Adverse Drug Reaction Monitoring of Antipsychotic Drugs and Mood Stabilizers in a Teaching Hospital

Background: Antipsychotics and mood stabilizers are associated with adverse effects which can affect the compliance and course of treatment in mental disorders. The present study was therefore undertaken to monitor the adverse drug reactions (ADRs) of the antipsychotics and mood stabilizers in the psychiatric outpatient unit of our hospital. Methods: Study was conducted from December 2011 to November 2012, the patients on antipsychotic drugs from psychiatry outpatient department (OPD) of Raichur Institute of Medical Sciences were considered for analysis. The patients were diagnosed by consultant psychiatrist. Data was collected in standard questionnaire format. All patients diagnosed with psychiatric disorder as per ICD 10 criteria and receiving treatment with antipsychotic or mood stabilizer were included. Assessment of causality and severity of recorded adverse events was done using WHO assessment scale and modified Siegel and Hartwig Scale respectively. Results: 45 ADRs were recorded among 778 patients. Extra pyramidal symptoms, anticholinergic side effects and Weight gain were the most common ADRs. Risperidone, chlorpromazine and olanzapine were the drugs causing maximum ADRs. Assessment of causality and severity of recorded adverse events showed possible to probable and mild to moderately severe respectively. Conclusion: Extrapyramidal symptoms were most common ADRs in our study followed by anticholinergic side effects. Risperidone was most commonly prescribed drug followed by chlorpromazine. Risperidone and chlorpromazine accounted for most of ADRs. Assessment of causality of recorded adverse events showed no certain cause and Assessment of severity of recorded adverse events showed no severe cases.


INTRODUCTION
According to WHO, adverse drug reaction is defined as "Any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function" [1] Adverse drug reactions (ADRs) are known to be the significant cause of morbidity and mortality both inpatients and outpatients settings. [2]The overall incidence of serious and fatal ADRs among hospitalized patients was found to be 6.7% and 0.32%, respectively. [3]While in outpatient settings, the incidence of ADRs ranges from 5% to 35%. [4]ADRs are recognized to be one the significant cause of hospital admissions and the incidence varied from 0.2% to 41.3%. [5]armacovigilance, the science and activities related to the detection, assessment, understanding and prevention of adverse effects or any drug related problem, is highly essential in India, where there is lack of adequate safety related data for drugs in general and psychotropic agents in particular.India seems to rate below 1% in ADR reporting, as against the world rate of 5%. [6]ychotropic 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 (ADR), [7,8] some of which may be fatal. [9]ADRs associated with psychotropic drugs can lead to noncompliance, and at times discontinuation of therapy. [10]Pharmacovigilance in psychiatry units can play a vital role in detecting ADRs and alerting physicians to the possibility and circumstances of such events, thereby protecting the user population from avoidable harm. [11]ence we conducted the study with the objectives to do surveillance and detect incidence of adverse drug reactions (ADRs) in outpatient department of Psychiatry, to access and analyze the ADRs according to their demographic distribution, reporting and presentations and to do causality and severity analysis of ADRs.

METHODS
A longitudinal observational study was conducted in patients attending outpatient department of psychiatry at Raichur Institute of Medical Sciences.The study was approved by institutional ethics committee.

Study period
December 2011 to November 2012.

Inclusion criteria
Patient visiting the psychiatry OPD and receiving antipsychotic drugs or mood stabilizers with a diagnosis of psychiatric illness as per ICD 10 criteria and patients above age of 12 years

Exclusion criteria
Diagnosed cases of mental retardation and dementia and patients on stimulant drugs.and severity was done using WHO assessment scale and modified Siegel and Hart wig Scale respectively.

RESULTS
Incidence of ADRs was 5.2%, 45 ADRs were recorded among 41 cases, 778 patients were screened, among 41 cases 23 were male and 18 were female.Extra pyramidal symptoms (15), anticholinergic side effects (10) and Weight gain (8) were the most common ADRs.Risperidone (22), chlorpromazine (9) and olanzapine (7) were the drugs causing maximum ADRs.Assessment of causality and severity of recorded adverse events showed possible to probable and mild to moderateseverity respectively (Table 1-7).

DISCUSSION
The overall incidence rate of ADRs in our study was found to be 5.2%.14][15][16][17][18][19] 32 out of these 41 patients belonged to 21-40 years age group.Previous studies have quoted mean age of patients with ADRs within the range observed in our study. [12,19]he most common antipsychotic drugs associated with ADR was risperidone followed by chlorpromazine and olanzapine.These drugs were most commonly prescribed in our psychiatry unit.A similar study done in IPGMER, Kolkata IN 2011 showed olanzapine as commonest drug causing ADR. [12]Among mood stabilizers lithium was more commonly prescribed unlike other study where valproate was more commonly prescribed drug. [21]Extrapyramidal Symptoms, anticholinergic side effects and weight gain were most common ADRs observed in our study in decreasing order of their occurrence.Extrapyramidal Symptoms was also seen with second generation antipsychotics in our study as they were prescribed more commonly in our psychiatry OPD.Sengupta et al had also found that neurological ADRs (tremors) were the most common ADRs followed by metabolic (weight gain) and gastrointestinal effects (constipation). [12]Causality assessment was done and no "certain" causes were seen since in cases where dechallenge was done, rechallenge was not attempted with the offending drug.This is in contrast to a brazilian study where 23 cases were found to be "definite" after rechallenge was attempted. [20]All ADRs reported were of mild to moderate severity.Study in India by Jose J et al [22] showed mild and moderate reactions accounted for 50.5% and 43.9% respectively.Grohmann R et al [23] conducted study in Germany in 2004 and showed that severe ADRs due to psychopharmacological agents occurred in 1.4% of exposed patients.The difference in the severity of ADRs might be due to difference in prescribing preferences at the different hospitals and there may be difference in the demographic characteristics of patients.

CONCLUSION
Extrapyramidal symptoms were most common ADRs in our study followed by anticholinergic side effects.Risperidone was most commonly prescribed drug followed by chlorpromazine.Risperidone and chlorpromazine accounted for most of ADRs.Assessment of causality of recorded adverse events showed no certain cause and Assessment of severity of recorded adverse events showed no severe cases.