The Integration of Olanzapine and Cognitive Behavioural Therapy for the Treatment of Schizophrenia: A Literature Review
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UNDERGRADUATE RESEARCH IN NATURAL AND CLINICAL SCIENCE AND TECHNOLOGY (URNCST) JOURNAL
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REVIEW OPEN ACCESS
The Integration of Olanzapine and Cognitive Behavioural
Therapy for the Treatment of Schizophrenia: A Literature
Review
Raymond Tolentino, BHSc Student [1]*, Aoife McMahon, BSc Student [2]
[1] Department of Health Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4L8
[2] Department of Biomedical Sciences, University of Guelph, Guelph, Ontario,
Canada N1G 2W1
*Corresponding Author: tolentr@mcmaster.ca
Abstract
Introduction: Schizophrenia is a serious psychiatric disorder that significantly impacts a person’s quality of life. This
condition is characterized by three groups of symptoms: positive, negative and cognitive. There have been developments of
new therapeutic methods for treating schizophrenia, both pharmacological and psychotherapeutic. Antipsychotic drugs such
as the second generation antipsychotic olanzapine are often the first course of treatment, for the purpose of controlling
symptoms. However, research has determined that using antipsychotics alone may limit its long-term effectiveness and
produce adverse effects. Psychosocial interventions like cognitive behavioural therapy (CBT) aim to reduce psychotic
symptoms and prevent relapse when used in conjunction with medication. This review aims to discuss the effectiveness of
the integration of olanzapine and CBT, and how these treatments improve symptom reduction, reduce relapse and reduce the
occurrence of adverse effects.
Methods: A literature search between the years of 2010 to 2020 was conducted using PubMed and PsycInfo. Keywords
included variations of “schizophrenia”, “treatment”, “olanzapine”, and “cognitive behavioural therapy”.
Results: Olanzapine by itself was found to improve symptom reduction, yet showed adverse effects such as weight gain and
extrapyramidal symptoms. CBT used as a lone treatment of schizophrenia showed less adverse effects than antipsychotics,
yet was significantly less effective than both antipsychotics alone and the combinatorial treatment of CBT and olanzapine.
The integration of olanzapine and CBT demonstrated an overall improvement in a schizophrenic patient’s health.
Discussion: The integration of olanzapine and CBT show promise for symptom reduction, relapse prevention, reduced
occurrence of adverse side effects, and the overall improvement of one’s health.
Conclusion: Individuals diagnosed with schizophrenia experience emotional, physical and social hardships, thus it is
imperative that physicians are aware of current treatments that can be tailored to best treat their patients.
Keywords: schizophrenia; treatment; olanzapine; cognitive behavioural therapy
Introduction that suggests that men are more likely to have early-onset
Schizophrenia is a serious psychiatric disorder, schizophrenia than women, particularly in young adulthood
affecting approximately 1% of the world’s population and [3]. Despite the extensive studies done in the field of
significantly impacting a person’s quality of life [1]. This schizophrenia and countless treatment options discovered, a
disabling condition is commonly characterized by three cure has yet to be found [4]. There have been vast
groups of symptoms: positive, negative and cognitive. developments over the years outlining new therapeutic
Positive symptoms include the presence of superimposed methods for treating schizophrenia, both pharmacological
behaviours, such as hallucinations and delusions [2]. and psychotherapeutic. Together, these methods of treatment
Negative symptoms represent the inability or absence of a aim to not only relieve the symptoms of schizophrenia, but
normal function, such as poverty of speech and a lack of to also increase the patient’s quality of life [3].
pleasure [2]. Cognitive symptoms fall under a new category, There have been various pharmacological interventions
including disorganized thoughts and difficulties with that have been prescribed for the treatment of schizophrenia
memory [2]. Schizophrenia is commonly diagnosed in including antipsychotics, antidepressants, and tranquillizers
patients who are in their late teens or early adulthood; [5]. The most commonly prescribed medication between the
however, diagnosis is not uncommon for patients in their years of 2000-2015 among pharmacological treatments was
middle ages [3]. There is an increasing amount of evidence antipsychotics, which was administered to 94.8% of patients
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in an observational study conducted by Toto et al. in 2019 adverse effects were found to be associated with these two
[5]. Antipsychotic drugs are often the first course of drugs [16]. Studies comparing these two antipsychotics
treatment, as patients usually experience positive symptoms found that olanzapine is more effective at treating negative
first, which need to be controlled [6]. Thus, during early symptoms and decreasing the overall clinical severity of
onset of the disease, treatment with antipsychotic drugs schizophrenia [16,17,18,19]. Adverse effects including
results in significant symptom reduction of hallucinations weight gain, hyperlipidemia and hyperglycemia were
and delusions [6]. comparable with both groups and did not show significant
A class of antipsychotic drugs that have been most variation [16]. Further studies show the superior efficacy of
commonly used are second-generation antipsychotics (SGA). olanzapine compared to other antipsychotics, based on its
This class of medication has been succeeded by first- high adherence and improvement of the Positive and
generation antipsychotics (FGA), and are found to be more Negative Syndrome Scale (PANSS) and Brief Psychiatric
effective in terms of improving cognitive function [7] and Rating Scale (BPRS) [20]. The PANSS is a 30-item scale
their association with fewer extrapyramidal symptoms [8] used to measure the severity of symptoms for individuals
when treating schizophrenia. These extrapyramidal diagnosed with schizophrenia [21], while the BPRS is a
symptoms are characterized as drug-induced movement 24-item scale used to measure psychiatric symptoms,
disorders, which can include motor restlessness [9]. The including depression, anxiety and hallucinations [22].
American Psychiatric Association (APA) also notes that Previous research has determined that using
SGAs, with the exception of clozapine, are the first-line of antipsychotics as a treatment alone may limit their long-
treatments for schizophrenia [8]. term effectiveness and produce further adverse effects [4].
FGAs are D2 antagonists, which means they work by In an empirical study conducted in 2013 by Valenica et al.,
blocking only the dopamine D2 neuroreceptor [10]. This is patients who received antipsychotic treatment combined
in contrast to SGAs, which typically function by blocking with psychosocial interventions, specifically social skills
both the dopamine and serotonin receptors, specifically the training, showed a higher symptom reduction rate
D2 dopamine and 5HT2A receptors, respectively [10]. A compared to those prescribed antipsychotics alone [23].
blockage caused by these SGAs would impact serotonin’s Psychosocial interventions are interpersonal activities that
roles in behaviour and motor activity, as well as involve educating the patient on their disorder, and the
dopamine’s involvement in motor function, emotion and importance of medication adherence, family involvement
cognition [10]. The inhibition of downstream signaling and counselling, social skills training, and cognitive
pathways by both classes of medications results in the behavioural therapy (CBT) [24]. Like antipsychotics, the
reduction or prevention of psychotic symptoms. particular psychosocial interventions used in a patient’s
The use of SGAs significantly increased from 2005 treatment plan should be tailored to the patient’s needs and
(62.5%) to 2010 (88.9%), due to various studies that showed preferences. Of these methods of psychotherapy, CBT has
they were more effective than FGAs [5]. The most common received much attention due to having a strong evidence
SGAs according to their prescription rates found in 2015 base for treating schizophrenia [25]. CBT is a highly
were clozapine (21.3%), olanzapine (20.7%), risperidone effective psychotherapeutic treatment for psychological
(17.7%) [5]. All three oral medications display antipsychotic disorders, dating back to the early 1950s where it was used
efficacy; however, adverse effects and neurophysiological to treat depression and anxiety [26]. CBT as a method of
activities vary between each medication. treating schizophrenia has been proven to ameliorate both
Clozapine was one of the first SGAs to be approved by positive and negative symptoms of the disorder, and reduce
the FDA in 1990 [11]. The drug was developed as an the chance of patient relapse [26]. When CBT is used as an
alternative option to then-current treatments for adjunct to pharmacotherapy, this course of treatment aims
schizophrenia such as chlorpromazine, due to their to reduce symptom relapse and increase antipsychotic
involvement in causing movement disorders [12]. Recent adherence [25]. A review conducted by Rector and Beck in
research has described clozapine to be a third-line treatment 2012 determined that patients undergoing CBT in
or to be used for treatment-resistant patients, due to the conjunction with pharmacotherapy demonstrated a greater
serious adverse effects associated with it [13]. These reduction of negative symptoms and patient relapse,
adverse effects include but are not limited to: compared to those who underwent pharmacotherapy alone
agranulocytosis, seizures, myocarditis, and respiratory and [26]. CBT involves various self-help and coping strategies
cardiac arrest [12,14]. Due to its status as a third-line with the patient’s illness, cognitive restructuring, and reality
treatment and its abundant amount of adverse effects, testing, with the overall goal being to develop healthier
clozapine as a method of treating schizophrenia will not be ways to manage their diagnosis [26]. CBT encourages
a focus in this review. social integration with a community, partaking in regular
Olanzapine and risperidone are considered to be first- exercise, and helps reduce suicidal ideation and other
line medications for schizophrenia [15]. Both drugs were violent thoughts and behaviours [24,27].
found to have similar beneficial effects in terms of This review aims to discuss current therapies that have
improvement of symptoms; however, minor variations of been shown to improve the overall treatment response
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outcome for schizophrenia, in the context of symptom those who had not received antipsychotics in 6 months, but
reduction, reduced relapse and reduced occurrence of were still receiving usual care [33]. It was also noted that
adverse effects. The effectiveness of using either CBT or CBT alone was significantly less effective than the
olanzapine as a method of treating schizophrenia, compared combinatorial treatment of CBT and antipsychotics [33].
to their combined use will be explored. Lastly, this review
will explore the advancements and limitations of these two Integration of Olanzapine and CBT
types of interventions that have been made throughout the The combined treatment of antipsychotics and CBT
last decade. demonstrated a reduced amount of adverse effects, a
reduction in relapse rate, a greater symptom reduction,
Methods treatment adherence, and an overall greater quality of life
A qualitative literature search was conducted using [34,35,36,37]. One study found a significant 7% lower
databases, PubMed and PsycInfo. Reports between the patient relapse rate in the combined intervention group, in
years of 2010 to 2020, with language restricted to English, comparison to the medication-only group [35]. This
were included and examined. Further criteria for inclusion improvement in symptom reduction was demonstrated
were as follows: i) patients between the ages of 16-64 within the improvement in the PANSS score [34,35,37].
diagnosed with early-onset schizophrenia characterized by
non-severe symptoms, ii) intervention includes cognitive Discussion
behavioural therapy, second-generation antipsychotics, Information on the treatment for schizophrenia, both
specifically olanzapine or a combination of both, and iii) pharmacological and psychosocial, is vast and extensive.
has the outcomes of symptom reduction, relapse prevention, This can be seen as overwhelming for both care providers
reduced occurrence of adverse side effects and overall and patients, where it may be difficult to establish a
improvement of one’s quality of life. treatment plan. SGAs are considered by the APA as the
Keywords included variations of “schizophrenia”, first-line of treatment for schizophrenia; however, the list of
“treatment”, “olanzapine”, and “cognitive behavioural SGAs is widespread [8]. This literature review aims to
therapy”. The process of data extraction was performed by provide a reference and basis for a combination of
the authors and was managed through a spreadsheet that psychosocial and pharmacological interventions, and its
outlined the articles and corresponding data. associated data which describes its effectiveness. The
combination of olanzapine and CBT as a treatment for
Results schizophrenic patients was found to demonstrate a reduction
Through the database search, 145 articles were in symptoms, adverse effects, and rate of relapse [34].
identified through the given inclusion criteria. After Additional psychiatric comorbidities are prevalent in
removing duplicates and reviewing the titles, 90 articles schizophrenic patients. The majority of studies took
remained. After reviewing the abstracts with the application depression and anxiety into account [30,31,33,34,36], while
of the exclusion criteria, 18 articles remained. Following other studies specified other comorbidities as part of their
screening the full-text articles, 10 studies were included and exclusion criteria [29,35,37]. Two studies had no indication
utilized for data collection and analysis. of any psychiatric comorbidity [28,32]. These comorbidities
serve as an external factor that may influence the overall
Olanzapine treatment outcome. It is understood and demonstrated that
Olanzapine demonstrated a vast improvement in every patient is different, and the treatment plan in which
symptom reduction as described by the PANSS and BPRS they are assigned will be unique according to their needs.
scales [28,29,30,31]. However, common adverse effects Thus, creating a specific treatment plan for each patient is
that were mentioned were significant weight gain vital for optimal treatment outcomes. It is important for care
[29,30,31] and extrapyramidal symptoms [31]. In addition, providers to have a reference base of the limitations and
the study by Jones et al. in 2015 found that olanzapine efficacy of the current medications and/or interventions in
resulted in reduced relapse and hospitalization, which was tailoring a treatment plan for their patients.
demonstrated before and after follow-up (8.3% vs 32.6%, A search of available treatments for schizophrenia
respectively) [32]. showed that olanzapine and CBT were ranked as one of the
best antipsychotic medications [5] and psychosocial
CBT interventions [25], respectively. As these two treatment
It was determined that CBT showed less adverse methods are individually successful, this review focuses on
effects than those who took antipsychotics, or a the possible outcomes of the integration of these two
combination of antipsychotics and CBT [33]. Two adverse treatment options. As previously mentioned, olanzapine
events occurred in the CBT group; one attempted overdose, provides a significant reduction of negative symptoms and
and one patient posed as a risk to others [33]. No other decreases the overall severity of schizophrenia [16,17,18,19].
adverse effects were observed [33]. The PANSS scores Recent literature investigating olanzapine’s recommended
were consistently lower in the CBT group, compared to dosage of 10 mg/day has determined that a lower dose, a
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reduction of 50%, has a higher response rate and study by Birur et al. in 2016, schizophrenic patients
improvement of negative symptoms in schizophrenic being treated with olanzapine observed a mean weight
individuals [38]. In addition, there has been an increased gain of 2 kg and incurred a significant number of
amount of research and trials conducted on this drug, with extrapyramidal symptoms [31]. It’s also important to note
studies investigating and comparing its efficacy and amount that using CBT in conjunction to antipsychotic treatment
of adverse effects with other antipsychotic medications has been determined to be less effective when the patient
[28,29,30]. Overall, olanzapine has remained quite consistent does not view themselves as having a mental health
over the past decade, with additions in terms of evidence and problem [42].
research, such as the impact of dose reduction [38]. As there are countless antipsychotic medications with
Similarly, CBT has proven to improve both negative various efficacies and side effects to treat schizophrenia,
and positive symptoms of the disorder and reduce patient care providers must create a comprehensive treatment plan
relapse [26]. CBT has not varied in relation to practice and that is tailored to the individual’s condition and needs.
method, as it is already such an adaptive form of treatment When creating a treatment plan, it’s necessary for the
with set guidelines [39,40]. Through the data and clinician to take into consideration the patient’s potential to
preliminary evidence described by Morrison et al. in 2018, incur adverse effects, as well as non-adherence [8]. Shared
it has been suggested that CBT may be advantageous for decision making (SDM) is a treatment approach which
individuals experiencing psychosis who choose to not take allows patients to have a more active role in the decision of
antipsychotic medication [34]. In addition, there have been their treatment, whilst collaborating with their clinician
recent explorations in terms of the integration of both [43]. Both the clinician and the patient must be committed
olanzapine and CBT. Based on the data extracted and to the SDM approach, with the patient being open and
analyzed from the literature review, it was found that the honest during consultations, and the clinician willingly
integration of olanzapine and CBT effectively reduced the sharing the responsibility of creating the treatment plan
positive, negative and cognitive symptoms of schizophrenia [43]. The patient’s preferences can be accounted for by
[34,35,36,37]. Morrison compared the effectiveness of CBT using stated-preference methods, such as surveys and
to various antipsychotics, such as olanzapine, for the discrete-choice experiments (DCE) [44]. These DCEs
treatment of schizophrenia [33,34]. Morrison’s main provide patients with a list of hypothetical treatment
findings were that CBT alone had less adverse effects than options, from which they can select their preferences [44].
antipsychotics or the combinatorial group; however, In a statistical analysis conducted by Levtain et al. in 2015,
antipsychotics integrated with CBT was significantly more 301 schizophrenic patients who completed a DCE indicated
efficacious than CBT alone [33,34]. Current literature that a reduction in positive symptoms is the most important
describes that a combination of psychosocial interventions outcome of their treatment [44]. This importance in the
and pharmacological treatments are best when treating reduction of positive symptoms provides insight into the
schizophrenia [41]. The integration of olanzapine and CBT surveyor's preferences, and it allows their physician to take
further emphasizes this claim, as the combination has this into consideration when collaboratively creating the
shown a greater reduction in symptoms, adverse effects, patient’s treatment plan.
and rate of relapse when compared to one treatment alone Due to the nature of the data and the overall concept of
[34]. this review, there are some limitations that are important to
Although olanzapine is associated with a limited consider. A limited number of articles were yielded during
number of adverse effects in the treatment of schizophrenia, the literature search and selection process. This can be due
these antipsychotics are associated with an increased risk of to the 10-year restriction that was imposed during the
weight gain, obesity and cardiovascular diseases [37]. The selection process. However, based on this finding, it can be
Superwellness Program conducted in 2017 assessed the argued that there has not been much research on this topic
effect of a CBT-based intervention on the weight gain of within the past decade. Due to this lack of data, additional
patients who were prescribed antipsychotics, namely research and examination are needed for the combinatorial
olanzapine, compared to those receiving treatment as usual treatment of olanzapine and CBT, in order to better
[37]. The results of this study revealed that the integration understand its effectiveness and interaction with one
of CBT had decreased the individuals’ body mass index another. Another limitation that was identified during the
(BMI) by 0.6 kg/m [2], whereas those who did not undergo literature review was the use of strictly CBT-only treatment
CBT had shown an increase in their BMI levels [37]. This for schizophrenia; as it’s uncommon for antipsychotics to
study determined that the longer the patient had been not be prescribed to a schizophrenic patient, there was a
diagnosed with schizophrenia, the less of an impact CBT low yield of articles for CBT-only treatment [8]. CBT-only
had on reducing BMI levels [37]. Thus, the decrease in treatment is mainly associated with psychiatric conditions,
BMI levels due to the integration of CBT with regular such as depression and anxiety [26]. When used in
antipsychotic treatment may reduce the risk of obesity, as conjunction with antipsychotics to treat schizophrenia, CBT
well as cardiovascular disease, particularly when integrated primarily aids in the reduction and management of
into treatment at the early stages of diagnosis [37]. In a symptoms [25,26]. In the review by Pontillo et al. in 2016,
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CBT reduces the perceived power of voices due to Authors' Contributions
schizophrenia, but not the actual experience of voices [45]. RT: made substantial contributions to the design of the
Additionally, there is no standardized treatment plan for study, collected and analysed data, drafted the manuscript,
schizophrenia in terms of which medication or psychosocial and gave final approval of the version to be published.
intervention a patient should be prescribed. Treatment AM: made substantial contributions to the design of the
programs are ever-changing, emphasizing the existence of study, collected and analysed data, drafted the manuscript,
second- and third-line medications as patients can become and gave final approval of the version to be published.
treatment-resistant [46]. Psychiatrists can either add,
modify or switch medications if they see the efficacy of the Acknowledgements
drug declining, or if no response is evident [47]. This The authors gratefully acknowledge their colleague and
further emphasizes the fact that schizophrenia is a multi- mentor, Sumeya Mukhtar for her support and guidance.
faceted and complex disease, where treatment plans are
tailored to the patient’s needs. Funding
This study was not funded.
Conclusion
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Article Information
Managing Editor: Jeremy Y. Ng
Peer Reviewers: Sumeya Mukhtar, Sonya Kouthouridis
Article Dates: Received Nov 03 20; Accepted Dec 21 20; Published Jan 18 21
Citation
Please cite this article as follows:
Tolentino R, McMahon A. The integration of olanzapine and cognitive behavioural therapy for the treatment of
schizophrenia: A literature review. URNCST Journal. 2021 Jan 18: 5(1). https://urncst.com/index.php/urncst/article/view/213
DOI Link: https://doi.org/10.26685/urncst.213
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