Pharmacology & Pharmacy, 2011, 2, 101-108
doi:10.4236/pp.2011.23013 Published Online July 2011 (http://www.scirp.org/journal/pp)
101
Amphetamine Versus Non Amphetamine-Related
First Episode Psychosis in Saudi Arabian Patients
Ehab Said El-Desoky, Ashraf M. A. El-Tantawy, Yasser M. Raya, Abdulhameed Al-Yahya
Pharmacology Department, Faculty of Medicine, Assiut University, Asyut, Egypt.
Received January 14th, 2011; revised March 5th, 2011; accepted May 15th, 2011.
ABSTRACT
Background: Amphetamines are illicit psychostimulant drugs that can induce psychotic symptoms. Very few studies
have been conducted in Kingdom of Saudi Arabia (SA) on amphetamine abuse and related psychosis. Recently, the pat-
tern of amphetamine abuse in SA showed a significant trend of increased frequency. Objectives: To investigate the ex-
tent of amphetamine abuse in a sample of Saudi patients hospitalized for first episode of acute psychosis. Also, to com-
pare in that sample between amphetamine psychosis and other psychoses regarding demographic data, premorbid per-
sonality and symptoms profile. Method: 106 patients with acute psychosis were hospitalized and screening of urine for
amphetamine was conducted for all. Patients’ psychiatric evaluation included interviewing, and ICD-10 criteria for
personality disorders. 30 healthy subjects were also included for comparison with patients. Results: 34/106 of psychotic
patients (32%) were positive for amphetamine in urine (≥ 1000 ng/ml). The frequency of personality disorders was sig-
nificantly higher (P < 0.01) in the patients (54/106; 51%) compared with healthy subjects (6/30; 20%). Also, the inci-
dence of personality disorders was significantly higher (P < 0.01) in amphetamine positive psychosis (25/34; 73.5%)
compared with amphetamine negative psychosis (29/72; 40%). Cluster B personality disorders particularly the antiso-
cial and borderline were significantly higher in amphetamine positive psychosis (13/34; 38%) compared with am-
phetamine negative psychoses (6/72; 8%). The symptom profile showed significant difference between amphetamine
positive and amphetamine negative psychosis as regards ideas of reference (50% vs. 14%), suspiciousness (44% vs.
11%), suicidal ideation (38% vs. 23%), paranoid delusions (29% vs. 17%) and increased pulse or blood pressure (29%
vs. 7%) respectively. Conclusion: Screening of amphetamine in urine among patients with first episode of acute psycho-
sis can help and support the clinical distinction of amphetamine psychosis from other types of psychosis. This is thera-
peutically critical since the line of treatment may be different between the two types of psychoses.
Keywords: Amphetamine, First Episode Psychosis
1. Introduction
In patients with psychosis like schizophrenia and/or bi-
polar disorder, substance abuse has been reported [1-4].
Previous studies have found high prevalence of schizo-
phrenia and other psychotic disorders among users of
illicit substances like cannabis [5] and amphetamines [6,
7]. Recently, a common co-occurrence of first episode
psychosis and substance use disorders like cannabis, al-
cohol and amphetamines has been reported [8-10].
In Saudi Arabia, the rapid development of socioecono-
mic status and the “oil boom” have led to the adoption of
novel recreational attitudes including drug abuse [11].
The annual incidence number of Saudi patients newly
admitted to the hospitals with abused drugs is increasing
especially for amphetamine at the expense of other sub-
stances like heroin, alcohol, and sedatives. The fre-
quency of amphetamine use among Saudi people of 40
years old or less increased markedly in the period
2000-2006 in comparison with the period 1986-1999
[12]. Different sources are available for abused am-
phetamine preparations by youth in Saudi Arabia like
clandestine laboratories and near by countries like
Yemen. The high incidence of amphetamine use in Saudi
population of young age in addition to the unavailability
of any previous studies regarding amphetamine use
Saudi psychotic patients have led to designing of this
study. The primary aim was to describe the current am-
phetamine use in a sample of Saudi patients experiencing
first episode of acute psychosis through urine screening
for the drug. Secondary aims were to find out any points
of difference in demographics and clinical picture that

102 Amphetamine Versus Non Amphetamine-Related First Episode Psychosis in Saudi Arabian Patients
can help differentiation between first episode psychotic
patients who were amphetamine positive and those who
were negative for amphetamine.
2. Patients and Methods
One hundred six adult Saudi patients attended the Psy-
chiatric Emergency Service of Buraidah Mental Health
Hospital in Al-Qassim Governorate, Kingdom of Saudi
Arabia in the period from January to July; 2008 and di-
agnosed as first episode of acute psychosis. Following
admission of each patient, one urine sample was col-
lected for amphetamine screening. It was sent immedi-
ately to the Toxicology Center of the Ministry of Health.
The Axsym analyzer of Abbott using the fluorescence
immunoassay technique was used in the screening and a
cutoff value ≥1000 ng/ml was considered positive for
amphetamine screening. Positive samples then were con-
firmed by Gas Chromatography Mass Spectrometry (GC-
MS) technique with cutoff values of ≥300 ng/ml for posi-
tive amphetamine samples [13].
2.1. Clinical Assessment
Each patient was interviewed (at admission, and then
daily) by an expert psychiatrist for clinical and psychiat-
ric assessment. The interview included questionnaire
about the socio-demographic data including educational
history, employment, socio-economic status, substance
use history and family history. Missing data was ob-
tained from patient’s relatives to complete the patient
profile. Questionnaire about family history included in-
quiry about family support (e.g. provision of housing,
food, clothing and money), parental substance abuse and
parental mental illness. All data were analyzed according
to the criteria of psychotic illness for diagnosis of acute
psychosis, and possible psychoactive substance use as
defined by the International Classification of Diseases
(ICD-10) [14]. The severity of psychotic symptoms in
each patient was evaluated by applying the positive and
negative syndrome scale (PANSS). The PANSS scale is
a 30-item standardized instrument that measures positive
symptoms such as hallucination and delusions, negative
symptoms such as affective blunting, emotional with-
drawal, and general symptoms such as motor retardation,
anxiety, disorientation) using a semi-structured interview
and chart review [15,16].
2.2. Personality Assessment
During admission period, and once the patient became
stable as regards psychotic symptoms, he was assessed
by the same expert psychiatrist for any personality disor-
der and its cluster according to a semi structured inter-
view for personality disorder evaluation [17,18]. The
clusters examined for personality disorders included:
Cluster A (e.g. schizoid, schizotypal or paranoid), Clus-
ter B (e.g. antisocial, borderline, histrionic or narcissis-
tic) and Cluster C (e.g. avoidant, dependent or obses-
sive). The study was carried out after approval from the
ethical committee, General Directorate of Health Affairs,
Al-Qassim Province, Ministry of Health, Kingdom of
Saudi Arabia and getting the acceptance of the responsi-
ble relatives concerning each patient.
2.3. Statistical Analysis
Data analysis was performed with a personal computer
using the SPSS statistical software program, version 13
(SPSS, 2002). The comparison of data between the psy-
chotic patients who were amphetamine positive and or
negative was based on whether the measurement of the
variable was categorical or scaled. Chi-square (
 2) test
or Fisher’s exact test (whenever appropriate) and un-
paired t-tests were used to determine the statistical sig-
nificance of the difference between the variables. Statis-
tical significance was considered at p < 0.05.
3. Results
Screening of urine samples for amphetamine in all pa-
tients (n = 106) revealed positive results in 34 subjects
(32%). The average concentration of amphetamine in
positive urine samples was 6189.8 ± 634.7 ng/ml. Table
1 showed the demographic features of the psychotic pa-
tients whether they were amphetamine positive or nega-
tive. Male gender was the most common sex in all pa-
tients (79/106; 74.5%) and all amphetamine positive cas-
es were males. The poor family support and history of
parental substance abuse were significantly recorded (p <
0.05) in amphetamine positive group while the parental
mental illness was significantly evident (p < 0.01) in
amphetamine negative psychotic group. However, low
education, unemployment, unmarried status and socio-
economic standard were not different between the two
groups.
Analysis of psychotic symptoms showed qualitative
similarity in many of the psychiatric symptoms tested
(though some incidence differences) between the two
psychotic groups. The observation indicates the difficulty
of symptoms-based discrimination between ampheta-
mine positive and amphetamine negative acute psychosis
(Table 2). Hallucinations including visual, auditory and
paranoid were evident in both although the incidence of
paranoid type of hallucination was significantly higher in
amphetamine positive group in comparison with the oth-
er group (19 % vs. 10 %; p < 0.05 respectively). As re-
gards other psychotic symptoms, significant incidence (p
< 0.001) of depression (44% vs. 13%), ideas of reference
(50% vs. 14%), and suspiciousness (44% vs. 11%) was
also observed in amphetamine positive psychosis in
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Amphetamine Versus Non Amphetamine-Related First Episode Psychosis in Saudi Arabian Patients 103
Table 1. Demographic characteristics of patients with first
episode psychosis: amphetamine positive versus ampheta-
mine negative groups.
Table 2. Comparison between amphetamine positive psy-
chosis and amphetamine negative psychosis regarding psy-
chiatric and autonomic symptoms & signs.
Demographic
data
Amphetamine-positive
psychotic group
Amphetamine nega-
tive psychotic groupp-value*
Total number 34 72
Age (years)** 23.3  9.4 ** 19.8  7.1**
Sex: male 34 (100%) 45 (62.5%) <0.01
female - 27 (37.5%)
Marital status
married 15 (44%) 31 (43%)
unmarried 19 (60%) 41 (57 %)
Education:
<12 years 29 (85%) 66 (92%)
>12 years 5 (15%) 6 (8.0%)
Employment:
employed 9 (27%) 36 (36%)
unemployed 25 (73%) 46 (64%)
Socioeconomic status
Low 7 (21%) 17 (24%)
Medium 21 (61%) 47 (65%)
High 6 (18%) 8 (11%)
Family history
Poor family
support 28 (82%) 49 (68%) <0.05
Parental sub-
stance use 9 (27%) 11 (15%) <0.05
Parental mental
illness 4 (12 %) 31 (43 %) <0.01
Symptoms &
signs
Amphetamine positive
psychotic group (n = 34)
Amphetamine negative
psychotic group (n = 72)
p-value
*
Psychiatric
Hallucina-
tions
Visual 27% (9) 18% (13)
Auditory 74% (25) 65% (47)
Paranoid
delusions 29% (10) 19% (14) <0.05
Depression44% (15) 13% (9) <0.001
Ideas of
reference 50% (17) 14% (10) <0.001
Suspicious-
ness 44% (15) 11% (8) <0.001
Violent be-
havior 21% (7) 17% (12)
Suicidal
ideations 38% (13) 24% (17)
Auto-
nomic** 29% (10) 7% (5) <0.01
*Chi-square; values in brackets are number of cases. ** Principally: dilated
pupils, tachycardia and increased pulse pressure.
comparison with amphetamine negative group respect-
tively. On the other hand, both psychotic groups were
similar in the incidence of other symptoms like violent
behavior and suicidal ideations.
Amphetamine is one of the autonomic sympath-
omi-metic drugs. When autonomic manifestations related
to amphetamine were checked in both groups of patients,
dilated pupils, tachycardia and increased pulse pressure
were significantly observed in amphetamine positive

104 Amphetamine Versus Non Amphetamine-Related First Episode Psychosis in Saudi Arabian Patients
Table 3. Psychiatric symptomatology: mean scores on the
Positive and Negative Symptom Scale (PANSS) between
patients with amphetamine positive and amphetamine neg-
ative psychosis.
Table 4. Personality Disorder among Patients with Am-
phetamine-related psychosis in comparison with ampheta-
mine-negative psychosis.
PANSS
(mean ± SD)
Amphetamine-
related psychotic
disorder (n = 34)
Amphetamine
negative psychosis
(n = 72)
p-value
Positive 18.3 ± 4.1 15.6 ± 6.5 <0.05
Negative 11.6 ± 4.7 21.3 ± 7.3 <0.01
General 28.5 ± 5.6 39.3 ± 9.3 <0.01
Total 58.4 ± 8.7 76.3 ± 10.5 <0.01
PANSS-PS = Positive and Negative Symptoms Scale.
psychotic group compared with the other group (29% vs.
7%; p < 0.01 respectively).
Amphetamine-related psychotic patients (ampheta-
mine positive group) showed significantly higher
PANSS positive psychotic scores than amphetamine
negative psychotic group. The later group had signifi-
cantly higher scores for both the negative and general
psychotic symptoms (Table 3). Personality disorder was
evident among not less half of studied psychotic patients
whether they were amphetamine positive or negative
(57/106; 54%). Table 4 showed significant incidence (p
< 0.01) of cluster B of personality disorder (e.g. antiso-
cial, borderline) in amphetamine related psychotic group
compared with the psychotic group negative to am-
phetamine (73.5 % vs. 44%; respectively). On the other
hand, no difference in the incidence of the other two
clusters of personality dis- order (cluster A & cluster C)
between the two groups of psychotic patients.
4. Discussions
The present study has revealed a prevalence of amphe-
Personality
Disorder
Amphetamine-positive
psychotic group (n = 34)
Amphetamine-negative
psychotic group (n = 72)p-value*
All 73.5% (25) 44% (32) <0.01
Clusters:
A 15% (5) 19%(14)
B 38% (13) 7% (5)
C 21% (7) 18% (13) <0.001
tamine use as defined in urine analysis among one third
of a sample of Saudi patients who were diagnosed as first
episode psychosis. Literature data showed a prevalence
of substance use in people with first episode psychosis of
approximately double that in the general population of
similar age [10,19,20]. Also, individuals with first epi-
sode psychosis may have a trend of increased sensitivity
(supersensitivity hypothesis) to develop substance use
disorder [21,22]. The patients with positive amphetamine
samples showed demographics of young age (23.3  9.4
years), all were men, and 60% were unmarried, a demo-
graphic criteria observed in amphetamine-related psy-
chotic patients [23]. The high incidence of amphetamine
use in the Saudi sample of patients (one third of the total)
supports a previous report of increased trend of am-
phetamine use in Saudi subjects since year 2000 [12].
Also, the presence of male gender only in positive sam-
ples for amphetamine reflects the strong and close style
of Saudi culture that might hinder facing the problem of
possible drug abuse among females or forward them for
treatment [12]. The early detection of substance use in
patients with first episode psychosis has an important
therapeutic implication for medical staff who usually
focus in their effort on chronic, not first episode patients.
Additionally, these patients underreport usually their
abuse of drugs. Therefore, misdiagnosis and inappropri-
ate medical treatment can happen [24].
The high concentrations of amphetamine in the posi-
tive urine samples of cases diagnosed as first episode
psychosis suggests the strong association between the
onset of first episode psychosis and amphetamine use [9,
25-27].
The poor family support and positive history of paren-
tal substance abuse in amphetamine positive psychotic
patients compared with amphetamine negative group is a
common finding observed in patients with substance use-
related psychosis [28].
The psychotic symptoms were qualitatively similar in
the two groups though they differ in between as regards
their incidence (Ta ble 2). This creates a difficult clinical
situation of differential diagnosis between amphetamine-
related psychosis and functional (primary) psychosis [29].
Amphetamine class of drugs like amphetamine and me-
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Amphetamine Versus Non Amphetamine-Related First Episode Psychosis in Saudi Arabian Patients 105
thamphetamine is known to increase the levels of mono-
amines (principally, dopamine) centrally [30]. Therefore,
exposure to these drugs in higher doses can play a role in
creating, accelerating or aggravating psychotic symp-
toms like aggression, depression, hallucination and para-
noia in patients with psychosis [31]. Auditory, visual and
paranoid hallucinations as well as delusions of reference
are typical symptoms not only in primary psychosis but
also in amphetamines-induced psychosis [32,33]. In the
current study, the significantly high prevalence of para-
noid hallucinations in amphetamine positive psychotic
Saudi patients is in agreement with previous studies [24,
27,34,35]. Amphetamine users may have a tendency to
develop depression; a finding seen also in the present
study among amphetamine positive psychotic group
(44%). Suicidal ideation showed non-significant differ-
ence in its incidence between the two groups (38% vs.
24% respectively). Similar result has been reported be-
fore [27]. Significant presence of autonomic symptoms
in amphetamine positive cases in addition to the positive
result of amphetamine in urine sample should draw the
attention of the psychiatrist to consider the ampheta-
mine-related psychosis beside the primary psychotic dis-
orders when dealing with the psychotic symptoms clini-
cally and therapeutically [20]. This concept is very im-
portant clinically as the psychiatrists may hospitalize the
patients unnecessarily and start the long-terms courses of
antipsychotic drugs that have the potential for serious
side effects [36-38]. It should be mentioned here that this
medical issue is not as simple as expected for the psy-
chiatrist to differentially diagnose the case of psychosis
if it is amphetamine related or functional especially there
is considerable variability in the dose of amphetamine
required and even the onset of psychotic symptoms [39].
Furthermore, the duration of psychotic symptoms is also
variable so that in Japanese group of psychotic patients
who were methamphetamine users, psychotic symptoms
persisted for more than a month in 41% of them [40].
In the present study, positive psychotic symptoms
were greater in amphetamine-related psychosis tan am-
phetamine negative group. This indicates that ampheta-
mine use possibly affects positive but not negative symp-
toms of schizophrenia [35]. The less prominence of
negative symptoms in amphetamine-related psychosis in
comparison with amphetamine negative psychotic group
may support the notion that substance use affects posi-
tive but may alleviate negative symptoms of schizophre-
nia [20,36,41]. Cigarette smoking has been found to in-
crease the positive symptoms in schizophrenia which
explains why 70 % or even more of patients with schizo-
phrenia in United States are nicotine dependents [36, 42].
In patients with psychoses, abnormal personality styles
are ascribed to possible alteration in the neurobiological
function of central neurotransmitters. In schizotypal per-
sonality disorder, an alteration in dopaminergic function
is suggested while disturbance in serotonergic activity is
suggested in subjects with borderline personality and
antisocial personality disorders [27,43,44]. The observa-
tion of different clusters of personality disorders in psy-
chotic Saudi patients irrespective amphetamine-related or
not coincides with literature data of expected personality
disorders in psychotic patients whether they were schizo-
phrenic or non-schizophrenic [45,46]. Although the psy-
chotic condition of many patients had stabilized before
assessment of personality disorders, the significant high
incidence of cluster B personality disorder especially
antisocial personality in amphetamine positive psychotic
patients (37%) raises the question of whether cluster B
disorder observed is just related to the psychotic element
or an extension to the acute amphetamine use. Previous
studies reported an association between amphetamine
use and both violence, and antisocial behavior of the
users [47,48].
This study is the first study that investigates the inci-
dence of amphetamine use in Saudi patients with first
episode psychosis. The one-third incidence of positive
samples for amphetamine among the studied Saudi pa-
tients raises the proposed question whether urine screen-
ing for possible drug abuse is necessary or not in patients
with first episode psychosis. Our findings in addition to
previous reports of the presence of substance misuse in
the majority of people with first-episode psychosis that
may have therapeutic implication [19,49,50] may support
urine screening for possible drug abuse among psychot-
ics. On the contrary, other investigators have not found
any effect of routine urine drug screening in a psychiatric
emergency service on disposition or the subsequent
length of inpatient stays. Their results did not support
routine use of drug screens in this setting [32]. In the
current Saudi study, assessment of the duration of stay in
the hospital for both amphetamine positive versus am-
phetamine negative cases was missing. This is a weak
point in our study that necessitates a further research to
check. Another weak point in the study is that we did not
assess the cost benefit relationship of routine screening
in diagnosis, treatment and decision of disposition of the
patient from the psychiatric emergency. The current
study has also some limitations. Although the clinical
condition of many patients had stabilized, some contin-
ued to have psychotic symptoms, which raises the ques-
tion of whether the personality disorder evaluations were
“colored” or not by the concomitant psychotic disorder.
Also, subjects with amphetamine related psychosis and
amphetamine negative psychosis must be followed up
carefully and undergo re-evaluation over time.
Conclusions: The incidence of amphetamine use in

106 Amphetamine Versus Non Amphetamine-Related First Episode Psychosis in Saudi Arabian Patients
Saudi patients with first episode psychosis is high. The
study supports the screening of urine for amphetamine
use in patients with acute psychosis. This laboratory
marker in addition to other clinical and demographic
parameters can help proper diagnosis. The diagnostic
distinction between amphetamine related psychosis and
other psychoses is critically important, because am-
phetamine psychosis requires a different management.
Further studies on wider scale and larger number of
Saudi psychotic patients are required to support our pre-
liminary results.
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