RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the candidate and Address (in block letters) / Dr. SWETHA MUNOLI
P.G IN PHARMACOLOGY ,
DEPARTMENT OF PHARMACOLOGY
RAICHUR INSTITUTE OF MEDICAL SCIENCES, HYDERABAD ROAD,
RAICHUR. 584102.
2. / Name of the Institution / RAICHUR INSTITUTE OF MEDICAL
SCIENCES, RAICHUR.
3. / Course of study and subject / M.D. (PHARMACOLOGY)
4. / Date of admission to the course / 23rd JUNE 2011
5. / Title of the topic
“ADVERSE DRUG REACTION MONITORING IN PSYCHIATRY
OUT PATIENT DEPARTMENT OF RIMS HOSPITAL”.
6. / BRIEF RESUME OF INTENDED WORK.
6.1 / Introduction and Need for the Study:
A medicine should always be presumed to be hurtful1. It is universally accepted that “No drug is absolutely free from side effects”. For example, even the so called safe drug paracetamol is associated with significant number of Adverse Drug Reactions (ADRs)2.
Though many drugs are precisely targeted to the causes and mechanisms of diseases, and are brilliantly effective in treating them, they may also have some minor or major negative effects on other parts of the body, or may interact negatively with the systems of the particular individual or with other drugs or substances that are taken by the individual. Whenever a drug is administered a risk is undertaken which may be due to the properties of the drug, patient factors and of the environment3.
Psychotropic drugs are plentiful in number and their use is increasing day by day. These drugs are capable of causing a number of adverse drug reactions (ADRs)4, 5 some of which may be fatal6. ADRs associated with psychotropic drugs can lead to noncompliance, and at times discontinuation of therapy7. Pharmacovigilance in psychiatry units can play a vital role in detecting ADRs and alerting physician to possibility and circumstances of such events, thereby protecting the user population from avoidable harm8.
This prompted us to evaluate the ADR profile of psychotropic drugs used by ambulatory patients in a teaching hospital of Raichur Institute of Medical Sciences, Raichur.
6.2 / Review of Literature:
In India, Pharmacovigilance is still at its developing stage. The data available does not clearly show the actual scenario but definitely gives some idea about the prevailing rate of ADRs.
Jose J et al. (2006)9 showed that the overall incidence of ADR calculated from the patient population was 0.15%. At least one ADR was reported in 1.14% of the hospitalized patients and in 0.012% of the outpatients. No significant difference was seen in the overall incidence of ADRs observed in males and females. Incidence of ADRs among elderly adults and older adults (0.23%) were significantly higher than other age groups. Type A reactions (72.5%) accounted for majority of the reports and a greater share of the ADRs were described to be very common (43.4%) in the literature. Upon causality assessment, majority of the reports were rated as probable (53.7%) mild and moderate reactions accounted for 50.5% and 43.9% respectively.
Grohmann R et al. (1984)10 showed that Life- threatening events were observed in 1.2% of patients undergoing intensive drug monitoring (IDM) as well as 1.2% of those undergoing organized spontaneous reporting system (OSR) in psychiatric inpatients in Germany. The most frequently observed ADR by IDM were sedation, extrapyramidal signs (EPS), disturbance of the autonomic nervous system and increase in transaminases, and by OSR- Parkinsonism, akathisia, sedation, toxic delirium and increased transaminases. The relative frequency of Grade III ADR was similar for neuroleptics and antidepressants (5.4% and 5.3% in OSR), a very low relative frequency of ADR Grade III was found for tranquilizers and hypnotics (0.7% and 0.2%).
Carlini EA et al. (2003)11 showed among the medications, antidepressants ranked first with 122 ARPMs (Adverse Reaction to Psychotropic Medications) being notified, followed by neuroleptics (46 ARPMs) and antiepileptic medicaments (25 ARPMs). The three main organs and systems affected by the adverse reactions (ARs) were Central Nervous System with 102 ARs, skin and mucosa with 44 and gastrointestinal with 21 ARPMs.
Giovani M et al. (1999)12 observed that the overall prevalence of Extra Pyramidal Signs (EPS) was 29.4% (N=458). Among the EPS diagnosed patients, parkinsonism as assessed by the presence of core parkinsonian symptoms (rigidity, tremors, bradykinesia) was present in 65.9% of patients (N=302), akathisia in 31.8% (N=145), and acute dystonia in 2.1%(N=10). Old age and long term neuroleptic drug (NL) treatment were significantly associated with EPS in both the univariate and the multivariate analysis, whereas no relationship was observed with average NL daily doses and current NL treatment.EPS was diagnosed in 50.2% of 285 patients with persistent tardive dyskinesia (TD). Distribution of EPS in patients with TD showed that tremor and akathisia were more frequent in peripheral TD cases than in orofacial TD cases.
Smith GC et al. (2002)13 conducted prospective study of 1,551 patients prescribed antidepressants, out of which 64% were females. One hundred and fifty eight (10.2%) of those patients prescribed an antidepressants were noted to have an ADR. The prevalence of ADRs within drug groups were tricyclics 11.7% Mono Amine Oxidase Inhibitors (MAOIs) / Reversible Inhibitors of MAO-A (RIMAs) 9.4%, Selective Serotonin Reuptake Inhibitor (SSRIs)/Selective Serotonin- Norepinephrine Reuptake Inhibitors (SNRIs ) 7.3%. Tricyclics were significantly more likely to be associated with an ADR than the other groups.
6.3 / Objective of the Study
1.  To do surveillance and detect incidence of adverse drug reactions (ADRs) in outpatient department of Psychiatry.
2.  To access and analyze the ADRs according to their demographic distribution, reporting and presentations.
3.  To do causality analysis of ADRs.
4.  To classify ADRs.
5.  To understand pattern of ADRs in study population (data collected by investigator) when compared with western population (data available in literature).
7. / MATERIALS AND METHODS
7.1 / Study Design:
A longitudinal observational study will be conducted in out-patient department of psychiatry at Raichur Institute of Medical Sciences, Raichur.
7.2 / Source of Data:
Patients attending the outpatient department of psychiatry in Raichur Institute of Medical Sciences, Raichur.
7.3 / Study period:
December 2011 to November 2012.
7.4 / Sample size:
Patients satisfying inclusion criteria attending outpatient department of psychiatry at Raichur Institute of Medical Sciences during study period from December 2011 to November 2012.
7.5 / Method of collection of data:
The present study will be conducted for a period of one year from December 2011 to November 2012, in outpatient department of psychiatry at Raichur Institute of Medical Sciences, Raichur. During this period patients satisfying the inclusion criteria will be individually recognized and information about their details, adverse drug reaction, suspected drug and the concomitantly administered drugs will be recorded in the Central Drugs Standard Control Organization (CDSCO) Adverse Drug Reaction reporting form. The study will be based on intensive monitoring and spontaneous or voluntary reporting system, which is predominant method of National Pharmacovigilance Programme (NPVP).
7.6 / Inclusion criteria:
1.  Patient visiting the psychiatry OPD and receiving any psychopharmacological agents with a diagnosis of psychiatric illness as per ICD 10 criteria
2.  Diagnosed cases of epilepsy
3.  Patients above age of 12 years
7.7 / Exclusion criteria:
1.  Diagnosed cases of mental retardation and dementia.
2.  Patients on stimulant drugs.
7.8 / Statistical analysis:

1. ADR will be collected from Dec 2011- Nov 2012

2. Data will be entered in Microsoft excel sheet and analyzed

3. The following data will be analyzed

a.  ADR type b. Frequency of ADR

c. System ,Organ ,Class involved d. Causality assessment

e. Class of drugs

and will be presented as percentage (%)

4. Incidence rate of ADRs will be calculated by using the formula:

IR=Number of patients with ADRs/

Number of patients exposed to drugs.

5. Student t test will be applied for continuous data and chi square test
for categorical data as appropriate
7.9 / Does the study require any investigation or interventions to be conducted on
patients ?or other humans or animals?
Yes.
Weight, Blood pressure, Body mass index (BMI), Skin fold thickness, Waist to hip ratio (WHR), relevant blood investigations for patients with suspected ADRs.
8.0 / Has ethical clearance been obtained from your institution?
YES, Ethical clearance is obtained from Institutional Ethics Committee
YES, Ethical clearance is obtained from Institutional Ethics Committee.
8.1 / LIST OF REFERENCES
1.  Holmes OW: Currents and counter- currents in medical sciences, in Medical Essays (1843-1892). Boston, Houghton Mifflin; 1911; 173-208.
2.  Palaian S, Mishra P, Shankar PR, Dubey AK, Bista D, Almeida R. Safety monitoring of drugs- Where do we stand? Kathmandu Univ Med J 2006;4(13):119-127.
3.  View point-watching for safer medicines part 1.WHO Collaborating centre for International Drug Monitoring, the Uppsala Monitoring Centre; 2002.
4.  Aronson JK. Risk perception in drug therapy. Br J Clin Pharmacol.2006;62:135-137.
5.  Rani FA, Byrne PJ, Murray ML, Carter P, Wong IC. Paediatric atypical antipsychotic monitoring safety (PAMS) study: Pilot study in children and adolescents in secondary and tertiary care settings. Drug saf. 2009;32:325-333.
6.  Glassman AH, Bigger JJ. Antipsychotic drugs, prolonged QTc interval, torsades de pointes and sudden death. Am J Psychiatry.2001;158:1774-1782.
7.  Cooper C, Bebbington P, King M, Brugha T, Meltzer H, Bhugra D, et al. Why people don’t take their psychotropic drug as prescribed: Result of 2000 National Psychiatry Morbidity survey. Acta Psychiatr Scand.2007; 116:47-53.
8.  Faich GA. US adverse drug reaction surveillance 1984-1994. Pharmacoepidemiol Drug saf.1996; 5:393-398.
9.  Jose J, Rao PM. Pattern of adverse drug reactions notified by spontaneous reporting in an Indian tertiary care teaching hospital. Pharmacol Res.2006;54:226-233
10. Grohmann R, Hippius H, Muller-Oerlinghausen B, Ruther E, Scherer J, Schmidt LG, et al. Eur j of Clin Pharmacol. 1984;26:727-734.
11. Carlini EA, Nappo SA. The Pharmacovigilance of Psychoactive medications in Brazil. Res Bras Psiquiatr. 2003;25(4):200-205
12. Giovanni M, Giuseppe B, Sandro P, Margherita C,Paola B. Extrapyramidal Syndromes in Neuroleptic- Treated Patients:Prevalence,Risk factors and Association with Tardive Dyskinesia. J Clin Psychopharmacol.1999; 19(3):203-208.
13. Smith GC, Clarke DM, Handrinos D, Tracer T. Adverse reactions to antidepressants in consultation-liaison psychiatry inpatients. Psychosomatics.2002; 43:228-233. Grohmann R, Hippius H, Muller-Oerlinghausen B, Ruther E, Scherer J, Schmidt LG, et al. Eur j of Clin Pharmacol. 1984;26:727-734.
9. /

Signature of candidate

10. / Remarks of the Guide / Psychopharmacology is an upcoming branch, many antipsychotic drugs are being prescribed for ailments on OPD basis but adverse drug reaction information of psychotropic drugs are lacking; hence this study is recommended and needs to be encouraged.
11. / Name and designation of
(in block letters)
11.1 Guide
11.2 Signature / DR. VASANT. R. CHAVAN M.D
ASSOCIATE PROFESSOR
DEPARTMENT OF PHARMACOLOGY
RAICHUR INSTITUTE OF MEDICAL SCIENCES, RAICHUR.
11.3 Co-guide
11.4 Signature / DR.B. RAMESH BABU M.D
ASSOCIATE PROFESSOR
DEPARTMENT OF PSYCHIATRY
RAICHUR INSTITUTE OF MEDICAL SCIENCES, RAICHUR.
11.5 Head of the Department
11.6 Signature / DR. VASANT.R.CHAVANM.D
ASSOCIATE PROFESSOR AND I/C HOD
DEPARTMENT OF PHARMACOLOGY
RAICHUR INSTITUTE OF MEDICAL SCIENCES, RAICHUR.
12. / 12.1 Remarks of the Dean/Director.
12.2 Name of the Dean cum Director
12.3 Signature / DR. THIPPERUDRAIAH .C
DEAN/DIRECTOR
RAICHUR INSTITUTE OF MEDICAL SCIENCES, RAICHUR.