Common Psychiatric Medications Silently Sabotage Brain Function in Psychosis Patients

New research shows anticholinergic drugs worsen cognitive abilities, but stopping them can restore mental clarity

Patients with schizophrenia and other psychotic disorders frequently struggle with memory and thinking problems that can be more disabling than hallucinations or delusions. Now, a comprehensive new study reveals that some of the very medications routinely prescribed to these patients may be making these cognitive problems significantly worse.

The meta-analysis, published last week in the American Journal of Psychiatry, examined 40 studies involving more than 5,000 patients with psychosis. It found that medications with anticholinergic properties—commonly used to treat side effects of antipsychotic drugs—are strongly linked to poorer cognitive performance across multiple domains of brain function.

“Anticholinergic burden is associated with the cognitive impairments observed in psychosis,” write lead author Valentina Mancini of the University of Oxford and colleagues. “From a clinical perspective, tapering off anticholinergic medication in patients with psychosis may improve cognition.”

The Cholinergic Connection

Cholinergic neurotransmission plays a crucial role in cognitive processing—the brain’s chemical messaging system that allows us to learn, remember, and think clearly. When medications block these signals by inhibiting acetylcholine (creating what researchers call “anticholinergic burden”), cognitive function suffers.

While many psychiatric patients understand that medications can cause physical side effects like weight gain or tremors, fewer realize these drugs might be compromising their mental clarity. This is particularly problematic because approximately 80% of people with psychosis already experience significant cognitive impairment that severely impacts their daily functioning and ability to maintain employment.

The researchers measured anticholinergic burden in three ways: through clinical scales that measure the collective anticholinergic properties of all medications a patient takes, through direct blood measurements of anticholinergic activity, and by studying what happens when patients stop taking these medications.

Memory and Learning Hit Hardest

Among all cognitive domains studied, verbal learning and memory showed the strongest negative correlation with anticholinergic burden. This means that as anticholinergic medication levels increased, patients’ ability to learn and remember verbal information decreased most dramatically.

The researchers found significant negative correlations between anticholinergic burden and multiple cognitive domains, including:

• Global cognition (r=−0.37)
• Verbal learning (r=−0.28)
• Processing speed (r=−0.24)
• Working memory (r=−0.22)
• Attention (r=−0.19)
• Executive functions (r=−0.17)
• Visual learning (r=−0.17)
• Social cognition (r=−0.12)

Perhaps most compelling were the results from studies that tracked patients after they stopped taking anticholinergic medications. These showed substantial improvements in cognitive function, with the largest improvements seen in working memory (d=0.94) and verbal learning (d=0.77).

Hidden in Plain Sight

The challenge for clinicians is that anticholinergic properties are found in many medications routinely prescribed to psychosis patients. These include not just dedicated anticholinergic drugs used to treat movement side effects of antipsychotics, but also many antipsychotics themselves (particularly olanzapine, clozapine, and quetiapine), along with certain antidepressants, antiepileptics, and antihistamines.

This “hidden” anticholinergic burden is compounded by the fact that people with chronic psychosis often have multiple health conditions requiring multiple medications.

“Despite their deleterious cognitive properties, compounds that competitively inhibit the binding of acetylcholine to muscarinic receptors are routinely prescribed for people with psychosis, for example, as treatments for extrapyramidal side effects of antipsychotics,” the researchers note.

An Overlooked Solution

The findings suggest that mental health professionals should consider reducing anticholinergic medication whenever possible. This could mean using antipsychotics with lower anticholinergic properties, minimizing the use of anticholinergic medications for side effects, or exploring non-pharmacological approaches.

The World Health Organization already recommends against prophylactic and long-term use of anticholinergic medications in people with psychosis. Despite this, they remain widely prescribed, with many patients taking them for extended periods.

The researchers caution that their findings are based primarily on observational studies, and more definitive randomized clinical trials are needed. They note that tapering studies were unblinded and lacked control groups, meaning that improvements could partly reflect practice effects from repeated testing.

Nevertheless, the consistency of findings across different measurement approaches strengthens the conclusion that anticholinergic medications are causing real cognitive harm to many psychosis patients.

For the millions of people worldwide living with schizophrenia and other psychotic disorders, cognitive impairment often persists even when other symptoms are well-controlled. These cognitive difficulties can severely limit rehabilitation, employment opportunities, and overall quality of life. If something as straightforward as medication adjustment could improve these impairments, it could represent a significant advancement in treatment.

In the meantime, patients shouldn’t stop taking their medications without medical supervision, but they may want to discuss the anticholinergic properties of their medication regimen with their healthcare providers to see if alternatives might be available.