Clinical Pearls

Do not expect basmisanil 240 mg twice a day to improve CIAS in routine practice; after 24 weeks, the MCCB neurocognitive composite T-score changed by 1.08± 5.78 [SD] with placebo and 1.36±4.80 [SD] with basmisanil (ES=0.05, P =.793).

An isolated cognitive signal is not enough to justify a procognitive claim; the delayed recall condition VPA total raw score II reached an ES of 0.45 (P<.1) at week 24, but no benefit emerged on verbal learning, working memory, other MCCB domains, functional measures, or symptom ratings.

Do not target younger patients or the deteriorated cognitive subtype for basmisanil, because the prespecified subgroup strategy failed: older patients showed ES =0.39, younger patients ES=−0.32, and subtype effects were ES=0.27 for preserved, ES =0 for deteriorated, and ES=−0.04 for compromised.

Repeated pre-randomization cognitive testing can suppress early placebo inflation in CIAS trials; with 3 MCCB administrations before randomization, no improvement in the placebo group was noted at week 12, and the second assessment showed a change of 1.08, below the 1.9 points cited from prior controlled trials.

High attrition does not necessarily mean poor tolerability in schizophrenia cognition trials; 81 (37.9%) patients withdrew prematurely, but safety-related withdrawals were only 3.7% to 5.6%, and worsening of psychosis was reported in 6.2% with placebo versus 3.8% with 240 mg basmisanil.