MY beautiful thesis presentation regarding the ongoing debate on safety and efficacy of two types of antipsychotics

1. COMPARISON OF SAFETY AND EFFECTIVENESS BETWEEN ATYPICAL AND
TYPICAL ANTIPSYCHOTICS IN SCHIZOPHRENIA
K. GOUTHAM
M. SWATHI
P. SRUJANI
Y. RADHIKA
Reg.No. 612171602008
Reg.No. 612171602013
Reg.No. 612171602017
Reg.No. 612171602023
UNDER THE SUPERVISION OF
BY
D. RAVI PRAKASH
PharmD
Assistant Professor

2. INTRODUCTION
Schizophrenia is a mental disorder characterized by abnormal social behaviour and failure to understand reality.
It is a severe, incapacitating psychiatric disorder that, in most cases, leads to progressive personal deterioration
in patients, as well as to a significant burden on family members and society in general
 About 0.3–0.7% of people are affected by schizophrenia during their lifetime. In 2013 there was estimated to
be 21 million cases globally (WHO).
 Positive Symptoms Delusions, Hallucinations, Disorganized thinking, and Psychomotor agitation
 Negative Symptoms Flattened affect, Poverty of speech, Avolition, Apathy, and Lack of Social drive. Two
negative symptoms that are particularly prominent in schizophrenia are diminished emotional expression and
avolition. Diminished emotional expression includes reduced emotions in the face, decreased eye contact,
intonation of speech, and a lack of movements of the hand that emotionally emphasize speech. Avolition is lack
of interest, a decrease in motivated self-initiated purposeful activities .
 Cognitive Symptoms Include decrements in declarative memory, working memory, language function, and
other executive functions as well as processing speed.

3. Treatment
• The treatment of schizophrenia changed drastically with the discovery of antipsychotics medications in
1950s, the release of clozapine in the US in 1989 and the subsequent development of atypical antipsychotics.
Approximately forty antipsychotic agents are available around the world, of which twenty are approved for
the use.
• In fact, these agents were identified as much by this EPS as by their efficacy in treating psychotic symptoms
and until recently, EPS were considered an unavoidable by-product of antipsychotic treatment.
• EPS can be categorized as acute (dystonia, akathisia, parkinsonism) and tardive (Tardive dyskinesia and
tardive dystonia) syndromes.
• Typical Antipsychotics (Dopaminergic)- Haloperidol, Chlorpromazine, Fluphenazine, Trifluoperazine
• Over the past decade, five atypical or newer generation antipsychotics (Clozapine, Olanzapine, Risperidone,
Quetiapine and Amisulpride) have been become available in India; these agents are principally distinguished
by their at-least equivalent antipsychotic efficacy to the older generation conventional antipsychotics with a
much lower propensity to cause EPS.

4. Safety and Effectiveness
• Safety has been defined as the therapeutic regimen that is causing less side effects in patients.
(Or)
It is a reasonable assurance that a drug is safe when it can be determined based on valid research evidence,
that the probable benefits to health from the use of drug for its intended uses and conditions of use, when
accompanied by adequate directions and warnings against unsafe use, outweigh the probable risks (FDA).
Risk can be thought of as “a measure of probability and severity of harm to human health.”
• Effectiveness is concerned with whether a treatment works under the usual conditions of care. Patients who
actually receive a medication in clinical practice may differ in many respects from the kinds of patients
usually enrolled in clinical trials. For example, they may or may not be as motivated as patients in clinical
trials, they may or may not have decisional capacity, or they may suffer from substantial comorbidities.
In order to identify drug effects under the conditions of routine clinical care, an effectiveness
trial generally involve heterogeneous patient population, compare active treatments to one another rather
than to placebo, and must yield information about clinically relevant outcomes.

5. Measurement of Safety
Rating scales for the assessment of neuroleptic side-effects have been published, such as those by Simpson
&Angus (1970) and Barnes (1989), but they all measure a very limited range of adverse events. The most
comprehensive scale so far developed for the assessment of neuroleptic side-effects is the 48-item UKU rating
scale (Lingjaerde et al. 1987), which has been shown to have good psychometric properties. The main
disadvantage of the scale is that it is intended for administration by a trained investigator and can take 30-
60minutes to administer. LUNSERS is a 41-item self-rating scale which requires respondents to indicate how
much they experienced each of the side-effects listed in the last month.
Measurement of Effectiveness
The commonly used rating scales for the measure of efficacy are PANSS, SANS, SAPS and BPRS. The PANSS is a
comprehensive tool and includes 30 items, it requires a long interview with the patient (30–40 minutes). The
SAPS and the SANS have been used in numerous clinical trials to assess the psychopathology of schizophrenia.
Because of their extensiveness, it may be difficult to administer them as part of a routine clinical interview. In
busy psychiatric services, short, simple-to-administer, and informative measures are needed to assess
psychopathological symptoms. The Brief Psychiatric Rating Scale (BPRS) is one of the most widely-used
instruments enabling the clinician to quickly gather information about the possible presence and severity of
various psychiatric symptoms.

6. AIM
To Compare the safety and effectiveness of the typical antipsychotics and atypical antipsychotics.
OBJECTIVES
1. To assess the safety (side effects) of the atypical and typical antipsychotics.
2. To assess the effectiveness of reducing symptoms of schizophrenia by the use of atypical antipsychotics
and typical antipsychotics.
NEED FOR STUDY
There is an ongoing debate over whether atypical antipsychotics are more effective than typical
antipsychotics in the treatment of schizophrenia, although atypical were intended to have greater efficacy
and better tolerability (e.g. induction of motor side effects) than the first-generation antipsychotics. So the
comparison of safety and effectiveness of atypical and typical antipsychotics has been recognized as an
important index for safe and effective use of antipsychotics in schizophrenia patients, because it reflects
the judgment of both patients and clinicians on the medication's effectiveness, safety, and tolerability.

7. REVIEW OF LITERATURE
An integrative literature review method was undertaken to review literature related to this study because it is more
flexible compared to other types of literature review methods such as systematic and meta-analysis reviews. This
chapter reviews the literature related to the areas of investigation and is organized in four main parts.
1. The first part gives background information about the definition and measurement of safety and efficacy.
2. The second part explains the process of the literature review that was undertaken to review studies related to the
safety and efficacy of FGAs vs SGAs in people with schizophrenia.
3. The third part presents the main themes that were identified based on the literature review: theme 1, the SGAs
showed more efficacy than FGAs in schizophrenia; theme 2, FGAs and SGAs showed no significant differences in
efficacy between them.
4. The final part provides discussion of the literature regarding the safety and efficacy of FGAs vs SGAs in people
with schizophrenia and the rational for this study.
The following English terms were used as keywords: “schizophrenia”, “antipsychotic”, “safety”, “efficacy”,
“effectiveness”, “typical”, “atypical”, “FGA”, SGA” and “tolerability”. First the databases PubMed, Pub Psych,
BASE, DOAJ and next the websites like Google Scholar and Researchgate were also consulted. The literature
publication years were first limited to 1990 to 2014. An initial search of the aforementioned databases was carried out,
followed by an analysis of the words contained in the titles and abstracts and the index terms used to describe the
article. Additional literature was sourced from the reference lists of articles found. After application of the inclusion
and exclusion criteria, only 21 studies were identified as relevant to the current study.

8. METHODOLOGY
Study Site: Government General Hospital(GGH), Kakinada
Study duration: 6 months
Study design: Panel study
Sample Size: 120
Study Criteria: Inpatient and Outpatient visiting to department of psychiatry enrolled in the study by considering the
following inclusion and exclusion criteria.
Instruments used: 1. LUNSERS (possible range: 0- 164)
2. BPRS (possible range: 24-168)
Source of Data Collection: Case sheets of the patients and enquiring the patients or the patient representative about their
side-effects and reduction of symptoms.
Method of Data Collection: Baseline – 8 weeks Follow-up
Participant consent form
Participant Information sheet
Data Collection form
BPRS-24
LUNSERS
Statistical Analysis: Two tailed t-test at p<0.05 (using Excel 2016)

9. Inclusion Criteria
1. Patients met ICD-10 criteria for schizophrenia.
2. Patients above 18 years and below 60 years age.
3. All patients receiving at least one antipsychotic for at
least 1 month.
4. Patients receiving anticholinergics as prophylactic
treatment.
5. The antipsychotics regimen had not been changed for
at least 1 month in any subject before recruiting in to
the study.
6. Had a level of understanding sufficient to
communicate with research staff and cooperated with
all examinations required by the protocol.
7. Understood the nature of study and signed a
participant consent form (required of each patient or
patient authorized legal representative)
Exclusion Criteria
1. Patients below 18 years and above 60 years age.
2. Patients having serious or unstable medical
illnesses.
3. Patients excluded if they have received the
diagnosis of schizoaffective disorder, mental
retardation, substance induced psychosis or any
other psychiatric disorder.
4. Patients who were either pregnant or lactating.
5. Patients receiving combination of typical and
atypical antipsychotics.
6. Simultaneous use of anticonvulsants,
antidepressants and mood stabilizers.

10. RESULTS

11. Characteristic Category Typical Atypical Total (%)
Age 35.59 ± 9.68 36.21 ± 9.23 35.98 ± 9.81
Gender
Male 28 29 57 (47.50)
Female 31 32 63 (52.50)
Education
Uneducated 10 14 24 (20.00)
Primary 17 12 29 (24.17)
Secondary 19 18 37 (30.83)
Diploma 5 6 11 (9.170)
Degree 8 11 19 (15.83)
Employment
Employed 37 38 75 (62.50)
Unemployed 22 23 45 (37.50)
Marital
status
Married 34 35 69 (57.50)
Unmarried 17 20 37 (30.83)
Separated 2 2 4 (03.33)
Divorced 6 4 10 (08.34)
Place
Rural 37 51 88 (73.33)
Urban 22 10 32 (26.67)
Table 1 Distribution of sociodemographic variables between
two treatment arms in patients with Schizophrenia
Figure 1 Patient Demographic Characteristics in two
treatment arms
0
10
20
30
40
50
60
70
80
90
100
Male
Female
Uneducated
Primary
Secondary
Diploma
Degree
Employed
Unemployed
Married
Unmarried
Seperated
Divorced
Rural
Urban
Gender Education Employment Marital status Place
Patient demographic characteristics
Typical Atypical Total

12. Symptoms
Atypical Typical
P value
Baseline Baseline
N=61 N=59
Means Std dev Means Std dev
Somatic concern 2 0.98 2 1.05 1.00
Anxiety 3.21 1.85 2.63 1.55 0.06
Depression 3.03 2.04 2.59 1.68 0.20
Suicidality 1.93 1.56 1.83 1.34 0.70
Guilt 1.51 1.03 1.58 1.18 0.74
Hostility 2.52 1.58 2.59 1.39 0.80
Elevated mood 1.97 1.37 1.88 1.13 0.71
Grandiosity 1.23 0.94 1.31 0.84 0.64
Suspiciousness 1.95 1.44 1.98 1.48 0.90
Hallucinations 2.16 1.75 1.78 1.2 0.17
Unusual Thought
content
1.48 1.13 1.36 0.8 0.51
Bizarre behaviour 1.18 0.76 1.2 0.61 0.86
Self- neglect 1.25 0.91 1.19 0.43 0.65
Symptoms
Atypical Typical
P value
Baseline Baseline
N=61 N=59
Means Std dev Means Std dev
Disorientation 1.38 0.78 1.27 0.49 0.37
Conceptual
Disorganisation
1.57 1.04 1.58 0.91 0.99
Blunted Effect 2.16 1.33 2.24 1.49 0.78
Emotional
Withdrawal
1.67 1.27 1.59 1.18 0.73
Motor Retardation 2.11 1.5 1.93 1.3 0.48
Tension 2.64 2.19 1.95 1.55 0.05
Uncooperativeness 1.33 0.68 1.42 0.77 0.47
Excitement 1.38 0.78 1.29 0.74 0.52
Distractibility 1.46 0.7 1.69 0.93 0.12
Motor Hyperactivity 1.15 0.65 1.17 0.42 0.83
Mannerisms and
Posturing
1.05 0.28 1.02 0.13 0.43
Total Score 43.49 12.83 41.41 11.09 0.34
Table 2 Baseline severity of illness scores of schizophrenia patients treated with atypical and typical
antipsychotics

13. Figure 2 Severity of illness at baseline in both treatment groups
0
0.5
1
1.5
2
2.5
3
3.5
BPRSscore
BPRS symptoms
Baseline severity of illness
Atypical Typical

14. BPRS Symptoms
Atypical Antipsychotics
P valueBaseline Follow up
N=61 N=61
Means Std dev Means Std dev
Somatic concern 2 0.98 2.02 0.92 0.92
Anxiety 3.21 1.85 2.48 1.61 0.02
Depression 3.03 2.04 2.36 1.51 0.04
Suicidality 1.93 1.56 1.31 0.65 0
Guilt 1.51 1.03 1.43 0.9 0.64
Hostility 2.52 1.58 2.46 1.48 0.81
Elevated mood 1.97 1.37 2.02 1.51 0.85
Grandiosity 1.23 0.94 1.31 0.9 0.62
Suspiciousness 1.95 1.44 1.87 1.28 0.74
Hallucinations 2.16 1.75 1.54 1.26 0.03
Unusual Thought
content
1.48 1.13 1.34 0.98 0.50
Bizarre Behaviour 1.18 0.76 1.16 0.71 0.90
Self-Neglect 1.25 0.91 1.31 0.56 0.63
Table 3 Treatment response of atypical antipsychotics from baseline to follow up using BPRS-24
BPRS Symptoms
Atypical Antipsychotics
P valueBaseline Follow up
N=61 N=61
Means Std dev Means Std dev
Disorientation 1.38 0.78 1.39 0.59 0.90
Conceptual
Disorganisation
1.57 1.04 1.51 0.87 0.71
Blunted Effect 2.16 1.33 1.93 1.28 0.33
Emotional
Withdrawal
1.67 1.27 1.69 1.16 0.94
Motor Retardation 2.11 1.5 1.57 0.87 0.02
Tension 2.64 2.19 1.66 1.12 0
Uncooperativeness 1.33 0.68 1.26 0.68 0.59
Excitement 1.38 0.78 1.51 0.94 0.40
Distractibility 1.46 0.7 1.3 0.49 0.14
Motor Hyperactivity 1.15 0.65 1.25 0.7 0.42
Mannerisms and
Posturing
1.05 0.28 1.2 0.54 0.06
Total Score 43.49 12.83 38.87 10.35 0.03

15. Figure 3 Treatment response of Atypical antipsychotics from baseline to follow up
1.00
1.50
2.00
2.50
3.00
3.50
BPRSscore
BPRS symptoms
Treatment Response of atypical antipsychotics
Basline Follow up

16. BPRS Symptoms
Typical Antipsychotics
P valueBaseline Follow up
N=59 N=59
Means Std dev Means Std dev
Somatic concern 2 1.05 2.42 1 0.01
Anxiety 2.63 1.55 2.49 1.24 0.56
Depression 2.59 1.68 2.31 1.25 0.22
Suicidality 1.83 1.34 1.41 0.79 0.03
Guilt 1.58 1.18 1.47 0.82 0.56
Hostility 2.59 1.39 2.64 1.32 0.82
Elevated mood 1.88 1.13 1.76 1.02 0.52
Grandiosity 1.31 0.84 1.41 0.75 0.44
Suspiciousness 1.98 1.48 1.92 1.1 0.72
Hallucinations 1.78 1.2 1.66 1.03 0.51
Unusual Thought
content
1.36 0.8 1.42 0.77 0.63
Bizarre Behaviour 1.2 0.61 1.17 0.42 0.67
Self- Neglect 1.19 0.43 1.47 0.84 0.01
Table 4 Treatment response of typical antipsychotics from baseline to follow up using BPRS-24
BPRS Symptoms
Typical Antipsychotics
P valueBaseline Follow up
N=59 N=59
Means Std dev Means Std dev
Disorientation 1.27 0.49 1.69 1.1 0
Conceptual
Disorganisation
1.58 0.91 1.69 1.15 0.48
Blunted Effect 2.24 1.49 2 1.07 0.23
Emotional
Withdrawal
1.59 1.18 1.73 0.78 0.43
Motor Retardation 1.93 1.3 1.86 0.92 0.73
Tension 1.95 1.55 1.66 1.01 0.19
Uncooperativeness 1.42 0.77 1.24 0.5 0.05
Excitement 1.29 0.74 1.47 0.77 0.15
Distractibility 1.69 0.93 1.54 0.65 0.30
Motor Hyperactivity 1.17 0.42 1.27 0.55 0.28
Mannerisms and
Posturing
1.02 0.13 1.27 0.58 0
Total Score 41.41 11.09 41 9.46 0.78

17. Figure 4 Treatment response of typical antipsychotics from baseline to follow up
1.00
1.20
1.40
1.60
1.80
2.00
2.20
2.40
2.60
2.80
Somaticconcern
Anxiety
Depression
Suicidality
Guilt
Hostility
Elevatedmood
Grandiosity
Suspiciousness
Hallucinations
UnusualThoughtcontent
BizarreBehaviour
SelfNeglect
Disorientation
ConceptualDisorganisation
BluntedEffect
EmotionalWithdrawl
MotorRetardation
Tension
Uncooperativeness
Excitement
Distractability
MotorHyperactivity
MannerismsandPosturing
BPRSscore
BPRS symptoms
Baseline follow up

18. Table 5 Change from baseline to endpoint in severity of illness scores of schizophrenia patients treated with atypical and
typical antipsychotics
Symptoms
Atypical Typical
P value
Change in
score
Change in
score
N=61 N=59
Mean Std dev Mean Std dev
Somatic concern 0.02 1.4 0.42 1.25 0.10
Anxiety -0.74 2.14 -0.14 1.76 0.09
Depression -0.67 2.15 -0.29 1.77 0.29
Suicidality -0.62 1.47 -0.42 1.46 0.46
Guilt -0.08 1.04 -0.1 1.35 0.93
Hostility -0.07 1.8 0.05 1.68 0.71
Elevated mood 0.05 1.68 -0.12 1.4 0.55
Grandiosity 0.08 0.53 0.1 0.99 0.89
Suspiciousness -0.08 1.43 -0.07 1.42 0.96
Hallucinations -0.62 1.58 -0.12 1.37 0.06
Unusual Thought
content
-0.13 1.16 0.07 1.08 0.33
Bizarre behaviour -0.02 0.53 -0.03 0.61 0.87
Self- neglect 0.07 1 0.29 0.83 0.19
Symptoms
Atypical Typical
P valueChange in score Change in score
N=61 N=59
Mean Std dev Mean Std dev
Disorientation 0.02 0.96 0.42 1.09 0.03
Conceptual
Disorganisation
-0.07 1.3 0.12 1.27 0.44
Blunted effect -0.23 1.75 -0.24 1.51 0.98
Emotional
Withdrawal
0.02 1.69 0.14 1.32 0.67
Motor Retardation -0.54 1.51 -0.07 1.52 0.09
Tension -0.98 2.47 -0.29 1.67 0.07
Uncooperativeness -0.07 0.87 -0.19 0.71 0.41
Excitement 0.13 1.04 0.19 0.99 0.77
Distractibility -0.16 0.71 -0.15 1.11 0.95
Motor Hyperactivity 0.1 0.68 0.1 0.71 0.98
Mannerisms and
Posturing
0.15 0.57 0.25 0.6 0.32
Total Score -4.62 13 -0.41 10.9 0.06
*Negative mean scores represent improvement of symptoms from baseline to follow up. *Positive scores represent deterioration of symptoms from baseline to follow up.

19. Figure 5 Change from baseline to endpoint in severity of illness scores of schizophrenia patients treated with
atypical and typical antipsychotics
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
Somaticconcern
Anxiety
Depression
Suicidality
Guilt
Hostility
Elevatedmood
Grandiosity
Suspiciousness
Hallucinations
UnusualThoughtcontent
Bizarrebehaviour
Selfneglect
Disorientation
ConceptualDisorganisation
Bluntedeffect
EmotionalWithdrawl
MotorRetardation
Tension
Uncooperativeness
Excitement
Distractability
MotorHyperactivity
MannerismsandPosturing
BPRSscore
BPRS symptoms
Effectiveness
Atypical Typical

20. Table 6 Baseline side effect scores of schizophrenia patients treated with atypical and typical antipsychotics
Side effects
Atypical Typical
p valueBaseline Baseline
N=61 N=59
Means Std dev Means Std dev
Weight 58.17 9.64 58.22 12.17 0.98
EXTRA-PYRAMIDAL SIDE EFFECTS 4.95 3.02 5.2 4.36 0.71
Muscle Stiffness 0.87 1.2 0.92 1.26 0.84
Slowing of movements 0.69 1.04 0.88 1.12 0.33
Muscle Spasms 0.57 0.99 0.66 1.12 0.65
Restlessness 1.3 1.41 1.15 1.36 0.57
Shakiness 1.13 1.32 1.14 1.31 0.99
Parts of body moving of their own accord 0.18 0.7 0.14 0.63 0.71
Over-wet or Drooling mouth 0.25 0.51 0.29 0.59 0.67
PSYCHIC SIDE EFFECTS 14.15 6.57 13.14 6.7 0.41
Difficulty Staying Awake during day 1.13 1.34 1.44 1.37 0.21
Increased dreaming 0.72 1.08 0.86 1.14 0.48
Difficulty in concentrating 1.57 1.55 1.27 1.41 0.27
Tension 2.16 1.39 1.76 1.39 0.12
Tiredness 1.84 1.45 1.56 1.38 0.29
Difficulty in Remembering things 1.25 1.53 1.34 1.46 0.73
Lack of Emotions 0.67 1.06 0.69 1.15 0.91
Depression 1.69 1.47 1.34 1.29 0.17
Sleeping too much 1.36 1.4 1.46 1.45 0.71
Difficulty getting sleep 1.61 1.42 1.44 1.34 0.51

21. Side effects
Atypical Typical
p valueBaseline Baseline
N=61 N=59
Means Std dev Means Std dev
ANTICHOLINERGIC SIDE EFFECTS 2.61 2.65 3.1 2.64 0.31
Dry Mouth 0.85 1.38 1.08 1.3 0.34
Constipation 0.49 0.98 0.44 0.79 0.75
Difficulty passing water 0.1 0.35 0.22 0.72 0.24
Blurred vision 0.61 1.11 0.81 0.97 0.28
Passing lot water 0.54 0.99 0.56 0.95 0.92
OTHER AUTONOMIC SIDE EFFECTS 4.33 2.87 4.39 3.57 0.92
Dizziness 0.69 1.12 0.83 1.21 0.5
Feeling Sick 1.62 1.4 1.64 1.45 0.94
Palpitations 0.89 1.03 0.75 0.99 0.45
Increased Sweating 0.87 1.15 0.88 1.13 0.95
Diarrhoea 0.25 0.54 0.27 0.74 0.83
ALLERGIC REACTIONS 0.93 1.46 1.07 2.24 0.7
Rash 0.08 0.42 0.25 0.78 0.13
Sensitivity to sun 0.39 0.74 0.24 0.71 0.25
New or unusual Skin Marks 0.1 0.35 0.19 0.68 0.37
Itchy Skin 0.33 0.93 0.39 0.98 0.72

22. Side effects
Atypical Typical
p valueBaseline Baseline
N=61 N=59
Means Std dev Means Std dev
HORMONAL 1.61 2.18 1.46 1.91 0.69
Swollen tend chest 0.48 0.92 0.41 0.81 0.67
Period problems 0.23 0.78 0.2 0.64 0.84
Increased Sex drive 0.2 0.68 0.03 0.26 0.09
Difficulty in Achieving
Climax
0.23 0.74 0.27 0.67 0.75
Reduced Sex drive 0.3 0.86 0.34 0.86 0.78
Periods less frequent 0.2 0.73 0.22 0.65 0.85
MISCELLANEOUS 2.7 2.03 2.73 2.06 0.95
Headache 1.38 1.28 1.25 1.27 0.6
Losing Weight 0.62 0.97 0.56 0.95 0.72
Putting on weight 0.38 0.71 0.63 1.03 0.12
Pins and Needles 0.34 0.95 0.27 0.83 0.65
LUNSERS TOTAL 27.08 12.35 27.27 14.03 0.94

23. Figure 6 Baseline side effect scores of schizophrenia patients treated with atypical and typical antipsychotics.
0
2
4
6
8
10
12
14
16
EPS Anticholinergic Other
Autonomic
Allergic Psychic Hormonal Miscellaneous
LUNSERSmeanscore
Side effects
Safety at baseline
Atypical typical

24. Table 7 Safety of atypical antipsychotics treatment from baseline to follow up
Side effects
Atypical Antipsychotics
p valueBaseline Follow up
N=61 N=61
Means Std dev Means Std dev
Weight 58.17 9.64 58.62 8.82 0.41
EXTRA-PYRAMIDAL SIDE EFFECTS 4.95 3.02 3.82 3.21 0.02
Muscle Stiffness 0.87 1.20 0.59 0.96 0.06
Slowing of movements 0.69 1.04 0.62 0.95 0.71
Muscle Spasms 0.57 0.99 0.46 0.94 0.32
Restlessness 1.30 1.41 1.13 1.48 0.47
Shakiness 1.13 1.32 0.59 0.90 0
Parts of body moving of their own accord 0.18 0.70 0.11 0.45 0.55
Over-wet or Drooling mouth 0.25 0.51 0.36 0.71 0.35
PSYCHIC SIDE EFFECTS 14.15 6.57 11.28 6.42 0
Difficulty Staying Awake during day 1.13 1.34 1.33 1.26 0.34
Increased dreaming 0.72 1.08 0.57 0.85 0.28
Difficulty in concentrating 1.57 1.55 1.05 1.51 0.02
Tension 2.16 1.39 1.28 1.50 0
Tiredness 1.84 1.45 1.25 1.39 0.01
Difficulty in Remembering things 1.25 1.53 1.15 1.33 0.63
Lack of Emotions 0.67 1.06 0.54 1.04 0.48
Depression 1.69 1.47 1.20 1.36 0.02
Sleeping too much 1.36 1.40 1.44 1.36 0.73
Difficulty getting sleep 1.61 1.42 1.48 1.37 0.60

25. Side effects
Atypical Antipsychotics
p valueBaseline Follow up
N=61 N=61
Means Std dev Means Std dev
ANTICHOLINERGIC SIDE EFFECTS 2.61 2.65 2.59 2.71 0.96
Dry Mouth 0.85 1.38 1 1.22 0.51
Constipation 0.49 0.98 0.31 0.76 0.15
Difficulty passing water 0.1 0.35 0.13 0.43 0.57
Blurred vision 0.61 1.11 0.62 0.95 0.91
Passing lot water 0.54 0.99 0.56 0.89 0.91
OTHER AUTONOMIC SIDE EFFECTS 4.33 2.87 3.03 2.80 0
Dizziness 0.69 1.12 0.49 0.83 0.21
Feeling Sick 1.62 1.40 1.18 1.34 0.08
Palpitations 0.89 1.03 0.54 0.91 0.02
Increased Sweating 0.87 1.15 0.77 0.97 0.58
Diarrhoea 0.25 0.54 0.10 0.35 0.08
ALLERGIC REACTIONS 0.93 1.46 0.82 1.66 0.62
Rash 0.08 0.42 0.21 0.55 0.16
Sensitivity to sun 0.39 0.74 0.49 0.94 0.44
New or unusual Skin Marks 0.1 0.35 0.07 0.31 0.60
Itchy Skin 0.33 0.93 0.11 0.49 0.09

26. Side effects
Atypical Antipsychotics
p valueBaseline Follow up
N=61 N=61
Means Std dev Means Std dev
HORMONAL 1.61 2.18 1.02 1.37 0.06
Swollen tend chest 0.48 0.92 0.36 0.66 0.37
Period problems 0.23 0.78 0.08 0.33 0.12
Increased Sex drive 0.2 0.68 0.21 0.64 0.83
Difficulty in Achieving
Climax
0.23 0.74 0.1 0.3 0.16
Reduced Sex drive 0.3 0.86 0.25 0.77 0.74
Periods less frequent 0.2 0.73 0.07 0.4 0.16
MISCELLANEOUS 2.7 2.03 2.03 1.83 0.03
Headache 1.38 1.28 0.92 1.2 0.01
Losing Weight 0.62 0.97 0.34 0.75 0.09
Putting on weight 0.38 0.71 0.52 0.7 0.22
Pins and Needles 0.34 0.95 0.28 0.73 0.57
LUNSERS TOTAL 27.08 12.35 21.13 12.91 0

27. Figure 7 Comparison of safety using LUNSERS scores at baseline and follow up in atypical antipsychotics
0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
EPS Anticholinergic Other
Autonomic
Allergic Psychic Hormonal Miscellaneous
LUNSERSmeanscore
Side effects
Safety of atypical antipsychotics
Baseline follow up

28. Side effects
Typical Antipsychotics
p valueBaseline Follow up
N=59 N=59
Means Std dev Means Std dev
Weight 58.22 12.17 58.16 12.35 0.86
EXTRA-PYRAMIDAL SIDE EFFECTS 5.2 4.36 5.71 3.99 0.41
Muscle Stiffness 0.92 1.26 0.83 1.09 0.68
Slowing of movements 0.88 1.12 0.97 1.09 0.65
Muscle Spasms 0.66 1.12 0.9 1.18 0.23
Restlessness 1.15 1.36 1.49 1.38 0.14
Shakiness 1.14 1.31 0.93 1 0.25
Parts of body moving of their own accord 0.14 0.63 0.07 0.31 0.47
Over-wet or Drooling mouth 0.29 0.59 0.46 0.82 0.11
PSYCHIC SIDE EFFECTS 13.14 6.7 13.93 6.76 0.44
Difficulty Staying Awake during day 1.44 1.37 1.63 1.29 0.42
Increased dreaming 0.86 1.14 1.08 1.19 0.24
Difficulty in concentrating 1.27 1.41 1.51 1.41 0.26
Tension 1.76 1.39 1.42 1.29 0.10
Tiredness 1.56 1.38 1.54 1.38 0.95
Difficulty in Remembering things 1.34 1.46 1.53 1.43 0.34
Lack of Emotions 0.69 1.15 0.76 0.92 0.71
Depression 1.34 1.29 1.46 1.41 0.58
Sleeping too much 1.46 1.45 1.85 1.37 0.10
Difficulty getting sleep 1.44 1.34 1.39 1.3 0.82
Table 8 Safety of typical antipsychotics treatment from baseline to follow up

29. Side effects
Typical Antipsychotics
p valueBaseline Follow up
N=59 N=59
Means Std dev Means Std dev
ANTICHOLINERGIC SIDE EFFECTS 3.1 2.64 3.54 2.3 0.31
Dry Mouth 1.08 1.3 1.56 1.38 0.04
Constipation 0.44 0.79 0.39 0.72 0.68
Difficulty passing water 0.22 0.72 0.17 0.5 0.64
Blurred vision 0.81 0.97 0.85 1.06 0.81
Passing lot water 0.56 0.95 0.58 0.89 0.91
OTHER AUTONOMIC SIDE EFFECTS 4.39 3.57 4.42 3.06 0.93
Dizziness 0.83 1.21 0.66 0.86 0.30
Feeling Sick 1.64 1.45 1.66 1.23 0.94
Palpitations 0.75 0.99 0.76 0.86 0.91
Increased Sweating 0.88 1.13 1.02 1.17 0.39
Diarrhoea 0.27 0.74 0.27 0.61 1
ALLERGIC REACTIONS 1.07 2.24 1.44 1.89 0.18
Rash 0.25 0.78 0.24 0.63 0.89
Sensitivity to sun 0.24 0.71 0.53 0.94 0.04
New or unusual Skin Marks 0.19 0.68 0.14 0.51 0.47
Itchy Skin 0.39 0.98 0.54 0.95 0.16

30. Side effects
Typical Antipsychotics
p valueBaseline Follow up
N=59 N=59
Means Std dev Means Std dev
HORMONAL 1.61 2.18 1.46 1.91 0.69
Swollen tend chest 0.48 0.92 0.41 0.81 0.67
Period problems 0.23 0.78 0.2 0.64 0.84
Increased Sex drive 0.2 0.68 0.03 0.26 0.09
Difficulty in Achieving
Climax
0.23 0.74 0.27 0.67 0.75
Reduced Sex drive 0.3 0.86 0.34 0.86 0.78
Periods less frequent 0.2 0.73 0.22 0.65 0.85
MISCELLANEOUS 2.7 2.03 2.73 2.06 0.95
Headache 1.38 1.28 1.25 1.27 0.60
Losing Weight 0.62 0.97 0.56 0.95 0.72
Putting on weight 0.38 0.71 0.63 1.03 0.12
Pins and Needles 0.34 0.95 0.27 0.83 0.65
LUNSERS TOTAL 27.08 12.35 27.27 14.03 0.94

31. Figure 8 Comparison of safety using LUNSERS scores at baseline and follow up in typical antipsychotics
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
9.00
10.00
11.00
12.00
13.00
14.00
15.00
EPS
Anticholinergic
OtherAutonomic
Allergic
Psychic
Hormonal
Miscellaneous
LUNSERSmeanscore
Side effects
Safety of typical antipsychotics
Baseline Follow up

32. Table 9 Comparison of safety between atypical and typical antipsychotics using LUNSERS baseline to endpoint change score
Side effects
Atypical Typical
p valueChange Score Change Score
N=61 N=59
Means Std dev Means Std dev
Weight 0.45 4.3 -0.06 2.47 0.43
EXTRA-PYRAMIDAL SIDE EFFECTS -1.13 3.61 0.51 4.72 0.03
Muscle Stiffness -0.28 1.16 -0.08 1.58 0.44
Slowing of movements -0.07 1.38 0.07 1.14 0.57
Muscle Spasms -0.11 0.9 0.24 1.49 0.12
Restlessness -0.16 1.74 0.34 1.75 0.12
Shakiness -0.54 1.23 -0.2 1.35 0.15
Parts of body moving of their own accord -0.07 0.85 -0.07 0.72 0.99
Over-wet or Drooling mouth 0.11 0.95 0.17 0.79 0.73
PSYCHIC SIDE EFFECTS -2.87 6.9 0.8 7.81 0.01
Difficulty Staying Awake during day 0.2 1.61 0.19 1.75 0.97
Increased dreaming -0.15 1.05 0.22 1.43 0.11
Difficulty in concentrating -0.52 1.76 0.24 1.59 0.01
Tension -0.89 1.66 -0.34 1.56 0.07
Tiredness -0.59 1.73 -0.02 2.03 0.10
Difficulty in Remembering things -0.1 1.61 0.19 1.5 0.32
Lack of Emotions -0.13 1.45 0.07 1.38 0.44
Depression -0.49 1.56 0.12 1.62 0.04
Sleeping too much 0.08 1.85 0.39 1.78 0.35
Difficulty getting sleep -0.13 1.92 -0.05 1.75 0.81

33. Side effects
Atypical Typical
p valueChange score Change Score
N=61 N=59
Means Std dev Means Std dev
ANTICHOLINERGIC SIDE EFFECTS -0.02 2.66 0.44 3.31 0.41
Dry Mouth 0.15 1.74 0.47 1.76 0.31
Constipation -0.18 0.97 -0.05 0.95 0.46
Difficulty passing water 0.03 0.45 -0.05 0.84 0.49
Blurred vision 0.02 1.13 0.03 1.07 0.93
Passing lot water 0.02 1.12 0.02 1.20 1
OTHER AUTONOMIC SIDE EFFECTS -1.30 3.47 0.03 3.14 0.03
Dizziness -0.20 1.21 -0.17 1.23 0.90
Feeling Sick -0.44 1.93 0.02 1.71 0.17
Palpitations -0.34 1.11 0.02 1.12 0.08
Increased Sweating -0.10 1.36 0.14 1.21 0.32
Diarrhoea -0.15 0.65 0 0.91 0.31
ALLERGIC REACTIONS -0.11 1.79 0.37 2.11 0.17
Rash 0.13 0.72 -0.02 0.92 0.33
Sensitivity to sun 0.10 1 0.29 1.05 0.31
New or unusual Skin Marks -0.03 0.48 -0.05 0.54 0.85
Itchy Skin -0.21 0.97 0.15 0.83 0.03

34. Side effects
Atypical Typical
p valueChange Score Change Score
N=61 N=59
Means Std dev Means Std dev
HORMONAL -0.59 2.37 0.10 2.22 0.10
Swollen tend chest -0.11 0.98 0.08 0.88 0.24
Period problems -0.15 0.73 0.05 0.63 0.11
Increased Sex drive 0.02 0.59 0.07 0.41 0.58
Difficulty in Achieving
Climax -0.13 0.72 0.05 0.95 0.24
Reduced Sex drive -0.05 1.18 -0.10 0.99 0.79
Periods less frequent -0.13 0.72 0 0.56 0.27
MISCELLANEOUS -0.67 2.37 -0.44 2.36 0.59
Headache -0.46 1.32 -0.07 1.51 0.13
Losing Weight -0.28 1.25 -0.24 1.10 0.85
Putting on weight 0.15 0.93 -0.03 1.44 0.41
Pins and Needles -0.07 0.89 -0.02 0.86 0.76
LUNSERS TOTAL -5.95 13.22 0.86 14.42 0.01

35. -7
-6
-5
-4
-3
-2
-1
0
1
2
LUNSERSscore
Side effects
Safety
Atypical Typical
Figure 9 Comparison of baseline to endpoint change in LUNSERS scores between atypical and typical antipsychotics

36. EFFECTIVENESS
There were statistically no significant differences in symptoms according to BPRS scores between two treatment
groups at baseline. At baseline the average symptom severity score was 43.49±12.83 and 41.41±11.09 for total
BPRS in atypical and typical antipsychotic treatment group respectively.
Response rate analysis: A more robust measure of respective treatment effects is clinical response, here it is defined
as significant reduction of symptoms scores from baseline to follow up. The two tailed t-test found atypical
antipsychotics treated patients achieved significantly higher response rate (43.49 to 38.87, p<0.03) than typical
antipsychotics treatment group (41.41 to 41.00, p= 0.78). Atypical antipsychotics are associated with significant
reduction in anxiety, depression, suicidality, hallucinations, motor retardation, tension and total scores. The typical
antipsychotics treatment group produced significant increase in symptoms such as somatic concern, self-neglect,
disorientation, mannerisms and significant reduction in suicidality scores. The typical antipsychotics treatment
group showed reduction in total BPRS scores and some of the symptoms from baseline to follow up but not quite
significantly.
Endpoint analysis: It is the comparison of mean change from baseline to follow up between two treatments. There is
no significant difference between two treatment groups in measure of effectiveness for BPRS change score even
though the treatment response is higher in atypical antipsychotics treatment group.
RESULTS DESCRIPTION

37. SAFETY
There is no significant difference in LUNSERS score at baseline between two treatment groups. The increase in side
effect score from baseline to follow up is considered as emergent side effects and decrease in side effect score from
baseline to follow up is considered as relieved side effects.
Extra-pyramidal side effects: The atypical antipsychotics treatment group showed significant reduction in
extrapyramidal side effects total score from base line to follow up after 8 weeks. Atypical antipsychotics showed
highly significant reduction in shakiness (tremors), and non-significant reduction in muscle stiffness (rigidity).
Typical antipsychotics showed no significant differences in side effects score from baseline to follow up. There is
significant increase in extrapyramidal side effect score in typical antipsychotics from baseline-to-follow up change
score.
Psychic side effects: Typical antipsychotics treatment group showed no significant differences from baseline to
follow up but the atypical antipsychotics treatment group showed significantly higher relieved side effects. Atypical
antipsychotics treatment group significantly relieved from side effects such as difficulty concentrating, tiredness,
depression and highly significant in case of tension. The change score from baseline to follow up was significantly
lower in atypical antipsychotics group than in typical antipsychotics.

38. Other side effects: The emergent side effect dry mouth is significantly higher in typical antipsychotic group
and there are no other significant differences in side effects from base line to follow up. There is significant
decrease in palpitations, highly significant decrease in other autonomic score and total LUNSERS score for
atypical antipsychotics from baseline to follow up. Weight gain was not significant in two treatment groups,
may be due to less time for follow up. The baseline average total Lunsers severity scores are 27.08±12.35 and
27.27±14.03 for atypical and typical antipsychotics with no significant differences at baseline. The change
mean score derived from subtracting baseline mean scores from follow up mean scores showed that atypical
antipsychotics has significantly improved from extrapyramidal, psychic, other autonomic side effects and more
significantly with LUNSERS total score at p<0.01 compared to the typical antipsychotic group.

39. This study compared the typical and atypical antipsychotics about the effectiveness and frequency of side effects in
the treatment of schizophrenia. The findings indicate that atypical antipsychotics treatment group showed
significantly higher clinical improvement by symptom reduction than typical antipsychotics treatment group, but it
failed to show significant difference in change scores between both treatment groups. In measure of safety the
atypical antipsychotics treatment group showed significant improvement from baseline to follow up and it also
showed significantly lower total LUNSERS change score than typical antipsychotic treatment group.
Effectiveness
Changes in BPRS scores to negative value from baseline to follow up scores indicating improvement at endpoint for
each symptom. Figure 5 shows comparison of change from the baseline to follow up for all BPRS symptoms between
atypical and typical antipsychotics treatment groups. For the anxiety, depression and tension symptoms the typical
antipsychotics treatment showed change scores of -0.13, -0.28 and -0.28, where as typical antipsychotics treatment
group showed improvement of -0.74, -0.67 and -0.98 respectively. The finding that atypical antipsychotics are
associated with less depression and anxiety is consistent with results from other reports that compared newer and
older antipsychotics. An 8-week study that compared multiple doses of risperidone with haloperidol (Chouinard G
et al.) found that largest difference between the typical and atypical antipsychotic were in terms that measured
mood and anxiety.
DISCUSSION

40. A 29-week study that compared clozapine and haloperidol also found that the largest difference between two
drugs was in the same BPRS cluster measuring anxious depression (Kane JM, Marder SR, Schooler NR, Wirshing
WC et al. 2001). A two-year study conducted on risperidone and haloperidol also found that decrease in range
of anxiety and depression symptoms, but there is no significant change with haloperidol group (Marder, Glynn,
Wirshing et al. 2003). The atypical antipsychotics treatment group have higher treatment response rate than
typical antipsychotics treatment group as shown in Table 3 and 4, which is found consistent with previous
reports (Tollefson, Beasley, Tran et al. 1997 and Lieberman, Tollefson, Tohen et al. (2003)) found that second
generation antipsychotic olanzapine achieved a significantly higher response rate than typical antipsychotic
haloperidol.
In our study there were no significant differences in terms of effectiveness between two
treatment groups according BPRS change score. Our results are consistent with the results from prior studies. A
52 week randomized study found no significant differences between the two treatment groups on measurement
of symptoms using BPRS (JA Lieberman et al. 2003). TEOSS study also found that second generation
antipsychotics olanzapine and risperidone didn’t demonstrate superior efficacy to molindone, first generation
antipsychotic in treatment of early onset schizophrenia and schizoaffective disorder (Sikich, Frazier et al. 2008).
CUtLASS 1 and CATIE study also found that second generation antipsychotics showed no advantage over second
generation in reduction of symptoms (SW Lewis, RM Murray, Kerwin et al (2006).

41. Safety
In our study atypical antipsychotics treatment group having significantly more relieved extrapyramidal side
effects than typical antipsychotics is in accordance with reports from older results Tollefson, Beasley, Tran et al
(1997). Typical antipsychotics treatment group experienced significantly higher treatment emergent dry mouth
which was found consistent with JA Lieberman et al. (2003) reported that typical antipsychotic, chlorpromazine
had higher risk for dry mouth compared atypical antipsychotic, clozapine. Atypical antipsychotics showed
significantly lesser emergent EPS, psychic and other autonomic side effects compared to typical antipsychotics
treatment group as shown in Table 9. Even though there is statistically significant difference in LUNSERS scores
between both treatments, the incidence of side effects total mean score is low in both treatment groups
according to LUNSERS scoring guide.
Atypical and typical antipsychotics showed no significant changes in weight gain from baseline to follow
up, may be due to less time for the follow up which was contrary to prior studies, Lieberman’ Tollefson, Tohen et
al. and Rosenheck R, Perlick D, Bingham S et al reported olanzapine was associated with more weight gain than
haloperidol and Sikich, Frazier, McClellan et al. (2008) risperidone and olanzapine were pronounced more
weight gain compared to molindone.

42. Limitations
1. A potential limitation is 8 weeks of follow up,
sample size and sampling method (not
randomized due to wide range of inclusion and
exclusion criteria).
2. Because of less time and due to need of
intervention in patients, metabolic side effects for
safety profile were not assessed in which atypical
antipsychotics were known to produce significant
changes.
3. Due to more time taking for evaluation of BPRS
and LUNSERS, medication adherence
and quality of life in patients taking antipsychotics
were not assessed.
Strengths of study
1. Included patients receiving prophylactic anticholinergic
Trihexyphenidyl in both typical and atypical antipsychotics
treatment.
2. Avoided patients taking antidepressants, mood stabilizers
and anticonvulsants.
3. Standardised scales like LUNSERS and BPRS-24 has been
used to assess the safety and effectiveness, which are used
in previous studies and found to have good reliability and
validity.
4. Less clinically experienced professionals could administer
the BPRS with high levels of interrater reliability.
5. The use of LUNSERS, a self -reported patient outcome
questionnaire with red herring score reduces high inter
rater variability.
6. Only schizophrenia patients were studied unlike the
previous studies which includes patients with multiple
diagnoses schizophrenia, schizoaffective disorder, substance
induced psychosis etc.

43. The present study results demonstrate that the atypical antipsychotics are safer than typical
antipsychotics in patients with diagnosis of schizophrenia in combination with anticholinergics.
Atypical antipsychotics exhibited less emergent and more relieved side effects in extrapyramidal
side effects, psychic side effects, and other autonomic side effects subscales apart from low total side
effect score in accordance with previous studies. Atypical antipsychotics produced higher treatment
response than typical antipsychotics in schizophrenia and showed more improvement in mood and
negative symptoms such as anxiety, suicidality, depression, tension and motor retardation over
typical antipsychotics in relation to prior studies, and there was no significant difference found in
treatment response for positive symptoms between atypical and typical antipsychotics except for
hallucinations, in which atypical antipsychotics showed better response. However, there was no
significant difference found between atypical and typical antipsychotics in terms of effectiveness in
the treatment of schizophrenia.
CONCLUSION

44. Thank You