Table 1.
Randomized, blinded, controlled trials of agents (available in the USA) for neuropsychiatric symptoms of dementia since 2004
| Study; funding sponsor | Study design (N); study length | Medication | Pt residence | Dementia type and severity | Outcomes | Outcomes related to specific symptoms | AEs |
|---|---|---|---|---|---|---|---|
| Antidepressants | |||||||
| Finkel et al. [56]; Pfizer Inc. | MC, DB, PC, PG (N = 245); 12 wk | SER (in pts on DON) | Outpatients | Probable or possible AD per NINCDS/ADRDA criteria and MMSE 8–23, Rosen-modified Hachinski Ischemia scale score ≤ 4, Clinical Dementia Rating scale score ≤ 2 | ND between groups in scores on primary outcome measure NPI total score, CGI-I, CGI-S | ND on various rating scales, including HAMD, CMAI-C | ND in changes in vital signs, weight, ECG measure, or laboratory values. Common AE in SER group: diarrhea |
| Weintraub et al. [55]; NIMH; Pfizer Inc. provided medication only | RAN, DB, PC, MC (N = 131); 24 wk (12-wk efficacy trial and 12 wk extension phase of responders) | SER | Unspecified but required pts with caregivers | Dementia due to AD per DSM-IV and MMSE scores 10–26 | ND between groups at wk 24 in scores on primary outcome measure mADCS-CGIC score | ND between groups in CSDD scores at wk 24 | Pts on SER had higher rates of pulmonary SAEs. Common AEs in SER group: diarrhea, dizziness, dry mouth |
| Porsteinsson et al. [54]; NIA and NIMH, and in part by NIH | RAN, PC, DB, MC, PG (N = 186); 9 wk | CIT | Unspecified, but required caregiver who spent at least several h/wk with the pt | Probable AD per NINCDS criteria and MMSE scores 5–28 with clinically significant agitation | Scores on primary outcome measures NBRS-A and mADCS-CGIC scores showed improvement in CIT arm | Improvement on CMAI, total NPI, and caregiver distress scores but not NPI agitation subscale or ADCS-ADL scale |
Worsening of cognition, increased fall frequency, increased risk of URTI, and QT interval prolongation observed with CIT. Common AE with CIT: diarrhea, fever |
| Mood stabilizers (anticonvulsants) | |||||||
| Tariot et al. [90]; The National Institute on Aging and Abbot Laboratories Inc. | RAN, DB, PC, parallel-arm multisite (N = 153); 6 wk | DS | Nursing homes | Probable or possible AD according to NINCDS-ADRDA criteria; MMSE score 4–24 | ND between groups in scores on primary outcome measure of change in agitation factor of BPRS | ND between groups on CMAI | More diarrhea with DS than PL. Common side effects (> 10% incidence) in both groups: GI disorders, general disorders (falls), infections/infestations, injury/poisoning/procedural complications, abnormal laboratory values, musculoskeletal and connective tissue disorders, nervous system disorders, psychiatric disorders, and skin/subcutaneous tissue disorders |
| Herrmann et al. [91]; Alzheimer’s Society of Canada | RAN, MC, DB, PC, CO (N = 14); 6 wk | VAL | LTC facilities | Probable AD of at least 1 year per NINCDS-ADRDA criteria and primary degenerative dementia per DSM-IV criteria; MMSE < 15 | ND between groups in scores on primary outcome measure NPI agitation/aggression subscale score | ND in CMAI score between groups | No statistically significant difference. Pts on VAL had more falls, sedation, loss of appetite, loose stools, thrombocytopenia |
| Sommer et al. [92]; Norwegian Research Council, Health East Hospital Trust, and Innlandet Hospital Trust; Novartis provided medication only | MC, RAN, DB, PC (N = 103); 8 wk | OXC | Nursing homes | Diagnosis of AD or vascular dementia according to ICD-10 diagnostic criteria for research; MMSE score 0–20 | ND between groups in scores on primary outcome measure change in agitation and aggression subscore of NPI-NH | ND between groups on BARS | Significantly more pts had “some AEs” with OXC. Common AEs included sedation and falls |
| Antipsychotics | |||||||
| Suh et al. [93]; Janssen Korea | RAN, DB, CO (N = 120); 18 wk | RIS, HAL | Semi-hospitalized LTC institution | Dementia of Alzheimer type, vascular dementia, or combination of both according to DSM-IV; FAST score of 4+ | Pts on RIS had greater improvement on BEHAVE-AD-K total score vs. pts on HAL. CGI-C scores also in favor of RIS treatment | ND between groups on BEHAVE-AD-K score items: psychosis, activity disturbances, affective disturbance, and anxieties and phobias. Pts on RIS had more improvement on aggressiveness and diurnal rhythm disturbances than pts on HAL. Pts on RIS also improved more on CMAI-K total score (including subscale items: aggressive behavior, physical nonaggressive behavior, and verbally agitated behavior) | HAL associated with worsening of EPS (based on ESRS total score and parkinsonism) vs. RIS. Pts on HAL also had more somnolence, insomnia, and sialorrhea than pts on RIS |
| De Deyn et al. [94]; Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. | RAN, DB, PC, MC (N = 208); 10 wk | ARI | Noninstitutional (e.g., ALF or adult communities, or living with a caregiver) | AD per DSM-IV; MMSE score 6–24 | ND between groups in primary outcome measure of mean change in caregiver-assessed NPI psychosis subscale. ND in CGI-I or CGI-S between groups. Pts with baseline NPI ≥ 12 had greater improvement on CGI-S scores and CGI-I responder rates (post hoc) | Greater improvement in ARI pts on BPRS psychosis subscale vs. PL pts | Statistically significant differences in AE NR. ND in movement-type AE between groups. Four deaths (ARI arm) unrelated to study drug. Common side effects included accidental injury, somnolence, UTI, bronchitis, hypertension |
| Deberdt et al. [95]; Eli Lilly and Company | MC, DB, PC (N = 494); 10 wk | OLA, RIS | Outpatient or residential setting (nursing homes or ALFs) | Dementia diagnoses defined by NINCDS-ADRDA or DSM-IV criteria; MMSE score 5–24 | No significant differences between groups in changes in any efficacy measure, including primary outcome measures of NPI psychosis total or CGI severity of psychosis | ND between groups in mean change on the scale scores CSDD, CMAI aggression | More somnolence and dyspnea with OLA vs. PL, abnormal gait, flu syndrome, asthenia in RIS vs. PL, urinary incontinence and hostility with active treatment vs. PL |
| Tariot et al. [96]; AstraZeneca Pharmaceuticals LP | RAN, MC, DB, PC (N = 284); 10 wk | QUE, HAL | Nursing homes (not bedridden) | Probable AD by DSM-IV criteria or possible AD per NINCDS-ADRDA criteria; MMSE ≥ 5 | Mean total BPRS and CGI-S scores improved for all pts; ND between groups in degree of improvement | Pts on QUE had improved BPRS agitation vs. pts on PL. ND between groups on NPI-NH agitation or BPRS thought disturbance scores. Pts on QUE had improved BPRS anergia vs. HAL |
Higher SAS scores for HAL vs. QUE. More somnolence and urinary incontinence with QUE vs. PL. More infections and convulsion with QUE vs. HAL or PL. Fewer instances of agitation with QUE vs. PL. More dyspepsia, pallor, fever, insomnia with HAL vs. QUE |
| Schneider et al. [97]; NIMH; Astra Zeneca Pharmaceuticals, Forest Pharmaceuticals, Janssen Pharmaceutical, and Eli Lilly provided medications only | RAN, MC, DB, PC (N = 421); 36 wk | OLA, QUE, RIS | Ambulatory and living at home or in ALF | Dementia of AD type per DSM-IV or probable AD on basis of history, physical exam, structural brain imaging; MMSE score 5–26 | No significant differences in primary outcome measure of time until all-cause discontinuation between groups (median time 5.3–8.1 wk). Longer median time to discontinuation due to lack of efficacy in OLA and RIS groups vs. PL. Discontinuation due to intolerance, AE, or death favored PL vs. active treatment | Specific symptom scores NR | No significant differences between groups with proportion of pts with at least one SAE or any AE, though pts discontinued antipsychotic treatment at greater rates than PL due to intolerance, AE, or death. More pts on OLA and RIS experienced EPS and weight/BMI change, pts on antipsychotics experienced more sedation, and more pts on OLA had cognitive disturbance and confusion/mental status changes. RIS pts had higher rates of prolactin elevation |
| Verhey et al. [98]; unspecified | RAN, MC, DB, two-arm (N = 58); 5 wk | OLA, HAL | Nursing homes and outpatients living in own home | Dementia according to DSM-IV criteria but, excluded other neurological conditions contributing to dementia, including Parkinson’s disease, Lewy body disease | ND between groups in primary outcome measure of reduction in mean total sum score from baseline to endpoint on CMAI. Both treatments improved CMAI scores at endpoint vs. baseline | ND between groups in terms of NPI and NPI items, including distress, psychosis, hyperactivity, mood. Reductions in both groups on change in scores over 5 wk on NPI and NPI items: hyperactivity, mood/apathy. No improvement in NPI psychosis in either group | ND between groups on AIMS, SAS, or UKU |
| Kurlan et al. [99]; National Institute on Aging; AstraZeneca, LP provided medication only |
MC RAN, DB, PC, PG (N = 40); 10 wk |
QUE |
Own residence or supervised care setting (e.g., nursing homes) |
Dementia defined by DSM-IV, probable AD per NINCDS-ADRDA criteria or Consortium diagnostic criteria for DLB or UK Brain Bank criteria for PD; MMSE score ≥ 8 | ND between groups in primary outcome measure of BPRS score. ND in secondary outcome measures of NPI, ADCS-CGIC, UPDRS, R-MDS-D, parkinsonism | No particular symptoms analyzed separately | ND between groups with any particular AE |
| Mintzer et al. [100]; Bristol-Myers Squibb company and Otsuka Pharmaceutical Development & Commercialization | MC, RAN, DB, PC (N = 487); 10 wk | ARI | Nursing homes or residential ALF | AD defined by DSM-IV criteria; MMSE score 6–22 | Primary outcome measure of mean change from baseline in NPI-NH psychosis subscale improved and differed for ARI 10 mg but not 2 or 5 mg vs. PL arm. BPRS core scores improved for all ARI arms from baseline to endpoint; only ARI 10 mg improved BPRS total scores at 10 wk | Individual items on NPI-NH showing improvement with ARI 10 mg vs. PL: delusions, agitation/aggression, anxiety, irritability. CMAI scores improved on ARI 5 and 10 mg | ND between groups on deaths, cerebrovascular AE, EPS, or other common AE |
| Rainer et al. [101]; AstraZeneca Pharmaceuticals | Rater-blinded, RAN, PG, MC (N = 72); 8 wk | QUE, RIS | Living with someone or daily contact with caregiver | Dementia of AD, vascular, mixed, or frontotemporal lobe type according to DSM-IV and ICD-10 criteria; MMSE score 10–26 | ND between groups on primary outcome measure of change from baseline to endpoint in NPI part 1 and 2 (caregiver burden/distress), though both medications showed overall improvement in symptoms using NPI | CMAI scores improved in each arm (not statistically significant), but ND between groups in change in scores | ND between groups on any particular AE. Sedation occurred more frequently (at least 10%) in QUE arm. AEs occurring more frequently (at least 10%) in RIS arm: diarrhea, muscle rigidity |
| Zhong et al. [102]; AstraZeneca Pharmaceuticals | RAN, DB, MC, PC, fixed dose (N = 333); 10 wk | QUE | Nursing homes or ALF | Probable or possible AD or vascular dementia according to DISM-IV or NINCDS-ADRDA criteria | Primary outcome measure was change from baseline to endpoint on PANSS-EC score, which was superior with QUE 200 mg/day (using OC, but not LOCF analysis) vs. PL, but no better for QUE 100 mg/day vs. PL. Pts improved on QUE 200 mg/day on CGI-C vs. PL. In AD subgroup, pts receiving QUE 200 mg/day had greater reduction in PANSS-EC vs. PL | ND between any QUE groups vs. PL on the following scores: NPI-NH, NPI-NH items (agitation, depression, psychosis), CMAI, and CMAI items (physically aggressive behavior, non-aggressive physical behavior, and verbal aggression). In AD subgroup, ND on NPI-NH and CMAI between groups | ND between groups in pts withdrawing due to AE. Common AEs (> 10%) reported among groups included falls, lethargy, skin laceration, UTI. Statistical significance unknown |
| Paleacu et al. [103]; AstraZeneca | DB, RAN, PC (N = 40); 6 wk | QUE | Unspecified | AD defined by DSM-IV; MMSE score < 24 | Coprimary endpoints included change in NPI score and CGI-C, but statistical significance (p value) NR for comparisons between QUE vs. PL, only for changes within treatments from endpoint vs. baseline scores. Authors appear to conclude ND on NPI score | Items on NPI with significant improvement in PL arm only: agitation, apathy. Items on NPI with significant improvement in both arms at endpoint vs. baseline: delusions, hallucinations, anxiety, euphoria, disinhibition, irritability, aberrant motor behavior, night-time behavior, appetite, and depression | ND in AEs between groups |
| Streim et al. [104]; Bristol-Myers Squibb company and Otsuka Pharmaceutical Company, Ltd | RAN, PG, DB, PC (N = 256); 10 wk | ARI | Institutional (nursing home or residential ALF) | AD per DSM-IV; MMSE score 6–22 | Coprimary endpoints were mean change from baseline on NPI-NH Psychosis subscale and CGI-S scores, which showed improvement in both groups, but were not significantly different between groups. ND between groups on NPI-NH total scores but BPRS scale scores improved | ND between groups on BPRS Psychosis subscale scores or Core scores. Pts on ARI showed more improvement than PL on Cornell Depression Scale and CMAI | Somnolence more frequent with ARI (14%) vs. PL (4%), statistical significance unknown. Statistical differences in body weight changes and weight gain ≥ 7% from baseline with ARI (decreased/less) and PL (increase/more) |
| De Deyn et al. [105]; AstraZeneca | RAN, DB, double-dummy, multisite, PG (N = 100); 6 wk | QUE IR and XR | Nursing homes or equivalent institutions | Dementia of AD type defined by DSM-IV or dementia in AD according to ICD-10; MMSE score of ≤ 23 | Primary outcome variable of incidence/type of AE was 69.1% in QUE XR group and 71.9% in QUE IR group; AE types were similar. Common (> 10%) AE in either group included somnolence, vomiting, sedation. Pts gaining ≥ 7% of baseline weight was 6.3% (QUE XR) and 15.6% (QUE IR). Statistical significance NR for any outcome measures | Improvements in CMAI and NPI disruption score, though statistical significance unknown | See “Outcomes” column (as this was a tolerability study) |
| Cholinesterase inhibitors and memantine | |||||||
| Holmes et al. [106]; Pfizer/Eisai | RAN, DB, PC, MC, withdrawal (N = 134); 24 wk (including 12 wk of open-label treatment) | DON | Unspecified | Probable AD per NINCDS-ADRDA criteria; MMSE score 10–27 | Primary outcome measure of NPI differed and improved in pts on DON vs. PL | During open-label phase, pts on DON improved at wk 12 vs. baseline on NPI items: agitation, anxiety, apathy, delusions, depression, disinhibition, hallucinations, irritability, and motor activity | NR |
| Cummings et al. [107]; National Institute on Aging | MC, RAN, DB, PC, PG, fixed dose (N = 404); 24 wk | MEM (in pts on DON) | In the community | Probable AD according to NINCDS-ADRDA criteria; MMSE score 5–14 | Primary outcome measure change from baseline on SIB and ADCS-ADL, reported in a previous paper. Scores on NPI significantly different for pts on MEM (improved) vs. PL | Significant differences in favor of MEM in NPI items: agitation/aggression, irritability/lability, appetite/eating changes. Fewer pts on MEM displayed emergence of agitation, irritability, and night-time behavior in pts with no behavioral symptoms in certain domains at baseline | Reported in previous trial paper |
| Howard et al. [108]; Medical Research Council and the Alzheimer’s Society | MC, blinded, RAN, PG (N = 272); 12 wk | DON |
Residential care facility or with a caregiver in the community |
Probable or possible AD per NINCDS-ADRDA criteria | Primary outcome measure of mean reduction in CMAI score from baseline to endpoint was not different between DON and PL groups. ND between groups on NPI | No specific symptom reported | Statistical significance NR, but AEs were similar with DON and PL. No AE occurred in > 5% of pts in either arm |
| Fox et al. [109]; Lundbeck | DB, RAN, PC (N = 149); 12 wk | MEM | Nursing or residential care homes and acute psychiatric wards | Probable AD; SMMSE score of ≤ 19, Hachinski Score ≤ 4 |
ND between groups in primary outcome measure (change in CMAI score). NPI scores also differed in favor of MEM. Significant reductions at endpoint vs. baseline with MEM for SIB but not CGI-C (statistical significance between groups unknown) |
No significant reduction in either group on CMAI scores | Statistical significance unknown, but AEs appeared similar. Common AEs (> 10%) in either group: fatigue, somnolence, confusion, hallucinations, abnormal gait |
| Multiple agents | |||||||
| Pollock et al. [110]; US Public Health Service and the Sandra A. Rotman Program in Neuropsychiatry | RAN, DB, controlled (N = 103); 12 wk | CIT, RIS | Admitted to geropsychiatric ward of hospital with possible discharge to nursing homes, personal care homes, or residential homes | Dementia of AD type, vascular dementia, DLB, mixed dementia, or dementia not otherwise specified | No significant difference between changes in NBRS agitation or psychosis scores. Psychosis scores reduced with both CIT and RIS. Agitation scores reduced with CIT but not RIS | See “outcomes” column | UKU Total and psychic subscale scores were significantly different between groups and worse for RIS vs. CIT. ND on other UKU subscales: neurologic, autonomic, or other |
| Culo et al. [111]; US Public Health Service and the Sandra A. Rotman Program in Neuropsychiatry | RAN, DB, controlled (subanalysis of previous trial by Pollock et al. [110]) (N = 97); 12 wk | CIT, RIS | Admitted to geropsychiatric ward of hospital with possible discharge to nursing homes, personal care homes, or residential homes | DLB and AD only | DLB pts improved less than AD pts based on NPI changes. No significant difference at endpoint vs. baseline between groups in pts with DLB. CGI-C showed pts with DLB did not improve or worsened vs. pts with AD (improved) | Specific symptom outcomes NR | No significant differences on discontinuations, and UKU scores between groups among AD vs. DLB. Pts with DLB displayed greater mean change (higher) in UKU scores on RIS vs. CIT |
| Freund-Levi et al. [112]; Janssen Pharmaceuticals | RAN, PG, controlled, fixed-dose, single-center (N = 100); 12 wk | GAL, RIS | Unspecified | Dementia according to DSM-IV or presence of mild cognitive impairment | CMAI scores declined with both groups; change statistically significantly improved with RIS vs. GAL | CMAI subscore item aggressive physical behavior differed between groups using LOCF but not OC | ND observed on SAS. Statistical significance NR for other common AE |
| Other agents | |||||||
| Peskind et al. [113]; Department of Veterans Affairs and the Joan C. Alhadeff Research Foundation | RAN, DB (N = 31); 6 wk | PRO | Nursing home | Probable or possible AD per NINCDS-ADRDA criteria | Primary outcome measure of NPI Total score and CGI-C mean score showed greater improvement for pts on PRO vs. PL | On individual NPI subscore items, PRO ND vs. PL | Blood pressure and heart rate decreases not significantly different between groups |
| Wang et al. [114]; NIA, the Joan Alhadeff Alzheimer’s disease Research Fund, and the VA Mental Illness Research, Education, and Clinical Center Special Fellowship in Advanced Psychiatry | RAN, DB, PC, single-site, PG (N = 22); 8 wk | PRA | Nursing home or community dwelling | Probable or possible AD by NINCDS-ADRDA criteria | Primary outcome measures of CGI-C and change from baseline on NPI and BPRS all showed greater improvement or positive changes in pts on PRA vs. PL | NPI subscores for specific items were displayed; PL scores and statistical significance NR | Statistical significance NR for AE list, though differences in blood pressure changes no different for PRA vs. PL |
| Rosenberg et al. [115]; National Institute on Aging | RAN, DB, PC, MC (N = 60); 6 wk | MET | Unspecified | Possible or probable AD per NINCDS-ADRDA criteria; MMSE ≥ 10 | Primary outcome measure of differences in change in AES showed ND with MET vs. PL. A second primary outcome measure of ADCS-CGI-C change in apathy showed improvement in favor of MET over PL | NPI apathy scores were in favor of MET | Pts on PL had more arthralgia. ND between groups in other reported AEs |
| Cummings et al. [78]; Avanir Pharmaceuticals Inc. | RAN, MC, DB, PC, sequential parallel comparison design (N = 220); 10 wk | DXQ | Outpatient, ALF, and nursing homes | Probable AD based on 2011 National Institute on Aging–Alzheimer Association criteria; MMSE score of 8–28 | Primary outcome measure (change from baseline in NPI agitation/aggression domain) improved for DXQ group vs. PL | Using sequential parallel comparison design, improvements were seen in favor of DXQ for CGI-C and ADCS-CGI-C, CSDD, NPI Total score (and aberrant motor behavior and irritability/lability domains and other selected groupings of NPI domains) | Statistical significance NR, though TEAE occurred in 61.2 and 43.3% of pts receiving DXQ or PL, respectively. Common TEAEs: falls, diarrhea, UTI, dizziness |
| van den Elsen et al. [116]; European Regional Development Fund and the Province of Gelderland; Echo Pharmaceuticals provided medical product only | RAN, DB, PC, MC (N = 50); 3 wk | THC | Nursing homes and outpatient | AD or vascular or mixed dementia per NINCDS-ADRDA or NINCDS-AIREN criteria | Primary outcome measure of change in NPI no different between THC and PL groups. NPI scores decreased in both groups. ND between groups on CGI-C | ND between groups on NPI subscale scores: agitation, aberrant motor behavior. ND between groups observed on CMAI | ND between groups on reported metabolic AE. Statistical significance not shown for common specific (not by organ class) AE (> 10%) reported in either group: dizziness, somnolence, cognitive disorder, fall |
| van den Elsen et al. [117]; European Regional Development Fund and the Province of Gelderland; Echo Pharmaceuticals provided medical product only | RAN, DB, PC, repeated CO, MC trial (N = 22); 12 wk | THC | Unspecified | Dementia type AD, vascular or mixed. According to NINCDS-ADRDA or NINCDS-AIREN criteria; CDR scores 0.5–3 | ND between groups on primary outcome of NPI | ND between groups on NPI subscale agitation/aggression or CMAI | Statistical significance between groups NR for reported AE. Psychiatric disorders > 10% for AE of either THC or PL at various time periods |
AD Alzheimer’s disease, ADCS-ADL Alzheimer Disease Cooperative Study-activities of daily living, ADCS-CGIC Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change, AE adverse effect, AES Apathy Evaluation Scale, AIMS Abnormal Involuntary Movement Scale, ALF assisted-living facilities, ARI aripiprazole, BARS Brief Agitation Rating Scale, BEHAVE-AD Behavioral Pathology in Alzheimer’s Disease Rating Scale, BEHAVE-AD-K Korean version of the Behavioral Pathology in Alzheimer’s Disease Rating Scale, BMI body mass index, BPRS Brief Psychiatric Rating Scale, CDR Clinical Dementia Rating Scale, CGI-C Clinical Global Impression of Change, CGI-I Clinical Global Impression – Improvement, CGI-S Clinical Global Impression – Severity, CIT citalopram, CMAI Cohen-Mansfield Agitation Inventory, CMAI-C Cohen-Mansfield Agitation Inventory-Community, CMAI-K Korean version of the Cohen-Mansfield Agitation Inventory, CO crossover, CSDD Cornell Scale for Depression in Dementia, DB double blind, DLB dementia with Lewy bodies, DON donepezil, DS divalproex sodium, DSM-IV Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, DXQ dextromethorphan-quinidine, ECG electrocardiogram, EPS extrapyramidal symptoms, ESRS Extrapyramidal Symptoms Rating Scale, FAST Functional Assessment Staging Test, GAL galantamine, GI gastrointestinal, h hour(s), HAL haloperidol, HAMD Hamilton Depression Rating Scale, ICD-10 International Statistical Classification of Diseases – tenth revision, IR immediate release, LOCF last observation carried forward, LTC long-term care, mADCS-CGIC modified Alzheimer Disease Cooperative Study – Clinical Global Impression of Change, MC multicenter, MEM memantine, MET methylphenidate, MMSE Mini-Mental State Examination, NBRS Neurobehavioral Rating Scale, NBRS-A Neurobehavioral Rating Scale, agitation subscale, ND no difference(s), NIA National Institute on Aging, NIH National Institutes of Health, NIMH National Institute of Mental Health, NINCDS National Institute of Neurological and Communication Disorders and Stroke-Alzheimer Disease and Related Disorders Association criteria, NINCDS-ADRDA National Institute of Neurological and Communication Disorders and Stroke-Alzheimer Disease and Related Disorders Association criteria, NINCDS-AIREN National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche en l’Enseignement en Neurosciences, NPI neuropsychiatric inventory, NPI-NH neuropsychiatric inventory nursing home version, NR not reported, OC observed cases, OLA olanzapine, OXC oxcarbazepine, PANSS-EC Positive and Negative Syndrome Scale – Excitement Component, PC placebo controlled, PD Parkinson’s disease, PG parallel group, PL placebo, PRA prazosin, PRO propranolol, pt(s) patient(s), QUE quetiapine, RAN randomized, RIS risperidone, R-MDS-D Rochester Movement Disorders Scale for Dementia, SAE serious adverse event, SAS Simpson Angus scale, SER sertraline, SIB Severe Impairment Battery, SMMSE Standardized Mini-Mental State Examination, TEAE treatment-emergent adverse event, THC tetrahydrocannabinol, UKU Udvalg for Kliniske UndersØgelser side-effect rating scale, UPDRS Unified Parkinson’s Disease Rating Scale, URTI upper respiratory tract infection, UTI urinary tract infection, VAL valproate, wk week, XR extended release