Journal of Affective Disorders ] (]]]]) ]]]]]]

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Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research report

Determinants of adherence to treatment in bipolar disorder:

A comprehensive review
Emilie Leclerc a,b,n, Rodrigo B. Mansur a,b, Elisa Brietzke a,b
a ~ Paulo,
Program for Recognition and Intervention in Individuals in At-Risk Mental States (PRISMA), Department of Psychiatry, Federal University of Sao
~ Paulo, Brazil
Sao
b
Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Federal University of Sa~ o Paulo, Sa~ o Paulo, Brazil

a r t i c l e i n f o abstract

Article history: Objective: Comprehensively review studies evaluating factors associated with adherence to treatment
Received 6 December 2012 in bipolar disorder (BD), as well as the results of interventions developed to enhance adherence in this
Accepted 29 January 2013 population.
Methods: The following search engines were consulted: PubMed, Scielo, LILACS and PsycINFO. The
Keywords: keywords used were Bipolar Disorder, Factor, Adherence, Nonadherence, Compliance and
Bipolar disorder Intervention. In addition, references list of selected studies were consulted searching for relevant
Adherence articles.
Psychoeducation Results: Adherence has been dened in various ways, with some considering adherence vs. nonadher-
Risk factors
ence, and other including a partial adherence measure. In addition, methods to assess adherence
Intervention
differ for each study. Several factors were related to poor adherence, including patient-related factors
(e.g. younger age, male gender, low level of education, alcohol and drugs comorbidity), disorder-related
factors (e.g. younger age of onset, severity of BD, insight and lack of awareness of illness) and
treatment-related factors (e.g. side effects of medications, effectiveness). To improve adherence, the
main recommendations are to provide customized interventions focusing on the underlying causes of
nonadherence, strong therapeutic alliance and different modalities based on psychoeducation.
Conclusion: Our results indicate that nonadherence is a multicausal phenomenon and strategies to
prevent and approaches them must include enhanced therapeutic alliance, exible topics, early
intervention, group setting, and psychoeducation.
Limitations: Different denitions and measures of adherence in the literature currently moderate the
generalization of the ndings in this review. Further studies are necessary regarding factors of
adherence in BD and interventions to improve it, especially on social factors like stigma and family.
& 2013 Elsevier B.V. All rights reserved.

1. Introduction cognitive performance, response to pharmacological and psycho-

Bipolar disorder (BD) is a common and often severe mood
disorder, which affects multiple dimensions of the life of the
patients (Colom et al., 2006). Functioning in BD is impaired in
several domains, such as social, occupational and/or educational,
and self-care (Michalak et al., 2008). One of the most robust
determinants of level of functioning in BD is a history of multiple
episodes, which impacts disability, chronicity and severity of
subsyndromal symptoms and quality of life (Magalhaes et al.,
2012).
The recurrence of episodes has been associated with deteriora-
tion in clinical and neurobiological parameters, including
n
Correspondence to: Rua Pedro de Toledo, 669- 31 andar, Vila Clementino, CEP
04039-032, Sa~ o Paulo, SP, Brazil.
Tel.: 55 11 5573 3599.
E-mail address: emilie.leclerc@gmail.com (E. Leclerc).
social treatments and brain structures (Kapczinski et al., 2009;
Taylor et al., 2011). These ndings are in agreement with the
recent paradigm of BD that considers this disorder not only a
cyclic, but also a progressive one (Berk et al., 2011). Nevertheless,
effective interventions focusing on reduction and delay of pro-
gression are not currently available. Because of this, to prevent
new mood episodes is the only alternative to presumably delay
evolution to disability (Brietzke et al., 2012).
Poor adherence to treatment is one of the main challenges to
control the symptoms and prevent the recurrence in BD. Treat-
ment nonadherence occurs at a rate between 12% and 64% among
individuals with the disorder (Suppes et al., 1991; Keck et al.,
1997; Schumann et al., 1999; Adams and Scott, 2000; Colom et al.,
2000; Vega et al., 2011). Poor adherence increases the likelihood
of relapse and neuroprogression, while it reduces the quality of
life of patients and increases the risk of suicide (Colom et al.,
2005; Gonzalez-Pinto et al., 2006; Lopez-Castroman et al., 2009).

0165-0327/$ - see front matter & 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jad.2013.01.036

Please cite this article as: Leclerc, E., et al., Determinants of adherence to treatment in bipolar disorder: A comprehensive review.
Journal of Affective Disorders (2013), http://dx.doi.org/10.1016/j.jad.2013.01.036i
2 E. Leclerc et al. / Journal of Affective Disorders ] (]]]]) ]]]]]]

The rst aspect to be considered when adherence is the object However, even with the best design each type of measure has its
of study is the different denitions of adherence that are found in drawbacks and no measure alone can be considered optimal
the literature. The most widely accepted is the one developed by (World Health Organization and Sabate!, 2003).
the World Health Organization (WHO) (Colom et al., 2005). The Direct measures of medication adherence encountered were
WHO basically denes treatment adherence as the extent to pills count (Gonzalez-Pinto et al., 2010; Sajatovic et al., 2012) or
which a patient follows the medical instructions of their health- blood sampling to evaluate the plasma levels of medications, such
care provider, and plays a key role in coming to an agreement as lithium, valproate or carbamazepine (Gonzalez-Pinto et al.,
about its own treatment (Velligan et al., 2009). The inclusion of an 2006; Colom et al., 2009; Mazza et al., 2009; Pacchiarotti et al.,
active engagement of the patient in the treatment is the differ- 2009; Jonsdottir et al., 2012).
entiation with the previously used and similar concept of com- Indirect measures commonly used were self-report questionnaire
pliance (Colom et al., 2005). Additionally, the WHO recognizes (Baldessarini et al., 2008; Barraco et al., 2012) or clinical assessment
that adherence necessarily reects not only to take medication led out by the psychiatrist (Gonzalez-Pinto et al., 2010; Jonsdottir
appropriately, but also to adopt a wider set of recommended et al., 2012). Johnson et al. (2007) used a more original approach with
behaviors with the objective to prevent, maintain and/or restore a stated-preference web-survey combining medication attributes
health. Examples of behavioral modications that can be recom- preference of BD patients and current self-reported adherence,
mended in BD to minimize mood instability are to reduce or avoid veried for internal validity. Another example is the study from
substance/alcohol use and to regulate sleep/awake cycle. Atten- Jonsdottir et al. (2012) that used a validated Likert scale (0100%)
dance to psychosocial treatment, time to drop-out or attendance lled out by patients, about how much of their prescribed medica-
to psychiatrist follow-up appointments have already been used to tion they have taken in the past week. Eker and Harkin (2012) used a
measure the treatment adherence from a broader perspective multifaceted approach, with a combination of scores from three
(Even et al., 2007; Cakir et al., 2009; Proudfoot et al., 2012). standardized instruments: the McEvoy Treatment Observation Form,
Nonetheless, several authors still keep the emphasis on adherence the Medication Adherence Rating Scale (MARS), and the Attitude
regarding solely medication and use the term adherence just in toward Neuroleptic Treatment (ANT). Even though self-report mea-
that aspect (Jonsdottir et al., 2012). sures are subjective, they were proven valid by Jonsdottir et al.
Because adherence is a at the same time a complex phenomenon (2010). Still, both subjective measure (i.e. self-reported and rated by
and a crucial step to acquire good outcomes in BD, to understand
which aspects of the patient, the treatment and the healthcare
provider have an impact on adherence is important to design new Table 1
Factors associated to poor adherence.
interventions to obtain and maintain adherence during treatment of
individuals with BD. Medication Psychosocial treatment
The objective of this study is to conduct the rst broad overview
regarding determinant of adherence in BD and efcacy of inter- Patient-related GenderMen GenderMen
ventions designed to improve adherence in this population. factors Younger age Older age
Low level of education Low level of education
Being single
Psychology Psychology
2. Methods Poor insight Lack of awareness of the
disease
The research questions that directed this review were: Which Lack of awareness of their External locus of control
disease
factors are associated to adherence among individuals with BD? and
Negative attitude to
Which interventions are effective to enhance adherence to treat- treatment
ment of individuals with BD?. To conduct this review, the following Fear of side-effects
search engines were consulted: PubMed, Scielo, LILACS and Psy- Negative attitude to
medication
cINFO. The keywords used were Bipolar Disorder, Factor,
Low overall life satisfaction
Adherence, Nonadherence, Compliance and Intervention. In Low cognitive functioning
addition, references list of selected studies were consulted searching Comorbidity
for relevant articles. Well-conducted observational studies, rando- Comorbid use of alcohol and
mized controlled trials (RCT), cross-sectional and case-control studies cannabis
Obsessive-compulsive
were considered. Expert consensus reviews were also included.
disorder
Articles from 1980 to 2012 were included from peer-reviewed
Social No social activities No family history of BD
publications only. We included articles published in English, French
and/or suicide
and Portuguese. We excluded review article and articles with data in Work impairment
repetition.
Chronology Younger age of onset
Current inpatient status
Hospitalization or suicide
3. Results attempt in past 12 months

Disease Mixed episode Depressive/manic episode

A total of 115 articles were identied, and after screening 27 characteristics Rapid cycling Longer duration of illness
were kept. Delusions and hallucinations Higher number of episodes
Severity of the illness
BD I diagnosis
3.1. Measures of medication adherence Higher number of episodes

Treatment Side effects of Poor response to

Medication adherence has been measured in various ways in related medications medication
the different studies with some authors considering adherence vs. Inadequate efcacy of Poor medication and
nonadherence, and others including one or more partial adher- medication medical follow-up
ence measures (Jonsdottir et al., 2012). Several different objective Use of antidepressant adherence
Low treatment dosage
and/or subjective measures have also been used in the literature.

Please cite this article as: Leclerc, E., et al., Determinants of adherence to treatment in bipolar disorder: A comprehensive review.
Journal of Affective Disorders (2013), http://dx.doi.org/10.1016/j.jad.2013.01.036i
 E. Leclerc et al. / Journal of Affective Disorders ] (]]]]) ]]]]]]
healthcare providers) tend to slightly overestimate the adherence
compared to objective ones (World Health Organization and Sabate!,
2003; Jonsdottir et al., 2010). Several studies also included interviews
with close family member or relative to evaluate the degree of
adherence to treatment, as a supplementary measure (Glick et al.,
1991; Miklowitz et al., 2003; Gonzalez-Pinto et al., 2006; Cakir et al.,
2009; Mazza et al., 2009; Pacchiarotti et al., 2009; Colom, 2010).
As no single technique is awless, a combination of both objective
and subjective measures is probably the most reliable way to estimate
medication adherence and it has been used in more recent studies
(Miklowitz et al., 2003; Gonzalez-Pinto et al., 2006; Cakir et al., 2009;
Mazza et al., 2009; Pacchiarotti et al., 2009; Colom, 2010; Jonsdottir
et al., 2012). This corresponds to WHOs current recommendation to
assess adherence (World Health Organization and Sabate!, 2003).
3.2. Factors associated with nonadherence
Several factors were related to adherence, including patient-
related factors, disorder-related factors and treatment-related factor.
A summarize of the most relevant in each category are described in
Table 1.
3.2.1. Patient-related factors associated to adherence
3.2.1.1. General factors
a. Gender: Women showed a slightly greater adherence than men
to medication (Gonzalez-Pinto et al., 2006, 2010) and to an
online psychoeducation group (Proudfoot et al., 2012), but
other studies report no signicant relation (Kleindienst and
Greil, 2004; Johnson et al., 2007; Baldessarini et al., 2008).
b. b. Age: A younger age (below 30 years old) may be a risk factor
for nonadherence to medication, medical visits and some
psychosocial treatment in patients with BD (Kleindienst and
Greil, 2004; Baldessarini et al., 2008; Mazza et al., 2009;
Gonzalez-Pinto et al., 2010; Proudfoot et al., 2012). On the
contrary, for the participation to a psychoeducation program, a
younger age was predictive of adherence (Even et al., 2007).
c. Education: A lower level of education is a risk factor of
nonadherence for medication and psychoeducation group in
some studies (Even et al., 2007; Johnson et al., 2007; Gonzalez-
Pinto et al., 2010), although this has not been the case for
every study (Gonzalez-Pinto et al., 2006).
d. Marital status: Single patients have a higher risk of nonadher-
ence to medication than others (Gonzalez-Pinto et al., 2006,
2010).
e. Activities: Not having social activities has been linked to
medication nonadherence (Gonzalez-Pinto et al., 2010). Work
impairment has also been linked to nonadherence (Gonzalez-
Pinto et al., 2010).
d. Family history: Having a stronger family history of BD and
suicide was related to being adherent to a psychoeducation
program (Cakir et al., 2009). Possibly, a family history of BD or
suicide may contribute to understand the importance of the
treatment and therefore raise the motivation. Gonzalez-Pinto
et al. (2006) have not found a signicant difference between
adherent and nonadherent patients regarding the presence or
not of a family history of BD.
3.2.1.2. Comorbidities
a. Alcohol and drug abuse: A comorbid use of alcohol and/or drugs
(especially cannabis) is one of the most strongly associated
Please cite this article as: Leclerc, E., et al., Determinants of adherence to treatment in bipolar disorder: A comprehensive review.
Journal of Affective Disorders (2013), http://dx.doi.org/10.1016/j.jad.2013.01.036i
3
factor to nonadherence to medication in BD patients in the
literature (Gonzalez-Pinto et al., 2006, 2010; Baldessarini et al.,
2008; Barraco et al., 2012; Jonsdottir et al., 2012). The
chronology of drug/alcohol use is relevant, considering that
patient with a use preceeding the onset are less adherent to
treatment, even though they still have a better outcome
(Pacchiarotti et al., 2009).
b. Others: A comorbid obsessive-compulsive disorder was related
to nonadherence in one study (Baldessarini et al., 2008).
3.2.1.3. Psychological factors
a. Insight: An expert survey and one study suggest that poor
insight might be related to nonadherence (Gonzalez-Pinto
et al., 2010; Velligan et al., 2010). According to Jonsdottir
et al. (2012) further studies are needed to conrm these results
because of the methodological limitations and low magnitude
of the association. Specically, the scale used to measure the
insight, the Birchwood Insight Scale, has been shown to work
well for BD I, but not BD II and both subtypes were included in
their study which could have underestimated the importance
of insight. Also corroborating this possible association,
Gonzalez-Pinto et al. (2010) found that on long term and at
the beginning of the maintenance phase, insight seems to be a
protective factor to nonadherence.
b. Awareness of disease and beliefs about medication: A general lack of
awareness of the disease is subjectively reported by doctors as
being a risk factor of nonadherence to medication (Velligan et al.,
2010). Patients who have doubts about their illness are indeed
more susceptible to be nonadherent to medication (Jonsdottir
et al., 2012), and this was also true for adherence to a psychoe-
ducation program (Even et al., 2007). With lithium treatment (but
not carbamazepine), the illness concept of the patient, measured
by trust in medication, trust in treating physician, and absence of
negative treatment expectations, is also related to better adher-
ence when positive (Kleindienst and Greil, 2004). In addition, a
general fear of any side-effects and a negative attitude toward
treatment are risk factors of nonadherence (Velligan et al., 2010;
Barraco et al., 2012).
c. Cognitive functioning: Even though some studies found a relation-
ship between nonadherence and low cognitive functioning (Vega
et al., 2011), according to the recent study of Jonsdottir et al.
(2012) cognitive dysfunction is not a risk factor for nonadherence
to medication. Nevertheless, studies investigating a possible link
between cognitive functioning and adherence in bipolar patients
are very scarce (Jonsdottir et al., 2012).
d. Other psychological factors: To be dissatised with ones life has
also been linked to nonadherence to medication (Gonzalez-
Pinto et al., 2010). Patients with a more external locus of
control were less likely to adhere to a psychoeducation
program (Even et al., 2007).
3.2.2. Disorder-related factors associated with nonadherence
a. Age of onset of the disease: A younger age of onset was a risk
factor of nonadherence in some (Gonzalez-Pinto et al., 2010;
Vega et al., 2011; Barraco et al., 2012), but not in every study
evaluating this issue (Gonzalez-Pinto et al., 2006). These
results are logical considering that the younger age, poor
adherence and severity of BD are related aspects mutually
inuencing each other, making it difcult to establish a clear
causeeffect relationship.
4 E. Leclerc et al. / Journal of Affective Disorders ] (]]]]) ]]]]]]
b. Hospitalization and suicide attempts: Those with a current inpatient
status are more at risk to be nonadherent (Gonzalez-Pinto et al.,
2010). Also, those who have been hospitalized or made a suicidal
attempt in the last 12 months were at risk of being nonadherent
(Gonzalez-Pinto et al., 2006, 2010).
c. Severity of BD: Generally, a greater affective morbidity is related to
nonadherence (Baldessarini et al., 2008). To have more break-
through episodes (especially manic and mixed states) has been
related to medication nonadherence (Gonzalez-Pinto et al., 2006).
Those in a mixed episode, with rapid cycling or with delusions and
hallucinations are more at risk to be nonadherent to medication
(Gonzalez-Pinto et al., 2010; Velligan et al., 2010). Similarly, Cakir,
et al. (2009) found out that patients with mixed episodes and a
signicantly lower total number of episodes were more likely to
adhere to a psychoeducation program. According to Even et al.
(2007), a shorter duration of illness is a predictive factor of
adherence to a psychoeducation program, but for medication
adherence, the duration of illness has not been related
(Gonzalez-Pinto et al., 2006). BD I diagnosis could be signicantly
associated with medication drop-out (Mazza et al., 2009), but not
all studies found this association to be signicant (Baldessarini
et al., 2008).
3.3. Treatment-related factors associated with nonadherence
a. Side effects of medications: Side-effects are related to nonad-
herence, but at a low level (Baldessarini et al., 2008; Jonsdottir
et al., 2012). Some side-effects have more impact on adherence
than other and in order of importance, weight gain, cognitive
impairment and severity of depressive symptoms (as an out-
come of medication) were the most associated with nonad-
herence to medication (Johnson et al., 2007). Experts reported
that a sedative side-effect of medication also contributed to
nonadherence (Velligan et al., 2010).
b. Efcacy: Inadequate efcacy of the medication was also suggested
as a risk factor that experts observed in patients (Velligan et al.,
2010). Patients using antidepressants had a higher rate of non-
adherence to their medication (Gonzalez-Pinto et al., 2010). Low
dosage is also associated with drop-out rate, especially with a BD I
diagnosis (Mazza et al., 2009). A good response to medication
treatment has been associated with adherence to a psychoeduca-
tion treatment (Cakir et al., 2009).
c. Others: A full medication and medical follow-up adherence
was related with adherence to psychosocial treatment (Cakir
et al., 2009).
3.4. Strategies to improve adherence in BD
Several strategies and programs were developed with the
objective to help with adherence to general treatment or medica-
tion, although systematic investigation of their efcacy was less
common. Overall, experts recommended customized interventions
focusing on the underlying causes of nonadherence (Velligan et al.,
2009). An experts consensus survey suggests that any services
targeting logistic problems involved in nonadherence are relevant
(Velligan et al., 2010). The experts survey results also point out
that it is important to use a multifaceted intervention since
commonly many problems are simultaneously present. Risk
factor assessment like those presented in this review helps to
identify the potential intervention targets, especially the poten-
tially modiable ones. In the next section, we summarized inter-
ventions or aspects involved in them, that have been shown to
enhance adherence in BD.
Please cite this article as: Leclerc, E., et al., Determinants of adherence to treatment in bipolar disorder: A comprehensive review.
Journal of Affective Disorders (2013), http://dx.doi.org/10.1016/j.jad.2013.01.036i
3.4.1. Strengthen therapeutic alliance
A study with individuals with BD type I have shown that a
stronger alliance with the practitioner predicted fewer manic
symptoms 6 months later, less negative attitude towards medica-
tion and less of a sense of stigma (Strauss and Johnson, 2006). The
early alliance is the most important predictor of the following
attitude to treatment and the results revealed that poor social
support and depressive symptoms may interfere with the early
development of a strong treatment alliance (Strauss and Johnson,
2006). Therefore, practitioners should be especially focused on
creating a strong alliance when patients present depressive
symptoms and social difculties during the rst encounters. In
addition, establishment of a good therapeutic relationship seems
to be a common component of several psychosocial interventions
for BD.
3.4.2. Psychological treatments
Psychological treatments for BD have been shown to have an
overall effect of enhancing medical adherence (Maurel et al.,
2010). Different types of treatment report signicant improve-
ments in therapeutic adherence, for example cognitive-behavioral
approach, interpersonal therapy and family therapy interventions
(Colom, 2010; Velligan et al., 2010; Lolich et al., 2012). In a pilot
study of 79 BD patients, Zaretsky et al. (2008) have found that
between psychoeducation and CBT, both were equally effective to
raise medication adherence in patients, except that CBT itself had
a higher drop-out rate that the authors attribute to the longer
course of treatment. This suggests that the total duration to
treatment is to be considered in order to be accessible to as much
patients as possible, and avoid early drop-out.
3.4.3. Psychoeducation programs
Regarding interventions focused on psychoeducation, a lot of
programs have been assessed with very positive results on
various levels, including adherence (Colom, 2010; Maurel et al.,
2010; Velligan et al., 2010; Lolich et al., 2012). These programs
usually last between 6 weeks and 6 months, sometimes with
follow-up sessions, and in a group setting for 90120 min, once
per week. The specic contents can vary, but generally they
provide information on BD, help in identifying potential stres-
sors/triggers, and teach to recognize early symptoms of relapse
and coping strategies. The Barcelona Psychoeducation Program is
a well-known example of an efcient psychoeducation program
(Colom et al., 2005). It aims to teach patients to improve their
awareness of their illness, have an early detection of mood
episodes prodromal signs, prevent substance abuse, regulate
day-to-day habits, and learn stress-coping strategies. In the RCT
study, when comparing between groups the results were positive
for the efcacy at the two-year follow-up, although there was not
more adherence between the control group (group meetings) and
the intervention group (psychoeducation program) at 5 years
follow-up (Colom et al., 2009).
Other programs based on psychoeducation obtained similar
results. In Turkey, a 6-week psychoeducation program inspired
by the Barcelona Psychoeducation Program was provided by
nurses for outpatients in the remission period was effective in
increasing patient adherence (Eker and Harkin, 2012). The Psy-
choeducation program consisted of six sessions, once a week,
lasting around 90120 min in groups of 1012 persons. The
intervention group had a rate of 40.0% (pre-test) of adherence
and after 6 weeks, the patients adherence was signicantly
higher at 86.7% (post-test). In the control group (weekly appoint-
ment with psychiatrist for 510 min with regular information on
BD), the treatment adherence went from 38.9% before the 6 weeks
to 24.2% after.
 E. Leclerc et al. / Journal of Affective Disorders ] (]]]]) ]]]]]]
An American psychoeducation six-week program called LGP
(Life Goal Program) is based on behavioral principles from social
learning and self-regulation theories (Sajatovic et al., 2012). A RCT
study made on 164 outpatients has found that the program
could be effective for adherence on short term (3-month and 6-
month follow-up), showing signicant temporal pattern of
improvements in attitudes and behaviors. Nevertheless, com-
pared to the control group the higher adherence was not statis-
tically signicant, and at a 12-month follow-up, there was no
difference at all with the control group. The authors claim that the
low attendance to the intervention mitigated the results, since
slightly more than half of the intervention group (51%) did not
participate in at least four of the six sessions and 37% did not
participate in any session at all. More recently, Sajatovic et al.
(2012) used a 3 months psychosocial intervention they called
customized adherence enhancement (CAE) with 43 medication
nonadherent patients and got a 34% 727% (mean7SD) nonad-
herence rate at start-up, down to 10%715% (post-intervention).
Though this study was only a prospective one, these results are
encouraging.
In Australia, a pilot RCT study was realized with 58 patients of
relatively brief psychoeducation group (12 weekly sessions of
90 min) in dyadic called the Systematic Illness Management Skills
Enhancement Program-Bipolar Disorder (SIMSEP-BD) (DSouza
et al., 2010). The particularity of this program was that a patient
brought a close companion and psychoeducation was provided to
both of them. The results were promising and the medication
adherence was signicantly better in the intervention group, with
intervention group at (M1.2, SD1.0) compared to treatment as
usual group (M 0.4, SD0.7) (as rated by Adherence Rating
Scale, 0 meaning nonadherence, 1 partial adherence and 2 for full
adherence) (DSouza et al., 2010). The authors attribute these
results in part to the participation of the companion, whose
contribution goes beyond social support by often helping to
recognize the symptoms earlier or reminding the patient to take
his medication.
Regarding family intervention, a psychoeducation program
with the patient and its family during the patients time in the
hospital has been tested with an RCT design (Glick et al., 1991).
This programs intervention results were associated with post-
hospital compliance to psychosocial treatment (which included
individual, group and family therapy), but only with female
patients. This intervention is not recent though, and difference
in generations may bring different results regarding gender.
Family Focused Therapy (FFT) has also shown its efcacy for
improving medication adherence over a course of a two-year
follow-up (Miklowitz et al., 2003). This program is focused on a
exible psychoeducation, communication skills and problem-
solving skills with a 9-month intensive follow-up with the
family.
In a recent study of Proudfoot et al. (2012), psychoeducation
combined with a peer support group online has shown a sig-
nicantly higher adherence rate; the adherence was augmented
by increasing the perception of control, decreasing the perception
of stigma and signicantly diminishing levels of anxiety and
depression. These ndings conrm that having a peer support
group helps to have a better adherence to a psychoeducation
treatment.
4. Discussion
Even though adherence is an issue of great importance for
successful treatment of BD, there are relatively few systematic
studies evaluating adherence in BD, especially regarding other
factors than the patient, illness or treatment related ones. The
Please cite this article as: Leclerc, E., et al., Determinants of adherence to treatment in bipolar disorder: A comprehensive review.
Journal of Affective Disorders (2013), http://dx.doi.org/10.1016/j.jad.2013.01.036i
5
rst problem is the lack of a consensus about adherence concept,
and most of the studies do not consider broader adherence and
remain focused exclusively on medication treatment. This is
restrictive since even a very collaborating and usually adherent
patient can temporarily have a low adherence to medication, due
to treatment-related or illness-related factors, such as medication
side-effects or a manic episode. In these circumstances, a broader
conception and evaluation of adherence can help to give a better
representation of the global situation, which may need to be
addressed in a different way or different intensity.
Several factors were associated to adherence, including
those related to patient, the disorder and the treatment.
Although these factors have being pointed as directly related
to adherence, they are presumably mutually inuencing each
other and the nature of the relationship (e.g. cause, consequen-
tial, confounder) among them remains difcult to assess.
For example, some of the psychological data related to
nonadherence, like an external locus of control, cognitive
dysfunction, fear of side-effect, and negative attitude toward
treatment, could be associated with depressive thoughts,
thus a general severity of mood symptoms in BD (all asso-
ciated factors). The results of this review claim for more
studies designed specically to address determinants and
modulators of adherence to treatment in BD. Also, even though
some data from intervention programs suggested that social
support, perception of stigma or other family-related charac-
teristics may as well play an important role in adherence, these
possible factors were poorly assessed in the encountered
studies.
Regarding interventions designed to improve adherence, up to
now psychoeducation is the psychosocial treatment of choice.
This result is coherent with the fact that many modiable
nonadherence risk factors are related to the attitude and beliefs
of the individual or locus of control, which are easily targeted
with a psychoeducative approach. This is probably why it has had
good results on adherence with individuals having BD. To be
engaged and active in the treatment, thus adherent, the patient
needs to be fully aware of its condition, since through this
empowerment informed decisions can be made.
Another point to consider is that even though some psycho-
social treatment can help, there is a second problem emerging.
Considering the drop-out rate of some of these programs, the
adherence and engagement to these interventions is also
problematic. Some patients can also avoid altogether any
contact with an external clinic except during acute episodes,
not even being reachable by these interventions. Program
developers should keep in mind this problematic and try to
minimize this effect as much as they can. Some strategies that
could help in that aspect are to get in contact, create an alliance
and introduce the program to the patient the earliest moment
possible at the beginning of the follow-up or the stabilization
period, even in the inpatient unit if possible.
Besides, psychoeducation programs are usually adminis-
tered in a group setting. Group interventions were compared
to individual interventions, and seem to be more efcient, thus
conrming the relevance of this practice. Other aspects of
intervention programs that can improve adherence are to be
multifaceted, exible/customizable, based on modiable risk
factors of nonadherence, with a reasonable length (probably
maximum of 6 months), and with weekly interventions of 90
120 min to maintain the regularity of habits. Actual data
suggest that family interventions could be relevant, but more
studies are needed. Research in the intervention eld of raising
adherence are still very scarce, but many pilot studies being
positive, if they are carried out it will probably bring valuable
data in the next few years.
6 E. Leclerc et al. / Journal of Affective Disorders ] (]]]]) ]]]]]]
Role of funding source
No funding source.
Conict of interest
All the authors declare that they do not have any conict of interests.
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