Because of a lack of definitive guidelines and clinical evidence, elderly
patients with bipolar disorder pose particular challenges in terms of
appropriate pharmacotherapy. Psychiatrists must consider the unique response
of elderly individuals to each drug and monitor these patients more closely
than is typically required for younger adults. So explained experts at a
session titled "Without a Map: Treating Geriatric Bipolar Disorder in
the Absence of Guidelines" at the annual meeting of the American
Association for Geriatric Psychiatry (AAGP) in March.
Kenneth Shulman, M.D., a professor of psychiatry at Sunnybrook Health
Sciences Centre at the University of Toronto and an expert in geriatric
psychiatry, discussed the diversity of underlying etiologies and
manifestations in older patients. In addition to those who have had bipolar
disorder from a young age, symptoms of mania and cycling mood may emerge later
in life as a result of vascular or neurological disorders. Stroke and brain
lesions have been linked to late-life bipolar disorder in past research.
Diagnosis is further complicated by presentations that mimic certain types of
dementia such as disinhibition syndrome and impaired cognitive functions.
Shulman cited data indicating that mania is associated with higher
mortality risk than is unipolar depression in the elderly. "Late-life
bipolar disorder causes a heavy burden on health care services," he
commented. Comorbidities, both nonpsychiatric and psychiatric, are common in
elderly patients and lead to worse outcomes and more complications. Shulman
recommended that clinicians conduct thorough assessments in older patients who
present symptoms of depression and mania, including neurological and
neuroimaging exams, cognitive function tests, cardiovascular disorder
screening, history of mood disorders earlier in life, or other
"Pharmacotherapy is a cornerstone of treatment of geriatric bipolar
disorder," said Robert Young, M.D., a professor of psychiatry at the
Institute of Geriatric Psychiatry at Weill Cornell Medical College.
Psychotherapy interventions, including individual, group, and family
therapies, are also applied in the clinical setting. He reminded clinicians
not to dismiss electroconvulsive therapy, which has been shown to be highly
effective and may work fairly rapidly in elderly patients.
The biggest difficulty facing clinicians is the lack of prospective,
randomized, controlled clinical trials in this patient population. Neither the
efficacy nor the minimum and maximum dosages have been clearly established for
lithium, valproate, carbamazepine, and other anticonvulsants.
Data on second-generation antipsychotics such as quetiapine and
aripiprazole suggest some efficacy in bipolar depression, but these data were
extracted from a small number of elderly patients in clinical trials who were
above age 60 but less than age 80 and were generally healthy and with few
comorbidities. "There are no available data regarding the efficacy of
atypical antipsychotic medication in the very old," Young said.
Evidence of the efficacy and safety of long-term maintenance treatment with
lithium and other agents is equally limited and generally based on
Young is the principal investigator of the ongoing multisite Acute
Pharmacotherapy of Late-Life Mania (GERI-BD) study funded by the National
Institute of Mental Health. It is a nine-week, randomized, double-blind,
concentration-controlled, parallel-group clinical trial of bipolar patients
over 60 years old. The study is expected to provide much-needed clinical
evidence for rational treatment.
"We have seen a growth in the use of atypical antipsychotic drugs as
the first-line treatment for mania in the past few years," said Martha
Sajatovic, M.D., a professor of psychiatry at Case Western Reserve University
School of Medicine and director of Geropsychiatry at University Hospitals of
Although a number of antipsychotic drugs have been approved by the Food and
Drug Administration (FDA) for the treatment of mania in adults, their safety
profile in frail elderly patients remains unclear. In 2005 the FDA issued
warnings on the use of second-generation antipsychotics for the treatment of
behavioral disorders in elderly patients with dementia because of increased
risk of death. Whether similar concerns apply to elderly bipolar patients
without dementia is unclear, Sajatovic noted.
Drug concentrations in plasma are affected by age, sex, genetic
differences, comorbid diseases, physiological variations, and drug-drug
interactions. For older patients, polypharmacy and multiple comorbidities are
two of the most prominent considerations in choosing the right drug and dosage
by the clinician. Sajatovic cited data showing that individuals with bipolar
disorder may develop dementia at a greater rate than others at the same age
without the disorder and that adverse drug reactions increase dramatically
with advancing age.
The pharmacokinetic and pharmacodynamic changes associated with aging means
that the dosage guidelines derived from clinical trials in younger adults
cannot be automatically extrapolated to older adults, both Sajatovic and Young
For example, decreased cardiac, renal, and liver functions common in the
elderly can reduce the clearance rate of most mood-stabilizing agents. Certain
drugs frequently used by the elderly, such as diuretics,
angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatory
drugs, can interact with lithium and put patients at risk for serious
toxicity. Both valproate and carbamazapine significantly inhibit or induce the
liver enzymes responsible for the metabolism of various concomitant drugs
including antidepressants and antipsychotics.
Sajatovic urged psychiatrists to consider comorbid medical conditions
carefully and obtain a complete medication history before and during a
patient's pharmacologic treatment for bipolar disorder.
"Primary care providers may change non-psychiatric drugs without the
knowledge of psychiatric specialists," she said. "Ask your
patients to bring all of their pill bottles."
This AAGP educational program was supported by an educational grant from
AstraZeneca. Sajatovic disclosed receiving grants from GlaxoSmtihkline and
being a consultant/speaker for Astrazeneca. Shulman and Young disclosed that
they had no potential conflicts regarding the content of the program.▪