Depression & Psychological Distress in Advanced Illness

First, exclude biological mimics

Before attributing low mood to depression, exclude reversible biological contributors: hypothyroidism (especially post-thyroidectomy or after immunotherapy), hypercalcaemia, corticosteroid effects, parkinsonism from antiemetics, anaemia, and cerebral metastases.

Distinguishing depression from grief/existential distress

Only after biological mimics are excluded should depression be differentiated from a normal grief reaction to an emotive diagnosis, or existential distress. Some difficulty distinguishing these states is inevitable — think of the assessment as gardening rather than rigid classification, tending to whichever contributing factors are present rather than forcing one label.

Routine depression screening is not recommended in this population — available screening tools aren’t validated for people with advanced illness, and the best management for a positive result is itself ambiguous. Clinical judgement and the patient’s own narrative matter more than a screening score.

Pharmacological management

Evidence quality is limited — a 2023 Cochrane review found the published trials “of low quality. “SSRIs take weeks to months to show benefit, but attrition from death/deteriorating illness in palliative-population trials exceeds 20% within just two weeks, making robust efficacy evidence practically difficult to generate. This doesn’t mean antidepressants don’t help individual patients — it means the evidence base is thin, and time matters.

Drug-specific considerations:

• Tamoxifen interaction — avoid fluoxetine, paroxetine and bupropion (CYP2D6 inhibitors, which reduce tamoxifen’s active metabolite); prefer venlafaxine, mirtazapine, citalopram or escitalopram instead.
• Dysphagia — choose crushable options (citalopram, escitalopram, mirtazapine) or liquid/disintegrating formulations.
• Benzodiazepines are less problematic in a palliative context than in general practice more broadly; subcutaneous dosing can help prevent withdrawal during the terminal phase.

Non-pharmacological approaches

No single intervention is unequivocally beneficial — options include CBT, dignity therapy, counselling, meaning-centred therapy, and mindfulness. Consider “time toxicity” — the opportunity cost of an intervention for a patient with limited life expectancy — and don’t push a patient to continue something they’re not benefiting from.

An integrated approach

Rather than defaulting straight to medication, address distress across domains:

• Physical — treat unaddressed pain and other symptoms first (“we try to fix things we are good at fixing”).
• Psychosocial — advance care planning, carer support, and family counselling (including for children in the family).
• Spiritual — offer pastoral care to all patients, regardless of faith.
• Existential — explore what the patient specifically means by “feeling depressed” and what their particular fears are.

Offer the patient a choice — psychology referral, another non-pharmacological modality, and/or medication — based on their own preference, rather than defaulting to one approach.