Melatonin in Hospice and Palliative Care: Why Less Is More

Sleep disturbance is one of the most pervasive and distressing symptoms in patients living with advanced illness. Families worry when their loved one is awake at night, clinicians search for safe non-opioid strategies to settle nighttime agitation, and patients often ask for something “natural” to help them sleep. For many providers, melatonin feels like a benign, low-risk option.

But melatonin is frequently misunderstood. While widely marketed as an over-the-counter sleep aid, it is not a sedative. It is a hormone, acting primarily as a timekeeper within the brain rather than a hypnotic. This distinction becomes critically important when prescribing melatonin in frail, elderly, or terminally ill patients—a population uniquely susceptible to side effects from even seemingly gentle interventions.

In hospice and palliative care, where our emphasis is on function, comfort, and minimizing medication burden, melatonin requires thoughtful and evidence-informed use. And surprisingly to many clinicians, lower doses are often not only safer—but more effective.

Melatonin as a Hormone, Not a Hypnotic

Melatonin is produced by the pineal gland in response to darkness and serves as a circadian signal, telling the body, “It’s time to prepare for sleep.” Endogenous melatonin peaks are equivalent to roughly 0.3 mg or less.

Pharmacologically, melatonin binds to MT1 and MT2 receptors, both of which saturate at extremely low hormone concentrations. Once these receptors are occupied, additional melatonin offers no added benefit—a concept lost in the consumer-facing supplement industry, where 5 mg, 10 mg, and even 20 mg doses are marketed as routine.

From a physiologic perspective, this is like shouting louder at someone who already heard you the first time.

Why Lower Doses Work Better: A Counterintuitive Truth

1. Receptor saturation occurs at low doses

Research consistently shows that melatonin’s chronobiotic effects—i.e., its ability to shift sleep timing and improve sleep onset—max out at 0.3–1 mg. Higher doses overshoot the normal physiologic window, causing hormone spillover without improving sleep quality.

2. High doses can disrupt circadian rhythms

Paradoxically, excessive melatonin can:

• Shift circadian timing unpredictably
• Increase nocturnal awakenings
• Prolong sleep onset
• Trigger intense or disturbing dreams

Rather than “stronger sleep,” the effect is often more fragmented, less restorative sleep.

3. Older adults have slower melatonin clearance

Hepatic metabolism declines with age and illness. In geriatric and hospice patients:

• Melatonin lasts longer
• Accumulates more easily
• Produces next-day sedation
• Mimics or worsens delirium

A supraphysiologic dose in a frail elder is functionally equivalent to giving a benzodiazepine to a younger adult—it can snowball into confusion, imbalance, or agitation.

4. More is not better because melatonin is not a sedating hypnotic

Melatonin does not force the body to sleep. It nudges biological rhythms toward an appropriate phase. Once that nudge has occurred, adding more melatonin is simply adding noise.

Implications for Hospice and Palliative Care

1. Geriatric physiology requires gentler dosing

In an 88-year-old with multimorbidity and poor hepatic clearance, a standard 5 mg melatonin dose behaves very differently than it does in a healthy 30-year-old.

Common consequences include:

• Daytime grogginess
• Increased fall risk
• Worsening sundowning
• Disrupted sleep–wake patterns
• Morning confusion
• Exacerbation of underlying cognitive impairment

These effects are often misinterpreted as “disease progression” rather than iatrogenic sedation or circadian destabilization.

2. In dementia, melatonin is helpful in small amounts—but harmful in excess

Patients with Alzheimer’s or vascular dementia often have fragmented circadian rhythms and diminished endogenous melatonin production. Low-dose melatonin (0.3–1 mg) can:

• Support sleep initiation
• Reduce sleep fragmentation
• Improve early-evening calmness

But higher doses often:

• Increase nighttime agitation
• Provoke vivid dreams or night terrors
• Cause morning confusion
• Increase daytime napping, which worsens insomnia cyclically

A delicate balance matters greatly in this population.

3. Hospice polypharmacy amplifies sedation load

Hospice patients commonly rely on:

• Opioids
• Benzodiazepines
• Antipsychotics
• Antidepressants
• Anticholinergics

These agents already influence arousal, sleep, cognition, and fall risk. Adding high-dose melatonin can unintentionally tip the balance toward:

• Excessive sedation
• Poor participation in care
• Decline in functional status
• Lower quality of life

Our goal is always to reduce symptom burden, not add another variable that complicates the clinical picture.

Practical Clinical Recommendations

Start Low

Most geriatric and hospice patients respond best to:

• 0.3 mg to 1 mg nightly, given 1–2 hours before bedtime.

If 1 mg is ineffective, doses can be cautiously increased to 2 mg. Very rarely is 3 mg appropriate, and doses above this level often worsen outcomes in the elderly.

Monitor closely for paradoxical effects

These include:

• Worsened nighttime agitation
• More daytime sleepiness
• Worsened cognition
• Reversal of sleep–wake cycles
• Increased fall frequency

If these symptoms emerge, reduce or discontinue melatonin.

Integrate non-pharmacologic interventions

Melatonin works best when paired with:

• Daytime sunlight or bright-light exposure
• Consistent wake time
• Reduced evening overstimulation
• Limiting late-day napping

These interventions are often more impactful than medication.

Melatonin at End of Life: Reframing the Goal

In the final weeks of life, sleep architecture becomes naturally disorganized. Patients may sleep round the clock, stay awake at night, or drift in and out of wakefulness unpredictably. These changes reflect the physiology of dying, not pathology.

In such cases:

• Melatonin may offer little benefit
• Irregular rhythms may not respond predictably
• Comfort, reassurance, and environmental adjustments often trump medication

We must revisit the question: Is the goal to restore normal sleep or simply to support comfort?

If melatonin does not meaningfully improve quality of life, it does not need to remain on the medication list.

Key Takeaway for Hospice Providers

Melatonin can be effective for sleep onset and circadian support, but only at low doses. High doses frequently worsen sleep, increase delirium, and impose unnecessary risk in frail elders. For hospice and palliative care patients, start low, monitor closely, and always prioritize comfort and clarity.

References

Auger, R.R., Burgess, H.J., Emens, J.S., Deriy, L.V., Thomas, S.M. and Sharkey, K.M. (2015) ‘Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An update for 2015: an American Academy of Sleep Medicine clinical practice guideline’, Journal of Clinical Sleep Medicine, 11(10), pp. 1199–1236.

Cruz-Sanabria, F., et al. (2023) ‘Melatonin as a chronobiotic with sleep-promoting properties’, Current Neuropharmacology, 21(4), pp. 951–987.

Emet, M., Ozcan, H., Ozel, L., Yayla, M., Halici, Z. and Hacimuftuoglu, A. (2016) ‘A review of melatonin, its receptors and drugs’, Eurasian Journal of Medicine, 48(2), pp. 135–141.

Gooneratne, N.S., Edwards, A.Y.Z., Zhou, C., Cuellar, N., Grandner, M.A. and Barrett, J.S. (2012) ‘Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults’, Journal of Pineal Research, 52(4), pp. 437–445.

Liu, J., Clough, S.J., Hutchinson, A.J., Adamah-Biassi, E.B., Popovska-Gorevski, M. and Dubocovich, M.L. (2016) ‘MT1 and MT2 melatonin receptors: a therapeutic perspective’, Annual Review of Pharmacology and Toxicology, 56, pp. 361–383.

Mahmoud, F., Sarhill, N. and Mazurczak, M.A. (2005) ‘The therapeutic application of melatonin in supportive care and palliative medicine’, American Journal of Hospice and Palliative Care, 22(4), pp. 295–309.