Donepezil, a medication primarily prescribed for Alzheimer’s disease, can indeed cause weight loss as a side effect in some individuals. This effect is not universal but has been reported enough to be recognized among the drug’s potential adverse reactions.
Donepezil works by inhibiting an enzyme called acetylcholinesterase, which normally breaks down acetylcholine, a neurotransmitter important for memory and cognition. By blocking this enzyme, donepezil increases acetylcholine levels in the brain, which helps improve cognitive function in people with Alzheimer’s disease. However, this increase in acetylcholine can also affect other bodily systems, including the digestive system, which may contribute to weight loss.
The weight loss associated with donepezil is often linked to side effects such as nausea, vomiting, and loss of appetite. These gastrointestinal symptoms can reduce food intake, leading to a decrease in body weight. Some patients, especially those who are already underweight or have a low body mass index (BMI), may be more susceptible to these side effects. In fact, individuals weighing less than 55 kilograms (about 121 pounds) may experience more pronounced side effects, including weight loss, nausea, and vomiting.
The mechanism behind this weight loss is not fully understood but is thought to be related to the drug’s cholinergic effects. Acetylcholine influences the parasympathetic nervous system, which controls digestion and appetite. Increased cholinergic activity can enhance gastrointestinal motility and secretions, sometimes causing discomfort, nausea, or reduced appetite. This can lead to decreased calorie intake and subsequent weight loss.
In clinical practice, weight loss in patients taking donepezil is a concern because many Alzheimer’s patients are already vulnerable to nutritional deficiencies and frailty. Unintended weight loss can worsen overall health, reduce muscle mass, and increase the risk of complications such as infections or falls. Therefore, healthcare providers monitor patients closely for signs of weight loss and may adjust the dose or consider alternative treatments if the weight loss is significant or harmful.
It is also important to note that weight loss is not the intended therapeutic effect of donepezil. The drug’s goal is to improve cognitive symptoms and slow the progression of dementia, not to affect body weight. However, because of its side effect profile, weight loss can occur as an unintended consequence.
In some experimental models, donepezil has shown effects on neuroinflammation and metabolic processes, but these findings are preliminary and do not directly translate to weight loss in humans. The primary clinical concern remains the gastrointestinal side effects that reduce appetite and food intake.
Patients and caregivers should be aware of this potential side effect and report any significant changes in weight or appetite to their healthcare provider. Nutritional support, dietary adjustments, or medication changes may be necessary to manage weight loss while continuing to treat cognitive symptoms.
In summary, donepezil can cause weight loss primarily through side effects like nausea and decreased appetite, which reduce food intake. This effect is more common in individuals with lower body weight and can be a significant clinical issue in managing Alzheimer’s disease patients. Monitoring and managing these side effects is an important part of treatment with donepezil.
