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99 (2008) 134–138www.elsevier.com/locate/schres

Schizophrenia Research

Suicide and severe mental illnesses. Cohort study within the UKgeneral practice research database

David Osborn a,⁎, Gus Levy a, Irwin Nazareth b, Michael King a

a Department of Mental Health Sciences, (Hampstead Campus), Royal Free and University College Medical School,Rowland Hill Street, London, NW3 2PF, UK

b Department of Primary Care and Population Sciences, (Hampstead Campus), Royal Free and University College Medical School,UCL, Rowland Hill Street, London, NW3 2PF, UK

Received 19 September 2007; received in revised form 13 November 2007; accepted 18 November 2007Available online 26 December 2007

Abstract

We aimed to evaluate suicide risk across the life-course in severe mental illnesses (SMI) including schizophrenia. Usingsurvival analysis, we compared suicide risk in cohorts of 46,136 people with SMI and 300,426 without. The overall unadjustedhazard ratio (HR) for suicide in SMI was 12.97 (95% CI: 9.75–17.25). The unadjusted HRs differed by age band: 18–30 years:19.56 (9.76–39.17); 30–50 years: 13.14 (8.64–19.99); 50–70 years: 16.39 (9.15–29.37); 70+: 3.25 (1.33–7.94). In schizophrenia,risk was significantly higher when young but marked risk persisted until age 70. Greatest risk was associated with: increasedconsultation rates; antidepressant prescriptions and living in less deprived areas.© 2007 Elsevier B.V. All rights reserved.

Keywords: Schizophrenia; Bipolar affective disorder; Suicide; Primary care; Risk factors

1. Introduction

Suicide is a public health priority in people withsevere mental illnesses (SMI) including schizophreniaand bipolar affective disorder (Department of Health,1999; Hawton et al., 2005). Although it is believed thatpeople with schizophrenia are at greatest risk of suicideearly in the illness (Palmer et al., 2005; Limosin et al.,2007) recent reviews have questioned this evidence andhave highlighted the lack of data from community

⁎ Corresponding author. Tel.: +44 20 77940500x33950; fax: +44 2078302808.

E-mail addresses: d.osborn@medsch.ucl.ac.uk (D. Osborn),g.levy@medsch.ucl.ac.uk (G. Levy), i.nazareth@medsch.ucl.ac.uk(I. Nazareth), m.king@medsch.ucl.ac.uk (M. King).

0920-9964/$ - see front matter © 2007 Elsevier B.V. All rights reserved.doi:10.1016/j.schres.2007.11.025

samples (Hawton et al., 2005; Palmer et al., 2005).Research on suicide in people with SMI has been limitedby relatively small sample sizes; inadequate follow-upperiods; few suicide events and sub-optimal statisticalanalyses. In the absence of an accurate estimation of theburden of suicide and the level of risk throughout thecourse of illness, we examined in a large communitysample the risk of suicide in people with SMI and thedemographic and family practice health service pre-dictors of suicide.

2. Methods

We undertook a cohort analysis of the risk of suicide inpeople on the UK general practice research database(GPRD) between 1987 and 2002, aged 18 years and over,

135D. Osborn et al. / Schizophrenia Research 99 (2008) 134–138

with and without SMI. We included every patient with aclinical diagnosis of schizophrenia, bipolar affectivedisorders and other psychotic illnesses including delu-sional disorders and depression with psychosis. Peoplewith drug induced or organic psychoses were excluded.The comparison cohort, without such diagnoses, wasrandomly selected to achieve a ratio of 1:6, to maximisethe statistical power to detect real differences. There wereno other exclusion criteria to ensure representativeness.

The GPRD contains routine clinical data from 755general practices representative of those in the UK andhas been used for pharmaco-epidemiological studies ofsuicide outcomes (Jick et al., 2004). In the UK, 95% ofthe population are registered with a general practice. Ifpeople with SMI are not registered with primary carepractitioners this is usually organised by their commu-nity mental health team. The primary care practices alsokeep registers of those with SMI. The validity of a GPRDdiagnosis of SMI has been confirmed (Nazareth et al.,1993a). Variables must be extracted a priori from theGPRD. We only chose variables which might be relatedto suicide andwhich are known to be valid and reliable inthe GPRD, which is a working clinical database. Forinstance, whilst prescriptions and consultation episodeswill be recorded accurately in the GPRD, the exactcontent of a consultation will be inconsistently enteredby different practitioners. In deciding which variables toextract for this study we focused on socio-demographicpredictors of suicide, consultation frequency prior tosuicide and treatment of depression. We obtained dataconcerning age, sex, SMI diagnosis, General Practice(GP) consultation rate, antidepressant medication,smoking, and social deprivation using the Carstairsindex for each general practice, categorised intoquintiles. The GPRD did not include accurate data ondeprivation or ethnicity at the level of the individual. TheCarstairs index of the GP was the only available measureand is a standard index of deprivation that is calculatedfor each geographical area on four variables. These are:male unemployment; households with no car; over-crowding and head of households in unskilled manualoccupation (Morris and Carstairs, 1991).

To assess change in consultation behaviour wecompared number of GP visits in the final 3 monthson the GPRD database with the number of visits made inthe same 3 months of the previous year. This comprisedthe last year of life in the case of suicide, whereas it wasthe last year on the data base for the remainder.

We performed survival analysis using Cox regressiontechniques in STATA (version 8.2) (StataCorp, 2003).We estimated hazard ratios for suicide firstly comparingpeople with and without SMI and then restricting the

analysis to people with SMI. In a multivariate analysiswe adjusted for major available explanatory variablesincluding age, calendar period and geographical socialdeprivation. We also used smoking as a “proxy co-variate” for the multivariate analysis since it isassociated with individual deprivation and with poorphysical and mental health.

A test of proportional hazards was employed todetermine whether hazard ratios were stable across ages.The cohort was stratified into age bands to estimate riskof suicide in different periods of life in the three mainSMI diagnostic groups.

Population attributable risk (PAR) was calculatedusing the hazard ratio for suicide and choosing theprevalence of SMI in the GPRD at the midpoint of thecohort (1994).

3. Results

The cohorts comprised 46,136 people with SMI and300,426 without SMI. The median follow-up time was4.7 years in the SMI group, but 4.3 years in thecomparison group. The majority of people attracted onlyone SMI diagnosis during their time in the GPRD(35,097/46,136=76.1%). The most common SMIdiagnoses were schizophrenia (40.2%), bipolar affectivedisorder (23.3%), delusional disorder (19.2%), depres-sive psychosis (5.9%) and schizoaffective disorder(5.3%) (Osborn et al., 2007). This afforded statisticalpower to examine suicide rates separately in schizo-phrenia and bipolar affective disorder and the remainingSMI diagnosis was grouped together for furtheranalyses. Where a person had attracted more than onediagnosis we applied two rules. Diagnoses of schizo-phrenia, schizoaffective disorder or bipolar disorderwere given priority over delusional disorder, briefpsychotic episodes, unipolar depressive psychoses ornon-specified psychoses. Where a diagnosis hadchanged between schizophrenia, bipolar disorder orschizoaffective disorder over time we utilised the mostrecent diagnosis.

In SMI, the crude rate for GP recorded suicide wasfar greater than in the comparison group (0.58 vs. 0.047per 1000 person years), yielding an overall unadjustedhazard ratio of 12.97 (Table 1). This increased risk wasobserved irrespective of SMI diagnosis, sex or age in theunder 70s. In the oldest group, the three-fold excess riskwas still significant. After adjustment in the multivariateanalysis, hazard ratios for suicide in SMI were smallerin magnitude. The individual variable responsible forthis difference in magnitude was GP prescription ofantidepressants.

Table 1Suicide mortality in people with and without severe mental illness

Total Suicides % suicide Crude hazard ratio Adjusted hazardratio a

SMI vs. comparison groupComparison 300,246 72 0.02 1.00 1.00SMI 46,136 143 0.31 12.97 (9.75, 17.25) 7.72 (5.66, 10.51)

Diagnosis Comparison 300,246 72 0.02 1.00 1.00Schizophrenia 18,555 48 0.26 10.99 (7.61, 15.85) 7.00 (4.78, 10.25)Bipolar disorder 10,742 41 0.38 15.20 (10.32, 22.37) 8.74 (5.80, 13.17)Other SMI 16,839 54 0.32 13.67 (9.60, 19.48) 7.85 (5.38, 11.46)

Sex Female comparison 156,781 18 0.01 1.00Female SMI 24,608 54 0.22 18.05 (10.49, 31.06) 9.82 (5.55, 17.38)Male comparison 143,465 54 0.04 1.00 1.00Male SMI 21,528 89 0.41 10.96 (7.81, 15.37) 6.75 (4.65, 9.81)

Age bands Comparison 18–30 102,653 12 0.01 1.00 1.00SMI 18–30 9600 24 0.25 19.56 (9.76, 39.17) 13.26 (6.24, 28.15)Comparison 30–50 134,455 33 0.02 1.00 1.00SMI 30–50 20,223 65 0.32 13.14 (8.64, 19.99) 7.80 (4.92, 12.36)Comparison 50–70 88,937 15 0.02 1.00 1.00SMI 50–70 17,265 46 0.27 16.39 (9.15, 29.37) 9.19 (4.93, 17.11)Comparison 70+ 50,152 12 0.02 1.00 1.00SMI 70+ 11,121 8 0.07 3.25 (1.33, 7.94) 2.08 (0.81, 5.31)

Social deprivation Comparison 20% mostdeprived

63,312 16 0.03 1.00 1.00

SMI 20% most deprived 12,469 32 0.26 10.26 (5.60, 18.79) 5.30 (2.77, 10.15)Comparison 20% leastdeprived

31,825 9 0.03 1.00 1.00

SMI 20% least deprived 3536 16 0.45 16.25 (7.13, 37.04) 10.52 (4.25, 26.05)

Within SMI group onlySex Female 24,608 54 0.22 1.00 1.00

Male 21,528 89 0.41 1.70 (1.20, 2.40) 1.94 (1.37, 2.76)Age bands b 18–30 9600 24 0.25 1.00 1.00

30–50 20,223 65 0.32 1.05 (0.66, 1.68) 1.13 (0.71, 1.81)50–70 17,265 46 0.27 0.85 (0.52, 1.39) 0.98 (0.59, 1.61)70+ 11,121 8 0.07 0.25 (0.11, 0.55) 0.30 (0.14, 0.69)

Social deprivation quintiles 1 least deprived 20% 3536 16 0.45 1.00 1.002 5526 24 0.43 0.87 (0.46, 1.65) 0.88 (0.47, 1.66)3 8507 28 0.33 0.72 (0.39, 1.33) 0.73 (0.40, 1.36)4 9542 29 0.30 0.63 (0.34, 1.16) 0.63 (0.34, 1.15)5 most deprived 20% 12,469 32 0.26 0.53 (0.29, 0.96) 0.54 (0.30, 0.99)

Consultation change in final 3 months b2 more visits 35,162 70 0.20 1.00 1.002–4 more visits 6361 38 0.60 3.53 (2.38, 5.24) 3.22 (2.16, 4.80)4 or more visits 4613 35 0.76 5.45 (3.63, 8.20) 4.51 (2.98, 6.83)

Antidepressant in last 6 months No 33,757 62 0.18 1.00 1.00Yes 12,379 81 0.65 3.27 (2.35, 4.55) 3.56 (2.55, 4.98)

a Adusted for sex, age, calendar period, geographical social deprivation, antidepressant prescription in last 6 months and smoking.b Age bands were compared using a Poisson model as a Cox model could not be estimated due to co-linearity between the age bands. Bold text:

95% CI's do not overlap zero. SMI: Severe mental illness.

136 D. Osborn et al. / Schizophrenia Research 99 (2008) 134–138

Hazard ratios for suicide in different age bands variedwith SMI diagnosis (Table 2). In bipolar disorder and otherSMI, highest rates occurred in the older age groups, butdifferences across age groups were not significant.Conversely, the hazard ratios for suicide in schizophreniadecreased significantly with age (test for proportionalhazards p=0.001). Stratifying by age band with thecomparison group as the baseline, the suicide HR for

schizophreniawas 22.6 (95%CI 10.1–50.4) in 18–30 yearolds; 11.2 (6.6–18.8) in 30–50 year olds and 8.77 (3.9–19.5) in 50–70 year olds. Of the 48 suicides in people withschizophrenia, 13 (27.1%) occurred in the 18–30 yearolds, 25 (52.1%) in the 30–50 year olds, 10 (20.8%) in the50–70 year olds, and none in the over 70 year olds.

In 1994 the overall GPRD prevalence of SMI was0.87% yielding an unadjusted population attributable

Table 2Hazard ratios for suicide in SMI by diagnosis and age group, comparedto controls

18–30 years 30–49 years 50–70 years

Schizophrenia 22.6 (10.1–50.4) 11.2 (6.6–8.8) 8.8 (3.9–19.5)Bipolar

disorder14.2 (4.0–50.5) 14.8 (8.2–26.6) 24.8 (12.5–49.4)

Other SMI(psychosis)

13.2 (5.4–32.4) 13.5 (7.9–23.0) 21.4 (10.8–42.6)

(95% confidence intervals).

137D. Osborn et al. / Schizophrenia Research 99 (2008) 134–138

risk percent of 9.4%. The PARs decreased over time,from 10.3% in 1988 to 7.7% in 2001.

Within the SMI group, increasing age was associatedwith high relative rates of suicide until 70 after whichthere was a decreased rate (Table 1). Those completingsuicide were more likely to be male and were over threetimes more likely to have received antidepressants in thelast 6 months.

In the 3 months prior to suicide, GP consultationsincreased by a mean of 1.90 (95% CI 1.34–2.47) visits,compared to the same 3 months of the previous year.Higher rates of suicide were associated with lower socialdeprivation scores.

4. Discussion

We report a major excess of suicide deaths inschizophrenia, bipolar disorder and other SMI. Our dataindicate that approximately one in ten of the suicidesrecorded in UK general practice may be attributable toSMI. Although the risk of suicide in schizophreniarelative to the comparison group was highest in peopleaged under 30, it was still raised eight-fold in 50 to70 year olds. Seventy-three percent of suicides inschizophrenia occurred in people aged 30 and over,demonstrating that the risk must be assumed throughoutthe illness. This counters current wisdom that themajority of suicides occur early in schizophrenia andthat suicide-prevention strategies are best deliveredearly in the course of the illness. The relative risk ofsuicide in other SMI was elevated throughout life, butrose sharply, after 50. While suicide rates are raisedacross all groups with SMI, those in the least sociallydeprived areas and those treated for depression are themost at risk.

The importance and novelty of these findings lie inthe large community nature of the sample, rather thanrelying on opportunistic follow-up of relatively smallnumbers of people from less generalisable settings suchas inpatient psychiatric units. The GPRD also provided a

valid community comparison group and allowed us tocontrol for other explanatory factors.

Limitations include the fact that the GPRD lacksvalidated accurate data regarding social, demographic,economic or psychiatric status at the level of theindividual. Data extraction is a major undertaking inthe GPRD and we deliberately chose variables whichare recorded reliably during clinical practice, to ensurethe validity of our results. Furthermore, although re-cording of causes of death and diagnosis of SMI arevalidated in the GPRD, it is a working clinical databaseand some degree of mis-coding is unavoidable. Patientswho are not in contact with general practitioners suchas the homeless may be underrepresented in thissample.

Our finding that SMI patients consult more often andare more likely to be depressed and prescribedantidepressants before their suicide may be a usefulclinical warning sign. In the UK, family practitionerseach have approximately 20 patients with SMI on theirlists and are being urged to monitor them morevigilantly. Patients with SMI consult their doctorsmore often than average (Nazareth et al., 1993b) andare usually well known to them. Although suicideremains an unusual event in SMI, the presence ofdepression and increased consultations in primary carecould alert GPs to monitor the extent of suicidal intent.The false negative rate would be high, but over half thesuicides in SMI were associated with 2 or more GPconsultations over 3 months, compared to the sameperiod in the preceding year.

Role of funding sourceThe study was funded by a Trial Platform grant from the UK

Medical Research Council. Reference: G0301032. The funder had nofurther involvement in the execution or writing of the study, ordecision to submit for publication.

ContributorsDO, IN & MK designed the study, wrote the protocol, supervised

the analysis, interpreted the results and contributed to the finalmanuscript.

DO wrote the initial draft.GL designed the study, analysed the data, interpreted the findings

and contributed to the final manuscript.GL had full access to all of the data in the study and takes

responsibility for the integrity of the data and the accuracy of the dataanalysis.

Conflict of interestNone for all contributing authors.

Acknowledgements

We are grateful to Dr Irene Petersen and Amir Islam for advice andassistance with data management.

138 D. Osborn et al. / Schizophrenia Research 99 (2008) 134–138

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