ASSESSMENT OF ADVERSE DRUG REACTIONS OF SECOND

GENERATION ANTIPSYCHOTICS AMONG PSYCHIATRIC PATIENTS

ATTENDIN AT THE PSYCHIATRIC WARD BULE HORA UNIVERSITY
MEDICAL CENTER, SOUTH WEST ETHIOPIA

BY: ABDULWAHAB AMAN

A RESEARCH PAPER SUBMITTED TO BULE HORA

UNIVERSITY, INSTITUTE OF HEALTH SCIENCES, SCHOOL OF
PHARMACY, IN PARTIAL FULFILLMENT OF THE

1
 REQUIREMENT FOR BACHELOR DEGREE IN PHARMACY (B.
PHARM)

BULE HORA, ETHIOPIA

MAY,2023

BULE HORA UNIVERSITY

INSTITUTE OF HEALTH SCIENCE

SCHOOL OF PHARMACY

ASSESSMENT OF ADVERSE DRUG REACTIONS OF SECOND

GENERATION ANTIPSYCHOTICS AMONG PSYCHIATRIC PATIENTS
ATTENDING AT THE PSYCHIATRIC WARD OF BULE HORA
UNIVERSITY TEACHING HOSPITAL, SOUTHWEST ETHIOPIA.

BY
: ABDULWAHAB AMAN

ADVISOR: HARO .M (Bsc, MPh.)

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 MAY, 2023

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ACKNOWLEDGMENT
I would like to express my sincere and deepest gratitude to my advisor Mr Haro M. for his
valuable and constructive suggestions during the planning and development of this research
paper. His willingness to give his time so generously has been very much appreciated. I would
like to express my very great appreciation to my friends and classmates who has provided me
their personal computer to perform this research.

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TABLE OF CONTENTS

Contents
ACKNOWLEDGMENT....................................................................................................................................i
TABLE OF CONTENTS...................................................................................................................................ii
List of Tables...............................................................................................................................................iv
List of Figures...............................................................................................................................................v
ABBREVIATIONS and ACRONYMS...............................................................................................................vi
ABSTRACT..................................................................................................................................................vii
Objective:...........................................................................................................................................vii

Method and Materials.......................................................................................................................vii

Result.................................................................................................................................................vii

Conclusion and Recommendation.....................................................................................................viii

1. INTRODUCTION.......................................................................................................................................1
1.1. Background...................................................................................................................................1

1.2. Statement of the Problem............................................................................................................3

1.3. Significance of the study...............................................................................................................4

2. LITERATURE REVIEW................................................................................................................................5
2.1. ADVERSE DRUG REACTION OF SECOND GENERATION ANTIPSYCHOTICS.....................................5

3. Objectives................................................................................................................................................9
3.1. General objective..........................................................................................................................9

3.2. Specific objectives.........................................................................................................................9

4. METHODS AND MATERIALS...................................................................................................................10

4.1. Study area...................................................................................................................................10

4.2. Populations.................................................................................................................................10

4.2.1. Source Population............................................................................................................10

4.2.2. Study Population..............................................................................................................10

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 4.2.3. Inclusion and Exclusion Criteria......................................................................................10

4.3. Study Design and period.............................................................................................................11

4.4. Sample Size Determination.........................................................................................................11

4.5. Sampling technique....................................................................................................................12

4.6. Variables.....................................................................................................................................12

4.6.1. Independent variables:.....................................................................................................12

4.6.2. Dependent variables:........................................................................................................12

4.7. Data Collection method and Instruments...................................................................................12

4.7.1. Data collection Instruments..............................................................................................12

4.7.2. Data collection method....................................................................................................13

4.8. Data quality Control....................................................................................................................13

4.9. Data analysis and interpretation.................................................................................................13

4.10. Ethical Consideration................................................................................................................13

4.11. Operational Definition..............................................................................................................14

5. RESULTS.................................................................................................................................................15
5.1. Sociodemographic characteristics..............................................................................................15

5.2. Common adverse drug reactions................................................................................................19

5.3 Measure taken to manage ADR...................................................................................................20

6. DISCUSSION...........................................................................................................................................21
7. Limitations of the study.........................................................................................................................22
8. CONCLUSION AND RECOMMENDATION................................................................................................23
8.1 Conclusion...................................................................................................................................23

8.2 Recommendation........................................................................................................................23

9.REFERENCE.............................................................................................................................................24

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List of Tables
Table 1: Socio demographic, patients medical conditions and number of medication used …...17.

Table 2: Medication prescribed and number of ADR……………………………………………18

Table 3: Common ADR with offending drugs…………………………………………………..19

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List of Figures
Figure 1: Socio demographic, ethnic groups patients registered at BHU TH psychiatry Clinic
from April 2023 to May 2023………………………………………………………………15
Figure 2: Socio demographic, study patients religious distribution of psychotic patient registered
at BHU TH psychiatry Clinic from April 2023 to May 2023……………………………16
Figure 3: Measurement taken to manage adverse effect of second generation antipsychotics of
psychotic patient registered in psychiatry Clinic …………………....17

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ABBREVIATIONS and ACRONYMS
AAA- Atypical Antipsychotic Agent

AAP- Atypical Anti Psychotics

ADR- Adverse Drug Reaction

CNS -Central Nervous System

CSA -Central Statistics of Ethiopia

DM- Diabetes Mellitus

ECG -Electro Cardio Graph

EEG -Electroencephalography

EPS -Extrapyramidal Symptoms

FGA - First Generation Antipsychotics

BHU TH- Bule hora University teaching hospital

MDD- Major Depressive Disorder

NMS- Neuroleptic Malignant Syndrome

OPD -Out Patient Department

OR - Odds Ratio

SGA-Second generation antipsychotics

WHO-World health organization

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ABSTRACT
Introduction: An antipsychotic drug is a tranquilizing psychiatric medication primarily used for
the treatment of psychosis, schizophrenia, bipolar disorder, delusions, paranoid disorder, mental
retardation, depression etc. These drugs also used in the management of non-psychotic disorders.
The second generation drugs are also known as atypical antipsychotics. These drugs are superior
to conventional antipsychotics as they significantly reduce both positive and negative symptoms
of schizophrenia and have lower risk of extra pyramidal symptoms (EPS). However, these drugs
have separate set of adverse drug reactions (ADRs). Second-generation antipsychotics (SGAs)
are replacing traditional antipsychotics as first line therapy for the treatment of schizophrenia.

Objective: To assess the adverse drug reactions of second generation antipsychotics among
psychiatric patients attending at the psychiatric ward of BHU teaching Hospital, southwest
Ethiopia.

Method and Materials: A retrospective cross sectional study was conducted using patient chart
in psychiatry clinic of the hospital, who has admitted in the last one year.The data was compiled
and analyzed manually.

Result: A total of 186 patient information card was reviewed out of which 106(57%) male and
80(43%) female. Regarding to the type of psychotic disorder, schizophrenia 78(41.93%), bipolar
affective disorder 48(25.83%), depression 46(24.73%), and other psychotic disorder 14(7.52%)
have been determined. The most frequently prescribed atypical antipsychotic was risperidone
(140) which is followed by clozapine (26) and olanzapine (20).A total of 70 ADR were identified
from 56 patient card with the majority of ADR with risperidone 51 (72.86%).The most frequent
(common) ADR was appetite disturbance 20(28.57%), weight gain 10(14.28%), dizziness
8(11.83%), insomnia 7(10%), extrapyramidal reaction 6(8.57%), and somnolence 6(8.57).

vii
Conclusion and Recommendation: Result of this study suggested that weight gain, appetite
disturbance, dizziness, EPR and insomnia are the major reported ADRs and resperidone is the
leading cause of most ADRs. The ADR of second generation antipsychotics should properly
documented and there should be proper treatment and also alternative drug should be available at
BHU TH psychiatry Clinic.

Key words: Adverse effect, Antipsychotics, Risperidone

viii
1. INTRODUCTION

1.1. Background

Psychosis is a medical term used to describe hearing or seeing things, or holding unusual beliefs
that other people do not share (1). Psychotic disorders are a diverse group of illnesses that have
their origins in abnormal brain function and are characterized by fundamental distortions of
thinking, perception and emotional response. These disorders include, among others,
schizophrenia, schizoaffective disorder, bipolar disorder and delusional disorder (2).
Schizophrenia is the most common and classic psychotic disorder. It is a group of disorders
characterized by psychotic symptoms that significantly impair functioning and that involve
disturbances in feeling, thinking and behavior. It affects 1‐2% of the population. The incidence
of schizophrenia has been reported to range from 0.03% -0.12%. World - wide 2 million new
cases appear each year (3).

Psychotic features occur in ~18.5% of patients who are diagnosed with MDD (Manic Depressive
Disorder) (4). Bipolar I disorder, manic or mixed with psychotic features estimated to occur in
~25% of Bipolar I patients (5). The percentage of people who suffer from any psychotic
symptom at any one time (prevalence) varies greatly from country to country, from as little as
0.66% in Vietnam to 45.84% in Nepal. Men are thought to develop psychotic disorders more
often and at younger ages than women. There are genetic, biological, environmental, and
psychological risk factors for developing a psychotic disorder (6). Depression is the 5th leading
illness among women and the 7th among men in developing countries (7).

The lifetime prevalence of all psychotic disorders was 3.06%, 0.87% for schizophrenia, 0.32%
for schizoaffective disorder, 0.07% for schizophrenia form disorder, 0.18% for delusional
disorder, 0.24% for bipolar I disorder, 0.35% for major depressive disorder with psychotic
features, 0.42% for substance-induced psychotic disorders, and 0.21% for psychotic disorders
due to a general medical condition (3,5).Most effective treatments for psychotic disorders are
comprehensive, involving appropriate medications, mental-health education, and psychotherapy
for the sufferer of psychosis(6)

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Antipsychotic medications are the cornerstone in the management of psychosis. They have been
available since the mid-1950s. The first antipsychotic was discovered by accident and then used
for schizophrenia. This was chlorpromazine (Thorazine), which was soon followed by
medications such as haloperidol (Haldol), fluphenazine (Prolixin), thiothixene (Navane),
trifluoperazine (Stelazine), perphenazine (Trilafon), and thioridazine (Mellaril). These
medications have become known as "neuroleptics". Since 1989, a new class of antipsychotics
(atypical antipsychotics agent) has been used. Clozapine (Clozaril), the first of the new class, is the
only agent that has been shown to be effective in situations where other antipsychotics have failed. Its use
is not associated with extrapyramidal side effects, but it does produce other side effects, including a
possible decrease in the number of white blood cells. Other atypical antipsychotics include risperidone
(Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify),
paliperidone (Invega), asenapine (Saphris), iloperidone (Fanapt), and lurasidone (Latuda)(6).

The AAAs (Atypical Antipsychotic Agents) is associated with several significant risks and the
rates and severity of particular side effects differ among the AAAs. These side effects can occur
with treatment initiation but some may also develop after sustained use. When evaluating side
effects, a clinician should consider not only the objective severity of the side effects, but also the
subjective distress in the individual patient, as both these factors are important contributors to
non-compliance and treatment failure. When choosing an AAA for a patient, it is essential to
evaluate the potential benefit to the patient in light of the associated risk of the use of the
medication. (8).
In Ethiopia at Butajira the 5-year follow-up result indicates 30% of patients lived in psychotic
episode which was higher than the five-year outcome reported for developed centers from high
income countries in the WHO. Lifetime prevalence of mood disorders is found to be 1.6% in
Addis Ababa and 6.2 % in Butajira (10).

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1.2. Statement of the Problem

The newer second-generation antipsychotics, especially clozapine and olanzapine, generally tend
to cause more problems relating to metabolic syndrome, such as obesity and type 2 diabetes
mellitus (11)

All atypical drugs, with the exception of ziprasidone, have been associated with weight
increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and
quetiapine (12). Seizures are most common with low-potency FGAs and clozapine, especially at
higher dosages (12, 13).

The study shows Weight gain, dizziness, sleep disturbance and appetite disturbance accounted
for nearly 78% of the patients with SGAs. With risperidone (at 4-6 mg/day) and olanzepine (at
10-15 mg/day), gastrointestinal and sleep disturbance were observed in the initial (within 7 days
to 2-3 months after treatment) course of treatment, while EPS, fatigue, seizure, increased
frequency of micturition and dizziness were observed after long-term (3-9 months) use (14).

One of the most challenging aspects of using second generation antipsychotics is monitoring,
preventing, and treating metabolic adverse effects (15). The reduced propensity of the second
generation antipsychotics to cause neurological adverse effects such as extrapyramidal symptoms
and tardive dyskinesia has been established. However, these agents have a different adverse
effect profile that may carry as much “baggage” as the older agents. Adverse effects such as
weight gain, hyperglycemia, hyper- or dyslipidemia, and hyperprolactinemia are all fairly
common occurrences with these agents. Other serious adverse effects, including neuroleptic
malignant syndrome (NMS) or pulmonary embolism, may also occur (16).

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1.3. Significance of the study

The reduced propensity of the second generation antipsychotics to cause neurological adverse
effects such as extrapyramidal symptoms and tardive dyskinesia has been established. However,
the SGAs are associated with elevated risks of dyslipidemia, significant weight gain, metabolic
syndrome, and diabetes mellitus (14). The present study adds to the existing information on the
prevalence of adverse effects of atypical antipsychotic drugs on psychotic patients on follow up
at JUMC psychiatric clinic. This study will also describes the average weight gain and changes
in other metabolic parameters seen with second generation antipsychotics to aid clinicians in
determining the most appropriate medication for their patient.
This study will show us some of the unique side effects profiles of second-generation
antipsychotics on psychotic patients registered at BHU TH ward, which will be vital information
for clinicians making treatment decisions for this population.

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2. LITERATURE REVIEW

2.1. ADVERSE DRUG REACTION OF SECOND GENERATION ANTIPSYCHOTICS

Significant weight gain may occur with the use of the AAAs. This weight gain appears to be
largest with clozapine and olanzapine, although clinically significant weight gain occurs during
treatment with risperidone and quetiapine. Based on primary data from adults, aripiprazole and
ziprasidone appear to have the lowest propensity for weight gain (16,17).

Studies evaluating the impact of AAAs on triglycerides and cholesterol have noted an
association between alterations in triglyceride levels with weight gain. All AAAs have a black-
box warning regarding the possibility of developing diabetes mellitus during pharmacotherapy
with these agents. Case reports of diabetes in youths being treated with a variety of the AAAs
exist (18). The prevalence of type-2 DM in people taking AAAs is more than twice higher than
in the general population (19). Additionally, there is evidence to suggest that the risk of diabetes
may be weight independent and differs between the AAAs (20).

The impact of the AAAs on the cardiovascular (CV) system has been of increasing interest. CV
changes that have been observed in youths treated with the AAAs include prolongation of the
QTc interval, orthostatic hypotension, tachycardia, and pericarditis. There are limited short-term
data, and even less long-term data concerning the clinical relevance of these changes (21).
Prolongation of the QTc interval of the electrocardiogram (ECG) may be associated with the
development of torsade de pointes, a ventricular arrhythmia that can cause syncope and may
progress to ventricular fibrillation and sudden death (22). The study shows there were no
different effects of olanzapine, risperidone, quetiapine and ziprasidone on QTc interval (23).

5
Antipsychotic-induced sexual dysfunction is related to the effects of the drugs on alpha-1 and
alpha-2 adrenergic, H1 histamine and dopaminergic receptors, in particular to the blockade of D2
receptors in pituitary lactotroph cells, which leads to an excess of prolactin secretion (24, 25).

Some AAP (e.g., risperidone and olanzapine) have a dose response relationship for extra
pyramidal side effects, while with others (e.g., clozapine, quetiapine) this relationship is not
apparent. On the basis of available data, tardive dyskinesia appears to occur significantly less
frequently with clozapine, risperidone, olanzapine and quetiapine than with typical
antipsychotics (26).Electroencephalogram (EEG) abnormalities have been reported with the use
of AAAs. While the greatest risk for seizures associated with the AAAs appears to be with
clozapine (27).

A long-term observational study was carried out for 5 months in the outpatient department
(OPD) of the psychiatry Calcutta medical college, indicates that, a total of 100 patients were
investigated for clinical study, of whom 91 (91.00%) were suspected to suffer from ADR. Of
these 91 patients, 53 (58.24%) were males and 36 (39.56%) were females and 2(2.20%) were
children. It was seen that a total of 91 patients were treated mostly with four different SGAs such
as clozapine, olanzapine, quetiapine, and risperidone. Among 91 patients in total 171 adverse
event were noted. Most common ADRs were weight gain 47(51.64%), sedation 11(12.08%),
insomnia 09(9.89%), G.I upset 08(8.79%), aggressive behavior 06(6.59%), dry mouth
05(5.49%), alopecia05(5.49%), anxiety 04(4.39%), sexual dysfunction 04(4.39%), fatigue
04(4.39%), dizziness 04(4.39%), tremor 03(3.29%), asthenia 03(3.29%), anorexia 03(3.29%),
cough 03(3.29%), headache 03(3.29%), concentration difficulty 02(2.19%), itching 02(2.19%),
nervousness02(2.19%). The spectrum of suspected ADRs as noted among 91 patients is
presented (27).

Another longitudinal prospective observational study of ADRs of atypical antipsychotic drugs

was carried out in the Psychiatry Department of P.D.U. Medical College, Rajkot. Totally 93
ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93) were seen with
risperidone and olanzapine, as they were the commonly prescribed drugs. Weight gain, dizziness,
sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With

6
risperidone (at 4-6 mg/day) and olanzapine (at 10-15 mg/day), gastrointestinal and sleep
disturbance were observed in the initial (within 7 days to 2-3 months after treatment) course of
treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were
observed after long-term (3-9 months) use. Weight gain olanzapine as well as risperidone, which
accounted for 15.53% of total ADRs. Incidence of insomnia was 9.60% and that of somnolence
was 8.60% in this study. Somnolence was more frequent in patients with olanzapine than with
risperidone. Anticholinergic side effects like dizziness, constipation, palpitation and hyper
salivation (paradoxical response with clozapine) accounted for 15.03% of the total ADRs.
Incidence of these side effects was least with risperidone (3 in 38 cases), more with olanzapine
(8 in 34 cases), while it was maximum with clozapine (4 in 6 cases). Clozapine and olanzapine
show higher affinity for the muscarinic receptors (28).

According to the study conducted at Australia in 2010 on people living with psychotic disorders,
most participant (91.6%) reported they were taking prescribed medication for their mental health
problem. Three quarters (74.0%) were taking atypical antipsychotics, with 16.4% taking
clozapine, which is prescribed most commonly in cases of schizophrenia that do not respond to
other antipsychotic medications. Just 15.2% were taking first generation, typical antipsychotics.
The three quarters of participants (77.4%) complained of medication side effects. Three-fifths
(61.0%) suffered impairment in their daily life as a result of these medication side effects and for
29.9% the impact of these impairments was moderate or severe. The side effects most frequently
reported were drowsiness or sleepiness during the day (44.7%), mouth drier or more watery than
usual (39.5%), weight increase (37.5%), inner restlessness (25.8%), trembling or shaking of
limbs (23.9%) and inability to relax (20.8%). Just over one third (37.5%) reported gaining weight
as a medication side effect (28).

Another prospective interventional study was conducted in mental health department of a tertiary
care hospital in South India over a period of 2 years (March 2012-February 2014). Of the 950
patients reviewed, 517 (54.42%) patients (220 outpatients and 297 inpatients) received at least
one antipsychotic medication. A total of 289 ADRs were identified from 217 patients with an
overall incidence rate of 41.97%. Average number of ADR per patient in this study was 1.6. The
median age of patients with and without ADRs was 34.5 years (range: 13-90 years). Females
were slightly more in ADR group (57.21% vs. 42. 25%). Number of medications prescribed was

7
same in both groups (average: 4.6; range: 1-13). Of the 298 suspected ADRs identified, nine
ADRs could not be evaluated due to the non-availability of the data. Of the 289 ADRs, 66.43%
(n = 192) were detected by intensive monitoring, while 33.56% (n = 97) were spontaneously
reported (29).

According to this study sixty seven different kinds of ADRs were observed in the study patients.
Central nervous system (CNS) and peripheral nervous system (n = 59) was the most commonly
affected system organ class. Weight gain (n = 30) was the most commonly observed ADR
followed by extrapyramidal side-effects (EPS) (n = 20) and menstrual irregularity (n = 18).
Metabolic disturbances, especially weight gain, were commonly associated with the use of
olanzapine. There were no fatal adverse events; however, one instance of bradycardia and
electrocardiogram (ECG) changes was reported with quetiapine, necessitating intensive care.
Olanzapine was most commonly implicated in reported ADRs (n = 92) followed by risperidone
(n = 59). Of the 289 ADRs, 80% required interventions, including drug dose reduction (n = 43)
and/or specific (n = 27), or symptomatic (n = 43) treatment (29).

In Ethiopia, mental illness is the leading non-communicable disorder in terms of burden.

Remarkably, in rural setting of the country, mental illness comprised 11% of the total burden of
disease; schizophrenia (0.5%), depression (5%), and bipolar disorder (5%) included in the top ten
most burdensome mental conditions.

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3. Objectives

3.1. General objective

To assess the adverse drug reactions of second generation antipsychotics among psychiatric
patients attending at psychiatric ward of Bule Hora University teaching Hospital, southwest
Ethiopia.

3.2. Specific objectives

To identify the most common ADR of second generation antipsychotic drugs in JUMC,
psychiatry clinic.

To determine the magnitude and pattern of adverse effect of second generation antipsychotics.

9
To identify measure taken to manage ADR of second generation antipsychotics.

4. METHODS AND MATERIALS

4.1. Study area

The study was conducted at psychiatric ward of Bule Hora University teaching Hospital(BHU
TH). It is one of the teaching hospital found in southwest of Ethiopia in Bule Hora town which is
467 Km from capital city, Addis Ababa.

4.2. Populations

4.2.1. Source Population

The source populations was information cards of all patients visiting Bule hora University
teaching Hospital(BHU TH) and who were diagnosed to have psychotic disorder from May 2022
to May 2023.

4.2.2. Study Population

All psychotic disorder patients who attended psychiatric ward of BHU TH who fulfill inclusion
criteria and visit the clinic during conducting the study was studied.

4.2.3. Inclusion and Exclusion Criteria

Inclusion criteria

All patient cards with at least one atypical antipsychotic drug were included in the study.

Exclusion criteria

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All Psychotic patients cards with no antipsychotic medication.

All cards of pregnant Psychotic patients.

All cards of psychotic patients who are prescribed other medicine in addition to second
generation antipsychotic drugs.

4.3. Study Design and period

A retrospective chart review of ADR of second generation antipsychotic drugs were carried out
at psychiatry ward of BHU TH from August 10 to 15, 2023 GC.

4.4. Sample Size Determination

The sample size for the study was determined by using the single population proportion formula:

n = z2pq
d2

Where: z= the standard normal value at confidence interval of 95%= 1.96

p=Prevalence estimated at 50%, q=1-p

d= Margin of sampling error tolerated

n= Minimum sample size required

Therefore, the sample size is:

ni=(1.96)2(0.5)(0.5) =384

(0.05)2

Since the total number of psychotic patient is less than 10,000 we can use the following
correctional formula.

Nf = ni×N /ni+N = 384 x 362/384+362 =186

Where ni = initial sample size which was 384.

N=sample population we take.

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Nf=exact sample size

4.5. Sampling technique

The study was conducted using a systematic random sampling, one patient information card
selected randomly and then gone through by every 1 interval.

4.6. Variables

4.6.1. Independent variables:

Age

Gender

Religions

Dose of anti-psychotics

4.6.2. Dependent variables:

Number and type of adverse effects

4.7. Data Collection method and Instruments

4.7.1. Data collection Instruments

Pen white gown

Pencil Paper

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4.7.2. Data collection method

Drugs received and ADRs experienced by the patients have been collected by reviewing patient
information card through questioner.

4.8. Data quality Control

To maintain quality of data, data collection tool were prepared for this specific study and pre-test
for its completeness of variables on patients in BHU TH psychiatric ward.

4.9. Data analysis and interpretation

All the data collected were analyzed manually and presented in the form of frequency table, graphs &
charts. The participants were categorized into ADR and non-ADR groups.

4.10. Ethical Consideration

Ethical approval to conduct this study were asked from ethical review board of College of Health
Sciences, Bulge Hora University. Permission to conduct the study was secured from the medical
director of Bule hora University teaching Hospital. The confidentiality of the information will
kept and no disclosure of the patients name.

13
4.11. Operational Definition

Adverse drug reaction: A response to a drug which is noxious and unintended and which
occurs at doses normally used in man for the prophylaxis, diagnosis or for modification of
physiological function (30).

Bipolar disorder: A brain disorder that causes unusual shifts in mood, energy, activity levels,
and the ability to carry out day-to-day tasks (11).

Extra pyramidal symptoms: Physical symptoms, including tremor, slurred speech, akathesia,
dystonia, anxiety, distress, paranoia, and bradyphrenia, that are primarily associated with
improper dosing of or unusual reactions to neuroleptic (antipsychotic) medications (31).

Paradoxical effect: An effect of medical treatment, usually a drug, opposite to the effect which would
normally be expected (23).

Psychosis: Psychosis is a serious mental disorder characterized by thinking and emotions that are so
impaired, that they indicate that the person experiencing them has lost contact with reality (1).

14
5. RESULTS

5.1. Sociodemographic characteristics

A total of 186 psychiatry ward patients card information which fulfill inclusion and exclusion
criteria were reviewed. Most patients were Oromo and Gedeo ethnic groups which is
141(75.80%) and 22(11.83%) respectively (fig.1).

22(11.83%) 29(4.32%)

15(8%)
key oromo
amhara
gurage
others

141(75.8%)

Fig.1: Socio demographic, ethnic groups of patients registered at BHU TH psychiatry ward from
September 2022to August 2023

15
Most of the patient under this study were muslims and orthodox which is 138 (74.20%) and
33(17.74%) respectively (fig.2).

4(2.15%)
others

11(5.91%)
protestant

33(17.74%)
orthodox

138(74.20%)
muslims

0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00%

Fig 2.Sociodemographic, study patients religious distribution of psychotic patient registered at

BHUTH psychiatry ward from 2020 to 2021.

Of 186 patients 106(57%) were males and 80(43%) were females. Most of the study patient age
were (19-29) and (30-39) which is 58(31.18%) and 51(27.42%) respectively. The number of
medication mostly prescribed were less than or equal to two (≤2). The most common patient
diagnosis were schizophrenia and bipolar disorder which was 78(41.94%) and 48(25.80%)
respectively (table 1). A total of 70 different ADR were identified on 56 patient cards with
prevalence of 30.02%. Average number of ADR per patient in this study was 1.3.

16
Table 1: Socio demographic details, patients’ medical conditions and number of medication
used by psychotic patients registered at BHU TH psychiatry ward from 2022to 2023.

Socio demographic details of the study patients

Variables Number (percentage) of patients

With ADR Without ADR Total

Gender Male 24 82 106

Female 32 48 80

Total 56 130 186

Age 0-18 2 8 10

19-29 18 40 58

30-39 19 33 52

40-49 10 26 36

50-59 2 10 12

60 and above 5 3 8

Total 56 130 186

Medication used

Number 2or less 52 128 180

3-4 4 2 6

5or more 0 0 0

17
 Patient diagnosis

Bipolar 14 34 48
affective
disorder

Depression 13 33 46

Schizophrenia 24 54 78

Others 5 9 14

A total of 186 patient card was reviewed those prescribed with three different SGA such as
risperidone, clozapine and olanzapine. The most frequently prescribed atypical antipsychotic was
risperidone (140) which is followed with clozapine (26) and olanzapine (20).The majority of
ADR were seen with resperidone 51 (72.86%).

Table 2: Medication prescribed and number of ADR of psychotic patients registered at BHU TH
psychiatry ward from 2022to 2023.

Medication No. of items the drugs have No. of adverse Percentage

prescribed been prescribed (n=186) events (n=70)

Risperidone 140 51 72.86

Clozapine 26 11 15.71

Olanzapine 20 8 11.43

18
5.2. Common adverse drug reactions

Among 56 patient cards 70 ADR were identified. The most frequent (common) ADR was loss
appetite 11(15.71%), weight gain 10(14.28%), increased appetite 9(12.86%), dizziness
8(11.83%), insomnia 7(10%), extrapyramidal reaction (8.57%), and somnolence 6(8.57%).
And less common ADRs were fatigue, headache, increased frequency of micturition, hyper
salivation, vomiting and diarrhea, constipation and seizure were identified. Of this ADR loss of
appetite (n=10), weight gain (n=8), increased appetite (n=7), extrapyramidal reaction (n=6) and
dizziness (n=6) were most frequently on patients with respiredone (8mg and 10mg daily). On
patients with clozapine (200mg-600mg daily) most frequently identified ADR were headache,
dizziness, insomnia, and constipation. And common ADR with olanzapine (10mg) were fatigue,
somnolence, weight gain, seizure, vomiting and diarrhea (table 3).

Table 3: Common ADR with offending drugs of psychotic patients registered at BHU TH psychiatry
ward from 2022to 2023.

Common ADR No. of events Percentage Offending

offending drugs
Loss of appetite 11 15.71 R(10),C(1)
Weight gain 10 14.28 R(8),O(2)
Increased appetite 9 12.86 R(7),C(2)
Dizziness 8 11.43 R (5),C(3)
Insomnia 7 10.00 R(5),C(2)
Somnolence 6 8.57 R(4),O(2)
Extrapyramidal reaction 6 8.57 R (6)
Fatigue 4 5.71 R (2),O(2)
Hyper salivation 2 2.86 Resperidone(2
)
Headache 2 2.86 Clozapine(2)
Increased frequency of 2 2.86 Resperidone(2
micturition )
Seizure 1 1.43 Olanzapine
Vomiting and diarrhea 1 1.43 Olanzapine
Constipation 1 1.43 Clozapine
Total ADR 70 100

19
5.3 Measure taken to manage ADR

Of the total 56 patient case with adverse events, for most ADRs (44.6%) of them no
measurement has been taken and dosage and regimen change (37.5%), treatment of ADR
without change in medication (14.28%) and discontinuation of drug (3.57%) (fig.3).

8(14.28
%)

2(3.57%)
key
no management
regimen change
25(44.60
%) treatment of ADR
Discontinuetion of drug

21(37.50
%)

Fig 3: Measurement taken to manage adverse effect of second generation antipsychotics of

psychotic patient registered at BHU TH psychiatry ward from 2022 to 2023.

20
6. DISCUSSION
Several studies are published on ADRs of antipsychotics, but less on atypical antipsychotics
(2,8,28,29). Compared with this studies evaluated ADR in either in patient or outpatient setting
or to both first and second generation antipsychotics. In this study, the prevalence of ADRs to
atypical antipsychotics was (30.11%). This was much higher compared to the previous study
done in America on atypical antipyschotics (8,) and very less when compared to India (29). This
might be due to life style of patients, inappropriate diagnosis and nonadherence to medication.

In the present study we found out that risperidone was the major cause of reported ADRs such as
weight gain and appetite disturbances followed by clozapine. This is in accordance with the
study conducted by lucca et al.2014 (5). The findings of the current study showed that, weight
gain, appetite disturbances and insomnia were the major ADRs due to atypical
antipsychotics.This was in agreement to the findings conducted by lucca et al.2014 (5).
On the present study there is loss of appetite with risperidone and clozapine which is accounted
for 15.71% of total ADRs which is different from previous study respiredone and quetiapine on
other study (28). There is age variation observed in reported loss of appetite in present study.

Weight gain is clinically significant if it exceeds 7% of the initial weight after 10 weeks. (2). It is
the most common metabolic adverse effects observed in present study as mentioned in (table).
On the present study there is recorded weight gain with risperidone and olanzapine, which is
accounted for 14.28% of total ADRs. This finding is immensely correlated with previous
published studies in which it is common with olanzapine (29) and quetiapine (2).
Magnitude of weight gain and its time course varies among atypical antipsychotics. Four out of
eight of events of weight gain with risperidone were documented after long-term (≥6 months)
use, while in four cases it occurred on short-term use. These findings are similar to previous
study where similarly olanzapine and risperidone are reported to be associated with the weight
gain at short as well as long-term use (28). In this study, measures taken to manage ADR include
dosage and regimen change 21(37.50), treatment of ADR 8(14.28) and discontinuation of drug
2(3.57) and others no measurement was taken.

21
7. Limitations of the study
The main challenge was that the ADRs of most psychotic patients who were receiving
antipsychotic drugs is not properly documented. So this limitation halts the study from assessing
ADR among all source population. However irrespective of the described limitations, this study
provides helpful information in the limited data situation of Ethiopia. In addition the time given
to perform this study were short and in the middle of many educational schedules.

8. CONCLUSION AND RECOMMENDATION

8.1 Conclusion

Result of this study suggested that weight gain, appetite disturbance, dizziness, EPR and
insomnia are the major reported ADRs and risperidone is the leading cause of most ADRs.

Dosage and regimen change, treatment of ADRs and discontinuation of the drug were the
measurements taken to manage the ADRs.

8.2 Recommendation

 Depending on the study results, the following recommendation has been taken.
 Most frequently prescribed drug was risperidone and most of adverse events were with
risperidone there should be alternative drug.
 The side effect of each atypical antipsychotic drug should be documented properly from
the patients.

22
  There should be study shows the factors that exacerbate the adverse effect of atypical
antipsychotics.
 Appropriate treatment for severe adverse effect of second generation antipsychotic should
be availed.
 Alternative medication to second generation antipsychotic drugs should be available to
the psychiatry ward.
 Second generation antipsychotic should be used at low dose or in combination with other
second generation or first generation antipsychotics.

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from olanzapine treatment in adolescents. J Child AdolescPsychopharmacol.
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ANNEXES

Annex –I: Data Collection Format

25
Questionnaire for assessment of adverse effect of second generation antipsychotic drugs at
BHU TH, psychiatry ward, from May 10 to 15, 2023

A/Socio demographic characteristic of the study participants.

Age A.≤18 B.19-29 C.30-49 D.50-59 E.≥60

Sex A. Male B. Female

Ethnicity A. Oromo B. Amhara

C. Harari D. Gurage E. Somali F. Tigre G. Others specify------------

Religion A. Muslim B. Orthodox

C. Protestant D. Others

B/Patient condition

5. Type of psychotic disorder of patients

A. psychosis B. bipolar affective disorder C. depression D. schizophrenia

E. others specify

C/Medication information

7. What medication is prescribed for the patients? It can be more than one.

A. Risperidone dose & duration --------------

B. olanzapine dose and duration -------------

C. clozapine dose duration --------------------- -

26
8. How many atypical antipsychotic medications have been given?

A . ≤2 B. 3-4 C. ≥5
9. Does there any adverse effect due to medication?

A. Yes B. No

27
10. If yes for Q. No 9 list of adverse effect recorded and related drugs to cause ADR.

S.No Adverse Drug that cause ADR

effects
clozapine Risperidone olanzapine

28
11. What was done in response to development of ADR?

A. discontinuation of drug

B. dosage and regimen change.

C. treatment of ADR without change in medication

D. continued with same therapy

29
30