Experts Warn on Mixing New Alzheimer’s Drug and Antidepressants

Mixing lecanemab (Leqembi) and certain antidepressants may signal caution, Swiss researchers said.

Some patients have a higher risk of intracerebral hemorrhage in the first 30 days after introducing selective serotonin reuptake inhibitors (SSRIs), reported Beatriz Pozuelo Moyano, MD, of the University of Lausanne, and co-authors.

“Our recommendations are to pay special attention to patients on SSRIs, particularly if they already have microhemorrhages,” Pozuelo Moyano and colleagues wrote in a letter published in Alzheimer’s & Dementia.

“The introduction of lecanemab treatment during the first 30 days after the introduction of SSRIs should be avoided,” they continued. “Patients on concomitant antiplatelet treatment may need additional monitoring because bleeding risk is increased by the concurrent use of these drugs.”

Monoclonal antibodies like lecanemab that target aggregated forms of beta amyloid can cause amyloid-related imaging abnormalities (ARIA) — either edema or effusion (ARIA-E) or ARIA with hemosiderin deposition (ARIA-H), which can include microhemorrhage, macrohemorrhage, or superficial siderosis.

Lecanemab received full FDA approval to treat Alzheimer’s disease in July 2023. Its prescribing information contains a box warning about ARIA and recommends caution when treating patients with an increased risk for intracerebral hemorrhage and who are on anticoagulants.

Patients with cerebral amyloid angiopathy (CAA) may have an increased risk of ARIAs, Pozuelo Moyano and co-authors noted. According to the drug’s appropriate use recommendations (AURs), lecanemab can be given to “patients with fewer than four microhemorrhages, which may still correspond to possible or probable CAA,” they wrote. “Considering this, a parallel prescription with SSRIs deserves close monitoring, as antidepressant use is associated with an increased risk of developing microbleeds.”

Depression prevalence ranges from 19% to 78% in dementia, they added, and apathy and depression are the most frequent behavioral and psychological symptoms of dementia in Alzheimer’s disease.

In a retrospective observational study, the researchers evaluated the prevalence of antidepressant drugs in patients eligible for lecanemab (according to the AURs) at the Leenaards Memory Center of Lausanne University Hospital.

They identified 47 eligible patients among the 410 Alzheimer’s patients evaluated in 2022; 32% were on antidepressant treatment. Most patients (80%) were on SSRIs.

“This prevalence is similar to those previously reported in Alzheimer’s disease patients in general,” Pozuelo Moyano and co-authors observed. “This high prevalence of Alzheimer’s disease patients eligible for lecanemab on antidepressant drugs, especially SSRIs, raises the question of an appropriate clinical management of these patients.”

“We estimate that in patients eligible for anti-amyloid drugs, the indication for antidepressant treatment and its dose should be periodically re-evaluated as the antiplatelet effect in antidepressants is dose dependent,” they stated. “It is important to also consider alternative choices, such as antidepressants with lower bleeding risk for mood disorders and antiepileptics (pregabalin and gabapentin) for an anxiety disorder or anxiety-type [behavioral and psychological symptoms of dementia].”

That recommendation is “very reasonable and is the kind of guidance that could be integrated into the AURs,” Jeffrey Cummings, MD, ScD, of the University of Nevada, Las Vegas, who led the workgroup that developed the lecanemab appropriate use recommendations, told MedPage Today.

While the observations in the study were not derived from patients on lecanemab, “this data set suggests that vigilance on larger data sets will inform future practice,” Cummings said.

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