Will the novel antipsychotics significantly ameliorate
neuropsychological deficits and improve adaptive functioning
in schizophrenia?
Authors: HAWKINS K. A. , MOHAMED S. , WOODS S. W. 
Published: July 2002

The recent and pending introduction of new antipsychotic medications
carries the hope of a
significant advance in the treatment of schizophrenia. Although the propensity
of these agents to
cause fewer motor side-effects than conventional neuroleptics may lead
to improved compliance and
clinical effectiveness, the promise of a significant impact upon the lives
of patients may primarily
reside in the evidence that the atypicals alleviate negative features such
as emotional flattening,
social withdrawal and impoverished speech. Auditory hallucinations and
delusional thinking are the
more dramatic expressions of illness, but these negative symptoms, along
with neuropsychological
deficits, are arguably more responsible for the persisting debilitation
exhibited by schizophrenics
(McKay, 1980; Pogue-Geile & Harrow, 1985; Breier et al. 1991;
Crow, 1991; Mukherjee et al. 1991;
Kane & Freeman, 1994; Perlick et al. 1992; Green, 1996; Green
et al. 1997). Negative symptoms
and neuropsychological deficits are minimally responsive to conventional
neuroleptics (Goldberg et al.
1991; Meltzer, 1992; Lee et al. 1994; Meltzer et al.
1994), leaving schizophrenics ill-equipped to
deal with the demands of normal living.The claim is often made that clozapine alleviates both negative symptoms
and neurocognitive
deficits (e.g. Meltzer, 1995a). Although there is hope that the newer antipsychotics
will do likewise,
the evidence for neurocognitive gains in particular is, so far, limited.
Only a few studies of the effects
of novel antipsychotics (such as risperidone, olanzapine, sertindole and
related in-trial agents) on
neuropsychological functioning have been undertaken. When effects have
been demonstrated, their
significance has remained unclear.This state of affairs is unsatisfactory, as a positive impact upon neuropsychological
functioning
would be of interest for more than just clinical reasons. An amelioration
of cognitive deficiencies
would suggest that these features are not inexorably tied to an irreversible
pathology, such as gross
neurodevelopmental aberrations or loss of neural tissue. Rather, such gains
would suggest a
treatable underlying pathophysiology, lending hope to other treatments,
including cognitive
rehabilitation. Since these deficits are increasingly viewed as fundamental
to our conceptions of
severe psychiatric illness (Goldberg et al. 1991; Green, 1996;
Nuechterlein & Subotnik, 1996),
neurocognitive changes might reciprocally shed light on these medications
and schizophrenia.
Finally, differential effects on cognition across medications should be
factored into cost–benefit
analyses, particularly when these effects are accompanied by broader adaptive
functioning gains.Is there any reason to believe that the novel antipsychotics will significantly
improve the
functional capacities of schizophrenics? Several considerations are relevant,
including purported
action mechanisms, animal behaviour findings, neurological effects, negative
symptoms effects and
existing cognitive outcome data.