Anton Vinoth.T M.Pharm, Prof .K. Nagarajan , Mr. Manikandan

A PROSPECTIVE AND COMPARATIVE STUDY ON THE EFFICACY OF THE ESCITALOPRAM AND CITALOPRAM IN MAJOR DEPRESSIVE DISORDER PATIENTS Anton Vinoth.T M.Pharm, Prof .K. Nagarajan , Mr. Manikandan Department of Pharmacy practice, K.M College of Pharmacy, Madurai, Tamilnadu.

ABSTRACT:

Mood disorders (affective disorders) are among the most common mental disorders encountered in clinical practice and divided into bipolar disorders and depressive disorders. The essential feature of these disorders is a major disturbance in mood.

Depression is common, affecting about 121 million people world wide. At its worst depression can lead to suicide, a tragic fatality associated with the loss of about 85000 lives every year. By the year 2020, depression is projected to reach the second

Major depression is among the most common mental disorders encountered in clinical practice. The problems associated with depression can become chronic or recurrent and lead to substantial impairment in an individual’s ability to take care of his or her everyday responsibilities. At its worst depression can lead to suicide, a tragic fatality associated with the loss of a large number of lives every year. Depression is the leading cause of disability as measured by YLDs and the leading contributor to the global burden of diseases (DALYs) in 2000.

The present study is done as it is the role of a clinical pharmacist to evaluate the efficacy and safety of the drugs acting through specific antidepressant mechanisms and to assess the possibility of matching patient symptom profile with antidepressant mechanism to achieve more rapid response or greater efficacy.

The aim of the study is to compare the efficacy of Citalopram and Escitalopram in the Major Depressive Disorder Patients during the first 8 weeks (acute phase) of treatment. Introduction:

The term depression is reserved in psychiatry to describe a specific entity having biologic and pharmacologic implications. Studies show that the physical and social dysfunctions produced by depression outweigh most chronic medical conditions. The medical outcomes study demonstrated that the degree of impairment in depressed patients is comparable only to patients with chronic heart disease. In turn, the cost of care for depression produces a tremendous burden upon society. If co-morbid with a medical condition, and may even shorten life expectancy.

Because of high prevalence and chronicity of depression, a complete antidepressant response remains an objective for clinicians and is still a key target for new drug developments. Approximately eight classes of antidepressants acting by different mechanisms are available for the physicians for treatment.

Despite the similarity of escitalopram and Citalopram, preclinical as well as various clinical studies (including double-blinded studies) have shown differentiated effects of Citalopram and escitalopram, as well as a clinical superiority compared with a variety of other SSRIs, such as paroxetine especially in severely depressed patients A head-to-head comparison of escitalopram with duloxetine (Cymbalta) found escitalopram to be both more tolerable and more effective. Compared with venlafaxine and sertraline, escitalopram was shown to have similar efficacy.

METHODOLOGY STUDY DESIGN:

 A prospective randomized interventional study is carried out Comparative study of Citalopram and Escitalopram in the Major Depressive Disorder patients

 This is an 8 week study. Participated patients shall be visiting the hospital for periodical review, for every 2 weeks.

 This study is conduct over a period of six months including the interpretation and analysis of results.

 Totally 20 patients are selected for each groups randomly and enroll for this study.

 The result will calculate with regular follow up to analyse the efficacy and safety of Citalopram and escitalopram in major depressive disorder patient.

 The result will calculate with the help of statistics, tables and graphs.

The study was conducted in 6 phases.

PHASE 1

 Discussion about the use of various types of antidepressants with the psychiatrists of M.S Chellamuthu Trust & Research Foundation Madurai.

 Enquiring of the relevance of this study with Dr.Ganesh Kumar M.B, B.S, DPM (Psychiatry), Consultant psychiatrist of M.S Chellamuthu Trust & Research Foundation Madurai.

 Collection of literatures.

PHASE 2

 Designing of the methodology of the study was done.

 Case report forms were prepared and the different rating scales of depression were collected.

PHASE 3

SELECTION OF SAMPLE 40 consecutive patients attending the psychiatric clinic during the study period were independently evaluated by the psychiatrist who initially did the clinical interview and arrived at a diagnosis using the ICD-10 criteria for research.

INCLUSION CRITERIA:

 Outpatients.

 Patients who met DSM-IV criteria for major depressive disorder (MDD), a single major depressive episode or recurrent major depressive episode without psychotic features, MDD are primary mental disorder.

 Age from 18-75 Years old, male or female.

 HAMD-17 total score at least 20 at baseline and first item’s score at least 2

 MADRS score greater than or equal to 22 at baseline.

 CGI-S at least 4 at baseline

 Written informed consent provided by patient himself/herself.

EXCLUSION CRITERIA:

 Severe suicide attempt.

 Any unstable medical illness would affect study or increase patient’s risk to participate this study, including disease of heart, lung, liver, kidney, cardiovascular system, eyes, nervous system, endocrine system, hematological system etc.

 History of epilepsy (except children febrile seizure/convulsion)  Known history of high intraocular pressure or angle closure glaucoma

 Psychoactive substance abuse or dependences within 1 year prior enrollment.

 Depressive episode due to other mental disorders or physical diseases.

 Bipolar disorder, rapid cycling/circulation

 Female patient during their pregnant and lactation period or childbearing potential during study.

 History of severe drug hypersensitivity.

 Patients cannot administrate drug according to medical order.

 HAMD total score decreased more than 25% from screening to baseline

 Use of Electroconvulsive therapy within half year prior enrollment.

 Known lack of efficacy to escitalopram by treatment before

PHASE 4

COLLECTION AND COMPILATION OF DATA

 Source of data:

Patient interview

Hamilton rating scale for depression

Montgomery-Åsberg Depression Rating Scale

Clinical Global impressions scale.

Patient case notes

Treatment chart

 Method of collection of data The patients satisfying the inclusion criteria were assessed for the severity of the illness using, (1) HAM-D scale which assess the score of the 17 symptoms of the disease and (2) CGI scale which classifies the patients onto different groups on the basis of the severity of the disease, (3) MADRS was originally a subscale of the Comprehensive Psychopathological Rating Scale.

 Hamilton Rating Scale for Depression

The Hamilton rating scale is designed to be used only on patients already diagnosed as suffering from depression. It is used for quantifying the results of an interview, and its value depends on the skill of the interviewer in eliciting the information.

The scale contains 21 items. Each item is measured on a five-point or three-point scale, and the scores are summed. If the score is higher patients has severe depression rate.

Depending on the version used, there are either 17 or 21 items for which an interviewer provides ratings. Besides the interview with the depressed patient, other information can be utilized in formulating ratings, such as information gathered from family, friends, and patient records. Hamilton stressed that the interview process be easygoing and informal and that there are no specific questions that must be asked.

OBSERVATION & RESULT:

PATIENT DEMOGRAPHIC CHARACTERISTICS

SEX DISTRIBUTION

Table. 1

TOTAL TOTAL SEX CITALOPRAM ESCITALOPRAM NO.OF PERCENTAGE PATIENTS MALE 8 8 16 40%

FEMALE 12 12 24 60%

Out of the 40 major depressions Patients 16(40%) were males and 24(60%) were females. The numbers of female patients were higher when compared to male patients .this result shows us that female patient was mostly affected by depression. See in table.1

Figure. 1

AGE GROUP

Table. 2

Age group Severity of illness Total no. of Percentage Borderline Mildly ill Moderately Markedly patients mentally ill ill ill 20-30 2(20%) 4(40%) 2(20%) 2(20%) 10 25%

31-40 3(25%) 7(58.33% 0(0%) 2(16.66%) 12 30% ) 41-50 2(15.38%) 6(46.15% 3(23.07%) 2(15.38%) 13 32.5% ) 51-60 1(25%) 3(75%) 0(0%) 0(0%) 4 10%

61-70 0(0%) 0(0%) 1(100%) 0(0%) 1 2.5%

Out of the 40 patients 10(25%) patients were under the age of 20-30, 12(30%) patients were under the age group of 31-40, 13(32.5%) patients were under the age of 41-50, 4(10%) patients were under the age group of 51-60, and 1(2.5%) was under the age group of 61-70. Table.2 data’s shows that the maximum number of patients were under the age group of 41-50.

Figure. 2

CLASSIFICATION OF PATIENTS BY THEIR AGE GROUP

Figure. 3 MARITAL STATUS

Table. 3

NO. OF FEMAL MARITAL STATUS MALE PERCENTAGE PATIENTS E

MARRIED 36 14 22 90%

UNMARRIED 4 2 2 10%

Of the 40 patients, 36(90%) were married and 4(10%) were Unmarried. This data’s clearly shows that most of married persons in this study were affected by depression, 14 males and 22 females were married so we came to know females were mostly affected by this disorder

Figure. 4

OCCUPATIONAL STATUS

Table. 4

OCCUPATION NO. OF PATIENTS PERCENTAGE

HOUSE WIFE 20 50%

BUSINESS 8 20%

PRIVATE EMPLOYEES 4 10%

GOVERNTMENT EMPLOYEES 0 0% STUDENT 0 0%

AGRICULTURE 3 7.5%

UNEMPLOYED 5 12.5%

Of the 40 patients, 20(50%) were house wife, 8(20%) patients were business men, 4(10%) patients were private employees, 3(7.5%) patients were agriculturist and 5(12.5%) patients were unemployed. This data shows that the maximum numbers of patients were housewives because they were not had a chance to share their feelings to any else, they dump their feelings themselves; it was create a depressive mind.

Figure. 5

ETIOLOGICAL FACTORS

Table. 5

FACTORS NO. OF .PATIENTS PERCENTAGE

PHYSICAL ILLNESS 11 27.5%

JOB PROBLEMS 4 10%

LOSS OF CLOSE FAMILY 5 12.5% MEMBERS

FINANCIAL PROBLEMS 2 5%

FAMILY PROBLEMS 4 10%

MARITAL CONFLICTS 5 12.5%

ACADEMIC PROBLEMS 1 2.5

NO SPECIFIC REASON 8 20

Out of the 40 patients, 11(27.5%) patients had physical illness as the etiological factor for depression. 5(12.5%) patients had marital conflict, 4(10%) patients had problems associated with job, 5(12.5%) patients were had a problem of loss of a close family member, 2(5%) patients had financial problems, 4(10%) had family problems, 1(2.5%) had academic problems and 8(20%) patients had no specific reasons as the etiological factor in table.5

Figure. 6

FAMILY HISTORY

Table. 6

CATEGORY NO.OF.PATIENTS PERCENTAGE

FAMILY HISTORY 2 5%

NO FAMILY HISTORY 38 95%

Out of 40 patients 2(5%) patients had a close relative with depression whereas 38(95%) had no family history. This data shows clearly us depression was not a genetical disorder.

Figure. 7

SEVERITY OF DISEASE

CLASSIFICATION OF PATIENTS ACORDING TO THE SEVERITY OF ILLNESS

Table. 7

SEVERITY OF ILLNESS NO.OF.PATIENTS PERCENTAGE

BORDER LINE MENTALY 8 20% ILL

MILDLY ILL 20 50% MODERATELY ILL 6 15%

MARKEDLY ILL 6 15%

On comparing the patients according to the severity of depression, more number of patients who came for treatment was mildly depressed (50%) followed by Border line mentally depressed (20%).The number of Moderately & Markedly depressed patients were (15%). The graphical representation in figure.9

Figure. 8

CLASSIFICATION OF PATIENTS ON THE BASIS OF HAM-D RATING FOR SUICIDAL TENDENCY

HAM-D TOTAL RATING FOR ESCITALOPRAM CITALOPRAM % NO.OF.PATIENTS SUICIDE

0 10 5 15 37.5%

1 7 12 19 47.5%

2 1 3 4 10%

3 0 2 2 5% Table. 8

Out of 40 patients who had a suicidal tendency, 15(37.5%) patients had HAM-D rating of 0(Absent) according to this 15 patients were not had any suicidal ideas. 19(47.5%) patients had HAM-D rating of 1(Feels that life is not worth living). 4(10%) patients had HAM-D rating of 2(Wishes he/she were dead or any thoughts of possible death to self). and 2(5%) patients had HAM-D rating of 3(Suicide ideas or gestures), according to before statement severe suicidal tendency was very less in both the drugs but comparatively citaloprm taking patients had suicide ideas or gestures Figure. 9 DISTRIBUTION OF PATIENTS ACCORDING TO THE DRUG PATTERN

Table. 9

DRUG NAME OF THE NO. OF. NON RESPONDER CATEGORY DRUGS PATIENTS RESPONDER

SELECTIVE ESCITALOPRAM 20 17(85%) 3(15%) SEROTONIN RE- UPTAKE INHIBITOR(SSRI ) CITALOPRAM 20 10(50%) 10(50%)

Out of 40 patients 20 patients were treated with Escitalopram in this 17 (85%) patients were responders, 3(15%) were non responders. Another 20 patients were treated with Citalopram in this 10(50%) patients were responders, 10(50%) were non responders. This result was shows us that Escitalopram taken patients had improved more in number compare to citalopram.

Figure. 10

EFFICACY OF THE DRUGS CITALOPRAM 20MG AND ESCITALOPRAM 10MG BASELINE VALUES HAMD MADRS DRUG MEAN SD MEAN SD

CITALOPRAM (Group A ) 27.75 2.2 32.4 3.46 ESCITALOPRAM 29.7 4.7 34.75 3.67 (Group B) 0.0227 0.0220 þ Not Significant Not Significant Table. 10 In this group A patients had a Mean value of 27.5 and SD value of 2.2 for HAMD scale. Mean value of 32.4 and SD value of 3.46 for MADRS scale. Group B patients had a Mean value of 29.9 and SD value of 4.7 for HAMD scale. Mean value of 34.75 and SD value of 3.67 for MADRS scale. Þ value for both groups in HAMD scale is 0.0227 and MADRS scale is 0.0220. These results were shows us that both the drugs in baseline visit had no significant effects.

PERCENTAGE OF CHANGES IN HAMD DURNG SECOND VISIT

Table. 11

CITALOPRAM ESCITALOPRAM

HAMD (Group A ) (Group B)

MEAN SD MEAN SD

Baseline (First visit) 27.75 2.2 29.7 4.7

Second visit 25.15 3.3 23.7 8.39

Change 2.6 3.1 6.2 8.8

% of change 9.17 10.82 19.78 26.22

þ 0.0513 Not Significant

Second visits Mean and SD values of group A drug was 25.15 and 3.3 respectively change values were 2.6 and 3.1, percentage of change was 9.17 and 10.82. Group B drug Mean and SD values were 23.7 and 23.7 respectively, change values were 6.2 and 8.8, and percentage of change was 19.78 and 26.22. Þ value of both the drugs was 0.0513 so efficacy was not significant (>0.05) at second visit.

Figure. 11 PERCENTAGE OF CHANGES IN HAMD DURNG THIRD VISIT

Table. 12

MEAN SD MEAN SD

Third visit 23.05 4.1 16.4 7.3

Change 4.7 4.13 13.5 9.39

% of change 16.66 14.65 43.27 26.31

þ 0.0002 Significant

Third visits Mean and SD values of group A drug was 23.05 and 4.1 respectively, change values from baseline were 4.7 and 4.13, percentage of change was 16.66 and 14.65. Group B drug Mean and SD values were 16.4 and 7.3 respectively, change values from baseline were 13.5 and 9.39, and percentage of change was 43.27 and 26.31. Þ value of both the drugs was 0.0002 so efficacy was significant (<0.05) at third visit.

Figure. 12

50 43.27

40 s e u

l 30 a v

H 20 16.66

n a e M 10

Group A Group B

PERCENTAGE OF CHANGES IN HAMD DURNG FOURTH VISIT

Table. 13

MEAN SD MEAN SD

Fourth visit 22.65 4.27 13.55 6.92

Change 5.1 4.26 16.35 10.04

% of change 18.l3 15.07 52.01 27.4

Fourth visits Mean and SD values of group A drug was 22.65 and 4.27 respectively, change values from baseline were 5.1 and 4.26, percentage of change was 18.13 and 15.07. Group B drug Mean and SD values were 13.55 and 6.92 respectively, change values from baseline were 16.35 and 10.04, and percentage of change was 52.01 and 27.4. Þ value of both the drugs was 0.0001 so efficacy was significant (<0.05) at fourth visit.

60 53.88

s 40 e u l a v

S 30 R D A M

n 20 a e M 10

Group A Group B

PERCENTAGE OF CHANGES IN HAMD DURNG FIFTH VISIT

Table. 14

MEAN SD MEAN SD

Fifth visit 22.55 4.16 13.25 6.77

Change 5.2 4.18 16.65 9.87

% of change 18.48 14.75 53.08 26.94

þ 0.0001 Significant Fifth visits Mean and SD values of group A drug was 22.55 and 4.16 respectively, change values from baseline were 5.2 and 4.18, percentage of change was 18.48 and 14.75. Group B drug Mean and SD values were 13.25 and 6.77 respectively, change values from baseline were 16.65 and 9.87, and percentage of change was 53.08 and 26.94. Þ value of both the drugs was 0.0001 so efficacy was significant (<0.05) at fifth visit.

Figure. 16

60 54.75

s 40 e u l a v

S 30 R D A M 17.81 n 20 a e M 10

Group A Group B

PERCENTAGE OF CHANGES IN MADRS DURNG SECOND VISIT

Table. 15

MADRS (Group A ) (Group B)

MEAN SD MEAN SD

Second visit 29.85 3.5 30.4 9.2

Change 2.55 4.36 4.35 7.18

% of change 7.05 13.36 13.43 22.87 þ 0. 6267 Not Significant

Second visits Mean and SD values of group A drug was 29.85 and 3.5 respectively change values were 2.55 and 4.36, percentage of change was 7.05 and 13.36. Group B drug Mean and SD values were 30.4 and 9.2 respectively, change values were 4.35 and 7.18, and percentage of change was 13.43 and 22.87. Þ value of both the drugs was 0.1441 so efficacy was not significant (>0.05) at second visit.

40 s e u l 30 a v

A 20 M 13.43 n a e M 10 7.05

Group A Group B

Figure. 17

PERCENTAGE OF CHANGES IN MADRS DURNG THIRD VISIT

Table. 16

MADRS (Group A ) (Group B)

MEAN SD MEAN SD

Baseline (First visit) 32.4 3.46 34.75 3.67 Third visit 26.9 4.28 21.05 10.25

Change 5.5 5.69 13.7 9.63

% of change 15.95 16.16 39.88 26.67

Third visits Mean and SD values of group A drug was 26.9 and 4.28 respectively change values were 5.5 and 5.69, percentage of change was 15.95 and 16.16. Group B drug Mean and SD values were 21.05 and 10.25 respectively, change values were 13.7 and 9.63, and percentage of change was 39.88 and 26.67. Þ value of both the drugs was 0.0007 so efficacy was significant (<0.05) at Third visit. Figure. 18

50 39.88 40 s e u l

a 30 v

S R D A 20 15.95 M

n a e M 10

Group A Group B

PERCENTAGE OF CHANGES IN MADRS DURNG FOURTH VISIT

Table. 17

MADRS CITALOPRAM ESCITALOPRAM

(Group A ) (Group B) MEAN SD MEAN SD

Fourth visit 26.55 4.48 16.25 9.78

Change 5.85 6.03 18.5 8.96

% of change 16.93 17.1 53.88 25.11

Fourth visits Mean and SD values of group A drug was 26.55 and 4.48 respectively change values were 5.85 and 6.03, percentage of change was 16.93and 17.1. Group B drug Mean and SD values were 16.25 and 9.78 respectively, change values were 18.5 and 8.96, and percentage of change was 53.88 and 25.11. Þ value of both the drugs was 0.0001so efficacy was significant (<0.05) at Fourth visit. Figure. 19

60 53.88

s 40 e u l a v

S 30 R D A M

n 20 a e M 10

Group A Group B

PERCENTAGE OF CHANGES IN MADRS DURNG FIFTH VISIT

Table. 18

MADRS CITALOPRAM ESCITALOPRAM (Group A ) (Group B)

MEAN SD MEAN SD

Fifth visit 26.3 4.6 15.95 9.91

Change 6.1 5.96 18.8 9.12

% of change 17.81 16.92 54.75 25.51

Fifth visits Mean and SD values of group A drug was 26.3 and 4.6 respectively change values were 6.1 and 5.96, percentage of change was 17.81and 16.92. Group B drug Mean and SD values were 15.95 and 9.91 respectively, change values were 18.8 and 9.12, and percentage of change was 54.75 and 25.51. Þ value of both the drugs was 0.0001so efficacy was significant (<0.05) at Fifth visit. Figure. 20

60 54.75

s 40 e u l a v

S 30 R D A M 17.81 n 20 a e M 10

Group A Group B

COMPARISION OF BOTH THE DRUGS HAM-D CITALOPRAM ESCITALOPRAM Percentage of changes at þ MEAN SD MEAN SD

0.0513 Not Second visit 9.17 10.82 19.78 26.22 Significant Third visit 16.66 14.65 43.27 26.31 0.0002 Significant Fourth visit 18.13 15.07 52.01 27.40 0.0001 Significant Fifth visit 18.48 14.75 53.08 26.94 0.0001 Significant

MADRS CITALOPRAM ESCITALOPRAM Percentage of þ changes at MEAN SD MEAN SD 0.1441 Not Second visit 7.05 13.36 13.43 22.87 Significant Third visit 15.95 16.16 39.88 26.67 0.0007 Significant Fourth visit 16.93 17.1 53.88 25.11 0.0001 Significant Fifth visit 17.81 16.92 54.75 25.51 0.0001 Significant

Table. 19

In HAMD rating scale percentage change in the mean value of citalopram had no significant value during 1st and 2nd visits but it was improved from 3rd visit onwards. During second visit the change was 9.17%, and then it will be gradually increased as 16.66%, 18.13%, 18.48%, during 3rd, 4th, 5th visits respectively.

In escitalopram groups percentage change in the mean value was improved from 3rd visit onwards but the percentage values were greater than citalopram groups. During second visit the value was 19.78% but third visit onwards the values were 43.27% for 3rd visit, 52.01% for 4th visit and 53.08% for 5th visit. Those results were gave us escitalopram had a great efficacy compare than citalopram groups.

In MADRS rating scale percentage change in the mean value of citalopram had no significant value during 1st and 2nd visits but it was improved from 3rd visit onwards. During second visit the change was 7.05%, and then it will be gradually increased as 15.95%, 16.93%, 17.81%, during 3rd, 4th, 5th visits respectively.

In escitalopram groups percentage change in the mean value was improved from 3rd visit onwards but the percentage values were greater than Citalopram groups. During second visit the value was 13.43% but third visit onwards the values were 39.88% for 3rd visit, 53.88% for 4th visit and 54.75% for 5th visit. Those results were gave us escitalopram had a great efficacy compare than citalopram groups.

Figure. 21

S 40 E G N

A 30 H C

20 % 10

0 2nd 3rd 4th 5th 2nd 3rd 4th 5th visit visit visit visit visit visit visit visit

Group A Group B

ASSESSMENT OF CLINICAL RESPONSE USING THE CLINICAL GLOBAL IMPRESSIONS SCALE (CGI SCALE)

Table. 20

DRUG GLOBAL IMPROVEMENT NO.OF.PATIENT PERCENTAGE CATEGORY ESCITALOPRAM MINIMALY IMPROVED 0 0%

MUCH IMPROVED 14 70% VERY MUCH IMPROVED 3 15% NO CHANGE 3 15%

During the second visit, all the 20 patients treated with Escitalopram 10mg showed a good response to the treatment. On assessment of response using rate of global improvement 14(70%) patients were Much Improved and 3(15%) patients were very much improved, 3(15%) patients were not significant in the treatment.

Figure. 22

Table. 21

During the second visit, all the 20 patients treated with Citalopram 20mg showed a good response to the treatment. On assessment of response using rate of global improvement 10(50%) patients were much improved, 10(50%) patients were not significant in the treatment.

Figure. 23

DRUG GLOBAL IMPROVEMENT NO.OF.PATIENT PERCENTAGE CATEGORY

MINIMALY IMPROVED 0 0%

MUCH IMPROVED 10 50% CITALOPRAM

VERY MUCH IMPROVED 0 0%

NO CHANGE 10 50% OBSRVATION OF SIDE EFFECTS IN GROUP OF PATIENTS WITH SPECIFIC GROUP OF DRUG

Table. 22

Side effects Category of drug No. of patients Percentage Observed

Nausea 3 15%

Vomiting 1 5% ESCITALOPRAM Stomach upset 1 5%

Dry mouth 1 5%

During the second visit, out of the twenty depressed patient treated with Escitalopram, 3 patient were reported as nausea, one reported vomiting, one patient reported stomach upset, and 1 reported as dry mouth, but 14 patients were not reported any side effects.

Figure. 24

Table. 23

Category of drug Side effects No. of patients Percentage Observed

CITALOPRAM Nausea 4 20%

Vomiting 2 10%

Stomach upset 1 5%

Dry mouth 2 10%

Constipation 2 10% Ejaculation disorder 2 10%

During the second visit, out of the twenty depressed patient treated with Citalopram, 4 patients reported as nausea. 2 patients reported vomiting, one reported as stomach upset, 2 patients reported as dry mouth, 2 patients were reported constipation, and 2 were reported as ejaculation disorder. In this 4 patients were not reported any side effect.

Figure.25

COMPARISION OF SIDE EFFECTS OF BOTH DRUGS

Table .24

CITALOPRAM ESCITALOPRAM SIDE EFFECTS NO. % NO %

Nausea 4 20 3 15

Vomiting 2 10 1 5

Stomach upset 1 5 1 5

Dry mouth 2 10 1 5

Constipation 2 10 0 0

Ejaculation disorder 2 10 0 0

Cases with no side effects 7 35 14 70

Group A Total of 20 patients 13 patients were affected by adverse effects like, nausea -4, vomiting-2, stomach upset-1, dry mouth- 2, constpation-2, and ejaculation disorder-2. Remaining 4 patients were not had any side effects.

Group B Total of 20 patients 6 patients were affected by adverse effects like, nausea -3, vomiting-1, stomach upset-1, and dry mouth- 1, Remaining 14 patients were not had any side effects.

In Escitalopram group less number (6) of patients were had side effects, so it was strongly recommended to the patient for major depressive condition; Citalopram more number (13) of patients were had side effects side effects, so some times the patients were switch over to escitalopram regimen

Figure. 26

COST EFFECTIVENESS OF THE COMPARITIVE DRUGS

Table. 25

DRUGS MRP/Tab TOTAL COST OF 8 WEEK STUDY

CITALOPRAM Rs 6.50 Rs 364.00

ESCITALOPRAM Rs 6.00 Rs 336.00

From the above calculation citalopram had more cost (Rs 6.50) than citalopram (Rs 6.00). On the basis of these results, Escitalopram was concluded to be more clinically effective and more cost-effective than Citalopram for the treatment of MDD, with a similar tolerability profile. See the figure.27

Figure. 27

CONCLUSION:

The study attempted is comprehensive because it included all trials in which the maximum dose for Escitalopram (20 mg) can be administered. According to the cut- off point taken to define severe depression based on the MADRS TOTAL SCORE (30), 40 patients were considered as severely depressed patients and so included in this study. Among them, 20 administered Escitalopram 10mg, and 20 administered Citalopram 20mg. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS TOTAL SCORE between Escitalopram and Citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Results showed that the mean change from baseline in the MADRS total score was significantly higher in the Escitalopram group compared with the Citalopram group (15.95±9.91 Vs 26.3±4.6; p=0.001, P<0.05). Response rates were significantly higher for Escitalopram than for Citalopram (85% vs. 50% respectively). A borderline significant difference was found for remission rate in the observed-cases analysis (54.75% ±25.51 Vs. 17.81% ± 16.92 respectively, p=0.0001).

Analyses of the HAM-D total score was significantly higher in the Escitalopram group compared with the Citalopram group (13.25±6.77 Vs 22.5±4.16; p=0.0001, P<0.05). Response rates were significantly higher for Escitalopram than for Citalopram (85% Vs. 50% respectively). A borderline significant difference was found for remission rate in the observed-cases analysis (53.08% ±26.94 Vs. 18.48% ± 14.75 respectively, p=0.0001).

CGI-I and CGI-S scores revealed consistent results. In CGI-S 14(70%) patients were Much Improved and 3(15%) patients were Very much improved in Escitalopram 10mg group, but in Citalopram only 10(50%) patients were got improvement.

Escitalopram is significantly more effective than Citalopram, and is associated with lower healthcare costs. This prospective economic analysis demonstrated that Escitalopram is a cost-effective first-line treatment option for major depressive disorder

This study shows that the new SSRI Escitalopram has better efficacy in the treatment of severe depression than Citalopram, its racemic parent. Mean differences between treatments groups were in favour of Escitalopram for all scales. The benefits of Escitalopram compared with Citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of Citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of Escitalopram as a legitimate first-line treatment for MDD. References:

1. Murdoch D, et al

2. Müller-Spahn F.M. et al

3. Connie Sánchez, Klaus P.

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