TREATMENT REFRACTORY SCHIZOPHRENIA
Jean-Pierre Lindenmayer, M.D.
Treatment resistance constitutes a signiﬁcant dilemma in schizophrenia since
it affects a substantial number of patients, their families and the health care
professionals involved in their care. Nonresponsiveness needs to be approached
as a multidimensional syndrome by specifying which symptoms in the spectrum
of positive symptoms, negative symptoms, excitement/hostility, cognitive symp-
toms, and anxiety/depression are failing to respond to treatment. This review
presents some of the clinical, demographic and biological correlates of nonre-
sponse, in addition to compliance issues, psychosocial factors or side effects and
as-yet-untreated comorbidities as a source for nonresponse. The effects of the
atypicals clozapine, olanzapine, risperidone and quetiapine as compared to typi-
cals are reviewed using available double-blind studies in this treatment refrac-
tory group of schizophrenia patients. The limited number of reports on the com-
parison of atypical compounds amongst each other are critically presented.
Given that a subset of patients still do not respond to these agents, clinicians are
using various augmentation strategies. We review studies with augmentation
strategies which remain difﬁcult to interpret given the open label and uncon-
trolled nature of most of these studies.
Treatment resistance in schizophrenia can have a devastating ef-
fect on individuals and families. It also represents a signiﬁcant
Jean-Pierre Lindenmayer, MD, is Director, Psychopharmacology Research
Unit, Manhattan Psychiatric Center-Nathan Kline Institute for Psychiatric Re-
search, New York; New York University School of Medicine, New York.
Address correspondence to J.P. Lindenmayer, MD, Clinical Director, Man-
hattan Psychiatric Center, Wards Island, New York, NY 10035; e-mail:
PSYCHIATRIC QUARTERLY, Vol. 71, No. 4, Winter 2000
0033-2720/00/1200-0373$18.00/0 2000 Human Sciences Press, Inc.