Table 1.
Characteristics of randomized placebo-controlled trials included in the meta-analysis
| Study | Level of evidence design | Antipsychotic | Duration (weeks) | Age (mean ± SD) & male% | Total | Dose | Outcomes | Discontinuation rates |
|---|---|---|---|---|---|---|---|---|
|
NCT00477672 200935 (United States, India, Europe) |
Randomised Double-blind Placebo-controlled |
Pim | 6 | 69.3±8.71 & 63.7% | 298 200 101 99 98 |
Intervention: 1.Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth 2. Pimavanserin tartrate (ACP-103) 40 mg, tablet, once daily by mouth Control: Placebo tablet, once daily by mouth, |
Antipsychotic efficacy: SAPS-H+D Motor symptoms: UPDRS Part II and Part III |
Pim: 16% Pla: 7.1% |
|
NCT00658567 200934 (United States. Europe) |
Randomised Double-blind Placebo-controlled |
Pim | 6 | 72.0±7.82 & 63.6% | 123 83 42 41 40 |
Intervention: 1.Pimavanserin tartrate (ACP-103) 10 mg, tablet, once daily by mouth 2. Pimavanserin tartrate (ACP-103) 20 mg, tablet, once daily by mouth Control: Placebo tablet, once daily by mouth |
Antipsychotic efficacy: SAPS-H+D Motor symptoms: UPDRS Part II and Part III |
Pim: 12% Pla: 20% |
| Meltzer et al 201025 | Randomised Double-blind Placebo-controlled |
Pim | 4 | 70.9±1.12 & 76.7% | 60 29 31 |
Intervention: Pimavanserin 20 mg (day 1) with possible increases to 40- or 60-mg daily doses on days 8 and 15 Control: Placebo tablet, once daily by mouth |
Antipsychotic efficacy: SAPS-H+D Motor symptoms: UPDRS Part II and Part III |
Pim: 31% Pla: 22% |
| Cummings et al 201423 | Randomised Double-blind Placebo-controlled |
Pim | 6 | 72.7±7.25 & 63.3% | 199 105 94 |
Intervention: Pimavanserin 40 mg, tablet, once daily by mouth Control: Placebo tablet, once daily by mouth |
Antipsychotic efficacy: SAPS-H+D Motor symptoms: UPDRS Part II and Part III |
Pim: 15% Pla: 7.4% |
| Pollak et al 200430 | Randomised Double-blind Placebo-controlled |
Clo | 4 | Clo:71.2±7.4 Pla: 72.8±8.2 & 53.3% |
60 32 28 |
Intervention: Clozapine 6.25 mg orally daily, titrated to maximum 50-mg daily dose Control: Placebo tablet, once daily by mouth |
Efficacy outcomes: CGI Positive PANSS Safety outcomes: UPDRS MMSE |
Clo: 0% Pla: 3.5% |
| The Parkinson Study Group 199933 | Randomised Double-blind Placebo-controlled |
Clo | 4 | Clo:70.8±8.6 Pla: 71.9±8.1 & 56.6% |
60 30 30 |
Intervention: Clozapine 6.25 mg orally daily, titrated to maximum 50-mg daily dose Control: Placebo tablet, once daily by mouth |
CGI BPRS UPDRS MMSE |
Clo: 0% Pla: 0% |
| Breier et al 2002 (USA)32 | Randomised Double-blind Placebo-controlled |
Ola | 4 | Ola:73.5±8.7 Pla: 71.7±6.8 & 69.9% |
83 41 42 |
Intervention: Olanzapine 2.5 mg orally daily, titrated to maximum 15 mg daily dose Control: Placebo tablet, once daily by mouth |
CGI BPRS UPDRS MMSE |
0% |
| Breier et al 2002 (Europe)32 | Randomised Double-blind Placebo-controlled |
Ola | 4 | Ola:70.9±6.3 Pla: 70.5±8.2 & 66.2% |
77 4928 |
Intervention: Olanzapine 2.5 mg orally daily, titrated to maximum 15 mg daily dose Control: Placebo tablet, once daily by mouth |
CGI BPRS UPDRS MMSE |
0% |
| Ondo et al 200231 | Randomised Double-blind Placebo-controlled |
Ola | 9 | 71.0±7.1 & 63.3% | 30 16 11 |
Intervention: Olanzapine 2.5–10 mg orally daily, Control: Placebo tablet, once daily by mouth |
UPDRS item 2 (thought disorder) MMSE |
13.3% |
| Nichols et al 201324 | Randomised Double-blind Placebo-controlled |
Ola | 4 | Ola(2.5):70.7±8.1 Ola(5):72.4±4.8 Pla: 71.3±6.5 |
23 14 6 8 9 |
Intervention: 1. Olanzapine 2.5 mg, tablet, once daily by mouth at bedtime 2. Olanzapine 5 mg, tablet, once daily by mouth at bedtime Control: Placebo tablet, once daily by mouth |
BPRS CGI |
Ola(2.5):66% Ola(5):38% Pla: 22% |
| Ondo et al 200529 | Randomised Double-blind Placebo-controlled |
Que | 12 | Que:74.0±7.0 Pla: 71.0±5.0 & 54.84% |
31 21 10 |
Intervention: Quetiapine 50 mg orally twice daily for 3 weeks, titrated up to 100 mg orally twice daily over another 3 weeks Control: Placebo tablet, twice daily by mouth |
BPRS Question 12 (BPRS) UPDRS |
Que:19% Pla:20% |
| Rabey et al 200728 | Randomised Double-blind Placebo-controlled |
Que | 12 | Que:75.5±8.1 Pla: 74.5±8.7 & 56.89% |
58 30 28 |
Intervention: Quetiapine 12.5 mg orally at bedtime, titrated to until symptoms cleared or side effects limited treatment Control: Placebo tablet, once daily by mouth |
BPRS UPDRS CGI |
Que:50% Pla:35.7% |
| Shotbolt et al 200926 | Randomised Double-blind Placebo-controlled |
Que | 12 | Que: 74.0±8.0 Pla:7 0.0±8.0 & 66.67% |
24 11 13 |
Intervention: Quetiapine 25 mg for week 1, 25 mg twice for week 2,50 mg twice for week 3, with an optional further increase to 50 mg am, 100 mg nocte if clinically indicated Control: Placebo tablet, daily by mouth |
BPRS UPDRS |
0% |
| Fernandez et al 200927 | Randomised Double-blind Placebo-controlled |
Que | 8 | Que: 64.6±8.0 Pla:71.5±7.46 & 66.67% |
16 8 8 |
Intervention: Olanzapine 25–150 mg orally daily, Control: Placebo tablet, daily by mouth |
BPRS CGI UPDRS |
Que:50% Pla:12.5% |
Abbreviations: Pim, Pimavanserin; Pla, Placebo; Clo, clozapine; Ola, Olanzapine; Que, Quetiapine; CGI, clinical global impression scale; PANSS, positive and negative syndrome scale; UPDRS, unified Parkinson’s disease rating scale; MMSE, mini mental test examination; BPRS, Brief Psychiatric Rating Scale ;SAPS-H+D, the Assessment of Positive Symptoms - Hallucinations and Delusions scales; UPDRS Part II, the Unified Parkinson’s Disease Rating Scale Activities of Daily Living; UPDRS Part III,the Unified Parkinson’s Disease Rating Scale Motor Examination.