Description of the Effectiveness and Tolerability of аgomelatine in the Treatment of Patients With Depression Occurred After SARS-CoV-2 Infection in the Daily Clinical Practice in Russia (TELESPHOR)
Conditions: Depression, COVID-19
Sponsor: Servier Russia

 
 
Multicenter observational program 
TELESPHOR 
 
Protocol №:IC4-20098-069-RUS 
NCT05323994 
 
 
 
DescripTion of the Effectiveness and tolerability of аgomeLatine in the 
trEatment of patientS with dePression occurred after tHe COVID 19 
infectiOn in the daily clinical practice in Russia 
 
02/02/2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Objectives  
Primary objective  
• 
To describe the antidepressive effectiveness of agomelatine in patients with depression 
episode occurred after COVID-19 assessed by HAMD-17 after 8 weeks of treatment in the 
daily clinical practice. 
Secondary objectives 
• 
To describe effectiveness of agomelatine on anxiety symptoms assotiated with the depression  
and assessed by HAMD-17 (point 10 and 11) after 8 weeks of treatment of patients included 
in the study. 
• 
To describe effectiveness of agomelatine on global improvement and social functioning 
assessed by CGI score after 8 weeks of treatment of patients included in the study. 
• 
To describe effectiveness of agomelatine on quality of life in patients with depression episode  
occurred after COVID-19 assessed by SF-36 questionnaire after 8 weeks of treatment of 
patients included in the study.   
• 
To describe tolerability of agomelatine after 8 weeks of treatment based on rate of adverse 
events leading to drug discontinuation in patients included in the study.    
 
 
Study variables 
Primary variables: 
• Mean change from baseline (BL) in total HAMD-17 score assessed at week 8 of the 
observational period. 
Secondary variables: 
• 
% of patients defined as responders to the treatment (HAMD-17 total score decrease ≥ 
50%) at week 8 of the observational period. 
• 
% of patients achieving disease remission (defined as HAMD-17 total score < 7) at week 
8 of the observational period. 
• 
Mean change from BL in HAMD-17 point 10 “psychological anxiety” assessed at week 
8 of the observational period.  
• 
Mean change from BL in HAMD-17 point 11 “somatic anxiety”assessed at week 8 of 
the observational period.  
• 
Mean change  in scores of the Clinical Global Impression scale (CGI), item 2 (global  
improvement) at W2,W4,W8 assessed at week 8 of the observational period. 
• 
Mean change from BL in total score of  the SF-36 QoL questionnaire reported by 
patients at week 8 of the observational period. 
• 
Mean change from BL in score of the SF-36 QoL questionnaire (physical component) 
reported by patients at week 8 of the observational period. 
• 
Mean change from BL in score of the SF-36 QoL questionnaire (psychiatric component) 
reported by patients at week 8 of the observational period. 

 
• 
Number of adverse events/ adverse drug reactions leading to drug discontinuation 
during the observational period. 
Methods and documentation  
        Study design and methodology 
This is a multi-centre, observational, non-interventional study, which will prospectively collect 
clinical and socio-demographic data from patients with depression occurred after COVID 19 in 
real clinical settings during 8 weeks of treatment.  
At Visit 0 (V0), investigating psychiatrist or neurologist will  evaluate patient’s eligibility for the 
study according to inclusion/non-inclusion criteria. Only patients who comply with all inclusion/ 
non inclusion creteria will be invited to participate in this observational study. Recommendation 
to start treatment with agomelatine to manage depressive episode is to be done by investigating 
psychiatrist/ neurologist before and independently from the decision to invite a patient to 
participate in the study. Agomelatine should be administered to patients in accordance to the 
instruction for medical use approved in the Russian Federation (RF).  
20 clinics and 20 of psychiatrists and neurologists across the country will participate in the study 
and it is estimated that each investigating physician will enroll at least 5 of patients.  
Once a patient will provide his/her consent to participate in the study, investigating physician will 
record information from appointments for the evaluation of treatment in a routine clinical practice. 
The frequency of the appointments reflects a routine clinical practice of management of outpatients 
with depressive disorders in the RF.   
Main millestones: 
Local Ethic Committee approval – 1q22 
First patient included – March 2022 
Last patient included – July 2022 
End of treatment period – September 2022 
Clinical statistic subdevelopment – August 2022 
Data based lock – October 2022 
Clinical statistic subdevelopment report – November-December 2022 
End of clinical study – February 2023 
Selection of the study population  
Inclusion criteria  
1. Obtained signed informed consent from the patient. 
2. Age of 18-65 years old. 

3. Out-patient with confirmed COVID 19 infection within 3 months period before the date 
of inclusion.  
4. Confirmed depression with total HAMD-17 score of 8-24 required treatment with 
antidepressive medicines. 
5. Decision to administer agomelatine preceeds the decision to include a patient in the 
study. 
  Non-inclusion criteria 
 Current participation in any clinical trial or during 30 day period  from inclusion visit. 
 Suicide risk (accoding clinical evaluation of investigator). 
 Psychotics symptoms (according clinical evaluation of investigator). 
 Schizophrenia, schizo-affective disorders, organic damages of CNS, dementia, epilepsy, 
multiple sclerosis, Parkinson disease, Alzeimert disease, Bipolar disorders. 
 Alcohol abuse or drug addiction in anamnesis. 
 Severe or decompensated somatic or neurological disorders. 
 MAO inhibitors during last 2 weeks. 
 Treatment by others psychotropic products (antipsychotics, anxiolitics etc.). 
 Any contraindications to agomelatine in accordance to the local SmPC. 
Exclusion criteria 
1. Patients with severe/decompensated psychiatric, somatic or neurological disorders. 
2. Patients with any sign of liver failure (increase of transaminase up to 3 times higher), which 
needs to stop treatment with agomelatine. 
3. Patients who participate in any clinical trial or survey. 
 
Therapeutic strategy during the study The assignment of a subject to a particular therapeutic 
strategy is not supposed by this protocol due to the observational nature of the study. Treatment 
approaches to depressed patients are based on local clinical recommendations and clinical 
experience of HCPs. Decision on agomelatine administration must be made with accordance to  
established SmPC, local standards and guidelines and must be independent from and proceeding 
the decision of the physician to include a patient in this study.  
Study plan and procedures 
A patient with depression occurred within 3 month period after onset of confirmed COVID 19 
infection who has already been recommended to initiate antidepressive treatment with agomelatine 
will be asked to provide a consent to participate in the study and in case of consent is positive the 
patient will be invited for 3 more visits starting from the date of the inclusion in the study according 
to clinical practice. Therefore clinical parameters needed for describing effectiveness and 
tolerability of agomelatine treatment will be prospectively collected at each of these visits. 

 
Antidepressive treatment of enrolled outpatients can be modified by investigating psychiatrist or 
neurologist at any time of the observation if required.   
 
Following visits are planned: 
1. Inclusion Visit 0 (V0) – inclusion in the study 
2. Follow up Visits 1-2 (V1-V2) – visits at week 2 and week 4 after V0. 
3. Final Visit 3 (V3) – visit at week 8 after V0.  
Table 1 – Planned study visits and collecting parameters at each visit 
Procedure 
Inclusion  
Visit 0 
 
 Visit 1 at 
W2 
Visit 2 at 
W4 
Visit 3 at  
W8 
Written informed consent 
X 
 
 
 
Assessment in accordance to inclusion/ non-
inclusion criteria  
X 
 
 
 
Assessment in accordance to exclusion 
criteria 
 
X 
X 
X 
Demographics 
X 
 
 
 
HAMD-17 
X 
X 
X 
X 
CGI -I 
 
X 
X 
X 
SF-36 
X 
X 
X 
X 
Current treatment with other concomitant 
medications  
X 
X 
X 
X 
Adverse events/drug reactions/ special 
situations reporting  
 
X 
X 
X 
 
 
 
 
 
 
Data evaluation/collection at the incusion visit (V0): 
HCPs participating in the study will prospectively evaluate patient’s eligibility to be enrolled in 
the study. Following data will be prospectively collected at the inclusion visit:  
• 
Obtained patient’s consent. 
• 
Meeting to inclusion/non-inclusion criteria. 
• 
Demographics. 
• 
Confirmation of COVID 19 infection within 3 month period.  
• 
HAMD-17 score. 
• 
Concomitant current use of other medications. 
• 
Quality of life assessment (SF-36). 
Data collection at the Follow up Visit (V1 – week 2): 
• 
HAMD-17 score. 

• 
CGI-Improvement score. 
• 
Presence of exclusion criteria. 
• 
Concomitant current use of other medications. 
• 
Quality of life assessment (SF-36). 
• 
Adverse events/drug reactions/special situations. 
• 
Change in therapy with agomelatine if occurred or required. 
Data collection at the Follow up Visit (V2 - week 4): 
• 
HAMD-17 score. 
• 
CGI-Improvement score. 
• 
Presence of exclusion criteria. 
• 
Concomitant current use of other medications. 
• 
Quality of life assessment (SF-36). 
• 
Adverse events/drug reactions/special situations. 
• 
Change in therapy with agomelatine if occurred or required. 
Data collection at the Final Visit (V3 - week 8): 
• 
HAMD-17 score. 
• 
CGI-Improvement score. 
• 
Presence of exclusion criteria. 
• 
Concomitant current use of other medications. 
• 
Quality of life assessment (SF-36). 
• 
Adverse events/drug reactions/special situations. 
• 
Change in therapy with agomelatine if occurred or required. 
 
 
 
 
 
 
 
 
 
 
 

 
 
Statistical analysis  
Due to non-interventional nature of the study design descriptive statistical methods will be used.  
Search statistical analysis will be performed in the following groups of patients: in the clinical 
study the primary end point of the study is a mean change from BL in HAMD-17 total score 
assessed at week 8 of the observational period. 
In the article of O.V. Vorob’eva “Valdoxan in the Treatment of Depression in Neurological 
Practice: Results of the Russian Multicenter Naturalistic Study “Resonance” from Zhurnal 
Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 112, No. 9, Iss. I, pp. 47—51, September, 
2012, was described the efficacy and tolerance of Valdoxan (agomelatine) in mild and moderate 
depression due to neurological diseases. Treatment efficacy was evaluated using standard 
psychometric tools, one of them was the 17-point Hamilton depression scale (HAMD-17).  
The mean total score on the HAMD-17 was 15.3 ± 3.8 points. Significant decreases in total points 
scores on the HAMD-17 were seen by the end of the first week of treatment. After completion of 
treatment courses (at six weeks of treatment), the mean score was 4.7 ± 3.2 points. At six weeks 
of treatment, responders (patients with total HAMD-17 scores which decreased at least twofold) 
constituted 82.33% of all patients treated.  
The following general assumptions were made for the sample size calculations: 
1) One-sided (directional) statistical hypothesis for mean: 
H0: m1 – m0 ≤ 0 
HA: m1 – m0 > 0 
where m1 stands for sample (study) mean of the corresponding variable (change from BL in HADS 
total score assessed at week 8 of the observational period), and m0 stands for the population mean 
(constant). 
2) Possible standard deviation is 3.8 points 

3) Planned study power is 90%, accordingly, type II (β) error is 0.1 
4) Overall significance level is 0.01 that corresponds to two-sided type I (α) error of 0.01 or 
one-sided type I (α) error of 0.005 
5) Dropout during the study period to 30%. 
Calculations for each of the parameters listed above were performed using the validated PASS 
sample size calculation software, with main outputs (screenshots) provided under the assumptions 
summarized above. 
 
As can be seen from the various scenarios provided depending on the planned difference, 
approximately 28 study subjects will be enough to detect at least a 3.0-point difference between 
the sample and population means with 90% power at 0.005 one-sided significance level. Dropout-
Inflated Enrollment Sample Size is 40 study subjects. 
Despite that sample size calculation is 40 patients, at least 100 patients with MDD will be 
invited to participate in the study. 
Safety  
Definitions 
Pharmacovigilance information  
Pharmacovigilance data include any unintended or adverse event associated with the use of a 
medicinal product in humans, whether or not considered drug related, including the following 
special situations (situations where no adverse event occurred but information needs to be 
collected): 
• 
exposure during pregnancy or breastfeeding;  
• 
overdose, abuse, misuse, off-label uses, medication error, occupational exposure (including 
professional one); 
• 
lack of efficacy. 
• 
any suspected transmission via a medicinal product of an infectious agent,  
• 
unintended therapeutic benefit.  

 
 
Adverse event (AE) 
Adverse event (AE) is any untoward medical occurrence in a patient or clinical-trial participant 
administered the medicinal product, which does not necessarily have a causal relationship with 
the use of this medicinal product. 
 
 An adverse event can therefore be any unfavorable and unintended sign (e.g. an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered as related to the medicinal product. 
 
Adverse (drug) reaction (ADR) 
 Adverse reaction (synonyms: Adverse drug reaction, Suspected adverse (drug) 
reaction, Adverse effect, Undesirable effect) is a response to a medicinal product which 
is noxious and unintended.  
Response” in this context means that a causal relationship between a medicinal product 
and an adverse event is at least a reasonable possibility.  
Adverse reactions may arise from use of the product within or outside the terms of the 
marketing authorization or from occupational exposure. Conditions of use outside the 
marketing authorization include off-label use, overdose, misuse, abuse and medication 
errors. 
Serious adverse (drug) reaction (SADR)  
Serious adverse reaction is an adverse reaction, which results in death, is life-threatening, 
requires in-patient hospitalisation or prolongation of existing hospitalisation, results in 
persistent or significant disability or incapacity, or is a congenital anomaly/birth defect. 
 Life threatening in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused 
death in case of more severe course. 
 Medical and scientific judgement should be exercised in deciding whether other situations 
should be considered as serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalisation but might jeopardize the patient 
or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation or 
development of dependency or abuse. 
Any suspected transmission via a medicinal product of an infectious agent is also  considered 
as a serious adverse reaction. 
 
Responsibilities 
• 
   Events to be reported 
• 
   All available information about the following events reported during the study will be 
recorded:  
All serious adverse drug reactions related to the use of Agomelatine  
• 
All non-serious adverse drug reactions related to the use of Agomelatine  
• 
All reports about special situations (see section Pharmacovigilance information) 

• 
All adverse events 
Specific attention should be paid to increase of ALT and/or AST, ALP value >3 ULN and 
increase of total bilirubin > 2 ULN. 
 
Responsibilities of investigator 
In prospective studies, at medical visits the investigator will ask a participating patient to 
indicate whether or not an adverse event (serious or not) has occurred. 
Investigator has to assess causal relationship between an adverse event and the investigated 
drug intake, as well as the seriousness criteria and later on the outcome of the event.  
 In case of Adverse Events, Adverse Drug Reactions or special situations that occurs during the 
study (both serious and non-serious), the investigator must complete the “Adverse event / 
Adverse drug reaction / Special Situation Reporting Form” (Appendix 4) without waiting for 
the clinical outcome or the results of additional investigations.  
 If the event is serious, it will be notified immediately (same or next working day at the latest) 
to Servier company in Russia via e-mail to address pvmail.rus@servier.com or by fax to number 
(495) 937-47-66. The anonymized copies of all the available and relevant laboratory findings, 
hospitalisation reports or other investigation results performed in connection with the adverse 
event should be attached to the form. 
All other events should be reported by investigator within 2 working days. 
The same rules apply for the transferring of additional information about the event.  
 The investigator must ensure the appropriate follow-up of the patient depending on the nature 
of event, until it resolves. The investigator will continue to notify follow up data according to 
timeframes defined above. 
If investigator does not follow-up a patients anymore (i.e. in case of hospitalization followed 
by the treatment by specialist or the participant's general practitioner,…), he/she will do every 
effort to contact the specialist or department in charge of follow-up of the patient, so as to have 
additional information and report it to Servier company in Russia. 
Responsibilities of sponsor/marketing authorization holder (MAH) 
 Independently of the regulatory obligations of investigator, the sponsor/MAH must report the 
pharmacovigilance data to the appropriate authorities in accordance with the Good Vigilance 
Practice and local regulations. 
Cases are closed when an adverse event has recovered or patient’s condition was stabilized and 
the report is deemed sufficiently detailed for adequate medical analysis of the case. 
 
Data Management 
• 
Data collection in this study is carried out using documentation forms. Centralized data entry 
will be performed by the responsible professional subcontractor for statistical analyses after 
receiving the documentation forms. The statistical analysis of the data and the creation of the 
final statistical report on the study will also be carried out by a responsible professional 
subcontractor for statistical analyses. 
• 
Discrepancies will be resolved by mutual agreement between both parties (Servier and 
professional subcontractor for statistical analysis). 
 
 

 
Biometrics 
• 
Due to the non-interventional nature of this study, statistical analysis will be conducted in a 
descriptive and searchable form. All indicators will be analyzed using descriptive statistics 
methods. For each indicator, the number of patients, the average value, the standard error, the 
minimum and maximum values, or the proportion of each category will be specified. All 
composite indicators will be 
• 
listed and presented in visual form as graphs and frequency distribution tables / indicator tables. 
• 
Absolute and percentage frequencies will be calculated for categorical variables. Only patients 
for whom data on the corresponding variables will be available will be included in the relative 
frequency calculations. 
• 
All reports of adverse drug reactions, adverse events, and special situations will be coded using 
MedDRA, and the results will be listed and classified according to classes for organ and organ 
systems (system-Organ-Class; SOC) by the statisticial agency during preparation of final 
report. 
 
Publications and communication 
• 
The sponsor is responsible for communicating and publishing research data. No part of the 
results of this study or other data may be published, presented or distributed without the express 
written permission of Sponsor. Participants in the study fully transfer to the Sponsor the 
authority for the first presentation, communication and publication of the results on behalf of 
all employees. No other communication or publication is permitted before this first publication. 
Any subsequent communication or publication must first be reviewed and approved by the 
Sponsor and should refer to the research and the first publication. 
 
Ethic aspects 
• 
The study will be conducted in accordance with the principles of the Helsinki Declaration, 
according to the version revised in Brazil in 2013. 
• 
The Protocol must be reviewed and approved by an independent ethics Committee after being 
submitted by the coordinator or sponsor in accordance with local regulatory requirements, 
especially with regard to data protection. 
 
Confidentiality of patient data 
• 
Researchers are required to maintain the confidentiality of information about patients included 
in this study. Confidential data should contain enough information to contact the patient in case 
of an emergency, or if further monitoring is required. 
To protect data privacy and keep patients anonymous, their identity will be encoded in the 
research documentation. Patients can be identified using a unique number that will be 
recorded and the CRF. In order to reveal the patient's identity, all researchers will have a 
confidential list of patient identification containing the names and phone numbers. Thus, 
only the researcher will be able to decode the patient's identity. 
 
 
 

Appendix 1. 
THE HAMILTON RATING SCALE FOR DEPRESSION (HAMD-17) 
 
Instructions. 
For assessment please choose one answer that best characterizes the patient's condition. 
For item 7 (work and activities) the researcher can obtain information from relatives or medical 
personnel. 
Item 16 (weight loss) requires an answer only by one of the proposed points 16A and 16B 
according to the "yes or no". The assessment of body weight changes is more preferable during 
therapy (16B). The assessment of weight change on anamnestic information (16A) is used only as 
initial, before starting therapy. 
 
1 
DEPRESSED MOOD  
(sadness, hopeless, helpless, worthless) 
  
0- Absent 
1- These feeling states indicated only on questioning 
2- These feeling states spontaneously reported verbally 
3- Communicates feeling states non-verbally—i.e., through facial expression, posture, 
voice, and tendency to weep 
4- Patient reports VIRTUALLY ONLY these feeling states in his spontaneous verbal 
and nonverbal communication 
 
2 
FEELINGS OF GUILT  
0- Absent 
1- Self-reproach, feels he has let people down 
2- Ideas of guilt or rumination over past errors or sinful deeds 
3- Present illness is a punishment. Delusions of guilt 
4- Hears accusatory or denunciatory voices and/or experiences threatening visual 
hallucinations 
 
3 
SUICIDE 
 
0 - Absent 

 
1 - Feels life is not worth living 
2 - Wishes he were dead or any thoughts of possible death to self 
3 - Suicidal ideas or gesture 
4 - Attempts at suicide (any serious attempt rates 4) 
 
4 
INSOMNIA EARLY  
 
0- No difficulty falling asleep 
1- Complains of occasional difficulty falling asleep—i.e., more than 1/2 hour 
2- Complains of nightly difficulty falling asleep 
 
5 
INSOMNIA MIDDLE 
 
0- No difficulty 
1- Patient complains of being restless and disturbed during the night 
2- Waking during the night—any getting out of bed rates 2 (except for purposes of 
voiding) 
 
6 
INSOMNIA LATE  
 
0- No difficulty 
1- Waking in early hours of the morning but goes back to sleep 
2- Unable to fall asleep again if he gets out of bed 
 
7 
WORK AND ACTIVITIES  
0- No difficulty 
1- Thoughts and feelings of incapacity, fatigue or weakness related to activities; work 
or hobbies 
2- Loss of interest in activity; hobbies or work—either directly reported by patient, or 
indirect in listlessness, indecision and vacillation (feels he has to push self to work 
or activities) 
3- Decrease in actual time spent in activities or decrease in productivity. In hospital 
settings the mark “3” is stated if patient’s activity is exhibited during at least 3 hours 
per day (working in a hospital or a hobby)  

4- Stopped working because of present illness. 
  In hospital settings the mark “4” is stated if patient does not exhibit activity or does 
not cope even with routine household activity without assistance. 
 
8 
RETARDATION: PSYCHOMOTOR  
(slowness of thought and speech; impaired ability to concentrate; decreased motor 
activity)  
0- Normal speech and thought 
1- Slight retardation at interview 
2- Obvious retardation at interview 
3- Interview difficult 
4- Complete stupor 
 
9 
AGITATION 
 
0- None 
1- Fidgetiness 
2- Playing with hands, hair, etc.  
3- Moving about, can't sit still 
4- Hand wringing, nail biting, hair-pulling, biting of lips 
 
10 
ANXIETY (PSYCHOLOGICAL)  
 
0- No difficulty 
1- Subjective tension and irritability 
2- Worrying about minor matters 
3- Apprehensive attitude apparent in face or speech 
4- Fears expressed without questioning 
 
 
11 
ANXIETY SOMATIC  

 
(Physiological concomitants of anxiety: gastrointestinal - dry mouth, "butterflies," 
indigestion, stomach cramps, belching, diarrhea; 
cardiovascular – palpitations, headache; respiratory – hyperventilation, dyspnea; 
urinary frequency; sweating) 
0- Absent 
1- Mild 
2- Moderate 
3- Severe 
4- Incapacitating 
 
12 
SOMATIC SYMPTOMS (GASTROINTESTINAL)  
 
0- None 
1- Loss of appetite but eating without encouragement from others. Food intake about 
normal 
2- Difficulty eating without urging from others. Requirement in laxatives and drugs 
for relief of gastrointestinal symptoms 
 
13 
SOMATIC SYMPTOMS GENERAL  
 
0- None 
1- Heaviness in limbs, back or head. Backaches, headache, muscle aches. Loss of 
energy and fatigability 
2- Any clear-cut symptom rates 
 
14 
GENITAL SYMPTOMS  
 
0- Absent 
1- Mild – loss of libido 
2- Severe – menstrual disturbances 
 
15 
HYPOCHONDRIASIS 

 
0- Not present 
1- Self-absorption (bodily)  
2- Preoccupation with health 
3- Frequent complaints, requests for help, etc. 
4- Hypochondriacal delusions 
 
 
16А 
 
 
 
16В 
 
LOSS OF WEIGHT (either А or B is used)  
 
А. When rating by history:  
0- No weight loss 
1- Probably weight loss associated with present illness 
2- Definite (according to patient) weight loss  
3- Not assessed 
 
B. If loss of weight is observed each week and is actual now  
0- Less than 0.5 kg per week  
1- More than 0.5 kg per week 
2- more than 1 kg per week  
3- Not assessed 
 
 
17 
INSIGHT 
  
0- Acknowledges being depressed and ill 
1- Acknowledges illness but attributes cause to bad food, climate, overwork, virus, 
need for rest, etc. 
2- Denies being ill at all 
 
Table for recording scores by Hamilton Depression Rating Scale 
 
Total score by HAMD-17 scale:________________ 

 
 
Assessment of the severity of condition using Hamilton Depression Rating Scale: 
0 – 7 «normal» (no marked symptoms of anxiety and depression) 
8 – 15 «mild depression» 
16 – 24 «moderate depression» 
25 and more «severe depression» 
 
 
 
 
 
 
.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix  2. 

 
 

 
 

 

 
 

 
 
 
 
 
 
 
 
 

 
Appendix  3. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Appendix 4  Form for reporting an adverse event / adverse drug reaction / special situations 
IC4-20098-069- RUSPlease send this form immediately by fax (495) 937-47-66 or by email to 
pvmail.rus@servier.com, or pass to the associate of the company. 
Year of birth or Age Gender 
 Height 
 Weight 
 Patient’s ID: 
 
|__|__|__|__| or |__|__|__| M / F 
 |__|__|__| 
 |__|__|__| 
 |_|_|_|_|_|_|_|_|_|_| 
  
Description of adverse event/reaction/special situation: 
Date of event onset 
 
|_|_| |_|_| |_|_|_|_| 
Date 
of 
event 
termination (in case 
of recovery) 
 
|_|_| |_|_| |_|_|_|_| 
 
 
 
Criteria of seriousness:  NO 
 
  YES (please, specify from stated below)  
 
 Death  
 
 Life threatening 
 
 Hospitalization or prolongation of existing hospitalisation 
 
 Persistent or significant disability or incapacity 
 
 Congenital anomaly/birth defect 
 
  Medically significant 
Outcome: 
 
 Recovered  
 
 Recovered with consequences (persistent  
 structural or functional impairment) 
 
 Not recovered  
 
 No recovered 
 
 Death  
 
 Unknown 
General disease(s) / Concomitant disease(s) (please indicate year when first diagnosed). 
Course adverse event/reaction/special situation (please enclose relevant findings, e.g. laboratory, hospital reports, 
histology, etc.): 
 
Causal relationship with intake of studied drug:  
 NO 
  
 YES  
 NOT APPLICABLE 
 
If «Yes», please indicate dates of the use of studied drug in the first line of the table below:  
 
If «No» or «Not applicable», please specify whether the adverse event/special situation is related to the medication 
of Servier company (which is specified in the table below): 
  NO     YES Please indicate the name of the medication of Servier company: ………………………… 
List of current 
medications  
Daily dose / 
route of 
administration
Dates of intake: 
from 
to 
Indication 
 
 
- 
 
 
 
 
 
 
 
- 
 
 
 
- 
 
 
 
 
 
Name (last, first, patronymic) of doctor:  
Speciality:  
Work address: 
Phone number: ________________________________________ 
 (city code) 
Date:  
 
 
Signature: 
*Special situations are cases when adverse event was not observed, but the information should be collected: the impact of the 
drug during pregnancy/breastfeeding, abuse, misuse, medication error, overdose, off-label use, occupational exposure, or lack of 
efficacy, any suspected transmission via medicinal product of an infection agent, unintended therapeutic benefit…  
Stamp 
(whenever possible)