Older adults presenting with an episode of mania most often have a history of primary bipolar disorder. DSM-5 criteria define a manic episode as:

• A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).
• During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:

• Inflated self-esteem or grandiosity
• Decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
• More talkative than usual or pressure to keep talking
• Flight of ideas or subjective experience that thoughts are racing
• Distractibility (i.e., attention easily drawn to unimportant or irrelevant external stimuli), as reported or observed
• Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (i.e., purposeless non-goal-directed activity)
• Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

• The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
• The episode is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition.

Evaluation of Mania:

Evaluation of new onset bipolar disorder or primary mania should begin with an evaluation to exclude secondary causes of mood disturbance and/or contributing factors. This evaluation should include:

• Comprehensive physical exam which includes a body mass index (BMI) calculation, blood pressure, and EKG.
• Comprehensive neurological examination to screen for possible dementia, specifically frontotemporal dementia.
• Medication list review, as some medications (e.g., corticosteroids, antidepressants), may cause mania.
• Assessment of mood state and severity using the Young Mania Rating Scale (Young 1978) or other mania rating instrument.
• Baseline labs including blood chemistry, complete blood count, thyroid stimulating hormone, vitamin B12, folate, liver function tests, calcium, urine toxicology screen, and fasting lipid panel (Zhou et al. 2022). HIV, niacin urinalysis, and FTA-Abs may also be checked, as indicated.
• Neuroimaging should be considered.

Treatment of Mania:

The initial treatment approach should begin by addressing contributing causes to the symptoms and then considering possible pharmacologic treatments. First, discontinue antidepressants as these may increase manic symptoms in some patients. Next, consider a trial of medication:

• Lithium exhibits some anti-suicidal benefits distinct from its mood-stabilizing properties and appears to have possible unique neuroprotective effects. Recent evidence suggests lithium can be started at 300 mg/day with a target serum level of 0.70-0.99. Trough lithium levels can be measured 5 days after any dose change. Side effects may include polyuria, polydipsia, nausea, diarrhea, and tremors, which can generally be managed (Gitlin 2020). More problematic side effects include weight gain, cognitive slowing, and possible longer-term effects of hypothyroidism, increased parathyroid hormone and calcium levels, and renal impairment. Medication interactions (e.g., diuretics, ACE inhibitors, and NSAIDs) require decreased lithium dosing. Monitoring of renal, thyroid function, and lithium levels should be done at least every 6 months.
• Divalproex is an anticonvulsant with good efficacy data for treatment of manic episodes. It is generally well tolerated in older adults. It can be started at 500 mg/day with target serum concentrations of 70-99 µg/ml. Common side effects include nausea, sedation, weight gain, and benign tremor. Divalproex has rarely been associated with liver failure and pancreatitis. Monitoring of weight, complete blood count, and liver function tests should be done every 3 months for the first year, then annually (Weintraub et al. 2020).
• Atypical antipsychotics can be used as an adjunct medication for partial response to lithium or divalproex or as monotherapy for patients unable to tolerate lithium or divalproex. There are no prospective controlled trials of atypical antipsychotics in the older adult bipolar population. There is post hoc evidence in controlled trials using quetiapine and olanzapine (Li et al. 2021). Side effects vary depending on the medication but may include sedation, weight gain, increased blood glucose, and hyperlipidemia. Check weight monthly, check labs every 3 months and then annually, and EKG and prolactin as clinically indicated. Assessing the patient using the Abnormal Involuntary Movement Scale (AIMS) annually may detect tardive dyskinesia in patients taking antipsychotics, although the risk is lower for atypical antipsychotics compared with typical antipsychotics.

In a recent double-blind controlled trial of lithium and divalproex for the treatment of mania in older patients (Laita et al. 2021), both medications were effective and adequately tolerated. Lithium was associated with a greater reduction in mania scores overall. Treatment guidelines for older persons with bipolar disorder emphasize lithium (effective, may prevent suicide, and is neuroprotective) and de-emphasize antipsychotics (metabolic side effects of diabetes, weight gain, hyperlipidemia). More double-blinded studies need to be done to better establish the efficacy and tolerability of treatments in bipolar disorder in older adults.