RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
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|RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES |
|BANGALORE, KARNATAKA |
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|ANNEXURE II |
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|PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION |
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|1 |Name of the candidate & address |Dr. DIVYASHREE. M |
| | |POST GRADUATE IN PHARMACOLOGY, |
| | |BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE-560002 |
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|2 |Name of the institution |BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE-560002 |
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|3 |Course of study and subject |M.D. PHARMACOLOGY |
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|4 |Date of admission to the course |21st MAY 2011 |
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|5 |Title of topic |“A COMPARATIVE STUDY OF EFFICACY AND SAFETY OF CONVENTIONAL VERSUS NEWER|
| | |ANTIDEPRESSANTS IN PATIENTS WITH DEPRESSIVE EPISODE IN A TERTIARY CARE |
| | |HOSPITAL” |
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|6 |BRIEF RESUME OF INTENDED WORK: |
| |6.1 Need for study: |
| |Depression is a disabling disorder associated with considerable co-morbidity, risk of suicide and social consequences with individual|
| |lifetime prevalence of 5-17%,current prevalence of 2-7% and by year 2020 is projected to rank second in disease |
| |burden.[1] |
| |Individual antidepressants are equally efficacious but the choice is largely determined by differences in side effects. Tricyclic |
| |antidepressants (TCAs), have been the ‘gold standard’ because of superior efficacy, but their usage is associated with reports of |
| |inadequate dosing, duration of therapy, cardiotoxicity because of multiplicity of actions. Specific serotonin reuptake inhibitors |
| |(SSRIs) have superseded the TCAs as the most widely prescribed antidepressants, owing to their superior tolerability, negligible |
| |cardiovascular risk and greater safety in overdose, but have a constellation of side effects like nausea, diarrhea, insomnia, |
| |agitation, anxiety, headache and sexual dysfunction.[2] However, Escitalopram a newer SSRI is better tolerated than other SSRIs. |
| |Desvenlafaxine, a novel dual acting SNRI ( Serotonin and norepinephrine reuptake inhibitors) ensures efficacy, and its |
| |lack of affinity to other receptors offers better tolerability profile |
| |Despite the availability of various classes of antidepressants, patient response is not satisfactory, upto 40% fail to show a |
| |response to first-line antidepressant, 50% discontinue treatment owing to side effects or insufficient response, and more than 50% |
| |fail to achieve remission, even if they initially respond. |
| |The advent of newer antidepressants and lack of comparative studies with conventional TCAs has prompted us to undertake this study. |
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| |6.2 Review of Literature: |
| |In a meta-analysis published by Ian M Anderson, there is no overall difference in efficacy between SSRIs and TCAs however, SSRIs are|
| |better tolerated, with significantly lower rates of treatment discontinuations due to side effects.[3] |
| |In a meta-analysis of adverse effects associated with SSRIs and TCAs, published by Evelinda Trindade et al, subset meta-analysis of |
| |trials restricted to adult outpatients indicated that there were 2% fewer drop-outs due to adverse effects with the SSRIs, a |
| |significant difference.[4] |
| |In a meta-analysis conducted in Canada, SNRIs had the highest efficacy remission rates, and the lowest overall dropout rates, |
| |suggesting clinical superiority compared to TCAs and SSRIs, in treating major depression.[5] |
| |Escitalopram the S-enantiomer of Citalopram which is seen to be more potent and better tolerated than citalopram, was superior to all|
| |comparators namely citalopram, fluoxetine, paroxetine, sertraline and venlafaxine XR [extended release] in overall treatment effect |
| |in a study published by Sidney H Kennedy et al.[6] |
| |In a study conducted in China, it was found that Escitalopram was superior to Fluoxetine on two items of Hamilton-D 17 score i.e. |
| |‘depressed mood’ and ‘work and interest’ though it was well tolerated and as efficacious as Fluoxetine in other symptoms.[7] |
| |In an analysis of Escitalopram versus SNRIs i.e. Venlafaxine-XR and Duloxetine, in the acute treatment of major depressive disorder |
| |significantly fewer escitalopram than SNRI patients prematurely withdrew from treatment due to adverse events.[8] |
| |Desvenlafaxine is the synthetic form of the isolated major active metabolite of Venlafaxine. In a placebo-controlled trial of |
| |Desvenlafaxine succinate in adult out-patients of major depressive disorder both Desvenlafaxine doses(200mg/day and 400mg/day) showed|
| |greater efficacy than placebo on the efficacy measures and was also significantly better than placebo on remission, Visual Analog |
| |Scale–Pain Intensity overall scores, and some Visual Analog Scale–Pain Intensity subscale scores.[9] |
| |In a study conducted by Edward Schweizer et al showed Venlafaxine has antidepressant activity comparable to that of Imipramine in |
| |outpatients with moderate-to-marked unipolar depression and Venlafaxine was as well tolerated as Imipramine, with a somewhat lower |
| |rate of attrition due to adverse effects.[10] |
| |6.3 Objectives of study: |
| |To compare the efficacy of newer antidepressants like Escitalopram and Desvenlafaxine versus conventional antidepressant like |
| |Imipramine in patients with Depressive episode. |
| |To evaluate the safety of newer antidepressants like Escitalopram and Desvenlafaxine versus conventional antidepressant like |
| |Imipramine in patients with Depressive episode. |
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| |MATERIALS AND METHODS: |
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| |7.1 Source of data: |
| |Outpatients and inpatients in the department of psychiatry, Victoria hospital, Bangalore. |
|7 |Methods of collection of data: |
| |Study design: Open label, Prospective, Comparative study. |
| |Study period: Nov 2011- May 2013. |
| |Sample size: 90 patients with depressive episode. |
| |After obtaining approval and clearance from the institution ethics committee, patients will be included for the study. |
| |The study subjects fulfilling the inclusion/exclusion criteria will be randomly assigned into 3 groups of 30 patients in each group. |
| |Group 1 : Patients treated with Imipramine 75-225mg/day orally OD |
| |Group 2: Patients treated with Escitalopram 10-20mg/day orally OD |
| |Group 3: Patients treated with Desvenlafaxine 50-100mg/day orally OD |
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| |Inclusion Criteria : |
| |Patients of either sex aged between 18-65years suffering from depressive episode |
| |Newly diagnosed patients of depressive episode fulfilling the criteria of ICD-10 (International Classification Of Disease-10, WHO |
| |2007) |
| |Patients with >/= 24 on MADRS (Montgomery Asberg Depression Rating Scale) score. |
| |Patients giving written informed consent. |
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| |E. Exclusion Criteria: |
| |Patients being treated with more than one antidepressant |
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| |Patients with Psychotic depression, Bipolar disorder, Schizophrenia or Anxiety disorders |
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| |3. Patients with current suicidal ideation |
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| |4. Patients with serious decompensated medical conditions like Congestive cardiac failure, Renal failure, Hepatic failure. |
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| |5. Patients with ischeamic heart disease, cardiac conduction defects and arrythmias |
| |6. Patients with ECG abnormalities and abnormal liver enzymes. |
| |7. Presence of alcohol and substance dependence, epilepsy, mental retardation, mental disorders other than depression. |
| |8. Pregnant and lactating women. |
| |Non complying patients who are unable to give consent for the study. |
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| |Methodology: |
| |Inpatients as well as outpatients at the department of psychiatry diagnosed to be suffering from depressive episode using ICD-10 |
| |criteria and fulfilling the inclusion/ exclusion criteria will be taken into the study after obtaining written informed consent. |
| |Demographic data, history, clinical examination and details of drug prescription by the treating Psychiatrist, will be recorded in |
| |the study proforma. Follow up will be recorded at 2 weeks, 4 weeks, 8 weeks and 12 weeks after administering the study drugs. |
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| |G. Assessment tools: |
| |Proforma for informed consent.(Annexure-1) |
| |ICD-10 criteria for diagnosis of depressive episode. (Annexure-4). |
| |A thorough physical/ psychiatric evaluation will be carried out and recorded in the protocol. |
| |Vital signs: |
| |- Height, weight and body mass index |
| |- Pulse rate(pulsations/min) |
| |- Blood pressure(mm Hg) |
| |Efficacy will be assessed by |
| |- Montgomery Asberg Depression Rating Scale (MADRS) (Annexure-5) |
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| |- Clinical global impression- severity of illness (CGI-S) (Annexure-6) |
| |- Clinical global impression- global improvement (CGI-I) (Annexure-6) |
| |- Treatment satisfaction questionnaire for medication (TSQM) (Annexure-7) |
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| |Relevant laboratory investigations (Annexure-3): |
| |Blood biochemistry- random blood glucose, Alanine transaminase and Aspartate transaminase, serum creatinine and electrolytes, Lipid |
| |profile. |
| |Electrocardiogram (ECG) |
| |Safety will be assessed by number, severity and drop outs due to adverse drug reactions. Adverse drug reactions will be recorded |
| |using a proforma for eliciting adverse drug reactions.(Annexure-8) |
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| |The detailed schedule of patient visit is as follows : |
| |Visit 1/ day1 / initial or baseline assessment- |
| |Patients will be informed fully about the purpose and requirements of the study and written informed consent will be obtained |
| |(Annexure-1). |
| |Patient will be enrolled as per inclusion/exclusion criteria. |
| |Details of patient’s demographic characteristic, medical history, concomitant medication and detailed physical/psychiatric evaluation|
| |will be recorded (Annexure-3). |
| |MADRS scores will be taken |
| |Blood samples for relevant baseline laboratory investigations will be collected and ECG taken (Annexure-3). |
| |Medication will be issued to the patient and instructed for regular follow up at 2 weeks, 4 weeks, 8 weeks and 12 weeks |
| |Visit 2/ 2 weeks - |
| |Medication compliance, any intercurrent illness or change in concomitant medication will be recorded. |
| |All observed or spontaneously volunteered adverse events will be recorded. |
| |A thorough physical/ psychiatric evaluation will be carried out and recorded. |
| |MADRS scores will be taken. |
| |Visit 3/ 4 weeks- |
| |Medication compliance, any intercurrent illness or change in concomitant medication will be recorded. |
| |All observed or spontaneously volunteered adverse events will be recorded. |
| |A thorough physical/ psychiatric evaluation will be carried out and recorded. |
| |Blood samples for relevant laboratory investigations will be collected and ECG recorded |
| |MADRS scores will be taken |
| |Visit 4/ 8 weeks- |
| |Medication compliance, any intercurrent illness or change in concomitant medication will be recorded. |
| |All observed or spontaneously volunteered adverse events will be recorded. |
| |A thorough physical/ psychiatric evaluation will be carried out and recorded. |
| |Blood samples for relevant laboratory investigations will be collected and ECG recorded |
| |MADRS scores will be taken. |
| |Visit 5/ 12 weeks- |
| |Medication compliance, any intercurrent illness or change in concomitant medication will be recorded. |
| |All observed or spontaneously volunteered adverse events will be recorded. |
| |If any adverse event is persistent or there is any abnormal laboratory value of clinical significance appropriate follow up will be |
| |made and patient will be advised about further therapy. |
| |A thorough clinical/ psychiatric examination will be repeated. |
| |MADRS, CGI-I, CGI-S and TSQM scores will be taken |
| |Blood samples for relevant laboratory investigations will be collected and ECG recorded |
| |The study termination form will be completed. |
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| |Statistical analysis: |
| |The data in this study will be assessed using Analysis of variance and Chi- square test. |
| |7.3 Does the study require any investigation to be conducted on patients or animals specify? |
| |It does not require any animal studies. |
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| |These are the following investigations done routinely for patients on antidepressant drugs- |
| |Random blood glucose |
| |Alanine transaminase and Aspartate transaminase |
| |Serum creatinine and electrolytes |
| |Lipid profile |
| |ECG |
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| |7.4 Has the ethical clearance been obtained from ethics committee of your Institution in case of 7.3? |
| |Yes. Clearance has been obtained from the ethics committee of BMCRI, Bangalore |
| |LIST OF REFERENCES : |
| | |
| |1) Akiskal HS, Rihmer Z, Angst J et al, editors. Mood disorders. In : Sadock BJ, Sadock VA, Ruiz P, editors. Kaplan and Sadocks, |
| |Comprehensive textbook of Psychiatry. 9th edn. Philadelphia : Lippincott Williams and Wilkins; 2009: 1629-1743. |
| |2) Baldessarini RJ, editor. Drug therapy of depression and anxiety disorders. In : Brunton LL, editor. Lazo JS, Parker KL, associate |
| |editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th edn. New York: Mc Graw Hill; 2006: 429-454. |
| |3) Anderson I M. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and |
| |tolerability. Journal of affective disorders 2000;58:19-36 |
| |4) Trindade E, Menon D, Topfer L, Coloma C. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic |
| |antidepressants: a meta-analysis. CMAJ. 1998; 159(10):1245-1252. |
| |5) Machado M, Iskedjian M, Ruiz I, Einarson T R. Remission, dropouts and adverse drug reaction rates in major depressive disorder: a|
|8 |meta-analysis of head-to-head trials. CMRO 2006; 22(9): 1825-37. |
| |6) Kennedy S H, Andersen H F, Lam R W. Efficacy of escitalopram in the treatment of major depressive disorder compared with |
| |conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J Psychiatry Neurosci 2006; 31(2):122-31. |
| |7) Mao P, Tang Y, Jiang F, Shu L, Gu X, Li M et al. Escitalopram in major depressive disorder : A multicenter, randomized, |
| |double-blind, fixed dose, parallel trial in a Chinese population. Depression and anxiety Jan 2008; 25 (1):46-54. |
| |8) Kornstein S G, Li D, Mao Y, Larsson S, Andersen H F and Papakostas G I. Escitalopram Versus SNRI Antidepressants in the Acute |
| |Treatment of Major Depressive Disorder: Integrative Analysis of Four Double-Blind, Randomized Clinical Trials. CNS Spectr June 2009; |
| |14(6): 326-333 |
| |9) Septien-Veleza L, Pitroskya B, Padmanabhan S K, Germaina J and Tourian K A. A randomized, double-blind, placebo-controlled trial|
| |of Desvenlafaxine succinate in the treatment of major depressive disorder. Int Clin Psychopharmacol 2007; 22:338–347. |
| |10) Edward S, Feighner J, Mandos L A, Rickels K. Comparison of venlafaxine and imipramine in the acute treatment of major depression|
| |in outpatients. J Clin Psychiatry Mar 1994 55(3): 104-108. |
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|9 |Signature of the candidate | |
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|10 |Remarks of the guide |The study has been recommended and forwarded to generate efficacy and |
| | |safety data in Indian patients, as currently there is paucity of data. |
|11.1 |Name and designation of the guide |Dr. C R Jayanthi |
| | |Professor and Head of the department |
| | |Department of Pharmacology |
| | |BMCRI, Bangalore |
|11.2 |Signature of the guide | |
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|11.3 |Name and designation of co-guide |Dr Chandrashekar |
| | |Professor and Head of the department |
| | |Department of Psychiatry |
| | |BMCRI, Bangalore |
|11.4 |Signature of the co-guide | |
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|11.5 |Head of the department |Dr. C R Jayanthi |
| | |Professor and Head of the department |
| | |Department of Pharmacology |
| | |BMCRI, Bangalore |
|11.6 |Signature of Head of the department | |
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|12.1 |Remarks of chairman and principal | |
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|12.2 |Signature | |
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