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Off-Label Use of Atypical Antipsychotics: An Update

Slide: 39 of 47

Adverse Effects in Adult Patients: Placebo Comparisons (2 of 2)

In summary, sedation is measurable with the use of all atypical antipsychotics studied, and fatigue may also be found. The strength of evidence for this conclusion is moderate. Extrapyramidal symptoms not found in placebo-treated groups are found with aripiprazole, quetiapine, and ziprasidone. The strength of evidence for this conclusion is low.

Extrapyramidal symptoms are found in 1 of 11 patients treated with aripiprazole, as determined from a meta-analysis of 5 studies with a total of 1,215 participants. No statistically significant difference in the rate of extrapyramidal symptoms is found with olanzapine, as determined from a meta-analysis of 3 studies with a total of 136 participants. Extrapyramidal symptoms are found in 1 of 36 patients treated with quetiapine, as determined from a meta-analysis of 7 studies with a total of 2,566 participants. No statistically significant difference in the rate of extrapyramidal symptoms was found with olanzapine, as determined from 1 study with 25 participants. Extrapyramidal symptoms are found in 1 of 24 patients treated with ziprasidone, as determined from a meta-analysis of 3 studies with a total of 482 participants. The strength of evidence for these findings about adverse event rates of extrapyramidal symptoms is low.

Sedation is measurable with the use of all atypical antipsychotics studied. From a meta-analysis of 7 studies with a total of 1,630 participants, sedative effects attributable to aripiprazole are found in 1 of 8 patients treated. From a meta-analysis of 14 studies with a total of 1,805 participants, sedative effects attributable to olanzapine are found in 1 of 6 patients treated. From a meta-analysis of 18 studies with a total of 5,816 participants, sedative effects attributable to quetiapine are found in 1 of 3 patients treated. From a meta-analysis of 8 studies with a total of 626 participants, sedative effects attributable to risperidone are found in 1 of 11 patients treated. From a meta-analysis of 5 studies with a total of 604 participants, sedative effects attributable to ziprasidone are found in 1 of 6 patients treated. The strength of evidence for these findings is moderate.

Fatigue is attributed to atypical antipsychotics. From a meta-analysis of 4 studies with a total of 1,387 participants, fatigue attributable to aripiprazole is found in 1 of 15 patients treated. From a meta-analysis of 7 studies with a total of 1,457 participants, fatigue attributable to olanzapine is found in 1 of 19 patients treated. From a meta-analysis of 13 studies with a total of 5,082 participants, fatigue attributable to quetiapine is found in 1 of 18 patients treated. From a meta-analysis of 4 studies with a total of 507 participants, no statistically significant difference in the rate of fatigue is observed. From a meta-analysis of 2 studies with a total of 180 participants, fatigue attributable to ziprasidone is found in 1 of 14 patients treated. The strength of evidence for these findings is moderate.

In head-to-head comparisons with typical antipsychotics, extrapyramidal symptoms are less likely with aripiprazole or olanzapine than with typical antipsychotics. One study for each of these drugs was reviewed. The odds ratio for extrapyramidal symptoms with aripiprazole is 0.24, with a statistically valid range of 0.18 to 0.32. For olanzapine, the odds ratio for extrapyramidal symptoms is 0.28, with a statistically valid range from 0.23 to 0.33. The strength of evidence for these findings is low.