Directory UMM :Data Elmu:jurnal:B:Biological Psichatry:Vol48.Issue6.2000:

The McLean–Harvard First-Episode Project: 6-Month
Symptomatic and Functional Outcome in Affective and
Nonaffective Psychosis
Mauricio Tohen, Stephen M. Strakowski, Carlos Zarate, Jr., John Hennen,
Andrew L. Stoll, Trisha Suppes, Gianni L. Faedda, Bruce M. Cohen,
Priscilla Gebre-Medhin, and Ross J. Baldessarini
Background: The McLean–Harvard First-Episode
Project recruited affective and nonaffective patients at
their first lifetime psychiatric hospitalization.
Methods: Baseline evaluation and 6-month follow-up in
257 cases yielded recovery outcomes defined by syndromal (absence of DSM-IV criteria for a current episode)
and functional (vocational and residential status at least
at baseline levels) status. Time to recovery was assessed
by survival analysis, and risk factors by multivariate
logistic regression.
Results: Syndromal recovery was attained by 77% of
cases over an average of 84 days. By diagnostic group,
syndromal recovery rates ranked (p 5 .001) major affective disorders (81%) . nonaffective acute psychoses
(74%) . schizoaffective disorders (70%) . schizophrenia
(36%). Functional recovery was significantly associated
to syndromal recovery, diagnosis, shorter hospitalization

normalized to year, and older age at onset. Average
hospital stay declined across the study period, but recovery did not vary with year of entry.
Conclusions: Syndromal recovery was achieved by nearly
one half of patients within 3 months of a first lifetime
hospitalization for a psychotic illness, but functional
recovery was not achieved by 6 months in nearly two
thirds of patients who had attained syndromal recovery.
Biol Psychiatry 2000;48:467– 476 © 2000 Society of Biological Psychiatry
Key Words: First episode, function, length of stay,
outcome, psychotic disorders, recovery

From The International Consortium for Bipolar Disorders Research; the Consolidated Department of Psychiatry & Neuroscience Program, Harvard Medical
School, Boston (MT, JH, ALS, BMC, RJB) and Bipolar & Psychotic Disorders
Program, McLean Hospital, Belmont (JH, PG-M, RJB), Massachusetts; Lilly
Research Laboratories, Indianapolis, Indiana (MT); the Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, Ohio (SMS); the
Department of Psychiatry, University of Massachusetts, Worcester (CZ); the
Department of Psychiatry, Univeristy of Texas Southwestern Medical Center,
Dallas (TS); and Lucio Bini Psychiatric Center of New York, New York (GLF).
Address reprint requests to Mauricio Tohen, M.D., Dr. PH, Lilly Research
Laboratories, Indianapolis IN 46285.

Received February 10, 2000; revised May 3, 2000; accepted May 5, 2000.

© 2000 Society of Biological Psychiatry

Introduction

M

any studies have been conducted to define the
course of psychotic disorders and identify predictors of their outcome; however, most outcome studies in
psychotic disorders have involved patients considered
to have schizophrenia and initiated follow-up at different stages of illness; very few have included patients
with affective disorders (Beiser et al 1988, 1989;
Bromet et al 1996; Craig et al 1997; Leff et al 1992;
Tohen et al 1990a). Findings from such studies have
been somewhat variable and are inconclusive, in part,
owing to inclusion of newly and chronically ill subjects
(Tohen 1991; Zis and Goodwin 1979). This situation
has encouraged greater interest in prospective studies of
first-episode patients with schizophrenia (Biehl et al

1986; Bromet et al 1996; Craig et al 1997; Gupta et al
1997; Johnstone et al 1990; Kane et al 1982; Lay et al
1997; Leff et al 1992; Lieberman et al 1993; Ram et al
1992; Schubart et al 1986; Scottish Schizophrenia
Research Group 1989; Tohen 1991; Tohen et al 1990b,
1992a, 1996; Varma et al 1996; Ventura et al 1992) and
bipolar disorder (Fennig et al 1996; Strakowski et al
1998; Tohen et al 1990b, 2000), as well as in the
prodomal phase of schizophrenia (McGorry et al 2000).
Studies begun at the start of the illnesses promise early
identification of clinical and biological factors that may
help to characterize patients with specific disorders as
well as serve to predict their later course and outcome.
Based on this background, The McLean–Harvard FirstEpisode Project has been observing a large number of
first-episode psychotic patients with a range of DSM-IV
diagnoses, prospectively, from their first lifetime hospitalization. We recently reported recovery results including
only patients with psychotic affective disorders (Tohen et
al 2000). This report considers 1) rates and elapsed time to
syndromal recovery, 2) occupational and residential measures of functional recovery, and 3) factors associated with
recovery in 257 patients with affective and nonaffective

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M. Tohen et al

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psychotic disorders at 6 months after their first psychiatric
hospital admission.

Methods and Materials
The McLean–Harvard First-Episode Project was initiated in
1989 and has been active continuously since then. In this
prospective, naturalistic follow-up study, treatment is not controlled by the investigators, although information about treatment
is collected during hospitalization and throughout follow-up.
Patients who presented with a psychotic syndrome were diagnosed by DSM-III-R (from 1989 to 1994) or DSM-IV criteria
since 1994 (American Psychiatric Association 1994), with all

diagnoses adapted to meet DSM-IV criteria for this report.
Subjects were recruited from the inpatient units of McLean
Hospital, a main psychiatric teaching hospital of Harvard Medical School.
Patients included met the following criteria: 1) age 16 years or
older; 2) in a first lifetime episode of a clinically defined
psychotic illness (including thought disorder, hallucinations,
delusions, or grossly disorganized behavior at the time of first
hospitalization) without symptomatic remission since onset; 3)
meeting DSM-IV criteria for a principal diagnosis of schizophrenia, schizophreniform, schizoaffective, bipolar, or major depressive disorders with psychotic features, delusional disorder, brief
reactive psychosis, or psychosis not otherwise specified (NOS);
and 4) providing written informed consent based on McLean
Hospital institutional review board approval. Exclusion criteria
were 1) presence of acute intoxication or a withdrawal syndrome
associated with drug or alcohol abuse, or delirium of any cause;
2) previous psychiatric hospitalizations, unless for alcohol or
substance abuse detoxification; 3) presence of mental retardation
or other organic mental disorder; 4) duration of illness of .1
year; and 5) prior treatment with an antipsychotic agent or mood
stabilizer for a total of .3 months. A specially trained research
assistant screens potential subjects by daily review of admission

notes of all newly admitted patients with psychotic symptoms, as
considered in preadmission assessments and verified by daily
reviews with treating psychiatrists on each inpatient unit.

Baseline Measures
DSM-IV Axis I diagnoses (American Psychiatric Association
1994) were determined using the Structured Clinical Interview
for DSM—patient version (SCID-P; Spitzer et al 1988) carried
out by professional raters (masters-level training and more than
a year of clinical experience). Final diagnoses were ascertained
with a best-estimate diagnostic procedure recommended by
Leckman et al 1982). Next, a detailed clinical narrative was
prepared using all available information (SCID-P, medical
records, and interviews of family members and primary treating
clinicians). This narrative was presented to two psychiatrists with
expertise in psychotic disorders, and a best-estimate procedure
determined primary and comorbid diagnoses. As part of the
best-estimate procedure, time of onset, defined as fulfilling DSM
criteria for any of the psychotic disorders under study, was
determined.

Clinical and demographic variables recorded at baseline included age, gender, race, days of hospital length of stay (LOS),
years of education, and employment status. Also, comorbidity
factors assessed included 1) other DSM Axis I disorders (current
and lifetime), 2) comorbid alcohol or other substance abuse
(current and lifetime), and 3) concurrent medical or neurologic
illness. This information was obtained from medical records,
SCID-P examination, and from the patient, relatives, and responsible clinicians, by research assistants trained to obtain such data
reliably. They evaluated patients within 72 hours of admission
and weekly thereafter until discharge.
Assessment scales included an expanded version of the Brief
Psychiatric Rating Scale (BPRS; Lukoff et al 1986) with 35
items (rated for severity, 1–7) plus an overall sum score (Tohen
et al 1992a, 2000), the Clinical Global Impressions (CGI; Guy
1976) and Global Assessment of Functioning (GAF; 0 –100
scale; American Psychiatric Association 1994) scales. Occupational status was rated with the Modified Vocational Status Index
(MVSI), and residential status rated with a Modified Location
Code Index (MLCI; Dion et al 1988; Tohen et al 1990a, 1992a,
1996, 2000). Baseline occupational level and residential status
were rated as the highest level achieved within the year before

admission, based on information collected from medical records
and family members as well as patients.

Outcome Measures
Patients were examined 6 months after hospital admission by an
experienced professional rater (PG-M) kept blind to the baseline
information. Follow-up information was obtained by telephone
or by direct interview, as reported previously (Tohen et al 1990a,
1992a, 2000). If a subject could not be interviewed by telephone
or face to face, follow-up information was obtained from a close
relative or another member of the patient’s household. Of the
reported follow-up assessments, 90% were by telephone, 60%
were with the subject only, and 40% with relatives and friends
with or without the subject.
In follow-up interviews, information elicited included sociodemographic changes, the course of the primary and comorbid
disorders, occupational and residential functional status, diagnostic status to define syndromal recovery, and estimated time of
such recovery (days since hospital admission). Follow-up interviews also included the MVSI and MLCI functional level scales
and the GAF. A statement of each subject’s general life satisfaction was also rated, as 1, very good; 2, good; 3, fair; 4, poor;
and 5, very poor.
Syndromal recovery was defined as no longer meeting criteria

for an ongoing episode of illness (Frank et al 1991; Prien et al
1991; Tohen et al 2000). These included a CGI score of 2 and
specific operational criteria, as follows:
1. For mania, the DSM mania “A” criteria were 3 in severity,
no mania “B” criteria were .3, and two B criteria were
scored 3.
2. For major depression with psychotic features, no DSM
criteria were .3, and not more than three were rated 3.
3. For schizophrenia and schizophreniform disorder, no
DSM A criteria were rated .2, and not more than two
criteria were 2.

6-Month Outcome in Psychotic Disorders

4. For delusional disorder and psychosis NOS, no affective,
delusional, or hallucinatory symptoms were rated .2.
Subjects with schizoaffective disorder had to meet recovery
criteria for both schizophrenia and either mania or depression. In
addition, syndromal recovery criteria require that these conditions be sustained for at least 8 weeks, and latency to the start of
this interval was scored in days from hospital admission.

Functional recovery was operationally defined categorically
by comparing MVSI (vocational status) and MLCI (living
situation) ratings obtained at admission and at 6-month followup. Functional recovery by 6-month follow-up requires a return
to at least the premorbid level of both vocational and residential
functioning, plus attainment of a rating of 1–5 for occupational
and 1– 4 for residential levels, as defined above.

Data Analysis
Interrater reliability was evaluated for the SCID-P for primary
(intraclass correlation coefficient [ICC] 5 .92) and secondary
(ICC 5 .90) diagnoses (Tohen et al 1990a, 1992a, 1996, 2000).
High interrater reliability was also obtained for the 35-item
BPRS (ICC 5 .96; Tohen et al 1990a, 1992a, 1996, 2000; Zarate
et al 1997b). Good to excellent agreement between telephone and
in-person interviews was also obtained (ICC 5 .90; Revicki et al
1997; Tohen et al 1990a).
By having the same investigator (PG-M) conduct all the
follow-up assessments, reliability for the recovery ratings across
the different years of recruitment was assured.
Each subject was first designated as recovered or not recovered by 6 months, based on the syndromal and functional criteria

just defined. Continuous demographic and clinical variables were
dichotomized to yield meaningful contrasts and to facilitate
estimates of odds ratios (ORs). Selected categoric variables also
were recoded to afford simple, meaningful contrasts. Age at
onset was trichotomized at 25, 26 – 49, and 50 years, and type of
onset or prodrome was coded as rapid (1– 6 months) or gradual
(.6 months). Diagnostic subgroup clusters defined by principal
discharge DSM diagnostic codes were 1) major affective disorders with psychotic features (manic, mixed, or NOS bipolar
disorders, or major depression), 2) acute nonaffective psychotic
disorders (schizophreniform, schizoaffective, delusional, or psychotic NOS), 3) schizoaffective disorders, and 4) schizophrenia.
Admission year (1989 –1996) was a categoric variable. Since
average LOS diminished yearly, individual LOS (days) was
normalized by ranking LOS for each year of admission and
forming binary variables to characterize hospitalizations, as
shorter, 25th, and longer, 75th percentile for LOS in each year.
Individual BPRS scale items were dichotomized as severe
(including ratings of 5–7) and nonsevere (0 – 4). Depressive,
manic, and psychotic subtotal ratings of the 35-item BPRS
(Lukoff et al 1986; Tohen et al 1990a, 1996) also were dichotomized to indicate presence or absence of severe item scores
(5–7), and BPRS total scores were median split to yield high/low
scoring subgroups.
Syndromal and functional 6-month recovery rates were compared with contingency tables (x2). Both types of recovery were
considered within diagnostic and other subgroups of interest

BIOL PSYCHIATRY
2000;48:467– 476

469

defined in Results and compared with 6-month GAF scores with
Mann–Whitney rank sum nonparametric methods. Frequencies
of categoric variables in recovery groups were compared by
cross-tabulations and x2 tests or Fisher exact p (if cell size , 10
subjects). Log-rank nonparametric tests were used to compare
distributions of continuous variables in subgroups. Variables
with suggestive (p , .20) bivariate associations with recovery
status were considered candidates for multivariate analyses.
Multiple logistic regression models evaluated candidate demographic and clinical variables for independent association with
syndromal and functional recovery. Deciles of fitted values and
partial residual plot methods were used to check the goodness of
fit of multivariate models (Hosmer and Lemeshow 1989). Explanatory variables with adjusted ORs significantly different
(p , .05) from 1.0 were retained for final multiple logistic
regression models. Finally, distributions of days to recovery were
compared between demographic and diagnostic groups by
Kaplan–Meier survival analysis of times to defined levels of
recovery, with SE or 95% confidence intervals (CIs), and
Mantel–Cox log-rank x2 tests of statistical significance (Lee
1992). Averaged continuous data are reported as means 6 SDs.
Statistical analyses were based on commercially available microcomputer programs (Stata, Stata Corp., College Station, TX;
Statview-II, Abacus Concepts, Berkeley, CA).

Results
Patient Population
During the 6-year period of study recruitment from 1989
through 1995, 22,100 patients were hospitalized, of whom
784 (3.6%) were identified as in a first lifetime episode of
psychotic illness. Of these, 296 (37.8%) were recruited
(174 men [58.8%] and 122 women [41.2%]; mean 6 SD
age at admission 5 31.9 6 5.0 years); 257 (86.8% of those
recruited) provided 6-month follow-up data for syndromal
outcome, and 253 (85.5%) for functional recovery. No
significant differences between recruited and nonrecruited
patients were found in a large number of demographic and
clinical measures. Diagnostic categories included major
affective disorders with psychotic features (N 5 172,
66.9%), including bipolar disorder (N 5 128, 49.8%)
and major depression (N 5 44, 17.1%); acute nonaffective psychotic disorders were next most frequent (N 5
51, 19.8%); schizoaffective disorders (N 5 20, 7.8%)
and schizophrenia (N 5 14, 5.5%) were least common
(Table 1). This distribution of diagnoses was consistent
with the recent case mix for all admissions for psychotic
disorders at McLean Hospital, but may not generalize to
other centers (Carpenter and Kirkpatrick 1988; Craig et al
1997; Lay et al 1997; Tohen et al 1992a; Varma et al 1996;
Ventura et al 1992).

6-Month Recovery Rates
Syndromal recovery was attained by 77.0% (198/257) of
patients, and functional recovery (meeting both vocational

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Table 1. Primary Diagnoses and Recovery in First-Psychosis Patients
Percent recovery
Syndromal
(N 5 257)

Functional
(N 5 253)

Computed days to 25%
(recovery 6 SE)

85.7
75.0
65.0
100.0

32.6
31.8
47.4
55.6

29.0 6 2.2
39.0 6 11.5
30.0 6 2.6
38.0 6 45.6

172 (66.9)

81.4

35.3

30.0 6 2.9

29 (11.3)
14 (5.4)
8 (3.1)

72.4
71.4
100.0

18.5
38.5
20.0

14.0 6 2.3
22.0 6 8.5
33.0 6 15.9

51 (19.8)

74.5

24.0

16.0 6 4.7

Schizoaffective disorder

20 (7.8)

70.0

0.0

31.0 6 11.0

Schizophrenia

14 (5.4)

35.7

15.4

65.0 6 98.9

257 (100.0)

77.0

29.2

29.0 6 2.3

Diagnosis

N of all
cases (%)

Major affective disorders with psychotic features
Bipolar, manic
98 (38.1)
Major depression
44 (17.1)
Bipolar, mixed
20 (7.8)
Bipolar, NOS
10 (3.9)
Subtotal
Nonaffective acute psychotic disorders
Psychosis NOS
Delusional disorder
Schizophreniform
Subtotal

Total

All diagnoses were updated to accord with DSM-IV. Functional recovery required meeting both occupational and residential criteria. Functional recovery rates were less
than syndromal rates for all categories (mean ratio of syndromal/functional recovery rates 5 2.64). Rates of syndromal recovery differed highly significantly among the four
diagnostic clusters [x2(3) 5 16, p 5 .0012], but functional recovery did not [x2(3) 5 2.61, ns]. Values of days to 25% chance of syndromal recovery were computed by
survival analysis (not all disorders attained 50% rates within 6 months) and differed significantly among the four clusters [x2(3) 5 9.24, p 5 .026]. NOS, not otherwise
specified.

and residential criteria) by 29.2% (74/253) by 6 months
after admission for a first lifetime hospitalization for
psychotic illness. Of patients achieving syndromal recovery, 64.8% failed to reach functional recovery status
within 6 months [x2(1) 5 12.2, p 5 .0005]. Women
tended to gain syndromal recovery more often than men
[81.1% vs. 71.5%; x2(1) 5 3.11, p 5 .078], but
functional recovery rates were similar in women and men
[27.4% vs. 31.3%; x2(1) 5 0.46, ns]. Occupational versus
residential functional recovery rates, overall, were 39.1%
(99/253) versus 73.1% (185/253). The mean functional
recovery rate across the nine diagnoses (28.9 6 17.2%)
was substantially less than syndromal recovery rate
(75.0 6 19.5%) in all nine diagnostic categories encountered (Table 1). Occupational and residential components
of functional recovery appear to measure different aspects
of recovery and were not correlated across diagnostic
groups [r(1b) 5 .05, ns].
Syndromal 6-month recovery rates for four clusters of
presumably related disorders ranked affective disorders
(81.4%), acute nonaffective psychoses (74.5%), schizoaffective disorder (70.0%), and schizophrenia (35.7%), and
differed highly significantly [x2(3) 5 16.0, p 5 .0012;
Table 1). Functional recovery in the same clusters ranked
acute nonaffective (74.5%), affective (35.3%), schizophrenia (15.4%), and schizoaffective [0%; x2(3) 5 2.61, ns).
Occupational criteria for recovery were evidently more
difficult to attain because, for most diagnoses, these rates

(40.7 6 21.0%) were 1.74-fold lower than residential
recovery rates (70.9 6 7.8%), and the average rate already
cited for meeting both functional criteria (28.9%) was
even lower. Rates based on occupational and residential
criteria also were not correlated across the nine diagnostic
groups [r(8) 5 .146, ns]. Residential recovery rates
varied little across diagnostic groups, ranging from 75.9%
in major affective disorders and 72.0% in acute nonaffective psychoses, to 61.5% in schizophrenia and 60.0% in
schizoaffective syndromes [x2(3) 5 3.33, ns]. In contrast,
occupational functional recovery rates varied significantly,
from 45.3% in affective disorders to 38.5% in schizophrenia and 28.0% in acute nonaffective psychoses, to a low of
15.0% in schizoaffective disorders [x2(3) 5 10.2, p 5
.017].
Syndromal recovery was also associated with higher
6-month GAF scores at 6 months after hospitalization:
mean GAFs were 70.8 6 16.0 in syndromally recovered
patients, but only 47.0 6 14.0 in nonrecovered subjects.
Mean GAF values for functionally recovered versus nonrecovered patients followed a similar trend (72.7 6 14.4
vs. 62.7 6 18.8). Both mean differences are highly
significant (rank sum z 5 8.40 and 3.70, respectively;
both ps , .001). Similarly, subjective measures of patients’ satisfaction with their life situation at 6-month
follow-up were also strongly associated with syndromal
and functional recovery. The mean patient satisfaction
score (1–5 scale) among syndromally recovered patients

6-Month Outcome in Psychotic Disorders

Figure 1. Actuarially computed Kaplan–Meier survival analysis
of times to syndromal recovery after hospitalization for a first
episode of psychotic illness. Shown are recovery functions for
patients who did (highest line) or did not (lowest line) achieve
functional recovery by both occupational and residential criteria
at 6 months after admission [highly significantly different;
x2(1) 5 16.8, p , .0001] and for all (N 5 257) subjects.

for whom such data were available (N 5 153) was
2.36 6 1.07, versus 3.31 6 1.05 among nonrecovered
patients (N 5 35; rank-sum z 5 2.28, p 5 .02). Also,
for functionally recovered (N 5 56) versus nonrecovered
(N 5 132) subjects, these satisfaction scores averaged
2.25 6 1.01 versus 2.66 6 1.16 (rank sum z 5 2.28, p 5
.02).

Time Course of Recovery
Kaplan–Meier survival analysis was employed to evaluate
the time course of recovery in subgroups of interest. The
overall computed times to the 25% and 50% levels of
syndromal recovery, 6 SE, were 29.0 6 2.3 and 61.0 6
2.7 days, respectively (Figure 1). Women attained syndromal recovery significantly more rapidly than men, with
their computed time to 50% recovery, 6 SE, at 43.0 6 9.0
versus 73.0 6 4.9 days (x2 5 6.98, p 5 .0083; not
shown). In addition, patients who had attained functional
recovery (meeting both criteria) by 6 months, as expected,
also reached 50% functional recovery (42.0 6 5.8 days)
sooner than those who did not (73.0 6 14.7 days, a
1.74-fold difference; x2 5 16.8, p , .0001; Figure 1).
Time functions were also compared for selected diagnostic groups. Computed times to 25% syndromal recov-

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2000;48:467– 476

471

Figure 2. Survival analysis (as for Figure 1) of time to syndromal recovery posthospitalization in first episode of (A) nonaffective acute psychotic disorders and major affective disorders
with psychotic features [which did not differ and are pooled:
x2(1) 5 0.07, ns], (B) schizoaffective disorder, and (C) schizophrenia. Computed days to 25% of patients recovering are shown
in Table 1. These functions differed significantly among the three
groups [x2(2) 5 9.16, p 5 .01], and A as well as the pooled
A 1 B function differed from schizophrenia [both x2s(1) 5 8.09,
p , .005].

ery for comparison across specific DSM-IV diagnoses and
diagnostic groups showed mainly minor variations among
disorders and averaged 29.0 6 2.3 days, overall (Table 1).
These recovery time functions were found to be relatively
brief among the acute nonaffective psychotic syndromes
(16.0 6 4.7), intermediate among major affective (30.0 6
2.9) and schizoaffective (31.0 6 11.0) disorders, and
longest in schizophrenia [65.0 6 98.9 days; Mantel–Cox
x2(3) 5 9.24, p 5 .026]. Syndromal recovery time
course functions are illustrated for three diagnostic groups:
1) major affective plus acute nonaffective psychotic disorders (bipolar diagnoses and unipolar major depression
were pooled with acute nonaffective psychoses because
their recovery time functions did not differ) were compared with the diagnostically ambiguous 2) schizoaffective group and 3) those with a discharge diagnosis of
schizophrenia [x2(2) 5 9.16, p 5 .010; Figure 2).

Factors Associated with 6-Month Recovery
Six factors were initially identified in bivariate analyses as
having at least suggestive (p , .20) associations with

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Table 2. Multivariate Logistic Regression Analysis of Factors
Associated with 6-Month Functional Recovery in FirstPsychosis Patients
Factor
Syndromal recovery
Diagnosisa
Hospital LOSb
Onset agec

Odds ratio

(95% CI)

z

p

2.85
2.34
1.67
1.02

1.20 – 6.81
1.18 – 4.63
1.13–2.45
1.00 –1.04

2.36
2.44
2.97
2.04

.018
.015
.003
.042

Factors are defined and shown in bivariate analyses in Tables 1 and 2. Subjects
(N 5 253) were rated for functional recovery, which required meeting both
vocational and residential criteria. The model is significant overall [x2(3) 5 31.6,
p , .0001] and accounts for 10.4% of the variance. CI, confidence interval; LOS,
length of stay.
a
Recovery was more likely with major affective and acute nonaffective
diagnoses, and least likely with schizophrenia.
b
Relatively shorter hospitalizations favored recovery, and longer LOS disfavored.
c
Relatively later onset age favored recovery, and earlier age disfavored.

syndromal recovery in 198 subjects, versus nonrecovery in
59 subjects, and so were considered candidates for multivariate analysis; these were 1) a major affective diagnosis,
2) relatively acute onset, 3) short hospitalization, 4)
relatively high baseline GAF scores, 5) ability to live
independently at follow-up (MLCI . 4), and 6) absence of
an additional Axis I comorbid condition. These factors and
sex were entered into a multivariate logistic regression
model; however, only diagnosis emerged as significant in
the multivariate analysis (OR 5 2.04 [95% CI 5 1.20 –
3.70], z 5 2.33, p 5 .019), with greater recovery
frequency among acute nonaffective and major affective
groups, as compared with schizoaffective or schizophrenic
groups. Surprisingly, various psychiatric, substance abuse,
and medical comorbidity factors, as well as measures of
illness severity at baseline assessment, had little ability to
predict syndromal recovery.
With respect to functional recovery (based on both
occupational and residential criteria being at least at
baseline levels at 6-month follow-up), five factors were
initially identified as having at least suggestive (p , .20)
associations with functional recovery in 74 subjects, versus nonrecovery in 179 subjects, and so were determined
to be candidates for multivariate analysis, along with sex.
Four factors were sustained (p , .05) in multivariate
analysis. In descending order of their apparent explanatory
power, these ranked 1) having previously attained syndromal recovery, 2) major affective diagnosis, 3) LOS standardized to admission year (shorter time in hospital was
associated with favorable outcome, and longer stay with
unfavorable), and 4) greater onset age. This four-factor
model was highly significant overall [x2(3) 5 31.6, p ,
.0001], and it accounted for a moderate amount of
variance (10.4%; Table 2). A possible confounding was
controlled by including in the same model LOS and year
of entry into the study.
For both measures of outcome, model fit was evaluated

Figure 3. Proportion of first-psychosis patients reaching syndromal and functional recovery by 6 months after hospital admission
vs. year of study entry, with the corresponding mean length of
hospital stay (LOS) for each year, as percent of the longest LOS
(43.0 6 22.3 days in 1989). Length of stay declined steadily with
years (r 5 2.923, p 5 .003), but its decline was uncorrelated
with either form of recovery (r 5 .495, ns).

by the area under the receiver operating curve, the ratio of
the likelihood functions (similar in interpretation to an r 2
value, and an indication of explanatory power), and the
Hosmer–Lemeshow goodness of fit statistic (Hosmer and
Lemeshow 1989); all of these measures indicated acceptable levels of fit of both multivariate models to the data.
Despite a sharp decline in the average hospital LOS
across the years of entry into the study that might be
expected to influence 6-month recovery status, there was
no significant relationship between syndromal or functional recovery rates and year of entry into the study
(Figure 3).

Discussion
The main findings from this study were that more than
three quarters of newly psychotic patients attained syndromal recovery with currently standard, clinically indicated
treatments within 6 months of a first lifetime psychiatric
hospitalization, but that functional recovery was reached
by fewer than a third of such patients. Generalizations
from this finding to other settings and patient populations
should be made cautiously. This study group was derived
from admissions to a private, university-affiliated psychiatric research and teaching center. Patients typically were
referred from local hospital emergency rooms or university health services and had acute and severe psychotic
symptoms that required treatment in a locked psychiatric
unit. This referral pattern may be different from those of
other institutions. One finding that particularly suggests
cautious generalization is the small proportion of patient

6-Month Outcome in Psychotic Disorders

subjects meeting DSM-IV criteria for schizophrenia
(5.4%; Table 1). Instead, our finding pertains largely to the
high proportion of patients presenting with affective disorders with psychotic features, or with various acute
nonaffective psychoses. Study inclusion criteria of not
being ill for more than 1 year and not being on psychotropic medications for more than 3 months limited the
number of patients with schizophrenia. Therefore, any
generalization of the schizophrenic cohort should be limited to similar patients. Another limitation of this study
was the lack of systematic information on admissions to
other facilities in the area where patients with first-episode
schizophrenia could have been admitted.
Important impressions arising from the present findings
include the following:
1. A large proportion of first-episode psychotic patients (77.0%) achieved syndromal or symptomatic
recovery within 6 months of hospitalization.
2. The time course of syndromal recovery was such
that 25% of all patients recovered within 6 weeks,
and 50% within 12 weeks for most disorders (Figure
1); only those diagnosed initially with schizophrenia
failed to reach the 50% level of recovery within 6
months.
3. Many subjects (79.8%) failed to achieve functional
recovery within 6 months (Table 1), even to the
level of moderate independence, and nearly two
thirds (64.8%) of those reaching syndromal recovery
failed to attain functional recovery. Functional recovery based on occupational level was less often
achieved than functional recovery based on residential status. Those who reached functional recovery
achieved syndromal recovery earlier than those who
did not (Figure 1).
Few predictive factors were significantly related to
syndromal recovery in multivariate analysis, other than the
diagnosis of a bipolar or major depressive syndrome with
psychotic features or a nonaffective acute psychotic disorder, although a relatively acute onset tended to be
associated (Tables 2 and 3). Several factors were significantly associated with functional recovery, however. They
included 1) having attained syndromal recovery, 2) diagnosis of a major affective disorder or a nonaffective acute
psychotic disorder, 3) relatively brief hospitalization, and
4) a relatively later age at onset (Table 2). Various
medical, psychiatric, or substance abuse comorbidity factors had little effect at this early stage of new psychotic
illness, in contrast to expectations based on studies of
populations with chronic psychotic illness (Drake et al
1996); however, a relatively small number of patients
(N 5 21) with a history of epileptic seizures were less

BIOL PSYCHIATRY
2000;48:467– 476

473

Table 3. Characteristics of 257 First-Psychosis Patients
Reaching Syndromal and Functional Recovery or Not within
6-Months after Hospitalization

Measure
N
Male
Onset age 25 years
Nonwhite
Not married
Education 16 years
Nonindependent livingb
Higher occupatione
Gradual onsetf
High baseline BPRS totalg
Axis I comorbidityh
Substance abuseh
Medical comorbidityh
Short hospitalizationi

All
subjects
257
58.8
38.9
15.6
76.3
23.4
66.1
37.0
55.6
49.6
33.5
13.6
35.6
26.8

Proportion of subjects (%)
Syndromally
Functionally
recovered
recovered
198
56.6
38.9
16.2
74.8
24.8
69.7c
36.9
62.1c
49.2
28.8c
13.1
35.8
29.8c

74
62.2
22.9a
12.2
67.7a
28.4
66.2d
54.1d
60.8
48.5
25.7
12.2
32.4
36.5a

BPRS, Brief Psychiatric Rating Scale.
a
Significantly different between functionally recovered and nonrecovered
subjects (p , .05).
b
Modified Location Code Index rating . 2.
c
Significantly different between syndromally recovered and nonrecovered
subjects (p , .05).
d
Statistical significance is indeterminate when outcome is defined by occupational and living situations.
e
Employed, student, homemaker (Modified Vocational Status Index rating ,
3).
f
Prodrome 6 months [x2 5 14.7, p , .001].
g
BPRS total score above median at admission.
h
Current Axis I, substance abuse or medical comorbidity [also, lifetime history
of such comorbidity was not related to outcome, although a history of epileptic
seizures was more frequent with nonrecovery: 4.04 vs. 22.0%; x2(1) 5 19.6, p ,
.001].
i
Length of stay 25% percentile for the year of admission [x2 5 3.82, p , .05].

likely to recovery syndromally (p 5 .001) or functionally (p 5 .04), based on multivariate modeling.
Another striking and unexpected finding was an evident
lack of relationship of 6-month outcomes to the year of
enrollment in this study between 1989 and 1996. We had
previously observed a progressive diminution in percent
improvement on standard rating scales (BPRS and CGI)
between initial hospitalization and discharge, along with a
largely economically driven shortening average length of
hospitalization during the same years at the study site
(Figure 3; Zarate et al 1997a). Both syndromal and
functional recovery rates were similar across the years of
entry into the study (Figure 3). These findings indicate that
outcome at 6 months after hospitalization was largely
unaffected by the marked recent decreases in average
LOS. Apparently, many first-psychosis patients sustained
the recovery process initiated during increasingly timelimited hospitalization (Figures 1 and 2). The fact that
decreased LOS did not worsen functional recovery suggests that the improvement in functional outcomes may
take place during the posthospitalization period.
Studies conducted at the University of Cincinnati have

474

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2000;48:467– 476

focused on similar outcomes. Keck and collaborators
(1998), in a 1-year follow-up study of 134 multipleepisode bipolar patients, found that syndromic recovery
occurred in 26% of patients and functional recovery in
24%. The relatively higher recovery rates in our bipolar
subgroup may be explained by the inclusion of firstepisode patients only. A similar study from the same group
in the University of Cincinnati focused on first-episode
affective psychosis (Strakowski et al 1998). In that study
56% of the patients achieved syndromic recovery and 35%
achieved functional recovery. In our study the 32.6% rate
of functional recovery is remarkably similar to the Cincinnati rate; however, the 85.7% of syndromic recovery in
our study is clearly higher than the 56% figure reported by
Strakowski and collaborators. In the Cincinnati study
higher socioeconomic status (SES) was a predictor of both
symptomatic and functional recovery. It is possible that
the higher SES of the McLean patients may explain the
higher rates of symptomatic recovery.
Our findings have clear implications for the long-term
aftercare of patients with psychotic disorders. It is encouraging that a majority of patients achieved a substantial
level of symptomatic recovery within even 3 months of
aftercare; however, this was not the case with patients
initially diagnosed with schizophrenia. Moreover, it is
especially disturbing that nearly two thirds of patients
considered syndromally recovered had not recovered functionally by 6 months after hospitalization, in that they
failed to return even to their baseline levels of residential
and, particularly, occupational functioning, or to minimal
levels of functional independence. For many patients, even
baseline functioning may already have been compromised
due to prodromal illness or comorbidity for some months
before the index hospitalization. It remains to be determined how many subjects, in which diagnostic groups,
will go on to further improvements or relapses with longer
follow-up, and that aspect of the investigation is ongoing.
An issue that has been addressed by our group and other
authors (Fennig et al 1994; Tohen et al 1992b) is the shift
of diagnosis. In this study, reassessment of diagnosis was
conducted at the 2-year follow-up; thus, this information is
not available for the 6-month follow-up period.
The inconsistency between syndromal and functional
recovery reported here parallels clinical experience, in
which substantial symptomatic recovery in acute phases of
psychotic illnesses may occur before, or without, return to
a baseline level or to a substantially improved functional
status. Even with major resolution of acute symptoms,
independent living, interactions with other persons, and,
particularly, ability to work productively may continue to
be compromised for prolonged periods or may result in
sustained disability, with its associated high indirect costs
to society (Greenberg et al 1993; Wyatt et al 1997; Wyatt

M. Tohen et al

and Henter 1995). There may be particular difficulties
associated with first episodes and the new experience of
psychotic illness, resulting in denial or demoralization that
can complicate efforts at treatment and rehabilitation. We
suggest that future research on treatment and outcomes in
new psychotic illness should emphasize functional outcome as well as symptomatic improvement.
These findings highlight a growing appreciation that
symptom-based assessments are insufficient to assure
long-term functional recovery and an improved quality of
life in psychotic patients. Recent improvements in diagnostic and clinical assessment methods in psychiatry have
supported advances in the scientific understanding of
psychotic disorders. Nevertheless, in our opinion even
modern psychiatry—including its outcomes research—
remains excessively preoccupied with medically oriented,
symptomatic assessments. These measures are important,
but represent an incomplete evaluation of clinical status
and level of recovery. Accordingly, we strongly encourage
further attempts to improve and to include various functional assessments in studies of treatment effects and
outcomes, particularly early in the course of the potentially
chronic and disabling psychotic disorders. The assessment
of functional recovery needs to be considered in clinical
trials. New treatments need to be compared to older
treatments in terms of their ability to improve functional
outcomes. In addition, the role of rehabilitation treatments
at the onset of major psychiatric disorders needs to be
evaluated to determine if new treatments provide longterm benefits. Challenges include the need to assess
baseline functional levels in light of relevant premorbid
disability and to understand differences between ability to
live more or less independently and ability to work
productively and gainfully.
In conclusion, although 77% of patients with psychotic
disorders were judged to have achieved substantial symptomatic recovery within 6 months of a first hospitalization, 65%
of these patients did not regain their premorbid functional
status as defined by occupational activities and living situations indicative of at least minimal independence, and those
diagnosed with schizophrenia did especially poorly by both
syndromal and functional criteria for recovery. The findings
support further efforts to improve functional as well as
symptomatic assessments of psychotic patients.
Supported in part by United States Public Health Service Grants Nos.
MH-04844, MH-01948, and MH-47370; grants from the Atlas Foundation and the Bruce J. Anderson Foundation; and the McLean Private
Donors Neuropsychopharmacology Research Fund.
Aspects of this work were presented at the conference “Bipolar
Disorder: From Preclinical to Clinical, Facing the New Millennium,”
January 19 –21, 2000, Scottsdale, Arizona. The conference was sponsored by the Society of Biological Psychiatry through an unrestricted
educational grant provided by Eli Lilly and Company.

6-Month Outcome in Psychotic Disorders

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