The study assessed prescriptions of 35 schizophrenia patients for potential drug-drug interactions (DDIs). 19 prescriptions were found to have DDIs, with 12 in male patients and 7 in females. More interactions (7) occurred in patients aged 19-29. The DDIs were classified as major (16%), moderate (58%), or minor (26%). Over half (53%) had a rapid onset, while 37% had a delayed onset. Common moderate interactions involved haloperidol combined with dicyclomine or alprazolam, which can worsen symptoms or increase haloperidol levels. The study highlights the need for assessing prescriptions with multiple drugs to prevent serious DDI

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* Corresponding author: Amareswara Reddy G.
E-mail address: amarpdtr@gmail.com.
Available online at www.ijrpp.com
Print ISSN: 2278 – 2648
Online ISSN: 2278 - 2656 IJRPP | Volume 2 | Issue 3 | 2013 Research article
A Pilot Study on the Drug-Drug interactions among the Schizophrenia
Patients in a Tertiary Care Teaching Hospital.
*,1
Amareswara Reddy G, 2
Samson Deepak A, 3
Siva Kumar Reddy K, 4
Samjeeva Kumar E
*1,2,3
P.Rami Reddy Memorial College of Pharmacy, Kadapa, Andhra Pradesh.
4
Associate Professor, Department of pharmacy practice, P.Rami Reddy Memorial College of
Pharmacy, Kadapa, Andhra Pradesh.
ABSTRACT
The present study is aimed to identify the possible drug-drug interactions in the prescriptions of schizophrenia
patients and the clinical implications of those drug-drug interactions with them. The study was done in a tertiary
care teaching hospital which has a fully fledged psychiatry department. An attempt was made to study drug-drug
interactions (DDI’s) in the prescriptions of schizophrenic patients. For a period of one month 35 prescriptions of
schizophrenic patients were prospectively evaluated for DDI’s by the simple random sampling method. The
information about medication was recorded in a specially designed data entry form and it was assessed for
possible and severe DDI’s by using primary, secondary and tertiary drug information sources. In the present
study, 35 prescriptions were assessed and 19 prescriptions out of them were found to have DDI’s. Out of 19
DDI’s, 12 interactions occurred in male patients and 7 occurred among females. More number of drug
interactions (7) was found in the 19-29 years age group. Based on severity, these interactions were classified as
major (16%), moderate (58%) and minor (26%). Out of total interactions, 53% occurred with rapid onset, 37%
with delayed onset and onset of 10% interactions were unspecified. The schizophrenic patients have to take
long term anti-psychotic medication therapy. Hence, prior assessment is mandatory for the prescriptions with
multiple drug therapy. This can minimize a lot of major and moderate drug-drug interactions, especially among
the patients with risk factors like cardiovascular and CNS disorders. Clinicians and pharmacists should use their
best judgments while prescribing or assessing drug therapy. The study opens door for larger studies to
emphasize the role of pharmacist in identifying and preventing DDI’s and provide safe advice on interaction
management which can greatly add to patient safety and well being.
Keywords: Schizophrenia, Anti Psychotics, Drug-Drug Interactions.
INTRODUCTION
Schizophrenia is a clinical syndrome of variable,
but profoundly disruptive, psychopathology that
involves cognition, emotion, perception, and other
aspects of behavior. The expression of these
manifestations varies across patients and over time,
but the effect of the illness is always severe and is
usually long-lasting. The term psychosis is broader
and involves infections, metabolic, endocrine and
drug induced causes of psychotic symptoms such
as mania, major depression and dementia [1].
Epidemiology
According to world mental health report 2001, 24
million people worldwide suffer from
schizophrenia. The point prevalence of
schizophrenia is about 0.5-1%. It affects men and
women with equal frequency, the disorder often
appears earlier in men, usually in the late teens or
early twenties, then in women who are generally
affected in the twenties to early thirties [2].
Clinical features
People with schizophrenia often suffer terrifying
symptoms such as hearing internal voices not heard
International Journal of Research in
Pharmacology & Pharmacotherapeutics

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by others, or believing that other peoples are
reading their minds, controlling their thoughts or
plotting to harm them. Available treatments can
relieve many symptoms but most people with
schizophrenia continue to suffer some symptoms
throughout their life. It has been estimated that not
more than 1 in 5 individuals recovers completely
[3].
Drug interactions in schizophrenia
Drug interactions are categorized into two types
namely pharmacokinetic interactions and
pharmacodynamic interactions. Pharmacodynamic
interactions result in either additive or antagonistic
pharmacological activity. Pharmacokinetic
interactions may be result of various processes like
alteration in GI absorption, displacement of drug
from plasma protein binding site, induction or
inhibition of metabolizing enzymes in liver. The
frequency and prevalence of drug interactions are
mainly reliant on concomitant medications and
complexicity of the regimens. It has been supposed
that prevalence of drug interaction is also
dependent upon factors like patient adherence,
hydration and nutritional status, degree of renal and
hepatic impairment, genetics and drug dosing [4].
The data regarding antipsychotic drug interactions
were limited to case reports and few specific
studies. So, the assessment of an interaction is quiet
difficult [5]. To estimate the clinical significance of
drug interaction they are categorized into three
types, a) Major- The effects of major interactions
may be potential life threatening and it require
medical Intervention to prevent or minimize these
effects, b) Moderate- The effects of moderate
interactions are exacerbation of patient’s clinical
status and/or require additional treatment or
hospitalization, c)Minor-The effects of minor
interactions have little clinical effects and these do
not require a major alteration in therapy[4]. In a
patient with a first episode of schizophrenia, the
treatment will be usually for 1-2 years. But in
patients with multiple episodes, treatment may be
required for many years [6].
The risk of drug-drug interaction is high in the
patient taking complex drug regimen. Common
examples of pharmacodynamic interactions are
additive anti-muscarinic effects of anti-psychotics
when concomitantly used with other medications
having anti-muscarinic effects e.g.(antihistamines,
antidepressants or anti-parkinsonism agents) may
result in urinary retention, constipation, blurred
vision or other anticholinergic effects. Finally this
results in impaired cognition particularly in the
elderly patients. Patients may be more likely to
experience symptomatic orthostatic hypotension
when an antipsychotic is used with other
medications that cause orthostasis E.g.
Antidepressants with alpha blockers,
antihypertensive agent or diuretics. The adverse
drug reactions and drug interactions are the major
barriers for the compliance and clinical
improvement in patients with schizophrenia who
need long term therapy [7]. The drugs of choice
for a patient should ideally be the most effective
and have the least potential to develop drug-drug
interaction, and the patient should have a positive
past history of response to the combination of
drugs.
AIM OF THE STUDY
The present study is aimed to identify the possible
drug-drug interactions in the prescriptions of
schizophrenia patients and the clinical implications
of those drug-drug interactions in them.
METHODOLOGY
The study was conducted in a 750 bedded tertiary
care teaching hospital in Andhra Pradesh. The
hospital has a full-fledged Psychiatry department
chaired by a psychiatrist. An attempt was made in
schizophrenia patients to study the drug-drug
interactions. In this study 35 patients were included
by simple random sampling method. Data entry
form was designed to document information about
patient, laboratory investigations and drugs
prescribed. Details of patients like name, age, sex,
educational back ground, economic status and
social habits were recorded. The patient’s past
medical and medication history, clinical
investigation and drugs used were also recorded.
The information about medications was recorded
from the medication chart of the patient in the
patient data collection form and the possible drug-
drug interactions were assessed by using primary,
secondary and tertiary sources [8].
Inclusion and Exclusion Criteria
The patients who were diagnosed as schizophrenic
according to DSM-V-TR are included in the study.
The willingness of the patient to participate in the
study was also taken into account. Exclusion
criteria include patients suffering from chronic
diseases, sufferers of renal or hepatic failure and

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pregnancy or lactating women, as these patients have altered drug metabolism in them.
RESULTS AND DISCUSSION
Table-1: Gender wise distribution of patients and number of prescriptions with drug-
drug interactions in them.
Table-2: Drug interactions found in the prescription
0
2
4
6
8
10
12
0-18 19-29 30-39 40 above
Numberofpatients
Age in years
Fig-1: Age wise distribution of schizophrenia patients
male
female
Gender
No. of patients
(n=35)
No. of prescriptions with
DDI’s
(n=19)
Male patients 19(54 %) 12
Female patients 16(46%) 7
Sl.No Drugs involved No. of
Prescriptions
(n=19)
Severity Onset Description of
interaction
1. Haloperidol +
Dicyclomine.Hcl
2 Moderate Rapid Worsening of
schizophrenia symptoms
2. Haloperidol +
Alprazolam
2 Moderate Delay Increased Haloperidol
concentration
3. Haloperidol+ Risperidone 1 Major Unspecified QT interval prolongation
4. Chlorpromazine +
Trihexyphenidyl
1 Moderate Delay Excessive
Anticholinergics effects
( excessive sedation, dry
mouth )

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Fig-2: Histogram showing number of prescriptions with drug-drug interactions out of total
prescriptions in different age groups
0
5
10
15
20
14-18 years 19-29 years 30-39 years >40 years
AGE GROUP
Total number of prescriptions
in both male and female
(n=35)
Number of prescriptions
found with drug-drug
interactions (n=19)
16%
58%
26%
Fig-3: Pie diagram showing severity
status of observed Drug interactions
Major
Moderat
e
Minor
53%
37%
10%
Fig-4: Pie chart showing onset of
Drug interactions
Rapid
Delayed
5 Fluphenazine +
Trihexyphenidyl
1 Moderate Rapid Enhanced anti
cholinergic effects
( hyperpyrexia, sedation,
dry mouth)
6 Chlorpromazine +
Atenolol
3 Moderate Delay Hypotension
7 Chlorpromazine +
Aluminium hydroxide
3 Minor Rapid Decreased effect of
Phenothiazines
8 Clozapine + Lorazepam 2 Minor Rapid CNS depression
9 Olanzapine +
Ciprofloxacin
1 Moderate Delay Orthostatic hypertension
10 Haloperidol + Propranolol 2 Major Rapid Hypotension and cardiac
arrest
11 Risperidone + valproic
acid
1 Moderate Unspecified Emotional upset,
abnormal dreams

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The prescribed antipsychotics and co-medicines
were assessed for severity and significance of drug-
drug interactions by using primary, secondary and
tertiary sources. Drug–drug interactions were
evaluated for 35 prescriptions and 19 prescriptions
were found to have drug-drug interactions. Out of
19 prescriptions with DDI’s, 12 interactions
occurred in male schizophrenic patients and 7
interactions occurred among females (table-1).
More number of drug interactions (7) was found in
the 19-29 years age group. Number of prescriptions
with drug-drug interactions out of total
prescriptions in different age groups is given in
figure-2. Based on severity, these interactions were
classified as major (16%), moderate (58%) and
minor (26%) (Fig-3). Out of total interactions, 53%
occurred with rapid onset, 37% with delayed onset
and onset of 10% interactions were unspecified
(fig-4). Drug combinations associated with major
interactions are Haloperidol + Risperidone and
Haloperidol + Propranolol. QT interval
prolongation was observed with haloperidol +
Risperidone and unexpected hypotension reaction
was seen with combination of haloperidol and
Propranolol. Drug combinations associated with
moderate interactions are haloperidol +
Dicyclomine, haloperidol + Alprazolam. Both these
combinations were found to increase dizziness,
drowsiness and xerostomia. Antipsychotic agents
like chlorpromazine and Fluphenazine when given
along with anticholinergic agent like
Trihexyphenidyl were found to show synergistic
effects of Trihexyphenidyl [9]. Few other
combinations associated with moderate, minor
interactions and their effects with onset of effect of
interaction are given in table-2. If the interaction is
of pharmacokinetics type, administration of the
drug can be adjusted by a gap of 4 to 5 hours and if
the interaction is of pharmacodynamic type, a safer
alternative should be prescribed.
CONCLUSION
As the improvement in schizophrenic patients is
seen only with long term therapy, being adhered to
the regimen all the way is very important. And,
development of drug interactions among prescribed
agents is one of the main reasons for non-
compliance and insufficient clinical betterment.
Hence, prior assessment is mandatory for the
prescriptions with multiple drug therapy. This can
minimize a lot of major and moderate drug-drug
interactions, especially among the patients with risk
factors like cardiovascular and CNS disorders.
Clinicians and pharmacists should use their best
judgments while prescribing or assessing drug
therapy. The study opens door for larger studies to
emphasize the role of pharmacist in identifying and
preventing drug-drug interactions and provide safe
advice on interaction management which can
greatly add to patient safety and well being.
ACKNOWLEDGEMENT
The authors are thankful for PRRM College of
pharmacy for providing access to MICRO
MEDEX® 2.0 drug information database and a
good number of drug reference books. The authors
acknowledge physicians and nurses of the
psychiatry department for their kind full support all
the way.
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[3] Joseph T. Dipiro et al. Schizophrenia, Pharmacotherapy. Mc Graw Hill publications, Edn 6, 2008, Pg.
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[4] George R Bailie, Curtis A Johnson, Med facts pocket guide of Drug Interactions, Edn 2, 2004, Pg. 3-6.
[5] Troy LZ, Jann MW. Drug interactions with antipsychotic agents: incidence and therapeutic
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