Table 3.

Practice guidelines for the treatment of AD

	EAN* Guidelines 2010 [76]	APA Guidelines 2014 [33]	CCCDTD4 Recommendations 2012 [75]
Mild to moderate AD	•Consider ChEIs at time of diagnosis, taking into account expected therapeutic benefits and potential safety issues	•Evidence remains modest for efficacy of ChEIs for mild to moderate AD	•ChEIs have demonstrated efficacy and are recommended for most patients with AD; direct comparisons do not suggest differences between agents, and selection will be based on AE profile, ease of use, familiarity, and differences between agents in PK and other MOAs
		•Insufficient evidence to show clinically meaningful advantages of higher doses of donepezil
		•Higher doses of rivastigmine patch may be associated with greater benefit
Moderate to severe AD	•Consider ChEIs at time of diagnosis, taking into account expected therapeutic benefits and potential safety issues	•Evidence remains modest for efficacy of ChEIs for moderate to severe AD	•Combination of a ChEI and memantine is rational and appears to be safe, but there is insufficient evidence to recommend for or against combination
	•Consider memantine, taking into account expected therapeutic benefits and potential safety issues	•Available evidence modest for efficacy of memantine for moderate to severe AD
		•Slight effect or unclear clinical significance for memantine and ChEI combination therapy
Depression	•Use SSRIs rather than tricyclic antidepressants to treat depression in AD	•Mixed evidence for the efficacy of antidepressants to treat depression	•A trial of an antidepressant could be considered
Agitation/psychosis	•Reserve antipsychotics for moderate or severe behavioral and psychological symptoms causing significant distress that have either not responded to other treatments (e.g., nonpharmacologic measures, ChEIs) or when other treatments are not appropriate	•Antipsychotics provide weak benefits for the treatment of psychosis and agitation •Antipsychotics can be tapered and discontinued without significant signs of withdrawal or return of behavioral symptoms in many patients with AD •Benefits of SSRI citalopram for agitation in patients shown in single trial, but treatment may be constrained by cardiac AEs	•Antipsychotics (e.g., risperidone, olanzapine, aripiprazole) are recommended for severe agitation, aggression, and psychosis if there is risk of harm to the patient and/or others; the potential benefit must be weighed against the significant risks such as cerebrovascular AEs and mortality
Not recommended	•Aspirin should not be used to treat AD, except in those with AD who also have other indications for its use •Vitamin E should not be used as a treatment for AD •Insufficient evidence to support the use of other agents, including anti-inflammatory drugs, selegiline, estrogens, pentoxifylline, statins, and porcine brain-derived proteolytic peptide fraction	•Alternative agents (including statins, anti-inflammatory drugs, vitamin E, and estrogens) are not generally recommended because of uncertain efficacy and safety	•Valproate should not be used for agitation and aggression in AD •Insufficient evidence to recommend for or against quetiapine in the management of severe agitation, aggression, and psychosis, and SSRIs or trazodone in the management of agitated patients

AD, Alzheimer disease; AE, adverse event; APA, American Psychiatric Association; CCCDTD4, 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia; ChEI, cholinesterase inhibitor; EAN, European Academy of Neurology; MOA, mechanism of action; PK, pharmacokinetics; SSRI, selective serotonin reuptake inhibitor. ^*Formerly known as European Federation of Neurological Societies and European Neurological Society.