Trajectory analysis of the mixed study 16 indicates that as
many as 73% of patients were in the early-good trajectory
group. Others suggest that only a minority of patients with
schizophrenia have an adequate response to treatment.7 The
small size of the mixed study examined here may result
in an overestimate of the proportion of patients expected
to have an early-good trajectory. Additionally, how the
delayed-partial response trajectory in study 16 compares
with the trajectories in study 30 is not entirely clear.
However, another consideration is that there are relatively
few studies that include clozapine as a treatment option for
nonrefractory patients.4 A limitation of using study 16 for
this purpose is that the proportion of putatively refractory
patients that may have been included is uncertain. However,
the overall lower age, shorter duration of illness, less severe
symptoms, and milder extrapyramidal side effects suggest
that this heterogeneous sample was not biased toward more
refractory patients. While clozapine does not appear to have
an advantage over other APs in the treatment of first-episode
schizophrenia,24–26 this remains a topic of research and
debate.27,28 Clozapine is less well studied in multi-episode,
nonrefractory patients, and could have a response profile and
effectiveness as a maintenance treatment more analogous
to that seen in refractory schizophrenia.29 The overall high
proportion of patients assigned to the early-good trajectory
group here is consistent with the high proportion of patients
with first-episode schizophrenia having complete resolution
of psychosis with AP treatment.30 In our analysis of patients
in the mixed study—early-good trajectory group—the
outcome of 63.4% reduction in mean BPRS item score would
be consistent with classification as much improved. Notably,
first-episode patients with delayed-partial response to other
APs may respond very well to clozapine.