International Journal of Neuroscience

ISSN: 0020-7454 (Print) 1543-5245 (Online) Journal homepage: http://www.tandfonline.com/loi/ines20

Impact of psychosis in bipolar disorder during

manic episodes

Elionor Nehme, Sahar Obeid, Souheil Hallit, Chadia Haddad, Wael Salame &
Fouad Tahan

To cite this article: Elionor Nehme, Sahar Obeid, Souheil Hallit, Chadia Haddad, Wael Salame &
Fouad Tahan (2018): Impact of psychosis in bipolar disorder during manic episodes, International
Journal of Neuroscience, DOI: 10.1080/00207454.2018.1486833

To link to this article: https://doi.org/10.1080/00207454.2018.1486833

Accepted author version posted online: 11

Jun 2018.

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 Impact of psychosis in bipolar disorder during manic episodes

Elionor Nehme1, Sahar Obeid2,3,4, Souheil Hallit2,5,6,7,8, Chadia Haddad2, Wael Salame2,9, Fouad
Tahan1,2,*

1 Lebanese University, Faculty of Sciences, Beirut, Lebanon

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2 Psychiatric Hospital of the Cross, Jal Eddib, Lebanon

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3 Holy Spirit University, Faculty of Philosophy and Human Sciences, Kaslik, Lebanon

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4 Lebanese University, Faculty of Pedagogy, Beirut, Lebanon

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5 Lebanese University, School of Pharmacy, Beirut, Lebanon

6 Saint Joseph University, Faculty of Pharmacy, Beirut, Lebanon

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7 Holy Spirit University, Faculty of Medicine, Kaslik, Lebanon
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8 INSPECT-LB: Institut National de Sante Publique, Epidemiologie Clinique et Toxicologie, Faculty of
Public Health, Lebanese University, Beirut, Lebanon
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9 Lebanese American University, Faculty of Medicine, Byblos, Lebanon

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* Corresponding author: Souheil Hallit. Psychiatric Hospital of the Cross, P.O. Box 60096, Jall-Eddib,
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Lebanon. Cell: +96171199660. Email: souheilhallit@hotmail.com and Fouad Tahan. Souheil Hallit.
Psychiatric Hospital of the Cross, P.O. Box 60096, Jall-Eddib, Lebanon. Cell: +9613662885. Email:
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drfouadtahan@gmail.com

This work has been done in the frame of the “Behavioral and Cognitive Neuroscience Master 2
program”, Faculty of Sciences, Lebanese University.
ABSTRACT

Objectives: To evaluate the effect of psychosis on prognosis as measured by the course of a

manic episode, symptoms severity and time to remission and identify existing differences in
positive and negative symptoms between psychotic and non-psychotic patients.

Study Design: 40 bipolar patients presenting with a diagnosis of acute mania were enrolled (18
psychotic patients and 22 non psychotic patients) in this cross-sectional study. Subjects were

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required to complete two self-reported questionnaires, the Young Mania Rating Scale (YMRS)

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for manic symptoms, and Positive and Negative Symptoms Scale (PANSS) for psychotic

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symptoms. Rating scales were administered at baseline and then again after three weeks of
pharmacologic treatment.

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Results: There were no difference in socio-demographic characteristics between psychotic and
non-psychotic subjects. Psychosis was associated with higher scores on the YMRS and PANSS
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(increased symptoms severity), compared to non-psychotic patients. Both groups demonstrated
clinical improvement and remission, with scores amongst psychotic patients remaining higher.
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Groups were similar in symptomatology except with regards to psychotic symptoms (the content,
insight, delusions, hallucinations, grandiosity, poor rapport, unusual thoughts).
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Conclusion: Psychosis can be considered a severity index in bipolar disorder, with decreased
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severity and overall clinical improvement and remission taking place in response to
pharmacotherapy.
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Keywords: psychosis; mania; bipolar disorder; PANSS; YMRS.

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Introduction
The occurrence of psychosis in mood disorders is well established, with the prevalence of
psychotic symptoms and/or presentations being higher in manic episodes than in depressive
states1. Psychosis, defined as a profound disturbance of thought content (delusions) and sensory
perception (hallucinations) regularly occurs in bipolar disorder (BD) and has been associated
with decreased cognitive functioning (1), longer periods of active illness (2), and higher relapse
rate (3). Alternatively, a recent study by Demmo and colleagues found no association between
cognitive impairment and a history of psychosis (4). Psychosis occurs frequently during mood

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episodes in patients with BD, with studies demonstrating prevalence rates ranging from 20% to
50% in acute bipolar mania. Approximately 58% of patients with BD have a lifetime history of

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at least one psychotic symptom (5, 6). Fewer studies have examined the impact of psychosis on
pharmacologic treatment efficacy in patients with manic-depressive illness (3, 6).

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Manic symptoms vary between patients, with evidence suggesting that several factors and
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multiple dimensions influence manic symptoms including early age at onset and severity of
mania (7), family history of mental illness (8), treatments response (9), the disorder’s natural
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history and the stability of symptoms across episodes (10). Several studies in bipolar patients had
examined differences in outcome between patients presenting with or without psychosis (2, 7,
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11-13). Results presented by Canuso et al. suggest that psychotic symptoms were associated with
increased symptom severity (13). Nonetheless, evidence remains limited and existing literature
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on the impact of psychosis on the natural history and prognosis of BD remains inconclusive.
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The current study aims to investigate how psychosis influences the course of a manic episode,
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symptom severity and time to remission. The study’s secondary objective is to identify existing
differences with respect to positive and negative symptoms of psychosis in the presence and
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absence of psychosis.
Method
Study Design
The study is an observational cross-sectional study that was conducted between April and
August 2017 at Psychiatric Hospital of the Cross, the biggest psychiatric hospital in Lebanon.
Participants (n=40) were recruited from both inpatient wards and amongst subjects presenting to
the hospital for urgent admission. 18 subjects met the DSM-5 criteria for a diagnosis of Bipolar
Disorder (manic episode) with psychotic features while 22 subjects met the diagnostic criteria for
Bipolar Disorder without psychotic features.

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Ethical Aspect

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The Psychiatric Hospital of the Cross Ethics and Research Committee, in compliance with the
Hospital’s Regulatory Research Protocol, waived the need for an IRB approval taking into

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consideration that it was an observational study that did not involve any patient identifiers,
maintained individual autonomy and confidentiality, and was associated with minimal harm of
subjects.
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All participants were briefed on the study objectives and protocol, and written informed consent
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was obtained from each participant. Subjects received no financial or nonfinancial compensation
for their participation, and all individuals were preserved the right to refuse participation with no
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direct or indirect consequences.

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Participants

Subjects were considered eligible for participation irrespective of whether they were hospitalized
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for the first time or for relapse. Participants were interviewed using the Structured Clinical
Interview for DSM-5 Axis I Disorders (SCID) (14). Additional information was extracted from
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the patient’s medical records when needed.

Subjects had to meet the following inclusion criteria to be considered eligible for the study: 1)
meeting the criteria for a diagnosis of bipolar disorder- manic episode according to the DSM-5
and 2) age between 17 and 68 years. Gender was not considered in this study. Exclusion criteria
were: 1) previous diagnosis with any other psychotic disorders; 2) substance use/abuse over the
six-month period preceding the study; or 3) meeting a diagnosis of Substance/Medication-
Induced Bipolar and Related Disorders according to the DSM-5. Individuals were also excluded
if they had a previous diagnosis of BD currently experiencing a depressive episode, treatment-
emergent mania/hypomania, or bipolar symptoms induced by other medical conditions.

Each patient was interviewed two times, separated by a three-week interval during which the
patient was still hospitalized, in order to identify the efficacy of treatment in reducing symptoms.
The time to remission is defined as the period during which symptoms of psychosis are reduced
or disappeared according to the PANSS and the YMRS scales.

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By the end of the recruitment period, 28 patients were interviewed twice, the rest of the patients

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were discharged before 3 weeks of treatment.

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Procedures and Assessment Measurements

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Each participant was required to complete two questionnaires, the Young Mania Rating Scale
(YMRS) and the Positive and Negative Syndrome Scale (PANSS). Taking into consideration
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that participants were Lebanese natives, the questionnaires were conducted in Arabic. The
questionnaire was administered at baseline (prior to treatment) and then again after three weeks
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of continuous pharmacotherapy. Was divided into two sections, the first pertaining to socio-
demographic characteristics (age, gender, educational level) and past psychiatric history
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(previous psychiatric diagnosis/diagnoses, age of onset, number of previous episodes, family

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history of mental disorders). The second part of the questionnaire was comprised of the self-
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administered YMRS and the PANSS.

The YMRS is one of the most frequently utilized rating scales to assess manic symptoms. The
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test includes 11 items and is based on one’s subjective report of his/her clinical condition over
the previous 48 hours (15). The PANSS is usually used to assess symptom severity related to
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psychosis. The PANSS, previously validated in Lebanon (16), includes 30 items, including
positive symptom subscale items (P1-P7), negative symptom subscale items (N1-N7) and
General psychopathology symptom items (G1-G16) (17).

The CGI (Clinical Global Impression Scale) was also utilized and provides an overall clinician-
determined summary and measures the global functioning prior to and after initiating a
medication (18).
Statistical Analysis and Data Interpretation
Data analysis was conducted using SPSS software version 23. The independent-sample t-test was
used when comparing two groups. When two variables were correlated we used the paired
sample t-test. For categorical variables, the 2 were used when applicable. A p-value< 0.05 was
considered as significant.

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Results

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Table 1 shows the sociodemographic characteristics of the study population. Forty patients were
enrolled in the study, 18 presenting with psychotic features (45%) compared to 22 without.

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42.5% of subjects reported a family history positive for mental illness. The mean age of the study
group was 38.98 ± 12.39 years old, with the majority being males (77.5%). Most subjects
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reported the onset illness was 6.60 (± 9.34) year prior, with an average of 4 (± 3)
hospitalizations. No significant associations between gender, age, family history of mental
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illness, first episode of illness and number of prior episodes, and the presence of psychosis, was
determined (p > 0.05).
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A comparison between patients lost to follow-up and those who were not, showed that a higher
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percentage of patients not lost to follow up had a family history of psychosis compared to those
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lost to follow up (53.6% vs 16.7%; p=0.03). No significant difference was found between both
groups in terms of age, gender and presence/absence of psychosis (Table 2).
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Results from the YMRS at baseline are listed in Table 3. The presence of psychosis was
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associated with a significantly higher mean score on each of the content (6.22 vs 4.27; p=0.011)
and the insight subscales (2.94 vs 2; p=0.026) when compared to patients presenting without
psychosis. No significant associations was found between psychosis and any of the other YMRS
subscales.

Results from the PANSS subscales comparing the two groups are presented in Table 4.
Psychosis was associated with significantly higher occurrence of delusions (5.22 vs 3.14;
p<0.001), hallucinatory behavior (2.44 vs 1.36; p=0.028), grandiosity (4.56 vs 3.09; p=0.022),
poor rapport (2.36 vs 1.5; p=0.009) and unusual thoughts (4.39 vs 2.36; p<0.001) symptoms
when compared to nonpsychotic patients. No significant difference was found between the 2
groups for any of the other PANSS symptoms.

Table 5 displays the bivariate analysis for the PANSS and YMRS scores, comparing psychotic
and nonpsychotic patients from baseline to those after three weeks of treatment, there was a
highly significant reduction in all scales and subscales after 3 weeks (p<0.001 for all variables),
except for the PANSS negative symptoms (p=0.190).

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The presence of any correlations between scores on each of the YMRS and PANSS scales in

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patients with or without psychosis, at baseline and after 3 weeks, are presented in Table 6.

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Psychosis was associated with a significantly higher mean on both the YMRS and PANSS scales
at baseline (34.15 vs 27.32; p=0.013 and 86.69 vs 76.23; p=0.009, respectively) and after 3

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weeks (18.23 vs 12.73; p=0.044 and 65.00 vs 56.93; p=0.036 respectively). No significant
reduction in both scales was found after 3 weeks between patients with or without psychosis
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(p>0.05 for both variables).
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Table 7 displays results from the CGI scale demarcating illness severity and consequent
improvement in response to pharmacotherapy in the presence and absence of psychosis. Baseline
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analysis suggests that psychosis is associated with a significantly higher illness severity than is
BD in the absence of psychosis (83.3% vs 31.8%; p=0.009). Post-intervention analysis revealed
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no significant inter-group differences as measured by the CGI scale, with global improvement
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being comparable between the two groups (p>0.05).

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A family history of psychiatric illness was not associated with significant differences in the
YMRS, and there was no correlation between the presence of mental illness in the family and the
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reduction of psychotic symptoms as assessed by the YMRS (p-value = 0.536). However, there
was a correlation between the family history of mental illness and the reduction of PANSS score
(p-value =0.004).
DISCUSSION

Results from the current study involving psychosis in BD are similar to results of other, larger
studies demonstrating that a significant number of patients with BD experience at least one
psychotic symptom during a manic episode (2, 6, 19). According to Goodwin and colleagues,
approximately 58% of patients presenting in mania have experienced at least one psychotic
symptom (20). Few studies have examined the prognostic implications of psychotic features in
bipolar disorder. Several factors could play a role including genetic predisposition, the structure
of the brain, altered neurotransmission and functional connectivity, substance abuse, family

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history of BD, brain injury or brain infection, certain medications or withdrawal from some
medications (21-23).

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Results suggest that thought content, insight, delusions, hallucinatory behavior, grandiosity, poor
rapport and unusual thought as assessed by YMRS and PANSS scales were significantly higher
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in patients with psychosis. Similarly, Canuso et al demonstrated that BD when associated with
psychosis was correlated with a higher score at the six items of the PANSS scale : grandiosity,
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delusions, lack of judgement/insight, excitement, persecution and hostility (13). Coryell and
colleagues also demonstrated that psychotic manic episodes were associated with increased
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severity and longer duration (i.e., prolonged persistence) (2).

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Rosen et al. suggested that psychosis was associated with a significantly worse social outcome
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(12). Tohen et al. demonstrated that patients with psychotic compared to non-psychotic first
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manic episodes had poorer outcome (24). These authors demonstrated also that patients with
mood-incongruent psychotic symptoms were generally more severe than when psychosis was
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congruent to mood (25). Controversially, Goldberg et al. had shown that there was no significant
difference in the outcome between psychotic and nonpsychotic bipolar patients (26).

Psychotic symptoms are considered a typical manifestation of severe manic episodes (20, 27).
Goodwin showed that 35% to 60% of manic episodes were accompanied by grandiose delusions,
while 18% to 65% were associated with persecutory delusions, and 7% to 48% of patients
experienced auditory hallucinations, and 19% display formal thought disorder (20). Racing
thoughts, the flight of ideas, and distractibility can be present in up to 71% of patients with
mania (20). Hallucinations and delusions are common features of manic episodes, but tend to be
brief and fragmented, and often have grandiose, religious, or paranoid themes that typically
resolve early during recovery phase (11, 28). These symptoms may represent the most prevalent
psychotic symptoms in bipolar mania patients which grandiosity is a hallmark feature of mania
(13).

Psychosis was also associated with significantly higher symptoms and illness severity.
Consistently, Carlson et al (11) and Rosen et al (29) proposed that psychotic symptoms are

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indicative of the most severe stage of mania. Other studies demonstrated that the presence of

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psychotic symptoms during the first manic episode are indicative of poorer prognosis and higher

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relapse rates at 4 years (24, 30). Psychotic mood episodes may represent illnesses which are
more severe than non-psychotic mood disorders perhaps resulting from greater genetic

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vulnerability (27).

Our results showed that there is no correlation between the presence of family history of mental
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illness and the risk of developing psychotic symptoms in the context of mania, In opposite to
what’s found in the literature that the presence of a first-degree relative with a psychotic
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affective disorder (unipolar or bipolar disorder) increases the risk of developing psychotic
symptoms among bipolar patients (8). Subjects with a parent or sibling with BD are much more
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likely to develop BD compared with children who do not have a positive family history (8).
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Genetic and molecular factors may affect the presence of psychosis in manic patients (8). In
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addition, the family history of mental illness information were retrieved from medical file rather
than direct interview of family members which could lead to underdiagnoses of psychiatric
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disorders in families.
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Limitations
This study is limited by the small sample size, considering their stay in the hospital was too
short-lived. Twelve patients (30%) were lost to follow up, which might have influenced our
results. Our study was performed using a cross-sectional design, thus, cannot infer causality.
Future research using a longitudinal design to study the comparison between psychosis and non-
psychosis in bipolar mania patients should be conducted. Information bias cannot be excluded
since the questionnaire was a self-assessment one. In addition, we did not screen specifically for
the effect of medications in psychotic symptoms. The study was also constrained by the lack of
validation of YMRS in the Lebanese population with serious mental illness; future research
should aim at validating this scale. The importance of this study lies in the fact that it is the first
to be conducted in Lebanon to assess the impact of psychosis in bipolar disorder during manic
episodes.

Conclusion

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These findings confirm previous findings of the presence of psychotic symptoms in patients with

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bipolar mania. All types of psychotic symptoms could occur in mania but certain psychotic

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symptoms can be more common. Further research and efforts are needed to improve
symptomatic assessments of psychotic mania patients.

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Conflicts of interest: None declared.
Funding: None.
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Tables

Table 1. sociodemographic characteristics of the study population

General Absence of Presence of
population psychosis psychosis

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Frequency Frequency
Frequency (%) p-value
(%) (%)

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Male 31 (77.5%) 17 (77.3%) 14 (77.8%)
Gender 0.97
Female 9 (22.5%) 5 (22.7%) 4 (22.2%)
Family history of mental Absence 23 (57.5%) 14 (63.6%) 9 (50.0%)

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0.385
illness Presence 17 (42.5%) 8 (36.4%) 9 (50.0%)
Age 38.98 ± 12.39 37.64 ± 12.46 40.61 ± 12.47 0.653
First episode 6.60 ± 9.34
an 5.77 ± 8.68 7.61 ± 10.26 0.866
Number of episodes 4±3 4±4 3±2 0.974
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Table 2. Comparison between participants lost to follow-up and those who remained in the study
concerning the sociodemographic characteristics.
Variable Not lost to follow-up Lost to follow-up p-value
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Gender 0.411
Male 23 (82.1%) 8 (66.7%)
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Female 5 (17.9%) 4 (33.3%)

Family history of mental illness 0.03
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No 13 (46.4%) 10 (83.3%)
Yes 15 (53.6%) 2 (16.7%)
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Presence of psychosis 0.781

No 15 (53.6%) 7 (58.3%)
Yes 13 (46.4%) 5 (41.7%)
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Age 36.92 ± 11.79 43.75 ± 12.94 0.112

Table 3. Subscales of YMRS at baseline between patients having or not psychosis
Baseline of YMRS Presence of psychosis Absence of psychosis
p-value
Mean ± SD Mean ± SD
Mood 2.78 ± 0.73 2.36 ± 1.05 0.165
Energy 2.17 ± 0.79 2.18 ± 0.91 0.956
Sexual interest 1.83 ± 1.25 1.95 ± 1.29 0.766
Sleep 2.28 ± 1.13 2.23 ± 1.30 0.911
Irritability 3.67 ± 1.57 3.09 ± 1.31 0.314
Speech 5.22 ± 1.83 4.36 ± 1.32 0.159
Language-Thought 1.67 ± 0.97 1.77 ± 1.33 0.733
Content 6.22 ± 2.26 4.27 ± 1.34 0.011

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Aggressive behavior 2 ± 1.53 1.64 ± 1.35 0.556

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Appearance 1.56 ± 0.92 1.45 ± 1.36 0.713
Insight 2.94 ± 1.21 2 ± 1.37 0.026

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Table 4: Bipolar patients’ mean scores on the three PANSS subscales at baseline
Baseline of PANSS scale
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Presence of psychosis
Mean ± SD
Absence of psychosis
Mean ± SD
p-value
Positive symptoms
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Delusions 5.22 ± 1.86 3.14 ± 1.36 < 0.001
Disorganize Concept 3.17 ± 1.20 3.14 ± 0.83 0.926
Hallucinatory behavior 2.44 ± 1.85 1.36 ± 0.58 0.028
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Excitement 3.56 ± 1.29 3.77 ± 0.87 0.531

Grandiosity 4.56 ± 2.31 3.09 ± 1.19 0.022
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Suspiciousness/persecution 3.11 ± 1.60 2.5 ± 1.41 0.207

Hostility 2.28 ± 1.07 2.36 ± 1.18 0.813
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Negative symptoms
Blunted affect 2.33 ± 1.33 2.32 ± 1.29 0.971
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Emotional withdrawal 2.17 ± 1.25 2.18 ± 1.18 0.969

Poor rapport 2.36 ± 1 .14 1.5 ± 0.79 0.009
Social withdrawal 2.5 ± 1.38 2.64 ± 1.29 0.749
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Difficulty in abstract thinking 2.33 ± 1.28 2.59 ± 0.85 0.472

lack of spontaneity and flow of
conversation 2.06 ± 1.21 2.09 ± 1.15 0.925
Stereotyped thinking 3.11 ± 1.08 2.64 ± 0.90 0.138
General psychopathology symptoms
Somatic concern 2.22 ± 1.22 2.41 ± 1.56 0.681
Anxiety 4.94 ± 1.47 4.32 ± 1.49 0.192
Guilt feelings 2.11 ± 1.53 2.14 ± 1.42 0.957
Tension 2.94 ± 1.11 3.05 ± 1.25 0.791
Mannerisms and posturing 3.06 ± 1.55 2.86 ± 1.17 0.658
Depression 2.61 ± 1.61 2.45 ± 1.77 0.773
Motor retardation 2.89 ± 1.32 2.23 ± 1.23 0.11
Uncooperativeness 2.94 ± 1.30 2.68 ± 1.29 0.527
Unusual thought content 4.39 ± 1.79 2.36 ± 0.90 <0.001
Disorientation 2.22 ± 1.48 1.86 ± 0.83 0.34
Poor attention 2.33 ± 1.33 2.18 ± 1.10 0.695
Lack of judgment and insight 2.28 ± 1.41 2.45 ± 1.41 0.695
Disturbance of volition 2.61 ± 1.42 2.45 ± 1.47 0.736
Poor impulse control 3.28 ± 1.27 3.14 ± 1.25 0.726
Preoccupation 1.28 ± 0.46 1.27 ± 0.55 0.975
Active social avoidance 2.5 ± 1.10 2.18 ± 1.30 0.414

t
ip
Table 5: PANSS and YMRS scores in bipolar patients with psychosis at baseline, and after

cr
3 weeks of treatments
At baseline After 3 weeks

us
p-value
Mean ± SD Mean ± SD
YMRS 34.15 ± 7.22 18.23 ± 7.44 <0.001
Total PANSS 86.69 ± 6.48
an 65.00 ± 9.09 <0.001
Positive PANSS 25.15 ± 6.21 16.53 ± 5.30 <0.001
PANSS Negative PANSS 16.15 ± 4.09 14.15 ± 4.09 0.190
M
subscales General psychopathology
45.38 ± 6.18 34.30 ± 4.13 <0.001
PANSS
d

Table 6: Comparison between YMRS and PANSS scale in patients with or without
e

psychosis at baseline and after 3 weeks

Absence of Presence of
pt

psychosis psychosis p-value

ce

Mean ± SD Mean ± SD
At baseline 27.32 ± 3.73 34.15 ± 7.22 0.013
Ac

YMRS After 3 weeks 12.73 ± 4.06 18.23 ± 7.44 0.029

Reduction after 3 weeks 14.60 ± 5.69 15.92 ± 6.17 0.982
At baseline 76.23 ± 12.42 86.69 ± 6.48 0.009
PANSS After 3 weeks 56.93 ± 9.84 65.00 ± 9.09 0.036
Reduction after 3 weeks 19.3 ± 12.75 21.69 ± 9.53 0.853
Table 7: Association of CGI severity and improvement score between patients with or
without psychosis
Presence of
Absence of psychosis
psychosis p-value
Frequency (%) Frequency (%)
Mildly ill 2 (9.1%) 0 (0.0%)
Moderately ill 11 (50.0%) 2 (11.1%)
CGI at baseline 0.009
Markedly ill 7 (31.8%) 15 (83.3%)

t
ip
Severely ill 2 (9.1%) 1 (5.6%)
Mildly ill 8 (53.3%) 3 (23.1%)

cr
Moderately ill 6 (40.0%) 8 (61.5%)
CGI after 3 weeks 0.108

us
Markedly ill 0 (0.0%) 0 (0.0%)
Severely ill 0 (0.0%) 0 (0.0%)
Minimally
improved
an
5 (33.3%) 5 (38.5%)
Global improvement 0.782
M
Highly
10 (66.7%) 8 (61.5%)
improved
e d
pt
ce
Ac