Download Experiences of medication adherence among

S YS T E M AT I C R E V I E W P R O T O C O L
Experiences of medication adherence among people with
schizophrenia: a systematic review protocol of
qualitative evidence
Nisakorn Pothimas 1 Patraporn Tungpunkom 2 Thidarat Kanungpiarn 1
1
Faculty of Nursing, Chiang Mai University, Thailand, 2Faculty of Nursing, Chiang Mai University, The Thailand Centre for Evidence-based Nursing,
Midwifery and Health Science (TCEBNMHS): a Collaborating Centre of the Joanna Briggs Institute
Review question/objective: The objective of this qualitative review is to synthesize the lived experiences of
medication adherence among people with schizophrenia. The specific review question is: what are the experiences
of taking prescribed medication among people with schizophrenia?
Keywords Experience; medication adherence; qualitative; schizophrenia; antipsychotic medication
Background
chizophrenia is a chronic and serious mental
illness that affects more than 21 million people
worldwide.1 The incidence rate of schizophrenia is
15.2 per 100,000 persons. This mental illness
affects both men and women. The study by
McGrath and colleagues2 presented the rate ratio
for males versus females as 1.4:1. The difference in
age at the onset between men and women was not
statistically significant. The mean age was 25 years
for women and 23 years for men.3 The median
lifetime prevalence for persons were 4.0 per
1000.2,4 Moreover, the finding from a systematic
review by Saha et al.4 indicated that the prevalence
of schizophrenia in migrant groups from eight
countries including Australia, Germany, India,
Israel, Taiwan, the Netherlands, United Kingdom
and the United States was higher than that in natives
of these countries. The median rate ratio for
migrant versus native born was 1.84. Furthermore,
the prevalence of this illness was related to
economic status. The countries that had high per
capita income showed lower prevalence than the
low-income countries.
The illness of schizophrenia is divided into
three phases, namely, the prodromal phase, the
active phase and the residual phase.5 First, the prodromal phase is a phase that can occur over several
S
Correspondence: Patraporn Tungpunkom, [email protected]
There is no conflict of interest in this project.
DOI: 10.11124/JBISRIR-2016-2538
JBI Database of Systematic Reviews and Implementation Reports
months or years.6 Signs and symptoms, such as social
withdrawal, deterioration of role functioning and
grooming, unusual behavior,5 interest in activities
that are para-normal and supernatural (e.g. black
magic, demons, ghosts)6 and problems with
language and communication,7 develop slowly
during this period. Second, the active phase occurs
after the prodromal period. This phase is characterized by psychotic symptoms, such as delusions, hallucinations and disturbances in behavior and
feelings.8 Finally, in the residual phase, people with
schizophrenia may present the psychotic symptoms
that are similar to those in the prodromal phase.7
During their lifetime, people with schizophrenia
could return to the active phase. Each time they
return to this phase, the residual symptoms increase,
whereas the ability to function normally may
decline.8
There are three broad categories of symptoms:
positive symptoms, negative symptoms and cognitive symptoms. Positive symptoms are psychotic
behaviors that do not occur in healthy individuals
and reflect a loss of contact with reality. Positive
symptoms vary in intensity from minor to severe and
include behaviors such as hallucinations, delusions
and movement disorder.7,8 Negative symptoms are
disruptions in normal emotions and behaviors and
are often harder to detect.8 Negative symptoms
include blunted affect or affective flattening, lack
of pleasure or interest, lack of energy, loss of normal
functions, lack of spontaneity and flow of conversation.9 Cognitive symptoms are relatively difficult to
recognize as part of the disorder such as poor ability
ß 2016 THE JOANNA BRIGGS INSTITUTE
©2016 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.
51
SYSTEMATIC REVIEW PROTOCOL
to understand information, trouble focusing or paying attention, and problems associated with the
ability to use information immediately after learning
it.8 The treatment for schizophrenia is aimed at
controlling symptoms and preventing psychotic
relapses. To this end, the crucial treatments are
antipsychotic medications and psychosocial treatments.10 Psychosocial treatments could enhance
coping strategies and emotional support such as
cognitive behavior therapy, personal therapy,
acceptance and commitment therapy and supportive
therapy.11
Antipsychotic medications are considered a firstline treatment to decrease psychotic symptoms such
as hallucinations and delusions in the acute phase.
Moreover, it is a major treatment to prevent exacerbation of psychotic symptoms for long periods.12
They are generally divided into two categories
including first-generation antipsychotics (typical
agents) and second-generation antipsychotics (atypical agents).13 First-generation antipsychotics or
typical agents are divided into three groups depending on the medication potency. The first group is
high-potency neuroleptics that are fluphenazine,
haloperidol, thiothixene and trifluoperazine. The
second group is moderate-potency neuroleptics consisting of molindone and loxapine. The last one is
low-potency neuroleptics, that is, chlorpromazine
and thioridazine.7 These agents are used to control
psychotic symptoms by blocking the dopamine reaction at the receptor site.7 High levels of dopamine
activate nerves in the brainstem, leading to faster
transmission of nerve impulses. This makes the
patients present psychotic symptoms such as hallucinations, bizarre thoughts and behavior. Therefore,
blocking this neurotransmitter can inhibit progression of uncommon thoughts and behavior.9
However, second-generation antipsychotics or atypical agents are the serotonin-dopamine antagonists
consisting of risperidone, olanzapine, quetiapine and
ziprasidone.7,9 They are used to treat positive and
negative symptoms9 by blocking specific serotonin
and dopamine at receptor sites.7 These agents induce
less adverse effects than the neuroleptic agents.9 The
adverse effects are generally associated with antipsychotic medications consisting of sedative, orthostatic hypotension, anticholinergic effects (e.g.
constipation, urinary retention, dry mouth, blurred
vision and cognitive impairment), extrapyramidal
symptoms (e.g. pseudoparkinsonism, akathisia,
JBI Database of Systematic Reviews and Implementation Reports
N Pothimas et al.
acute dystonia and tardive dyskinesia), hyperprolactinemia, sexual dysfunction, agranulocytosis, cardiac arrthymias, seizures and metabolic syndrome.14
A literature review found that individuals with
schizophrenia have significant problems with adherence to antipsychotic medications. The results of the
study by Quach et al.15 of 547 schizophrenia patients
with a first psychotic episode found poor medication
adherence in approximately 39 and 35% at one and
two years follow-up, respectively, whereas the rates
of good adherence were 51 and 44% at one and two
years follow-up, respectively. Similarly, the study by
Adelufosi et al.16 showed that medication adherence
and medication non-adherence of 313 respondents
were 59.7 and 40.3%, respectively. The findings are
in line with the study by Dassa et al.17 who presented
the medication adherence and non-adherence rates
of 291 patients as 69.42% and approximately 30%,
respectively. Furthermore, the study by Amr et al.18
demonstrated that 26% of 92 schizophrenia patients
adhered to antipsychotic agents, whereas the other
74% was medication non-adherent. Moreover, Ngui
et al.19 revealed that 12.57% of patients consistently
showed good adherence and nearly 35% showed
inconsistent adherence, whereas about 52% showed
consistently poor adherence.
From the literature reviewed, the factors associated with medication adherence can be divided into
three groups, namely, clinical factors, personal factors and social support factors. The clinical factor
that includes the severity of psychotic symptoms
affects the patient’s medication adherence. It was
found that patients who have low severity of psychotic symptoms tend to adhere to medications.20
The severity of psychotic symptoms, especially
positive symptoms, is more likely to decrease
medication adherence, for example patients who
feel persecuted or are afraid that they will be poisoned would be reluctant to take medication.21
Therefore, persons with schizophrenia with less
severe psychotic symptoms will show more adherence to the treatment regimen. This is because their
insight into and awareness of their illness, that is, the
personal factor 20, play a major role in influencing
adherence behavior.21 In addition, positive attitudes
toward medication which stem from a belief that
antipsychotic medications can help improve their
symptoms22 and help them cope with life,23
represent another factor that contributes to persons
with schizophrenia adhering to medication. Social
ß 2016 THE JOANNA BRIGGS INSTITUTE
©2016 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.
52
SYSTEMATIC REVIEW PROTOCOL
support factors such as support from family and
friends could also assist in people with schizophrenia
adhering to medication.24 Like adherent factors,
medication non-adherence factors can be divided
into three groups. The severity of psychotic symptoms, especially positive symptoms, is mostly
found in the clinical factor, leading to medication
non-adherence.20,25–28 The personal factors such
as lack of insight into illness,20,25,27–29 substance
use disorders,27,28 unemployment,27 poor functioning25,27 and negative attitudes to antipsychotic medications affect non-adherence.30 Schizophrenia
patients feel that antipsychotic medications threaten
their self-esteem and stigmatize them. When they
stop taking medicine, it helps them think that they
are not crazy.24 According to the social support
factors, patients who live alone tend to have
poor adherence or discontinuation of long-term
treatment.29
Non-adherence to antipsychotic medications is an
important problem as it leads to psychotic relapse,
readmission and attempted suicide among people
with schizophrenia.31 Moreover, medication nonadherence has significant cost implications with costs
associated with relapse being significantly high.
Ascher-Svanum and colleagues32 found that the direct
costs in US dollars of relapse during the first year were
about three times higher ($33,187 $47,616) in
those who relapsed versus those who did not relapse
($11,771 $10,611). Similarly, Hong et al.33 found
that the costs of relapse were about two times
(£14,055 £7417) higher in those with relapses as
compared with those without relapses.33 Similarly,
Almond et al.34 found that the costs of relapse were
over four times higher than the costs for non-relapse
patients.34 Therefore, it is useful to understand the
experiences and perspectives of people with schizophrenia who can maintain long-term treatment.
However, there is no systematic review about the
experiences of medication adherence among people
with schizophrenia in the Cochrane Library or Joanna
Briggs Institute (JBI) Database of Systematic Reviews
and Implementation Reports.
Therefore, the objective of this review is to synthesize those primary studies that explored lived
experiences of medication adherence among people
with schizophrenia. The results can shed some light
on both positive and negative factors associated with
medication adherence, especially subjective experiences from the insider’s point of view. It can lead to
JBI Database of Systematic Reviews and Implementation Reports
N Pothimas et al.
recommendations for practice based on the patients’
perspectives. It also can serve as a basis to further
develop effective programs for enhancing antipsychotic medication adherence in schizophrenia
patients.
Inclusion criteria
Types of participants
This review will consider studies that include
patients aged 18 years and over who have been
diagnosed with schizophrenia spectrum disorders
(schizophrenia, schizophreniform, undifferentiated
schizophrenia and schizoaffective disorder). The
diagnostic criteria are based on any editions of the
American Psychiatric Association’s Diagnostic and
Statistical Manual of Mental Disorders or the International Statistical Classification of Diseased and
Related Health Problems-10. Studies related to
patients with organic brain disorder or mental retardation, alcohol or drug abuse will be excluded.
Phenomena of interest
This review will consider primary studies that
explored the experiences of medication adherence
among people with schizophrenia.
Context
This review considers studies that have been conducted on people with schizophrenia who were
hospitalized or living in the community.
Types of studies
The review will consider any qualitative studies that
focus on the experiences of medication adherence of
people with schizophrenia, using research methodologies including, but not limited to, phenomenology, grounded theory and ethnography.
Search strategy
Prior to reviewing the experiences of medication
adherence among people with schizophrenia, this
topic will be searched in the Cochrane Library
and JBI Database of Systematic Reviews and Implementation Reports to ensure that there are no prior
systematic reviews. An extensive search strategy will
be conducted to find both published and unpublished studies in English and Thai from 1999 to
2015, because the first reported study exploring
the experiences related to taking antipsychotic
ß 2016 THE JOANNA BRIGGS INSTITUTE
©2016 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.
53
SYSTEMATIC REVIEW PROTOCOL
medication of people with schizophrenia was first
investigated in the year of 1999. A three-step search
strategy will be conducted for this review as follows:
An initial limited search of MEDLINE and
CINAHL will be undertaken followed by an
analysis of the text words contained in the title,
abstracts and subject descriptors/MeSH terms in
relevant articles to identify additional keywords.
All identified keywords and their synonyms
will be used for the comprehensive search of
electronic databases. The databases to be
searched will include CINAHL, PubMed, Science
Direct, Scopus, PsycINFO and ProQuest Dissertation and Theses.
Reference lists and bibliographies of retrieved
articles will be searched for further relevant
articles. To avoid publication bias, handsearching will be undertaken in journals that are not
listed on databases but are known to contain
literature on this topic of investigation to ensure
all relevant materials are captured. The database
of Thailand in the National Research Council of
Thailand will be used to find the relevant articles
that are published in English.
Assessment of methodological quality
First, the qualitative articles retrieved will be
assessed by two independent reviewers for methodological validity by using the standardized critical
appraisal instrument from the Joanna Briggs Institute Qualitative Assessment and Review Instrument
(JBI-QARI) (Appendix I). Disagreement between the
reviewers will be resolved through discussion, or
with a third reviewer.
Data extraction
The data will be extracted by using the standardized
data extraction tool from JBI-QARI (Appendix II).
The data extracted will include specific details about
the methodology method, phenomena of interest,
setting, geographical location, cultural content,
participants, data analysis and authors’ conclusions.
Data synthesis
Qualitative research findings will be pooled using
JBI-QARI. This will involve the aggregation or synthesis of findings to generate a set of statements that
represent that aggregation, through assembling the
findings rated according to their quality and
JBI Database of Systematic Reviews and Implementation Reports
N Pothimas et al.
categorizing these findings on the basis of similarity
in meaning. These categories will then be subjected
to a meta-synthesis to produce a single comprehensive set of synthesized findings that can be used as a
basis for evidence-based practice. Wherever textual
pooling is not possible, the findings will be presented
in narrative form.
Acknowledgments
The reviewers would like to acknowledge the Thailand Centre for Evidence Based Nursing, Midwifery
and Health Science for providing workshop training
for conducting reviews.
References
1. World Health Organization. Schizophrenia. 2014 [Internet].
[cited 2015 June 16th]. Available from: http://www.who.int/
mental_health/management/schizophrenia/en/.
2. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: a
concise overview of incidence, prevalence, and mortality.
Epidemiol Rev 2008;30:67–76.
3. Morgan VA, Castle DJ, Jablensky AV. Do women express and
experience psychosis differently from men? Epidemiological evidence from the Australian National Study of Low
Prevalence (Psychotic) Disorders. Aust N Z J Psychiatry
2008;42(1):74–82.
4. Saha S, Chant D, Welham J, McGrath J. A systematic review
of the prevalence of schizophrenia. PLoS Med 2005;2(5):
413–33.
5. American Psychiatric Association. Diagnostic and statistical
manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000.
6. Grover S, Davuluri T, Chakrabarti S. Religion, spirituality, and
schizophrenia: a review. Indian J Psychol Med 2014;36(2):
119–24.
7. O’Brien PG, Kennedy WZ, Ballard KA. Psychiatric mental
health nursing: an introduction to therapy and practice
Boston: Jones and Bartlett publishers; 2008.
8. Centre for Addiction and Mental Health. What is schizophrenia. 2012 [internet]. [Retrieved 2015 June 14th]. Available
from: http://www.camh.ca/en/hospital/health_information/
a_z_mental_health_and_addiction_information/schizophre
nia/schizophrenia_information_guide/Pages/schizophrenia_
whatis.aspx.
9. Shives LR. Basic concepts of psychiatric-mental health
nursing. 6th ed. Philadelphia: Lippincott Williams & Wilkins;
2005.
10. Lotrakul M. Schizophrenia. 2011 [internet]. [Retrieved 2015
May 28th]. Available from: http://www.ramamental.com/
medicalstudent/generalpsyc/schizophrenia_article/.
11. Dickerson FB, Lehman AF. Evidence-based psychotherapy
for schizophrenia 2011 update. J Nerv Ment Dis 2011;199(8):
520–6.
ß 2016 THE JOANNA BRIGGS INSTITUTE
©2016 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.
54
SYSTEMATIC REVIEW PROTOCOL
12. The National Health Service. Schizophrenia treatment. 2014
[internet]. [Retrieved 2015 June 14th]. Available from: http://
www.nhs.uk/Conditions/Schizophrenia/Pages/Treatment.
aspx.
13. Centre for Addiction and Mental Health. Understanding
psychiatric medications: antipsychotics. 2012 [internet].
[Retrieved 2015 June 14th]. Available from: http://
www.camh.ca/en/education/about/camh_publications/
Pages/understanding_psych_meds.aspx.
14. Muench J, Hamer A. Adverse effects of antipsychotic medications. Am Fam Physician 2010;81(5):617–22.
15. Quach PL, Mors O, Christensen TØ, Krarup G, Jørgensen P,
Bertelsen M, et al. Predictors of poor adherence to medication among patients with first-episode schizophreniaspectrum disorder. Early Interv Psychiatry 2009;3(1):66–74.
16. Adelufosi AO, Adebowale TO, Abayode O, Mosanya JT.
Medication adherence and quality of life among Nigeria
outpatients with schizophrenia. Gen Hosp Psychiatry
2012;34(1):2–79.
17. Dassa D, Boyer L, Benoit M, Bourcet S, Raymondet P, Bottai T.
Factors associated with medication non-adherence in
patients suffering from schizophrenia: a cross-sectional
study in a universal coverage health-care system. Aust N
Z J Psychiatry 2010;44(10):921–8.
18. Amr M, El-Mogy A, El-Masry R. Adherence in Egyptian
patients with schizophrenia: the role of insight, medication beliefs and spirituality. Arab J Psychiatr 2013;24(1):
60–8.
19. Ngui AN, Vasiliadis HM, Tempier R. Factors associated with
adherence over time to antipsychotic drug treatment. Clin
Epidemiol Glob Health 2015;3(1):3–9.
20. Kao YC, Liu YP. Compliance and schizophrenia: the predictive potential of insight into illness, symptoms, and side
effects. Compr Psychiatry 2010;51(6):557–65.
21. Meguid M, Essawy HI, Sabry WM, Khalifa DA, Bastawy MA, Ali
RR. Understanding medications non adherence in a sample
of Egyptian patients with schizophrenia in relation to illness
severity and insight. J Psychiatry 2015;18(5):1–7.
22. Perkins DO. Predictors of noncompliance in patients with
schizophrenia. J Clin Psychiatry 2002;63(12):1121–212.
23. Yamada K, Watanabe K, Nemoto N, Fujita H, Chikaraishi C,
Yamauchi K, et al. Prediction of medication noncompliance
in outpatients with schizophrenia: 2-year follow-up study.
Psychiatry Res 2006;141(1):61–9.
JBI Database of Systematic Reviews and Implementation Reports
N Pothimas et al.
24. Tranulis C, Goff D, Henderson DC, Freudenreich OF. Becoming adherent to ntipsychotics: a qualitative study of treatment-experienced schizophrenia patients. Psychiatr Serv
2011;62(8):888–92.
25. Brain C, Allerby K, Sameby B, Quinlan P, Joas E, Karilampi U,
et al. Drug attitude and other predict of medication adherence in schizophrenia: 12 months of electronic monitoring
(MEMS1) in the Swedish COAST-study. Eur Neuropharmacol 2013;23(12):1754–62.
26. Liu-Seifert H, Osuntokun OO, Feldman PD. Factors associated with adherence to treatment with olanzapine and
other atypical antipsychotic medications in patients with
schizophrenia. Compr Psychiatry 2012;53(1):107–15.
27. Nosé M, Brabui C, Tansella M. How often do patients with
psychosis fail to adhere to treatment programmes? A
systematic review. Psychol Med 2003;33(7):1149–60.
28. Kamali M, Kelly BD, Clarke M, Browne S, Gervin M, Kinsella A,
et al. A prospective evaluation of adherence to medication
in first episode schizophrenia. Eur Psychiatry 2006;21(1):
29–33.
29. Tsang HWH, Fung KMT, Corrigan PW. Psychosocial and
socio-demographic correlates of medication compliance
among people with schizophrenia. J Behav Ther Exp Psy
2009;40(1):3–14.
30. Gaebel W, Riesbeck M, von Wilmsdorff M, Burns T, Derks EM,
Kahn RS, et al. Drug attitude as predictor for effectiveness in
first-episode schizophrenia: results of an open randomized
trial (EUFEST). Eur Neuropharmacol 2010;20(5):310–6.
31. Novick D, Haro JM, Suarez D, Perez V, Dittmann RW, Haddad
PM. Predictors and clinical consequences of non-adherence
with antipsychotic medication in the outpatient treatment
of schizophrenia. Psychiatry Res 2010;176(2–3):109–13.
32. Ascher-Svanum H, Zhu B, Faries DE, Salkever D, Slade EP,
Peng X, et al. The cost of relapse and the predictors of
relapse in the treatment of schizophrenia. BMC Psychiatry
2010;10(2):1–7.
33. Hong J, Windmeijer F, Novick D, Haro JM, Brown J. The cost
of relapse in patients with schizophrenia in the European
SOHO (Schizophrenia Outpatient Health Outcomes) study.
Prog Neuropsychopharmacolo Biol Psychiatry 2009;33(5):
835–41.
34. Almond S, Knapp M, Francois C, Toumi M, brugha T. Relapse
in schizophrenia: costs, clinical outcomes and quality of life.
Br J Psychiatry 2004;184(4):346–51.
ß 2016 THE JOANNA BRIGGS INSTITUTE
©2016 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.
55
SYSTEMATIC REVIEW PROTOCOL
N Pothimas et al.
Appendix I: Appraisal instrument
QARI appraisal instrument
JBI Database of Systematic Reviews and Implementation Reports
ß 2016 THE JOANNA BRIGGS INSTITUTE
©2016 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.
56
SYSTEMATIC REVIEW PROTOCOL
N Pothimas et al.
Appendix II: Data extraction instrument
QARI data extraction instrument
JBI Database of Systematic Reviews and Implementation Reports
ß 2016 THE JOANNA BRIGGS INSTITUTE
©2016 Joanna Briggs Institute. Unauthorized reproduction of this article is prohibited.
57