Duration of Psychosis and Outcome in First-Episode Schizophrenia Antony D. Loebel, M.D., Jeffrey David I. Mayerhoff, M.D., Stephen
Objective; illness
This
study
on outcome
and
were
Outcome
was
degree
measured remission.
treatment
was duration
time
according
preceded
by a substantial
of illness before treatment as well as with level ofremission.
significant
when
and
diagnosis
come, were controlled in a regression at onset, mode of onset, premorbid Conclusions: process
which,
bidity. (AmJ
C
onsiderable
factors with
that
ofpsychosis schizophrenia. if not ameliorated
of these findings 149:1183-1188)
attention
focused
has
been
influence
schizophrenia.
the outcome
These
have
early
of affective sociated tributed
and
gradual
features,
and
with poorer to the notion
illness
determine
At the same
included
on
clinical
of patients premonbid
Presented
in part
of onset,
gender
the
have
absence
all been
as-
outcome. These findings have conthat factors inherent in a patient’s
outcome
time,
mode
male
(1).
several
at the
143rd
investigators annual
have
meeting
ofthe
described American
Psy-
chiatric Association, New York, May 12-17, 1990, and the International Congress on Schizophrenia Research, Tucson, Ariz., April 2125, 1991. Received June 26, 1991; revision received Dec. 10, 1991; accepted Jan. 1 7, 1 992. From the Research Department, Hillside Hospital. Address reprint requests to Dr. Lieberman, Long Island JewishHillside Medical Center, 75-59 263rd St., Glen Oaks, NY 11004. Supported in part by NIMH grant MH-4l646 and Research Scientist Development Award MH-00537 to Dr. Lieberman and by grant MH-41960
from
the
NIMH
of Schizophrenia. The authors thank Sabina lington, and Greta Schimmel Copyright
Am
]
© 1 992
Psychiatry
Clinical
Research
Center
for
the
Meyer, Camille Valentino, Gwen for assistance in data collection.
American
Psychiatric
I 49:9,
September
Criteria
standardized and throughout
of untreated Seventy
Association.
1992
period.
patients
entered
the study
treatment and the follow-up
uniform period.
as well as before initial
According
to survival
found to be significantly associated with The effect ofduration ofillness on outcome variables,
themselves
associated
Duration ofiliness was not correlated or severity of illness at entry into
are
factors such as the patient’s level of social and educational functioning, age at onset of illness, mode of onset of illness, diagnosis, and gender. Poor premorbid adjustment,
ofduration Method:
with
out-
with age the study.
before treatment may be an important predictor of outAcute psychotic symptoms could reflect an active morbid by neuroleptic drug treatment, may result in lasting mor-
Further implications Psychiatry 1992;
may
Diagnostic
prepsychotic was
gender
analysis. adjustment,
Duration
in first-episode
come
to the Research received illness
effect patients.
in terms of time to remission ofacute psychotic symptoms Results: The mean duration ofpsychotic symptoms
52 weeks,
to remission
remained
the potential
schizophrenic
for up to 3 years. All patients during the acute phase of their
ofsymptom
analysis,
to assess
offirst-episode
diagnosed
followed both
assessments
undertaken
in a group
schizophrenia
with
was
A. Lieberman, M.D., Jose M.J. Alvir, D.P.H., H. Geisler, M.D., and Sally R. Szymanski, D.O.
Study
Wel-
discussed.
the potential impact on outcome of duration of untreated illness, i.e., the time interval between symptom onset and institution of neunoleptic treatment (2-9). Crow et al. (2) reported that among 120 patients in their first episode of schizophrenia who were followed for 2 years in a randomized, placebo-controlled trial of maintenance neuroleptic treatment, relapse subsequent to initial hospital discharge was substantially more common in those whose pretreatment illness lasted more than 1 year. Relapse rates in this group were high: only 1 8% of the patients who were given active treatment and none who were given placebo remained free of relapse after 2 years. May et a!. (3-5) randomly assigned 228 first-admission schizophrenic patients to five treatment groups, three of which did not include drug treatment (psychotherapy, milieu therapy, and ECT groups) and two of which did (drug alone and drug plus psychotherapy). Patients from the first three groups who did not respond were subsequently treated with antipsychotic drugs. In this investigation the drugtreated groups showed the best response and, together with the ECT group, showed the best outcome for up to 3 years (as measured by clinical, social, and psychological test criteria). Thus, the groups initially not treated with medication were found to have a poorer
1183
DURATION
AND
OUTCOME
IN SCHIZOPHRENIA
outcome over the follow-up period, despite the fact that subsequent treatment after the index admission was similar (although not standardized) among all groups. Wyatt (6, 7) has recently shown, in a new analysis of these data, that following discharge, patients who had not been treated with neuroleptics and who were discharged within 6 months of initial hospitalization required significantly more rehospitalizatiion and as much subsequent neuroleptic treatment as patients who had initially received neuroleptics. Thus, even patients who initially responded well to nonneuroleptic treatment subsequently fared worse than patients who were initially treated with neuroleptics. Further evidence for the finding that early neurobeptic treatment can enhance treatment response and outcome in schizophrenia
may
be
derived
from
early
studies
on
antipsychotic drug use (6, 8). Angnist and Schulz (8) reviewed 10 of these investigations (performed in the 1 950s) that studied both acute and chronic patients who had not previously received drug treatment. Poorer response to neuroleptics was found among the chronic patients in six studies, suggesting that delay in drug treatment may lead to a significantly worse outcome. Lo and Lo (9), in a retrospective 10-year follow-up study of 133 Chinese schizophrenic patients aged 14 to 60 years, found that shorter duration of untreated illness prior to the initial acute episode was significantly associated with favorable outcome (p
Objective; illness
This
study
on outcome
and
were
Outcome
was
degree
measured remission.
treatment
was duration
time
according
preceded
by a substantial
of illness before treatment as well as with level ofremission.
significant
when
and
diagnosis
come, were controlled in a regression at onset, mode of onset, premorbid Conclusions: process
which,
bidity. (AmJ
C
onsiderable
factors with
that
ofpsychosis schizophrenia. if not ameliorated
of these findings 149:1183-1188)
attention
focused
has
been
influence
schizophrenia.
the outcome
These
have
early
of affective sociated tributed
and
gradual
features,
and
with poorer to the notion
illness
determine
At the same
included
on
clinical
of patients premonbid
Presented
in part
of onset,
gender
the
have
absence
all been
as-
outcome. These findings have conthat factors inherent in a patient’s
outcome
time,
mode
male
(1).
several
at the
143rd
investigators annual
have
meeting
ofthe
described American
Psy-
chiatric Association, New York, May 12-17, 1990, and the International Congress on Schizophrenia Research, Tucson, Ariz., April 2125, 1991. Received June 26, 1991; revision received Dec. 10, 1991; accepted Jan. 1 7, 1 992. From the Research Department, Hillside Hospital. Address reprint requests to Dr. Lieberman, Long Island JewishHillside Medical Center, 75-59 263rd St., Glen Oaks, NY 11004. Supported in part by NIMH grant MH-4l646 and Research Scientist Development Award MH-00537 to Dr. Lieberman and by grant MH-41960
from
the
NIMH
of Schizophrenia. The authors thank Sabina lington, and Greta Schimmel Copyright
Am
]
© 1 992
Psychiatry
Clinical
Research
Center
for
the
Meyer, Camille Valentino, Gwen for assistance in data collection.
American
Psychiatric
I 49:9,
September
Criteria
standardized and throughout
of untreated Seventy
Association.
1992
period.
patients
entered
the study
treatment and the follow-up
uniform period.
as well as before initial
According
to survival
found to be significantly associated with The effect ofduration ofillness on outcome variables,
themselves
associated
Duration ofiliness was not correlated or severity of illness at entry into
are
factors such as the patient’s level of social and educational functioning, age at onset of illness, mode of onset of illness, diagnosis, and gender. Poor premorbid adjustment,
ofduration Method:
with
out-
with age the study.
before treatment may be an important predictor of outAcute psychotic symptoms could reflect an active morbid by neuroleptic drug treatment, may result in lasting mor-
Further implications Psychiatry 1992;
may
Diagnostic
prepsychotic was
gender
analysis. adjustment,
Duration
in first-episode
come
to the Research received illness
effect patients.
in terms of time to remission ofacute psychotic symptoms Results: The mean duration ofpsychotic symptoms
52 weeks,
to remission
remained
the potential
schizophrenic
for up to 3 years. All patients during the acute phase of their
ofsymptom
analysis,
to assess
offirst-episode
diagnosed
followed both
assessments
undertaken
in a group
schizophrenia
with
was
A. Lieberman, M.D., Jose M.J. Alvir, D.P.H., H. Geisler, M.D., and Sally R. Szymanski, D.O.
Study
Wel-
discussed.
the potential impact on outcome of duration of untreated illness, i.e., the time interval between symptom onset and institution of neunoleptic treatment (2-9). Crow et al. (2) reported that among 120 patients in their first episode of schizophrenia who were followed for 2 years in a randomized, placebo-controlled trial of maintenance neuroleptic treatment, relapse subsequent to initial hospital discharge was substantially more common in those whose pretreatment illness lasted more than 1 year. Relapse rates in this group were high: only 1 8% of the patients who were given active treatment and none who were given placebo remained free of relapse after 2 years. May et a!. (3-5) randomly assigned 228 first-admission schizophrenic patients to five treatment groups, three of which did not include drug treatment (psychotherapy, milieu therapy, and ECT groups) and two of which did (drug alone and drug plus psychotherapy). Patients from the first three groups who did not respond were subsequently treated with antipsychotic drugs. In this investigation the drugtreated groups showed the best response and, together with the ECT group, showed the best outcome for up to 3 years (as measured by clinical, social, and psychological test criteria). Thus, the groups initially not treated with medication were found to have a poorer
1183
DURATION
AND
OUTCOME
IN SCHIZOPHRENIA
outcome over the follow-up period, despite the fact that subsequent treatment after the index admission was similar (although not standardized) among all groups. Wyatt (6, 7) has recently shown, in a new analysis of these data, that following discharge, patients who had not been treated with neuroleptics and who were discharged within 6 months of initial hospitalization required significantly more rehospitalizatiion and as much subsequent neuroleptic treatment as patients who had initially received neuroleptics. Thus, even patients who initially responded well to nonneuroleptic treatment subsequently fared worse than patients who were initially treated with neuroleptics. Further evidence for the finding that early neurobeptic treatment can enhance treatment response and outcome in schizophrenia
may
be
derived
from
early
studies
on
antipsychotic drug use (6, 8). Angnist and Schulz (8) reviewed 10 of these investigations (performed in the 1 950s) that studied both acute and chronic patients who had not previously received drug treatment. Poorer response to neuroleptics was found among the chronic patients in six studies, suggesting that delay in drug treatment may lead to a significantly worse outcome. Lo and Lo (9), in a retrospective 10-year follow-up study of 133 Chinese schizophrenic patients aged 14 to 60 years, found that shorter duration of untreated illness prior to the initial acute episode was significantly associated with favorable outcome (p
