Cholinesterase inhibitor drugs, their side effects and their use in psychiatric conditions

Cholinesterase inhibitors are widely used for the symptomatic treatment of Alzheimer's disease. There are several cholinesterase inhibitors available by prescription, and there are some herbs that have compounds in them that have cholinesterase inhibitor activity. Galantamine can be extracted from an herb and is available over the counter.
   Pharmacological treatment of moderate-to-severe Alzheimer's disease patients may be beneficial in some patients. However, cost-benefit data are limited, and the long-term effects and the optimal duration of treatment as patients continue to progress to more severe stages are unknown and require further investigation.

Cholinesterase is an enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation. Cholinesterase inhibitors include familiar drugs such as Aricept and Exelon.

Donepezil is a cholinesterase inhibitor drug.

Galantamine is a cholinesterase inhibitor drug also available without a prescription.

Rivastigmine (sold under the trade name Exelon) is a cholinesterase inhibitor drug for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson's disease.

Risk of falls
Cholinesterase inhibitors, commonly used to treat people with Alzheimer's disease, increase the risk of fainting. Dr. Sudeep S. Gill, at St. Mary's of the Lake Hospital, Kingston says, "These drugs can sometimes slow the heart rate and provoke fainting resulting in injuries related to fainting and falling, such as hip fractures." Some patients may undergo unnecessary procedures such as insertion of permanent pacemakers, rather than simply stopping the offending drug. Dr. Sudeep Gill says, "physicians should carefully consider these findings when weighing the potential benefits and risks of cholinesterase inhibitor treatment for their patients with dementia." Archives of Internal Medicine, 2009.

Atomoxetine augmentation of cholinesterase inhibitor therapy in patients with Alzheimer disease: 6-month, randomized, double-blind, placebo-controlled, parallel-trial study;
American Journal of Geriatric Psychiatry 2009
To examine the efficacy and tolerability of atomoxetine in improving cognitive performance of patients with Alzheimer dementia. A randomized, double-blind, placebo controlled, parallel-groups study, starting with a 5-33-day screening and evaluation period, followed by a 6-month treatment period. Male or female patients, aged 55 years and older, with mild-to-moderate Alzheimer disease (Mini-Mental State Examination score between 10 and 26) at baseline. Atomoxetine (25-80 mg/day) or placebo for up to 6 months, added to ongoing cholinesterase-inhibitor therapy. The atomoxetine group showed a significantly greater increase of heart rate, and the mean increase in diastolic blood pressure and decrease in weight differed significantly from the decrease in pressure and weight increase in the placebo group. No other clinically meaningful safety results were obtained. Addition of atomoxetine to ongoing cholinesterase-inhibitor therapy was generally well tolerated but did not significantly improve cognitive function.

Inquiries
I was wondering if I could have your opinion about the long term effects of cholinesterase inhibitor use. Wouldn't your body compensate for the increased amount of ACh in your synapses, and find new mechanisms for removing it? Would healthy people then form some sort of dependence on the supplement, or become desensitized?
    There is much we don't know about the long term use of such medications. We prefer not to use them for prolonged periods. If they are needed to be taken for extended periods, it may be wise to take breaks from use.