EFFECTS ON DRIVING ABILITY
Antidepressants are prescribed most often for clinical depression and severe cases of depression. Jones, Shinar, and Walsh (2003) provide a breakdown of the subclasses of antidepressants with examples. Subclasses include: the tricyclic antidepressants (e.g., amitriptyline and doxepin); the serotonin-specific reuptake inhibitors (SSRI) including fluoxetine (Prozac); monoamine oxidase inhibitors (MAOIs), including phenelzine (Nardil); and several new drugs such as venlafaxine (Effexor) and nefazodone (Serzone). With regard to antidepressants, Walsh et al. (2004) cites EMCDDA (1999) who reviewed controlled experimental studies and concluded that impaired performance is associated with the use of most sedative tricyclic antidepressants. New-generation antidepressants do not seem to interfere with performance, except when used at higher doses. Analytical epidemiological studies, using predominantly older drivers, have documented increased crash risks, with a relative risk of 2.3 Leveille, Buchner, Koepsell, McCloskey, Wolf, and Gagner (1994).
Ramaekers (2003) summarized the major results of all studies published from 1983 to 2000 that investigated the effect of antidepressants on driving performance. This report considered two broad classes of antidepressants: sedating antidepressants, i.e., drugs developed for the management of depression that have depressant side effects, and nonsedating, i.e., drugs developed for the management of depression that lack significant sedating effects. The sedating antidepressants are the tricyclic antidepressants amitriptyline, imipramine, and doxepin and the related compounds mianserin and mirtazapine. Examples of nonsedating antidepressants include the monoamine oxidase inhibitor moclobemide, the selective serotonin reuptake inhibitors fluoxetine, paroxetine, and nefazodone, and the serotonin and norepinephrine uptake inhibitor (SNRI) venlafaxine.32 The effect of antidepressants on driving behavior was assessed with the standard deviation of lateral position (SDLP) test. A detailed description of this methodology for measuring driver performance follows in the section of this report titled “On-Road Testing.”
Ramaekers (2003) found that acute doses of sedating antidepressants produced effects in the SDLP that were comparable to those seen in subjects with a blood alcohol concentration of .08 grams per deciliter. The tricyclic antidepressants had little effect on the SDLP after one week of treatment, but the effect of mianserin persisted throughout the treatment period. Nocturnal doses of sedating antidepressants did not alter the SDLP when assessed the next day after treatment. The nonsedating antidepressants failed to alter the SDLP. Increases in the SDLP were, however, observed after the combined use of nonsedating antidepressants and benzodiazepines; these effects were attributed to pharmacokinetic drug interactions: Effects were seen when the cytochromes P450-dependent metabolism of the benzodiazepine was inhibited by the antidepressant given.
Lithium is used for the treatment of bipolar disorder, but its use is associated with impaired memory and slow reaction times (Honig et al., 1999) . A recent case-control study of 5,579 subjects age 67 to 84 found that the current use of lithium was higher (rate ratio = 2.08) among subjects who had been involved in an injurious motor vehicle crash compared with control subjects (Etminan et al., 2004) . No information about drug interactions with lithium was reported in this study.
32 It should be noted that although Ramaekers (2003) categorized paroxetine and nefazodone as nonsedating, in practice they are considered to be sedating. Personal communication from Richard Marottoli , M.D., M.P.H., Yale University School of Medicine to Kathy Lococo, 7/20/2005.