Section 5: Medications

1. Alcohol

2. Anticholinergics

3. Anticonvulsants

4. Antidepressants

  1. Bupropion
  2. Mirtazapine
  3. Monoamine oxidase (MAO) inhibitors
  4. Selective serotonin reuptake inhibitors (SSRI)
  5. Tricyclic antidepressants (TCA)

5. Antiemetics

6. Antihistamines

7. Antihypertensives

8. Antiparkinsonians

9. Antipsychotics

10. Benzodiazepenes and other sedatives/anxiolytics

11. Muscle relaxants

12. Narcotic analgesics

13. Nonsteroidal anti-inflammatory drugs (NSAID)

14. Stimulants

Many commonly used prescription and over-the-counter medications can impair driving performance. In general, any drug with a prominent central nervous system (CNS) effect has the potential to impair an individual’s ability to operate a motor vehicle. The level of impairment varies from patient to patient, between different medications within the same therapeutic class, and in combination with other medications or alcohol.

Medication side effects that can affect driving performance include drowsiness, dizziness, blurred vision, unsteadiness, fainting, slowed reaction time, and extrapyramidal side effects. In many cases, these side effects are dose-dependent and attenuate with time.

Whenever possible, the physician should prescribe non-impairing medications. If the physician must prescribe or change the dosage of a medication that can potentially impair driving performance, he/she should counsel the patient regarding the side effects. He/she should also recommend that the patient take the first few doses in a safe environment to determine the presence and extent of any side effects, and that he/she temporarily cease driving as needed until the body has adjusted to the medication.

In addition to being alert to potential side effects, the patient should also understand that with certain medications, subjective effects do not always correlate with impairment.20-23 Medications that cause drowsiness, euphoria, and/or anterograde amnesia may also diminish insight, and the patient may experience impairment without being aware of it. In the case of these medications, the concerned physician and patient may wish to consider formal psychomotor testing (up to and including driving simulation) or driver evaluation (including on-road assessment) performed by a driver rehabilitation specialist, while off and on the medication to determine the extent of impairment.

When prescribing new medications, the physician should always consider the patient’s existing regimen of prescription and non-prescription medications, including medications taken seasonally. Combinations of drugs may affect drug metabolism and excretion to produce additive or synergistic interactions. In fact, use of multiple psychoactive medications is a common cause of hospitalization for delirium among older adults.24 Because individuals react differently to drug combinations, the degree of impairment caused by polypharmacy may vary from patient to patient. With polypharmacy’s strong but unpredictable potential to produce impairment, physicians should add new medications at the lowest dosage possible, counsel the patient to be alert to any impairing side effects, and adjust the dosages of individual medications as needed to achieve therapeutic effects with a minimum of impairment.


Section 5: Medications


Alcohol

As little as one serving of alcohol (1.25 oz. 80 proof liquor, 12 oz. beer, 5 oz. wine) has the potential to impair driving performance in many individuals. In many cases, individuals may be impaired without being aware of it. Furthermore, alcohol can potentiate the central nervous system (CNS) effects of medications to produce profound and dangerous levels of impairment. Physicians should always warn their patients against drinking and driving, and against combining alcohol with their CNS-active medications.

For recommendations on alcohol abuse, see Section 6.

Anticholinergics

When a patient takes single or multiple medications with anticholinergic activity (including some antidepressants, antihistamines, antiemetics, antipsychotics, and antiparkinsonian drugs), the physician should be alert to the possibility of anticholinergic toxicity and adjust medication dosages accordingly.

Anticholinergic effects that can impair driving performance include blurred vision, sedation, confusion, ataxia, tremulousness, and myoclonic jerking. Patients should be counseled about these symptoms and should alert their physician immediately if these symptoms occur. Patients should also be advised that psychomotor and cognitive impairment may be present even in the absence of subjective symptoms.

Subtle deficits in attention, memory, and reasoning may occur with therapeutic dosages of anticholinergic drugs without signs of frank toxicity. These deficits have often been mistaken for symptoms of early dementia in elderly patients. Physicians are advised to be aware of this possibility.

Anticonvulsants
The patient should temporarily cease driving during the time of medication initiation, withdrawal, or dosage change due to the risk of recurrent seizure and potential medication side effects that may impair driving performance.

If there is significant risk of recurrent seizure during medication withdrawal or change, the patient should cease driving during this time and for at least three months thereafter. (See Section 4 for further recommendations.)

Note that many anticonvulsants (eg, valproic acid, carbamazepine, gabapentine, lamotrigine and topiramate) are also being used as mood stabilizers for treatment of bipolar disorder and as sedating agents for anxiety. These are typically an adjunct to antidepressants, antipsychotics and/or anxiolytics. By themselves, anticonvulsants may be mildly impairing, but the combined medication effects on psychomotor performance tend to be more severe. When coprescribing anticonvulsants and other psychoactive drugs, it is wise to start with low doses of each and gradually increase the dosage of each one separately to minimize side effects.

Antidepressants Impairing side effects vary among the different classes of antidepressants, and even within certain classes of antidepressants. In general, antidepressants that possess antagonistic activity at cholinergic, alpha-1-adrenergic, and histaminergic receptors are the most impairing. Whenever possible, physicians should initiate antidepressant therapy with the least impairing medication possible.

Patients should be advised not to drive during the initial phase of antidepressant dosage adjustment(s) if they experience drowsiness, lightheadedness, or other side effects that may impair driving performance. Patients should also be advised that they may experience impairment in the absence of any subjective symptoms.

Bupropion
Side effects of bupropion (also known as Wellbutrin® and Zyban®) include anxiety, restlessness and insomnia (leading to daytime drowsiness). Patients should be counseled about these side effects and their potential to impair driving performance. Because bupropion may cause seizures at high doses, it should not be prescribed to patients with epilepsy, brain injuries, eating disorders, or other factors predisposing to seizure activity.

Mirtazapine
Mirtazapine (also known as Remeron®) is typically taken only at night due to its sedating effects. It has been shown to cause substantial impairment for many hours after dosing. Whenever possible, it should be avoided in patients who wish to continue driving.

Monoamine oxidase (MAO) inhibitors
Side effects of MAO inhibitors that may impair driving performance include blurred vision, overstimulation, insomnia (leading to daytime drowsiness), orthostatic hypotension (with transient cognitive deficits), and hypertensive crisis (presenting with severe headaches and/or mental status changes). The latter can be caused by failure to adhere to dietary and medication restrictions. Patients should be counseled about these side effects and their potential to impair driving performance.

Selective serotonin reuptake inhibitors (SSRI)
Common side effects of SSRIs that may impair driving performance include sleep changes (insomnia or sedation), headache, anxiety, and restlessness. While these side effects tend to be mild and well-tolerated, physicians should counsel patients to be alert to their potential to affect driving performance.

Tricyclic antidepressants (TCA)
Common side effects of TCAs that may impair driving performance include sedation, blurred vision, orthostatic hypotension, tremor, excitement, and heart palpitations. In studies involving healthy volunteers, the more sedating TCAs have been shown to impair psychomotor function, motor coordination, and open-road driving. Other studies appear to indicate an increased crash risk for drivers who take TCAs.24

Whenever possible, TCAs should be avoided in patients who wish to continue driving. If non-impairing alternatives are not available, then the physician should advise patients of the potential side effects and recommend temporary driving cessation during the initial phase of medication initiation/dosage adjustment. Patients should also be advised that they may experience impairment even in the absence of subjective symptoms.

Antiemetics Numerous classes of drugs—including anticholinergics, antihistamines, antipsychotics, cannabinoids, benzodiazepenes, 5HT antagonists, and glucocorticoids—are used for their antiemetic effect. Side effects of antiemetics that may impair driving performance include sedation, blurred vision, headache, confusion, and dystonias. Significant impairment may be present even in the absence of subjective symptoms. Patients should be counseled about side effects and their potential to impair driving performance, and should be advised that they may experience impairment even in the absence of subjective symptoms.

For more detailed information, see also the recommendations for anticholinergics, antihistamines, antipsychotics, and benzodiazepenes.

Antihistamines In many patients, the older antihistamines (such as diphenhydramine and chlorpheniramine) have pronounced central nervous system effects. In studies involving healthy volunteers, sedating antihistamines have been shown to impair psychomotor performance, simulated driving, and open-road driving.24 Furthermore, subjects may experience impairment even in the absence of subjective symptoms of impairment.23 In contrast, most nonsedating antihistamines do not produce these types of impairment after being taken in recommended doses.24 However, even nonsedating antihistamines may cause impairments if taken in higher-than-recommended doses, and one of them— cetirizine—may be slightly impairing to certain patients in normal doses.

Patients who take a sedating antihistamine should be advised not to drive while on the medication. If these patients wish to continue driving, they should be prescribed a nonsedating antihistamine.

Antihypertensives With their hypotensive properties, common side effects of antihypertensives that may impair driving performance include lightheadedness, dizziness, and fatigue. In addition, antihypertensives with a prominent central nervous system effect, including beta-blockers and the sympatholytic drugs clonidine, guanfacine and methyldopa, may cause sedation, confusion, insomnia, and nervousness.

Patients should be counseled about these side effects and their potential to impair driving performance. In addition, patients taking antihypertensives that may potentially cause electrolyte imbalance (ie, diuretics) should be counseled about the symptoms of electrolyte imbalance and their potential to impair driving performance.

Antiparkinsonians Several medications and classes of medications including levodopa, antimuscarinics (anticholinergics), amantadine, and dopamine agonists may be used in the treatment of Parkinson’s disease symptoms. Common side effects of antiparkinsonian drugs that may impair driving performance include excessive daytime sleepiness, lightheadedness, dizziness, blurred vision, and confusion. (See also the recommendations for anticholinergics.)

Patients should be counseled about these side effects and advised not to drive if they experience side effects. Based on the extent of disease symptoms and medication side effects, the physician may also consider referring patients for formal psychomotor testing or for driver evaluation (including on-road assessment) performed by a driver rehabilitation specialist.

Antipsychotics Most—if not all—antipsychotic medications have a strong potential to impair driving performance through various central nervous system effects. Some of the original or “classic” antipsychotics are heavily sedating, and all produce extrapyramidal side effects (EPS). Although the modern or “atypical” drugs have a lower tendency to cause EPS, they, too, are sedating.

Patients should be counseled about these side effects and advised not to drive if they experience side effects severe enough to impair driving performance. The physician should consider referring the patient for formal psychomotor testing or for driver evaluation (including on-road assessment) performed by a driver rehabilitation specialist. If medication therapy is initiated while the patient is hospitalized, the impact of side effects on driving performance should be discussed prior to discharge.

Benzodiazepenes and other sedatives/anxiolytics Studies have demonstrated impairments in vision, attention, motor coordination, and driving performance with benzodiazepene use. Evening doses of long-acting benzodiazepenes have been shown to markedly impair psychomotor function the following day, while comparable doses of short-acting compounds produce a lesser impairment.24 In contrast, benzodiazepene-like hypnotics (such as zolpidem and zaleplon) have a more rapid rate of elimination. Studies of driving performance and psychomotor function have shown that five hours after taking zaleplon and nine hours after taking zolpidem at recommended doses, it is generally safe to drive again.25-27

Patients should be prescribed evening doses of the shortest-acting hypnotics whenever possible. Patients who take longer-acting compounds or daytime doses of any hypnotic should be advised of the potential for impairment, even in the absence of subjective symptoms. These patients should also be advised to avoid driving, particularly during the initial phase of dosage adjustment(s).

Muscle relaxants Most skeletal muscle relaxants (eg, carisoprodol and cyclobenzaprine) have significant central nervous system effects. Patients should be counseled about these side effects and advised not to drive during the initial phase of dosage adjustment(s) if they experience side effects severe enough to affect safe driving performance.

Nonsteroidal anti-inflammatory drugs (NSAID)

Isolated case reports of confusion following the use of the NSAIDs phenylbutazone and indomethacin suggest that they may rarely impair driving performance.28 If the patient reports this side effect, the physician should consider adjusting the dosage or changing the medication.

Narcotic analgesics Patients should be counseled about the impairing effects of narcotic analgesics (ie, opioids) and the potential for impairment even in the absence of subjective symptoms. They should also be advised not to drive while on these medications.

In addition, many narcotic analgesics have a high potential for abuse. Accordingly, physicians should always be alert to signs of abuse. (For more information, see the recommendations for substance abuse in Section 6.)

Stimulants Common side effects of traditional stimulants (such as amphetamines and methylphenidate) that may impair driving performance include euphoria, overconfidence, nervousness, irritability, anxiety, insomnia, headache, and rebound effects as the stimulant wears off. Patients should be counseled about these side effects and advised not to drive during the initial phase of dosage adjustment(s) if they experience side effects severe enough to impair driving performance. (The novel stimulant, modafinil, is not euphorogenic, nor does it appear to cause rebound effects. However, its safety for use when driving has not yet been demonstrated.)

In addition, many stimulants have a high potential for abuse. Accordingly, physicians should always be alert to signs of abuse. (For more information, see the recommendations for substance abuse in Section 6.)


20 Mattila M. Acute and subacute effects of diazepam on human performance: Comparison of plain tablet and controlled release capsule. Pharmacology and Toxicology. 1988;63(5):369-374.

21 Roache JD, Griffiths RR. Comparison of triazolam and pentobarbital: performance impairment, subjective effects and abuse liability. Journal of Pharmacology and Experimental Therapeutics. 1985;234(1):120-133.

22 Aranko K, Mattila MJ, Bordignon D. Psychomotor effects of alprazolam and diazepam during acute and subacute treatment, and during the follow-up phase. Acta Pharmacologica et Toxicologica. 1985;56(5):364-372.

23 Weiler JM, Bloomfield JR, Woodworth GG, et al. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: A randomized placebo-controlled trial in the Iowa driving simulator. Annals of Internal Medicine. 2000;132(5):354-363.

24 Ray WA, Purushottam BT, Shorr RI. Medications and the older driver. Clinics in Geriatric Medicine. 1993;9(2):413-438.

25 Vermeeren A, Danlou PE, O’Hanlon JF. Residual effects of zaleplon 10 and 20 mg on memory and actual driving performance following administration 5 and 2 hours before awakening. British Journal of Clinical Pharmacology. 1999;48:367-374.

26 Vermeeren A, Muntjewerff ND, van Boxtel M, et al. Residual effects of zaleplon and zopiclone versus the effects of alcohol on actual car driving performance [abstract]. European Neuropsychopharmacology. 2000;10(suppl 3):S394.

27 Volkerts ER, Verster JC, Heuckelem JHG, et al. The impact on car-driving performance of zaleplon and zolpiden administration during the night [abstract]. European Neuropsychopharmacology. 2000;10(suppl 3):S395.

28 Ray WA, Gurwitz J, Decker MD, Kennedy DL. Medications and the safety of the older driver: Is there a basis for concern? Human Factors. 1992;34(1):33-47.


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