Serotonergic Drugs: Agonists/Antagonists at Specific Serotonergic Subreceptors for the Treatment of Cognitive, Depressant and Psychotic Symptoms in Alzheimer's Disease

IntroductionUnderstanding the natural course of neuropsychiatric symptoms (NPS) in dementia is important for planning patient care and trial design, but few studies have described the long-term course of NPS in individuals.MethodPrimary inclusion of 223 patients with suspected mild dementia from general practice were followed by annual assessment, including the Neuropsychiatric Inventory (NPI), for up to 12 years. Total and item NPI scores were classified as stable, relapsing, single episodic or not present based on 4.96 (s.d. 2.3) observations (98% completeness of longitudinal data) for 113 patients with Alzheimer's disease and 84 patients with LBD (68 dementia with Lewy bodies and 16 Parkinson's disease dementia).ResultsWe found that 80% had stable NPI total ≥1, 50% had stable modest NPI total ≥12 and 25% had stable NPI total ≥24 scores. Very severe NPS (≥48) were mostly single episodes, but 8% of patients with Alzheimer's disease had stable severe NPS. Patients with Alzheimer's disease and the highest 20% NPI total scores had a more stable or relapsing course of four key symptoms: aberrant motor behaviour, aggression/agitation, delusions and irritability (odds ratio 55, P < 0.001). This was not seen in LBD. Finally, 57% of patients with Alzheimer's disease and 84% of patients with LBD had reoccurring psychotic symptoms.ConclusionsWe observed a highly individual course of NPS, with most presenting as a single episode or relapsing; a stable course was less common, especially in LBD. These findings demonstrate the importance of an individualised approach (i.e. personalised medicine) in dementia care.

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Psychotic Symptoms in Alzheimer's Disease and 5-HTTLPR Polymorphism of the Serotonin Transporter Gene: Evidence for an Association

Journal of Alzheimer s Disease ◽

10.3233/jad-2009-0950 ◽

2009 ◽

Vol 16 (1) ◽

pp. 173-180 ◽

Cited By ~ 9

Author(s):

Davide Quaranta ◽

Alessandra Bizzarro ◽

Camillo Marra ◽

Maria Gabriella Vita ◽

Davide Seripa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Serotonin Transporter ◽

Serotonin Transporter Gene ◽

Psychotic Symptoms ◽

Transporter Gene

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Exacerbation of psychotic symptoms as clinical presentation of Wernicke encephalopathy in an Alzheimer's disease patient

Journal of General and Family Medicine ◽

10.1002/jgf2.330 ◽

2020 ◽

Vol 21 (5) ◽

pp. 185-187

Author(s):

Nozomu Uchida ◽

Mayumi Ishida ◽

Izumi Sato ◽

Takao Takahashi ◽

Daisuke Furuya ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Presentation ◽

Disease Patient ◽

Psychotic Symptoms ◽

Wernicke Encephalopathy

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The ABC of Alzheimer's Disease: Behavioral Symptoms and Their Treatment

International Psychogeriatrics ◽

10.1017/s1041610203008652 ◽

2002 ◽

Vol 14 (S1) ◽

pp. 27-49 ◽

Cited By ~ 33

Author(s):

George T. Grossberg

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Treatment Options ◽

Lewy Body Dementia ◽

Economic Cost ◽

Brain Regions ◽

Behavioral Symptoms ◽

Psychotic Symptoms ◽

Ache Inhibitors ◽

Che Inhibitors

Behavioral and psychological symptoms of dementia (BPSD) are a common manifestation of Alzheimer's disease (AD) and other dementia syndromes. Patients experience prominent and multiple symptoms, which are both distressing and a source of considerable social, health, and economic cost. Development of symptoms is in part related to progressive neurodegeneration and cholinergic deficiency in brain regions important in the regulation of behavioral and emotional responses including the cortex, hippocampus, and limbic system. Cholinesterase (ChE) inhibitors offer a mechanism-based approach to therapy to enhance endogenous cholinergic neurotransmission. Studies using ChE inhibitors have demonstrated their clear potential to improve or stabilize existing BPSD. Differences have been noted between selective acetylcholinesterase (AChE) inhibitors (donepezil and galantamine) and dual ChE inhibitors (rivastigmine) in terms of treatment response. While donepezil has shown efficacy in moderate to severe noninstitutionalized AD patients, conflicting results have been obtained in mild to moderate patients and in nursing home patients. Galantamine has been shown to delay the onset of BPSD during a five-month study but has been otherwise poorly studied to-date. Both donepezil and galantamine have not as yet demonstrated efficacy in reducing psychotic symptoms or in reducing levels of concomitant psychotropic medication use. Studies with the dual ChE inhibitor rivastigmine in mild to moderately severe AD and in Lewy body dementia (LBD) have shown improvements in behavioral symptoms including psychosis. Improvements have been maintained over a period of up to two years. In addition, institutionalized patients with severe AD have shown symptomatic benefits with a reduction in the requirement for additional psychotropic drugs following treatment with rivastigmine. The psychotropic properties associated with rivastigmine may in part be mediated through effects on butyrylcholinesterase. Current treatment options are limited for patients with dementia syndromes other than AD. However, data concerning rivastigmine in patients with LBD and preliminary studies in Parkinson's disease dementia and vascular dementia suggest a role for ChE inhibitors across the spectrum of dementia syndromes. Finally, studies that incorporated a delayed start design demonstrate that ChE inhibitors may delay the progression of BPSD.

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Pharmacotherapy of agitation and psychotic symptoms in Alzheimer’s disease

Expert Review of Neurotherapeutics ◽

10.1586/14737175.2.5.655 ◽

2002 ◽

Vol 2 (5) ◽

pp. 655-664 ◽

Cited By ~ 1

Author(s):

Nicolaas PLG Verhoeff

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Psychotic Symptoms

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P1-151: GENETIC OVERLAP BETWEEN PSYCHOTIC SYMPTOMS ACROSS THE LIFESPAN: FINDINGS FROM SCHIZOPHRENIA, COGNITIVELY NORMAL OLDER ADULTS AND ALZHEIMER'S DISEASE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.155 ◽

2006 ◽

Vol 14 (7S_Part_6) ◽

pp. P335-P335

Author(s):

Byron Creese ◽

Sverre Bergh ◽

Dag Aarsland ◽

Fred Andersen ◽

Helen Brooker ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Psychotic Symptoms ◽

Cognitively Normal ◽

Genetic Overlap

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P.5.a.005 Adjunctive use of amisulpride on acetylcholine inhibitors therapy for the treatment of psychotic symptoms in Alzheimer's disease

European Neuropsychopharmacology ◽

10.1016/s0924-977x(09)70999-x ◽

2009 ◽

Vol 19 ◽

pp. S622

Author(s):

C. Theleritis ◽

A. Politis ◽

M. Passa ◽

F. LentidaM ◽

E. Stamouli ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Psychotic Symptoms

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Escitalopram versus risperidone for the treatment of behavioral and psychotic symptoms associated with Alzheimer's disease: a randomized double-blind pilot study

International Psychogeriatrics ◽

10.1017/s1041610211000743 ◽

2011 ◽

Vol 23 (9) ◽

pp. 1515-1519 ◽

Cited By ~ 26

Author(s):

Yoram Barak ◽

Igor Plopski ◽

Shelly Tadger ◽

Diana Paleacu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Adverse Events ◽

Controlled Trial ◽

Treated Group ◽

Psychotic Symptoms ◽

Completion Rates ◽

Double Blind ◽

Once Daily ◽

Risperidone Group

ABSTRACTBackground: Antipsychotics are frequently used to treat psychosis, aggression and agitation in patients with Alzheimer's disease (AD), but safety warnings abound. Escitalopram was investigated since citalopram has demonstrated some effectiveness in AD. We compared escitalopram and risperidone for psychotic symptoms and agitation associated with AD.Methods: Inpatients with AD, who had been hospitalized because of behavioral symptoms, were recruited to a six-week randomized, double-blind, controlled trial. Participants (n = 40) were randomized to once daily risperidone 1 mg or escitalopram 10 mg.Results: The NPI total score improved in both groups. Onset was earlier in the risperidone-treated group, but improvement did not significantly differ between groups by study end. Completion rates differed for escitalopram (75%) and risperidone (55%), mainly due to adverse events. There were no adverse events in the escitalopram group, while in the risperidone group two patients suffered severe extrapyramidal symptoms and four patients suffered acute physical illness necessitating transfer to general hospital.Conclusion: Escitalopram and risperidone did not differ in efficacy in reducing psychotic symptoms and agitation in patients with AD. Completion rates were higher for escitalopram-treated patients. Replication in larger trials with ambulatory patients is needed.

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