Mood disorders in late life

Scope and classification. DSM-5 split the former "mood disorders" chapter into two — depressive disorders and bipolar disorders. Depressive disorders comprise major depressive disorder, persistent depressive disorder (merging dysthymia and chronic depression, ≥2 years), depressive disorder due to another medical condition, and substance/medication-induced depressive disorder. Bipolar disorders comprise bipolar I, bipolar II and cyclothymia. Additions relevant to late life include the "with anxious distress" specifier and the removal of the bereavement exclusion.

Burden. Depression is the commonest psychiatric disorder in older people — major depression in 1–5% of the community, clinically relevant depressive symptoms in 8–16%, rising markedly in primary care, medical wards and long-term care. Bipolar disorder affects only 0.5–1% of over-65s but accounts for 5–10% of geriatric psychiatry outpatients. Clinically significant subthreshold syndromes increase with age and still carry adverse outcomes.

Why late-life mood disorder is different. Comorbidity is the hallmark of geriatric psychiatry, and this is most pronounced in depression. Chronic physical illness and its drug treatment produce overlapping symptoms — fatigue, slowness, loss of initiative and sleep disturbance. Presentation is atypical — somatic complaints, hypochondriasis, anxiety, irritability and cognitive complaints rather than expressed sadness. Psychomotor symptoms and nihilistic delusions are more frequently reported in older inpatients, sometimes even in the absence of lowered mood.

Depression subtypes of examination importance. Psychotic depression — nihilistic and guilt delusions, high suicide risk, requiring antidepressant plus antipsychotic, or ECT. Melancholic depression with psychomotor change — predicts response to TCAs, dopaminergic agents and ECT. "Vascular depression", now ischaemic subcortical depression or depression–executive dysfunction syndrome — late onset, apathy, impaired insight, executive dysfunction and deep white-matter change; its clinical validity is now regarded as limited, with vascular factors and inflammation mutually reinforcing each other.

Secondary and organic mood disorders — always exclude. Hypothyroidism and hyperthyroidism, vitamin B12 and folate deficiency, hyponatraemia (mEq/L), hypercalcaemia (mg/dL), stroke (post-stroke depression; right frontal or basotemporal stroke causing secondary mania), Parkinson's disease, dementia, occult malignancy (especially pancreatic) and chronic pain. Drugs: corticosteroids, levodopa and dopamine agonists, beta-blockers, interferon, and 5-alpha reductase inhibitors linked to depression and suicidality.

Bipolar disorder in late life. Two groups — early-onset illness ageing into old age (about two-thirds) and late-onset first episode after 50 (about one-third). Late-onset mania is secondary mania until proved otherwise — cerebrovascular disease, stroke, frontotemporal dementia, hyperthyroidism, steroids, levodopa and antidepressants. Mania is attenuated — irritability, dysphoria, confusion and paranoia rather than euphoria; mixed states and prolonged depressive episodes dominate. GERI-BD found lithium and divalproex comparably effective in acute mania in those aged ≥60.

Conditions that mimic mood disorder. Apathy syndrome — prevalent after stroke and in dementia, characterised by lack of drive with absence of dysphoria and absence of neurovegetative symptoms; SSRIs and antidopaminergic drugs may worsen it, and low-dose methylphenidate may help in severe cases. Also delirium, dementia (pseudodementia versus true dementia), complicated or prolonged grief, and personality disorder with mood lability.

Assessment. History with informant account; GDS-15, or the Cornell Scale for Depression in Dementia where cognition is impaired; MMSE/MoCA; physical examination with attention to vascular risk factors, weight, mobility, balance and ADLs. Investigations: CBC, sodium and potassium (mEq/L), calcium (mg/dL), glucose (mg/dL), liver function, TSH, vitamin B12 and folate, plus ECG before a TCA or lithium. Assess suicidal ideation in every case.

Principles of management across the spectrum. Match intensity to severity — watchful waiting → psychotherapy → antidepressant → augmentation → ECT. Antidepressants are as effective in older as in younger adults; psychotherapy is helpful in mild-to-moderate illness; ECT is probably more effective in severe depression in older people than in the young. For bipolar illness — a mood stabiliser at lower doses and lower serum levels, with antidepressant monotherapy contraindicated. Always include functional recovery, treatment of comorbid physical illness, and multidisciplinary team care.

Course, prognosis and impact. Late-life depression has a more chronic course than in younger adults, although over 80% of those without significant medical comorbidity or dementia recover and remain well when optimally treated. Worse outcome is predicted by greater severity of depression and more serious physical illness. Mortality is increased — mainly cardiovascular, with suicide risk rising with age, especially in men — and both severity and duration of symptoms predict mortality, with loneliness amplifying the effect. Depression also worsens the course of physical illness and increases healthcare consumption.

Depression as a modifiable dementia risk factor — 2024 Lancet Commission. The updated Lancet Commission on dementia prevention, intervention and care (2024) retains depression among the modifiable risk factors contributing to the population burden of dementia. Combined with cohort evidence that 10-year trajectories of depressive symptoms predict incident dementia, this reframes active treatment of late-life depression as a dementia-prevention intervention, and mandates cognitive assessment and cognitive follow-up in every older patient with depression.

OPTIMUM trial (NEJM 2023) and ISBD lithium targets. In treatment-resistant late-life depression, aripiprazole augmentation outperformed switching to bupropion (remission approximately 28% versus 19%) with a lower fall risk. On the bipolar side, the ISBD Older-Age Bipolar Disorder Task Force now supports age-stratified lithium targets of 0.4–0.8 mEq/L for ages 60–79 and 0.4–0.7 mEq/L for those aged ≥80, rather than the standard adult range.