Your new patient Alice is an 81-year-old woman with a history of hypertension, hyperlipidemia, and type II diabetes and no prior psychiatric history. Her children express their concerns about her “recent personality change.” Alice euphorically tells you in a hyperverbal and tangential manner about various talk show hosts who directly communicate with her through the television late at night.

Although less common, a first episode of mania can present in late life. Older patients will often present with standard manic symptoms, such as mood disturbance; increased energy and goal-directed activity; grandiosity; decreased sleep; pressured speech; flight of ideas; distractibility; etc. But older patients may also show more irritability, confusion, and mixed depressive and manic symptoms.

Manic symptoms can have many etiologies. Younger adults typically have primary mania due to a psychiatric cause like bipolar disorder (BD) or schizoaffective disorder. Mania in older adults is much more likely to be secondary to medical or neurological causes, a medication side effect, or substance use. In a small retrospective study of 50 adults over age 65 admitted to a psychiatric unit for mania, over 70% had a comorbid neurological disorder (Brooks JO and Hoblyn JC, Am J Psychiatry 2005;162(11):2033–2038). This article will review the differential diagnosis and management of new-onset manic symptoms in older adults.

Differential diagnosis of secondary mania

Secondary mania should be considered in older adults presenting with mania when:

• The patient does not have a known primary mood or psychotic disorder
• The patient has new-onset medical or neurological symptoms preceding the manic symptoms
• The presentation is atypical (eg, mood instability with mixed states, lack of full recovery between episodes)

Older adults with new-onset secondary mania are also more likely to have cognitive impairment than younger adults with secondary mania. Thus, when creating a differential diagnosis, dementia (especially behavioral variant frontotemporal dementia) and hyperactive delirium are generally at the top. Typically, manic symptoms within the context of waxing and waning consciousness are due to delirium and are best treated by addressing the underlying cause of the delirium. A patient may also experience delirious mania, which presents with features of both mania and delirium. When manic symptoms occur within the context of progressive cognitive decline, they are more often due to the behavioral and psychological symptoms of dementia. The “Comparison of Mania Due to BD, Delirium, and Dementia” table highlights the cognitive changes associated with each of these conditions.

Causes of secondary mania fall into four major categories:

• Illicit substances
• Medical (typically infectious, cardiovascular, or endocrine issues)
• Medications
• Neurological issues (most common cause)

A helpful mnemonic to remember the causes of secondary mania is “E-MANIC,” which stands for Endocrine, Medications, Abuse of alcohol or illicit drugs, Neurologic, Infections, Cardiovascular causes (Khouzam H and Gill T, Current Psychiatry 2008;7(2):87–90). See “Common Causes of Secondary Mania in Older Adults (E-MANIC)” table.

With so many potential causes of mania, I first make sure I am not missing BD (or “primary mania”). Collateral is most helpful here, as insight is often severely impaired in mania, and patients may not recall episodes that occurred decades ago. In women, I ask about a history of postpartum mood changes, as pregnancy and birth can trigger a first episode of a mood disorder. I also ask about a family history of BD, especially among first-degree relatives.

If I’m sure a patient’s history is negative for prior manic episodes, I adopt the order of the E-MANIC mnemonic based on my estimate of the most likely causes. I generally start with a review of the patient’s medications (Peet M and Peters S, Drug Safety 1995;12(2):146–153).

I ask about:

• Amphetamines/stimulants
• Antibiotics such as clarithromycin
• Antidepressants, especially tricyclics and venlafaxine
• Blood pressure medications
• Dopaminergic agents such as levodopa, pramipexole, and bromocriptine
• Herbal or dietary supplements
• OTC nasal decongestants containing ephedrine and pseudoephedrine
• Steroids or bronchodilators
• Sympathomimetics such as ­epinephrine

Oddly, some atypical antipsychotics (including aripiprazole, olanzapine, quetiapine, and ziprasidone) have also been associated with mania, despite being approved treatments for mania. This is likely due to blocking of serotonin receptors.

After medications, I think about substance use. A wide variety of substances can mimic mania. These include but are not limited to amphetamines, cannabis/synthetic cannabinoids, cocaine, inhalants, LSD, MDMA, opioids, PCP, and steroids. Importantly, heavy alcohol and caffeine use can contribute to manic symptoms.

After ruling out exogenous causes, I think about medical causes of mania. These include endocrine or electrolyte abnormalities, such as Cushing syndrome, hyperthyroidism or hyponatremia, or vitamin B12 deficiency. I also think about infectious diseases, such as encephalitis, HIV/AIDS, and neurosyphilis, as well as diseases associated with vascular impairment, such as lupus.

If I’m pretty sure there is no medication, substance, or medical cause to explain a patient’s mania, I then move on to neurological issues, as these are the most common causes of secondary mania in older adults. I think through traumatic brain injuries (TBIs), such as from falls or motor vehicle collisions; right-sided frontal strokes; neoplasms (particularly lesions in the orbitofrontal or temporal lobes, or subcortical limbic brain lesions); epilepsy (including during the interictal period); multiple sclerosis; or recent neurosurgical procedures (Brooks and Hoblyn, 2005).

Assessing for secondary mania

I tailor my workup for secondary mania to the patient’s specific presentation (see “Standard Workup for Secondary Mania in Older Adults” table). If no obvious source is found at this point, it’s important to perform a good neurological exam and consider a head CT to rule out intracranial pathologies. Additional testing may include an MRI and/or EEG. If I am still unsure of the cause, I consider obtaining a CSF analysis to look for infection and an autoimmune panel (Carlino AR et al, Psychosomatics 2013;54(1):94–97).

You learn that Alice had a recent fall and consider that a TBI could be the cause of her manic symptoms. You order a head CT as well as lab work. Alice’s head CT is normal, but her vitamin B12 level is low at 150 pg/mL (<200 pg/mL is considered deficient).

Treating secondary mania

The treatment for secondary mania is typically the same as for primary mania, with concurrent treatment of the underlying cause. Like younger adults, older adults are typically treated with a mood stabilizer and an atypical antipsychotic. Valproic acid, olanzapine, quetiapine, risperidone, and sometimes aripiprazole are first-line treatments (Brooks and Hoblyn, 2005). Lithium is also a first-line treatment, though in practice it is often not tolerated in this population due to the high prevalence of renal failure, thyroid dysfunction, cardiac insufficiency, and concurrent NSAID use in older adults. Lithium can also lower the seizure threshold, which is undesirable with certain underlying neurological causes. Benzodiazepines are also used more sparingly in older adults due to potential side effects.

Once an episode of secondary mania has resolved, a patient usually doesn’t need to remain on prophylactic medication to prevent future episodes. Clinicians can taper medication once the patient has returned to baseline and the underlying cause has been treated. For nonreversible conditions like strokes or severe TBIs, the patient will likely need to remain on medications longer.

Alice ultimately starts IM vitamin B12 repletion, risperidone, and valproic acid. Within a few days she starts to feel significantly better. Once she has returned to her baseline and her vitamin B12 levels have normalized, you discuss a taper off of risperidone and valproic acid with her family, which she tolerates very well.

CARLAT VERDICT

Mania in older adults is usually secondary to medical or neurological causes, a medication side effect, or substance use. Unless the patient has a strong personal or family history of a primary psychiatric disorder, complete a basic medical workup to look for an underlying cause. Treatment for secondary mania is typically the same regardless of etiology, although therapeutic medication does are often lower in older adults. Treatment choice is often guided by comorbidites and drug interactions. 

Comparison of Mania Due to BD, Delirium, and Dementia
Click here for a PDF of the Table

Common Causes of Secondary Mania in Older Adults (E-MANIC)
Click here for a PDF of the Table

 

Standard Workup for Secondary Mania in Older AdultClick here for a PDF of the Table