Cholinesterase inhibitors

What are cholinesterase inhibitors?

Cholinesterase inhibitors (ChEI), or anticholinesterase, have been proposed as an additional therapy to standard antipsychotic treatments in an attempt to improve functional outcomes and treat symptoms that are not addressed by the antipsychotic medication alone. Cholinesterase inhibitors work by blocking the cholinesterase enzymes that break down acetylcholine neurotransmitters (ACh), increasing neurotransmitter action. Their action is in contrast to anticholinergic medications, which have an opposite effect, and block the action of cholinergic neurotransmitters on their receptors. There are two key forms of cholinesterase enzymes, acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). There are several different cholinesterase inhibitor drugs that target these enzymes, which vary in their specificity for each of these enzymes (‘singleaction’ or ‘dual-action’). Essentially, cholinesterase inhibitors work by blocking the cholinesterase enzyme from metabolising ACh, resulting in increased availability of ACh in neuron synapses and increasing ACh activity on cholinergic receptors (called nicotinic and muscarinic receptors). These receptors are known to be involved in cognition, and the use of cholinesterase inhibitors has previously shown some efficacy for improving cognition in Alzheimer’s disease. Aspects of cognition are known to be impaired in schizophrenia (See Cognition topics). Cholinesterase inhibitors have also been proposed as treatments for visual hallucinations, possibly due to depleted ACh levels in the cortex including regions involved in visual processing and interpretation.

What is the evidence for cholinesterase inhibitors?

High quality evidence suggests a medium-sized effect of adjunctive donepezil or galantamine for improving overall and negative symptoms compared to placebo. Moderate to high quality evidence suggests benefit of AChEI (single- and dual-action) for improving verbal learning, memory, and attention, with no benefit for motor function, language or executive functioning. High quality evidence suggests single-action AChEI alone (donepezil) may confer some benefit for attention and short-term memory.

March 2019

Last updated at: 11:43 pm, 20th March 2019
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