Bipolar disorder in the elderly - Future Medicine

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Bipolar disorder in the elderly Annemiek Dols1, Ralph Kupka1, Lars Vedel Kessing2,3, Max Stek1 & Martha Sajatovic* 15th Congress of the International Psychogeriatric Association: Reinventing Aging through Innovation, Care, Research, Technology The Hague, The Netherlands, 6–9 September 2011 Over 1200 participants from a wide array of psychogeriatric disciplines attended the 15th world congress of the International Psychogeriatric Association (IPA) in The Netherlands. In previous years, the meetings and activities of the IPA were strongly focused on research restricted to diagnosis and care of individuals with dementia. In recent years, there has been a shift of attention towards other psychiatric disorders in the elderly such as schizophrenia, substance abuse and bipolar disorder, which were for a long time nearly invisible in the scientific literature. The symposium venue was located in The Hague, a typical Dutch town not far from the coastline and home to several famous international institutions in the field of peace and justice. This successful meeting with the theme ‘Reinventing Aging through Innovation, Care, Research, Technology’ was co-chaired by Anne Margriet Pot (Professor of Geropsychology, Amsterdam, The Netherlands) and Frans Verhey (Professor of Neuropsychiatry, Maastricht, The Netherlands). A special symposium on ‘Bipolar Disorder in the Elderly’ also took place during the 4‑day meeting. This symposium was organized by The Netherlands Psychiatric Association, Faculty of Old Age Psychiatry and is an example of a neglected topic in geriatric mental health and represents the important diverse mental disorders that a large proportion of older adults and their families can experience. The symposium was co-chaired by Max Stek, Professor of Old Age Psychiatry and Chair of the Dutch Faculty of Old Age from The Netherlands and Martha Sajatovic from the USA. Presenting faculty were Ralph Kupka and Annemiek Dols from The Netherlands and Lars Kessing from Denmark.

An overview of geriatric bipolar disorder

Bipolar disorders (BDs) are complex genetically and neurochemically based illnesses, which affect approximately 2.6% of the population aged 18 years and older. Martha Sajatovic, Professor of Psychiatry at Case Western Reserve University (Cleveland, OH, USA) and Director of the Neurological Outcomes Center at University Hospitals Case Medical Center (Cleveland, OH, USA) presented an overview of late-life bipolar‑ ity. By contrast to rather low rates in the commu‑ nity, BD is present in 6% of geriatric outpatient visits, 8–10% of geriatric inpatient admissions, 3% of nursing home residents and 17% of geriat‑ ric patients presenting to psychiatric emergency departments. Given the global increase in the elderly population it is anticipated that absolute numbers of elderly patients with BD will also increase. While the evidence base on late-life BD has been limited, the last decade has seen growth in this much‑needed area of focus. As with younger adults, BD in the elderly may be underdetected and undertreated and 10% of BD cases first occur after the age of 50 years. Comorbidities, such as anxiety, substance abuse and medical illness, complicate diagnosis and treatment. BD elders are especially vulnerable 10.2217/AHE.11.75 © 2011 Future Medicine Ltd

to adverse pharmacotherapy effects as a result of their multiple chronic diseases, use of mul‑ tiple concomitant medications, and the phar‑ macokinetic and pharmacodynamic changes that accompany aging. Adverse drug reactions are a function of increase in age with the num‑ ber of adverse drug reactions per 10,000 indi‑ viduals relatively low before the age of 40 years; increasing sharply in the fifth decade of life and reaching 60  per  10,000 in the 80‑year‑olds. Factors that affect the types of adverse effects observed in older patients include age, gender, genetics, timing of medication, body habitus and pharmacokinetic drug interactions. Lithium, anticonvulsants, atypical antipsy‑ chotics, antidepressants and electroconvulsive therapy are all established treatments for mixedage patients with BD, and data are accumulating on the use of these modalities in geriatric BD. A growing body of evidence has identified bio‑ markers that are associated with disease, disease trajectory or duration, and with aspects of treat‑ ment response both in mixed-age and elderly BD populations [1,2] . Preliminary open-label trials in BD elders and secondary analyses from mixedage populations have suggested a beneficial role for lithium and the novel anticonvulsant Aging Health (2011) 7(6), 797–800

VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands 2 Psychiatric Center, Copenhagen University Hospital, Copenhagen, Denmark 3 Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark *Author for correspondence: University Hospitals Case Medical Center, 10524 Euclid Avenue, Cleveland, OH 44106, USA Tel.: +1 216 844 2808 Fax: +1 216 844 2742 [email protected] 1

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CONFERENCE SCENE – Dols, Kupka, Kessing, Stek & Sajatovic lamotrigine as well as the atypical antipsychot‑ ics quetiapine, olanzapine and aripiprazole [3,4] . However, larger and controlled trials are needed to validate the findings from smaller-sample analyses. While preliminary data on pharma‑ cotherapies is encouraging, treatment nonad‑ herence remains substantial in geriatric bipolar patients as is the case with younger BD popu‑ lations. Finally, psychological therapies appear promising, but have been understudied. BD across the lifespan

BD is a highly hereditary mood disorder that typically has its first manifestations in adoles‑ cence and early adulthood. Onset in prepuber‑ tal childhood is currently a matter of consider‑ able controversy. New cases of BD may occur at any age. In retrospective ana­lysis, subsyn‑ dromal symptoms of mood disorder may pre‑ cede the onset of full-blown episodes for years. Ralph Kupka (Professor of BDs, GGZ inGeest, VU University Medical Center, Amsterdam, The Netherlands) discussed the characteristics of BD across the lifespan. A staging model has been proposed, including an asymptomatic at-risk period, subsyndromal or aspecific prodromes, a first full-blown mood episode (either depression, which would lead to the diagnosis of depressive disorder, or mania/hypomania, directly indicat‑ ing BD), recurrent BD with or without inter­ episodic symptomatic or functional impairment, and chronic or treatment-resistant BD [5] . These stages can occur early or later in life, and evolve slowly or rapidly. It is unclear whether child‑ hood-onset, adolescent/adult-onset, and late-life BD have shared or distinct etiological and patho‑ genetic underpinnings. In shorter-term studies, it has been estimated that approximately 10% of patients with unipolar depression convert to BD over time but some longer-term studies suggest conversion rates of up to 40–50% over a lifetime [6,7] . At every age, BD has a different impact on the emotional and psychosocial development of the patients, and treatment approaches will be adapted accordingly. Conversely, the demands of each stage in life may influence the illness course. For women, hormonal influences appear to play an important role, since both the postpartum period and perimenopause are associated with increased incidence of mood disorders in general and BDs in particular. Cumulative risk factors in the longitudinal course are diagnostic delay, comorbid substance abuse, treatment nonadher‑ ence, psychosocial and circadian disruptions, the effect of multiple episodes (i.e., episode sen‑ sitization and kindling), cognitive deficits and 798

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medical comorbidity. In contrast to what many believe or hope, there is no evidence that BD fades out with increasing age. True late-onset BD (i.e., after the age of 50 years) differs in various aspects from early-onset BD, and is associated with more somatic determinants. Data from a large longitudinal international cohort study from the Stanley Bipolar Treatment Network, including patients aged from 18 to 82  years, show fewer patients with late-onset BD had a family history of mood disorder than early-onset patients [8] . Patients over the age of 50 years had a later onset of illness than younger patients (mean age of onset 25.9  vs  19.1  years). Time spent symptomatic during the first year of prospective follow-up increased with the total duration of illness, but not with age per se, despite adequate treatment. This underscores the necessity of early and continuous intervention in patients with this chronic, evolving disorder. Late-life mania

Mania can occur at any age, with de novo manic symptoms described in patients in their eighth and ninth decades. Late-onset mania can be caused by late-onset BD but also by a somatic condition or medication. The literature is sparse on this topic. Annemiek Dols (GGZ inGeest, Free University, Amsterdam, The Netherlands) presented a comprehensive critical review of studies reporting the prevalence of late-life mania in different patient populations. The estimated prevalence of mania in older patients in geropsychiatric hospitals was 8%. Late-onset mania had a mean prevalence of 20% in admitted bipolar patients. Reviewing the data on older bipolar patients admitted for mania one can conclude that medical comorbid‑ ity seems frequently, and in all cases potentially, related. In addition, several studies in late-onset mania patients aged 50  years and older show increased neurological comorbidity, suggesting that vascular risk factors prime development of mania [9] . Studies in older bipolar outpatients show that, as in younger adults, (hypo)manic symptoms are not as frequent as depressive symptoms, but still approximately 5% of bipolar patients experience (hypo)mania each year. It is not possible to draw firm conclusions on prevalence rates in commu‑ nities, nursing homes and other study samples because of limited data. Estimation of the prevalence of mania in the elderly is hampered by several factors. First, mania is not a diagnosis but part of a psychiatric diagnosis such as late-onset BD or schizoaffective future science group

Bipolar disorder in the elderly –

disorder, or due to an organic syndrome such as delirium, dementia or secondary mania. Second, there seems to be an overlap between the psy‑ chiatric diagnosis of ‘mania’ and the neurologic ‘disinhibition syndrome.’ The last condition can include distractibility, euphoria, emotional labil‑ ity and impulsive behavior and is mostly seen in patients with lesions in the orbitofrontal circuit. The disinhibition syndrome appears to overlap at most with the psychiatric concept of vascular mania as was initially proposed by Steffens and Krishnan [10] . Then, the concept of secondary mania is more challenging in the elderly. The list of medications, metabolic disturbances and neurological conditions that can cause secondary mania is extensive [11] . While secondary mania can occur at any age it can be expected to occur more often in the elderly, given the higher preva‑ lence of potentially related medical conditions and pharmacotherapy in older adults. However, one could argue that coincidental somatic find‑ ings should not be considered as a cause of manic symptoms, since the vast majority of patients with physical comorbidity do not develop manic symptoms. These factors can all account for an underestimation of the prevalence of late-life and late-onset mania. Based on the sparse published literature late-life mania is not rare, but further research is warranted to understand late-life mania and to help these patients with proper diagnostics and treatment tools/diagnostic considerations. BD, dementia & lithium

Lars Vedel Kessing, Professor of Psychiatry at the University of Copenhagen in Denmark, discussed the role of cognition in BD and the neuroprotective effects of lithium. Cognitive disturbances in patients with BD have attracted more attention during recent decades. Crosssectional data have shown that cognitive prob‑ lems are prevalent also during remitted phases of BD across a number of cognitive domains, including sustained attention, processing speed, memory and executive function. These cogni‑ tive disturbances have an impeding effect on patients’ social and occupational function. It is estimated that overall approximately half of euthymic bipolar patients over the age of 60 years exhibit neuropsychological deficits. Furthermore, a wealth of studies suggest that depression is a predictor of subsequent dementia although causality and pathogenesis continue to be unclear. The prevalence of dementia in patients with BD has received inadequate atten‑ tion but results from a few studies suggest that future science group

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patients with BD may be at increased risk of developing dementia in the long run [12,13] . It is well known that the risk of recurrence of affective episodes increases with the number of prior affec‑ tive episodes and some evidence further suggests that the rate of dementia also increases with the number of affective episodes as the illness goes on [14] . The pathogenetic mechanisms are unknown but a key hypothesis has emerged in relation to glycogen synthase kinase  3B, which is a key enzyme in the metabolism of amyloid precursor protein and in the phosphorylation of the tau pro‑ tein involved in the pathogenesis of Alzheimer’s disease [15,16] . Preliminary new data suggest that glycogen synthase kinase 3B activity is increased in patients with mild cognitive impairment and in Alzheimer’s disease [17] and also in patients with late-life depression [18] . Interestingly, among the many effects of lithium, it inhibits glycogen synthase kinase 3 [15,16] . Accordingly, findings from large register-based studies suggest that continued treatment with lithium reduces the risk of developing dementia in the long run among patients with BDs [19,20] . Other recent data suggest that lithium may prevent amnestic mild cognitive impairment from progressing to Alzheimer’s disease [21] . Lithium has previously been suggested to have neuroprotective effects and potentially to prevent the progression of other neurodegenerative disorders such as Parkinson’s disease, stroke and Huntington’s chorea although data to confirm these speculations are still miss‑ ing. The wide clinical and molecular effects of lithium may begin to emerge after more than 60 years of use in BD. Conclusion

The 15th Congress of the International Psychogeriatric Association (IPA) brought together scientific and clinical experts as well as bright, promising young researchers to pres‑ ent data and new ideas intended to facilitate advances in care for older individuals with men‑ tal disorders including dementing illness, mood disorders and psychoses. The active discussion that followed the symposium on geriatric BD highlighted the strong interest among research‑ ers and clinicians in better understanding how conditions that occur across the lifespan may be manifested in elderly patients. In line with the overall theme of the congress it is critical that continued effort be focused on improving the care of people with serious mood conditions such as BD across the lifespan. Research and innovation specifically focused on the older individual have the potential to improve health Aging Health (2011) 7(6)

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CONFERENCE SCENE – Dols, Kupka, Kessing, Stek & Sajatovic outcomes for geriatric patients and their fami‑ lies. The next international meeting of the IPA in Cairns, Australia from 8–11 September 2012 and their next world congress in 2013 in Seoul, South Korea will again bring together scientific and clinical experts in the field of care for older individuals with mental disorders. Financial & competing interests disclosure R Kupka has received a research grant from AstraZeneca. LV Kessing has been a consultant for Bristol-Myers Squibb, Eli Lilly, Lundbeck, AstraZeneca, Pfizer, Wyeth, Servier

References Papers of special note have been highlighted as: • of interest •• of considerable interest 1.

••

2.

3.

4.

5.

Forester BP, Streeter CC, Berlow YA et al. Brain lithium levels and effects on cognition and mood in geriatric bipolar disorder: a lithium‑7 magnetic resonance spectroscopy study. Am. J. Geriatr. Psychiatry 17(1), 13–23 (2009). Identifies that brain and serum lithium levels may be discrepant among older adults with bipolar disorder, and that higher brain lithium levels may be associated with toxic symptoms in the elderly. The clinical implication is that serum lithium levels alone may be unreliable in determining toxicity risk in bipolar elders. Yatham LN, Kapczinski F, Andreazza AC, Trevor YL, Lam RW, Kauer-Sant’Anna M. Accelerated age-related decrease in brainderived neurotrophic factor levels in bipolar disorder. Int. J. Neuropsychopharmacol. 12(1), 137–139 (2009). Sajatovic M, Gildengers A, Al Jurdi RK et al. Multisite, open-label, prospective trial of lamotrigine for geriatric bipolar depression: a preliminary report. Bipolar Disord. 13(3), 294–302 (2011). Sajatovic M, Chen P. Geriatric bipolar disorder. Psychiatr. Clin. North Am. 34(2), 319–333, vii (2011). Berk M, Conus P, Lucas N et al. Setting the stage: from prodrome to treatment resistance in bipolar disorder. Bipolar Disord. 9(7), 671–678 (2007).

6.

Angst J, Preisig M. Course of a clinical cohort of unipolar, bipolar and schizoaffective patients. Results of a prospective study from 1959 to 1985. Schweiz. Arch. Neurol. Psychiatr. 146(1), 5–16 (1995).

7.

Benazzi F, Akiskal HS. How best to identify a bipolar-related subtype among major depressive patients without spontaneous

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and Janssen-Cilag. M Sajatovic has received research grants from GlaxoSmithKline, AstraZeneca, Pfizer, Merck and Ortho-McNeil Janssen, is a consultant for the Cognition Group of United BioSource Corporation (UBC), and has received royalties from Springer Press, Johns Hopkins University Press and Oxford Press. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

hypomania: superiority of age at onset criterion over recurrence and polarity? J. Affect. Disord. 107(1–3), 77–88 (2008). 8.

Leverich GS, Nolen WA, Rush AJ et al. The Stanley Foundation Bipolar Treatment Outcome Network. I. Longitudinal methodology. J. Affect. Disord. 67(1–3), 33–44 (2001).

9.

Sajatovic M, Blow FC. Bipolar Disorder in Late Life. Johns Hopkins University Press, Baltimore, MD, USA (2007).

Arch. Psychiatry Clin. Neurosci. 259(1), 16–22 (2009). 16. Fountoulakis KN, Vieta E, Bouras C et al.

A systematic review of existing data on long-term lithium therapy: neuroprotective or neurotoxic? Int. J. Neuropsychopharmacol. 11(2), 269–287 (2008). 17. Forlenza OV, Torres CA, Talib LL et al.

Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer’s disease. J. Psychiatr. Res. 45(2), 220–224 (2011).

10. Steffens DC, Krishnan KR. Structural

neuroimaging and mood disorders: recent findings, implications for classification, and future directions. Biol. Psychiatry 43(10), 705–712 (1998).

18. Diniz BS, Talib LL, Joaquim HP, de Paula

VR, Gattaz WF, Forlenza OV. Platelet GSK3B activity in patients with late-life depression: marker of depressive episode severity and cognitive impairment? World J. Biol. Psychiatry 12(3), 216–222 (2011).

11. Van Gerpen MW, Johnson JE, Winstead

DK. Mania in the geriatric patient population: a review of the literature. Am. J. Geriatr. Psychiatry 7(3), 188–202 (1999). •

Summarizes all literature from 1960 to 1997 on geriatric mania and discusses epidemiology, psychopathology, neuropathology, differential diagnosis, evaluation, treatment and outcomes. An extensive overview of all possible causes of secondary mania is provided.

19. Kessing LV, Sondergard L, Forman JL,

Andersen PK. Lithium treatment and risk of dementia. Arch. Gen. Psychiatry 65(11), 1331–1335 (2008). •

12. Kessing LV, Olsen EW, Mortensen PB,

Andersen PK. Dementia in affective disorder: a case-register study. Acta Psychiatr. Scand. 100(3), 176–185 (1999). 13. Kessing LV, Nilsson FM. Increased risk of

developing dementia in patients with major affective disorders compared with patients with other medical illnesses. J. Affect. Disord. 73(3), 261–269 (2003).

20. Kessing LV, Forman JL, Andersen PK. Does

lithium protect against dementia? Bipolar Disord. 12(1), 87–94 (2010). 21. Forlenza OV, Diniz BS, Radanovic M,

Santos FS, Talib LL, Gattaz WF. Disease‑modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br. J. Psychiatry 198, 351–356 (2011).

14. Kessing LV, Andersen PK. Does the risk of

developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder? J. Neurol. Neurosurg. Psychiatry 75(12), 1662–1666 (2004). 15. Mendes CT, Mury FB, de Sa ME et al.

Lithium reduces Gsk3b mRNA levels: implications for Alzheimer disease. Eur.

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Includes data of dementia on all individuals who were prescribed lithium in Denmark during a 10‑year period (n = more than 16,000) as well as a third part of the general population. Continued lithium treatment was associated with a reduced rate of dementia to the same level as the rate for the general population.



Randomized 2-year trial of low-dose lithium versus placebo among individuals with amnestic mild cognitive impairment.

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