Dementia Is More Than Memory Loss: Neuropsychiatric Symptoms of Dementia and Their Nonpharmacological and Pharmacological Management
Abstract
Nonpharmacological Interventions
Summary
Pharmacological and Biological Therapies
Authors, Year | Study Type | Study Features | Outcomes |
---|---|---|---|
Ballard and Waite, 2006 (32) | Meta-analysis | 16 RCTs, AD; atypical antipsychotics vs. placebo; one atypical antipsychotic vs. other atypical antipsychotics | Risperidone (N=5) compared to placebo was found to be beneficial in treating total behaviors (BEHAVE-AD and NPI total score [0.5 mg/day, p=0.01; 1.0 mg/day, p=0.004; 2.0 mg/day, p=0.01]), beneficial in treating aggression (CMAI [1 mg/day, p=0.007; 2 mg/day vs. 1 mg/day, p=0.01], BEHAVE‐AD aggressiveness subscore [1 mg/day, p=0.0002; 2 mg/day, p<0.0001]), and beneficial in treating psychosis (BEHAVE‐AD subscore [three trials] and NPI subscore [one trial] [1 mg/day, p=0.01]) |
Olanzapine (N=5) (5–10 mg/day) compared to placebo appeared to improve aggressive behaviors (NPI-NH aggression domain, p=0.03), anxiety (NPI-NH anxiety domain, p=0.01), and euphoria (NPI-NH euphoria/elation domain, p=0.05) | |||
Aripiprazole (N=3, but data were available from only one study) (2–15 mg/day) compared to placebo appeared to improve psychosis (BPRS psychosis domain, p=0.03) | |||
Schneider et al., 2006 (33) | RCT | AD; olanzapine, quetiapine, and risperidone vs. placebo | Discontinuation of treatment for any reason: no significant differences between the three antipsychotics—olanzapine (median=8.1 weeks), quetiapine (median=5.3 weeks), and risperidone (median=7.4 weeks)—compared to placebo (median=8.0 weeks) (p=0.52) |
Median time to discontinuation of treatment due to lack of efficacy: superiority for olanzapine (median=22.1 weeks) and risperidone (median=26.7 weeks) compared to quetiapine (median=9.1 weeks) and placebo (median=9.0 weeks) (p=0.002) | |||
CGIC scale: no significant difference between olanzapine (32%), quetiapine (26%), risperidone (29%), and placebo (21%) (p=0.22) | |||
Schneider et al., 2006 (34) | Meta-analysis | 15 RCTs, dementia; atypical antipsychotics vs. placebo | Aripiprazole showed benefits on BPRS change scores (p=0.002), NPI change scores (p=0.02), and the CMAI (p=0.002), but no benefits on the BPRS psychosis subscale (p=0.14) or NPI psychosis subscale (p=0.08) |
Olanzapine showed no benefits on BPRS change score (p=0.24), NPI change score (p=0.25), BPRS psychosis subscale (p=0.38), or NPI psychosis subscale (p=0.97) | |||
Quetiapine showed benefits on the CGIC (p=0.005), but no benefits on the BPRS (p=0.08), the PANSS-EC (p=0.12), or the NPI psychosis subscale (p=0.97) | |||
Risperidone showed benefits on the BEHAVE-AD (p=0.0008), BEHAVE-AD psychosis subscale (p=0.0002), and CMAI (p<0.00001), but no benefit on the NPI psychosis subscale (p=0.47) | |||
Yury and Fisher, 2007 (79) | Meta-analysis | 7 RCTs, dementia; atypical antipsychotics vs. placebo | The mean effect size for primary outcome measures was 0.45 for atypical antipsychotics and 0.32 for placebo; the mean effect size for all the measures of behavioral problems was 0.43 for atypical antipsychotics and 0.26 for placebo |
Katz et al., 2007 (80) | Meta-analysis | 4 RCTs, AD; risperidone vs. placebo | On the BEHAVE-AD psychosis subscale, effect sizes were 0.87 for risperidone and 0.57 for placebo; at the endpoint, the estimated effect size between the two groups was 0.15; on the CGI scale, at the endpoint, the estimated effect size between risperidone and placebo was 0.17; among individuals with more severe symptoms, the effect sizes were 1.14 for risperidone and 0.61 for placebo; at the endpoint, the estimated effect size between the two groups was 0.29 |
Sultzer et al., 2008 (78) | RCT | Olanzapine, quetiapine, and risperidone vs. placebo | On NPI total score, olanzapine and risperidone were better than placebo (olanzapine, p=0.007; risperidone, p<0.001); on the CGIC, risperidone was better than placebo (p<0.001); on the BPRS hostile suspiciousness factor, olanzapine and risperidone were better than placebo (olanzapine, p=0.006; risperidone, p=0.003); on the BPRS psychosis factor, risperidone was better than placebo (p=0.010); on the BPRS withdrawn depression factor, olanzapine was worse than placebo (p=0.003); there were no differences between the antipsychotics and placebo on the BPRS cognitive dysfunction factor (p=0.14) and the Cornell Depression Scale (p=0.64) |
Cheung and Stapelberg 2011 (81) | Meta-analysis | 5 RCTs, dementia; quetiapine vs. placebo | NPI total score: mean difference=−3.05 between quetiapine and placebo; CGIC score: mean difference=−0.31 between quetiapine and placebo |
Maher et al., 2011 (82) | Meta-analysis | 18 RCTs, dementia; atypical antipsychotics vs. placebo | For NPS, effect sizes for aripiprazole, olanzapine, and risperidone were 0.12–0.20, and for quetiapine, 0.11; for psychosis, effect sizes were 0.20 for aripiprazole, 0.05 for olanzapine, 0.05 for risperidone, and −0.03 for quetiapine |
Ma et al., 2014 (83) | Meta-analysis | 16 RCTs, dementia; atypical antipsychotics vs. placebo | For atypical antipsychotics compared to placebo, the weighted mean difference was −1.58 on the BPRS, −1.84 on the CMAI, −2.8 on the NPI, −0.32 on the −0.32, and −0.19 on the CGI-S |
Wang et al., 2015 (84) | Meta-analysis | 6 RCTs, AD; atypical antipsychotics vs. placebo | For atypical antipsychotics compared to placebo, on NPI total score, SMD=0.21; for aripiprazole, SMD=−0.20; for olanzapine, SMD=−0.18 |
Smeets et al., 2018 (85) | Meta-analysis | 16 RCTs, dementia; atypical antipsychotics vs. placebo | For agitation when measured with agitation outcome scales, atypical antipsychotics showed negligible effects (SMD=−0.15); for psychosis when measured with psychosis outcome scales, atypical antipsychotics showed negligible effects (SMD=−0.11); on any NPS, a small effect was observed on agitation (SMD=−0.29), and a negligible effect on psychosis (SMD=−0.13); on generic NPS scales, a small effect was observed on agitation (SMD=−0.22), and a negligible effect on psychosis (SMD=−0.11) |
Yunusa et al., 2019 (36) | NMA | 17 RCTs, dementia; atypical antipsychotics vs. placebo | Aripiprazole: improvements on the NPI (SMD=−0.17), the BPRS (SMD=−0.20), and the on CMAI (SMD=−0.30); olanzapine: no improvements on the NPI, BPRS, or CMAI; quetiapine: no improvements on the NPI, improvements on the BPRS (SMD= −0.24), and no improvements on the CMAI; risperidone: no improvements on the NPI or the BPRS, and improvements on the CMAI (SMD=−0.26); there were no statistically significant differences between the antipsychotics on the NPI, BPRS, or CMAI |
In the surface under the cumulative ranking curve (SUCRA), the highest probability of effectiveness on the NPI was for aripiprazole (85.3%); on the BPRS, for quetiapine (80.2%) and aripiprazole (72.9%); and on the CMAI, for aripiprazole (73.8%) and risperidone (68.6%) | |||
Ballard et al., 2018 (39) and 2019 (40) | RCT | Pimavanserin vs. placebo | At week 6, the NPI-NH psychosis score was −3.76 for pimavanserin and −1.93 for placebo (p=0.045) |
Among patients with more severe symptoms at baseline (NPI-NH psychosis score ≥12), the mean change from baseline was −10.15 for pimavanserin and −5.72 for placebo (p=0.011); pimavanserin was better than placebo in treating hallucinations (p=0.046) and delusions (p=0.034) | |||
Among patients with mild psychotic symptoms (NPI-NH psychosis score <12), the mean change from baseline was −0.58 for pimavanserin and −0.16 for placebo (p=0.694); NPI-NH total scores did not differ between the pimavanserin and placebo groups either at 6 weeks or 12 weeks | |||
At the end of the study period (week 12), no benefit was noted for the pimavanserin group compared to placebo group among the overall study population (p=0.561) or among those with more severe symptoms (NPI-NH psychosis score ≥12) (p=0.497) | |||
Grossberg et al., 2020 (41) | 2 RCTs | Brexpiprazole vs. placebo | In study 1, compared to placebo, on CMAI total score, there was a benefit for brexpiprazole at 2 mg/day (p=0.04), but not at 1 mg/day (p=0.90); on the CGI-S, no benefits were noted for brexpiprazole at either 2 mg/day (p=0.16) or 1 mg/day (p=0.44) |
In study 2, compared to placebo, on CMAI total score, no benefit was noted for brexpiprazole at 0.5–2 mg/day (p=0.15); on the CGI-S, post analyses showed benefit with brexpiprazole (p<0.001) among individuals who were titrated to 2 mg/day over 4 weeks |
Atypical Antipsychotics
Adverse Effects of Atypical Antipsychotics in Patients With NPS
Category, Authors, Year | Study Type | Study Features | Outcomes |
---|---|---|---|
Death | |||
Schneider et al., 2005 (91) | Meta-analysis | 15 RCTs, dementia; atypical antipsychotics vs. placebo | Odds of death were greater among individuals randomized to receive medications (118, 3.5%) compared to those receiving placebo (40, 2.3%); OR=1.54 (p=0.02); risk difference=0.01 (p=0.01) |
The risk differences for death among individuals receiving medications compared to placebo were as follows: aripiprazole vs. placebo, 0.01 (p=0.20); olanzapine vs. placebo, 0.01 (p=0.07); quetiapine vs. placebo, 0.02 (p=0.22); risperidone vs. placebo 0.01 (p=0.33); the overall RR was 1.65 (p=0.003) | |||
No heterogeneity was observed between trials of individuals with higher cognitive function (MMSE score >10) when compared to individuals with lower cognitive function; between individuals with psychosis of AD when compared with those trials that did not select patients with psychosis; or between trials of inpatients compared to outpatients | |||
Mittal et al., 2011 (42); Rubino et al., 2020 (43) | Review from FDA advisory | 17 RCTs, dementia; antipsychotics vs. placebo | 15 studies showed an increases in mortality in drug-treated groups compared to placebo-treated groups (1.6–1.7 times); most deaths were due to heart-related events (e.g., heart failure sudden death) or infections (e.g., pneumonia) |
Manufacturers were required to have a boxed warning describing the risks and indicating that these drugs are not approved for treatment of NPS; the warning was subsequently extended to all antipsychotics | |||
Zhai et al., 2016 (44) | Meta-analysis | 9 epidemiological studies, AD; antipsychotic medications vs. no antipsychotics | In pooled data from eight observational studies, the risk for death was greater among individuals treated with antipsychotics compared to those who were not (RR=1.36); mortality rates among individuals treated with atypical or conventional antipsychotics were the same (RR=1.75) |
Wang et al., 2005 (45) | Retrospective cohort study | Conventional vs. atypical antipsychotics | Mortality among patients treated with conventional antipsychotics was higher than with atypical antipsychotics at all intervals studied; ≤180 days: RR=1.37; <40 days: RR=1.56; 40–79 days: RR=1.37; 80–180 days: RR=1.27 |
HRs were higher 1) when higher dosages of the conventional antipsychotic (greater than the median) were used compared to lower dosages (1.73 vs. 1.14); 2) less than 40 days compared with 80–180 days after beginning therapy (1.56 vs. 1.27); 3) among individuals without dementia compared to those with dementia (1.45 vs. 1.29); and 4) among individuals not in a nursing home compared to those in a nursing home (1.42 vs. 1.26) | |||
Schwertner et al., 2019 (46) | Registry-based cohort study | Dementia; conventional and atypical antipsychotic use vs. nonuse of antipsychotics | The use of conventional and atypical antipsychotics was associated with increased mortality risk compared to no antipsychotic use (HR=1.4); antipsychotic use was associated with increased risk of mortality compared with nonuse of antipsychotics in AD (atypical: HR=1.5), in mixed dementia (conventional: HR=1.3; atypical: HR=1.3), in unspecified dementia (atypical: HR=1.3), in vascular dementia (conventional HR=1.6 vs. atypical HR=1.3) |
In AD, for mortality risk with conventional vs atypical antipsychotic use, the HR was 0.7; in LBD, for mortality risk with conventional antipsychotic use vs. nonuse of antipsychotics the HR was 1.4, and for risk with atypical antipsychotic use vs. nonuse of antipsychotics, the HR was 1.4 | |||
Yunusa et al., 2019 (36) | NMA | 17 RCTs, dementia; atypical antipsychotics vs. placebo | For risk of death, no difference between any of the antipsychotics or between the antipsychotics and placebo; SUCRA indicated that the highest probability of safety in terms of mortality was 87.3% for placebo, 55.4% for risperidone, 37.9% for aripiprazole, 37.1% for quetiapine, and 32.4% for olanzapine |
Cerebrovascular adverse events | |||
Herrmann and Lanctôt 2005 (47) | Post hoc analyses of pooled results from RCTs | 11 RCTs, dementias; olanzapine and risperidone vs. placebo | Olanzapine had a higher exposure-adjusted CVAE incidence in the drug group (15/1178, 1.3%) compared to the placebo group (2/478, 0.4%) (p=0.016); risperidone had higher rates of serious CVAEs in the drug group (15/1009, 1.5%) compared to the placebo group (4/712, 0.6%) (p=0.27); rates of nonserious CVAEs were higher in the drug group (18/1009, 1.8%) compared to the placebo group (4/712, 0.6%) (p=0.026) |
Rao et al., 2016 (49) | Meta-analysis | Five population-based studies, dementia; atypical and conventional antipsychotics vs. nonuse of antipsychotics | CVA: no difference in risk among individuals treated with atypical antipsychotics compared to conventional antipsychotics (RR=1.02); no difference in risk among individuals who were treated with atypical antipsychotics compared to no antipsychotics (RR=0.95) Stroke: no difference in risk among individuals treated with atypical antipsychotics compared to conventional antipsychotics (p=0.96) |
Hsu et al., 2017 (50) | Meta-analysis | 10 observational studies, dementia; atypical antipsychotics and conventional antipsychotics | Use of any antipsychotic was associated with an increased risk of CVA (OR=1.45); the risk was increased among the elderly (OR=1.49) and among individuals with dementia (OR=1.17) |
Yunusa et al., 2019 (36) | NMA | 17 RCTs, dementia; atypical antipsychotics vs. placebo | Compared to placebo, risk of CVAEs was increased for olanzapine (OR=4.28) and risperidone (OR=3.85); compared to placebo, there was no increased risk of CVAEs for aripiprazole (OR=1.09) or quetiapine (OR=1.36); none of the included antipsychotics were significantly different from each other on the risk of CVAEs |
According to the SUCRA, the highest probability of safety on CVAEs with antipsychotics compared to placebo was for aripiprazole (69.1%), followed by quetiapine (65.1%), risperidone (19.6%), and olanzapine (15.8%) | |||
Gill et al., 2005 (48) | Population-based retrospective cohort study | Dementia; atypical vs. conventional antipsychotics | Rates of ischemic stroke were no different among individuals treated with atypical antipsychotics compared to individuals treated with conventional antipsychotics (aHR=1.01) The risk of stroke among individuals receiving conventional antipsychotics compared to those treated with olanzapine (aHR) was 0.91; compared to those treated with quetiapine, 0.78; and compared to those treated with risperidone, 1.04. The risk of stroke among chronic atypical antipsychotic users compared to chronic conventional antipsychotic users (aHR) was 0.89 |
Cognition | |||
Wolf et al., 2017 (52) | Meta-analysis | 10 RCTs, dementia; antipsychotics vs. placebo | The use of atypical antipsychotics showed a tendency for cognitive worsening compared to placebo (SMD=−0.109); only 2 of the 10 studies showed significant effects on cognition (one study for aripiprazole [SMD=−0.498] and one study for olanzapine [SMD=−0.411]) |
The test for heterogeneity was significant among the aripiprazole (p=0.03) and olanzapine studies (p=0.01) but not in the quetiapine (p=0.69) and risperidone (p=0.89) studies; when the two studies (one for aripiprazole and one for olanzapine) were excluded, the SMD was 0 (p=0.95) | |||
There was correlation between cognitive impairment and treatment duration (p<0.02): the longer the duration of study, the greater the cognitive impairment; the higher baseline cognition as measured by MMSE, the greater the cognitive worsening with antipsychotic treatment (p<0.005); these correlations disappeared when the two studies with significant effects on cognition were removed | |||
Vigen et al., 2011 (51) | RCT | AD; olanzapine, quetiapine, and risperidone vs. placebo | There was a decline in cognition among individuals with AD who were treated with olanzapine, quetiapine, or risperidone compared to individuals treated with placebo, on the MMSE (p=0.004), the BPRS cognitive subscale (p=0.05), and a cognitive summary score summarizing change on 18 cognitive tests (p=0.004) |
Pimavanserin | |||
Ballard et al., 2018 (39) | RCT | Pimavanserin vs. placebo | Any adverse event: 98% for pimavanserin and 93% for placebo; any serious adverse event: 17% for pimavanserin and 11% for placebo; any serious adverse event causing discontinuation: 9% for pimavanserin and 12% for placebo; weight loss of ≥7%: 15% for pimavanserin and 2% for placebo; QTc change: 9.5 ms for pimavanserin and −2 ms for placebo |
Brexpiprazole | |||
Grossberg et al., 2020 (41) | 2 RCTs | Brexpiprazole vs. placebo | In study 1, the incidence of TEAEs over 12 weeks was 65.0% for brexpiprazole 2 mg/day, 49.0% for brexpiprazole 0.5–1 mg/day, and 45.9% for placebo; TEAEs with incidence ≥5% among patients receiving brexpiprazole 2 mg/day were headache (9.3% vs. 8.1% with placebo), insomnia (5.7% vs. 4.4%), dizziness (5.7% vs. 3.0%), and urinary tract infection (5.0% vs. 1.5%); among patients receiving brexpiprazole 0.5–1 mg/day, headache (7.6%); the rate discontinuation due to TEAEs was 4.3% for brexpiprazole 2 mg/day, 8.9% for brexpiprazole 0.5–1 mg/day, and 5.2% for placebo |
In study 2, the incidence of TEAEs over 12 weeks was 56.8% for brexpiprazole 0.5–2 mg/day and 58.4% for placebo; TEAEs with incidence ≥5% among patients receiving brexpiprazole 0.5–2 mg/day were headache (7.6% vs. 12.4% with placebo) and somnolence (6.1% vs. 3.6%); the incidence of serious TEAEs was 5.3% for brexpiprazole 0.5–2 mg/day and 4.4% for placebo; the rate of discontinuation due to TEAEs was 6.8% for brexpiprazole 0.5–2 mg/day and 0.7% for placebo | |||
Combined adverse effects reported in meta-analyses | |||
Ballard and Waite, 2006 (32) | 16 RCTs | AD; atypical antipsychotics vs. placebo; one atypical antipsychotic medication vs. other atypical antipsychotic medications | Risperidone vs. placebo: compared with the placebo group, the risperidone group had more adverse effects (1 mg/day: OR=1.43, p=0.05; 2 mg/day: OR=1.94, p=0.005), somnolence (1 mg/day: OR=2.38, p=<0.00001; 2 mg/day: OR=4.46, p<0.00001), urinary tract infection (2 mg/day: OR=1.82, p=0.05), upper respiratory infection (1 mg/day: OR=2.93, p=0.03), EPS (1 mg/day: OR=1.78, p=0.05), gait abnormality (1 mg/day: OR=5.31, p=0.0002), asthenia (1 mg/day: OR=4.37, p=0.05), and CVAEs (all dosages pooled: OR=3.64, p=0.0007) |
Risperidone 2 mg/day vs. 1 mg/day: compared with the 1 mg/day group, the 2 mg/day group had more dropouts (OR=1.65, p=0.04), falls (OR=2.24, p=0.008), EPS (OR=1.83, p=0.05), and pain (OR=1.90, p=0.02) | |||
Olanzapine vs. placebo: compared to the placebo group, the olanzapine group had more dropouts due to adverse effects (OR=3.34, p=0.0005), abnormal gait (5–10 mg/day: OR=9.41, p=0.03; >10 mg/day: OR=9.41, p=0.04), somnolence (5–10 mg/day: OR=3.72, p=0.000; >10 mg/day: OR=8.20, p=0.001), fever (OR=4.55, p=0.04), and urinary incontinence (OR=9.6, p=0.03) | |||
Aripiprazole vs. placebo: compared to the placebo group, the aripiprazole group had more somnolence (OR=8.24, p=0.05) | |||
Quetiapine: compared to the placebo group, cognition was worse in the quetiapine 50–100 mg/day group (p=0.01) | |||
Schneider et al., 2006 (34) | 15 RCTs | Dementia; atypical antipsychotics vs. placebo | Somnolence: drug-treated group compared to placebo group, OR=2.84; olanzapine group compared to aripiprazole and placebo groups, RD=0.16 vs. 0.06 |
EPS: drug-treated group compared to placebo group, OR=1.51; highest risk for EPS was in the risperidone group compared to the placebo group, OR=1.8 and RD=0.06; abnormal gait: risperidone and olanzapine groups compared to the placebo group, OR=3.42; edema: risperidone and olanzapine groups compared to placebo group, OR=1.99; urinary tract infections and urinary incontinence: drug-treated group compared to placebo group, OR=1.51; CVAEs: drug-treated group compared to placebo group, OR=2.13; higher in the risperidone group compared to the placebo group (OR=3.43) | |||
Katz et al., 2007 (80) | 4 RCTs | AD; risperidone vs. placebo | Somnolence: 18% in risperidone group, compared to 8% in placebo group; EPS: 12% in risperidone group, compared to 6% in placebo group; CVAEs: 1.6% in risperidone group, compared to 0.8% in placebo group; deaths within 30 days of the last dose: 3.1% in risperidone group, compared to 1.8% in placebo group (not statistically significant); no association between all-cause mortality and severity of behavioral symptoms at baseline |
Maher et al., 2011 (82) | 18 RCTs | Dementia; atypical antipsychotics vs. placebo | CVAEs: olanzapine and risperidone groups compared to placebo group, ORs were 2.30 and 2.10, respectively; CVA: risperidone group compared to placebo group, OR=3.12; increased appetite and weight gain: olanzapine and risperidone groups compared to placebo group, pooled ORs were 4.70 and 3.40, respectively, and NNH was 25; anticholinergic effects: olanzapine group compared to placebo group, OR=3.30 and NNH=6; sedation and fatigue: olanzapine, quetiapine, and risperidone groups compared to placebo group, ORs were 4.60, 5.20, and 2.30, respectively; EPS: olanzapine and risperidone groups compared to placebo group, ORs were 15.20 and 3.00, respectively, and NNHs were 10 and 20, respectively; urinary tract symptoms: olanzapine, quetiapine, and risperidone groups compared to placebo group, ORs were 9.5, 2.4, and 1.6, respectively, and NNH was 16–36 |
Six head-to-head trials indicated that olanzapine use caused more neurological symptoms, including confusion, dizziness, headaches, etc., compared to risperidone use (OR=1.54) | |||
Ma et al., 2014 (83) | 16 RCTs | Dementia; atypical antipsychotics vs. placebo | EPS: drug-treated group (15.2%) compared to placebo group (8.6%), OR=1.74; risk higher in the olanzapine and risperidone groups; somnolence: drug-treated group (17%) compared to placebo group (7.2%), OR=2.95; risk higher in the aripiprazole, olanzapine, quetiapine, and risperidone groups; CVAEs: drug-treated group (2.1%) compared to placebo group (0.9%), OR=2.50; gait abnormality: drug-treated group (6.9%) compared to placebo group (1.7%), OR=1.74; risk higher in the olanzapine and risperidone groups; deaths within 30 days of drug discontinuation: drug-treated group (3.6%) compared to placebo group (2.3%), OR=1.5; subgroup meta-analyses did not identify any higher risk of death among the aripiprazole, olanzapine, quetiapine, or risperidone groups; edema: drug-treated group (9.3%) compared to placebo group (5.2%), OR=1.8; urinary tract infection: drug-treated group (14.9%) compared to placebo group (10.9%), OR=1.35; falls: drug-treated group (15.2%) compared to placebo group (18.8%) |
Wang et al., 2015 (84) | 6 RCTs | AD; atypical antipsychotics vs. placebo | Adverse effects: atypical antipsychotic group compared to placebo group, RR=1.17; dropout due to adverse events: atypical antipsychotic group compared to the placebo group, RR=2.24 |
Death.
Cerebrovascular adverse events (CVAEs).
Cognition.
Effects of Withdrawal of Antipsychotics
Author, Year | Study Type | Outcomes |
---|---|---|
Declercq et al., 2013 (53) | 9 trials, dementia; antipsychotic withdrawal vs. antipsychotic continuation | Eight of nine trials reported no overall difference between groups on withdrawal (remaining in study off antipsychotics) and NPS |
In one trial, time to relapse was reduced among the withdrawal group compared to the continuation group (p=0.04) | ||
In a second trial, in the first 16 weeks, rates of relapse were higher in the placebo group compared to the antipsychotic group (HR=1.94, p=0.004); in the next 16 weeks, rates of relapse were higher in the antipsychotic withdrawal group compared to the continuation group (HR=4.88, p=0.02) | ||
In two trials, individuals with more severe baseline NPS had a worsening of symptoms in the withdrawal group compared to the continuation group (p=0.009) | ||
Pan et al., 2014 (55) | 9 trials, dementia; antipsychotic withdrawal vs. antipsychotic continuation | NPS symptoms worsened more in the antipsychotic withdrawal group compared to the continuation group, but the difference did not reach statistical significance (SMD=0.19) |
A greater proportion of individuals had worsening of NPS in the antipsychotic withdrawal group compared to the continuation group (RR=1.78) | ||
A greater proportion of individuals had early study terminations in the antipsychotic withdrawal group compared to the continuation group, but the difference did not reach statistical significance (RR=1.11) | ||
A lower proportion of individuals died during the study period in the antipsychotic withdrawal group compared to the continuation group, but the difference did not reach statistical significance (RR=0.83) | ||
Tariot et al., 2021 (56) | RCT | Among 217 individuals who had sustained response to pimavanserin, 105 were assigned to receive pimavanserin and 112 to receive placebo; relapse rates were 13% for the pimavanserin group and 28% for the placebo group (HR=0.35, p=0.005); adverse effects were reported in 41% of the pimavanserin group and 36% of the placebo group |
Summary
Other Pharmacological and Biological Treatment Modalities
Acetylcholinesterase Inhibitors
Memantine
Antidepressants
Mood Stabilizers
Cannabinoids
Repetitive Transcranial Magnetic Stimulation
Electroconvulsive Therapy (ECT)
Summary
Prevention of Dementia and NPS
Clinical Practice Guidelines
Future Research Directions
Conclusions
References
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