from asymptomatic to severe or
fatal (Wiersinga et al., 2020). In addition to the acute symptoms, a
growing body of scientific and clinical evidence highlights long-term
consequences that can affect multiple organ systems (Gupta et al.,
2020). Depression, anxiety, fatigue, sleep difficulties, and cognitive
impairment have been found to be the most common long-term
neuropsychiatric consequences following COVID-19, highlighting the
importance for consensus on specific neuropsychiatric needs in the
multidisciplinary management of patients after the acute disease
(Khraisat et al., 2022; Medvedev, 2021). In a systematic review of
psychiatric sequelae in COVID-19 patients the most frequently reported
symptoms were depression and/or anxiety, examined in 47 of the 66
included studies (Schou et al., 2021). Clinically
significant depression has been noted in approximately 30-40% of
patients at 1, 3, and 6 months after COVID-19, suggesting that long-term
depressive effects occur in many patients after the acute infection
(Rogers et al., 2020; Renaud-Charest et al., 2021). A Chinese study
which examined the long-term health consequences of COVID-19 following
discharge from hospital reported anxiety, depression, and sleep
difficulties were present in approximately one-quarter of patients in
the 6 months post-discharge (Huang et al., 2021).
Depression after COVID-19 can affect survivors’ cognitive performance,
symptoms of fatigue, and daily functioning, increasing the burden of
noncommunicable illness associated with psychiatric disability (Rogers
et al., 2020; Renaud-Charest et al., 2021). Some authors have noted the
presence of continued sleep−wake cycle disturbances after recovery from
COVID-19 (Salehinejad et al., 2022; Xu et al., 2022; Abuhammad et al.,
2023). However, no assessment of the affective state of these patients
has been made, suggesting that in some patients sleep disturbances may
be part of the affective disorders
Despite the large number of affected patients, there are a paucity of
data on the effectiveness of pharmacological treatments for depression
disorders in post-acute COVID-19 patients. Some studies have focused on
the potential antiviral properties of antidepressants such as fluoxetine
(Pashaei, 2021; Hoertel et al., 2021; Dąbrowska et al., 2021) and
fluvoxamine (Lenze et al., 2020; Boretti, 2023; Dobrodeeva et al.,
2022), mostly during the active COVID-19 infection period. In contrast,
research on the efficacy of antidepressants for post-COVID depressive
disorders is limited to a few studies with selective serotonin reuptake
inhibitors (SSRI) (Dobrodeeva et al., 2022; Mazza et al., 2022; Di
Nicola et al., 2023).
Agomelatine is an antidepressant acting as a melatonergic MT1/MT2
receptor agonist with 5-HT2C serotonergic receptor antagonist
properties. It is effective against a range of depressive symptoms in
patients with moderate to severe major depressive episode (MDE) with an
effect size comparable to that of other currently available
antidepressive drugs (de Bodinat et al., 2010; Taylor et al., 2014;
Cipriani et al., 2018). Efficacy has been demonstrated in short-term and
long-term controlled studies, as well as in clinical practice and in
patients with somatic diseases (Medvedev et al., 2016; Medvedev, 2018;
Medvedev, 2017; Medvedev et al., 2019; Demyttenaere et al., 2013;
Kennedy & Rizvi, 2010; Kennedy et al, 2016). Other aspects of clinical
efficacy such as well-being, improvement of sleep disorders, daily
functioning, and sexual function have also been demonstrated (Kennedy &
Rizvi, 2010). The safety profile of agomelatine has been established in
a number of randomized controlled trials. These have demonstrated an
incidence of adverse events with agomelatine similar to that observed
for placebo (agomelatine 42.4% versus placebo 42.5%) (Olié & Kasper,
2007) and sertraline (agomelatine 48.0% versus sertraline 49.1%)
(Kasper et al., 2010), and lower than that observed with venlafaxine
(agomelatine 51.2% versus venlafaxine 57.1%) (Lemoine et al., 2007)
and escitalopram (agomelatine 66.2% versus escitalopram 81.8%)
(Quera-Salva et al., 2011). Good tolerability is important for adherence
and persistence with treatment and ultimately for a drug’s
effectiveness. A recent network meta-analysis has confirmed the
favorable safety profile of agomelatine (Cipriani et al., 2018).
Agomelatine may be a favorable therapeutic choice for use in patients
with depression onset after COVID-19, but data are currently lacking on
its clinical effectiveness in this population in routine clinical
practice. The primary objective of the current study was therefore to
describe the antidepressive effectiveness and tolerability of
agomelatine in patients with a post-COVID-19 MDE in an outpatient
setting.