RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES



| |

|RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES |

|BANGALORE, KARNATAKA |

| |

|ANNEXURE II |

| |

|PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION |

| | | |

|1 |Name of the candidate & address |Dr. DIVYASHREE. M |

| | |POST GRADUATE IN PHARMACOLOGY, |

| | |BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE-560002 |

| | | |

|2 |Name of the institution |BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE-560002 |

| | | |

|3 |Course of study and subject |M.D. PHARMACOLOGY |

| | | |

|4 |Date of admission to the course |21st MAY 2011 |

| | | |

|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” |

| | |

|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| |(SSRIs) have superseded the TCAs as the most widely prescribed antidepressants, owing to their superior tolerability, negligible |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. |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| |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. |

| | |

| |MATERIALS AND METHODS: |

| | |

| |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 |

| | |

| | |

| |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. |

| | |

| |E. Exclusion Criteria: |

| |Patients being treated with more than one antidepressant |

| | |

| |Patients with Psychotic depression, Bipolar disorder, Schizophrenia or Anxiety disorders |

| | |

| |3. Patients with current suicidal ideation |

| | |

| |4. Patients with serious decompensated medical conditions like Congestive cardiac failure, Renal failure, Hepatic failure. |

| | |

| |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. |

| | |

| |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. |

| | |

| |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) |

| | |

| |- 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) |

| | |

| |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) |

| | |

| |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. |

| | |

| |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. |

| | |

| |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 |

| | |

| |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. |

| | |

|9 |Signature of the candidate | |

| | | |

|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 | |

| | | |

|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 | |

| | | |

|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 | |

| | | |

|12.1 |Remarks of chairman and principal | |

| | | |

|12.2 |Signature | |

| | | |

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download