PMID- 35247186
OWN - NLM
STAT- MEDLINE
DCOM- 20220503
LR  - 20220618
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 39
IP  - 5
DP  - 2022 May
TI  - Comparative Outcomes of Commonly Used Off-Label Atypical Antipsychotics in the 
      Treatment of Dementia-Related Psychosis: A Network Meta-analysis.
PG  - 1993-2008
LID - 10.1007/s12325-022-02075-8 [doi]
AB  - INTRODUCTION: Dementia-related psychosis (DRP) is characterized by hallucinations 
      and delusions, which may increase the debilitating effects of underlying 
      dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, 
      safety, and acceptability of atypical antipsychotics (AAPs) commonly used off 
      label to treat DRP. METHODS: We included 22 eligible studies from a systematic 
      literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and 
      brexpiprazole) used off label to treat DRP. Study outcomes were: (1) 
      efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) 
      safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, 
      fractures, injuries, etc.), and (3) acceptability-discontinuations due to all 
      causes, lack of efficacy, and adverse events (AEs). We used random-effects 
      modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH 
      psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, 
      with their respective 95% confidence intervals (CIs). RESULTS: Compared with 
      placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD 
      - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical 
      improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine 
      (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality 
      (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), 
      brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 
      5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 
      0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and 
      olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds 
      of CVAEs compared to placebo. Compared with placebo, odds of all-cause 
      discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 
      0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 
      95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly 
      lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) 
      compared to placebo, while results for quetiapine and risperidone were not 
      significant. Compared with placebo, the odds of discontinuation due to AEs (19 
      studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), 
      brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 
      1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% 
      CI 1.02, 1.94). CONCLUSIONS: Overall results demonstrate that, compared with 
      placebo, quetiapine is not associated with improvement in psychosis in patients 
      with dementia, while olanzapine and aripiprazole have non-significant small 
      numerical improvements. These off-label AAPs (quetiapine, risperidone, 
      olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of 
      mortality, CVAEs, and discontinuations due to AEs than placebo. These results 
      underscore the ongoing unmet need for newer pharmacological options with a more 
      favorable benefit-risk profile for the treatment of DRP.
CI  - (c) 2022. The Author(s).
FAU - Yunusa, Ismaeel
AU  - Yunusa I
AD  - College of Pharmacy, University of South Carolina, Columbia, SC, USA.
FAU - Rashid, Nazia
AU  - Rashid N
AD  - Acadia Pharmaceuticals, Inc, San Diego, CA, USA.
FAU - Demos, George N
AU  - Demos GN
AD  - Acadia Pharmaceuticals, Inc, San Diego, CA, USA.
FAU - Mahadik, Bhargavi S
AU  - Mahadik BS
AD  - Anlitiks Inc., Dover, MA, USA. b.mahadik@anlitiks.com.
FAU - Abler, Victor C
AU  - Abler VC
AD  - Acadia Pharmaceuticals, Inc, San Diego, CA, USA.
FAU - Rajagopalan, Krithika
AU  - Rajagopalan K
AD  - Anlitiks Inc., Dover, MA, USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20220305
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Antipsychotic Agents)
RN  - 12794-10-4 (Benzodiazepines)
RN  - 2S3PL1B6UJ (Quetiapine Fumarate)
RN  - 82VFR53I78 (Aripiprazole)
RN  - L6UH7ZF8HC (Risperidone)
RN  - N7U69T4SZR (Olanzapine)
MH  - *Antipsychotic Agents/therapeutic use
MH  - Aripiprazole/therapeutic use
MH  - Benzodiazepines/therapeutic use
MH  - *Dementia/complications/drug therapy
MH  - Humans
MH  - Network Meta-Analysis
MH  - Off-Label Use
MH  - Olanzapine/therapeutic use
MH  - *Psychotic Disorders/drug therapy/etiology
MH  - Quetiapine Fumarate/therapeutic use
MH  - Risperidone/adverse effects
MH  - Treatment Outcome
PMC - PMC9056477
OTO - NOTNLM
OT  - Acceptability
OT  - Atypical antipsychotics
OT  - Delusions
OT  - Dementia-related psychosis
OT  - Efficacy
OT  - Hallucination
OT  - Network meta-analysis
OT  - Safety
EDAT- 2022/03/06 06:00
MHDA- 2022/05/04 06:00
PMCR- 2022/03/05
CRDT- 2022/03/05 12:07
PHST- 2021/11/20 00:00 [received]
PHST- 2022/02/03 00:00 [accepted]
PHST- 2022/03/06 06:00 [pubmed]
PHST- 2022/05/04 06:00 [medline]
PHST- 2022/03/05 12:07 [entrez]
PHST- 2022/03/05 00:00 [pmc-release]
AID - 10.1007/s12325-022-02075-8 [pii]
AID - 2075 [pii]
AID - 10.1007/s12325-022-02075-8 [doi]
PST - ppublish
SO  - Adv Ther. 2022 May;39(5):1993-2008. doi: 10.1007/s12325-022-02075-8. Epub 2022 
      Mar 5.