Update on Pharmacological Treatment of Neuropsychiatric Symptoms of Dementia

Abstract

Neuropsychiatric symptoms (NPS) commonly occur in dementia and are a major source of burden and distress for both patients and their caregivers. Nonpharmacological treatments are often of limited benefit, particularly when NPS are severe, and at present no medication is approved by the Food and Drug Administration to treat any NPS. This paper reviews the most recent evidence available for nine proposed treatments (eight medications or classes, plus electroconvulsive therapy (ECT)). Guidance will also be provided regarding a suggested algorithm for pharmacological treatment selection. The strongest evidence is for atypical antipsychotics, but they have a high burden of adverse effect in dementia, including increased mortality risk. Selective serotonin reuptake inhibitors (SSRIs) are likely safer, but evidence for efficacy is currently less strong. The strongest evidence exists for citalopram, but increased risk for QTc prolongation may limit use. Research suggests that mood stabilizers use may be ineffective and unsafe, although select patients may benefit. Benzodiazepines have had limited study, and due to high adverse effect burden, should be reserved for patients who have not responded to or cannot tolerate other classes of medication, and used only after careful weighing of risks and benefits. Cannabinoids, prazosin, dextromethorphan/quinidine, and pimavanserin all have some limited but promising data supporting their use. Electroconvulsive therapy may be helpful for severe NPS, but its impracticality likely limits use. NPS in dementia cause marked burden and suffering. In severe cases for which pharmacological treatment is indicated, the strongest evidence exists for atypical antipsychotics, but given their high adverse effect burden, SSRIs should be considered, if deemed appropriate, as first line treatment. Third or lower tier treatments can include anticonvulsants, cannabinoids, prazosin, dextromethorphan/quinidine, and pimavanserin. Benzodiazepines should be reserved for select situations with careful weighing of risks and benefits. ECT may be effective for severe NPS, but is likely of limited practical use.