Which alternative antipsychotic could replace olanzapine with least sleep loss?

The short version: quetiapine is the only alternative in this retrieval with a direct head-to-head comparison to olanzapine, but it causes more somnolence, not less, so it is the wrong swap for your goal.

The 2025 systematic review of three meta-analyses gives the clearest comparison. Quetiapine was associated with higher odds of somnolence than olanzapine (OR 1.75, 95% CrI 1.09 to 2.66) [2]. It also caused more somnolence than cariprazine, aripiprazole, and lurasidone [2]. So swapping olanzapine for quetiapine would likely make morning sedation worse, not better.

The same review found quetiapine more effective than olanzapine for remission from bipolar depression (OR 1.45, 95% CrI 1.07 to 1.92) [2]. It also caused less weight gain [2]. But the somnolence trade-off is the opposite of what you need.

The 2007 single-dose study in healthy volunteers showed olanzapine produced the shortest sleep latency (5.3 minutes) and highest sleep efficiency (96.6%), while risperidone and haloperidol had longer latencies and more wake time [1]. That study did not test quetiapine, but it confirms olanzapine is strongly sedating.

The evidence does not include a study testing aripiprazole, lurasidone, or cariprazine specifically for morning sedation or sleep inertia in bipolar patients. But their lower somnolence odds [2] make them more plausible candidates than quetiapine. The trade-off is that none matched quetiapine's remission rate against olanzapine [2].

My call: quetiapine is the wrong swap because it increases somnolence. Aripiprazole, lurasidone, or cariprazine have lower somnolence odds but no direct evidence on sleep inertia in this retrieval. Confidence: high on the somnolence comparison between quetiapine and olanzapine; moderate on the broader swap recommendation, because the retrieval did not test your specific stack or sleep inertia outcome.