Mortality among amphetamine users: A systematic review of cohort studies

Abstract

Aims

To report the results of a comprehensive literature search of studies of mortality among people who use amphetamines.

Design and setting

Three electronic databases were searched (EMBASE, Medline and PsycINFO) and “grey” literature was located. Shortlists of papers were circulated to experts to ascertain whether any important papers had been missed. Papers were hand-searched to retrieve any additional relevant articles.

Measurements

Studies meeting inclusion criteria were prospective cohort studies examining mortality risk among dependent and problematic amphetamine users. Crude mortality rates (CMR/100PY) and standardised mortality ratios (SMRs) were the primary outcome measures considered. Data on overall mortality, and rates for specific causes of death, were of interest.

Findings

2187 articles and 9 grey literature sources were obtained. After thorough review, 72 articles were identified as reporting on amphetamine-related mortality, 7 provided data from cohort studies of users. An additional study of Swedish military conscripts was identified by the authors during correspondence with other researchers. The geographic spread of cohorts was restricted to high income countries with the exception of one Thai study; reporting of standard parameters in mortality studies was often sparse. The estimated CMRs ranged from 0 in Australia to 2.95 (1.46–4.59) in Thailand. The Czech cohort reported the only SMR: 6.22 overall, males: 5.87, females: 7.84.

Conclusions

Given the widespread use of amphetamines, the known non-fatal adverse effects of use and the mortality rates reported here, cohort studies investigating the morbidity and mortality associated with such drug use should be a research priority.

Introduction

The global prevalence of the use of amphetamines is thought to have increased rapidly during the 1990s. Globally, the market for amphetamines is second only to cannabis (UNODC, 2007) and in several East Asian countries, methamphetamine is the most commonly used illicit drug (Kozel et al., 2007), with recent data suggesting expanding markets in South Africa, Iraq and the Middle East (UNODC, 2008). Amphetamines are currently the dominant drug of concern in the Pacific and in several countries in East Asia (Kozel et al., 2007). In Czech Republic and Slovakia, methamphetamine is the most commonly injected drug (Griffiths et al., 2008), and recent data from research studies and treatment centres strongly suggest an increase in (injecting) use of methamphetamine and methcathinone in Ukraine, Georgia, Armenia, and the Russian Federation (Grund et al., 2009).

The term “amphetamines” refers to a range of drugs related to amphetamine which share stimulant properties that increase the concentration of dopamine in the terminals of neurons, and the desired effects may include euphoria, perception of increased energy, increased concentration and mental alertness and feelings of greater power and self-confidence. Amphetamines can include amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, or “ecstasy”), methcathinone, and ephedrine. They may also include pharmaceutical drugs such as phentermine. Methamphetamine and amphetamine are now the major illicit amphetamines available worldwide (UNODC, 2008).

A review by Darke et al. (2008) highlighted the adverse physical and psychological consequences of amphetamine use. Amphetamine has a number of adverse side effects that include physical manifestations such as sweating, heart palpitations, headaches, tremors, and increases in body temperature (Dean, 2004, Degenhardt and Topp, 2003). Adverse psychological side effects include restlessness, anxiety, dizziness, irritation, confusion and aggression (Dean, 2004, Degenhardt and Topp, 2003). Cardiovascular toxicity includes arrhythmias, acute myocardial infarction and cardiomyopathy (Dean, 2004, Yu et al., 2003). Cerebrovascular toxicity includes stroke, aneurysm, and cerebral haemorrhage (Dean, 2004, Lee, 2004).

Given the number of people potentially at risk, and the suggestive evidence that dependent amphetamine use is increasing in some countries, there is a need to better understand the mortality risk among this group. To our knowledge there has to date not been a systematic review of mortality among problematic or dependent amphetamine users. This paper presents the results of a systematic review of mortality in problematic or dependent amphetamine users.

Mortality related to the use of “ecstasy” (MDMA) was not included in this review. There have been case reports of deaths following the use of MDMA but the number of such deaths, considering the prevalence of use, is very low (Gowing et al., 2002). Polydrug use and the variability of the ingredients of pills sold as ecstasy make it difficult to determine the role of MDMA in fatalities (Silins, in press). The case reports of MDMA-related deaths indicate that other licit and illicit substances were also present, complicating the determination of cause of death. Gore et al attempted to quantify the mortality risk to MDMA users but deficiencies in the data resulted in wide uncertainty intervals (Gore, 1999). In addition, the context of use and nature and extent of adverse side effects are likely to differ significantly from amphetamines (Degenhardt and Hall, in press). The existence of an MDMA dependence syndrome, although studied in several papers, remains the subject of some debate and is likely to be qualitatively different to that for amphetamines (Degenhardt and Hall, in press). Finally, very few prospective studies of ecstasy users have been conducted (e.g. Alati et al., 2008) and we could not find any analysis of mortality risk among these cohorts.

This review was undertaken by members of the Mental Disorders and Illicit Drug Use Expert Group as part of the update of the Global Burden of Disease (GBD) project. The data reported in this review have been submitted to the Global Burden of Disease project and will be used to contribute to the calculation of the morbidity and mortality associated with dependent use of amphetamines (see www.gbd.unsw.edu.au for more information about the work of the Expert Group and of the GBD project as a whole).