Let’s Celebrate! by retired nurse and artist Ken Roberts
A first manic episode after 40 is a sign of vascular or neurodegenerative disease
STUDY: Lancksweerdt B et al, Expert Review of Neurotherapeutics 2026
STUDY TYPE: Narrative review
FUNDING: Independent
Summary
Most people with bipolar disorder have their first episode in their teens or twenties. When mania or hypomania first shows up after age 40, it often reflects a different underlying biology, more vascular and neurodegenerative, than classic early-onset bipolar disorder, changing both the workup and the treatment.
Age at onset in bipolar disorder clusters into three groups, roughly 17, 26, and 42 years, supporting late-onset as a biologically distinct subgroup rather than bipolar disorder that simply showed up late. Compared with early-onset patients, late-onset tends to bring milder mania, more irritability than euphoria, fewer psychotic features, and more depressive episodes.
It also carries a heavier cerebrovascular burden and roughly double the risk of dementia, making it easy to confuse with prodromal frontotemporal or vascular dementia. Red flags for a fuller workup, MRI, labs, neuropsychological testing (eg, MoCA), include no family history, fluctuating consciousness, focal neurological signs, rapid cognitive decline, or an unexpected treatment response.
Treatment
Lithium is first choice, with superior long-term efficacy and possible protection against cognitive decline, though older adults need closer monitoring of renal function and interactions with ACE inhibitors, NSAIDs, and diuretics. Target lithium levels run lower here: 0.4 to 0.8 mmol/L for ages 60 to 79, 0.4 to 0.7 for 80 and older.
Lamotrigine fits better when depressive relapse dominates; antipsychotics stay second-line given cognitive and anticholinergic burden (and risk of TD is nearly twice as high in older adults).
These recommendations are based on broad knowledge of these medications, and awareness of their effects in geriatrics, rather than specific trials in late-onset bipolar, as these patients are usually excluded from bipolar disorder research.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
