Soc Psychiatry Psychiatr Epidemiol DOI 10.1007/s00127-013-0786-8
ORIGINAL PAPER
Race, ethnicity, and the duration of untreated psychosis: a systematic review Kelly K. Anderson • Nina Flora • Suzanne Archie Craig Morgan • Kwame McKenzie
•
Received: 1 February 2013 / Accepted: 23 October 2013 Springer-Verlag Berlin Heidelberg 2013
Abstract Purpose An extended duration of untreated psychosis (DUP) is associated with poor outcome in first-episode psychosis (FEP). Some have suggested that minority ethnic groups have longer treatment delays, and this could lead to worse outcomes. We systematically reviewed the literature on racial and ethnic differences in DUP in patients with FEP. Methods We searched electronic databases and conducted forward and backward tracking to identify studies that had compared DUP for people with FEP from different racial or ethnic groups. Results We identified ten papers that reported on the association between race or ethnicity and DUP. Overall, these studies did not find evidence of differences between groups; however, three of ten studies suggested that Black patients generally, and Black-African patients specifically, may have a shorter DUP relative to White patients. There
K. K. Anderson (&) N. Flora K. McKenzie Social and Epidemiological Research, Centre for Addiction and Mental Health (CAMH), 455 Spadina Avenue, Suite 300, Toronto, ON M5S 2G8, Canada e-mail: [email protected] S. Archie Department of Psychiatry and Behavioural Neurosciences, McMaster University, 25 Charlton Avenue East, Suite 703, Hamilton, ON L8N 1Y2, Canada C. Morgan Section of Social Psychiatry, Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, UK K. McKenzie Department of Psychiatry, University of Toronto, 455 Spadina Avenue, Suite 300, Toronto, ON M5S 2G8, Canada
were methodological limitations in most studies with respect to ethnicity classification, sample size, and adjustment for potential confounders. Conclusion Racial and ethnic differences in DUP were rarely found. This could reflect that DUP does not differ between groups, or may reflect the methodological limitations of prior research. Studies that are designed and powered to examine these differences in treatment delay are needed to determine whether there are differences in DUP for minority groups. Keywords First-episode psychosis Duration of untreated psychosis Ethnicity Race Treatment delay Early intervention
Background An extended period from the onset of psychotic symptoms to the initiation of treatment is associated with poor outcomes in first-episode psychosis (FEP), as measured by remission of symptoms, levels of subsequent functioning, and quality of life [1–3]. This period has been termed the duration of untreated psychosis (DUP), and is considered to be a potentially modifiable predictor of prognosis in FEP and a target for secondary prevention. A comprehensive understanding of the factors that determine and moderate DUP could help to inform the development of more effective services. A review by Compton and Broussard [4] discusses the myriad of factors that may operate at different levels to influence DUP, and they classify these factors as demographic, pre-morbid and onset-related, illness-related, family-level, societal, and health services/system-level factors. The evidence base for many of the potential determinants of DUP is scant or inconclusive.
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The race and ethnicity of a person are examples of demographic factors that have the potential to impact the DUP. There is a considerable literature on the utility of race and ethnicity as concepts [5, 6]. Race typically refers to physical features, such as skin color or hair texture, which may reflect a person’s ancestry, and examples of categories that are commonly used to describe race include White, Black, or Asian. Ethnicity is a complex term used to describe perceived social groupings based on a sense of belonging, place of origin, and other factors such as language, religion, and sometimes race [7]. For example, descriptors that might be used to classify ethnicity include Black-Caribbean, Black-African, White-European, or White-Canadian. Both racial and ethnic categorizations have been used in comparative research between minority and majority groups. Racial and ethnic groupings are not mutually exclusive, and in the social world they may map onto each other. They both may have an impact on DUP because as variables they capture shared socio-cultural factors that have an effect on access to care. However, because they are different concepts there may be differences in the mechanism through which they are associated with DUP. Because of this, we have investigated both categories and we will distinguish between the concepts where it is important and relevant to do so. Numerous barriers to mental health care have been reported for different ethnic and racial groups, and the reasons for these are numerous and varied. Different groups may hold different beliefs about the cause of psychotic symptoms, their perceived severity, and the most appropriate course of action [8, 9]. Language barriers or a lack of information regarding the availability of services and how to access them may influence an individual’s decision to seek help [10]. There may be differences in the degree or type of stigma in different communities [11]. Finally, there may be differences in the accessibility of services to different groups because of the cost, the location of services, the use of models that are not considered appropriate by some groups, or the perception that services are not culturally competent or trustworthy [12]. As a result of these barriers to care, some groups may take alternative routes to accessing services, and differences in pathways to care for psychotic disorders have been documented between groups [13]. The majority of prior research in this area has focused on people of African or Caribbean origin in high-income countries, and has reported that these groups were more likely than the majority ethnic group to access care through involuntary hospitalizations and the criminal justice system, and less likely to have general practitioner (GP) involvement on the pathway to care [14]. Both barriers to care and differences in pathways to care could lead to differences in DUP. It is often assumed that
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these barriers to care result in minority groups with FEP having a longer DUP [15]. However, given the multi-faceted nature of the pathways to care [16], it is not immediately clear what the impact of race or ethnicity will be. There is currently no consensus on whether or how race and ethnicity have an impact on DUP. Despite the large body of research on various factors associated with DUP [4], there has been no systematic review or meta-analysis of the social determinants of DUP, with the exception of gender [17]. The aim of this study was to systematically review the literature on ethnic and racial differences in DUP among patients with first-episode psychosis. Because DUP is affected by the availability and accessibility of services within a given health system, and there are differences in service provision between low-, middle-, and high-income countries, we restricted this review to research conducted in high-income countries to help ensure comparability across the studies.
Methods Systematic review We conducted an electronic search of the MEDLINE (1950–2012), HealthStar (1966–2012), EMBASE (1980–2012), and PsycINFO (1967–2012) databases using the OvidSP platform, and we also searched Web of Knowledge. The MEDLINE and HealthStar search terms are presented in ‘‘Appendix’’, and this strategy was adapted for EMBASE and PsycINFO using analogous terms relevant to these databases. The Web of Knowledge was searched using key words. The search strategy was developed in consultation with a librarian. We obtained further studies by manually searching personal files and the bibliographies of all relevant studies and review articles. We performed forward citation searching using Web of Knowledge to locate all articles that had cited the included studies. When abstracts or unpublished studies were retrieved in our search, we contacted the corresponding authors to determine whether the work had subsequently been published in a peer-reviewed journal. We regularly updated all segments of the literature search, with the final update in September 2012. Each study was reviewed for the following inclusion criteria: (a) the study measured DUP among individuals with FEP; (b) the article reported DUP by race or ethnic group, or used race or ethnicity as a covariate in the analyses; (c) the study was conducted in a high-income country [18]; (d) the findings were published in a peerreviewed journal. We did not impose any restrictions with respect to date or language of publication.
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For all included papers, two independent reviewers extracted data on key elements of study design, the definition and measurement of DUP, the methods used for assigning race or ethnicity, and measures of the central tendency and dispersion of DUP by racial or ethnic group. All papers were assigned a quality assessment score using a rating scale based on a tool used in previously published systematic reviews on ethnic differences in pathways to care (Table 1) [13, 19]. Discrepancies between the reviewers were resolved by consensus. Where important methodological details were missing from the paper, such as the definition of DUP or the methods used for assigning race or ethnicity, we consulted other studies from the same research group and patient sample, where available, to obtain the missing information. However, the quality assessment ratings were done solely based on information contained within the included paper. Authors were contacted for further information or clarification when the data were aggregated or unclear.
Table 1 Rating system for methodological quality (adapted from Bhui et al. [13] and Sass et al. [19]) Legend
Adequacy of sample size -
No power calculation or inadequate sample to detect racial or ethnic differences
?
Authors demonstrate that the sample was powered to detect racial or ethnic differences
Definition of the first episode of psychosis -
Not described
•
Based on first hospitalization
?
Based on duration of antipsychotic treatment or first presentation to a clinical setting
Adjustment for confounding variables -
None
• ?
Age and/or gender Other co-morbidities or risk factors for the outcome of interesta (see below)
Quality of race or ethnicity measurement
Meta-analysis For all studies identified in the systematic review, we contacted the corresponding author to obtain log-transformed means and standard deviations for DUP. These were needed due to the positively skewed distribution of DUP, and studies were excluded from the meta-analysis if the authors were unable to provide these data. For all studies for which we had log-transformed data, we calculated the standardized mean difference (SMD) with 95 % confidence intervals (CI) using Cohen’s d for each racial or ethnic subgroup, relative to the majority racial or ethnic group. We meta-analyzed these effect estimates using the metan procedure in Stata 11.0. There was an insufficient number of papers to compare most of the racial or ethnic variables. Therefore, we restricted the analysis to data comparing the two groups most commonly investigated, specifically a Black grouping, made up of African or Caribbean origin populations, and an Asian grouping. These were compared to a White grouping representing the majority racial group. One of the studies presented data separately for Black-African and BlackCaribbean patients [15], and another divided the samples by first-generation Black-African and Black-Caribbean groups and second-generation Black-British groups [20]; therefore, we pooled these estimates by calculating weighted means and standard deviations to allow comparability with other studies. Two studies also divided the White sample by native-born individuals and immigrants [20, 21], and these groups were also pooled for the metaanalysis. There were insufficient data available for a metaanalysis of estimates for other racial groups, or for disaggregated racial or ethnic groups.
Description
-
Not reported
•
Third party report (e.g., staff categorization, name-based method)
?
Self-reported race or ethnicity
Use of race or ethnicity in the analysis •
Ethnic groups dichotomized (e.g., white vs. others) Reasonable groupings by race
?
All analyses done on specific ethnic groups without amalgamation
Definition of DUP -
Definition of DUP unclear (e.g., no description of start/end point)
?
Clear definition of DUP
Measurement of DUP ?
Not described/non-systematic method used for dating DUP Use of a standardized measurement tool for dating DUP
Source of data on DUP -
Not described/chart review or third party report only
•
Patient report only
?
Patient report corroborated with chart review or third party information
-, Criteria not met; •, Criteria partially met; ?, Criteria satisfied a
Risk factors include socio-economic factors (SES, employment, household size, marital status); Co-morbidities include drug and alcohol use, coexisting psychiatric conditions, violence to others
Statistical heterogeneity was assessed using the I2 statistic, with values of 25, 50, and 75 % suggestive of low, moderate, and high heterogeneity, respectively [22]. There was a high likelihood of methodological and contextual heterogeneity due to the different definitions used for DUP, race and ethnicity, as well as the different health service contexts of each of the studies; therefore, we opted to use a random effects model to compute a summary effect size
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[23]. The source of the heterogeneity was explored using a meta-regression model [24]. The study characteristics that were used as predictor variables in the model included country of origin, as well as quality assessment ratings for the method of defining the first episode of psychosis, the measurement of race or ethnicity, and the tool used for measuring and defining the DUP (Table 1).
trial, which is substantially different from the other studies which measured the time to antipsychotic prescription or first contact with services. In total, ten studies met the inclusion criteria for our review, and the authors of seven of these studies provided the required data for inclusion in the meta-analysis (Fig. 1). Study characteristics
Results The electronic database search retrieved 527 studies, of which 38 were potentially relevant for this review. We identified an additional 12 papers from personal files and the manual search, for a total of 50 full-text articles reviewed for inclusion. We excluded 40 studies for the following reasons (not mutually exclusive): not a FEP population (n = 5); review article, case report, or research letter (n = 5); DUP was not measured (n = 9); race and ethnicity were not measured (n = 6); no comparison group (n = 10); study was conducted in a low- or middle-income country (n = 4); the study reported duplicate data from samples that were already included in the review (n = 7). As a post hoc exclusion, we removed a multi-site clinical trial from the review [25] because the endpoint for DUP for a large proportion of patients was entry into the clinical
Fig. 1 Flow chart of the search strategy and exclusion process for the systematic review
Medline and HealthStar Search (n = 205)
The characteristics and findings of included studies are summarized in Tables 2 and 3, and the quality assessment ratings for study methodology are presented in Table 4. The studies primarily used observational designs and were conducted in Canada, England, New Zealand, Singapore, or the USA. The size of the study samples varied substantially, ranging from 55 to 535 participants (median across studies = 256). Approximately, half of the studies (n = 5) restricted their samples to non-affective psychoses. The first episode of psychosis was defined based on the use of antipsychotic medication in four studies, first contact with services in three studies, and first inpatient admission in three studies (Table 2). Most studies (n = 6) used a standardized instrument for measuring DUP, and nearly all (n = 9) used multiple data sources to corroborate information. The studies used similar starting points for measuring DUP, specifically the
EMBASE Search (n = 225)
PsycINFO Search (n = 86)
Web of Knowledge Search (n = 233)
Unique citations screened for relevancy (n = 527) Forward and backward citation searching (n = 8)
Studies excluded (n = 489)
Full-text version retrieved for more detailed evaluation (n = 50) Review of personal files (n = 4)
Studies meeting the inclusion criteria (n = 10)
Studies excluded from review, with reasons (n = 40)* -
Not a first-episode population (n=5) Review article/case report/letter (n=5) DUP not measured (n=9) No ethnicity (n=6) No comparison group (n=10) Low-income country (n=4) Clinical trial (n=1) Duplicate data (n=7)
Studies excluded from metaanalysis (n = 3) - Required data not available from authors (n=3)
Data available for meta-analysis (n = 7)
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276 (with DUP)
van der Ven et al. [21]
55
248
535 (with DUP)
414
Brunet et al. [31]
Drake [28]
Ghali et al. 2013 [20]
Morgan et al. 2006 [15]
England
193 (with DUP)
n
Archie et al. [27]
Canada
Study
Cases from secondary or tertiary services in catchment area
EI services across eight sites
Day- and inpatient-unit admissions from defined catchment area
Mental health services
EI program
EI programs across four sites
Source of sample
Patient interview Family interview
Medical records
Collateral history
Medical records
Patient interview
Clinician interview
Family interview
Patient interview
Medical records
Family interview
Patient interview
Medical records
Clinician interviewa
Family interviewa
Patient interviewa
Medical recordsa
Clinician interview
Family interview
Patient interview
Medical records
Source of data
Table 2 Characteristics of studies included in the systematic review (n = 10)
ICD-10 (SCAN)
Not described
DSM-IV (clinical diagnosis)
ICD-10 (WHO Checklist)
DSM-IV (SCID)
DSM-IV (SCID)
Diagnostic criteria (tool)
73
Not described
100
100
74
100
Non-affective (%)
Patients presenting to services for the first time with an ICD10 diagnosis of psychosisd
First presentation to psychiatric services for affective or nonaffective psychosis
First or second admission (within 2 years of first admission) to day- or inpatient-unit for psychosisc
New referrals to mental health services for a psychotic disorder
Psychotic symptoms in a patient who had received less than 1 month of prior antipsychotic treatment
Psychotic symptoms in a patient who had received less than 1 month of prior antipsychotic treatment
Definition of first-episode psychosis
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103
Haas et al. [29]
Inpatient admission
Three inpatient psychiatric units
EI program
EI program
Source of sample
Clinician interview
Family interview
Patient interview
Medical records
Family interview
Patient interview
Medical records
Family interview
Patient interview
Medical records
Family interviewe
Patient interviewe
Source of data
DSM-III-R (SCID)
DSM-IV (SCID)
DSM-IV (SCID)
DSM-IV (clinical Diagnosis)
Diagnostic criteria (tool)
100
100
90
64
Non-affective (%)
Diagnosis of schizophreniaspectrum psychosis with no prior history of admission for a psychotic disorderf
Psychotic symptoms in patients with no prior hospitalization for psychosis and less than 3 months of antipsychotic treatment
First presentation of psychosis with less than 1 week of prior antipsychotic treatment
First presentation of psychosis with less than 12 weeks of prior antipsychotic treatment
Definition of first-episode psychosis
f
e
d
c
b
As per prior paper [50]
As per subsequent paper [49]
As per subsequent paper [48]
As per prior paper [47]
As per prior paper [46]
DUP duration of untreated psychosis, EI early intervention, DSM diagnostic and statistical menu of mental disorders, SCID structured clinical interview for DSM, ICD International Classification of Diseases; WHO World Health Organization; SCAN schedules for clinical assessment in neuropsychiatry a As per prior paper [39]
264 (from author)
334
182
n
Compton et al. [32]
USA
Pek et al. [26]
Singapore
Turner et al. [30]
New Zealand
Study
Table 2 continued
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Onset of delusions and hallucinations
One symptom from the positive scale of the PANSS C 4
NOS
Ghali et al. [20]
(2) Date of referral to early intervention services
One symptom from the positive scale of the PANSS C 4, or a cluster of symptoms totaling C 7, for longer than 2 weeks
Drake [28]
England Brunet et al. [31]
Onset of psychotic symptomsa
Onset of psychosis
Canada Archie et al. [27]
van der Ven et al. [21]
Start point for DUP
Study
(1) Initiation of regular antipsychotic treatment with adherence of at least 75 % for 1 month (used in meta-analysis) Staff assigned
Not described
Antipsychotic treatment at recommended dosage levels for 1 month, or leading to symptom reduction
Initiation of antipsychotic treatmenta
Earlier of date of initiation of antipsychotic medication for at least 1 month, or date of entry to EI services
End point for DUP
White-British
Ad-Hoc Algorithm
Pathways Encounter Form
CORS
CORS
DUP tool
49 84 126 21
16 White-other Black-British Black-Caribbean
19 13
African-Caribbeanb Other b
Self-Reportb
134
3 26 4 216
Black South Asian Mixed Whiteb
36 25 17 21 35
African and Caribbeanb Asianb Central/South Americab Middle East/North Africanb European/North Americanb
21
30 25 20 142
Blackb Asianb Otherb White non-migrantsb
White
118
n
10 14 8
9 10
12
N/A
17 22 11 25 18
31 29 20 15
22
Median
DUP (weeks)
Whiteb
Race/ethnicity categories
Not Described
Staff assigned based on place of origin
Self-report
Race/ethnicity measurement
Table 3 Findings on duration of untreated psychosis and racial/ethnic group for studies included in the systematic review (n = 10)
28 26 34
6–28 6–40
5–36
N/A
5–34 10–56 3–75 8–66 4–41
3–57 7–63 3–66 6–52
3–52
IQR
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Onset of psychotic symptoms
Onset of positive psychotic symptoms
Onset of delusions, hallucinations, thought disorder, or disorganized behavior
One positive scale symptom on the PANSS C 4
Presence of positive psychotic symptoms for at least 1 week
Start point for DUP
First administration of antipsychotic medication
First hospital admission
Establishment of definitive diagnosis and treatment
Initiation of antipsychotic treatment
Contact with secondary mental health services
End point for DUP
Not Described
CORS SOS
Not described
Not described
PPHS
DUP tool
Not described
Not described
Not described
Not described
Self-report staff assigned
Race/ethnicity measurement
21 243 68
24 4 4 3
Blackb White
Black Asian Hispanic Other
64 18 7
Malay Indian Others Whiteb
245
24
Aboriginal (Maori)b Chinese
135
129 68
African-Caribbeanb Black-Africanb Non-Aboriginalb
110 60 217
n
31 N/A
20
N/A
9
4
12 8
8 9 8
Median
DUP (weeks)
Black-African South Asian White-Britishb
Race/ethnicity categories
7–119 N/A
3–119
N/A
2–35
1–17
4–77 1–21
22 23 2–39
IQR
N/A Data not available, DUP duration of untreated psychosis, IQR interquartile range, EI early intervention, CORS circumstances of onset or relapse schedule, PANSS Positive and Negative Syndrome Scale, NOS Nottingham Onset Schedule, PPHS Psychiatric and Personal History Schedule, SOS Symptom Onset in Schizophrenia Inventory a As per prior paper [39] b Data obtained from corresponding author
Haas et al. [29]
USA Compton et al. [32]
Singapore Pek et al. [26]
New Zealand Turner et al. [30]
Morgan et al. [15]
Study
Table 3 continued
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Soc Psychiatry Psychiatr Epidemiol Table 4 Quality assessment ratings for studies included in the systematic review (n = 10)
Archie et al. [27]
Adequacy of sample size
Definition of FEP
Adjustment for confounding
Race/ethnicity measurement
Race/ethnicity categories
Definition of DUP
Measurement of DUP
DUP data source
-
?
-
?
•
?
?
?
Brunet et al. [31]
-
?
-
-
•
?
?
?
Compton et al. [32]
-
?
-
-
•
?
?
?
Drake [28]
-
-
-
-
•
-
-
?
Ghali et al. [20]
-
?
?
•
?
?
?
?
Haas et al. [29]
-
-
-
-
•
?
-
?
Morgan et al. [15] Pek et al. [26]
-
?
? -
? -
? ?
? ?
? -
? ?
Turner et al. [30]
-
?
-
-
-
?
-
-
van der Ven et al. [21]
-
?
-
•
•
-
?
?
Ratings are based solely on the information contained within the included article. See Table 1 for scoring criteria -, Criteria not met; •, Criteria partially met; ?, Criteria satisfied
onset of positive psychotic symptoms. However, the endpoints for DUP varied across the studies, with the majority (n = 7) using the initiation of adequate antipsychotic treatment as the end of DUP (Table 3). One study measured two different end-points for DUP, specifically the initiation of antipsychotic treatment and entry into early intervention services, to assess the impact of this definition on observed estimates [20]. Few studies (n = 5) reported how race or ethnicity was measured, and among those who did, three used a measure involving self-report. Only three studies performed analyses on specific ethnic groups without amalgamation by race [15, 20, 26], and two distinguished between the first- and second-generation immigrant populations of African, Caribbean, or European origin [20, 21]. The classifications of race and ethnicity that were used in each of the studies are shown in Table 3. None of the included studies met all of our criteria for methodological quality (Table 4). The most common problems across the studies were as follows: not using a self-report measure for race or ethnicity, or not describing how it was measured (n = 8); lumping different ethnic groups together by race (n = 7); and lack of adjustment for potential confounding (n = 8). None of the studies demonstrated that the sample size was adequate for detecting racial or ethnic differences in DUP (Table 4). Racial and ethnic differences in DUP Only two studies included in our review explicitly stated that the primary objective was to examine racial or ethnic differences in DUP [15, 20]. The objective of the remaining studies was to look at differences between groups in symptomatology [21] or pathways to care [27], to examine other determinants of DUP [26], to look at the association
between DUP and clinical outcomes [28, 29], or to describe pathways to care generally [30]. The two remaining studies did not present data on DUP for different groups, but rather used these variables as a covariate when examining other determinants of the DUP [31, 32]. Given that most studies were not designed to examine racial or differences in DUP, it is not surprising that none of the studies demonstrated that they had achieved an adequate sample size to achieve this objective. Only three studies found evidence of racial or ethnic differences in DUP. Haas and colleagues dichotomized DUP and found that a greater proportion of Black-American patients had a DUP of less than 1 year, whereas a greater proportion of Asian-American patients had a delay of 1 year or longer. There were no differences observed for White, Hispanic, or Other racial groups [29]. Morgan and colleagues [15] found that patients of Black-African origin had a significantly shorter DUP compared with both WhiteBritish and Black-Caribbean patients. Similarly, Ghali and colleagues [20] found that White-British patients had a significantly longer DUP when compared with BlackAfrican patients, but the differences for Black-Caribbean patients did not reach statistical significance, possibly owing to the much smaller sample size. The second-generation immigrant Black group, and the first-generation immigrant White group, also had a shorter DUP than the White-British group when entry into early intervention services was used as the endpoint, but not when the initiation of antipsychotic medication was the endpoint for DUP [20]. In contrast to Haas and colleagues, Ghali and colleagues [20] found that patients of South Asian origin had a shorter DUP, compared with the White-British group. Interestingly, some of these differences in DUP between the ethnic groups were attenuated once differences in the pathway to care were accounted for. The remaining studies
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Soc Psychiatry Psychiatr Epidemiol % Study
Year
Country
SMD (95% CI)
Weight
Archie et al.
2010
Canada
0.23 (-0.17, 0.63)
12.26
Drake et al.
2000
England
-0.12 (-0.59, 0.35)
9.81
Ghali et al.
2013
England
-0.22 (-0.40, -0.04)
27.11
Morgan et al.
2006
England
0.08 (-0.12, 0.27)
26.02
van der Ven et al.
2012
Canada
-0.02 (-0.38, 0.34)
14.26
Compton et al.
2008
United States
0.30 (-0.14, 0.75)
10.55
0.01 (-0.16, 0.18)
100.00
Black vs. White
Subtotal (I-squared = 46.3%, p = 0.097) . Asian vs. White Archie et al.
2010
Canada
0.26 (-0.18, 0.69)
30.18
Ghali et al.
2013
England
-0.32 (-0.60, -0.03)
38.87
van der Ven et al.
2012
Canada
0.14 (-0.28, 0.56)
30.95
-0.00 (-0.38, 0.37)
100.00
Subtotal (I-squared = 66.6%, p = 0.050) . NOTE: Weights are from random effects analysis
-1
0
Shorter DUP
1
Longer DUP
Fig. 2 Meta-analysis of the log-transformed standardized mean difference (SMD) in duration of untreated psychosis for Black and Asian racial groups relative to White
did not find a statistically significant association between race and DUP [21, 26–28, 30–32]. Meta-analysis Our meta-analysis computing an overall effect of Black and Asian groups relative to White did not show evidence of differences in DUP between these groups (Fig. 2). The pooled SMD in DUP for Black patients was 0.01 (95 % CI = -0.16, 0.18). The pooled SMD in DUP was 0.00 (95 % CI = -0.38, 0.37) for Asian patients. There was evidence of moderate heterogeneity in these data (Black I2 = 46.3 %; Asian I2 = 66.6 %), and the source of this was explored using meta-regression techniques; however, none of the study-level variables included in our models was a significant source of heterogeneity (data not shown).
Discussion Main findings Our systematic review of the literature found little evidence to support the belief that particular racial or ethnic groups have a longer DUP at the first episode of psychosis, as only three of ten studies reported differences across groups. The relatively small number of studies that examined such differences in DUP, as well as the methodological limitations of available studies, makes it difficult to draw firm
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conclusions. The three studies that did report differences suggest that in high-income countries, Black patients generally [29], and Black-African patients in particular [15, 20], may have shorter treatment delays relative to White patients. The two studies that found significant differences in DUP for Asian patients compared to White patients had conflicting findings [20, 29]. The evidence for many of the social determinants of DUP is scant or inconclusive [4]. The determinants of DUP operate at many levels, including the individual and their family, as well as the larger cultural, societal, and health service context. Both race and ethnicity are complex constructs, and the interplay between the determinants of DUP and these variables is likely to be similarly convoluted. A person’s racial or ethnic identity may have different interactions with both barriers and pathways to care. Given this, and the possibility that the various interactions may either increase or decrease the DUP, it may not be surprising that most studies report no differences between groups. With few exceptions, the studies included in our review assessed racial differences in treatment delay, with little consideration of ethnicity, culture, or immigration status. The utility of race as a research variable has been questioned, in part due to the significant heterogeneity of people within each category. The articles by Ghali, Morgan, Pek [15, 20, 26], and their respective colleagues were the only studies to analyze differences in DUP with no amalgamation of ethnic groups into racial groups. It is noteworthy that the two studies that disaggregated the Black group by
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ethnicity found that patients of African origin specifically tended to have a shorter DUP [15, 20]. Lumping African origin and Caribbean origin groups together as Black, as we did in the meta-analysis, may mask significant differences in DUP between these groups. A lack of dis-aggregation of racial groups was common across the included studies, which could have led to a similar cancellation of effects. Given this, the results we present for the metaanalysis of racial differences in DUP should be interpreted with caution. The tests for the meta-analysis found evidence of moderate heterogeneity among the studies, which indicates that these data arise from different populations and difficulties may arise from pooling these samples. Additional heterogeneity within the groups could arise from the role that immigration status plays. First-generation immigrants with FEP in the Netherlands have a significantly longer DUP than second-generation or native-born individuals [33]. This could reflect many factors such as differences in knowledge of local availability of services, a reluctance to seek help from mainstream services, or language barriers. However, most studies did not report whether their groups were immigrants and whether they were first- or secondgeneration. Of exception, Ghali and colleagues did report DUP estimates separately for first-generation White immigrants and White-British people, and also for first-generation African and Caribbean people and second-generation Black-British people. Although the impact of immigration status was not formally tested, there does appear to be a trend for the second-generation of both groups to have a longer DUP than the first-generation immigrants [20], which is in contrast to the findings from the Netherlands [33]. Additional studies are needed to elucidate the role of immigration status on treatment delay in FEP. A further limitation to the studies included in our review is that all studies, with the exception of two [15, 20], used simple univariate analyses to examine the association between racial or ethnic groups and DUP, and did not adjust the effect estimates for potential confounding factors. Although much of the prior literature on the determinants of treatment delay have been inconclusive, several factors are consistently found to be associated with DUP, including age of onset, premorbid functioning, mode of onset of psychosis, negative symptoms, social functioning, insight, and a diagnosis of non-affective psychosis [4]. Indicators of the pathway to care have also been shown to be associated with treatment delay [20, 34]. If these factors are also associated with a person’s racial or ethnic background, a failure to adjust for their confounding effects using multivariate models will obscure the true association between race or ethnicity and DUP. There is some evidence to suggest that there may be racial and ethnic differences in the clinical presentation of first-episode
psychosis [21, 35] and the pathway to care [14], as well as differences in social factors [36, 37], suggesting that a rigorous analysis of the association between race or ethnicity and DUP should account for these and other potentially confounding variables. The limited sample size of most included studies, the problems with group definition, and the heterogeneity of the samples are key limitations in the available literature. However, there also needs to be some attention given to how DUP is defined and operationalized. Ghali and colleagues [20] reported differences in the observed association between ethnicity and DUP when admission to early intervention services was used as the endpoint of DUP, rather than the initiation of antipsychotic medication. Additionally, delay in treatment has been conceptualized by others as consisting of two phases; a help-seeking phase, which is the period between symptom onset and first contact with health services, and a referral phase, which consists of the time between first contact and referral to an appropriate treatment program for first-episode psychosis [31, 38, 39]. There may be independent associations between group membership and each of these phases. For instance, patients of African and Caribbean origin are more likely to come into contact with police and emergency services on their pathways to care [14]. These groups may be reluctant to seek help initially and have a longer help-seeking delay, but then subsequently have a relatively short referral delay as a consequence of their contact with emergency services. As a result, they would appear to have a similar overall DUP to comparison groups, but the sub-components that comprise the DUP are of different lengths. The findings from a previous study by Harrison and colleagues support this [40], although this study did not meet inclusion criteria for our review. The investigators found no difference in the duration of untreated illness between Black-Caribbean patients and the general population, but did find that contact with services came later for Black-Caribbean patients. However, once contact was made, Black-Caribbean patients received psychiatric care sooner than the general population [40]. It has also been suggested that White patients may be more likely to be seen earlier in primary care, which may delay contact with secondary services [15]. Indeed, prior research suggests that individuals who are in contact with primary care services have longer delays between first contact and contact with specialized services [20, 34, 41], whereas those who are in contact with emergency services have shorter delays [20, 41]. Consequently, differences in the propensity to utilize primary care or emergency services may distort cross-group comparisons of the overall DUP. A more detailed assessment of the determinants of different components of DUP may be more informative for determining whether differences exist and the potential mechanisms behind such differences. This level of detail
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may be required to inform the development of interventions aimed at reducing treatment delay. Limitations Our findings should be interpreted in light of a number of limitations. We were only able to identify ten studies that reported data on race or ethnicity and DUP, despite the large number of studies to date that have reported DUP estimates or examined its determinants [1–4]. This raises the question of publication bias, as studies may have examined the association between DUP and race or ethnicity and failed to report negative findings. Additionally, we were unable to obtain log-transformed data from three of the studies, so the meta-analysis does not include the totality of evidence on ethnic differences in DUP. The quality assessment tool that we employed has not been previously validated. The studies included in our review used various tools to measure DUP, and the cross cultural validity of these measures has not been previously assessed. The included studies also did not typically report estimates of reliability, which is necessary to ensure there are not systematic differences in estimating the DUP across groups [15]. Furthermore, the included studies varied with respect to the way that DUP was operationalized, which is a common problem across studies reporting DUP [42], and the use of different start- or end-points for DUP could have an impact on observed trends. The conclusions drawn from these data should be interpreted in light of this heterogeneity in the outcome measure. Research implications In spite of these limitations to our review, we are able to conclude that prior research on racial and ethnic differences in DUP has substantial methodological limitations. Studies that are designed and powered to examine differences in treatment delay are needed to further our understanding of the challenges faced by patients with psychosis when seeking help for a first-episode. Additionally, our review highlights the need for consistent and routine data collection across early intervention services to allow comparability across different programs and health service contexts. This would include the measurement of ethnicity with minimal aggregation by racial group, as well as the use of standardized and validated measurement tools for DUP and pathways to care. However, the challenges associated with establishing such a consensus are substantial, and have been discussed elsewhere in the literature [5, 42–44]. Knowledge of the impact of both race and ethnicity on treatment delay is crucial for the field of early psychosis for a number of reasons. Firstly, the association between DUP
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and adverse clinical and functional outcomes is well known, and racial and ethnic differences in outcomes for psychosis have also been previously documented, although inconsistently across the literature [45]. If race or ethnicity is related to DUP, then there are important implications for its role as a confounding factor in the observed association between DUP and outcome. Secondly, information on the impact of race, ethnicity, and other determinants is crucial for informing the development of interventions aimed at reducing DUP and improving outcomes. Finally, as highincome countries become more culturally varied and ethnically diverse, information on racial and ethnic differences in treatment delay is imperative to inform the provision of culturally appropriate and equitable mental health services. Acknowledgments We are grateful to the authors of the included studies who generously shared data and information to aid in the completion of this review. We also appreciate the guidance provided by the Biostatistics Consulting Unit at the Centre for Addiction and Mental Health (CAMH). This study was funded by a Canadian Institutes of Health Research (CIHR) Operating Grant (Grant #220976). Kelly Anderson is supported by a Postdoctoral Fellowship Award from CIHR. Craig Morgan is supported by funding from the Medical Research Council (Ref: G0500817), Wellcome Trust (Grant Number WT087417), and European Union (European Community’s Seventh Framework Program (Grant Agreement No. HEALTH-F22009-241909) (Project EU-GEI). The authors have no conflicts of interest with respect to the publication of this manuscript.
Appendix: Terms used for Medline search strategy [exp. Schizophrenia and Disorders with Psychotic Features/OR exp. Affective Disorders, Psychotic/OR psychosis.mp OR psychotic disorder$.mp OR schizophreni$.mp OR severe mental illness$.mp] AND [exp. Population Groups/OR ethnic$.mp OR visible minorit$.mp OR ethno$.mp OR immigra$.mp OR migration.mp OR afro$.mp OR africa$.mp OR caribbean.mp OR black.mp OR europ$.mp OR white.mp] AND [exp. Time Factors/OR duration of untreated psychosis.mp OR
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duration of untreated illness.mp OR DUP.mp OR DUI.mp OR treatment delay.mp OR referral delay.mp OR help-seeking delay.mp OR early intervention.mp]
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18. The World Bank (2012) How we classify countries. http://data. worldbank.org/about/country-classifications. Accessed 1 Apr 2012 19. Sass B, Moffat J, Bhui K, McKenzie K (2009) Enhancing pathways to care for black and minority ethnic populations: a systematic review. Int Rev Psychiatry 21:430–438. doi:10.1080/ 09540260802204121 20. Ghali S, Fisher HL, Joyce J et al (2013) Ethnic variations in pathways into early intervention services for psychosis. Br J Psychiatry 202:277–283. doi:10.1192/bjp.bp.111.097865 21. Van der Ven E, Bourque F, Joober R et al (2012) Comparing the clinical presentation of first-episode psychosis across different migrant and ethnic minority groups in Montreal, Quebec. Can J Psychiatry 57:300–308 22. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. doi:10.1136/bmj.327.7414.557 23. Field AP, Gillett R (2010) How to do a meta-analysis. Br J Math Stat Psychol 63:665–694. doi:10.1348/000711010X502733 24. Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012 25. Perkins D, Lieberman JA, Gu H et al (2004) Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders. Br J Psychiatry 185:18–24. doi:10.1192/bjp.185.1.18 26. Pek E, Mythily S, Chong S (2006) Clinical and social correlates of duration of untreated psychosis in first-episode psychosis patients. Ann Acad Med Singapore 35:24–26 27. Archie S, Akhtar-Danesh N, Norman R et al (2010) Ethnic diversity and pathways to care for a first episode of psychosis in Ontario. Schizophr Bull 36:688–701. doi:10.1093/schbul/sbn137 28. Drake RJ (2000) Causes and consequences of duration of untreated psychosis in schizophrenia. Br J Psychiatry 177: 511–515. doi:10.1192/bjp.177.6.511 29. Haas GL, Garratt LS, Sweeney JA (1998) Delay to first antipsychotic medication in schizophrenia: impact on symptomatology and clinical course of illness. J Psychiatr Res 32:151–159 30. Turner M, Smith-Hamel C, Mulder R (2006) Pathways to care in a New Zealand first-episode of psychosis cohort. Aust N Z J Psychiatry 40:421–428. doi:10.1111/j.1440-1614.2006.01818.x 31. Brunet K, Birchwood M, Lester H, Thornhill K (2007) Delays in mental health services and duration of untreated psychosis. Psychiatr Bull 31:408–410. doi:10.1192/pb.bp.10 32. Compton MT, Chien VH, Leiner AS et al (2008) Mode of onset of psychosis and family involvement in help-seeking as determinants of duration of untreated psychosis. Soc Psychiatry Psychiatr Epidemiol 43:975–982. doi:10.1007/s00127-008-0397-y 33. Boonstra N, Sterk B, Wunderink L et al (2012) Association of treatment delay, migration and urbanicity in psychosis. Eur Psychiatry 27:500–505. doi:10.1016/j.eurpsy.2011.05.001 34. Anderson KK, Fuhrer R, Schmitz N, Malla AK (2013) Determinants of negative pathways to care and their impact on service disengagement in first-episode psychosis. Soc Psychiatry Psychiatr Epidemiol 48:125–136. doi:10.1007/s00127-012-0571-0 35. Veling W, Selten J-P, Mackenbach JP, Hoek HW (2007) Symptoms at first contact for psychotic disorder: comparison between native Dutch and ethnic minorities. Schizophr Res 95:30–38. doi:10.1016/j.schres.2007.06.024 36. Morgan C, Abdul-Al R, Lappin JM et al (2006) Clinical and social determinants of duration of untreated psychosis in the AESOP first-episode psychosis study. Br J Psychiatry 189:446–452. doi:10.1192/bjp.bp.106.021303 37. Mallett R, Leff J, Bhugra D et al (2002) Social environment, ethnicity and schizophrenia. A case-control study. Soc Psychiatry Psychiatr Epidemiol 37:329–335. doi:10.1007/s00127-002-0557-4
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45. Chorlton E, McKenzie K, Morgan C, Doody G (2012) Course and outcome of psychosis in black Caribbean populations and other ethnic groups living in the UK: a systematic review. Int J Soc Psychiatry 58:400–408. doi:10.1177/0020764011403070 46. Kuipers E, Holloway F, Rabe-Hesketh S, Tennakoon L (2004) An RCT of early intervention in psychosis: croydon Outreach and Assertive Support Team (COAST). Soc Psychiatry Psychiatr Epidemiol 39:358–363. doi:10.1007/s00127-004-0754-4 47. Lewis S (2002) Randomised controlled trial of cognitive– behavioural therapy in early schizophrenia: acute-phase outcomes. Br J Psychiatry 181:91–97. doi:10.1192/bjp.181.43.s91 48. Fearon P, Kirkbride JB, Morgan C et al (2006) Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study. Psychol Med 36: 1541–1550. doi:10.1017/S0033291706008774 49. Turner MA, Boden JM, Smith-Hamel C, Mulder RT (2009) Outcomes for 236 patients from a 2-year early intervention in psychosis service. Acta Psych Scand 120:129–137. doi:10.1111/j. 1600-0447.2009.01386.x 50. Haas GL, Sweeney JA (1992) Premorbid and onset features of first-episode schizophrenia. Schizophr Bull 18:373–386
ORIGINAL PAPER
Race, ethnicity, and the duration of untreated psychosis: a systematic review Kelly K. Anderson • Nina Flora • Suzanne Archie Craig Morgan • Kwame McKenzie
•
Received: 1 February 2013 / Accepted: 23 October 2013 Springer-Verlag Berlin Heidelberg 2013
Abstract Purpose An extended duration of untreated psychosis (DUP) is associated with poor outcome in first-episode psychosis (FEP). Some have suggested that minority ethnic groups have longer treatment delays, and this could lead to worse outcomes. We systematically reviewed the literature on racial and ethnic differences in DUP in patients with FEP. Methods We searched electronic databases and conducted forward and backward tracking to identify studies that had compared DUP for people with FEP from different racial or ethnic groups. Results We identified ten papers that reported on the association between race or ethnicity and DUP. Overall, these studies did not find evidence of differences between groups; however, three of ten studies suggested that Black patients generally, and Black-African patients specifically, may have a shorter DUP relative to White patients. There
K. K. Anderson (&) N. Flora K. McKenzie Social and Epidemiological Research, Centre for Addiction and Mental Health (CAMH), 455 Spadina Avenue, Suite 300, Toronto, ON M5S 2G8, Canada e-mail: [email protected] S. Archie Department of Psychiatry and Behavioural Neurosciences, McMaster University, 25 Charlton Avenue East, Suite 703, Hamilton, ON L8N 1Y2, Canada C. Morgan Section of Social Psychiatry, Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, UK K. McKenzie Department of Psychiatry, University of Toronto, 455 Spadina Avenue, Suite 300, Toronto, ON M5S 2G8, Canada
were methodological limitations in most studies with respect to ethnicity classification, sample size, and adjustment for potential confounders. Conclusion Racial and ethnic differences in DUP were rarely found. This could reflect that DUP does not differ between groups, or may reflect the methodological limitations of prior research. Studies that are designed and powered to examine these differences in treatment delay are needed to determine whether there are differences in DUP for minority groups. Keywords First-episode psychosis Duration of untreated psychosis Ethnicity Race Treatment delay Early intervention
Background An extended period from the onset of psychotic symptoms to the initiation of treatment is associated with poor outcomes in first-episode psychosis (FEP), as measured by remission of symptoms, levels of subsequent functioning, and quality of life [1–3]. This period has been termed the duration of untreated psychosis (DUP), and is considered to be a potentially modifiable predictor of prognosis in FEP and a target for secondary prevention. A comprehensive understanding of the factors that determine and moderate DUP could help to inform the development of more effective services. A review by Compton and Broussard [4] discusses the myriad of factors that may operate at different levels to influence DUP, and they classify these factors as demographic, pre-morbid and onset-related, illness-related, family-level, societal, and health services/system-level factors. The evidence base for many of the potential determinants of DUP is scant or inconclusive.
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The race and ethnicity of a person are examples of demographic factors that have the potential to impact the DUP. There is a considerable literature on the utility of race and ethnicity as concepts [5, 6]. Race typically refers to physical features, such as skin color or hair texture, which may reflect a person’s ancestry, and examples of categories that are commonly used to describe race include White, Black, or Asian. Ethnicity is a complex term used to describe perceived social groupings based on a sense of belonging, place of origin, and other factors such as language, religion, and sometimes race [7]. For example, descriptors that might be used to classify ethnicity include Black-Caribbean, Black-African, White-European, or White-Canadian. Both racial and ethnic categorizations have been used in comparative research between minority and majority groups. Racial and ethnic groupings are not mutually exclusive, and in the social world they may map onto each other. They both may have an impact on DUP because as variables they capture shared socio-cultural factors that have an effect on access to care. However, because they are different concepts there may be differences in the mechanism through which they are associated with DUP. Because of this, we have investigated both categories and we will distinguish between the concepts where it is important and relevant to do so. Numerous barriers to mental health care have been reported for different ethnic and racial groups, and the reasons for these are numerous and varied. Different groups may hold different beliefs about the cause of psychotic symptoms, their perceived severity, and the most appropriate course of action [8, 9]. Language barriers or a lack of information regarding the availability of services and how to access them may influence an individual’s decision to seek help [10]. There may be differences in the degree or type of stigma in different communities [11]. Finally, there may be differences in the accessibility of services to different groups because of the cost, the location of services, the use of models that are not considered appropriate by some groups, or the perception that services are not culturally competent or trustworthy [12]. As a result of these barriers to care, some groups may take alternative routes to accessing services, and differences in pathways to care for psychotic disorders have been documented between groups [13]. The majority of prior research in this area has focused on people of African or Caribbean origin in high-income countries, and has reported that these groups were more likely than the majority ethnic group to access care through involuntary hospitalizations and the criminal justice system, and less likely to have general practitioner (GP) involvement on the pathway to care [14]. Both barriers to care and differences in pathways to care could lead to differences in DUP. It is often assumed that
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these barriers to care result in minority groups with FEP having a longer DUP [15]. However, given the multi-faceted nature of the pathways to care [16], it is not immediately clear what the impact of race or ethnicity will be. There is currently no consensus on whether or how race and ethnicity have an impact on DUP. Despite the large body of research on various factors associated with DUP [4], there has been no systematic review or meta-analysis of the social determinants of DUP, with the exception of gender [17]. The aim of this study was to systematically review the literature on ethnic and racial differences in DUP among patients with first-episode psychosis. Because DUP is affected by the availability and accessibility of services within a given health system, and there are differences in service provision between low-, middle-, and high-income countries, we restricted this review to research conducted in high-income countries to help ensure comparability across the studies.
Methods Systematic review We conducted an electronic search of the MEDLINE (1950–2012), HealthStar (1966–2012), EMBASE (1980–2012), and PsycINFO (1967–2012) databases using the OvidSP platform, and we also searched Web of Knowledge. The MEDLINE and HealthStar search terms are presented in ‘‘Appendix’’, and this strategy was adapted for EMBASE and PsycINFO using analogous terms relevant to these databases. The Web of Knowledge was searched using key words. The search strategy was developed in consultation with a librarian. We obtained further studies by manually searching personal files and the bibliographies of all relevant studies and review articles. We performed forward citation searching using Web of Knowledge to locate all articles that had cited the included studies. When abstracts or unpublished studies were retrieved in our search, we contacted the corresponding authors to determine whether the work had subsequently been published in a peer-reviewed journal. We regularly updated all segments of the literature search, with the final update in September 2012. Each study was reviewed for the following inclusion criteria: (a) the study measured DUP among individuals with FEP; (b) the article reported DUP by race or ethnic group, or used race or ethnicity as a covariate in the analyses; (c) the study was conducted in a high-income country [18]; (d) the findings were published in a peerreviewed journal. We did not impose any restrictions with respect to date or language of publication.
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For all included papers, two independent reviewers extracted data on key elements of study design, the definition and measurement of DUP, the methods used for assigning race or ethnicity, and measures of the central tendency and dispersion of DUP by racial or ethnic group. All papers were assigned a quality assessment score using a rating scale based on a tool used in previously published systematic reviews on ethnic differences in pathways to care (Table 1) [13, 19]. Discrepancies between the reviewers were resolved by consensus. Where important methodological details were missing from the paper, such as the definition of DUP or the methods used for assigning race or ethnicity, we consulted other studies from the same research group and patient sample, where available, to obtain the missing information. However, the quality assessment ratings were done solely based on information contained within the included paper. Authors were contacted for further information or clarification when the data were aggregated or unclear.
Table 1 Rating system for methodological quality (adapted from Bhui et al. [13] and Sass et al. [19]) Legend
Adequacy of sample size -
No power calculation or inadequate sample to detect racial or ethnic differences
?
Authors demonstrate that the sample was powered to detect racial or ethnic differences
Definition of the first episode of psychosis -
Not described
•
Based on first hospitalization
?
Based on duration of antipsychotic treatment or first presentation to a clinical setting
Adjustment for confounding variables -
None
• ?
Age and/or gender Other co-morbidities or risk factors for the outcome of interesta (see below)
Quality of race or ethnicity measurement
Meta-analysis For all studies identified in the systematic review, we contacted the corresponding author to obtain log-transformed means and standard deviations for DUP. These were needed due to the positively skewed distribution of DUP, and studies were excluded from the meta-analysis if the authors were unable to provide these data. For all studies for which we had log-transformed data, we calculated the standardized mean difference (SMD) with 95 % confidence intervals (CI) using Cohen’s d for each racial or ethnic subgroup, relative to the majority racial or ethnic group. We meta-analyzed these effect estimates using the metan procedure in Stata 11.0. There was an insufficient number of papers to compare most of the racial or ethnic variables. Therefore, we restricted the analysis to data comparing the two groups most commonly investigated, specifically a Black grouping, made up of African or Caribbean origin populations, and an Asian grouping. These were compared to a White grouping representing the majority racial group. One of the studies presented data separately for Black-African and BlackCaribbean patients [15], and another divided the samples by first-generation Black-African and Black-Caribbean groups and second-generation Black-British groups [20]; therefore, we pooled these estimates by calculating weighted means and standard deviations to allow comparability with other studies. Two studies also divided the White sample by native-born individuals and immigrants [20, 21], and these groups were also pooled for the metaanalysis. There were insufficient data available for a metaanalysis of estimates for other racial groups, or for disaggregated racial or ethnic groups.
Description
-
Not reported
•
Third party report (e.g., staff categorization, name-based method)
?
Self-reported race or ethnicity
Use of race or ethnicity in the analysis •
Ethnic groups dichotomized (e.g., white vs. others) Reasonable groupings by race
?
All analyses done on specific ethnic groups without amalgamation
Definition of DUP -
Definition of DUP unclear (e.g., no description of start/end point)
?
Clear definition of DUP
Measurement of DUP ?
Not described/non-systematic method used for dating DUP Use of a standardized measurement tool for dating DUP
Source of data on DUP -
Not described/chart review or third party report only
•
Patient report only
?
Patient report corroborated with chart review or third party information
-, Criteria not met; •, Criteria partially met; ?, Criteria satisfied a
Risk factors include socio-economic factors (SES, employment, household size, marital status); Co-morbidities include drug and alcohol use, coexisting psychiatric conditions, violence to others
Statistical heterogeneity was assessed using the I2 statistic, with values of 25, 50, and 75 % suggestive of low, moderate, and high heterogeneity, respectively [22]. There was a high likelihood of methodological and contextual heterogeneity due to the different definitions used for DUP, race and ethnicity, as well as the different health service contexts of each of the studies; therefore, we opted to use a random effects model to compute a summary effect size
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[23]. The source of the heterogeneity was explored using a meta-regression model [24]. The study characteristics that were used as predictor variables in the model included country of origin, as well as quality assessment ratings for the method of defining the first episode of psychosis, the measurement of race or ethnicity, and the tool used for measuring and defining the DUP (Table 1).
trial, which is substantially different from the other studies which measured the time to antipsychotic prescription or first contact with services. In total, ten studies met the inclusion criteria for our review, and the authors of seven of these studies provided the required data for inclusion in the meta-analysis (Fig. 1). Study characteristics
Results The electronic database search retrieved 527 studies, of which 38 were potentially relevant for this review. We identified an additional 12 papers from personal files and the manual search, for a total of 50 full-text articles reviewed for inclusion. We excluded 40 studies for the following reasons (not mutually exclusive): not a FEP population (n = 5); review article, case report, or research letter (n = 5); DUP was not measured (n = 9); race and ethnicity were not measured (n = 6); no comparison group (n = 10); study was conducted in a low- or middle-income country (n = 4); the study reported duplicate data from samples that were already included in the review (n = 7). As a post hoc exclusion, we removed a multi-site clinical trial from the review [25] because the endpoint for DUP for a large proportion of patients was entry into the clinical
Fig. 1 Flow chart of the search strategy and exclusion process for the systematic review
Medline and HealthStar Search (n = 205)
The characteristics and findings of included studies are summarized in Tables 2 and 3, and the quality assessment ratings for study methodology are presented in Table 4. The studies primarily used observational designs and were conducted in Canada, England, New Zealand, Singapore, or the USA. The size of the study samples varied substantially, ranging from 55 to 535 participants (median across studies = 256). Approximately, half of the studies (n = 5) restricted their samples to non-affective psychoses. The first episode of psychosis was defined based on the use of antipsychotic medication in four studies, first contact with services in three studies, and first inpatient admission in three studies (Table 2). Most studies (n = 6) used a standardized instrument for measuring DUP, and nearly all (n = 9) used multiple data sources to corroborate information. The studies used similar starting points for measuring DUP, specifically the
EMBASE Search (n = 225)
PsycINFO Search (n = 86)
Web of Knowledge Search (n = 233)
Unique citations screened for relevancy (n = 527) Forward and backward citation searching (n = 8)
Studies excluded (n = 489)
Full-text version retrieved for more detailed evaluation (n = 50) Review of personal files (n = 4)
Studies meeting the inclusion criteria (n = 10)
Studies excluded from review, with reasons (n = 40)* -
Not a first-episode population (n=5) Review article/case report/letter (n=5) DUP not measured (n=9) No ethnicity (n=6) No comparison group (n=10) Low-income country (n=4) Clinical trial (n=1) Duplicate data (n=7)
Studies excluded from metaanalysis (n = 3) - Required data not available from authors (n=3)
Data available for meta-analysis (n = 7)
123
276 (with DUP)
van der Ven et al. [21]
55
248
535 (with DUP)
414
Brunet et al. [31]
Drake [28]
Ghali et al. 2013 [20]
Morgan et al. 2006 [15]
England
193 (with DUP)
n
Archie et al. [27]
Canada
Study
Cases from secondary or tertiary services in catchment area
EI services across eight sites
Day- and inpatient-unit admissions from defined catchment area
Mental health services
EI program
EI programs across four sites
Source of sample
Patient interview Family interview
Medical records
Collateral history
Medical records
Patient interview
Clinician interview
Family interview
Patient interview
Medical records
Family interview
Patient interview
Medical records
Clinician interviewa
Family interviewa
Patient interviewa
Medical recordsa
Clinician interview
Family interview
Patient interview
Medical records
Source of data
Table 2 Characteristics of studies included in the systematic review (n = 10)
ICD-10 (SCAN)
Not described
DSM-IV (clinical diagnosis)
ICD-10 (WHO Checklist)
DSM-IV (SCID)
DSM-IV (SCID)
Diagnostic criteria (tool)
73
Not described
100
100
74
100
Non-affective (%)
Patients presenting to services for the first time with an ICD10 diagnosis of psychosisd
First presentation to psychiatric services for affective or nonaffective psychosis
First or second admission (within 2 years of first admission) to day- or inpatient-unit for psychosisc
New referrals to mental health services for a psychotic disorder
Psychotic symptoms in a patient who had received less than 1 month of prior antipsychotic treatment
Psychotic symptoms in a patient who had received less than 1 month of prior antipsychotic treatment
Definition of first-episode psychosis
Soc Psychiatry Psychiatr Epidemiol
123
123
103
Haas et al. [29]
Inpatient admission
Three inpatient psychiatric units
EI program
EI program
Source of sample
Clinician interview
Family interview
Patient interview
Medical records
Family interview
Patient interview
Medical records
Family interview
Patient interview
Medical records
Family interviewe
Patient interviewe
Source of data
DSM-III-R (SCID)
DSM-IV (SCID)
DSM-IV (SCID)
DSM-IV (clinical Diagnosis)
Diagnostic criteria (tool)
100
100
90
64
Non-affective (%)
Diagnosis of schizophreniaspectrum psychosis with no prior history of admission for a psychotic disorderf
Psychotic symptoms in patients with no prior hospitalization for psychosis and less than 3 months of antipsychotic treatment
First presentation of psychosis with less than 1 week of prior antipsychotic treatment
First presentation of psychosis with less than 12 weeks of prior antipsychotic treatment
Definition of first-episode psychosis
f
e
d
c
b
As per prior paper [50]
As per subsequent paper [49]
As per subsequent paper [48]
As per prior paper [47]
As per prior paper [46]
DUP duration of untreated psychosis, EI early intervention, DSM diagnostic and statistical menu of mental disorders, SCID structured clinical interview for DSM, ICD International Classification of Diseases; WHO World Health Organization; SCAN schedules for clinical assessment in neuropsychiatry a As per prior paper [39]
264 (from author)
334
182
n
Compton et al. [32]
USA
Pek et al. [26]
Singapore
Turner et al. [30]
New Zealand
Study
Table 2 continued
Soc Psychiatry Psychiatr Epidemiol
Onset of delusions and hallucinations
One symptom from the positive scale of the PANSS C 4
NOS
Ghali et al. [20]
(2) Date of referral to early intervention services
One symptom from the positive scale of the PANSS C 4, or a cluster of symptoms totaling C 7, for longer than 2 weeks
Drake [28]
England Brunet et al. [31]
Onset of psychotic symptomsa
Onset of psychosis
Canada Archie et al. [27]
van der Ven et al. [21]
Start point for DUP
Study
(1) Initiation of regular antipsychotic treatment with adherence of at least 75 % for 1 month (used in meta-analysis) Staff assigned
Not described
Antipsychotic treatment at recommended dosage levels for 1 month, or leading to symptom reduction
Initiation of antipsychotic treatmenta
Earlier of date of initiation of antipsychotic medication for at least 1 month, or date of entry to EI services
End point for DUP
White-British
Ad-Hoc Algorithm
Pathways Encounter Form
CORS
CORS
DUP tool
49 84 126 21
16 White-other Black-British Black-Caribbean
19 13
African-Caribbeanb Other b
Self-Reportb
134
3 26 4 216
Black South Asian Mixed Whiteb
36 25 17 21 35
African and Caribbeanb Asianb Central/South Americab Middle East/North Africanb European/North Americanb
21
30 25 20 142
Blackb Asianb Otherb White non-migrantsb
White
118
n
10 14 8
9 10
12
N/A
17 22 11 25 18
31 29 20 15
22
Median
DUP (weeks)
Whiteb
Race/ethnicity categories
Not Described
Staff assigned based on place of origin
Self-report
Race/ethnicity measurement
Table 3 Findings on duration of untreated psychosis and racial/ethnic group for studies included in the systematic review (n = 10)
28 26 34
6–28 6–40
5–36
N/A
5–34 10–56 3–75 8–66 4–41
3–57 7–63 3–66 6–52
3–52
IQR
Soc Psychiatry Psychiatr Epidemiol
123
123
Onset of psychotic symptoms
Onset of positive psychotic symptoms
Onset of delusions, hallucinations, thought disorder, or disorganized behavior
One positive scale symptom on the PANSS C 4
Presence of positive psychotic symptoms for at least 1 week
Start point for DUP
First administration of antipsychotic medication
First hospital admission
Establishment of definitive diagnosis and treatment
Initiation of antipsychotic treatment
Contact with secondary mental health services
End point for DUP
Not Described
CORS SOS
Not described
Not described
PPHS
DUP tool
Not described
Not described
Not described
Not described
Self-report staff assigned
Race/ethnicity measurement
21 243 68
24 4 4 3
Blackb White
Black Asian Hispanic Other
64 18 7
Malay Indian Others Whiteb
245
24
Aboriginal (Maori)b Chinese
135
129 68
African-Caribbeanb Black-Africanb Non-Aboriginalb
110 60 217
n
31 N/A
20
N/A
9
4
12 8
8 9 8
Median
DUP (weeks)
Black-African South Asian White-Britishb
Race/ethnicity categories
7–119 N/A
3–119
N/A
2–35
1–17
4–77 1–21
22 23 2–39
IQR
N/A Data not available, DUP duration of untreated psychosis, IQR interquartile range, EI early intervention, CORS circumstances of onset or relapse schedule, PANSS Positive and Negative Syndrome Scale, NOS Nottingham Onset Schedule, PPHS Psychiatric and Personal History Schedule, SOS Symptom Onset in Schizophrenia Inventory a As per prior paper [39] b Data obtained from corresponding author
Haas et al. [29]
USA Compton et al. [32]
Singapore Pek et al. [26]
New Zealand Turner et al. [30]
Morgan et al. [15]
Study
Table 3 continued
Soc Psychiatry Psychiatr Epidemiol
Soc Psychiatry Psychiatr Epidemiol Table 4 Quality assessment ratings for studies included in the systematic review (n = 10)
Archie et al. [27]
Adequacy of sample size
Definition of FEP
Adjustment for confounding
Race/ethnicity measurement
Race/ethnicity categories
Definition of DUP
Measurement of DUP
DUP data source
-
?
-
?
•
?
?
?
Brunet et al. [31]
-
?
-
-
•
?
?
?
Compton et al. [32]
-
?
-
-
•
?
?
?
Drake [28]
-
-
-
-
•
-
-
?
Ghali et al. [20]
-
?
?
•
?
?
?
?
Haas et al. [29]
-
-
-
-
•
?
-
?
Morgan et al. [15] Pek et al. [26]
-
?
? -
? -
? ?
? ?
? -
? ?
Turner et al. [30]
-
?
-
-
-
?
-
-
van der Ven et al. [21]
-
?
-
•
•
-
?
?
Ratings are based solely on the information contained within the included article. See Table 1 for scoring criteria -, Criteria not met; •, Criteria partially met; ?, Criteria satisfied
onset of positive psychotic symptoms. However, the endpoints for DUP varied across the studies, with the majority (n = 7) using the initiation of adequate antipsychotic treatment as the end of DUP (Table 3). One study measured two different end-points for DUP, specifically the initiation of antipsychotic treatment and entry into early intervention services, to assess the impact of this definition on observed estimates [20]. Few studies (n = 5) reported how race or ethnicity was measured, and among those who did, three used a measure involving self-report. Only three studies performed analyses on specific ethnic groups without amalgamation by race [15, 20, 26], and two distinguished between the first- and second-generation immigrant populations of African, Caribbean, or European origin [20, 21]. The classifications of race and ethnicity that were used in each of the studies are shown in Table 3. None of the included studies met all of our criteria for methodological quality (Table 4). The most common problems across the studies were as follows: not using a self-report measure for race or ethnicity, or not describing how it was measured (n = 8); lumping different ethnic groups together by race (n = 7); and lack of adjustment for potential confounding (n = 8). None of the studies demonstrated that the sample size was adequate for detecting racial or ethnic differences in DUP (Table 4). Racial and ethnic differences in DUP Only two studies included in our review explicitly stated that the primary objective was to examine racial or ethnic differences in DUP [15, 20]. The objective of the remaining studies was to look at differences between groups in symptomatology [21] or pathways to care [27], to examine other determinants of DUP [26], to look at the association
between DUP and clinical outcomes [28, 29], or to describe pathways to care generally [30]. The two remaining studies did not present data on DUP for different groups, but rather used these variables as a covariate when examining other determinants of the DUP [31, 32]. Given that most studies were not designed to examine racial or differences in DUP, it is not surprising that none of the studies demonstrated that they had achieved an adequate sample size to achieve this objective. Only three studies found evidence of racial or ethnic differences in DUP. Haas and colleagues dichotomized DUP and found that a greater proportion of Black-American patients had a DUP of less than 1 year, whereas a greater proportion of Asian-American patients had a delay of 1 year or longer. There were no differences observed for White, Hispanic, or Other racial groups [29]. Morgan and colleagues [15] found that patients of Black-African origin had a significantly shorter DUP compared with both WhiteBritish and Black-Caribbean patients. Similarly, Ghali and colleagues [20] found that White-British patients had a significantly longer DUP when compared with BlackAfrican patients, but the differences for Black-Caribbean patients did not reach statistical significance, possibly owing to the much smaller sample size. The second-generation immigrant Black group, and the first-generation immigrant White group, also had a shorter DUP than the White-British group when entry into early intervention services was used as the endpoint, but not when the initiation of antipsychotic medication was the endpoint for DUP [20]. In contrast to Haas and colleagues, Ghali and colleagues [20] found that patients of South Asian origin had a shorter DUP, compared with the White-British group. Interestingly, some of these differences in DUP between the ethnic groups were attenuated once differences in the pathway to care were accounted for. The remaining studies
123
Soc Psychiatry Psychiatr Epidemiol % Study
Year
Country
SMD (95% CI)
Weight
Archie et al.
2010
Canada
0.23 (-0.17, 0.63)
12.26
Drake et al.
2000
England
-0.12 (-0.59, 0.35)
9.81
Ghali et al.
2013
England
-0.22 (-0.40, -0.04)
27.11
Morgan et al.
2006
England
0.08 (-0.12, 0.27)
26.02
van der Ven et al.
2012
Canada
-0.02 (-0.38, 0.34)
14.26
Compton et al.
2008
United States
0.30 (-0.14, 0.75)
10.55
0.01 (-0.16, 0.18)
100.00
Black vs. White
Subtotal (I-squared = 46.3%, p = 0.097) . Asian vs. White Archie et al.
2010
Canada
0.26 (-0.18, 0.69)
30.18
Ghali et al.
2013
England
-0.32 (-0.60, -0.03)
38.87
van der Ven et al.
2012
Canada
0.14 (-0.28, 0.56)
30.95
-0.00 (-0.38, 0.37)
100.00
Subtotal (I-squared = 66.6%, p = 0.050) . NOTE: Weights are from random effects analysis
-1
0
Shorter DUP
1
Longer DUP
Fig. 2 Meta-analysis of the log-transformed standardized mean difference (SMD) in duration of untreated psychosis for Black and Asian racial groups relative to White
did not find a statistically significant association between race and DUP [21, 26–28, 30–32]. Meta-analysis Our meta-analysis computing an overall effect of Black and Asian groups relative to White did not show evidence of differences in DUP between these groups (Fig. 2). The pooled SMD in DUP for Black patients was 0.01 (95 % CI = -0.16, 0.18). The pooled SMD in DUP was 0.00 (95 % CI = -0.38, 0.37) for Asian patients. There was evidence of moderate heterogeneity in these data (Black I2 = 46.3 %; Asian I2 = 66.6 %), and the source of this was explored using meta-regression techniques; however, none of the study-level variables included in our models was a significant source of heterogeneity (data not shown).
Discussion Main findings Our systematic review of the literature found little evidence to support the belief that particular racial or ethnic groups have a longer DUP at the first episode of psychosis, as only three of ten studies reported differences across groups. The relatively small number of studies that examined such differences in DUP, as well as the methodological limitations of available studies, makes it difficult to draw firm
123
conclusions. The three studies that did report differences suggest that in high-income countries, Black patients generally [29], and Black-African patients in particular [15, 20], may have shorter treatment delays relative to White patients. The two studies that found significant differences in DUP for Asian patients compared to White patients had conflicting findings [20, 29]. The evidence for many of the social determinants of DUP is scant or inconclusive [4]. The determinants of DUP operate at many levels, including the individual and their family, as well as the larger cultural, societal, and health service context. Both race and ethnicity are complex constructs, and the interplay between the determinants of DUP and these variables is likely to be similarly convoluted. A person’s racial or ethnic identity may have different interactions with both barriers and pathways to care. Given this, and the possibility that the various interactions may either increase or decrease the DUP, it may not be surprising that most studies report no differences between groups. With few exceptions, the studies included in our review assessed racial differences in treatment delay, with little consideration of ethnicity, culture, or immigration status. The utility of race as a research variable has been questioned, in part due to the significant heterogeneity of people within each category. The articles by Ghali, Morgan, Pek [15, 20, 26], and their respective colleagues were the only studies to analyze differences in DUP with no amalgamation of ethnic groups into racial groups. It is noteworthy that the two studies that disaggregated the Black group by
Soc Psychiatry Psychiatr Epidemiol
ethnicity found that patients of African origin specifically tended to have a shorter DUP [15, 20]. Lumping African origin and Caribbean origin groups together as Black, as we did in the meta-analysis, may mask significant differences in DUP between these groups. A lack of dis-aggregation of racial groups was common across the included studies, which could have led to a similar cancellation of effects. Given this, the results we present for the metaanalysis of racial differences in DUP should be interpreted with caution. The tests for the meta-analysis found evidence of moderate heterogeneity among the studies, which indicates that these data arise from different populations and difficulties may arise from pooling these samples. Additional heterogeneity within the groups could arise from the role that immigration status plays. First-generation immigrants with FEP in the Netherlands have a significantly longer DUP than second-generation or native-born individuals [33]. This could reflect many factors such as differences in knowledge of local availability of services, a reluctance to seek help from mainstream services, or language barriers. However, most studies did not report whether their groups were immigrants and whether they were first- or secondgeneration. Of exception, Ghali and colleagues did report DUP estimates separately for first-generation White immigrants and White-British people, and also for first-generation African and Caribbean people and second-generation Black-British people. Although the impact of immigration status was not formally tested, there does appear to be a trend for the second-generation of both groups to have a longer DUP than the first-generation immigrants [20], which is in contrast to the findings from the Netherlands [33]. Additional studies are needed to elucidate the role of immigration status on treatment delay in FEP. A further limitation to the studies included in our review is that all studies, with the exception of two [15, 20], used simple univariate analyses to examine the association between racial or ethnic groups and DUP, and did not adjust the effect estimates for potential confounding factors. Although much of the prior literature on the determinants of treatment delay have been inconclusive, several factors are consistently found to be associated with DUP, including age of onset, premorbid functioning, mode of onset of psychosis, negative symptoms, social functioning, insight, and a diagnosis of non-affective psychosis [4]. Indicators of the pathway to care have also been shown to be associated with treatment delay [20, 34]. If these factors are also associated with a person’s racial or ethnic background, a failure to adjust for their confounding effects using multivariate models will obscure the true association between race or ethnicity and DUP. There is some evidence to suggest that there may be racial and ethnic differences in the clinical presentation of first-episode
psychosis [21, 35] and the pathway to care [14], as well as differences in social factors [36, 37], suggesting that a rigorous analysis of the association between race or ethnicity and DUP should account for these and other potentially confounding variables. The limited sample size of most included studies, the problems with group definition, and the heterogeneity of the samples are key limitations in the available literature. However, there also needs to be some attention given to how DUP is defined and operationalized. Ghali and colleagues [20] reported differences in the observed association between ethnicity and DUP when admission to early intervention services was used as the endpoint of DUP, rather than the initiation of antipsychotic medication. Additionally, delay in treatment has been conceptualized by others as consisting of two phases; a help-seeking phase, which is the period between symptom onset and first contact with health services, and a referral phase, which consists of the time between first contact and referral to an appropriate treatment program for first-episode psychosis [31, 38, 39]. There may be independent associations between group membership and each of these phases. For instance, patients of African and Caribbean origin are more likely to come into contact with police and emergency services on their pathways to care [14]. These groups may be reluctant to seek help initially and have a longer help-seeking delay, but then subsequently have a relatively short referral delay as a consequence of their contact with emergency services. As a result, they would appear to have a similar overall DUP to comparison groups, but the sub-components that comprise the DUP are of different lengths. The findings from a previous study by Harrison and colleagues support this [40], although this study did not meet inclusion criteria for our review. The investigators found no difference in the duration of untreated illness between Black-Caribbean patients and the general population, but did find that contact with services came later for Black-Caribbean patients. However, once contact was made, Black-Caribbean patients received psychiatric care sooner than the general population [40]. It has also been suggested that White patients may be more likely to be seen earlier in primary care, which may delay contact with secondary services [15]. Indeed, prior research suggests that individuals who are in contact with primary care services have longer delays between first contact and contact with specialized services [20, 34, 41], whereas those who are in contact with emergency services have shorter delays [20, 41]. Consequently, differences in the propensity to utilize primary care or emergency services may distort cross-group comparisons of the overall DUP. A more detailed assessment of the determinants of different components of DUP may be more informative for determining whether differences exist and the potential mechanisms behind such differences. This level of detail
123
Soc Psychiatry Psychiatr Epidemiol
may be required to inform the development of interventions aimed at reducing treatment delay. Limitations Our findings should be interpreted in light of a number of limitations. We were only able to identify ten studies that reported data on race or ethnicity and DUP, despite the large number of studies to date that have reported DUP estimates or examined its determinants [1–4]. This raises the question of publication bias, as studies may have examined the association between DUP and race or ethnicity and failed to report negative findings. Additionally, we were unable to obtain log-transformed data from three of the studies, so the meta-analysis does not include the totality of evidence on ethnic differences in DUP. The quality assessment tool that we employed has not been previously validated. The studies included in our review used various tools to measure DUP, and the cross cultural validity of these measures has not been previously assessed. The included studies also did not typically report estimates of reliability, which is necessary to ensure there are not systematic differences in estimating the DUP across groups [15]. Furthermore, the included studies varied with respect to the way that DUP was operationalized, which is a common problem across studies reporting DUP [42], and the use of different start- or end-points for DUP could have an impact on observed trends. The conclusions drawn from these data should be interpreted in light of this heterogeneity in the outcome measure. Research implications In spite of these limitations to our review, we are able to conclude that prior research on racial and ethnic differences in DUP has substantial methodological limitations. Studies that are designed and powered to examine differences in treatment delay are needed to further our understanding of the challenges faced by patients with psychosis when seeking help for a first-episode. Additionally, our review highlights the need for consistent and routine data collection across early intervention services to allow comparability across different programs and health service contexts. This would include the measurement of ethnicity with minimal aggregation by racial group, as well as the use of standardized and validated measurement tools for DUP and pathways to care. However, the challenges associated with establishing such a consensus are substantial, and have been discussed elsewhere in the literature [5, 42–44]. Knowledge of the impact of both race and ethnicity on treatment delay is crucial for the field of early psychosis for a number of reasons. Firstly, the association between DUP
123
and adverse clinical and functional outcomes is well known, and racial and ethnic differences in outcomes for psychosis have also been previously documented, although inconsistently across the literature [45]. If race or ethnicity is related to DUP, then there are important implications for its role as a confounding factor in the observed association between DUP and outcome. Secondly, information on the impact of race, ethnicity, and other determinants is crucial for informing the development of interventions aimed at reducing DUP and improving outcomes. Finally, as highincome countries become more culturally varied and ethnically diverse, information on racial and ethnic differences in treatment delay is imperative to inform the provision of culturally appropriate and equitable mental health services. Acknowledgments We are grateful to the authors of the included studies who generously shared data and information to aid in the completion of this review. We also appreciate the guidance provided by the Biostatistics Consulting Unit at the Centre for Addiction and Mental Health (CAMH). This study was funded by a Canadian Institutes of Health Research (CIHR) Operating Grant (Grant #220976). Kelly Anderson is supported by a Postdoctoral Fellowship Award from CIHR. Craig Morgan is supported by funding from the Medical Research Council (Ref: G0500817), Wellcome Trust (Grant Number WT087417), and European Union (European Community’s Seventh Framework Program (Grant Agreement No. HEALTH-F22009-241909) (Project EU-GEI). The authors have no conflicts of interest with respect to the publication of this manuscript.
Appendix: Terms used for Medline search strategy [exp. Schizophrenia and Disorders with Psychotic Features/OR exp. Affective Disorders, Psychotic/OR psychosis.mp OR psychotic disorder$.mp OR schizophreni$.mp OR severe mental illness$.mp] AND [exp. Population Groups/OR ethnic$.mp OR visible minorit$.mp OR ethno$.mp OR immigra$.mp OR migration.mp OR afro$.mp OR africa$.mp OR caribbean.mp OR black.mp OR europ$.mp OR white.mp] AND [exp. Time Factors/OR duration of untreated psychosis.mp OR
Soc Psychiatry Psychiatr Epidemiol
duration of untreated illness.mp OR DUP.mp OR DUI.mp OR treatment delay.mp OR referral delay.mp OR help-seeking delay.mp OR early intervention.mp]
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