These commonly prescribed drugs may cause cognitive impairment

Chronic and acute drug-induced cognitive impairment are common but preventable issues in medicine. Certain classes of drugs have a greater risk for these impairments, with vulnerable patient populations often at higher risk. Specifically, older age, existing cognitive impairment, and dementia are all risk factors for drug-induced cognitive impairment.

Of note, alteration in cognitive impairment is likely multifactorial and secondary to age-related/pathophysiological changes in blood-brain permeability, neurochemistry, pharmacokinetics, pharmacodynamics, and neurochemistry.

Here’s an evidence-based look at some common drugs that can cause cognitive impairment.

Poor cognitive performance

In a population-based, cross-sectional cohort study in BMJ Open, researchers scoured the UK Biobank for correlations between common medications and cognitive function. The study sample included UK Biobank participants aged 37-73 years who completed cognitive tests at baseline visits between 2006 and 2010.

Primary endpoints included cognitive test outcomes on verbal-numerical reasoning test (n = 165,493), memory test (n = 482,766), and reaction time test (n = 496,813). After accounting for covariates—including age, education, household income, psychostimulant/nootropic medication use, and comorbidities—the researchers found that most drugs (262 of 368) were not related to any cognitive test results. However, drugs indicated for nervous system disorders, including antiepileptics and antipsychotics, were linked to poorer cognitive performance—possibly because these drug classes are typically used for diseases that have an element of cognitive impairment as part of the core syndrome.

Commonly used drugs for non-nervous system disorders were also linked to impaired cognitive performance. These drugs included antihypertensives, antidiabetic medications, proton pump inhibitors, and laxatives.

Psychotropic drugs

Per the study, here’s a list of specific cognitive impairments associated with psychotropic drugs (reflecting P-values < 0.05 and < 0.005):

• Impairments in verbal-numerical reasoning: Amitriptyline, benzodiazepines, topiramate, paracetamol

• Impairments in memory: Amitriptyline, benzodiazepines, levetiracetam, paracetamol, quetiapine, topiramate

• Impairments in reaction time: amitriptyline, benzamides, benzodiazepines, carbamazepine, fluoxetine, gabapentin, lamotrigine, levetiracetam, mirtazapine, olanzapine, opioids, paracetamol, risperidone, sertraline, trazodone, valproic acid

Non-psychotropic drugs

Per the study, here’s a list of specific cognitive impairments associated with commonly used non-psychotropic drugs (reflecting P-values < 0.05 and < 0.005):

• Impairments in verbal-numerical reasoning: Amlodipine, calcium-channel blockers, diabetes drugs, iron, proton-pump inhibitors, sulfonamides

• Impairments in memory: Amlodipine, calcium-channel blockers, nifedipine  

• Impairments in reaction time: Amlodipine, anticholinergics, beta-blockers, calcium, calcium-channel blockers, contact laxatives, corticosteroids, diabetes drugs, first-generation antihistamines, H2-receptor antagonists, insulin, nifedipine, osmotic laxatives, proton-pump inhibitors, second-generation antihistamines, stool softeners, sulfasalazine, sulfonamides, sulfonylureas, vitamin B1

Cardiovascular agents are of particular concern with respect to cognitive impairment.

“In general, use of all antihypertensives, especially in the case of polypharmacy or inappropriate dosing, can lead to hypotension and/or bradycardia, and thus lead to mental/cognitive status change due to decreased cerebral perfusion,” wrote the author of one literature review published in Mental Health Clinician. “In addition, cardiovascular agents with central bioavailability, such as digoxin and select antiarrhythmics, and antihypertensives may carry a risk for cognitive impairment due to various mechanisms proposed, such as antagonism of central muscarinic acetylcholine receptors, neurotransmission imbalance in the brain, and disruption of physiologic function of sodium/potassium ATPase in the neuronal cells.”

The author goes on to note that physicians should do a full medication history as the first step in managing patients with acute, subacute, and chronic changes in cognitive function to determine whether such effects may be attributed to medication use.

“Because medication-induced cognitive impairment is often reversible, it is important to conduct comprehensive medication reconciliation in order to provide for early identification and withdrawal of the offending agent(s). In addition, preventative strategies directed at avoiding high-risk medications when possible, especially in the most susceptible, and/or appropriately adjusting doses based on age- or pathophysiology-related changes and close follow-up and monitoring, may prevent complications,” advised the author.