Psychosis_overview of Systematic Reviews_2010

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REVIEW

An overview of systematic reviews on cannabis and psychosis:

Discussing apparently conflicting resultsdar_132 304..317

SILVIA MINOZZI, MARINA DAVOLI, ANNA M. BARGAGLI, LAURA AMATO,SIMONA VECCHI & CARLO A. PERUCCI

Department of Epidemiology, Local Health Unit Roma E, Roma, Italy

AbstractIssues. Cross-sectional surveys have revealed that cannabis is the most widely used illicit substance in Western countries.

Cannabis intoxication can lead to acute, transient psychotic symptoms and the short-term exacerbation of pre-existing psychoticsymptoms. However, controversy exists about whether cannabis can actually cause long-term psychosis. Approach. Wesummarised the findings of systematic reviews on the association between cannabis use and psychosis, searching MEDLINE,EMBASE and CINAHL up to August 2007.We assessed the methodological quality, selected the better quality reviews andanalysed reasons for discordant results. Key Findings.We included five systematic reviews. Four of the reviews performed ameta-analysis and showed a consistent association between cannabis use and psychosis; the fifth review considered psychologicalproblems more broadly, did not perform a meta-analysis and reported an inconsistent association.The reasons for discordance

were: different outcomes (psychosis vs. psychological problems), different inclusion criteria for primary studies and differentmethods for summarising the results. Implications.This overview shows a consistent association between cannabis use andpsychotic symptoms,though it is not possible to draw firm conclusions about a causal relationship. Reverse causality and residualconfounding cannot be excluded. An interaction with other environmental and genetic factors is difficult to ascertain.

Conclusion.We conclude that there is insufficient knowledge to determine the level of risk associated with cannabis use inrelation to psychotic symptoms and that more information is needed on both the risks of cannabis use and the benefits of

preventive interventions to support evidence-based approaches in this area. [Minozzi S, Davoli M, Bargagli AM, Amato L,

Vecchi S, Perucci CA. An overview of systematic reviews on cannabis and psychosis: Discussing apparently conflict-ing results. Drug Alcohol Rev 2010;29;304317]

Key words: cannabis, marijuana abuse, psychotic disorders, systematic review.

Introduction

Cross-sectional studies of the general population and

students have consistently revealed that cannabis is the

most widely used illicit substance in many regions of

the world, including Europe [1], North America and

Australia [2,3]. Cannabis is also the second most fre-

quently cited drug in reports on individuals enteringsubstance abuse treatment for the first time [15].

Clients seeking treatment for cannabis use canpresent

with social impairment, such as complaints from family

members, loss of friendship, financial difficulties,

impaired work or school performance, loss of self-

confidence, memory loss,legal problems and psychiatric

distress, such as somatisation, depression, anxiety, irri-

tability, phobic anxiety, paranoid ideation and psychosis

[68]. Cannabis intoxication can lead to acute, transient

psychotic symptoms in some individuals [9] and

produce a short-term exacerbation or recurrence of

pre-existing psychotic symptoms [1012]. However,controversy remains about whether cannabis use can

actually cause long-term psychosis [1].

There is evidence of an association between cannabis

use and the development of psychotic symptoms, but

Silvia Minozzi MD, Marina Davoli MD, MSc, Anna M. Bargagli BSc, Laura Amato MD, Simona Vecchi BSc, Carlo A. Perucci MD.Correspondence to Dr Marina Davoli, Department of Epidemiology, Local Health Unit Roma E, Via di Santa Costanza 53, 00198 Rome, Italy.Tel: +390683060483; Fax: +390683060374; E-mail: [email protected] of Interest: none

Received:19 September 2008; accepted for publication 2 July 2009.

R E V I E W

Drug and Alcohol Review (May 2010), 29, 304317DOI: 10.1111/j.1465-3362.2009.00132.x

2009 Australasian Professional Society on Alcohol and other Drugs


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the nature of this association is widely debated. Four

main hypotheses have been formulated to explain the

observed association [13]:

1. Confounding: the association is spurious; can-

nabis use is often associated with the use of other

drugs or with other factors responsible for the

later onset of psychosis.2. Interaction: cannabis is a component cause; psy-

chosis is caused only in vulnerable people and in

interaction with other environmental and genetic

factors.

3. Reverse causality: people with psychosis use can-

nabis more often in an attempt to cope with nega-

tive symptoms that stem from psychosis

(depression, anxiety or dysphoria) or to alleviate

the side-effects of antipsychotic medication.

4. Etiological: cannabis is the direct cause of psycho-

sis; it alone is a necessary and sufficient cause.

Systematic reviews critically appraise and summarisethe published evidence concerning a particular

problem and have gained prominence as useful tools for

evidence-based decision making. The number of sys-

tematic reviews has increased at least 500-fold during

the past 10 years, and they have been applied exten-

sively in the field of drug addiction. This increase has

lead to an increased number of reviews addressing very

similar questions, with a concomitant increase in con-

flicting results. Such a discrepancy causes difficulties

for decision makers, clinicians and patients.

The aim of this overview was to summarise the major

findings of published systematic reviews on the associa-

tion between cannabis use and psychosis, and to

analyse the possible reasons for the discordant results

among them.

Methods

Search strategy

We performed a systematic search of MEDLINE,

EMBASE and CINAHL from 2000 to August 2007.

For each database, separate detailed search strategies

were developed based on controlled vocabulary and

free text terms, combining the following search terms

and the boolean operators or/and: [Substance-relateddisorders or cannabis or marihuana or marijuana] and

[psychosis or psychotic disorders or schizophrenia or

psychotic*]. A methodological search filter for review

articles was added. We also checked the references of

existing reviews for potentially relevant papers. There

was no language restriction.

Inclusion criteria

We included systematic reviews that clearly state the

objective, define the inclusion criteria for primary

studies, report the raw data of the primary studies

included, and include observational studies that assess

the relationship between cannabis use and psychosis.

Data extraction and quality assessment

Two authors independently extracted data and assessed

the quality of the included reviews using the Overview

Quality Assessment Questionnaire (OQAQ) scale [14];

any disagreement was resolved by discussion among the

authors.

The OQAQ scale is composed of nine items designed

to assess specific aspects of the methodological quality

of systematic reviews and one overall assessment item

that requires assessors to assign a quality score on a

7-point scale, where 1 represents the presence of exten-

sive flaws and 7 represents minimal flaws.

Analysis of discordant reviews

In order to analyse the reasons for discordant results

among the reviews, we used the following criteria pro-

posed by Jadad [15]:

Differences in methodological quality. Differences in clinical question: population, expo-

sure, outcomes.

Differences in study selection: search strategy,inclusion criteria.

Differences in data extraction: methods tomeasure exposure and outcomes.

Differences in the assessment of study quality:

methods and interpretation of quality assessments.

Differences in methods to incorporate qualityassessments into the review.

Differences in the ability to combine studies: sta-tistical methods, criteria to judge the ability to

combine studies.

We also retrieved the full text of primary studies

included in the reviews in order to understand better

the reasons for inclusion or exclusion and to determine

the appropriateness of any statistical synthesis of the

results.

Results

We identified 41 reports. Twenty-one reports were

excluded on the basis of the title and abstract because

they were not pertinent to the objective of our review,

and the full text of 20 articles was retrieved for more

detailed evaluation. Fifteen of the 20 articles were

excluded because they did not fulfil the inclusion cri-

teria.Thus, five systematic reviews were included in the

present review [1620].

Systematic reviews on cannabis and psychosis 305



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Characteristics of included reviews

Four of the five included reviews [16,17,19,20]

assessed the association between cannabis exposure

and the occurrence of schizophrenia (any type),

schizophrenia-like disorders, psychosis not otherwise

specified, or psychotic symptoms; the fifth review

assessed the association between any illicit drug use and

the occurrence of any psychological or social harm, but

it also included studies assessing the association

between cannabis use and psychosis considered as psy-

chological or social harm [18]. One of the reviews [20]

also assessed the relationship between cannabis use and

affective disorders (depression, suicidal ideation or

attempt, anxiety). Three of the reviews [16,18,20]

included only longitudinal cohort studies, whereas the

other two [17,19] included both cross-sectional and

longitudinal cohort studies. Table 1 shows the study

design of each study included and excluded in each of

the five reviews.Overall, eight longitudinal cohort studies [2132]

assessing the association between cannabis exposure

and psychosis development were identified and

included in the reviews. Macleod [18] included 16 lon-

gitudinal studies, only four of which were on the asso-

ciation between cannabis use and psychosis and

included in the other reviews. The other studies in that

review assessed the effect of cannabis use on affective

disorders, adult role, job success and quality of social

relationships.

Methodological quality

The methodological quality of three of the reviews was

poor (overall quality score 2/7 [16,17] and 3/7 [19]),

whereas the other two were of good quality (overall

quality score 5/7 [18] and 6/7 [20]) (Table 2).The main

weaknesses concerned the comprehensiveness of the

bibliographic search (cannot tell for 2/5 reviews), the

avoidance of selection bias (cannot tell for 4/5 reviews),

the assessment of the methodological quality of

primary studies (not done in 3/5 reviews). In one review

[18], conclusions were not supported by the data

because the results of the primary studies were not

clearly described. Only one review [20] reported thenumber of excluded studies and the reasons for exclu-

sion. The information provided about the studies

included in the reviews was not detailed enough to

ascertain important information on the primary studies

for all but one of the reviews [20], which provided a

detailed table of the study characteristics. In particular,

the reviews had no clear information regarding:

Study design: some studies were described ascasecontrol studies but appear in the description

as cross-sectional studies, which invalidated any

result on possible causal association;

Exposure assessment: how cannabis use wasassessed and if frequency, length and amount of

use were considered;

The assessment of confounding: how the use ofother drugs was assessed and if frequency, length

and amount of other drug use were considered;

The outcome definition: whether primary studiesconsidered schizophrenia using the Diagnostic

and Statistical Manual of Mental Disorders

(DSM-IV) or International Classification of

Disease (ICD-10) criteria, or schizophreniform

disorders or psychotic symptoms. One review

[18] used the term psychological problems as the

outcome, and it is not clear which outcomes used

in the primary studies were considered under this

broader term;

Effect measure estimate: why and how odds ratios(OR) were calculated in cohort studies, how theytook losses to follow up into consideration; if the

overall estimates reported in the reviews were

computed using consistent measures of exposure

(heavy users or any users) and outcome; and

how confounding was incorporated into the

pooled estimate.

Findings

Four of the reviews [16,17,19,20] performed a meta-

analysis and were concordant in finding an association

between cannabis use and the occurrence of psychotic

disorders (Table 3). Nevertheless, the way of combin-

ing results varied among the individual reviews:

Arsenault et al. [16] included a duplication of Swedish

conscript data in the meta-analysis and combined

results for ever use and dependence; Henquet et al.

[17] and Semple et al. [19] combined cross-sectional

and longitudinal data in the meta-analysis and did not

distinguish between ever use and dependence; Semple

et al. [19] combined the crude odd ratios; and Mooreet al. [20] combined only longitudinal studies, pre-

sented separate results for ever use and most frequent

use and combined the adjusted OR. None of the

reviews found significant statistical heterogeneity. Thereview without a meta-analysis [18] found an inconsis-

tent association between cannabis use and psychologi-

cal problems.The authors reported that the adjustment

for confounding factors lead to substantial attenuation

of the association but did not report the original data.

To analyse possible reasons for the discordant results,

we restricted our analysis to the two higher quality

reviews [18,20]. The comparability of the two reviews

using Jadads criteria is reported in Table 4. The main

difference between the two reviews was outcome defi-

306 S. Minozzi et al.



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Table1.

Primarystudiesincludedandexcludedinsystematicreviews

Primarystudies

Studydesign,outcomes

Arseneault

etal.2004[16]

Henquet

etal.2005[17]

Macleo

detal.

2004

[18]

Sempleetal.

2005[19]

Mooreetal.

2007[20]

Dateofbibliographicsearch

Notreported

Notreported

June

2003

January2004

September2006

Andrassonetal.1987[21],

Zammitetal.2002[22],

Zammit2004[23]

(SwedishConscripts

study)

Longitudinalpopulation

based(conscripts)

schizophrenia

Ye

s

Yes

Yes

Yes

Yes

Arsenaultetal.2002[24],

Caspietal.2005[25]

(Dunedinstudy)

Birthcohort

Psychoticsymptoms

Schizophreniformdisorders

Ye

s

Yes

Yes

Yes

Yes

vanOsetal.2002[26]

(NEMESISstudy)


basedPsychoticsymptoms

Ye

s

Yes

N

o

Yes

Yes

Fergussonetal.2003[27],

2005[28](CHDSstudy)

Birthcohort

Psychoticsymptoms

Ye

s

Yes

Yes

Yes(notincludedin

meta-analysis

Yes

Henquetetal.2005[29]

(EDSPstudy)


based

Psychoticsymptoms

No

Yes

N

o

No

Yes

Weiseretal.2002[30]

Adolescentlongitudinal

populationbased.

Schizophreniaspectrum

personalitydisorders

No

Yes

Includedas

lowquality

study.No

tconsidered

forsumm

aryresults

No

N

o.Excludedbecause

nodataspecifically

oncannabisuse

Tien&Anthony

1990[31](ECAstudy)

LongitudinalPopulation


No

No

N

o

Yes(notincludedin

meta-analysis)

Yes

Wilesetal.2006[32]

(NPMS)



No

No

N

o

No

Yes

Stefanisetal.2004[33]

Cross-sectional

Psychoticsymptoms

No

Yes

N

o

No

N

o.Excludedbecause

crosssectional

Rolfeetal.1993[34]

Crosssectional

schizophrenia

No

No

N

o

Yes

N

o.Excludedbecause

crosssectional

Agostietal.2002[35]

Crosssectional

Nonaffectivepsychosis

No

No

N

o

Yes

N

o.Excludedbecause

crosssectional

Degenhardt&Hall

2001a[36]

Crosssectional.

Psychoticsymptoms

No

No

N

o

Yes

N

o.Excludedbecause

crosssectional

(continued)




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Table1.(Continued)

Primarystudies

Studydesign,outcomes

Arseneault

etal.2004[16]

Henquet

etal.2005[17]

M

acleodetal.

2004[18]

Sempleetal.

2005[19]

Mooreetal.

2007[20]

Dateofbibliographicsearch

N

otreported

Notreported

June2003

January2004

September2006

Degenhardtetal.2001b[37]

Crosssectional.

Psychoticsymptoms

No

No

No

Yes

No.Excludedbecause

crosssectional

Farreletal.2002[38]

Crosssectional.

Psychosis

No

No

No

Yes

No.Excludedbecause

p

opulationareprison

sample

Grechetal.1998[39]

Crosssectional.

Psychosis

No

No

No

Yes

No.Excludedbecause

p

articipantshad

a

lreadypsychotic

symptoms

Milleretal.2002[40]

Crosssectional.

Psychoticsymptoms

No

No

No

Yes

No.Excludedbecause

crosssectional

Phillips&Johnson2002[41]

Longitudinalstudy;very

high-riskpopulation

Psychoticsymptoms

No

No

No

Yes

No

Resnicketal.1997[42],

Dornbuschetal.1999[43]

(NationalLongitudinal

Studyonadolescenthealth)


basedViolentbehavior

No

No

Yes

No

Guyetal.1993[44],Stein

etal.1993[45](Boston

Schoolsproject)


basedJobinvolvement

No

No

Yes

No

No.Excludedbecause

n

odataspecifically

o

ncannabisuse

Brooketal.1998[46]

(Childreninthe

communityproject)


basedAffectiveoutcomes

No

No

Yes

No

No.Includedfor

a

ffectiveoutcomes

Brooketal.1996[47],1999

[48](Childreninthe

communityproject)


basedViolentbehaviour,

adultrole

No

No

Yes

No

No.Excludedbecause

n

otexamined

p

sychoticoraffective

o

utcomes

Brooketal.1999[49](East

Harlemstudy)


based.Behavioural

outcomes

No

No

Yes

No

No

Brunswick&Messeri1986

[50],1999[51](Central

HarlemStudy)


based.Physicalhealth,

behaviouroutcomes,social

attainment

No

No

Yes

No

No.Excludedbecause

n

otexamined

p

sychoticoraffective

o

utcomes




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Newcombetal.1993[52],

1999[53](LAschools

study)


based.Affectiveoutcomes

No

No

Yes

No

No

.Includedfor

a

ffectiveoutcomes

Kandeletal.1995[54](New

Yorkschoolsstudy)


based.Incomeoutcome

No

No

Yes

No

No

.Excludedbecause

n

otexamined

p

sychoticoraffective

o

utcomes

Friedmanetal.1996[55]

(NationalCollaborative

PerinatalProject,NCPP)


based.Delinquency,

antisocialbehaviour

No

No

Yes

No

No

Kaestner1994[56],Windle

1997[57]National

Longitudinalsurveyof

youth)


based.Incomeoutcome

No

No

Yes

No

No

Whiteetal.1999[58]

(PittsburghYouthStudy)


based.Violentbehaviour

No

No

Yes

No

No

Ellicksonetal.1998[59],

2000[60](ProjectAlert)


based.Violentbehaviour

No

No

Yes

No

No

Brayetal.2000[61](South

easternpublicschools

study


based.Educational

attainment

No

No

Yes

No

No

Bates&Labouvie1997[62]

(Woodlawnstudy)


based.Alcoholuse

No

No

Yes

No

No

.Excludedbecause

n

otexamined

p

sychoticoraffective

o

utcomes

Juon&Ensminger1997[63]

(Woodlawnstudy)


based.Suicidalideationor

attempts

No

No

Yes

No

No

.includedfor

a

ffectiveoutcome




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nition, which could also explain differences in the

included studies. Macleod et al. [18] considered any

psychological problem without any further explana-tion or definition, whereas Moore et al. [20] consid-

ered only psychotic disorders and affective disorders

defined by the DSM-IV. Furthermore, six studies

included by Macleod as studies considering psycho-

social problems as the outcome measure were also

included by Moore, but three were defined as studies

assessing affective disorders and three as studies

assessing psychosis as the outcome measures. Again,

in the list of studies excluded by Moore, there were

six that were included by Macleod as high-quality

studies; the reason for excluding these studies was a

lack of considering psychotic or affective outcomes

(four studies) or no specific data on cannabis use (twostudies). The other major difference was in reporting

the outcomes of primary studies: Moore reported an

adjusted OR with a 95% confidence interval for each

study, whereas Macleod gave a generic qualitative

description that was more prone to interpretation.

Macleod stated that the association was often substan-

tially reduced, adjusting for confounding factors, but

did not report the data, whereas Moore clearly

reported how much the association was reduced for

each study.

Table 2. Quality of conduct (OQAQ checklist)

ItemArseneault et al.

2004 [16]Henquet et al.

2005 [17]Macleod et al.

2004 [18]Semple et al.

2005 [19]Moore et al.

2007 [20]

Search methods described Partially No Yes Yes YesSearch comprehensive Cant tell Cant tell Yes Yes YesInclusion criteria reported Yes Yes Yes Yes YesSelection bias avoided Cant tell Cant tell Cant tell Cant tell YesCriteria for quality assessment reported Partially No Yes No PartiallyCriteria used appropriate No No Yes No YesMethods to combine findings reported Yes Yes Yes Yes YesFindings appropriately combined No No Yes No YesConclusions supported by the data Yes Yes No Yes YesOverall score of scientific quality (*) 2 2 5 3 6

*Score from 1 (extensive flaws) to 7 (minimal flaws); OQAQ: Overview Quality Assessment Questionnaire.

Table 3. Results of meta-analysis

Author Meta-analysis of included studies n studies included

Arseneault et al. 2004[16]

Adjusted OR: 2.34 (95% CI: 1.69, 2.95)Longitudinal studies.Ever use and dependence considered altogetherThe same cohort from the Swedish conscripts study was includedtwice in the meta-analysis (Andreasson et al. and Zammit et al.results)

Five studies, n ofparticipants 101 497

Henquet et al. 2005[17]

Adjusted OR: 2.1 (95% CI: 1.7, 2.5)Cross-sectional and longitudinal studiesEver use and dependence considered altogether

Seven studies, n ofparticipants 112 218

Macleod et al. 2004[18]

Meta-analysis not performedInconsistent association between cannabis use and psychological

problems (data not reported). The adjustment for confoundingfactors lead to substantial attenuation of the association

Sixteen studies, n ofparticipants not

reported

Semple et al. 2005 [19] Crude OR: 2.93 (95% CI: 2.36, 3.64)Cross-sectional and longitudinal studiesEver use and dependence considered altogether

Seven studies , n ofparticipants 51 688

Moore et al. 2007 [20] Adjusted OR: ever use OR 1.41 (95% CI: 1.20, 1.65)Heavy users: OR 2.09 (95% CI: 1.54, 2.84)Longitudinal studies

Seven studies, n ofparticipants notreported

CI, confidence interval; OR, odds ratio.




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Characteristics of longitudinal primary studies

We analysed the primary studies included in the meta-

analysis by Moore et al. [20] to assess if they were

homogeneous enough to allow the pooling of their

results (Table 5).

The main difference among the studies was in the

length of follow up: 11.5 years in two studies [33,35],

45 years in two studies [28,32] and more than 9 years

in three studies [24,26,30] (range 127 years).

The other parameters that were considered did not

differ among the studies:

The presence of psychotic symptoms at baselinewere assessed using structured and validated

instruments;

Table 4. Source of discordant results among the two higher quality reviews (criteria proposed by Jadad)

Criteria Macleod et al. 2004 [18] Moore et al. 2007 [20]

Clinical questionPopulation General population aged 25 or younger General population; excluded people with

mental illness or substance related

problemsExposure Any illicit drug (results repor ted for cannabis) Cannabis useOutcomes Any psychological or social harm Psychosis (schizophrenia, schizophreniform

or other psychotic disorders, psychoticsymptoms.

Affective, mood or bipolar disorders,depression, suicidal ideation or attempts,anxiety, neurosis and mania

Study selection and inclusionSelection criteria Population based prospective studies assessing

the association between any drug use amongyoung people and any psychological or socialharm

Population based prospective studiesassessing the association between cannabisuse and psychosis or affective disorders

Search strategy Medline, Embase, CINAHL, PsychLIT, Web ofScience, specialised databases, contact with

authors. No language restriction. Up to June2003

Medline, Embase, CINAHL, PsycINFO, ISIWeb, specialised databases, contact with

authors. No language restriction. Up toSeptember 2006

Included studies 48 longitudinal studies, three of which includedin Moore for the outcome psychosis andthree for the outcome affective disorders

7 longitudinal studies for psychosis, three ofwhich included in Macleod. 15 cohortstudies for affective disorders, three ofwhich included in Macleod

Data extractionMethods to measure

outcomesNo raw data reported; only descriptive OR with 95% confidence interval adjusted

for confoundingEnd points Psychological problems without further

descriptionRisk of psychosis

Risk of affective disordersAssessment of study qualityMethod to assess

qualityTwo reviewers independently Two reviewers independently

Quality criteria used Sample size and representativeness, age at

recruitment, duration and completeness offollow up, validity and reliability of exposureand outcomes measures, degree of adjustmentfor potential confounding factors

Sampling strategy, response rate, missing

data, attrition, attempts to address reversecausation, intoxication effects andconfounding factors.

Methods to incorporatequality assessment inreview

Considered only the 16 studies judged of bettermethodological quality

Not stated

Assessment of the ability to combine resultsStatistical methods Not used Meta-analysis of adjusted OR using the Der

Simonian and Laird random effects modelClinical criteria to

judge the ability tocombine results

Quantitative synthesis considered misleadingbecause heterogeneity in primary studies formethod to assess exposure and outcomes

Studies on psychosis judged homogeneousenough to perform a meta-analysis.

Studies on affective disorders judged tooheterogeneous to perform a meta-analysis

OR, odds ratio.




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Table5.Characteristicoflongitudinalstudiesonpsychosisoutcomesincludedinthereviews

Study

Participantsand

baselinescreening

Exposure

Outcome

Follow-up

attrition

Confoundingfactor

considered

Dose-response

effect

Andrassonetal.

1987[21],

Zammitetal.

2002[22],

Zammit2004[23]

(Swedish

Conscriptsstudy)

n:50053

Adultp

opulationbased

conscripts

Sweden

Baseline:psychiatric

intervie

wforICD-8

diagnosis

Everuse

Frequency:1

time,

24times,510

times,1150times,

>50times

Admissionfor

ICD-10

diagnosisof

schizophreniaor

schizoaffective

disorders

27years

A

ttrition:data

notreported

Psychiatricdiagnosisa

t

baseline,IQ,

interpersonal

relationship,

disturbedbehaviour

inchildhood,family

historyofpsychiatric

illness,alcohol

misuse,otherdrug

use

Evidenceofa

dose-response

effect

Tien&Anthony

1990[31](ECA

study)

n:2295

adultpopulationbased

cohort

USA

Baseline:DISinterviewfor

psychoticsymptoms

DISinterviewfo

r

lifetimeeveru

seand

dailyuse

DISinterviewforany

self-reported

psychoticexperience

1ye

ar

A

ttrition:20%

Age,gender,school

attendance,

educationallevel,

employmentand

maritalstatus,

baselinemental

healthproblem,other

drugandalcoholus

e

Notstudied.

Strongereffect

fordailyuse

thaneveruse

Arsenaultetal.2002

[24],Caspietal.

2005[25]

(DUNEDIN

study)

n:759Birthcohort

NewZealand

Baseline.11years

DIS-C

forpsychotic

symptoms

Everuseinthepast

year

Frequencyof

usein

thepastyear

Usebeforeage15

DISfor

schizophreniform

disorders(DSM-IV

criteria)and

psychotic

symptoms

11years

sex,socioeconomic

status,otherdrug

use,Psychotic

symptomsatbaselin

e

Notstudied

vanOsetal.2002

[26](NEMESIS

study)

n:4045

adultpopulationbased

cohort.

Netherlands

Baseline:Gsectionof

M-CID

Iforpsychotic

symptoms

LsectionofM-CIDI

Anyuse

Frequency:

1week,

daily

SCL-90for

psychotic

symptoms

9ye

ars

A

ttrition:17%

Sex,socio-economic

variables,family

functioning,child

abuse,child

neuroticism,IQ,self

esteem,novelty

seeking,prior

psychoticsymptoms

ormentaldisorders,

otherdrugabuse

Evidenceofa

dose-response

effect

Henquetetal.2005

[29](EDSPstudy)

n:2437adultpopulationbased

cohort

Germany

Baseline:SCL-90Rfor

psychopathological

experience

LsectionofM

-CIDI

Everuse(>5times)

Frequency:

Psychosis_overview of Systematic Reviews_2010

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