Patterns, predictors and impact of substanceuse in early psychosis: a longitudinal study

Addington J, Addington D. Patterns, predictors and impact ofsubstance use in early psychosis: a longitudinal study.

Objective: The purpose was to determine the prevalence of substanceuse and its impact on outcome 3 years after presentation for a first-episode of psychosis.Method: Subjects were 203 consecutive admissions to an earlypsychosis program. Assessments included substance use, positive,negative and depressive symptoms and social functioning. Assessmentsoccurred at baseline, and 1-, 2- and 3-year follow-ups.Results: The prevalence of substance misuse was high with 51% havinga substance use disorder (SUD), 33% with cannabis SUD and 35%with an alcohol SUD. Numbers with an alcohol SUD declinedconsiderably by 1 year and for cannabis SUD by 2 years. Substancemisuse was significantly associated with male gender, young age andage of onset and cannabis misuse with increased positive symptoms.Conclusion: This study confirms the high rates of substance misuse, inparticular cannabis, in first-episode psychosis. It further demonstratesthat these rates can be reduced.

J. Addington1,2, D. Addington2

1Department of Psychiatry, University of Toronto,Toronto, ON and 2Department of Psychiatry, Universityof Calgary, Calgary, AB, Canada

Key words: substances; cannabis; alcohol;schizophrenia; psychosis

Jean Addington, Centre for Addiction and MentalHealth, 250 College Street, Toronto, ON, M5T 1R8,Canada.E-mail: jean_addington@camh.net

Accepted for publication August 23, 2006

Significant outcomes

• More than half of first episode patients present with a comorbid substance use disorder.• The most common substances are alcohol and cannabis.• There is a significant decline in substance use over 2 years.

Limitations

• Detailed data on frequencies of use and quantities are not available.• Assessment of substance use was based on client-report.• This was a naturalistic uncontrolled open study.

Introduction

Reported rates of substance misuse in schizophre-nia and other psychotic disorders are significantlyhigher than those reported for the general popu-lation (1–3). Studies that have examined theprevalence of substance misuse at the first psy-chotic episode suggest a high prevalence of drugand alcohol misuse, in particular cannabis andalcohol amongst individuals newly diagnosed witha psychotic disorder (4–8).

This well-supported comorbidity has raised thequestion of the direction of causality. In a recentreview (9), Verdoux presented evidence from severalprospective studies with population based samplesand suggested that there is a dose–response rela-tionship between exposure to cannabis and the laterrisk of psychosis exposure (10–13). Further, there isevidence, mainly from studies with non-psychoticsamples, of the possibility that cannabis is a riskfactor for psychosis in those who have a vulnerab-ility (14). Further work is clearly needed in this area.

Acta Psychiatr Scand 2007: 115: 304–309All rights reservedDOI: 10.1111/j.1600-0447.2006.00900.x

Copyright � 2006 The AuthorsJournal Compilation � 2006 Blackwell Munksgaard

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However, a third concern of more immediateclinical relevance is whether the use of cannabisand indeed of other substances is a prognosticfactor in the early stages of psychosis. In a range ofstudies, drug misuse, in most cases cannabis, hasbeen associated with younger age of onset (4, 15–18), male gender (4,15,16,18), non-African-Carib-bean ethnicity (4), lack of cognitive deficits (19,20),earlier psychotic relapses (21), increased symptoms(6,22–24) and suicidal behavior (25). Increasedcannabis use has also impacted the longer-termcourse of illness in terms of reduced likelihood ofremission and increased symptoms (6,22).

Aims of the Study

The aim of this present study was to determine theprevalence of substance use and its impact onoutcome over the course of 3 years following thepresentation at a specialized program for firstepisode psychosis.

Material and methods

Subjects

Subjects were 203 (142 men, 61 women) individualswho had completed both baseline and 1 yearfollow-up assessments out of the first 300 patientsadmitted to the Calgary Early Psychosis Program(EPP). These individuals were experiencing theirfirst episode of psychosis and had not receivedmore than 3 months of previous adequate treat-ment (26). Patients were all attending EPP, acomprehensive treatment program, which serves anurban population of 930 000, which most likelyincludes the majority of potential incidence casesand is a first contact for treatment and not a firstadmission to hospital sample (27). On average, ofthose not completing an assessment, 47% weredropouts, 37% had moved away for legitimatereasons and were obtaining treatment elsewhere,

and 16% were attending the program but failed toattend the assessment.The majority of the sample was single (76.6%),

with a mean age of 25 years (SD ¼ 8.38), hadcompleted some high school (30.3%), lived withtheir parents (55.4%), and was Caucasian (68.9%).The majority was admitted to EPP as out-patientsand 33% were admitted as in-patients.Subjects were diagnosed according to DSM- IV

criteria (28), using the Structured Clinical Inter-view for DSM-IV (SCID-I) (29). Diagnoses at1 year were as follows, schizophrenia (n ¼ 142,69.9%), schizophreniform disorder (n ¼ 31,15.3%) schizoaffective disorder (n ¼ 4, 2%), delu-sional disorder (n ¼ 4, 2%), psychotic disorderNOS (n ¼ 15, 7.4%), brief psychotic disorder(n ¼ 5, 2.5%), and substance-induced psychoticdisorder (n ¼ 2, 1%). There was a wide range ofcomorbid substance use disorders (SUD) at base-line and 1 year. These are presented in Table 1.

Measures

Symptoms were assessed with the Positive andNegative Syndrome Scale (PANSS) (30) and theCalgary Depression Scale for Schizophrenia(CDSS) (31). Social functioning was assessed byusing the Quality of Life Scale (QLS) (32) and thePremorbid Adjustment Scale (overall score) wasused to determine premorbid functioning (PAS)(33). The Case Manager Rating Scale for SUD wasused to assess the level of substance use over thepast year (CMRS) (34). Level of use was ranked as:none, mild, moderate, severe, or extremely severe.

Procedures

This study received approval from the local ethicscommittee and all participants signed informedconsent. Raters were experienced research clini-cians who demonstrated good reliability at start upand thereafter every 6 months. Criteria for

Table 1. Frequency of substance use diagnoses (SCID) at baseline and 1 year

Substance diagnosis (abuse or dependence)

Total baseline sample n ¼ 300 Sample who completed baseline and 1 year n ¼ 203

Baseline frequency Percent Baseline frequency Percent 1-year frequency Percent

No substance diagnosis 163 54.3% 98 48.3% 137 67.5%Alcohol 33 11% 33 16.3% 18 8.9%Cannabis 41 13.7% 30 14.8% 24 11.8%Amphetamine 4 1.3% 1 0.5% 1 0.5%Hallucinogens 3 1% 2 1.0% 0 0%Cocaine 0 0% 0 0% 1 0.5%Alcohol and cannabis 31 10.3% 22 10.8% 19 9.4%Alcohol and other drug 3 1% 2 1% 1 0.5%Alcohol, cannabis and other drug 22 7.3% 15 7.4% 2 1.0%Total 300 100% 203 100% 203 100%

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reliability are that the scoring of each item on thePANSS, CDSS and QLS is within one point andthere is at least 80% agreement on total scores andsubscale scores for all measures. Agreement iscalculated as the number of ratings within onepoint divided by the total number of ratings. TheDSM-IV diagnoses were made by using the SCID-Iby JA and DA. Inter-rater reliability was deter-mined by 100% agreement on the diagnosis and atleast 80% agreement for symptom presence. Ourraters met well-established gold standards at eachreliability training. Kappas and ICCs are notavailable.Assessments were conducted at baseline, 12, 24

and 36 months. The SCID was administered onlyat baseline and 1 year. All other measures wereadministered at all four assessment points. Dataare available for 203 patients at baseline and at12 months, 159 at 24 months and 143 at36 months. This is part of a longitudinal evalua-tion of EPP.

Results

We compared those who dropped out at differenttime points on the CMRS, CDSS, QLS, andPANSS ratings completed at baseline, 1 year and2 years. We compared (i) the 97 who dropped outat 1 year with the 203 who remained at 1 year onbaseline data; (ii) the 44 who dropped out at2 years with the 159 who remained at 2 years onbaseline and 1 year data; (iii) the 16 who droppedout at 3 years with the 143 who remained at3 years on baseline, 1- and 2-year data; (iv) the 143who did all assessments, the 1-year dropouts, the 2-year dropouts and the 3-year dropouts on demo-graphics. On all these comparisons, there were nodifferences with two exceptions. The only signifi-cant differences in all those comparisons is thatthose who dropped out at 2 years had significantlyhigher negative symptoms at 1 year than those whocompleted the 2-year assessment (16.2 vs. 14.00,t ¼ 2.07, P ¼ 0.02) and those who dropped out at3 years had significantly higher negative symptomsat 2 years than those who completed the 2 yearassessment (15.4 vs. 14.5, t ¼ 2.10, P ¼ 0.04).Table 1 describes the percentages meeting var-

ious substance diagnoses. We have included thepercentages for the full sample of all consecutiveadmissions to EPP at baseline as well as thediagnoses for those who remained. Using a chi-square to determine if there were diagnosticdifferences between the 203 who had a diagnosisat 1 year compared with the 97 who dropped out.The analysis was significant (v2 ¼ 24.06, Pexact ¼ 0.001). The most notable differences were

that 48% of those who remained were non-userswhereas 67% of the dropouts were non-users. Thiswas most likely accounted for by the fact that ofthose who dropped out 0% used alcohol onlywhereas 16% of the 203 who remained usedalcohol only. These results suggest that if thereare significant differences between those whodropped out and those who remained non-usersare more likely to drop out and those who misusealcohol are more likely to remain.At admission, 105 subjects (51.7%) met DSM-

IV criteria for one or more current substance abuseor dependence diagnoses, the most common diag-noses being alcohol (35.5%) and cannabis (33%).A few subjects used hallucinogens and misuse ofcocaine, stimulants, and opioids was rare. By1 year only 66 (32.5%) had an SUD diagnosis.Using McNemar’s test, these changes were signi-ficant (P < 0.0001).Ratings on the CMRS of none or mild use were

equivalent to having no diagnosis and moderate toextremely severe were equivalent to having adiagnosis of abuse or dependence. Using theCMRS ratings subjects were categorized as abuseor no abuse for alcohol, cannabis and all otherdrugs combined. From baseline to 3 years (baselineto 1 year, 2 years and 3 years), percentages withalcohol misuse changed from 35%-20%-18%-18%, percentages with cannabis misuse changedfrom 33%-16%-7%-7% and for other drug misusepercentages changed from 10%-2%-2%-2%.Using Cochran Q-test for related samples, thesechanges were significant (Q ¼ 18.23, 71.44, 25.92;P < 0.001). Using McNemar’s test, significantchanges occurred between baseline and 1 year foralcohol (v2 ¼ 15.56, P < 0.0001) and for otherdrugs (v2 ¼ 17.42, P < 0.001) and for cannabisbetween baseline and 1 year (v2 ¼ 25.4,P < 0.001) and between one and 2-year follow-ups (binomial test due to small numbers;P < 0.01). The McNemar’s tests indicated thatthere was no statistically significant changedetected between 1 and 2 years, or 2 and 3 years,for alcohol and for other drugs and no change forcannabis between 2 and 3 years.Spearman’s correlations were used to compare

ratings for alcohol and cannabis on DSM-IV andon the CMRS. At baseline for alcohol q ¼ 0.83(P < 0.001) and for cannabis q ¼ 0.88(P < 0.001). At 1 year for alcohol q ¼ 0.65 (P <0.001) and for cannabis q ¼ 0.66 (P < 0.001).This suggests concordance between the twomeasures of substance misuse.Because of the very small number of subjects

misusing hallucinogens, cocaine, stimulants, opi-oids, and sedatives over time, only alcohol and

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cannabis were considered in the following assess-ments. Based on the CMRS ratings, a series ofindependent t-tests and chi-squared tests wereconducted to compare those who misused cannabisand alcohol at each of the follow-ups to those whodid not in order to determine the possible impact ofsubstances on outcome. There were gender differ-ences for both alcohol and cannabis with menusing more than females at each assessment(v2ranged from 20.95 at baseline (P < 0.001) to3.56 at year three (P ¼ 0.04)). There were consis-tent associations with being younger and youngage of onset for both alcohol and cannabis at eachtime period. For alcohol t-values ranged from 2.07to 2.93 (P ¼ 0.04). For cannabis, t-values rangedfrom 3.8 to 5.04 (P < 0.001). There were nodifferences in premorbid functioning for those whoused and those who did not.Results of t-tests using the CMRS demonstrated

that at each of the follow-up assessments therewere no differences between those who did and didnot use alcohol in positive or negative symptoms,depression, or quality of life. These results arepresented in Table 2.However, those who used cannabis as rated on

the CMRS generally had higher ratings on positivesymptoms. We then in a subsequent analysisexamined only those 143 subjects who had com-

pleted assessments at each point in time and foundsimilar results. The one difference in this analyseswas that at 2 years the difference in positivesymptoms between the 125 (mean ¼ 11.13,SD ¼ 4.34) who used cannabis and the 10(mean ¼ 12.90, SD ¼ 4.38) who did not was notsignificant.Based on the CMRS ratings, using an ancova, we

compared those who misused cannabis and thosewho did not on positive symptoms at 1, 2 and3 years, depression at 1 year and QLS at 2 yearsand controlled for age of onset, age and gender asthese were also associated with cannabis misuse.After controlling for age, age of onset and gender,the groups still differed in that those misusingcannabis had significantly higher levels of positivesymptoms at 1 year [F(4, 195) ¼ 4.01, P ¼ 0.04],at 2 years [F(4, 154 ¼ 3.77 P ¼ 0.047)] and at3 years [F(4, 135) ¼ 4.43 (P ¼ 0.04)]. After con-trolling for age, age of onset and gender, thegroups still differed in that that those usingcannabis had increased levels of depression [F(4,154) ¼ 10.60, P ¼ 0.001)]. Thus, after adjustingfor the effects of age, age of onset and gender, thedifferences between the cannabis misuse groupswere non-significant on depression, negative symp-toms and quality of life except for depression at1 year.

Table 2. t-Tests comparing those using cannabis and alcohol� on outcome measures (total sample)

Substance(time)

Non-usersvs. users

Calgary DepressionScale for schizophrenia mean (SD)

Positive and Negative SyndromeScale (PANSS) positive mean (SD)

PANSS negativemean (SD)

Quality of LifeScale mean (SD)

Alcohol (baseline) 130 4.25 (4.18) 16.48 (4.57) 15.26 (6.41) 57.83 (19.92)71 3.86 (3.04) 17.55 (4.80) 15.23 (6.27) 52.49 (20.66)

t-Value 0.77 )1.55 0.41 1.78Alcohol (1-year) 155 2.47 (3.39) 11.67 (4.63) 15.62 (5.89) 68.03 (22.02)

40 2.62 (3.34) 12.10 (4.58) 16.36 (6.13) 69.40 (23.20)t-Value )0.24 )0.52 )0.70 )0.35Alcohol (2 years) 129 1.87 (2.79) 11.24 (4.41) 15.30 (6.00) 71.98 (20.62)

29 2.86 (3.46) 12.21 (5.01) 15.28 (6.14) 68.18 (27.68)t-Value )1.65 )1.04 0.02 0.83Alcohol (3 years) 117 2.16 (3.31) 10.67 (4.09) 15.08 (6.27) 73.27 (22.32)

25 1.64 (2.04) 11.84 (6.47) 15.08 (6.47) 70.96 (22.56)t-Value 0.76 )1.16 )0.002 0.47Cannabis (baseline) 130 4.20 (4.18) 16.56 (4.45) 15.66 (6.29) 56.09 (19.80)

71 3.96 (3.04) 17.41 (5.03) 14.51 (6.42) 55.65 (21.33)t-Value 0.43 )1.23 1.23 0.15Cannabis (1 year) 163 2.17 (3.16) 11.40 (4.47) 15.82 (6.07) 68.55 (22.52)

31 4.23 (3.94) 13.65 (4.97) 15.52 (5.22) 67.03 (20.79)t-Value )3.19** )2.52* 0.26 0.34Cannabis (2 years) 146 1.93 (2.90) 11.15 (4.32) 15.24 (6.08) 72.40 (22.06)

12 3.50 (3.21) 14.67 (5.76) 16.00 (5.15) 56.82 (15.68)t-Value )1.79 )2.64** )0.42 2.30*Cannabis (3 years) 132 1.93 (2.99) 10.64 (4.48) 14.86 (6.33) 73.66 (22.03)

10 3.90 (4.36) 13.90 (5.30) 17.90 (5.11) 61.33 (24.36)t-Value )1.94 )2.19* )1.48 1.61

*P < 0.05, **P < 0.01.�As rated on the CMRS.

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Discussion

In this first episode sample, more than half (52%)of the individuals presenting for treatment have acomorbid diagnosis of SUD. These rates arecomparable with those reported elsewhere(6,22,24). This is significantly higher than theprevalence in the Canadian general population(35). Considering that substance misuse is morelikely to be under rather than over reported (36),this is clearly a major health issue. Cannabis andalcohol are the predominant substances of abusewith 33% having a cannabis SUD and 35% analcohol SUD. Typical of other population studies,the use of cocaine, other stimulants, opioids, andsedatives were rare (37). Based on both DSMdiagnoses and CMRS ratings, there was a signifi-cant decline over the first year in numbers of thosewith an alcohol SUD and a SUD for other drugs.For cannabis, the decline continued such that by2 years only 7% had a SUD.As in other studies, alcohol and cannabis misuse

across the 3 years was significantly associated withbeing male, younger age and younger age at onset.There were no differences between those whomisused and those who did not on any of the socialor symptom outcome measures. The one exceptionwas that those who used cannabis had consistentlyhigher levels of positive symptoms at all assessmentpoints and higher levels of depression at 1 year. Asthe impact of cannabis was limited to positivesymptoms, this suggests that cannabis may have itspopulation impact by moving an otherwise vulner-able population from an �at-risk� state to psychosis.Furthermore, once an individual has developed apsychotic illness, using cannabis may have a negat-ive impact on outcome particularly with respect topositive symptoms.In EPP, we have made every attempt to follow

recommendations to address substance use as anintegral part our treatment (38–42). For allpatients, we address substance use at all stages ofthe program, which includes their work with thecase manager, psychiatrist, in the group programand in work with families (43–44). These firstepisode patients with a comorbid SUD are knownto be a difficult group to treat and these observedreductions give some hope that some success maybe possible.The strength of this study is that it has a large

sample, an incidence cohort from a geographicallycircumscribed area, comprehensive diagnoses andclinical assessments, was a first contact for treat-ment and not a first admission to hospital sampleand had a 3-year follow-up. There are severallimitations. Firstly, age and demographic-matched

general population data are not available althoughsome of the gender differences in risk factors foralcohol and cannabis would be the same for thegeneral population. Generally, the use of controlsis difficult in substance use research as controlscould be non-psychotic substance users or thosewith psychosis who do not use. More detailed dataon the months and frequencies of substance use arenot available. We do not have measures of quan-tities of drugs used, although that in itself is adifficult process. Furthermore, assessment of sub-stance use was based on client-report and was notcorroborated with biological measures. Again bio-logical measures may be intrusive, may limit thesample and for some substances are only validwithin a few days. Finally, although we report asignificant reduction over time this was a natural-istic uncontrolled open study and thus it is difficultto accurately determine the reasons for the reduc-tions. This does mean that it is not possible todetermine the extent to which these results can begeneralized to other contexts. Methodologicaldifficulties abound in research with substanceusing samples particularly with respect to sampleswhere dropouts are all too common and wheremeasurement is difficult. Further work is requiredto examine the impact of intervention on comorbidsubstance misuse in early psychosis and to explorefurther ways to help those who despite potentiallyeffective treatment continue to misuse substances.

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