88 (2006) 127–134www.elsevier.com/locate/schres

Schizophrenia Research

Long-term outcomes in chronically hospitalized geriatric patientswith schizophrenia: Retrospective comparison of firstgeneration and second generation antipsychotics☆

Leonard White a,b,⁎, Joseph I. Friedman a,b,1, Christopher R. Bowie b, Martin Evers b,Philip D. Harvey b,2, Michael Parrella a,b, Emilian Mihaila b, Kenneth L. Davis b,3

a Clinical Neuroscience Center, Pilgrim Psychiatric Center, West Brentwood, NY, USAb Department of Psychiatry, Mt Sinai School of Medicine, New York, NY, USA

Received 24 February 2006; received in revised form 23 June 2006; accepted 26 June 2006Available online 22 August 2006

Abstract

Introduction: Some groups have reported the longitudinal course of elderly poor outcome schizophrenic patients to be characterized byprogressive decline in cognitive functions and functional capacity. Although many of these patients experience minimal reduction ofpsychotic symptoms, there may be beneficial effects of antipsychotic treatments on cognitive functions and functional capacity.Methods: This naturalistic study compared the longitudinal course of psychotic symptoms, cognitive functions and functionalimpairment in geriatric schizophrenic patients treated with first generation (N=97) or second generation (N=78) antipsychoticmedications. Mixed effects linear regression analyses were used to examine the effects of treatment (first generation vs. secondgeneration antipsychotic), time and treatment × time.Results: Cognitive functions (Mini Mental State Examination time effect estimate=− .41, pb .001; ADAS-L Cog time effectestimate= .64, pb .001) and self-care skills (ADAS-L Self-Care time effect estimate= .65, pb .001) declined over time for thesubject group as a whole and this decline was not modified by treatment with second generation antipsychotics relative to firstgeneration antipsychotics. Similarly, second generation antipsychotic treatment produced no effect on the progressive worsening ofnegative symptom over time.Conclusion: This long-term naturalistic study of poor outcome geriatric patients with schizophrenia did not find atypicalantipsychotics to produce any differential protective effect relative to typical antipsychotics on the long-term manifestations ofsymptoms, cognition and self-care in poor outcome geriatric schizophrenic patients.© 2006 Elsevier B.V. All rights reserved.

Keywords: Schizophrenia; Geriatric; Antipsychotic; Cognition

☆ Earlier versions of this paper were presented at the Mt. Sinai Cognition Conference, Savannah, Georgia, March 31–April 1, 2005 and XXInternational Conference on Schizophrenia Research Savannah, Georgia, April 2–April 6, 2005.⁎ Corresponding author. Pilgrim Psychiatric Center, 998 Crooked Hill Road, Bldg 47, Brentwood, NY, 11717, USA. Tel.: +1 631 761 2144;

fax: +1 631 761 2718.E-mail address: pgcnlww@omh.state.ny.us (L. White).

1 Joseph I. Friedman, MD has a financial interest/relationship or affiliation in the form of: Grant Research Support from Eli Lilly and Company.2 Philip D. Harvey, PhD has a financial interest/relationship or affiliation in the form of: Consultant for AstraZeneca Pharmaceuticals LP; Janssen

Pharmaceutica Products LP; Eli Lilly and Company and Novartis Pharmaceuticals.3 Kenneth L. Davis MD has a financial interest/ relationship or affiliation in the form of: Consultant for Janssen Pharmaceutica Products, L.P.

0920-9964/$ - see front matter © 2006 Elsevier B.V. All rights reserved.doi:10.1016/j.schres.2006.06.038

128 L. White et al. / Schizophrenia Research 88 (2006) 127–134

1. Introduction

The introduction of second generation antipsychotics(SGAs) was a significant advance in the treatment ofschizophrenia. In addition to the increased efficacy ofSGAs for treatment of some symptoms (Davis et al.,2003) and lower risk for many of the side effects of firstgeneration antipsychotics (FGAs) (Tandon and Jibson,2002), clinical studies have consistently demonstratedimprovement in cognitive symptoms, albeit to a smallextent (Harvey and Keefe, 2001).Moreover, receptor, cellculture, and animal behavior studies suggest a possibleneuroprotective effect of antipsychotic medication (Jann,2004). Whether such protective effects halt or slow theprogressive worsening of cognitive functions and symp-toms observed in some older schizophrenic patients(Friedman et al., 2001; Harvey et al., 2003a, 1999b)remains to be elucidated. It should be noted that a recentcomprehensive study of the effectiveness of antipsychoticmedications finds that the FGA perphenazine generallyperformed aswell as SGAs suggesting that SGAsmay nottruly offer superior efficacy and tolerability relative toFGA medication (Lieberman et al., 2005).

Although cognitive and functional impairments arevery common in patients with schizophrenia, little wasknown about the longitudinal course of these impairmentsuntil recently. A review of the recent literature investi-gating the trajectory of neurocognitive deficits across timein patients with schizophrenia (Kurtz, 2005) has identifiedtwo distinct groups. Studies of primarily community-dwelling outpatients with schizophrenia find that overallmeasures of IQ and gross cognitive status do not showdeterioration greater than that associated with benignaging. In contrast, studies of middle-aged and elderlyinstitutionalized patients with schizophrenia haverevealed markedly different findings. There is evidencein this population of a decline in gross measures ofcognitive status. Thus while many schizophrenic patientsdemonstrate a static course of illness over the lifespan,recent evidence suggests that poor outcome patients mayexperience declines in their functioning in late life. Pooroutcome may be defined by longitudinal functionalcriterion: at least 5 years of continuous and completedependence on others for obtaining and maintaining thebasic necessities of life, including food, clothing, andshelter (Keefe et al., 1996).

Several studies of older patients with a lifetime courseof poor outcome and chronic institutional stay haveindicated that these patients manifest such profoundcognitive impairments as to warrant a secondarydiagnosis of dementia (Bowie et al., 2002; Davidsonet al., 1996; Friedman et al., 2001; Harvey, 2001b;Harvey

et al., 2001; McBride et al., 2002). Moreover, these samepatients exhibit a progressive deterioration in theircognitive and functional skills appreciable over follow-ups as short as 30 months (Harvey, 2001a; Harvey et al.,1999a,b). These age-related changes are unique toschizophrenia and have been differentiated from normalage-related changes and from the changes associated withAlzheimer's disease (Friedman et al., 2001). Risk factorsfor this decline include lower educational attainment andmore severe positive symptoms (Harvey et al., 2003a).

Available data from controlled (Jeste et al., 2003;Kennedy et al., 2003) and uncontrolled trials (Barak et al.,2002a,b; Davidson et al., 2000) evaluating SGAs in elderlypatients with schizophrenia have demonstrated efficacy insymptom reduction and overall global clinical improve-ment. The duration of most studies is one year or less withonly two studies lasting 18months (Barak et al., 2002a) and12 months (Davidson et al., 2000) and of the other threeshorter than 6 months (Jeste et al., 2003; Kennedy et al.,2003; Barak et al., 2002b). Furthermore, Harvey et al.(2003b) demonstrated efficacy of SGAs in improving thecognitive functions of elderly schizophrenic patients over arelatively brief period (8 weeks). Despite these findings, nostudies to date have examined the long-term cognitive andfunctional effects of SGAs in elderly poor outcomeschizophrenic patients with progressive cognitive deficits.Although SGAsmay have only limited effects on symptomreduction in treatment refractory patients with schizophre-nia (Chakos et al., 2001), these drugs may halt or slow theprogressive deterioration of cognitive and functionalabilities given the basic science data suggesting neuropro-tective effects of SGAs (Jann, 2004).

Therefore, we performed a retrospective analysis oflongitudinal symptom, cognitive, and functional datafrom a naturalistic follow-up study of elderly pooroutcome patients with schizophrenia comparing theeffects of treatment with FGAs to treatment with SGAs.We hypothesized that elderly poor outcome schizophrenicpatients treated with SGAs would demonstrate a slowingof the progressive deterioration in cognitive and func-tional abilities relative to patients treated with FGAs.

2. Materials and methods

2.1. Subjects

This research was approved by the local institutionalreview board prior to the enrollment of any subjects.These IRBs allowed for a waiver of signed informedconsent. Subjects were part of an ongoing longitudinalstudy of elderly inpatients at Pilgrim Psychiatric Center(PPC), Brentwood, New York. Between 1991 and 2002,

129L. White et al. / Schizophrenia Research 88 (2006) 127–134

1119 subjects were assessed at PPC upon entry into thislongitudinal study. Lifetime research diagnosis of schizo-phrenia (DSM-III-R criteria) was determined by review oflifetime medical records and patient interview wheninformative. All subjects exceeded the minimal longitu-dinal criterion for definition of poor outcome schizophre-nia: at least 5 years of continuous and completedependence on others for obtaining and maintaining thebasic necessities of life, including food, clothing, andshelter (Keefe et al., 1996). One-hundred twenty-five ofthe assessed patients were excluded immediately from theanalysis due to other psychiatric disorders such as mentalretardation, substance-induced psychotic disorder, majoraffective disorder or onset before age 18 or after age 45.Two-hundred twenty-two additional subjects were ex-cluded due to stroke, Alzheimer's disease, Parkinson'sdisease or other neurological conditions associated withcognitive or functional impairment. Twelve more caseswere uncooperative with the assessment procedures. Ofthe 760 remaining eligible cases, 683 were assessed twoor more times. Five-hundred fifteen of these patients werebeing treatedwith some formof antipsychoticmedication,while 168 of remaining cases were not receiving anyantipsychotic and were not further considered in theseanalyses.

2.2. Final case selection and group determination

After review of the distribution of maximum length offollow-up for all cases we determined to exclude caseswhose maximum length of follow-up was less than2.75 years. This cut-off for case inclusion maximizes thenumber of cases available for analysis while avoiding anunderestimation of potential cognitive decline by exam-ining performance over too short a follow-up interval.Indeed, cognitive decline in elderly chronic inpatients asmeasured by the Mini Mental Status Examination(MMSE; Folstein et al., 1975) has been reported to ave-rage about 1 MMSE point per year (Friedman et al.,2001). Therefore, 340 of the remaining 515 cases wereexcluded due to a follow-up interval less than 2.75 yearsleaving a total study sample of 175. It is important to notethat the exclusion of all cases as outlined above wascarried out blind to treatment.

2.3. Assessment and outcome variables

Trained research staff that was not responsible for theclinical care of the subjects conducted the assessments.Training of raters and quality checks of assessmentswere conducted by the same personnel throughout thestudy (L.W.&M.P.). Antipsychotic choice was at the

discretion of the treating psychiatrists who wereindependent of this study. Assessments for this cohortwere conducted between 1991 and 2001 with subjectsassessed a minimum of two times to a maximum of fourtimes as availability permitted. The average total lengthof follow-up was 5.49 years (SD=1.95) with follow-upintervals between assessments being unequal in length.

Symptoms of schizophrenia were rated with thePositive and Negative Syndrome Scale (PANSS) (Kayet al., 2006). The PANSS is a 30-item rating scale withitems scored on a scale of 1–7 with 1 indicating notpresent and 7 indicating extreme severity. Seven itemsrate ‘positive symptoms’, 7 items ‘negative symptoms’and 16 items rate ‘general psychopathology’. In addition,subjects were assessed with the MMSE and theAlzheimer's Disease Assessment Scale-Late Version(ADAS-L) (Mohs, 1989) a modification of the Alzhei-mer's Disease Assessment Scale (ADAS) (Rosen et al.,1984). The ADAS-L has been shown to be reliable(Harvey et al., 1992) and valid (Kincaid et al., 1995) forthe assessment of cognitive and functional impairment ingeriatric schizophrenia. Previous research (Harvey et al.,2003a) has shown that it is also sensitive to cognitive andfunctional decline. Total score on the ADAS-L Self-Caresubscale indexed the severity of functional impairment.The ADAS-L Self-Care items assess toileting, feeding,dressing, and physical ambulation. Items are scored on ascale of 0–4 where 0 indicates no impairment and 4indicates severe impairment. The ADAS-L Cog is a validinstrument for measuring severely impaired cognition ingeriatric schizophrenic inpatients and surpasses theMMSE at correctly distinguishing severe to profoundimpairment; while the MMSE is superior for identifyingabsent or questionable impairment (Bowie et al., 2002).Higher score on the MMSE indicates less impairment ofcognition while higher score on the ADAS-L Cogindicates more impairment.

2.4. Data analysis

Students t test or Chi square (χ2) statistics were used tocompare baseline clinical characteristics of FGAs andSGAs treatment groups. Statistical analysis of treatmenteffects over time was carried out using mixed effectslinear modeling adjusted for baseline differences withcovariates. These covariates were age at assessment andage at first hospitalization. This statistical method ofmixed effect analysis is valid for evaluation of longitu-dinal naturalistic studies where treatment assignment isnon-random and number of assessments per subject andinterval between assessments vary (Gibbons, 2000).Mixed effects linear regression analyses were used to

130 L. White et al. / Schizophrenia Research 88 (2006) 127–134

model the effects of treatment (FGAs vs. SGAs) time, andtreatment by time interaction. Analyses of the followingdependent variables were conducted; PANSS positivesymptom score, PANSS negative symptoms score,ADAS-L Cog, MMSE, ADAS-L Self-Care score.

3. Results

3.1. Baseline characteristics of treatment groups

Ninety-seven subjects received FGA treatment for theduration of the follow-up while seventy-eight subjectswere switched to an SGA sometime during the follow-upperiod. Forty-nine subjects were switched to risperidone(mean daily dose=3.06 mg, SD=1.65), twenty-four toolanzapine (mean daily dose=13.85 mg, SD=7.59), twoto quetiapine (mean daily dose=100mg, SD=70.71), andthree to clozapine (mean daily dose=333.33 mg,SD=407.23). The exact time of switch from typical toSGA treatment was not available and only the follow-upinterval over which the switch was made was available.The average total length of follow-up for the groupswitched to SGA treatment was 6.27 years (SD=2.6), and80% of these subjects were switched during the finalfollow-up interval between assessments. The averagetime of this final follow-up interval was 2.33 years(SD=1.73). Moreover, none of these subjects wereswitched back to FGA treatment during their inclusionin this study.

The specific FGAmedication and dosage administeredto the 97 subjects in the FGA treatment group variedacross the treatment intervals. Oral haloperidol (mean

Table 1Baseline clinical characteristics by treatment group

Baseline variable FGAs group (N=97)

Mean SD

Length of follow-up (years) 4.7 1.3Age (years) 75.3 6.6Age 1st hospitalization 28.3 8.8Education (years) 9.2 2.8Positive symptoms 18.6 7.4Negative symptoms 27.5 8.3ADAS-L Self-Carea 2.5 3.2MMSE 12.9 9.2ADAS-L Coga 13.6 11.9

Gender % male 39Ethnicity %Caucasian 80.4African American 12.4Hispanic 6.2

a Higher scores indicate poorer performance.

daily dose=11 mg, SD=16) was administered at the timeof 21% of the assessments and haloperidol decanoate IM(mean q 4 week dose=68.25mg, SD=49.6) at 10% of theassessments, fluphenazine decanoate IM (mean q 2 weekdose=25mg, SD=17.7) was administered at less than 1%of the assessments and oral fluphenazine (mean daily dose18 mg, SD=23) at 2% of the assessments. Thiothixine(mean daily dose=11 mg, SD=18) was administered atthe time of 25% of the assessments and thioridizine (meandaily dose=133mg, SD=113) at 10% of the assessments.Other medications used in the FGA group werechlorpromazine (mean daily dose=163 mg, SD 160) at3% of the assessments; perphenazine (mean dailydose=11 mg, SD=9) at 2% of the assessments;mesoridizine (mean daily dose=50 mg, SD=0) at 1%and trifluoperizine (mean daily dose 3 mg, SD=1) atb1%. At 25% of the assessments subjects in the FGAgroup were not receiving any antipsychotic medication.Moreover, anticholinergic medication use (primarilybenztropine) occurred at an approximate equal frequencyin the FGA and SGA treated groups (12.7% vs 13%respectively in the last assessment period). Finally,cholinesterase inhibitor use was absent from bothtreatment groups for the duration of the follow-up.

The results of statistical comparisons of clinicalcharacteristics of the typical and atypical treatmentgroups at baseline are summarized in Table 1. Thetypical group was 3.2 years younger at the time of firsthospitalization than the atypical group and 3.2 yearsolder at the time of baseline assessment. To control forbaseline age and age at first hospitalization differencesbetween treatment groups, baseline age and age at first

SGAs group (N=78) t (df) p

Mean SD

6.27 2.6 −4.7 (173) b .00172.2 6.2 3.2 (173) .00225.1 9.7 2.2 (161) .0329.9 2.7 −1.6 (160) .11918.6 5.6 .05 (157) .9628.9 9.2 −1.1 (157) .282.73 3.1 − .47 (173) .6314.2 9.2 − .89 (173) .3713.1 12.4 .24 (173) .81

χ2 (df) p51 15.6 (1) b .001

91 24.5 (3) b .0017.71.3

Table 2Linear mixed effects results comparing first generation antipsychotic (FGAs) treatment to second generation antipsychotic (SGAs) treatment

Variable Treatment Time Treatment × time interaction

Estimate (SE) p-value Estimate (SE) p-value Estimate (SE) p-value

MMSE −2.3 (1.44) .88 − .42 (.1) b .001 .22 (.16) .167ADAS-L Cog − .83 (2.6) .77 .64 (.15) b .001 − .29 (.23) .20ADAS-L Self-Care .01 (.45) .97 .65 (.08) b .001 − .16 (.13) .21Positive symptoms −1.01 (.83) .23 − .18 (.13) .18 .27 (.21) .19Negative symptoms −3.1 (1.3) .018 .30 (.15) .051 .25 (.24) .29

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hospitalization were entered as covariates in the mixedeffects models.

3.2. Analysis of changes over time as a function oftreatment

Table 2 presents a summary of the linear mixed effectsanalyses with age at first assessment and age of firsthospitalization as covariates. The time effect for theMMSE was statistically significant (Estimate=− .41,pb .001). The effect of treatment and treatment × timeinteractions was non-significant. The results for ADAS-LCog and ADAS-L Self-Care were similar to the results forthe MMSE. Time effects were statistically significant forADAS-L Cog (Estimate=.64, pb .001) and ADAS-LSelf-Care (Estimate= .65, pb .001) but the effect oftreatment and the treatment × time interactions was bothnon-significant. There was a statistically significanttreatment effect on negative symptoms (Estimate=−3.1,p=.018) and a near significant time effect (Estimate= .30,p=.051). The time × treatment interaction for negativesymptoms was non-significant. These results suggest across-sectional advantage of atypical antipsychotics onnegative symptom severity but no advantage of SGAs toFGAs in modifying the course of negative symptoms inthese poor outcome patients. For positive symptomtreatment effects, time effects and treatment × time effectswere non-significant. Relationships between the covari-ates and the outcomes were overall consistent across thetreatment groups (FGAs vs. SGAs).

4. Discussion

Findings of the present study do not support thehypothesis that SGAs are more protective againstcognitive and functional decline in geriatric poor outcomeschizophrenic patients than FGAs. In other words,cognitive functions, functional ability and negativesymptoms all worsened in geriatric poor outcome schizo-phrenic patients irrespective of the class of antipsychoticused. To our knowledge, this study had the longest follow-up interval relative to other longitudinal studies of the

effects of FGAs and SGAs in elderly schizophrenicpatients.

The cognitive impairment of the elderly pooroutcome patients with schizophrenia in the presentstudy is so profound as to warrant a secondary diagnosisof dementia. Although no causal relationship has beenestablished, there is some evidence of acceleratedcognitive decline in primary dementia patients receivingboth FGAs (McShane et al., 1997) and SGAs (Schneideret al., 2006) for behavioral disturbances. However, therate of cognitive decline for the dementia patientsobserved in the year before the start of treatment withFGA medication in the McShane et al. (1997) study (5MMSE points per year) and following the start of FGAtreatment (12 MMSE points per year) (McShane et al.,1997) far exceeds the rate of cognitive decline observedin both treatment groups in the present study.While thereis evidence of progressive brain changes in those pooroutcome schizophrenic patients who develop progres-sive cognitive worsening in late age (Davis et al., 1998),there is a lack of Alzheimer's disease and other dementiarelated pathology in the brains of these schizophrenicpatients at post-mortem (Purohit et al., 1998). Therefore,differences in the cognitive effects of antipsychotics inpatients with primary dementia and schizophrenicpatients with secondary dementia were not surprising.Understanding the neurobiology of the progressive brainchanges in poor outcome schizophrenic patients withprogressive cognitive decline may lead to the identifi-cation of new treatment targets to address the severecognitive and functional impairments of poor outcomegeriatric schizophrenia. Studies of post-mortem braintissue from a number of subjects in the very cohort wesampled in the present study have increased ourknowledge of the fundamental neurobiological abnor-malities underlying these cognitive and functionalimpairments. For example, cognitive deficits in pooroutcome elderly schizophrenic patients have not beenrelated to cholinergic deficits (Haroutunian et al., 1994).Instead, cognitive impairment during late life has beenrelated to cortical noradrenergic and serotonergic deficitsidentified at post-mortem (Powchik et al., 1998). More

132 L. White et al. / Schizophrenia Research 88 (2006) 127–134

recently, genetic (Hakak et al., 2001) and histopatholog-ical studies (Hof et al., 2003) have provided evidence ofabnormalities in white matter of the brains of schizo-phrenic patients that serve to connect neuronal networksimportant for cognition. It is possible that a worsening ofthis pathological state may account for a portion of thecognitive and functional decline in these poor outcomeschizophrenic patients. Therefore, this decline may notbe effectively treated until these pathological changes aretargeted.

The present investigation encountered many of thelimitations associated with a naturalistic research design.Subjects in this study were evaluated at different intervalsand not all subjects were assessed the same number oftimes. Mixed effects modeling provides a general frame-work for the analysis of repeatedmeasures appropriate fornaturalistic studies because not every case needs to sharethe same number of assessments nor the same timing ofthe assessments (Nich and Carroll, 1997). Random effectsmodeling provides valid estimates if drop outs are thoughtto be related to observed previous levels of the dependentvariable (i.e. subjects with very bad or very good scoresdrop out). Another significant limitation of the presentstudy was our inability to calculate an exact time ofexposure to SGA treatment. Instead, information onwhich follow-up interval over which the switch was madewas available. 80% of the subjects switching treatmentdid so during the final follow-up interval between assess-ments that averaged 2.33 years. It is unlikely that, bychance, most subjects were switched just prior to ourassessments and therefore subjects were most likelyexposed to SGA treatment for longer than the 8 weekperiod in which the geriatric schizophrenic patientstreated in the Harvey et al. (2003b) study demonstratedsignificant cognitive improvements.

Non-random treatment assignment, a characteristic ofnaturalistic studies, resulted in treatment group differ-ences in age at first assessment and age at first hospital-ization. Patients treated with SGAs were younger atbaseline and were younger at the time of their firstpsychiatric hospitalization. These differences were statis-tically controlled by means of covariance but additio-nal unaccounted for sources of bias may exist. Forexample, clinicians may have selected already declin-ing patients to be switched to SGAs because of theirreported cognitive enhancing effects. If such a biasin treatment assignment did occur a worse outcomegroup would have been assigned to the SGA cohortworking against a finding in cognitive and functionalenhancement with SGA's over time. Other possiblemediating factors not accounted for in this study maybe pre-existing medical co-morbidities, medical ill-

nesses that might have emerged during follow-up anddrug–drug interactions.

One of the advantages of an study of antipsychotictreatment effects in inpatients is that medication is dis-pensed and monitored by nursing staff and non-adherenceto treatment is minimized. Long acting injectable anti-psychotic medications are a well accepted method fortreatment of the non-adherent patient. In the FGA treatedgroup eleven percent of the assessments were performedwhen subjects were treated with long acting preparationssuggesting that treating psychiatrists were attentive to theissue of noncompliance. Limited data indicate that FGAsadminister to elderly patients as depot injections areassociated with positive outcomes (Masand and Gupta,2003).

Clinically determined medication regimens raise thepossibility that treatment dose of SGAs may not havebeen maximized and may have resulted in underestima-tion of treatment effects of SGAs. This does not appear tobe the case however, as the mean daily doses of SGAsused in the present study approximate the OBRA geriatricdose recommendations of risperidone 2 mg and olanza-pine 10 mg (Gurvich and Cunningham, 2000) and arecomparable to the effective geriatric dose of risperidone (1to 3 mg/day) and olanzapine (5 to 20 mg/day), reported inearlier studies of patients of similar age and overalllifetime outcome (Harvey et al., 2003b; Jeste et al., 2003).

Findings from this study are provocative as theyhighlight a significant limitation in the treatment of elderlypoor outcome schizophrenic patients however the findingsmust be considered preliminary. The significant limita-tions of such a naturalistic study necessitate additionallong-term studies of the effectiveness of second generationantipsychotics in the geriatric schizophrenic population.

Acknowledgement

This work was supported by grant 950MH66392-01awarded by NIMH to Kenneth M. Davis M.D.

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