Drugs targeting non-cognitive symptoms of Alzheimer’s disease
| Drug name | Target and rationale | Status on clinical trial(start date–end date) | AD stage | Results | Clinical trial identifier (NCT number) |
|---|---|---|---|---|---|
| Methylphenidate | Block DAT. And increase the dopamine level | Completed phase 3, (2016–2020) | Apathy in AD | Mild improvement of apathy, measured at 6 months compared to placebo | 02346201 |
| Prazosin | Antagonist of alpha1-adrenergic receptor | Completed (2018–2022) | Moderate to severe disruptive behavior | Non-significant improvement of agitation | 03710642 |
| Pimavanserin (Nuplazid) | Inverse agonist and antagonist of 5-HT2A in neurotransmission | Completed phase 2 (2017–2019) | Probable AD who has symptoms of agitation and aggression | (1) Promising reduction of psychosis score in AD, also see [74] and (2) delay in psychosis relapse (p < 0.05) and a lower risk of relapse with the continuation of the drug [75] | 0311894703325556 |
| ITI-007 (Lumateperone) | 5-HT2A serotonin receptor antagonist | Terminated phase 3 (2019) due to pre-specified interim analysis indicating futility | Probably AD | Terminated | 02817906 |
| Lemborexant (Dayvigo) | Orexin receptor antagonist | Completed (2016–2020) | Mild-moderate | Approved for insomnia, lower nighttime activity, and improved circadian rhythmicity | 03001557 |
| Suvorexant (Belsomra, MK-4305) | Orexin receptor antagonist | Completed (2016–2018) | Mild-moderate | Approved for insomnia in AD, lengthened total night sleep time | 02750306 |
AD: Alzheimer’s disease; DAT: dopamine transporter; 5-HT2A: 5-hydroxytryptamine 2A