International Psychogeriatrics (2016), 28:6, 945–950 

C International Psychogeriatric Association 2016

doi:10.1017/S1041610215002380

Attitudes towards pharmacotherapy in late-life bipolar

disorder
...........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Soham Rej,1 Josien Schuurmans,2 Dominique Elie,3 Max L. Stek,2 Kenneth Shulman1
and Annemiek Dols2
1
Department of Psychiatry, Division of Geriatric Psychiatry, University of Toronto, Toronto, Canada
2
Department of Old Age Psychiatry, GGZ inGeest/VUmc, Amsterdam, the Netherlands
3
Department of Psychiatry, McGill University, Montreal, Canada

ABSTRACT

Background: Lithium remains a first-line treatment for bipolar disorder, but clinicians have considerable
concern over potential adverse effects, especially in older adults. Older patients’ attitude towards lithium
has not been investigated, even though negative attitudes are closely associated with reduced adherence. We
examine the attitude towards lithium pharmacotherapy in older adults with bipolar disorder.
Methods: In a cross-sectional study of 78 patients aged >60 years with bipolar disorder, the association
between lithium use and attitudes towards psychotropic pharmacotherapy was assessed using the Drug
Attitude Inventory (DAI-10), including multivariate analyses.
Results: Compared to patients using alternative psychopharmacological treatments (n=30), lithium users
(n=48) showed higher self-reported contentedness, subjective somatic health, and social functioning scores.
Although 58.7% of lithium users reported severe adverse effects, lithium users had more positive attitudes
towards psychotropic pharmacotherapy compared to non-users (DAI-10 mean score 6.0 vs. 3.9, p =0.01),
and this effect was independent of potential confounders.
Conclusions: Older bipolar patients using lithium have a more positive attitude towards psychotropic
pharmacotherapy, despite high rates of adverse effects. Future longitudinal studies could investigate whether
positive medication attitudes lead to improved treatment adherence and reduced bipolar disorder relapse in
older lithium users.

Key words: lithium, patient attitudes towards pharmacotherapy, adherence, geriatric, bipolar disorder

Introduction Despite lithium’s effectiveness, it also has the

potential for adverse effects such as renal disease,
Lithium remains a highly effective treatment for hypothyroidism, hyperparathyroidism, weight gain,
bipolar disorder (Yatham et al., 2013). It is useful and fine tremor (McKnight et al., 2012). Because of
in mania and is believed to prevent long-term this increased risk and concern for drug interactions
manic and depressive relapse better than other (Ghose, 1991), many psychiatrists avoid prescribing
agents (Geddes et al., 2010; Simhandl et al., lithium, especially in older adults (Shulman et al.,
2014). Although other pharmacological agents can 2003). Interestingly, these effects often appear
be helpful in bipolar disorder, including in acute as a consequence of normal aging and medical
bipolar depression (Yatham et al., 2013; Selle et al., comorbidity present in bipolar disorder rather
2014), up to 30–40% of patients may respond better than being caused by lithium itself (Rej et al.,
to lithium than to alternative medications (Geddes 2015). Also, certain effects are seen in alternative
et al., 2010; Grof, 2010). pharmacotherapies (e.g. weight gain) (Dols et al.,
2013). Still, the general opinion about lithium
Correspondence should be addressed to: Soham Rej, MD, MSc, Division is negative amongst clinicians (Strejilevich et al.,
of Geriatric Psychiatry, Sunnybrook Health Sciences Centre, University
of Toronto, 2075 Baycrest Avenue, Room FG-08, Toronto, ON, M4N 2011). This has contributed to less than 8% lithium
3M5, Canada. Phone: +(416) 480-6133; Fax: +(416) 480-5070. Email: prescription rates of bipolar disorder in North
soham.rej@mail.mcgill.ca. Received 2 May 2015; revision requested 9 Jul 2015; American patients (Carney and Goodwin, 2005)
revised version received 27 Sep 2015; accepted 6 Dec 2015. First published
online 18 January 2016. compared to 30%–55% rates seen in Europe and
This research has not been previously published or presented. worldwide (Hayes et al., 2011; Kessing et al., 2011;
946 S. Rej et al.
Renes et al., 2014). Because of the importance
of the therapeutic alliance and clinicians’ support
in maintaining patients’ positive attitudes towards
bipolar treatment (Pompili et al., 2013; Chang et al.,
2014), clinicians’ negative attitudes could translate
into poor patient attitudes towards lithium.
Since patients’ negative attitudes towards lithium
pharmacotherapy are closely associated with
reduced adherence and bipolar disorder relapse
(Rosa et al., 2007; Arvilommi et al., 2014),
this is potentially concerning. Amongst a variety
of reasons for bipolar pharmacotherapy non-
adherence such as illness severity, poor insight,
poor therapeutic alliance, cognitive dysfunction,
and other comorbidities (Pompili et al., 2013), one
of the primary reasons for lithium non-adherence
is adverse effects (73%), which is not the case
for other bipolar medications (Arvilommi et al.,
2014). It is not known, though, whether negative
pharmacotherapy attitudes are more frequent
amongst lithium users in late life, a time when
adverse medication effects become increasingly
common (Dols et al., 2014; Rej et al., 2014). To
the best of our knowledge, older patients’ attitudes
towards lithium have not been investigated.
In this paper, we hypothesize that lithium use
is independently associated with negative attitudes
towards psychotropic pharmacotherapy in a Dutch
sample of older adults diagnosed with bipolar
disorder.
Methods
Study design
This was a cross-sectional study of 78 patients
aged >60 years with bipolar disorder from a
psychiatric catchment area in the new western and
southern district of Amsterdam, the Netherlands, a
geographically well-defined urban area comprising
18.4 % of Amsterdam’s total population. Of all
catchment area inhabitants, 27,199 (19.8%) were
aged 60 years and over on January 1, 2012.
Using an electronic record system, we included
all 139 patients in the catchment area identified
as having a diagnosis of bipolar disorder by their
clinician. Of these, 25 were not eligible due
to exclusion criteria: having an actual diagnosis
other than bipolar disorder during our screening
procedure (n = 10, please see Demographic and
Clinical Characteristics), inability to communicate in
Dutch or English (n = 1), a concurrent diagnosis
of mental retardation (n = 4), dementia (n = 8),
or highly unstable psychiatric status (n = 1, e.g.
currently in a compulsory psychiatric admission).
An additional 13 patients refused to provide consent
and 23 declined participation in study interviews,
consenting only to medical record review. This
left 78 patients who provided written consent
for complete study interview. The study was
approved by the Medical Ethics Committee of the
VU University Medical Center, Amsterdam, the
Netherlands. The study’s full methodology has been
previously described (Dols et al., 2014).
Demographic and clinical characteristics
Characteristics potentially affecting patients’ atti-
tudes towards psychotropic pharmacotherapy were
recorded, including age and sex. DSM-IV TR
bipolar diagnosis and subtype was confirmed using
the Mini International Neuropsychiatric Interview
Plus (MINI), a structured diagnostic interview that
assesses psychiatric patients’ diagnoses according
to DSM-IV and ICD-10 criteria (Sheehan et al.,
1998; van Vliet and de Beurs, 2007). Duration of
illness and number of psychiatric admissions was
assessed by psychiatric interview and medical record
review. Mania symptoms were ascertained using the
Young Mania Rating Scale (YMRS), an 11-item
clinician-rated scale, with scores ranging 0–60, and
a score of ࣘ12 indicating symptomatic remission
(Young et al., 1978). Depression symptoms were
examined using the Center for Epidemiologic
Studies Depression Scale (CES-D), a 20-item self-
report scale, with scores ranging 0–60, and a
score of ࣘ12 indicating symptomatic remission
(Radloff, 1977). Subjective overall quality of life was
assessed using the Manchester Short Assessment
of Quality of Life (MANSA) (Priebe et al., 1999),
a brief 12-item instrument for assessing quality
of life. Current somatic complaints and somatic
history (e.g. hypertension, diabetes) were obtained
during a structured interview (Kriegsman et al.,
1996). Cognition was evaluated through the Mini-
Mental State Examination (MMSE), a clinician-
rated scale scored 0–30, with scores <24 highly
specific for dementia (Folstein et al., 1975).
Patient’s psychiatrists assessed global social and
occupational functioning on a scale of 0–100
using the Social and Occupational Functioning
Assessment Scale (SOFAS) (American Psychiatric
et al., 2000). The presence of self-reported
“severely-experienced” lithium-associated adverse
effects was based on a previously developed tool
(Wilting et al., 2009). Patients were asked in which
capacity (none, slightly, moderately, severely),
the following effects were experienced: headache,
dizziness, fatigue, blurry/double vision, trouble
concentrating, memory problems, nausea, diarrhea,
appetite changes, dry mouth, thirst, polyuria,
constipation, sexual dysfunction, sweating, tremor,
muscle weakness, and coordination problems. Side

effects self-reported as “severe” may not necessarily
have been disabling.
Outcomes
Our main outcome was a well-validated measure
of patients’ attitudes towards pharmacotherapy, the
DAI-10 (Awad, 1993). It included ten true/false
questions such as “For me, the good things about
medication outweigh the bad,” “Medications makes
me feel tired and sluggish,” with some items reverse-
scored. The DAI-10 is scored from 0 to 10, with
higher scores indicating more positive attitudes
towards psychotropic pharmacotherapy.
Statistical analysis
Demographic and clinical characteristics were
described (mean, standard deviation, %). Bivariate
associations between lithium use and demo-
graphic/clinical variables were assessed using χ2
for binary variables, T-test for normally distributed
continuous variables, and Mann–Whitney U tests,
as appropriate.
To determine whether there was a significant
difference between lithium and non-lithium patients
in drug attitudes, we performed Analysis of Variance
and Co-Variance (ANCOVA). Differences on
relevant clinical and demographic variables between
lithium and non-lithium users were entered as
covariates to see if these may have had an effect.
Additionally, bivariate linear regression between
number of severe adverse effects and DAI-10 scores
was performed amongst lithium users, to see if these
had an impact on drug attitudes in the lithium
sample. Adverse effect data unfortunately were not
available in non-lithium users. A two-tailed p < 0.05
was considered significant.
Results
Demographic and clinical characteristics
There were 48 lithium users and 30 non-users
(using anticonvulsants and other agents). Lithium
users had higher rates of type-I bipolar disorder, but
better subjective quality of life, and somatic health,
as well as social functioning (SOFAS) (Table 1).
Adverse effects in the lithium sub-sample
Amongst lithium users, 58.7% reported at least one
severely rated adverse effect. Over 78% reported at
least one moderate to severely rated adverse effect,
the most common being polyuria (42.6%), thirst
(40.4 %), tremor (31.9%), and fatigue (25.5%).
The mean number of moderate to severely rated
adverse effects was 3.4 (SD 2.6).
Pharmacotherapy attitudes in late-life bipolar 947
Attitudes towards bipolar pharmacology
(DAI-10) and correlates
Compared with non-lithium users, lithium users
had more positive attitudes towards psychotropic
pharmacotherapy (mean DAI-10 Score 6.0 (±2.8)
vs. 3.9 (±4.6), (t (74) = 2.6, p = 0.01).
In ANCOVA analyses comparing lithium
with non-lithium users, this significant difference
in DAI-10 scores was confirmed, even when
controlling for the difference in distribution of
bipolar subtype, and the difference in subjective
somatic health, subjective quality of life, and
global social functioning between both groups
(F (1, 69) = 7.62, p = 0.007). As well, lithium
use was associated with higher DAI-10 scores,
independently of euthymic versus not-euthymic
state.
Amongst lithium users (n = 48), there was no
significant relationship between the number of self-
reported moderate to severely rated adverse effects
and DAI-10 scores (β = 0.03, p = 0.84).
Discussion
This is the first study to demonstrate that geriatric
bipolar patients on lithium have more positive
attitudes towards their psychopharmacological
treatment than counterparts using alternative
medications. These attitudes appear independent
of higher rates of type-I bipolar disorder and lower
somatic comorbidity in lithium users. Furthermore,
drug attitudes in geriatric bipolar patients on
lithium seem to be unrelated to the presence of
self-reported adverse effects. This contrasts with
previous perspectives regarding patients’ attitudes
toward mood stabilizers. For instance, Kessing et al.
showed that depressed and bipolar disorder patients
had negative views on mood stabilizer use, including
lithium (Kessing et al., 2006), although in that
sample most of the largely non-geriatric patients
were not currently using mood stabilizers.
Our study also shows that older lithium users
report better subjective somatic health, even though
more than 50% of them report having significant
adverse effects. In a sense, our findings are
counterintuitive, since medication adverse effects
are usually correlated with negative attitudes
toward medication and poor adherence (Arvilommi
et al., 2014). The positive effects of lithium
treatment may have outweighed medication adverse
effects. Similarly, the positive attitudes of treating
physicians in the Netherlands, where most patients
with bipolar disorder are prescribed lithium, may
have had an impact on positive patient attitudes.
This suggests that our sample consisted mostly
of lithium users who were physically well enough
948 S. Rej et al.

Table 1. Differences between lithium and non-lithium users in an out-patient sample of geriatric bipolar
patients
TOTAL NON-
(N = 7 8 ) LITHIUM LITHIUM STATISTICS
(M E A N USERS USERS χ2 / F / T ( D F ) ,
( ±S D ) O R % (N = 4 8 ) (N = 3 0 ) P-VALUE
.........................................................................................................................................................................................................................................................................................................................

Demographic characteristics
Mean age in years (±SD) 68.5 (±7.8) 68.7(±8.1)years 68.1(± 7.5)years t(76) = 0.32 p = 0.75
Female (%) 48.7% 52.1% 43.3% χ2 = 0.57 p = 0.45
Illness severity variables
Bipolar 1(%) 53.8% 62.5% 40.0% χ2 = 3.76 p = 0.05
Bipolar 2(%) 46.2% 37.5% 60.0%
Duration of illness (years) 35.1 (±14.3) 35.3 (±15.4) 34.8 (±12.6) t(76) = 0.15 p = 0.88
Current state∗
Euthymic 60,8% 60.0% 62.5% χ2 = 0.05 p = 0.83
Not euthymic 39.2% 40% 37.5%
Past history of psychiatric admissions
None 23.1% 20.8% 26.7% χ2 = 1.09 p = 0.58
One 29.5% 27.1% 33.3%
more than one 47.4% 52.1% 40.0%
Past history of compulsory 41.7% 39.5% 45.5% χ2 = 0.21 p = 0.65
admissions
Somatic (physical) health variables
Subjective somatic health score 2.23 (0.81) 2.06 (0.73) 2.50 (0.86) t(75) = 2.38 p = 0.02
Number of somatic illnesses 2.5 (1.87) 1.94 (1.73) 2.5 (1.87) t(76) = 1.35 p = 0.18
Number of somatic illness 19.2% 20.8% 16.7% χ2 = 0.21 p = 0.77
Medication use variables
Number of psychotropic meds 1.97 (1.12) 1.94 (1.08) 2.03 (1.19) t(76) = −0.37 p = 0.72
Anticonvulsant medication (%) 26.9% 10.4% 53.3% χ2 = 17.3 p <0.001
Antipsychotic medication (%) 39.7% 31.2% 53.3% χ2 = 3.76 p = 0.06
Antidepressant medication (%) 26.9% 20.8% 36.7% χ2 = 2.35 p = 0.10
Benzodiazepines (%) 38.5% 31.2% 50% χ2 = 2.74 p = 0.10
Number of medications (including 4.38 (3.16) 3.96 (3.01) 5.07 (3.31) T (76) = −1.52 p = 0.13
somatic medication)
Any serious adverse effect of lithium? NA 58.7% NA NA
Any moderate to serious adverse NA 78.3% NA NA
effect of lithium?
Scores on psychometric scales
Subjective overall quality of life 5.00 (1.36) 5.29 (1.05) 4.53 (1.66) t(76) = 2.48 p = 0.02
(MANSA item)
MMSE score 27.7 (±2.1) 28.0 (±1.8) 27.2 (± 2.4) t (76) = 1.7 p = 0.09
SOFAS 63.1 (±11.8) 67.2(± 11.1) 60.5 (±12.6) t (76) = 2.46 p = 0.02
CES-D 11.1 (±10.3) 10.2 (±9.0) 12.5 (±12.0) t (76) = 0.95 p = 0.35
YMRS 8.9 (±10.5) 9.4 (±11.8) 8.2 (±9.5) t(76) = 0.47 p = 0.64

Abbreviations: MMSE: Mini-Mental state examination, SOFAS: Social and Occupational Functioning Assessment Scale.CES-D:
Center for Epidemiologic Studies Depression Scale, YMRS: Young Mania Rating Scale.
MANSA: Manchester Short Assessment of Quality of Life.
N.B. A euthymic state was defined as having both a YMRS ࣘ 12 and a CES-D ࣘ12. Being “not euthymic” was defined as having a score
of >12 on either the CES-D or the YMRS, or on both.

to be continued on lithium by their physicians. It for reduced bipolar disorder relapse in lithium users
is possible that in the 30–40% of bipolar disorder (Geddes et al., 2010).
who respond preferentially to lithium (Geddes et al., The possible reasons for the association between
2010), lithium’s considerable benefits on mental lithium use and more positive bipolar drug attitudes
health may outweigh its negative aspects (Miura have interesting implications for future research
et al., 2014), thereby leading to better medication and eventual knowledge translation into clinical
attitudes. Future studies could assess whether practice. If patients’ attitudes and choice of lithium
positive medication attitudes lead to improved are based on clinicians’ positive attitudes (clinicians
treatment adherence as an additional mechanism in our Dutch sample had very positive attitudes

compared to some North American samples
(Baldessarini et al., 2007), then the effects of greater
clinician education around lithium prescribing
should be investigated. If capacity for tolerating
severe side effects is what might separate lithium
users from non-users, then patient support for side
effects might be important. If attitudes toward
medications are a product of long-term lithium
use and benefit, then “success stories” may help
navigate consumers towards lithium.
Limitations
There are limitations of this study. Our cross-
sectional design made causation difficult to assess.
Our sample size was modest, but nonetheless
adequate compared to other studies in late-life
bipolar disorder. Because of the modest sample size,
it was difficult to control for α-inflation, but we used
a pre-specified hypothesis and multivariate analyses
in our attempt to prevent a false-positive result. In
lithium users, duration of lithium use and reason
for using lithium (aside from bipolar disorder)
were not available. For the non-lithium user group,
subjective adverse effect data and previous history
of lithium intolerance were not available, making it
difficult to assess whether medication intolerance
contributed to the more negative drug attitudes
in the non-lithium users. A higher proportion
of non-lithium users had bipolar disorder type
II, which is sometimes associated with harder-
to-treat depression (Selle et al., 2014) and can
thus theoretically affect drug attitudes. However,
depression (CES-D) scores did not differ between
lithium/non-lithium groups, and bipolar disorder
subtype did not independently predict medication
attitudes.
Conclusions
Despite considerable adverse effects, older lithium
users with bipolar disorder maintain a more positive
attitude toward psychotropic pharmacotherapy
compared to non-lithium users.
Conflicts of interest
None.
Description of authors’ roles
S. Rej co-designed the research question and
statistical analysis plan, and wrote the paper. J.
Schuurmans was responsible for statistical design
of the study, conducted the statistical analyses,
and critically reviewed all drafts of the manuscript.
Pharmacotherapy attitudes in late-life bipolar 949
M. Stek, D. Elie, and K. Shulman contributed to
formulation of the research question and statistical
design, and contributed significantly to the writing
of the manuscript, reviewing all drafts. A. Dols
designed and conducted the parent study, was
involved in data collection, co-designed the research
question and statistical analysis plan, and critically
reviewed all manuscript drafts.
Acknowledgments
Soham Rej has received training and salary support
from the Canadian Institutes of Health Research
(CIHR) and the Fonds de Recherche Quebec –
Santé (FRQS). No specific funding was received
for this study.
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