Posts Tagged ‘Opiods’

Drugging and Driving: Benzos, opioids and antidepressants and increased risk of driving accidents

May 11, 2011 1 comment

ResearchBlogging.orgThere are many reasons why one might find it preferable not to drive an automobile: For one, it’s expensive (gas, insurance, repairs, and tickets). It pollutes the environment. And its dangerous. Based on data from the Federal Highway Administration, there are over 6 million auto accidents in the United States every year on average. And around 40,000 of those accidents result in people being killed by people driving under the influence of alcohol.

A new study from Australian researchers provides another reason to hop on the bus or train rather than get behind the wheel. The study looked at the association between driving and taking prescription medications. And the results were not very promising, showing that users of many prescription medications are at increased risk for car accidents.

The researchers performed what is called a meta-study, in which all the research that can be located pertaining to a given topic, and meeting certain criteria of validity and reliability, is combined into a single pool of data in an attempt to achieve maximal statistical power. Two different types of studies were examined:

1. Epidemiological studies. These are studies of patterns of association between prescription drugs and driving accidents based on real-life data coming from a variety of sources. There are several advantages and drawbacks to these kinds of studies and Wikipedia is a good place to get some background. These studies utilize real world data, so one can at least be relatively confident that the data represent natural phenomena. On the other hand, epidemiological studies are correlational; in other words, the data can indicate two variables are related, but can’t definitively tell you about the causal direction of the relationship.

2. Experimental Studies. These are controlled studies that allow researchers to explore causal relationships between variables. Again, wiki is a good place to go for a primer. Experimental studies can explore causality, if they’re designed correctly, but may lack “ecological validity”; that is, they may not represent “real world” conditions.

The goal of this  meta-study was to ascertain whether the data from numerous sources, including epidemiological and experimental studies, converged on the same conclusions.

Several classes of prescription drugs were examined:
1. Benzodiazepines: these include drugs such as diazepam, flurazepam, flunitrazepam and nitrazepam. They’re commonly prescribed for generalized anxiety disorder, panic disorder, insomnia, seizures and alcohol withdrawal.
2. Non-benzo hypnotics: Include drugs like pentobarbital. These are frequently prescribed for insomnia.
3. Antidepressants, which can be divided into two classes: SSRIs and TCAs. SSRIs include drugs like Lexapro, Prozac, and Celexa. TCAs, or trycylic antidepressants, include drugs like mipramine (Tofranil) and maprotiline (Ludiomil).
4. Anxiolytics (anti-anxiety drugs)
5. Opioids

For those interested in the details, please consult the study. I’ll just be presenting a simplified summary of the findings. But before I get there, just a couple of quick thoughts. Meta studies can often be difficult to interpret. In this study there are many potential confounding variables, such as a huge variety of different types of drug, varying range of dose, the problem that those on medication also have depression, anxiety, and other disorders (making it difficult to parse out the effects of the drug alone), tolerance effects, age and gender effects, the possibility that the epidemiological studies only include the worst cases (only accidents that resulted in injury), and so on. It becomes very difficult to make conclusive or generalizable statements about the findings. Some researchers are opposed to meta studies for that very reason. That being said, the evidence here does seem to have reasonably converged toward a handful of conclusions. Keeping the limitations in mind, here they are:

1. Benzodiazepine users show 60-80% increased risk of traffic accidents. Drivers responsible for causing an accident are 40% more likely to be positive for benzos than those who are not responsible. Elderly people show decreased risk (versus non-elderly).

2. Benzodiazepine users who also drink alcohol show a 7.7 fold increase in risk for traffic accidents

The 2- to 3-fold increase in accident risk associated with … long-acting benzodiazepines and zopiclone is equivalent to what has been observed with a blood alcohol concentration of 0.05–0.08 g/dL,[100,101] which is above the legal limits for driving in most countries…

The authors recommend that anyone prescribed benzodiazepine should abstain from driving for the first four weeks of treatment.

3. Anxiolytics seems to impair drivers independent of the drug’s half life. (A half life is the duration of action of a drug and indicates the period of time required for the concentration of the  drug in the body to be reduced in half.)

4. Impairment caused by hypnotics tends to be related to the drug’s half life.

For hypnotic medication, an option for prescribers is to avoid these hypnotics (flurazepam, flunitrazepam, nitrazepam and zopiclone) if patients are engaged in driving. Relatively safer alternatives would be shorter acting hypnotics, such as triazolam, temazepam, zolpidem and zaleplon, which were not found to cause driving impairment, at least in experimental studies (although there is evidence that some of the drugs are associated with increased accident risk)…

5. As far as antidepressants go, no clear distinction emerged between sedative and non-sedative subclasses (according to epidemiological studies). One major confounding variable in the studies examined is depression itself, as cognitive and psychomotor deficits are associated with depression alone. Furthermore, antidepressants might interact differently depending on stage of treatment, e.g. effects of antidepressants take one to two weeks to appear, so driving may be even more impaired over this time period than depression alone or after drug effects kick in.

Sedative antidepressants probably lead to worse driving for the first 3-4 weeks, and until tolerance to sedative effects increases and depression lifts. This is supported by some experimental evidence. (Patient groups with sedative/non-sedative antidepressants improved their driving skills after a few weeks). Epidemiological studies suffer from the confound of comparing groups on anti-depressants (people with depression) with those not on anti-depressants (people who don’t have depression) and are therefore of limited utility.

6. Opioids – There weren’t enough studies of opioids and driving to make any conclusions.

I wasn’t able to locate data indicating how many people in the US are currently taking the drugs mentioned in this study. What I did find was that antidepressants (many of which are probably sedatives) are the most popular prescription drug for adults aged 20 to 59 in the US. And the most recent annual data (from the CDC) suggests that 48% of Americans took at least one prescription drug in the past month. This suggests the possibility that the number of those driving under the influence of cognitively-impairing prescription drugs is likely to be in the millions country wide. Cause for concern? Perhaps. Prescription drugs use is on the rise. And much of the US population lives in geographic regions where there are few alternatives to driving.

Dassanayake T, Michie P, Carter G, & Jones A (2011). Effects of benzodiazepines, antidepressants and opioids on driving: a systematic review and meta-analysis of epidemiological and experimental evidence. Drug safety : an international journal of medical toxicology and drug experience, 34 (2), 125-56 PMID: 21247221

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