Prescribing Trends in Schizophrenia Final

Prescribing Trends in Schizophrenia: Literature Review
Prescribing Trends in Schizophrenia: Literature Review
This study will seek to investigate first episode schizophrenia. It will explore the trends in
prescribing for schizophrenia as well as how “evidence-based medicine” has influenced
decision-making for schizophrenia treatment. To achieve this, research evidence, clinical
expertise/experience, patient values, and organizational issues affecting decision-making, in a
prescription for schizophrenia, will be adequately addressed.
Review of Literature
Schizophrenia is a critical disease affecting the brain and requires special attention. The
choice of treatment method that is antipsychotic treatment is a crucial issue challenging
schizophrenia treatment (Edlinger et al., 2009). Edlinger et al. (2009) carried out a study to
investigate various factors affecting decision-making in an antipsychotic prescription for
treatment of schizophrenia. The study took place in Innsbruck where 108 patients (both in and
outpatients) were the respondents. The main factors investigated in the survey include
“sociodemographic and illness-related variables, pre-treatment, the reasons for the change of
treatment (lack of efficacy, side effects, non-compliance), side effects of pre-treatment and body-
mass-index (BMI)(Edlinger et al., 2009, p. 246). From the study, it was evident that socio-
demographic as well as other “illness-related variables had no influence on physicians’ decision-
making on the choice of treatment for schizophrenia.
Another study done by Heres et al. (2011) tried to demonstrate the several factors that
affect decision-making in an antipsychotic prescription for First-Episode Patients (FEP). The
survey involved 198 participants, who were “psychiatrists attending the congress of the German
Society of Psychiatry, Psychotherapy, and Nervous Diseases (DGPPN) held in November 2008
(Heres et al., 2011, p. 297). The results indicated that the participants reported 3 out of the 12
factors used in the study. These factors were “rejection of the offer by FEP,” lack of prior
exposure to relapse and inadequacy of the of the Second Generation Antipsychotics (SGA) depot
drugs (Heres et al., 2011, Pp. 298-299). The survey provides the factors mentioned above as the
original statements influencing psychiatrists’ choice of treatment to administer to First-Episode
Patients. Implications from the study are that, instead of making assumptions of patients’ likes
and dislikes, psychiatrists should prefer depot treatment as the standard and routine choice for all
patients including FEP.
Additionally, to comprehend the several trends in schizophrenia and this has affected the
choice of a prescription; numerous scientific studies have been carried out on the subject matter.
Quality Prescribing for Schizophrenia
Patel et al. (2014) did a study to elaborate on the audit done by the National Audit of
Schizophrenia (NAS) in England and Wales. This audit examined the clinical guidelines in place
for schizophrenia in the in England and Wales. The audit was done 5055 schizophrenia patients
where most of them attested to pharmacological treatment that was by the stipulated national
guidelines. However, despite these positive remarks, it was found that at least 15.9% of the total
sample (95%CI: 14.916.9) were prescribed two or more antipsychotics concurrently
and10.1%ofpatients (95%CI: 9.310.9) were prescribed medication in excess of recommended
limits” (Patel et al. 2014, p. 499). Similarly, the results of the audit proved that 23.7% of the
patients under study received clozapine. These findings gave a chance for UK to be compared
with other countries like the equivalent US guidelines on clinical/pharmacological treatment
(Patel et al., 2014). They also gave the implication that professionalism needs to be enhanced
among mental health practitioners. A study done by Ho et al. (2011), demonstrates why it is
significant to uphold professionalism in the mental health field. The study proved that prolonged
use of antipsychotics significantly influences the brain volumes. The long-term use of
antipsychotics was “associated with a greater decrease in brain tissue volumes” (Ho et al., 2011,
p. 134). These results could contain substantial implications concerning the clinical decision-
making on prescribing for schizophrenia.
The use of antipsychotics treatment has both positive and negative results. In their study,
Edlinger et al. (2009) demonstrated “persistent positive and negative symptoms” evident in
“First-Episode Patients” (p. 246). Similarly, Patel et al. (2014) explain the emphasis placed on
adequate trials of both antipsychotics and clozapine in schizophrenia treatment, by both UK and
US guidelines. It is, therefore, paramount for more studies to be done exploring the quality of
prescribing for antipsychotics as well as clozapine in the quest to manage schizophrenia in the
Clinical Expertise/Experience and Guidelines
Several studies have been done to relate “clinical expertise/experience” with respect to
decision-making on prescribing for schizophrenia. A study by Ito, Koyama and Higuchi (2005),
provides evidence that due to their experience, psychiatrists have a perception towards the use of
drugs for the treatment of schizophrenia. The study included “139 patients with schizophrenia, in
19 acute psychiatric units in Japanese hospitals, who were due to be discharged between October
and December 2003 (Ito, Koyama & Higuchi, 2005, p. 243). The results of this study were that
only 27% of the participants were on preferred or standard dosage; 73% were not on a typical
dosage. Among the 27%, 78% were on atypical antipsychotics while for the 73%, 94% of them
were using more than one drug” and at least 33% of them were on an excessive dosage
prescription (Ito, Koyama & Higuchi, 2005, p. 244). From the results, it was evident that
“psychiatrists’ perceptions of the use of algorithms and nurses’ requests for more drugs, as well
as the clinical variables of the patients” are the main contributors to excessive antipsychotic
dosage (Ito, Koyama & Higuchi, 2005, p. 245). It is clear that despite the elaborate guidelines
provided by clinical experts in the mental health field, the practitioners ignore them and apply
their experience perceptions to give non-standard treatment to patients; using their judgment and
expertise to make a decision on treatment choice.
A book by Taylor, Paton and Kerwin (2005) elaborates the guidelines providing essential
advice to the clinician, in prescribing treatments for schizophrenia, in the UK and other
countries. The book gives an excellent explanation of the national guidelines in the UK, which
are also applicable in other nations. These guidelines play a crucial role in clinical decision-
making. A study by Warnez and Severini (2014) investigates the efficiency/effectiveness of
clozapine in refractory schizophrenia treatment. The study used “publications in the last 10-year
period (2004 and 2014)” which were obtained from PubMed, Psychinfo, EMBASE and
Cochrane databases(Warnez and Severini, 2014 p. 2). The findings from this study indicate
underutilization of clozapine, despite the primary emphasis of its use by the clinical guidelines.
This creates the implication that more research needs to be done to provide adequate and reliable
evidence for the effectiveness of clozapine, which will erase the fears by psychiatrists that the
treatment may cause severe side effects.
Trends in Prescribing for Schizophrenia
Over the years, there has been a dramatic increase in the use of antipsychotic drugs
especially in developed states such as UK and US. A study carried out by Pincus et al. (1998)
was geared at investigating how the increased recommendations for psychotropic medication
have influenced the prescribing patterns. The study utilized available data to investigate the
changes between the year 1985 and 1995. To achieve this, Pincus et al. (1998) used information
from “National Ambulatory Medical Care Surveys conducted in 1985, 1993 and 1994” (p. 526).
These surveys took place in the United States. From the surveys, it was noted that there was a
significant increase in the number of patients, going for psychotic medication, by 12.91 million,
which was “from 32.73 million to 45.54 million(Pincus et al., 1998, p. 528). In 1985, females
comprised 67.1% of the total visits for treatment while in 1994; the percentage of females going
for the medication was 64.1%. The number of those with 18 years and below increased from
1.10 million to 3.78 million. These results were evident due to the following recommendation for
various medications to manage schizophrenia.
A study by Siris et al. (2001) demonstrated the standard clinical practices as well as
prescribing trends in schizophrenia. The research took place in the US, Canada, Europe, and
Australia were around 80, 000 participants were involved. The researchers issued questionnaires
with 48 items that were fixed and open questions. There were 37,513 participants chosen in the
USA, 43,454 in Canada, and others in Europe and Australia who received the questionnaires.
From the USA, 1,128 members responded; of whom were all psychiatrists. Responses to
questionnaires regarding treatment approaches and care scenarios demonstrated that the level of
adjunctive prescribing of antidepressants in the USA is often higher than other regions,” (Siris et
al. 2001, p. 185).
Clark et al. (2002) carried out a study to investigate the implications of the trends in
antipsychotic combination therapy. The study focused on Medicaid pharmaceutical claims for
“836 new Hampshire beneficiaries with schizophrenia or schizoaffective disorder” in the year
1995-1999 (Clark et al., 2002, p. 75). Information was obtained from 1995 Medicaid claims and
was to come up with the focused group. Out of the 836 participants, 237 had schizoaffective
disorder while 599 had schizophrenia. Above 51.2% of the “599” group and 46% of the “237”
were males. From the study, it was evident that there was a significant increase in prescription of
antidepressants over the study period (5 years). The results indicated an increase of 57% in the
number individuals taking more than one antipsychotic drug. Subsequently, atypical
antipsychotics and the traditional neuroleptics realized a more than double increase in use
between 1995 and 1999. Additionally, by December 1999, around 4% of the total 836
participants took a combination of atypical antipsychotics and neuroleptics (Clark et al., 2002).
From the study, it was evident that combination treatment was more recommended to minimize
side effects and maximize efficacy. These are examples of factors influencing the choice of
therapy to apply to the management of schizophrenia patients.
Other studies have also been done on the antipsychotic prescribing trends for
schizophrenia. Verdoux, Tournier and Begaud (2010) carried out research, which aimed at
exploring the trends in antipsychotic drugs’ prescription. They researched for articles from peer-
reviewed journals that had original published studies in English, with samples from a real
population and done between 2000 and July 2008. Also, they considered studies done after the
introduction of Second Generation Antipsychotics (SGAPs) in US, Canada, Australia, and
Europe as well as prescribing trends with a minimum of two estimations. All studies used in the
assessment demonstrated a moderate increase in antipsychotic prescriptions (Verdoux, Tournier
& Begaud, 2010, p. 6). The study recognized international guidelines as one of the main
contributors to the increased use of SGAPs as the conventional treatment. Similarly, there was
the factor of the need for lengthened period of therapy, as evident in researches done in United
Kingdom (Verdoux, Tournier & Begaud, 2010). The other factor influencing the use of
antipsychotics was found to be the current “extension of licensed indications obtained for”
various second-generation antipsychotics (Verdoux, Tournier & Begaud, 2010, p. 8). According
to Verdoux, Tournier & Begaud (2010), the increasing “proportion of off-label prescriptions” of
the antipsychotic drugs was also a factor leading to their increased usage (p. 8). However, despite
the tremendous increase in the antipsychotics (APs) users, there is a call for concern due to the
observed side effects from AP use in psychiatric treatment (Verdoux, Tournier & Begaud, 2010).
Therefore, it is crucial for clinical expertise to address the issue of side effects from APs.
A study was done by Hayes et al. (2011) aimed at investigating the dynamic prescribing
patterns for psychiatric medication in primary care. The study took place in the United Kingdom
and involved 4,700 patients (participants). The participants were patients in the primary care
database provided Health Improvement Network (THIN) (Hayes et al., 2011). These patients had
received treatment for a psychiatric disorder (bipolar disorder) in the year 1995 and 2009. The
research focused on the period in which participants was prescribed to a particular medication, as
well as their ages, sex, and social status. 40.6% of the participants were under the prescription of
more than one AP drugs in 1995. This percentage increased to 78.5% in the year 2009. An
overall proportion of 26.4% increase was identified; this was an increase in the time utilized on
any AP medication between the year 1995 and 2009 (Hayes et al., 2011, p. 3). The study also
examined time spent on other treatment (mood stabilizers) where an increase of 29.9% was
observed. According to Hayes et al. (2011), the increase was mainly for females in both types of
medications investigated. The research supported that the prescribing trend was as a result of
licensing and guidelines factors. This signifies that the two factors play a crucial role in the
decision-making regarding psychiatric treatment.
Decision-making on prescriptions for schizophrenia is a broad topic that has attracted
numerous studies. These researches have been geared towards the investigation of the recent
trends in prescribing for antipsychotics. Harrison et al. (2012) carried a unique study that aimed
at exploring the “prescribing trends” on “antipsychotic medication” among “children and
adolescents” (p. 139). The research was geared towards explaining the dramatic increase in the
antipsychotic treatment in children and adolescents. According to Harrison et al. (2012), the
approval of “AP” use in some adolescents as well as children has led to increasing prescriptions
for the same despite the inadequate “information in their long-term side effects” (p. 139).
Similarly, there are no strategized oversights developed to guide the use of antipsychotics in
children and adolescents, despite the approval by the Food and Drug Administration (Harrison et
al., 2012). This calls for more studies to understand the concept, lay down some standardized
oversights and educate on the side effects (especially long-term) to the children.
First Episode of Schizophrenia and Prescribing Trends
The effectiveness of antipsychotics can also be considered as a trending factor affecting
the choice of psychiatric medication. A study by Whale et al. (2016) purposed to identify various
advantages of antipsychotic treatment in first episode patients. The research adopted a
“naturalistic cohort design” (Whale et al., 2016, p. 323). Initially, the researchers had identified
510 patients who qualified for the first episode patients’ category. However, due to some
circumstances, others were excluded from the study resulting in a final sample of 427
participants. The highest percentage of these participants was males. The investigators focused
on 4 antipsychotics, which were “aripiprazole, olanzapine, quetiapine, and risperidone, which
was 97.8% representation of prescriptions “for first-line treatment” of first-episode patients
(Whale et al., 2016, p. 326). The findings indicated that within the first three months of
discontinued treatment, the risk maximum. Similarly, it was observed that there was an
insignificant difference in the time of discontinuation among commonly prescribed AP drugs.
According to Whale et al. (2016), it was clear that effectiveness of the antipsychotic medication
had no current significance in the decision of what antipsychotic to prescribe for first episode
patients. Lieberman et al. (2005) have also carried out a study on the effectiveness of
antipsychotic drugs. They emphasized on the effectiveness of different types of antipsychotics on
schizophrenia patients especially those with chronic schizophrenia.
Robinson et al. (1999) carried out research on the first episode of schizophrenia, which
aimed at investigating relapse. The researchers selected a sample of 104 patients to take part in
the relapse analyses. The participants who had a response “to the treatment of their index
episode” on schizophrenia treatment were prone to a risk of experiencing relapse (Robinson et
al., 1999, p. 241). 108 patients had been treated; however, only 104 of them were monitored for
at least two months after a response to the treatment. The sample contained equal numbers of
males and females. For the five years after the initial recovery, the 1
cumulative relapse was
rated at 81.9% while the second was at 78.0% and the 3
was 86.2%. The research also revealed
that the risk for relapse by the discontinuity of antipsychotic treatments increased by close to five
times. Similarly, analyses demonstrated that participants “with poor premorbid adaptation to
school and premorbid social withdrawal relapse earlier,” (Robinson et al., 1999, p. 241).
Additionally, from the study, it was clear that majority of first episode patients, who recovered
from schizoaffective disorder or schizophrenia, were prone to psychiatric relapse within the first
five years. Subsequently, the high risk for relapse within five years of recovery from FEP can be
minimized through maintenance and carefully monitoring patients under antipsychotic
Other Factors Affecting Prescribing Treatment Decision
A study conducted by Mohamed et al. (1999) aimed at investigating cognitive
impairments as the primary “characteristic of schizophrenia” (p. 749). The research involved 94
first episode patients and 305 normal individuals, who were all exposed to neuropsychological
analyses. Out of the ninety-four FEP participants, 73 were neuroleptic naïve; fourteen had prior
treatment for less than 7 days, and the others (seven) had been treated for less than 14 days. Tests
were carried out to compare the 21 participants with prior treatment with those that had no
medication. It was observed that there was an insignificant difference in their performances.
From the tests, it was evident that participants with “first-episode schizophrenia” as well as
“neuroleptic-naïve patients” exhibited significant “impairments in most aspects of cognition,”
(Mohamed et al., 1999, p. 752). From the study, it is evident that more advanced models need to
be emphasized in creating awareness of schizophrenia. Similarly, there is an emphasis on
circuitry in the brain that is distributed by schizophrenia effects.
Apart from Europe and America, there are other studies done in parts of Asia to support
the changes in prescription patterns for psychiatric medication. Sim et al. (2004) carried out
research to elaborate on inadequate data regarding prescription trends in Asia. The study
purposed to investigate antipsychotic polypharmacy prevalence in patients who have
schizophrenia with a comparison between those receiving one type and those receiving more
than 1 type of antipsychotic. The research included 2,399 participants (patients with
schizophrenia) who came from 6 different states in East Asia. Daily doses of antipsychotic
medications were converted to Standard Chlorpromazine Equivalents (CPZ),” (Sim et al., 2004,
p. 178). From the study, 45.7% of the participants exhibited antipsychotic polypharmacy,
common in China, Taiwan, Singapore, Korea, Hong Kong and Japan as the highest. However,
this prevalence of antipsychotic polypharmacy was unevenly distributed among the states under
survey. Medication usage, socio-demographic features, as well as clinical features were found to
be the most common factors influencing poly-pharmacy. It is also true that “association of poly-
pharmacy with less use of atypical antipsychotic further increases and compounds the side-
effects burden,” (Sim et al., 2004, p. 182). Similarly, it is evident that social, clinical and cultural
factors are the major issues affecting the prescribing trend in East Asia. These involved
interplaying factors are similar in other countries and contribute to the common components
influencing the choice of an antipsychotic treatment for schizophrenia.
From many types of research, social, clinical and cultural factors have been discussed as
the primary interplaying factors that affect decision-making on medication for schizophrenia.
However, apart from these factors, some studies have identified the cost of treatment as another
factor playing a role treatment choice. Gilmer et al. (2007) conducted research to investigate the
trends as well as the cost of treatment with second-generation antipsychotic drugs. The study
focused on Medicaid beneficiaries who suffered from schizophrenia. It took place in San Diego,
California, USA. 15,962 individuals were identified from Medicaid Data; these were
schizophrenia patients receiving antipsychotic treatment between the year 1999 and 2004. They
divided oral antipsychotics into four categories; “first-generation antipsychotic medications only,
single second-generation medication in addition to first-generation drugs and multiple second-
generation medications” (Gilmer et al., 2007 p. 1008). The researchers investigated participants
receiving SGAPs treatments, time spent in polypharmacy; patients admitted as well the cost of
pharmaceuticals. The findings were patients undergoing SGAP medication increased by 10.4%
in 2004 “(from 3.3% in 1999 to 13.7% in 2004)” (Gilmer et al., 2007, p. 1007). Consequently, it
was observed that the cost of antipsychotic treatment increased from $ 4,128 to $ 5,231. The
percentage of those under second-generation polypharmacy, receiving the treatment for twelve
months, was observed to increase by 9.3%, which was from 5.1% to 14.4%. “Annual expenditure
on antipsychotic medication saw the largest gains of any therapeutic class, increasing from $ 250
million in 1999 to $ 719 million in 2004,” (Gilmer et al., 2007, p. 1010). However, this did not
reflect to reduce in antipsychotic patient admission or improvement in adherence to treatment.
Similarly, from the study, there is a major concern for the hiking costs for antipsychotic
medications in Medicaid programs. Consequently, this leads to increased examination of SGAP
prescriptions, which results to the dictation of the practice to reduce the high costs. Therefore,
the cost of medication is another factor influencing decision-making for prescribing
antipsychotics in the management of schizophrenia.
On other studies, it has been revealed that advanced antipsychotics have a superior
effectiveness over conventional ones. A study done by Koro et al. (2002) investigated effects
exhibited by Olanzapine as well as Risperidone exposure to patients who have schizophrenia.
They focused on the risk of hyperlipidemia in these patients. This study used data obtained from
England and Wales (General Practice Research Database) that included 3.5 million individuals.
“A total of 18309 individuals diagnosed as having schizophrenia were identified,” (Koro et al.,
2002, p. 1021). They used “conditional logistic regression” in deriving “adjusted odds ratios
(ORs), controlling for sex, age, and other medications and diseases influencing lipid levels,”
(Koro et al., 2002, p. 1021). From the study, it was observed, “between June 1, 1987, and
September 24, 2000, 20865 subjects were diagnosed” with “schizophrenia and received
treatment” for the disease (Koro et al., 2002, p. 1023). 7 % of the participants were followed up
for just three months then excluded from the study. 5% of the participants diagnosed with
hyperlipidemia were treated at the commencing period of the study and were also excluded;
hence, the study was done on 18309 members. The participants were equally divided; that is, the
number of males and females was almost equal. 85% of these participants were under a
prescription of at least one “non-depot conventional antipsychotic medications,” 22% were under
depot conventional antipsychotic medication; 5%, for Olanzapine; 8%, for Risperidone; and
3%, other newer antipsychotic agents” (Koro et al., 2002, p. 1023). The study revealed that
17.04/1000 person-years exhibited hyperlipidemia after antipsychotic treatment. Similarly,
females had a higher rate of hyperlipidemia than males. The analyses showed that there was an
increased risk of hyperlipidemia among Olanzapine-treated patients, adjusted for demographic
risk factors and concomitant medications and disorders” (Koro et al., 2002, p. 1024). Therefore,
Olanzapine is considered to increase chances of hyperlipidemia to schizophrenic participants as
observed from the study. It is, therefore, important for psychiatrists to consider the risk-benefit
ratio when choosing the right antipsychotic to use.
Clark, R. E. et al. (2002). Recent Trends in Antipsychotic Combination Therapy of
Schizophrenia and Schizoaffective Disorder: Implications for State Mental Health Policy.
Schizophrenia Bulletin, 28(l), 75-84.
Edlinger, M. et al. (2009). Factors Influencing the Choice of New-Generation Antipsychotic
Medication in the Treatment of Patients with Schizophrenia. Schizophrenia Research,
Gilmer, T. P. et al. (2007). Antipsychotic Polypharmacy Trends Among Medi-Cal Beneficiaries
With Schizophrenia in San Diego County, 19992004. Psychiatric Services 58, 1007
Harrison, J. N. et al. (2012). Antipsychotic Medication Prescribing Trends in Children and
Adolescents. J Pediatr Health Care, 26, 139-145.
Hayes, J. et al. (2011). Prescribing Trends in Bipolar Disorder: Cohort Study in the United
Kingdom THIN Primary Care Database 19952009. PLoS ONE, 6(12), 1-9.
Heres, S. et al. (2011). Psychiatrists’ Attitude to Antipsychotic Depot Treatment in Patients with
First-Episode Schizophrenia. European Psychiatry, 26, 297301.
Ho, B. C. et al. (2011). Long-term Antipsychotic Treatment and Brain Volumes. Arch Gen
Psychiatry, 68(2), 128-137.
Ito, H., Koyama, A. & Higuchi, T. (2005). Polypharmacy and Excessive Dosing: Psychiatrists’
Perceptions of Antipsychotic Drug Prescription. British Journal of Psychiatry, 187, 243-
Koro, C. E. et al. (2002). An Assessment of the Independent Effects of Olanzapine and
Risperidone Exposure on the Risk of Hyperlipidemia in Schizophrenic Patients. Arch
Gen Psychiatry, 59, 1021-1026.
Lieberman, J. A. et al. (2005). Effectiveness of Antipsychotic Drugs in Patients with Chronic
Schizophrenia. The New England Journal of Medicine, 353, 1209-1223.
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Psychiatry, 56, 749-754.
Patel, M. X. et al. (2014). Quality of Prescribing for Schizophrenia: Evidence from a National
Audit in England and Wales. European Neuropsychophar Macology, 24, 499509.
Pincus, H. A. et al. (1998). Prescribing Trends in Psychotropic Medication. JAMA, 279(7), 526-
Robison, D. et al. (1999). Predictors of Relapse Following Response from a First Episode of
Schizophrenia or Schizoaffective Disorder. Arch Gen Psychiatry, 56, 241-247.
Sim, K. et al. (2004). Antipsychotic Polypharmacy in Patients with Schizophrenia: A Multicentre
Comparative Study in East Asia. Br J Clin Pharmacol, 58(2), 178-183.
Siris, S. G. et al. (2001). Depression in Schizophrenia: Recognition and Management in the
USA. Schizophrenia Research, 47, 185-197.
Taylor, D., Paton, C. & Kerwin, R. (2006). The Maudsley. Broken Sound Parkway NW: CRC
Verdoux, H., Tournier, M. & Begaud, B. (2010). Antipsychotic Prescribing Trends: A Review of
Pharmaco-Epidemiological Studies. Acta Psychiatr Scand, 121, 410.
Warnez, S. & Severini, S. A. (2014). Clozapine: A Review of Clinical Practice Guidelines and
Prescribing Trends. BMC Psychiatry, 14(102), 1-5.
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