Dozens of common medications, both prescription and over-the-counter, can impair your ability to drive safely. The list is longer than most people expect: it includes allergy pills, sleep aids, muscle relaxants, antidepressants, opioid painkillers, anti-anxiety drugs, antiseizure medications, and even some diarrhea and bladder-control treatments. In an NHTSA study of seriously or fatally injured road users, nearly 56% tested positive for at least one drug, with sedatives detected in 7.5% and opioids in 9.3% of cases.
Antihistamines and Allergy Medications
First-generation antihistamines are among the most widely underestimated driving hazards because they’re sold without a prescription. Diphenhydramine (the active ingredient in Benadryl and many nighttime cold formulas) is the biggest offender. In a driving simulator study, a single 50 mg dose of diphenhydramine impaired lane-keeping and steering stability more than a blood alcohol level of 0.10%, which is above the legal limit in every U.S. state. Participants were drowsier after taking diphenhydramine than after drinking alcohol, yet many didn’t fully recognize how impaired they were.
Diphenhydramine has a half-life of about 8 hours, meaning it takes that long for your body to clear just half the dose. Impairment peaks around 2 to 4 hours after you take it but can linger well beyond that window. Other first-generation antihistamines like chlorpheniramine and hydroxyzine carry similar risks, with hydroxyzine’s half-life stretching to roughly 29 hours.
Second-generation antihistamines like loratadine (Claritin), fexofenadine (Allegra), and cetirizine (Zyrtec) were designed to cause less drowsiness. Fexofenadine and loratadine are generally considered safe for driving. Cetirizine sits in a gray area: it causes noticeably more sedation than the other two, especially at higher doses.
Sleep Aids and Sedatives
Sleeping pills pose an obvious risk, but the surprise is how long that risk persists into the next morning. Zolpidem (sold as Ambien) is the most studied example. Eight hours after taking a 10 mg immediate-release dose, 15% of women and 3% of men still had blood levels high enough to impair driving. With the extended-release version at 12.5 mg, those numbers jumped to 33% of women and 25% of men.
Women clear zolpidem more slowly than men, which led the FDA to cut the recommended dose for women in half: from 10 mg to 5 mg for immediate-release products and from 12.5 mg to 6.25 mg for extended-release formulations. For people taking the extended-release version at any dose, the FDA advises against driving the entire day after use, even after a full night’s sleep.
A particularly dangerous detail: people impaired by residual zolpidem frequently don’t realize they’re impaired. Self-perception is not a reliable gauge, so “feeling fine” the next morning doesn’t mean you’re safe to drive.
Benzodiazepines and Anti-Anxiety Drugs
Benzodiazepines, prescribed for anxiety, panic disorders, and sometimes insomnia, consistently show up in driving impairment research. These medications slow reaction time, reduce coordination, and impair divided attention, which is the ability to track multiple things at once (other cars, traffic signals, pedestrians). The sedation can be profound, especially in the first days of treatment or after a dose increase. Longer-acting benzodiazepines carry risk well into the following day, similar to the pattern seen with sleep aids.
Opioid Pain Medications
Opioids, including prescription painkillers and cough suppressants containing codeine or hydrocodone, cause sedation, slowed reaction times, and impaired concentration. In the NHTSA study of injured road users, opioids were detected in 9.3% of cases. The risk is highest when you first start taking an opioid or when your dose changes. Some people develop partial tolerance to the sedating effects over time, but impairment in complex tasks like driving can persist even when you no longer feel obviously drowsy.
Antidepressants
Not all antidepressants carry the same driving risk. Older tricyclic antidepressants (TCAs) are the worst performers, causing measurable impairment in reaction time, stress tolerance, and selective attention. Patients on TCAs performed significantly worse on psychomotor and visual perception tests compared to those on newer medications.
SSRIs (like fluoxetine or sertraline) are considerably safer for driving, though they can still alter sleep patterns and occasionally cause tremor. Mirtazapine, another newer antidepressant, showed a significant impact on divided attention and alertness even at standard doses. Venlafaxine also performed worse than SSRIs in driving-related assessments. If driving ability is a concern, SSRIs generally have the most favorable profile among antidepressants.
Muscle Relaxants
Cyclobenzaprine is the most commonly prescribed muscle relaxant for back pain, and it causes substantial driving impairment. In a controlled study, cyclobenzaprine significantly worsened lane-keeping ability compared to placebo, with participants drifting more within their lane and responding to stimuli with less consistency. By day two of treatment, reaction time variability was significantly worse. Drowsiness affected about 30% of people taking cyclobenzaprine, and roughly 9% experienced dizziness. Older adults are especially vulnerable because muscle relaxants’ sedating and balance-disrupting effects compound age-related changes in coordination.
Antiseizure and Antipsychotic Drugs
Antiseizure medications (also called anticonvulsants) can cause dizziness, drowsiness, and impaired coordination. These effects tend to be most pronounced when starting treatment or adjusting doses, though some degree of cognitive slowing can persist. Antipsychotic medications carry similar risks, with sedation and slowed processing speed being the primary concerns for driving safety.
Other Medications to Watch For
Several other categories make the FDA’s list of drugs that could make driving dangerous:
- Medications for diarrhea or bladder control often have anticholinergic properties that cause blurred vision, dizziness, and confusion.
- Motion sickness treatments frequently contain first-generation antihistamines or scopolamine, both strongly sedating.
- Eye drops and ophthalmic medications can cause temporary blurred vision or dizziness.
- Stimulants including diet pills and high-dose caffeine products may seem like they’d help alertness, but they can cause jitteriness, impaired judgment, and rebound fatigue.
- Cannabis-derived products including CBD may impair driving ability.
- Diabetes medications that lower blood sugar can cause confusion, dizziness, and slowed thinking if blood sugar drops too low while driving.
Why the First Few Days Matter Most
For most sedating medications, impairment is strongest when you first start taking them or when your dose increases. Your body may partially adjust over days to weeks, but that adjustment is unpredictable and incomplete for many drugs. A practical approach: avoid driving for at least the first several days after starting any medication known to cause drowsiness, and pay close attention to how you feel during routine tasks before getting behind the wheel.
Keep in mind that combining even mildly impairing medications can multiply the effect. Taking an antihistamine on top of a muscle relaxant, or drinking alcohol while on a benzodiazepine, can produce impairment far greater than either substance alone. Nearly 20% of seriously injured road users in the NHTSA study tested positive for two or more drug categories simultaneously. The label on your medication bottle is a starting point, but it won’t account for everything else in your system.