METHODS
Study design
TELESPHOR was a multicenter, observational study conducted in outpatient
ambulatory state and private clinics in four cities in Russia between
March 2022 and February 2023. The study included adults aged 18-65 who
experienced an MDE within 3 months of polymerase chain reaction (PCR)
confirmed SARS-CoV-2 infection in whom treatment with agomelatine was
initiated. The depressive episode was measured with the 17 item Hamilton
Rating Scale for Depression (HAMD-17) where scores of 0–7 are
considered normal, 8–16 suggest mild depression, 17–23 moderate
depression, and scores over 24 are indicative of severe depression
(Zimmerman et al., 2013). In the current study, patients with a total
HAMD-17 score of 8-24 were considered to be suffering an MDE. Patients
ineligible to participate in the study were those diagnosed with
suicidal risk (score ≥2 in item 3 of the HAMD-17 scale and/or according
to clinical evaluation by the investigator), psychotic symptoms
(according to clinical evaluation by the investigator), or other mental
disorder or disease; noncompensated serious somatic or neurological
disease; and COVID-19 that could not be confirmed. Agomelatine was
administered in accordance with the approved Summary of Product
Characteristics (SmPC) in Russia, local standards and guidelines.
At baseline, severity of depression, level of anxiety, and quality of
life (QoL) status in addition to clinical and sociodemographic data were
collected from all included patients. Data on the history of COVID-19
infection and its severity were collected retrospectively and extracted
from medical records. Patients were seen at baseline, with further
clinic visits at 2, 4, and 8 weeks of prospective observation. Due to
the observational nature of the study, the protocol did not mandate any
assignment of the included patients to one or another treatment
strategy. Agomelatine prescription was not decided in advance by a trial
protocol, but was determined by the current prescribing practice of the
investigating physician and was separate from the decision to include a
patient in the study. All included patients were recommended to start
treatment with agomelatine 25 mg/day taken at bedtime for at least 8
weeks. In case of insufficient effectiveness of agomelatine after 2
weeks of treatment, and based on the investigating physician’s opinion,
the daily dose could be increased to 50 mg/day at bedtime.
The primary outcome was the mean change in HAMD-17 total score from
baseline to week 8 under agomelatine treatment. Key secondary
effectiveness outcomes were changes in the HAMD-17 item 10 “anxiety
psychic” and item 11 “anxiety somatic” scores, and
investigator-determined global severity of the patient’s illness
assessed by the Clinical Global Impressions-Improvement of Illness Scale
(CGI-I). Patient QoL was assessed with the 36 item Short Form survey
(SF-36). Additional secondary effectiveness outcomes included the
proportion of patients with a response to agomelatine treatment (defined
as a decrease of ≥50% in the baseline HAMD-17 score), as well as the
proportion of those with remission (defined as a HAMD-17 total score ≤7
at week 8 of the observational period). The number and proportion of
patients with reported adverse events and adverse drug reactions were
analyzed, including those that could lead to discontinuation of the drug
during the study.
The study protocol was approved by the Moscow Inter-Academic Ethics
Committee on March 17, 2022 (approval protocol # 3) and was conducted
in compliance with the Declaration of Helsinki, and local regulatory
requirements. All participants provided their informed consent before
inclusion in the study (NCT05323994).