Several types of medications can help manage sundowning, the pattern of increased confusion, agitation, and restlessness that often hits people with dementia in the late afternoon and evening. There is no single drug designed specifically for sundowning, but doctors typically work through a sequence of options starting with the gentlest approaches and escalating only when needed.
Melatonin for Sleep and Circadian Rhythm
Melatonin is often the first thing tried because it directly targets the disrupted body clock that drives sundowning. The brain’s internal clock deteriorates as dementia progresses, and melatonin production drops along with it. Replacing that melatonin at bedtime can reset the sleep-wake cycle enough to reduce evening agitation.
The evidence behind melatonin for sundowning is surprisingly strong. In one study, seven out of ten dementia patients taking 3 mg at bedtime showed a significant decrease in sundowning and more consistent sleep onset times. A longer-term study followed 14 Alzheimer’s patients taking 6 to 9 mg nightly for two to three years. Sleep quality improved, and sundowning was no longer detectable in 12 of those 14 patients. Another trial of 45 Alzheimer’s patients taking 6 mg daily for four months confirmed both better sleep and suppression of sundowning behavior. Combining melatonin with bright light therapy during the day appears to strengthen the effect further, increasing daytime wakefulness and activity levels.
Doses in studies have ranged from 2.5 mg to 10 mg, with 3 to 6 mg at bedtime being the most common starting point. Melatonin is well tolerated and works regardless of what other dementia medications someone is already taking, which makes it a practical first step.
Antidepressants for Agitation
SSRIs, the same class of drugs widely used for depression and anxiety, are considered a first-line treatment for agitation and mood symptoms in dementia. They can reduce aggression, improve impulse control, and lift the kind of irritability that fuels sundowning episodes.
Not all SSRIs perform equally for this purpose. A network analysis ranking their effectiveness for dementia-related agitation found citalopram at the top, with a 94.8% probability of being the most effective option compared to other antidepressants studied. Citalopram showed a statistically significant benefit over placebo, while sertraline ranked second but did not reach statistical significance on its own. Escitalopram has shown promise in smaller studies, though detailed efficacy data remain limited. Fluoxetine ranked lowest among the SSRIs tested. Trazodone, an older antidepressant with sedating properties, is also sometimes used but ranked below placebo in overall efficacy for agitation.
The practical takeaway: if a doctor prescribes an SSRI for sundowning-related agitation, citalopram has the strongest track record. These medications take several weeks to reach full effect, so they’re best suited as ongoing treatment rather than a quick fix for an acute episode.
Antipsychotics: Effective but Risky
When melatonin and antidepressants don’t bring enough relief, atypical antipsychotics are the next tier. These drugs block dopamine signaling in the brain, which can reduce hallucinations, delusions, and the aggressive or irrational behavior that sometimes accompanies severe sundowning.
In 2023, the FDA approved brexpiprazole (brand name Rexulti) as the first drug specifically indicated for agitation associated with Alzheimer’s disease. Its approval was based on two 12-week clinical trials. The typical dosing starts low at 0.5 mg daily for the first week, increases to 1 mg in the second week, and reaches a target dose of 2 mg daily by week three, with a maximum of 3 mg if needed.
Before Rexulti’s approval, doctors commonly prescribed other atypical antipsychotics off-label. Risperidone at around 0.5 to 1 mg daily has been shown to reduce agitation and aggression in dementia patients, with 1 mg daily considered appropriate for most elderly patients. Olanzapine at 5 mg daily appears most effective for elderly patients with dementia-related psychosis, with frail patients typically starting at 2.5 mg.
The Black Box Warning
Every atypical antipsychotic carries an FDA black box warning, the most serious safety alert the agency issues, for use in elderly dementia patients. A meta-analysis of 17 placebo-controlled trials found that dementia patients taking these drugs had 1.6 to 1.7 times the risk of death compared to those on placebo. In absolute terms, about 4.5% of drug-treated patients died during a typical 10-week trial period versus 2.6% on placebo. Deaths were primarily cardiovascular (heart failure, sudden death) or infectious (pneumonia). There is also a significantly higher incidence of stroke and transient ischemic attacks. This warning applies to risperidone, olanzapine, aripiprazole, and brexpiprazole alike.
This doesn’t mean antipsychotics are never appropriate. It means they’re reserved for situations where the agitation is severe enough to pose a safety risk, and where gentler options haven’t worked. Doctors use the lowest possible dose for the shortest time they can.
Cholinesterase Inhibitors and Memantine
Many people with Alzheimer’s already take cholinesterase inhibitors (donepezil, rivastigmine, or galantamine) to slow cognitive decline. These drugs have been shown to reduce behavioral disturbances in dementia patients more broadly, and some isolated reports suggest they may help with sleep disruption and circadian rhythm problems. However, the evidence for a direct effect on sundowning specifically is inconsistent, and they’re not prescribed for that purpose alone.
Memantine, the other major class of Alzheimer’s medication, has no specific data supporting its use for sundowning.
Dronabinol: An Emerging Option
Dronabinol, a synthetic form of THC (the active compound in cannabis), showed meaningful results in a recent three-week clinical trial of 75 participants with moderate to severe Alzheimer’s disease. Patients receiving dronabinol had significantly greater reductions in agitation compared to placebo, with a moderate effect size of 0.53 on one of the two primary measures used. The drug was well tolerated. Somnolence (sleepiness) was the only notable side effect, with no increased risk of delirium, falls, or intoxication.
This is still early-stage evidence from a small, short trial. Dronabinol is not yet standard practice for sundowning, but it represents a potential addition to the toolkit, particularly for patients who can’t tolerate antipsychotics.
How These Medications Are Typically Combined
Doctors rarely rely on a single medication for sundowning. A common approach starts with melatonin to stabilize the sleep-wake cycle, adds an SSRI like citalopram if daytime agitation and mood instability persist, and reserves antipsychotics for breakthrough episodes of severe agitation or psychosis. If the person is already on a cholinesterase inhibitor for their underlying dementia, that medication stays in place since it may provide some background benefit.
The timing of medication also matters. Because sundowning follows a predictable daily pattern, some doctors time doses so that sedating medications peak in the late afternoon or early evening, right before the window when symptoms typically worsen. Melatonin given at bedtime helps consolidate nighttime sleep, which in turn reduces the sleep deprivation that can make the next day’s sundowning worse.