Mania in Bipolar Disorder in Old Age

The world’s elderly population is growing rapidly. By 2025-2030, the population over 60 years old will grow 3.5 times faster than the general population. Like their younger peers, older people with serious mental disorders, such as bipolar disorder (BD), experience the stigma and stress of dealing with a chronic psychiatric condition, often complicated by aging-related issues such as mobility limited, chronic pain, frailty or other mental or physical problems.

Old-life bipolar disorder (OABD), defined by many reports as BD in individuals aged ≥60 years, accounts for up to 25% of the BD population. Furthermore, OABD represents a highly heterogeneous group that includes individuals with variable age of onset of first manic presentation, which may represent potentially different pathogenesis, clinical course, and care needs.

The primary objective of this review is to provide a brief overview of the most recent publications (within the last 3 years) focused on mania in OABD. While the evidence base is still limited, a growing literature reflects the urgent need to better understand the pathology, presentation and trajectory of disease, and treatment needs for geriatric mania.

This review will specifically focus on epidemiology and diagnosis/differential diagnosis, as well as updates on available treatments, including lithium, other pharmacological treatments, and non-pharmacological approaches for geriatric mania.

The population over 60 is growing faster than the general population. Given the projected increase and need for data that can inform treatment, this review provides a brief overview of the most recent publications focused on mania in late-life bipolar disorder (OABD), including epidemiology, diagnosis, and treatments. .

The age limits for defining OABD range between 50 and 65 years. The clinical presentation of OABD and disease course are highly variable, often characterized by mood episode recurrence, medical comorbidity, cognitive deficits, and impaired functioning. There are few pharmacotherapy data on mania in OABD. Lithium and valproate were tested in a single randomized controlled trial, and there are more limited quality data with other compounds.

The clinical presentation and disease course in OABD are variable, suggesting a heterogeneous nature.

Studies on clinical characteristics comparing late-onset OABD with early-onset OABD suggested that the former has higher levels of premorbid psychosocial functional deficits, less severe psychopathology, and more cognitive impairment, while the latter has a stronger family history. , more depressive and mixed episodes, and more substance use.

Clinical features of OABD generally include more frequent and severe cognitive impairment, more comorbid medical conditions, less anxiety, less substance use disorder, and less hypersexuality.

A multisite community sample of 71 subjects aged 55 years or older and 147 subjects younger than 55 years in the National Network of Depression Centers (NNDC) Clinical Care Registry (CCR) at 15 medical centers in the US. found higher rates of antidepressant use in OABD (71.9%) compared with that of the younger cohort (50.0%) and a lower severity of depressive symptoms and a similar degree of manic symptoms. These findings suggest considering the possibility that OABD may have enhanced antidepressant response and lower rates of switch to manic or mixed states compared with younger cohorts.

Mania in OABD appears qualitatively similar to mania in the younger cohort. Hyperactivity, aggression, insomnia, and self-neglect pose risks to self and others, as in younger patients. There is some evidence to suggest a negative association between age and overall severity of mania.

Psychosis (i.e., delusions, hallucinations) may be present, although psychosis is less common in older patients compared to younger BD patients. Cognitive deficits occur in approximately 40 to 50% of euthymic OABD, primarily in the domains of attention, cognitive flexibility (task switching), memory, semantic fluency (generation of words that belong to particular categories), and verbal fluency (generation of words that begin with particular). OABD can develop neurocognitive disorders at a higher rate than expected.

Comorbidity occurs frequently in OABD, with an average of 3-4 comorbid medical conditions. The most common diseases are arthritis (20%), cardiovascular diseases (10-50%), diabetes mellitus (20-30%), endocrinopathies (20%), hypertension (45-70%) and syndrome metabolic (up to 50%).

It is suggested that despite high rates of medical comorbidity, cardiovascular disease has not been adequately recognized or treated in OABD. Substance use disorders and anxiety disorders are the two most common psychiatric comorbidities in OABD, although they are less prevalent than those in younger cohorts.

Historically, mania has always been defined by the presence of at least two symptoms (elevated mood and grandiosity) and four signs (hyperactivity, pressured speech, irritability, and new activities with painful consequences).

In the DSM-5, the main criteria for mania were slightly modified: "A defined period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy" by the introduction of the latter criterion. This may decrease the prevalence of manic episodes.

Mania may occur in older patients with established bipolarity, as a new-onset condition in older patients with a previous history of recurrent depression, in the context of schizoaffective disorder (primary mania), or due to a specific medical cause (secondary mania), as well as part of delirium or dementia.

Mania in old age and physical health are closely related and different hypotheses have been proposed. In general, medical comorbidities are common in OABD and even more so in older patients admitted for a manic episode.

Somatic factors may be a true cause of mania (secondary mania), or may trigger mania as the first manifestation of TB in a person with a latent vulnerability, with or without a history of depressive episodes. However, somatic comorbidity may also be present without any causal relationship to mania.

Evidence for mania treatments in bipolar disorder in the elderly

There have been relatively few data examining pharmacotherapy of mania in OABD.

Lithium has a long history of use ; However, its effectiveness in geriatric patients is mainly based on small open-label and retrospective studies.

Valproate has also been used for acute mania , with geriatric data from uncontrolled studies.

Many atypical antipsychotics have evidence from randomized controlled trials (RCTs) in adult mania, and there is geriatric evidence for quetiapine (pooled data from RCTs in adults of mixed ages), as well as open trials of aripiprazole and asenapine, and case series of risperidone and clozapine.

There are also case series for gabapentin and carbamazepine, as well as expert consensus for the use of electroconvulsive therapy in refractory cases.

In general, open-label and observational studies find that medications effective in adults with BD will also be effective in OABD, and smaller reports often examine and find clinical improvement in symptoms of mania and depression.

A study funded by the US National Institute of Mental Health (NIMH) found that while older patients were often treated with lower doses of BD medications to optimize tolerability and prevent events Adversely, some elderly patients with BD required similar serum levels for remission as their younger counterparts.

The last 3 years (2014–2016) have produced some encouraging new reports. The first was a large 3-week RCT of valproate versus lithium for mania and hypomania (n > 200), the only RCT in OABD. The authors found that both lithium and valproate are effective in acute mania/hypomania, with overall similar short-term tolerability.

There was also a 12-week open-label trial of asenapine in the treatment of OABD (n = 15). The study found improvements on a variety of psychiatric symptom scales, including the Brief Psychiatric Rating Scale, Clinical Global Impression Depression and Mania subscales.

Finally, there was a 12-month RCT of psychosocial skills training and preventive healthcare intervention in older adults with severe mental illness, which included 36 patients with BD. This intervention improved functioning and reduced psychiatric symptoms.

Based on the available geriatric literature and clinical experience, some medication recommendations can be made. Monotherapy with lithium or valproate can be tried first. If this is not effective or poorly tolerated, atypical antipsychotics such as quetiapine, asenapine, aripiprazole or risperidone may be used and/or added if there is a partial response. Carbamazepine and gabapentin could then be considered as additional treatment options.

For manic episodes refractory to other medications, clozapine and ECT could be tried. In case the episodes are refractory even to these medications, additional suggestions based on adult literature can be found in the international BD guidelines. Since depression, subsyndromal symptoms, and euthymia often predominate in OABD, a therapeutic approach that favors medications that also have protective effects against depression (e.g., lithium, valproate, lurasidone, quetiapine, aripiprazole) is useful. long-term in the management of these patients.

Prescribing is a challenge in OABD. In general, low doses should be initiated for most therapeutic agents (e.g., 150 mg/night for lithium or 125–250 mg/night for valproate), with cautious adjustments to reach the lower end of the therapeutic range for adults (e.g., 0.4–0.8 mmol/L for lithium, with 0.4–0.6 mmol/L even potentially useful in patients with mania over 80 years of age). The dose could then be titrated based on efficacy and tolerability.

It is worth noting that some OABDs will require standard adult doses for remission. There is also significant potential for pharmacokinetic issues, such as reduced metabolism and elimination of many BD drugs, drug interactions, and adverse events in OABD, requiring ongoing monitoring for treatment of adverse effects.

Given the high prevalence of obesity in BD and the association especially of antipsychotics and valproate with metabolic syndrome, regular monitoring of weight gain, metabolic syndrome, diabetes, hypertension, and hypercholesterolemia is useful. Liver, hematologic, and endocrine laboratory tests may also be helpful for certain medications. Ideally, lithium level and renal monitoring should be performed at least every 3 to 6 months, as well as 5 to 7 days after a lithium dose adjustment or an adjustment of certain concurrent anti-inflammatory or antihypertensive medications.

Pharmacological treatments should be combined with a whole-person treatment approach for OABD: psychosocial skills training, preventive healthcare intervention, and group psychoeducation, which can help reduce long-term symptom burden. Working closely with families and social workers can improve social support and improve clinical outcomes in these patients.

Given the common occurrence of cognitive impairment in OABD, annual cognitive assessment may be helpful.

Using a collaborative care model with primary care and specialist physicians, including regular monitoring for adverse effects of medications, promotion of regular exercise, and proper diet, can optimize physical health.

Geriatric mania is qualitatively similar to mania in younger cohorts, although there is some evidence to suggest that the overall severity of mania is decreased in OABD.

The clinical presentation and disease course in OABD is highly variable, but is often characterized by recurrent mood episodes, high medical comorbidity, cognitive deficits, and impaired functioning and burden on family caregivers.

Mania may occur in older patients with established BD, as a new-onset condition in older patients with a previous history of recurrent depression, in the context of a schizoaffective disorder (primary mania), or due to a specific medical cause (secondary mania). , as well as part of a delirium or dementia.

Mania in old age and physical health, especially neurological conditions, are closely related. A possible link between frontotemporal dementia (FTD) and BD has been suggested by several case reports of patients presenting with manic symptoms as a first manifestation of FTD and of patients with a lifelong diagnosis of BD evolving into a behavioral variant of FTD (Table 3).

There has been little data examining pharmacotherapy of mania in OABD. Lithium and valproate have been tested in a single randomized controlled trial, and there are more limited quality data for other compounds, including atypical antipsychotic drugs. Given demographic changes projecting greater numbers of OABDs making up a growing proportion of the population facing bipolarity, it is important that the field and data keep pace with clinical demand.

Evidence gaps include the need for data on the prognosis and trajectory of people with various types of comorbidity, including classic neurodegenerative conditions such as dementia.

Much of the existing epidemiological and treatment data relate to "young and old" people with TB aged 60 years, and more information is needed on how people in their 70s and 80s present and respond to treatment.

Prospective randomized controlled trials focusing specifically on OABD are needed, but barring the imminent availability of such laborious (and expensive) efforts, investigation of large, observational databases may help improve our understanding of how to best choose and use drugs. existing pharmacological therapies for OABD. Finally, optimal methods for providing psychosocial approaches and integrated healthcare for patients and families facing extensive comorbidity in OABD need further investigation.