738374

research-article2017
APY0010.1177/1039856217738374Australasian PsychiatryGallur et al.

Australasian
Old Age Psychiatry Psychiatry
Australasian Psychiatry

Recommencing lithium in Older 2017, Vol 25(6) 571­–573

© The Royal Australian and
New Zealand College of Psychiatrists 2017

Adults with Bipolar I Disorder Reprints and permissions:

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DOI: 10.1177/1039856217738374
https://doi.org/10.1177/1039856217738374
journals.sagepub.com/home/apy

Lara Gallur  Psychiatry Registrar, Central Adelaide Local Health Network, Adelaide, SA; Clinical Lecturer, Discipline of
Psychiatry, University of Adelaide, Adelaide, SA, Australia
Alice Powell  Geriatric Medicine Registrar, Central Adelaide Local Health Network, Adelaide, SA, Australia
Patrick Flynn  Senior Consultant Old Age Psychiatrist, Central Adelaide Local Health Network, Adelaide, SA, Australia

Abstract
Objectives: This paper addresses considerations in recommencing lithium in elderly patients with Bipolar I Disorder
and medical comorbidity. We focus on nephrotoxicity and cognitive impairment.
Methods: Case reports and review of relevant literature.
Results: Three elderly psychogeriatric inpatients admitted with severe manic relapse following lithium cessation are
described. In all cases, lithium was recommenced safely with good response.
Conclusions: Even with medical comorbidity it may be possible to recommence modified lithium therapy.

Keywords:  bipolar disorder, cognition, elderly, lithium, renal impairment

B
ipolar I disorder (BD I) in the elderly encompasses
patients with recurrent early-onset illness and
those with an index episode after age 50. Ninety
per cent of elderly patients with BD I have an early-
onset.1 The adage that BD I burns out with advancing
age is questionable, with lifetime follow-up studies dem-
onstrating an ongoing risk of recurrence even beyond
age 70.2 The number of episodes appears to increase the
recurrence rate.3 Psychiatrists are often asked whether
prophylaxis should continue in elderly euthymic
patients who develop medical issues.
Late-onset BD I has less evidence of a genetic predisposi-
tion, but more cerebrovascular risk factors,4,5 and poten-
tially a vascular aetiology.4,5 Numerous studies have
examined neuroimaging abnormalities and inflamma-
tory mechanisms of cognitive decline.6 First presenta-
tion mania necessitates thorough investigation to
exclude organic causes and identify medical comorbid-
ity.5,7 Post-stroke mania and mania associated with cog-
nitive impairment are also reported.5,6
Lithium is indicated for the treatment of mania and
ongoing prophylaxis, reducing the frequency and sever-
ity of episodes.8 Lithium has a narrow therapeutic index
and many interactions, leading to reduced prescribing in
the elderly.9,10 Concerns exist about the risk of manic
relapse following lithium cessation.8 Relapse occurs even
in those who have been stable, though the risk can be
lowered through gradual discontinuation.11 Recom­
mendations regarding the optimum serum level are
highly variable.12 A 2011 review recommended a range
of 0.5–0.6 mmol/L for patients over 50, on interacting
medications, or with diabetes insipidus, renal impair-
ment or thyroid dysfunction.12
We describe three cases involving elderly patients who
experienced a manic relapse of BD I following lithium
cessation.
Case 1
A 66 year-old man was diagnosed with BD I at age 21. He
had several early episodes of mania, with one requiring
electroconvulsive therapy (ECT). He had been stable for
many years with a lithium level of 0.8 mmol/L.
He developed worsening hypertension requiring escalat-
ing doses of antihypertensives: amlodipine, candesartan
and hydrochlorothiazide. Following a dose increase of
hydrochlorothiazide to 25 mg, he developed ­symptomatic
Corresponding author:
Lara Gallur, Central Adelaide Local Health Network, The
Queen Elizabeth Hospital, 28 Woodville Road, Woodville
South, SA 5011, Australia.
Email: lara.gallur@health.sa.gov.au

571

lithium toxicity with a serum level of 1.36 mmol/L and
was advised to cease lithium. He was hospitalised with
mania with psychotic features three weeks later.
On admission, lithium was recommenced along with
short-term olanzapine. One week later he developed
catatonic features with echopraxia, posturing and severe
agitation requiring seclusion. There was no improve-
ment with 6  mg of intramuscular lorazepam over
8 hours. He developed an acute kidney injury (AKI) and
elevated creatinine kinase at 1220 due to dehydration
and motor agitation.
All medications were ceased. He was transferred to the
intensive care unit (ICU) for fluid resuscitation and
given a midazolam infusion. He was treated with emer-
gency consent 100% bitemporal ECT over two consecu-
tive days in ICU with complete resolution of catatonia
and psychosis after the second treatment.
Lithium, amlodipine and candesartan were reintro-
duced, with resolution of mania within one week and no
adverse effects at a lithium level of 0.8  mmol/L.
Hydrochlorothiazide was discontinued.
Case 2
An 85 year-old man was diagnosed with BD I at age 76
during an episode of paroxetine-induced mania, during
which he had an extra-marital affair. He had no further
episodes of mania whilst on lithium for nine years,
though experienced lithium-induced hypothyroidism,
treated with thyroxine.
He was initially hospitalised with symptomatic lithium
toxicity at 1.9 mmol/L, associated with a urinary tract
infection. Lithium was ceased. Three weeks later he pre-
sented with mania characterised by increased spending
and libido.
His combative behaviour on the medical ward necessi-
tated the use of physical restraint. He subsequently
developed bilateral lower leg skin tears that developed
into severe erysipelas and lipodermatosclerosis. He
required three weeks of intravenous antibiotic and topi-
cal steroid treatment. Sodium valproate, aripiprazole,
olanzapine and quetiapine were sequentially trialled but
all were ceased as either ineffective or not tolerated.
Lithium was recommenced with rapid resolution of
mania. Cognitive deficits persisted with a Montreal
Cognitive Assessment of 23/30.13 A Single Photon
Emission Computed Tomography (SPECT) scan demon-
strated reduced medial temporal blood flow.
Case 3
A 75 year-old man was hospitalised with first episode
mania treated with lithium and quetiapine. He had had
a right frontal lobe ischaemic stroke one year earlier,
ischaemic heart disease, paroxysmal atrial fibrillation,
chronic kidney disease (CKD) and hypertension.
572
Australasian Psychiatry 25(6)
He was reviewed by a geriatrician due to complaints of
short-term memory loss, slowed cognition and deterio-
ration in computer skills. His Mini-Mental State
Examination14 was 28/30 and Addenbrooke’s Cognitive
Examination15 was 78/100, indicative of mild cognitive
impairment. An MRI demonstrated hippocampal vol-
ume loss, medial frontoparietal atrophy and small vessel
ischaemic changes. Psychotropics were withdrawn after
diagnosis of early vascular dementia.
Seven months later he was hospitalised with mania.
Lithium was recommenced, along with short-term olan-
zapine. There was gradual resolution of mania without
impact upon renal function.
Discussion
There are limitations in drawing conclusions about the
use of lithium in elderly patients with BD I from three
case studies. However, these patients illustrate how lith-
ium can be used safely and effectively even with medical
comorbidity. They share a common aetiology of manic
relapse after lithium cessation for medical reasons.
Lithium was safely reintroduced, leading to remission.
In hindsight, alternative approaches may have pre-
vented relapse. We note that two patients were treated
with olanzapine, but as this was only short-term treat-
ment for agitation, ongoing mood stability can be attrib-
uted to lithium.
CKD is a common cause for lithium cessation. Lithium
is renally eliminated in the elderly at approximately
half the rate of younger patients.16 The most robust
predictors of CKD are age, hypertension, diabetes,
ischaemic heart disease, nephrogenic diabetes insipi-
dus, AKI and the use of loop diuretics, hydrochloro-
thiazides and antipsychotics.10 The impact of the
duration of lithium therapy on renal function is con-
troversial. A decline in renal function has been found
in some studies investigating older patients with pre-
morbid CKD, but those with a normal baseline did not
deteriorate.10
Various strategies are used to prevent CKD in older lith-
ium users. These include restricting lithium levels to
< 0.8 mmol, vigilance around medication interactions,
maintaining adequate hydration, and treatment of AKI,
nephrogenic diabetes insipidus and cardiovascular risk
factors.10 With appropriate dosing and monitoring, lith-
ium does not appear to be associated with an increased
risk of CKD or renal decline.10
Even when there is significant renal dysfunction, there
may be a compelling argument to continue lithium ther-
apy. This can usually be determined with nephrologist
consultation and strategies to mitigate further renal
decline. For example, in patients with lithium-induced
nephrogenic diabetes insipidus, amiloride can be used.17
There have even been instances in which lithium has
been used in end stage renal disease including transplant
and dialysis patients.18
Gallur et al.
BD I episodes are associated with cognitive impairment
in both younger and elderly populations. Dementia is
frequently associated with BD I in the long term,4,6 pos-
sibly related to the cumulative burden of disease.
Cognitive dysfunction may be secondary to medical
comorbidity such as cerebrovascular disease and sub-
stance misuse. Additionally, lithium is associated with
potentially irreversible neurotoxicity, even with normal
serum levels.19
Better control of BD I may reduce or delay dementia and
there is evidence for a neuroprotective effect of lith-
ium.20 A large 10-year follow-up study conducted in
Denmark demonstrated that those on lithium therapy
have higher rates of dementia. However, continued lith-
ium usage rather than cessation was associated with a
decrease in the rate of dementia to the same level as the
rate for the general population.20 There is evidence from
preclinical studies of the positive effects of lithium on
neurogenesis, brain remodelling, angiogenesis, stem cell
functioning and inflammation.21 Lithium use is also
associated with greater cortical grey matter density22 and
a reduced risk of stroke.23
A recent review concluded that current evidence sup-
ports primary treatment of BD I with lithium, and the
limitation of other medications to short-term treatment
during acute episodes, or as an adjunct for partial
responders.24 Anticonvulsants such as sodium valproate
and carbamazepine are less effective than lithium for
long-term prophylaxis of BD I,7 and research regarding
the efficacy of atypical antipsychotics is evolving.7
Atypical antipsychotics have multiple anticholinergic,
extrapyramidal and metabolic side effects. They are also
associated with an increased risk of cardiovascular events
including fatal arrhythmias and stroke, blood dyscrasias,
venous thromboembolic disease and pneumonia.25
These risks are particularly significant in elderly patients.
Conclusions
Lithium continues to have a role in the treatment of BD
I in the elderly. The risks associated with mania should
be considered before withdrawing prophylactic lithium.
If discontinuation is required, this should occur slowly.
If there is medical comorbidity but a previous good
response to lithium, it may be possible to recommence
modified treatment.
Disclosure
The authors report no conflict of interest. The authors alone are responsible for the content
and writing of the paper.
Funding
The authors received no financial support for the research, authorship, and/or publication of
this article.
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