Chapter 5 – Mania in Late Life


Mania in late life is a serious disorder that demands specialist assessment and management. However, it is greatly under-researched. The mainstay of the older adult psychiatry workload will inevitably be concerned with assessing and managing dementia and depression, but the steady rise in the ageing population with longer survival means that there will be an increase in absolute numbers of older people presenting with mania. There are no specific treatment algorithms available for mania in late life. This chapter reviews mania and hypomania in late life and concentrates on diagnosis, assessment, and treatment, as well as on the management considerations associated with this important age group.

Chapter 5 Mania in Late Life

Felicity Richards and Martin Curtice


Mania in late life is a serious disorder that demands specialist assessment and management. However, it is greatly under-researched. The mainstay of the older adult psychiatry workload will inevitably be concerned with assessing and managing dementia and depression, but the steady rise in the ageing population with longer survival means that there will be an increase in absolute numbers of older people presenting with mania. There are no specific treatment algorithms available for mania in late life. This chapter reviews mania and hypomania in late life and concentrates on diagnosis, assessment, and treatment, as well as on the management considerations associated with this important age group.

Few studies have addressed the specific difficulties faced by older-adult psychiatrists when a patient presents with mania or hypomania in late life. The numbers of patients with atypical and typical presentations of mania in later life are not insignificant and with the steady rise of the ageing population, coupled with better healthcare and greater survival, there will be increasing demands on service provision. Along with diagnostic uncertainties at presentation, mania in older adults tends to be more debilitating and severe than in the younger population, resulting in more frequent hospital admissions,1 higher rates of psychotic symptoms,2 with higher levels of comorbidity and polypharmacy, and no specific treatment algorithms available to address these management considerations in older adults.

The literature on mania and hypomania in late life (defined as over 65 years of age) is scant and research papers tend to use different age cut-offs, preventing easy transfer of practical information. Nevertheless, we aim here to give an overview of mania and hypomania in this important age group.

Classification of Bipolar Disorder

There are two ways available to clinicians to classify episodes of bipolar disorder. Both the ICD-113 and the DSM-54 allow for diagnoses of mania (with or without psychotic symptoms) and hypomania. It is unusual for an episode of mania or hypomania to occur in isolation.

According to ICD-11, ‘Although the diagnosis can be made based on evidence of a single manic or mixed episode, typically manic or mixed episodes alternate with depressive episodes over the course of the disorder’.3 A mixed episode ‘is characterized by either a mixture or very rapid alternation between prominent manic and depressive symptoms on most days during a period of at least 2 weeks’.3 ICD-11 also characterizes whether the current episode of bipolar affective disorder is mania or depression, and these are further divided into whether psychotic features are present or not.

DSM-5 classifies episodes into bipolar I and bipolar II disorders. Bipolar I disorder involves one or more manic or mixed episodes. The manic episode may be preceded by or may be followed by hypomanic or major depressive episodes, but are not required for diagnosis. Bipolar II disorder is characterized by one or more major depressive episodes, accompanied by at least one hypomanic episode but never having had a full manic episode.

Terms Specific to Mania in Late Life

Mania or hypomania may persist into late life as part of a lifelong affective illness, with these patients ‘graduating’ from the general adult services. Although mania usually presents before the age of 30, with a further peak in females in their 50s, it can present for the first time in old age, with a third peak (especially in males) in the eighth and ninth decades.2

Many patients are believed to convert to mania in later life, commonly following recurrent depression. This can either be a part of the natural progression of illness or be a manifestation of antidepressant-induced mania. It has been proposed that treatment with tricyclic antidepressants is twice as likely to result in a manic episode compared with treatment with selective serotonin reuptake inhibitors or placebo. Venlafaxine or other dual-action medications have also been found to increase the risk of a switch from depression into mania.5

Other useful concepts and subtypes have been put forward for use, especially in older adults, including ‘secondary mania’ (or ‘disinhibition syndrome’) and ‘vascular mania’.

Secondary Mania

It is accepted that patients with forms of neurological illness can present with affective disorders. The concept of secondary mania, first described by Krauthammer and Klerman,6 was used to explain late-onset presentations of mania associated with a diverse group of medical conditions. Neurologists tend to favour the term ‘disinhibition syndrome’, but the clinical presentation and features are similar.

Secondary manias can be seen in patients with multiple sclerosis, Parkinson’s disease, temporal lobe epilepsy, AIDS, dementia, and traumatic brain injury.7 Indeed, secondary mania is seen in 9% of patients with traumatic brain injury, with a preponderance of basal temporal lesions noted in these patients. A positive family history of affective disorder and subcortical atrophy before injury are added risk factors.8

A number of further studies have supported the concept of an association with neurological comorbidity. Tohen and colleagues found that patients with a first-episode mania in old age were twice as likely to have a comorbid neurological disorder compared with those who had experienced multiple episodes.9 Many studies have suggested that secondary mania/disinhibition syndromes are associated with right-sided lesions, based on the hypothesis that disrupting connections within the orbitofrontal circuit mediates manic symptoms.8 Indeed, Goodwin and colleagues state that any lesion involving right-sided cortical or subcortical areas may be associated with secondary mania.5 Other examples highlighting the heterogeneous nature of the causes of secondary mania include metabolic disturbance, endocrine disorders, such as thyrotoxicosis and hydrocortisone replacement, neoplasia, and infection, all of which can also present as a delirium, often adding to diagnostic uncertainty.8 A systematic review of 35 case reports of first-episode mania or hypomania in the over-50s found that 82% had a suspected underlying organic origin. In 28% of these cases, treatment of the organic cause contributed to successful remission of the manic episode.10

Vascular Mania

Steffans and Krishnan proposed vascular mania as a subtype of mania.11 The concept is similar to that of ‘vascular depression’ proposed by Alexopoulous and colleagues,12 and is used to explain the high rates of manic symptoms seen in those who have evidence of cerebrovascular disease. This concept is supported by the relatively acute onset of manic symptoms that can occur following a cerebrovascular event, the higher prevalence of silent cerebral infarcts on neuroimaging in late-onset patients, and the association of hyperintensities with risk factors such as hypertension, heart disease, and diabetes.8, 13


There appear to be discrepancies between the reported occurrence of bipolar disorder in the older adult population and no clear consensus on mania/hypomania. A number of studies have consistently reported that the prevalence of bipolar disorder has an inverse relationship with age, with a decline in prevalence with increasing age.14, 15 About 10% of all bipolar cases are over the age of 50 years in their first episode.16

One study reported an overall prevalence of late-life mania estimated to be 6% in older psychiatric inpatients, and a mean prevalence of late-onset mania of 44.2% in older inpatients with bipolar disorder.17 Another study suggested that up to 0.5% of people over 65 will have bipolar disorder. A 1-year incidence rate of 0.1% among adults over 65 has been indicated.18 This is lower than that for adults aged 45–65 (0.4%) and 18–44 (1.4%).2

Burden of Bipolar Disorder in Older People


Older patients can have a disproportionate impact on health services and some estimate that bipolar disorder accounts for approximately 8–10% of admissions to psychiatric units, similar to that of younger adults, and 6% of older adult psychiatry outpatient visits.2 Research predicts increasing numbers of patients accessing services. A report by the King’s Fund estimated the projected greatest proportional increase in the number of people with bipolar disorder and related conditions is still in those aged 65 and over.14 However, the increase in the number of older people will not significantly affect the total number of new patients because of the lower prevalence in this group.

In the UK, the mean service costs of bipolar disorder and related conditions for those aged 65 and over are projected to be approximately four times greater than for younger age groups, owing to higher average inpatient and residential care costs.14 In this study, the elements used to estimate total costs were prescribed drugs, inpatient care, other National Health Service (NHS) services, supported accommodation, day care, other social services, informal care, and lost employment.

Among older people, the rate of hospital admission for bipolar disorder is the same as that for schizophrenia, although the length of stay is shorter.2 Compared with older outpatients with unipolar disorder, those with bipolar disorder use four times the amount of mental health services, including inpatient hospitalization, case management, skills training, and community support.19 The overall cost of annual care of older adults with bipolar disorder and comorbid dementia is more than twice that for those with bipolar disorder alone.20

Morbidity and Mortality

According to the King’s Fund report on integrating physical and mental health, people with severe mental illness such as bipolar are at a particularly high risk of physical ill health as a result of medication side effects, lifestyle-related risk factors, and socioeconomic determinants.21 Bipolar disorders in particular are associated with higher morbidity and mortality. The increase in the number of comorbid medical conditions is directly proportional to age, and approximately 67% of over-70-year-olds who have bipolar disorder have at least one significant medical condition,22 with another study stating that older people with bipolar disorder have an average of three to four comorbid medical conditions.23 Patients with bipolar disorder, especially bipolar I (one or more manic episode(s) or mixed episode(s)), have increased mortality from cardiovascular causes in particular. The difference in cardiovascular mortality risk may reflect the physical health consequences of mania/hypomania because depressive symptom burden is not related to cardiovascular mortality.24

An increase in morbidity from obesity and type 2 diabetes mellitus has been reported in people with bipolar disorder compared with the general population. Explanations for these possible increased risks include comorbidity with substance misuse and other medical conditions, inadequate prevention of cardiovascular risk factors (such as smoking, obesity, and lack of exercise), the side effects of psychotropic medications, and poor engagement with general medical care.25


Bipolar disorder is associated with a high suicide risk (lifetime risk of 8–20%),26 especially during depressive episodes or mixed states. However, there is a lack of literature specifically concerning completed and attempted suicide in those over 65 with mania or hypomania. Factors for completed suicide in working-age patients that can be extrapolated to older people include inadequate treatment (medication) and inadequate follow-up by mental health services.27 With the above in mind, older patients with bipolar disorder should be recognized as high risk and be provided with long-term intensive support.


A family history of affective illness appears to increase the risk of bipolar disorder at any age. However, older patients with first-onset mania appear to have fewer first-degree relatives with affective illness, compared with patients presenting earlier. Figures are inconclusive, with results ranging from 24% to 88% for the presence of a positive family history.8

As we have already discussed, physical illnesses, particularly neurological conditions, can also be associated with mania (so-called secondary mania) as can cerebrovascular incidents (i.e. ‘vascular mania’). So the aetiology of mania involves genetic and other biological factors.

Diagnosis and Assessment

In the diagnosis of mania in late life, clinicians commonly use either the ICD-11 or the DSM-5 classification. However, it is important to note that rather than the classic symptoms of elevated mood and grandiosity, mania in the older person can cause initial diagnostic uncertainty, with irritability, distractibility, and disorientation being prominent presenting symptoms,28 masking delirium, cognitive impairment, or indeed depression. The differentiation between delirium and mania or hypomania can be aided by observation over time.1 Mania, therefore, should be included in the differential diagnosis of all older patients with a relatively acute onset of agitation and confusion, despite lack of a previous history of affective disturbance (see Box 5.1).

Box 5.1 Differential diagnosis of mania in late life

  • Delirium – hyperactive type

  • Dementia – especially with frontotemporal involvement

  • Stroke

  • Early-onset mania, as part of coexisting bipolar affective disorder

  • Secondary mania, i.e. due to medications, physical illness

  • Late-onset schizophrenia-like psychosis

  • Acute and transient psychotic disorders

Taking a comprehensive history, ideally with a collateral account, is invaluable. For a first presentation of mania, the history may reveal past episodes of hypomania or depression, not severe enough to warrant referral, treatment, or intervention by mental health services. Classification of mania in later life will be helpful in deciding on management and future care.

Full investigations should include a complete physical examination, including neurological examination (see Box 5.2). Routine blood tests should be carried out and an electrocardiogram (ECG) taken, especially if antipsychotics, lithium, or valproate are being considered.

Box 5.2 Investigations for mania in late life

  • Physical examination, including neurological examination

  • Blood investigations – urea and electrolytes, glomerular filtration rate, liver function tests, thyroid function tests, full blood count, vitamin B12 and folate, bone profile, and glucose

  • Midstream specimen of urine

  • ECG

  • Chest X-ray

  • Computed tomography (CT) and/or magnetic resonance imaging (MRI) if indicated (in the presence of neurological signs)

Full exploration of any causes of delirium should be excluded, to include a midstream specimen of urine. Mania in older adults is associated with a high rate of medical and neurological disease.9 Consequently, all patients presenting with first-onset mania should be carefully screened for contributing medical disorders and brain imaging is useful in this context.

Owing to the known associations with bipolar disorder and cardiovascular risk, initial assessment should also include careful history of common cardiovascular risk factors, such as smoking, excessive alcohol use, hypertension, hypercholesterolaemia, and diabetes.8

Considering the causes of secondary mania discussed earlier, medication(s) should be examined and any recent changes identified: antidepressants, antibiotics (‘antibiomania’), in particular clarithromycin and other macrolides, steroids, and oestrogens are all examples of inducing agents for secondary mania.28, 29

Screening Instruments

The diagnosis of mania relies on clinical evidence and assessment. In clinical practice there are no screening tools available for easy use in psychiatric or general hospital settings. Diagnostic scales can aid in clinical diagnosis, but are mainly used in the research setting.30 Self-report questionnaires may be more difficult to use with older people because of sensory impairments.

Psychiatric Comorbidity

Anxiety Disorders and Substance Misuse

Psychiatric comorbidity in bipolar disorder is widely documented. Reports have indicated that generalized anxiety disorder shows a lifetime prevalence of 20.5% and a 12-month prevalence of 9.5% in older patients with bipolar disorder. For panic disorder, lifetime prevalence is as high as 19%, whereas 12-month prevalence is 11.9%.31 Similarly, comorbid post-traumatic stress disorder, substance misuse, ‘other anxiety’, or dementia have been found to occur in nearly 29% of older adults with bipolar disorder.20

Substance misuse, a significant comorbidity in younger adults with bipolar disorder, is less common in older cohorts, but nevertheless occurs more frequently than in healthy older controls. A lifetime and 20-month prevalence of 38% for comorbid alcohol use disorders has been reported,31 and patients with bipolar disorder with a lifetime history of substance misuse appear to have a greater number of hospital admissions.2

Cognitive Impairment

Cognitive impairment in late-onset bipolar disorder has been widely reported and is associated with more severe cognitive impairment than in early-onset disorder.32 Compared with age-matched controls, patients with bipolar disorder score lower on most cognitive measures and patients with late-onset disorder show more impairment in psychomotor performance and mental flexibility. Older adults whose onset of bipolar illness had been before the age of 50 were found to have impairment across a range of domains, including selective attention, verbal memory, and verbal fluency, in the euthymic state. It has been concluded that older patients with bipolar disorder may have substantial cognitive impairments, perhaps indicating a trait-like cognitive disability related to the disease.33


Management of mania or hypomania in late life is complex. Onset is often relatively sudden and severe and individuals will therefore most likely need inpatient admission, either as informal patients or commonly under the Mental Health Act – usually as a result of the risks a manic episode can pose to the patient and to others from poor judgement and associated actions.5 Before and following admission, the importance of good working and understanding of this disorder within multidisciplinary teams is vital. The recognition and management of concurrent physical illnesses is as much the job of the older-adult psychiatrist as of the general practitioner. Importantly, clinicians should be aware that older people can be at risk of the development of sudden-onset depressive symptoms following recovery from a manic episode.

It is not uncommon for patients to have poor engagement with primary care and contact with psychiatric services can often aid in screening for physical disorders. Issues such as adherence and the practicalities of medication prescribing in this age group need to be addressed. And clinicians need to be aware of the risks of polypharmacy and potential drug–drug interactions with a number of the psychotropics discussed later. Care planning should consider the patient’s social situation and the effects that the illness can have on family members and carers.

Pharmacological Management

Treatment of older people often involves compromise because the side effects of treatment may be as harmful as the condition being treated. There continue to be no specific treatment algorithms for mania in late life,5 with a scarcity of published controlled trials in the older population. In practice, treatment for older adults with mania or hypomania generally follows similar guidelines as for other groups. However, certain precautions should be taken because of the differences in pharmacokinetics, side effects, concomitant medication use, and comorbidity. Adherence at times can be difficult, because of the nature of acute episodes, the presence of cognitive impairment, or a reluctance to take medication.

As a general guide, medication doses are lower and should be titrated with care, owing to the reduced volume of distribution and reduced renal clearance in older people, which is especially important if thinking about lithium initiation. Pharmacotherapy can be divided into different phases of treatment: acute (manic or mixed episodes) and maintenance treatment. Comprehensive guidance is available from the British Association of Psychopharmacology,5 and from NICE (see Box 5.3).34

Sep 27, 2020 | Posted by in PSYCHIATRY | Comments Off on Chapter 5 – Mania in Late Life
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