Injection methamphetamine use is associated with an increased risk of attempted suicide: a prospective cohort study.

Abstract

Methamphetamine (MA) use is a growing public health concern in many settings around the world. While some physical and mental health effects associated with injection MA use have been well described, little is known about the relationship between injecting MA and suicidal behavior. We sought to determine whether MA injection was associated with an increased risk of attempting suicide among a prospective cohort of injection drug users (IDUs) in Vancouver, Canada.
Between 2001 and 2008, eligible participants enrolled in the Vancouver Injection Drug Users Study (VIDUS) completed semi-annual questionnaires that elicited information regarding sociodemographics, drug use patterns, and mental health problems including suicidal behavior. We used Cox proportional hazards models with time-dependent covariates to determine whether self-reported MA injection was an independent predictor of attempting suicide at subsequent time points.
Of 1873 eligible participants, 149 (8.0%) reported a suicide attempt, resulting in an incidence density of 2.5 per 100 person-years. Participants who attempted suicide were more likely to be younger (median: 35 vs. 40, p<0.01), female (48.3% vs. 35.1%, p<0.01), and of Aboriginal ancestry (43.6% vs. 31.3%, p<0.01). In a Cox proportional hazards model, MA injection was associated with an 80% increase in the risk of attempting suicide (adjusted hazard ratio=1.80, 95% CI: 1.08-2.99, p=0.02).
These findings suggest that IDUs who inject MA should be monitored for suicidal behavior. Improved integration of mental health and suicide prevention interventions within harm reduction and drug treatment programs may be fruitful.

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Injection Methamphetamine Use is Associated with an Increased
Risk of Attempted Suicide: A Prospective Cohort Study
Brandon DL Marshall1,2, Sandro Galea2, Evan Wood1,3, and Thomas Kerr1,3
1 British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, 608-1081 Burrard
Street, Vancouver, BC, Canada, V6Z 1Y6
2 Department of Epidemiology, Columbia University Mailman School of Public Health, 722 W
168th Street, New York, NY, USA, 10032-3727
3 Department of Medicine, University of British Columbia, St. Paul’s Hospital, 608-1081 Burrard
Street, Vancouver, BC, Canada, V6Z 1Y6
Abstract
Background—Methamphetamine (MA) use is a growing public health concern in many settings
around the world. While some physical and mental health effects associated with injection MA use
have been well described, little is known about the relationship between injecting MA and suicidal
behavior. We sought to determine whether MA injection was associated with an increased risk of
attempting suicide among a prospective cohort of injection drug users (IDUs) in Vancouver,
Canada.
Methods—Between 2001 and 2008, eligible participants enrolled in the Vancouver Injection
Drug Users Study (VIDUS) completed semi-annual questionnaires that elicited information
regarding sociodemographics, drug use patterns, and mental health problems including suicidal
behavior. We used Cox proportional hazards models with time-dependent covariates to determine
whether self-reported MA injection was an independent predictor of attempting suicide at
subsequent time points.
Results—Of 1873 eligible participants, 149 (8.0%) reported a suicide attempt, resulting in an
incidence density of 2.51 per 100 person-years. Participants who attempted suicide were more
likely to be younger (median: 35 vs. 40, p<0.01), female (48.3% vs. 35.1%, p<0.01), and of
Aboriginal ancestry (43.6% vs. 31.3%, p<0.01). In a Cox proportional hazards model, MA
injection was associated with an 80% increase in the risk of attempting suicide (adjusted hazard
ratio = 1.80, 95%CI: 1.08 – 2.99, p=0.02).
© 2011 Elsevier Ireland Ltd. All rights reserved.
Send correspondence to: Brandon DL Marshall, Postdoctoral Research Fellow, Department of Epidemiology, Columbia University
Mailman School of Public Health, 722 W 168th Street, New York, NY, 10032-3727, Tel: 212-305-2433, Fax: 212-305-1460
bmarshall@cfenet.ubc.ca.
Contributors: Authors BDLM and TK designed the study and wrote the protocol. Author BDLM managed the literature searches and
summaries of previous related work. Author BDLM undertook the statistical analysis with significant scientific input from SG and
TK. Author BDLM wrote the first draft of the manuscript and authors SG, EW, and TK contributed to the main content and provided
critical comments on the final draft. All authors approved the final manuscript
Conflict of interest: All authors declare that they have no conflicts of interest.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
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Author Manuscript
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Published in final edited form as:
Drug Alcohol Depend. 2011 December 1; 119(1-2): 134–137. doi:10.1016/j.drugalcdep.2011.05.012.
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Conclusions—These findings suggest that IDUs who inject MA should be monitored for
suicidal behavior. Improved integration of mental health and suicide prevention interventions
within harm reduction and drug treatment programs may be fruitful.
Keywords
methamphetamine; suicide; injection; drug use; Canada; epidemiology
1. INTRODUCTION
Over the past decade, the availability and use of methamphetamines (MA) has become a
significant public health concern in many regions, with parts of North America, Eastern
Europe, and Southeast Asia experiencing the greatest increases (Global SMART
Programme, 2010; Gonzales et al., 2010; McKetin et al., 2008a). In fact, the global annual
prevalence of MA use and other amphetamine-type substances (0.3% – 1.2% of the
population aged 15 to 64) now exceeds that of opiates and cocaine combined (United
Nations Office on Drugs and Crime, 2010). Although the majority of people who use MA do
so through non-injection routes of consumption, parenteral use is increasingly common and
of particular public health concern (Maxwell and Rutkowski, 2008). Previous studies have
demonstrated that persons who inject MA are: more severely dependent than non-injectors
(McKetin et al., 2008b), at an increased risk of non-fatal overdose (Fairbairn et al., 2008),
more likely to engage in HIV risk behavior (Braine et al., 2005; Fairbairn et al., 2007;
Hayashi et al., 2010; Lorvick et al., 2006), and more likely to experience social stigma
(Semple et al., 2004).
Persons who inject MA are also more likely to have co-occurring psychiatric disorders
compared to non-injection MA users (Hall et al., 1996; Zweben et al., 2004). Consistent
with this observation, preliminary evidence from treatment samples indicates that MA
injectors are more likely to attempt suicide than persons who snort or smoke the drug
(Glasner-Edwards et al., 2008; Zweben et al., 2004). However, it is not clear if injecting MA
augments what is already a greatly elevated risk of suicidal behavior among IDUs,
compared to non-IDUs, in general (Havens et al., 2004).
Determining which subpopulations of IDUs are most likely to attempt suicide has important
policy and programmatic implications, and may serve to inform suicide prevention efforts
and mental health service delivery. However, we know of no longitudinal studies that have
considered whether IDUs who use MA are more likely to attempt suicide than IDUs who do
not use MA. The purpose of this study was thus to answer this question using data derived
from a longstanding community-recruited prospective cohort of IDUs in Vancouver,
Canada.
2. METHODS
2.1 Study Design
Data for this analysis were derived from an ongoing open prospective cohort known as the
Vancouver Injection Drug Users Study (VIDUS). The study began enrolment in May 1996
and recruits individuals through word of mouth, street outreach, and referrals. Sampling and
follow-up methodologies have been described in detail previously (Strathdee et al., 1997;
Tyndall et al., 2003). Participants are eligible if they satisfy the following: are at least 14
years of age; reside in the Greater Vancouver region; injected drugs during the past six
months; and provide informed consent. At baseline and at each six-month visit thereafter,
participants complete an interviewer-administered questionnaire that elicits information
pertaining to sociodemographic characteristics, drug use, treatment utilization, and HIV risk
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behaviors. Nurses also assess participants for various health conditions (including suicidal
behavior), and obtain blood specimens for HIV and hepatitis C serology. Participants
receive $20 CAD for each visit. The study has been approved by the University of British
Columbia/Providence Health Care Research Ethics Board.
2.2 Participants and Measures
Questions assessing lifetime and recent suicidal behavior were first added to the study
instrument in May 2001; therefore, all participants who completed at least one interview
after this date were eligible for inclusion. The study period was defined as the seven-year
interval ending in May 2008.
The primary outcome for this analysis was time to first report of suicidal behavior, defined
as a positive response to the question, “In the past 6 months, have you attempted suicide?”
The primary exposure of interest was self-reported MA injection at least once in the past six
months (yes vs. no). In a sub-analysis, we also considered MA injection as a categorical
variable with the following levels: no MA injection, infrequent (i.e., <daily) MA injection,
and frequent (i.e., ! daily) MA injection. We assessed as potential confounders measured
variables that have been identified as risk factors for suicidal behavior in IDUs (Darke and
Kaye, 2004; Havens et al., 2006; Havens et al., 2004). These included the following
sociodemographics: age (per year older), years injecting (per year), sex (female vs. male),
relationship status (married/common law/regular partner vs. single/dating), sexual
orientation (lesbian, gay, bisexual, transgendered [LGBT] vs. heterosexual) and belonging to
a minority group. We dichotomized participants as being Aboriginal (self-identified
Aboriginal, First Nations, Inuit, or Métis ancestry) versus other due to increased rates of
suicide in Aboriginal communities observed previously (Malchy et al., 1997). Other
potential confounders examined included: homelessness, incarceration, current enrolment in
a methadone maintenance program, experiencing physical violence, sex trade work, and any
use of non-injection crack, injectable heroin, injectable cocaine, and non-injection
methamphetamine (all yes vs. no). Non-injection heroin use and frequent (! daily) non-
injection MA use are rarely reported by VIDUS participants and thus were not included as
potential predictors of suicidal behavior. Unless otherwise indicated, all variables refer to
behaviors occurring in the six-month period preceding the date of the interview.
2.3 Statistical analyses
As a first step, we compared the sociodemographic characteristics of those who reported
attempting suicide over the study period versus those who did not using the Pearson chi-
square test for categorical variables and the Wilcoxon test for continuous variables. We then
used survival analysis to determine the association between MA injection and time to first
suicide attempt among cohort participants. Since the study instrument assessed past six-
month suicidal behavior, the exact date of first suicide attempt was estimated as occurring
three months prior to the date of the interview. All participants who reported a suicide
attempt were right-censored as of this date. Persons who never reported a suicide attempt
were right-censored as of their last study visit. We used the person-time method to calculate
the incidence of suicidal behavior over the study period.
In order to account for potential confounders and repeated measures over time, Cox
proportional hazards models with time-dependent covariates were used to calculate the
unadjusted and adjusted hazard ratios for each variable. To avoid associations attributable to
reverse causation, the covariate values obtained at the follow-up prior to that in which a
suicide attempt was recorded were used to predict the likelihood of this outcome. All
covariates significant at an a priori cut-off of p < 0.05 were included in a final multivariate
model. In order to determine whether polydrug use (i.e., injecting MA plus at least one other
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drug concurrently during the past six months) further increased the risk of attempted suicide,
interaction effects were assessed post hoc, and if significant, added to the final model. The
variable corresponding to years injecting was excluded as it was found to be collinear with
age. The proportional hazard assumption was assessed by examining time-by-covariate
interactions (Hess, 1994). All statistical analyses were conducted using SAS 9.1.3, and all p-
values are two-sided.
3. RESULTS
Over the study period, 1873 eligible participants contributed 5948 years of follow-up. The
median age of the sample was 31 (interquartile range [IQR]: 32 – 46), 677 (36.2%) were
female, and 601 (32.1%) were of Aboriginal ancestry. In total, 149 (8.0%) persons reported
a suicide attempt, resulting in an incidence density of 2.51 per 100 person-years (95%CI:
2.13 – 2.93 per 100 person-years). Participants who attempted suicide were younger,
reported fewer years injecting, and were more likely to be female and Aboriginal (Table 1).
We did not observe differential loss to follow-up among study participants: the group who
failed to return after their first visit did not differ with respect to age (p = 0.67), sex (p =
0.67), or ancestry (p = 0.97).
Factors associated with time to first suicide attempt are shown in Table 2. In a multivariate
model, MA injection remained a strong predictor of attempting suicide (adjusted hazard
ratio [AHR] = 1.80, 95%CI: 1.08 – 2.99, p = 0.02). Tests of time-by-covariate interactions
demonstrated that the proportional hazards assumption was met. Each of three interaction
effects (i.e., injecting MA plus injecting cocaine, injecting heroin, or crack) was non-
significant, indicating that polydrug use neither increased nor decreased the risk of
attempted suicide in this sample.
As a final step, we examined whether a dose-response relationship was observed between
frequency of MA injection and increased likelihood of suicidal behavior. Considering MA
injection as a categorical variable provided evidence that such a relationship exists.
Compared to periods of no MA injection, infrequent MA injection was a predictor of
attempting suicide (HR = 2.12, 95%CI: 1.23 – 3.66, p = 0.01), while frequent MA injection
was associated with the greatest risk of attempting suicide (HR = 2.68, 95%CI: 1.08 – 6.60,
p = 0.03).
4. DISCUSSION
In this seven-year study, we found that IDUs who injected methamphetamine had an 80%
greater risk of attempting suicide than those who did not, even after taking into account a
wide range of potential confounders. Sub-analyses indicated a dose-response relationship
between frequency of injecting MA and suicidal behavior.
Our results support earlier cross-sectional analyses of persons participating in an MA
outpatient treatment intervention demonstrating that, at program entry, IDUs reported more
lifetime suicide attempts than non-IDUs (Glasner-Edwards et al., 2008; Zweben et al.,
2004). Although an elevated prevalence of attempted suicide has been observed previously
among populations of non-injection MA users in the US (Kalechstein et al., 2000) and
Taiwan (Yen and Shieh, 2005), our results suggest that persons who inject MA should be
considered at a very high risk of suicide among populations of MA users and the broader
global IDU community. Further, this study both builds on previous findings and overcomes
many of the limitations of cross-sectional designs by following individuals prospectively
and using survival analysis to ensure that the exposure of interest preceded the reports of
suicide attempt.
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Although the etiologic pathway between injecting MA and suicidal behavior requires further
investigation, it is likely that a combination of neurobiological, social, and structural
mechanisms account for this association. For example, chronic MA users experience
reduced dopamine neurotransmission (Volkow et al., 2001; Wang et al., 2004), which itself
may play a role in inducing anhedonia, depression and suicidal behavior (Roy et al., 1992).
However, given that these studies focus on non-injection MA users, it is not clear if similar
neurobiologic mechanisms may explain the differential attempted suicide rates observed
between MA using IDUs and non-MA using IDUs in this study. Compared to other IDU, it
is possible that MA users have more isolated social networks and thus poorer social support
systems (Shaw et al., 2008). MA injectors may also face unique barriers to accessing IDU-
focused health and social services (Marshall et al., 2011). For example, addiction treatment
programs and supportive housing services that cater to opioid injectors may be unable to
accommodate the specific health needs of IDUs who use MA or are experiencing MA-
induced withdrawal symptoms (Degenhardt et al., 2010). Future studies that combine
neurobiologic analyses with social epidemiologic approaches may provide greater insight
into these potential mechanisms.
This study has several limitations that should be noted. First, although a variety of
techniques are undertaken to ensure that the sample is representative, caution is
recommended when generalizing these findings to other settings. A second limitation is that
both the exposure and outcome of interest are self-reported. Given that suicide is a highly
stigmatized behavior, it is likely that the observed incidence of attempted suicide is an
underestimate. Third, although previous studies have shown that suicidal ideation is elevated
among MA-using women (Kalechstein et al., 2000), we were unable to conduct gender-
stratified analyses due to the relatively small number of events and females in our sample.
Fourth, we were unable to control for several previously identified risk factors for suicide
among MA users. For example, although history of prior suicidal behavior, comorbid mental
health conditions including depressive disorder, and history of abuse are important
predictors of suicide attempts (Dube et al., 2001; Forman et al., 2004; Henriksson et al.,
1993), this information was either not collected or not available for the entire study period. It
is therefore possible that residual confounding may explain some of the observed association
between MA injection and suicidal behavior, and thus our results should be interpreted with
caution.
This study has a number of implications for clinic- and community-based services for IDUs.
The high rate of attempted suicide observed in this and in other studies suggests that suicide
prevention efforts should be an integral part of substance abuse treatment programs
(Glasner-Edwards et al., 2008; Lloyd et al., 2007). Further, out-of-treatment IDUs who
inject MA, particularly frequently, would likely benefit from improved suicide risk
assessment and other mental health support services within health care and community-
based settings. Although the incorporation of harm reduction principles within community-
based mental health programs is a relatively new phenomenon (Mancini and Linhorst,
2010), improved integration between harm reduction interventions and mental health
programs including suicide prevention efforts for this population may be fruitful.
In summary, these results demonstrate an increased risk of attempted suicide among IDUs
who use methamphetamine. While the precise mechanisms underlying the association
between MA injection and suicidal behavior remain to be elucidated, this study provides
preliminary evidence that persons who inject methamphetamine should be a major focus of
future suicide prevention efforts.
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Acknowledgments
Role of funding source: Funding for this study was provided by a National Institutes of Health (NIH) grant R01-
DA011591 and a Canadian Institutes of Health Research (CIHR) grant RAA-79918. Thomas Kerr is supported by a
Scholar Award from the Michael Smith Foundation for Health Research (MSFHR) and an Investigator Award from
the CIHR. Brandon Marshall is supported by postdoctoral fellowships from the CIHR and the International AIDS
Society/National Institute on Drug Abuse. All funding bodies had no further role in study design; in the collection,
analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
The authors thank the study participants for their contribution to the research, as well as current and past
investigators and staff. We would specifically like to thank Deborah Graham, Peter Vann, Caitlin Johnston, Steve
Kain, and Calvin Lai for their research and administrative assistance. We would particularly like to thank Marta
Prescott for her assistance with the statistical analysis.
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Table 1
Sociodemographic characteristics of injection drug users (IDU) who did and who did not attempt suicide,
2001–2008 (N = 1873).
Characteristic
Attempted Suicide N (%)
N = 149¶
Did Not Attempt Suicide N (%)
N = 1724¶
P-value
Age† (median, IQR)
35 (29 – 43)40 (33 – 46) <0.01
Years injecting‡ (median, IQR)
17 (14 – 21)19 (16 – 26)<0.01
Sex (n, %)
Female72 (48.3) 605 (35.1)<0.01
Male77 (51.7)1119 (64.9)
Ethnicity (n, %)
Caucasian73 (49.0) 1042 (60.8)0.01
Aboriginal*
65 (43.6) 536 (31.3)
Asian7 (4.7)59 (3.4)
Other4 (2.7)78 (4.5)
Sexual Orientation (n, %)
LGBTa
19 (16.1) 139 (10.4)0.06
Heterosexual99 (83.9)1199 (89.6)
Note:
†age at first interview during follow-up;
‡number of years injecting at first study visit;
*Aboriginal includes self-identified First Nation, Inuit, or Métis ancestry; a LGBT = lesbian, gay, bisexual, or transgendered/transsexual;
¶note: columns do not add to 100% due to missing or unavailable data.
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Table 2
Cox proportional hazards model of time to first suicide attempt among a cohort of injection drug users in Vancouver, 2001–2008 (n = 1873).
Characteristic
Unadjusted HR* (95% CI)
P – value
Adjusted HR* (95% CI)
P – value
Age (per year older)
0.96 (0.95 – 0.98)
<0.01
0.98 (0.96 – 1.00)
0.05
Sex (female vs. male)
1.59 (1.15 – 2.19)
0.01
1.32 (0.91 – 1.92)
0.15
Ethnicity (Aboriginal ancestry vs. other)
1.59 (1.15 – 2.19)
0.01
1.36 (0.93 – 1.97)
0.11
Sexual Orientation (LGBTa vs. heterosexual)
1.55 (0.95 – 2.54)
0.08
Relationships Status (married vs. single/dating)
1.14 (0.76 – 1.69)
0.53
Homeless† (yes vs. no)
1.74 (1.17 – 2.59)
0.01
1.22 (0.79 – 1.87)
0.37
Non-injection Crack Use† (yes vs. no)
1.61 (1.09 – 2.38)
0.02
1.28 (0.79 – 1.87)
0.21
Injection Heroin Use† (yes vs. no)
1.47 (1.01 – 2.16)
0.04
1.16 (0.78 – 1.71)
0.46
Injection Cocaine Use† (yes vs. no)
1.54 (1.07 – 2.23)
0.02
1.29 (0.87 – 1.92)
0.21
Injection Methamphetamine Use† (yes vs. no)
2.15 (1.32 – 3.49)
<0.01
1.80 (1.08 – 2.99)
0.02
Non-injection Methamphetamine Use† (yes vs. no)
1.48 (0.69 – 3.17)
0.32
Incarceration† (yes vs. no)
1.13 (0.71 – 1.78)
0.61
Methadone Maintenance Therapy‡ (yes vs. no)
0.81 (0.56 – 1.17)
0.26
Experience Physical Violence† (yes vs. no)
1.54 (1.04 – 2.28)
0.03
1.38 (0.92 – 2.06)
0.12
Sex Trade Work† (yes vs. no)
1.46 (0.94 – 2.26)
0.09
Note:
*HR = Hazard Ratio; a LGBT = lesbian, gay, bisexual, transgender/transsexual;
†refers to activities in the past 6 months;
‡refers to current experiences.
Drug Alcohol Depend. Author manuscript; available in PMC 2012 December 1.