| Discontinuation compared to continuation of antipsychotic medication for behavioural and psychological symptoms in older participants with dementia |
| Patient or population: older people with dementia who had been taking an antipsychotic drug for at least 3 months
Setting: any setting
Intervention: discontinuation of long‐term antipsychotic drug use
Comparison: continuation of long‐term antipsychotic drug use |
| Success of withdrawal from antipsychotics Measured with a variety of outcomes related to failure to complete the study Follow‐up: 1 to 8 months | In 7 studies there was no overall difference in the outcomes reported for success of withdrawal. In two studies of participants with psychosis, aggression or agitation who had responded to antipsychotic treatment, discontinuation accelerated symptomatic relapse without affecting the number of participants experiencing a relapse in one study and was associated with a higher rate of symptomatic relapse in the other study. In one small study a high proportion of the participants in the discontinuation group failed to complete the study. | 575 (9 RCTs) | ⊕⊕⊝⊝ LOWab | Our intended primary outcome, success of withdrawal defined as the ability to complete the study in the allocated study group, i.e. no failure due to worsening of NPS or relapse to antipsychotic drug use, was not reported in any study. We used the difference between groups in the number of non‐completers of the study as a proxy for our primary outcome. However, data could not be pooled due to variability in outcome measures. |
| Behavioural and psychological symptoms Assessed with various scales. Follow up: 1 to 8 months | In 2 pooled studies there was no difference in NPI scores between the continuation and discontinuation groups (see Data and analyses and Figure 1). In five non‐pooled studies, there was no difference in the outcomes on scales measuring overall behaviour and psychological symptoms between groups. | 519 (7 RCTs) | ⊕⊕⊝⊝
LOW⊝b⊝c | Data could only be pooled for 2 studies due to variability in outcome measures. The two pooled studies performed subgroup analyses according to baseline NPI‐score (≤ 14 or > 14). In one study, some participants with milder symptoms at baseline were less agitated at three months in the discontinuation group. In both studies, discontinuation led to worsening of NPS in some participants with more severe baseline NPS. |
| Adverse events Assessed with various scales. Follow‐up: 1 to 8 months | In 5 studies, there was no evidence of a difference between groups in adverse events. | 381 (5 RCTs) | ⊕⊕⊝⊝ LOWab | Data could not be pooled due to variability in outcome measures. Adverse events of antipsychotics were not systematically reported. |
| Quality of life (QoL) Assessed with DCM or QoL‐AD. Follow‐up: 3 months to 25 weeks | In 2 studies, there was no evidence of an effect on quality of life. | 119 (2 RCTs) | ⊕⊕⊝⊝
LOWbc | Data could not be pooled due to variability in outcome measures. There was no difference between discontinuation and continuation group in the overall cohort or in subgroups with baseline NPI score above or below the median (14). |
| Cognitive function Assessed with various scales. Follow‐up: 1 to 8 months | In 5 studies, there was no evidence of an impact on scales measuring overall cognitive function. In one of these trials, discontinuation improved a measure of verbal fluency. | 365 (5 RCTs) | ⊕⊕⊝⊝
LOWbc | Data could not be pooled due to variability in outcome measures. |
| Use of physical restraint Follow‐up: 1 month | In one study there was no effect on the use of physical restraint. | 36 (1 RCT) | ⊕⊝⊝⊝
VERY LOWcd | Conclusion made by the authors but not supported by data. |
| Mortality Assessed with various scales. Follow‐up: 4 to 12 months | In two studies there was no evidence of an effect on mortality. | 275 (2 RCTs) | ⊕⊝⊝⊝
VERY LOWcd | Data could not be pooled due to clinical heterogeneity. In a long‐term follow‐up of 36 months after the 12 months randomised discontinuation trial (Devanand 2012), we were uncertain whether discontinuation decreased mortality. |
| *The basis for the assumed risk (e.g. the median control group risk across the studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; |
| GRADE Working Group grades of evidence
High‐quality evidence: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate‐quality evidence: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low‐quality evidence: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low‐quality evidence: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect. |
