Treatment of behavioral and psychological symptoms of dementias with psychopharmaceuticals: a review

Figures & data

Table 1 Recommended daily doses of antipsychotics to treat BPSD and the available drug forms

Antipsychotic	Daily dosing
Risperidone (tbl., sol.)	0.25–1 mg
Olanzapine (tbl., inj.)	2.5–7.5 mg
Quetiapine (tbl.)	12.5–150 mg
Aripiprazole (tbl., inj.)	5–10 mg
Haloperidol (tbl., gtt., inj.)	0.5–5 mg

Abbreviation: BPSD, behavioral and psychological symptoms of dementia.

Table 2 Recommendations on the use of antipsychotics to treat BPSD

Steps	Recommended procedures
Assessment of BPSD	1. Patients with dementia should be assessed for the type, frequency, severity, clinical pattern, and timing of the symptoms (1C)
	2. Assess for pain and other potentially modifiable factors and for subtypes of dementia that may influence the choice of treatment (1C)
	3. Use quantitative measures to assess agitation and psychosis, if present (1C)
Development of comprehensive treatment plan	4. Individualized treatment plan includes appropriate nonpharmacological and pharmacological interventions (1C)
Assessment of benefits and risks of antipsychotic treatment for the patient	5. Antipsychotic medication should be used for treatment of agitation or psychosis only when symptoms are severe or dangerous and/or cause significant distress to the patient (1B)
	6. Review response to nonpharmacological interventions prior to use of an antipsychotic medication (1C)
	7. If feasible, discuss risk/benefit with the patient and obtain his/her or the caregiver’s consent (1C)
AP treatment – dosage, duration, and monitoring	8. Initiate at a low dose to be titrated up to the minimum effective dose as tolerated (1B)
	9. If significant adverse effects occur, review the patient’s status and taper or discontinue the antipsychotic medication (1C)
	10. If no significant response occurs after 4 weeks of an adequate dose, taper and withdraw the medication (1B)
	11. If positive response occurs, consider and discuss tapering the dose with the patient/surrogate regarding experience with tapering attempts (1C)
	12. If adequate response occurs, the dose of antipsychotic medication could be tapered or withdrawn, unless the patient experienced recurrence of symptoms with prior attempts at tapering (1C)
	13. If the dose of antipsychotic medication is being tapered, assess the symptoms at least monthly for a minimum of 4 months after discontinuation to identify recurrence of symptoms (1C)
Use of specific antipsychotic medication, depending on clinical context	14. In the absence of delirium, haloperidol should not be used as a first-line agent (1B)
	15. Long-acting injectable antipsychotics should not be used, unless it is indicated for co-occurring psychotic disorder (1B)

Notes: Recommendations in brackets: 1=recommended – benefits of the intervention overweigh its harms, 2=uncertain benefit/potential harm ratio. Strength of evidence: A – high, B – moderate, C – low.¹¹

Abbreviation: BPSD, behavioral and psychological symptoms of dementia.

Table 3 Summary of metabolism, pharmacokinetic, and pharmacodynamic interactions of cognitive enhancersa

Drugs	Metabolism	Drugs increasing levels	Drugs decreasing levels	Pharmacodynamic interactions
Donepezil	CYP3A4 and 2D6	Fluoxetine Ketoconazole Itraconazole Erythromycin Quinidine	Rifampicin Phenytoin Carbamazepine Alcohol	Anticholinergic medication – An Cholinomimetics (succinylcholine) – S Peripheral ChE-I (neostigmine) – S Beta blockers – CV Amiodarone – CV Ca channel blockers – CV
Rivastigmine	Extrahepatic	–	–	Anticholinergic medication – An Cholinomimetics (succinylcholine) – S Peripheral ChE-I (neostigmine) – S Beta blockers – CV Amiodarone – CV Ca channel blockers – CV
Galantamine	CYP3A4 and 2D6	Paroxetine Fluoxetine Fluvoxamine Amitriptyline Ketoconazole Erythromycin Ritonavir Quinidine	?	Anticholinergic medication – An Cholinomimetics (succinylcholine) – S Peripheral ChE-I (neostigmine) – S Beta blockers – CV Amiodarone – CV Ca channel blockers – CV
Memantine	Primarily extrahepatic, renal excretion	Cimetidine Ranitidine Procainamide Quinidine Nicotine Urine alkalizing drugsb	?	Increase in effect of L-dopa, dopaminergic and anticholinergic medication Amantadine, ketamine, dextromethorphan – FTP It is necessary to adjust the dosage of spasmolytic medication, dantrolene, and baclofen

Notes:

a According to Taylor et al¹ and Masopust et al.⁶²

b Carbonic anhydrase inhibitors (diuretics), sodium bicarbonate. The question mark (?) indicates “unknown”. The en dash (–) indicates “none”.

Abbreviations: An, antagonistic effect; CV, effect on cardiac action, slowing of transduction; FTP, risk of pharmacotoxic psychosis; S, synergic effect.

ReusVIFochtmannLJEylerAEThe American Psychiatric Association Practice Guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementiaAm J Psychiatry201617354354627133416

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TaylorDPatonCKapurSPrescribing Guidelines in Psychiatry12th edWest Sussex, UKJohn Wiley & Sons2015

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MasopustJMalýRVališMRisk of venous thromboembolism during treatment with antipsychotic agentsPsychiatry Clin Neurosci20126654155223252920

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