Cholinesterase inhibitors in brain damage

[participant3]

Is there evidence in the role of cholinesterase inhibitors slowing progression of cognitive decline in patients with brain damage?

[chantell.reagan]

Several studies (including a 24-week randomized placebo-controlled study with 18 patients) have provided preliminary evidence suggesting that donepezil may enhance response in patients with chronic or postacute traumatic brain injury.

In a recent 12-week randomized placebo-controlled study with 157 patients with chronic traumatic brain injury, rivastigmine and placebo achieved a similar response; however, rivastigmine was significantly more effective than placebo in a subgroup with moderate to severe memory deficits.

One study evaluated the use of different cholinesterase inhibitors in patients with chronic traumatic brain injury. Tenovuo et al reported on 111 outpatients with at least 1 of the following symptoms: fatigue, poor memory, diminished attention, or diminished initiation that were randomized to the treatment with donepezil, galantamine, or rivastigmine (41 patients tried more than one of these agents). A marked positive response was observed in 61% of patients and a modest or no response in 39% of patients. The positive effect was observed in the form of better vigilance and attention causing better general function. The therapeutic response was noted quickly and at low doses with no significant differences between the three drugs either in effect or tolerability. The age, sex, type of injury, severity of brain injury or elapsed time after injury did not affect the response. Adverse effects or inadequate therapeutic response were the main causes for discontinuation that occurred at nearly equal frequency.

In addition, the Brain Trauma Foundation does have guidelines for traumatic brain injury, but cholinesterase inhibitors not mentioned.

Sources:

Zhang L et al. Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil. 2004;85:1050-5.

Whelan FJ et al. Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Ann Clin Psychiatry. 2000;12:131-5.

Walker W et al. The effects of Donepezil on traumatic brain injury acute rehabilitation outcomes. Brain Inj. 2004;18(8):739-50.

JM Silver et al. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology 2006;67:748-755.

Tenovou O. Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury-clinical experience in 111 patients. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2005:29;61-7.

Yoo JH et al. Relevance of donepezil in enhancing learning and memory in special populations: a review of the literature. J Autism Dev Disord. 2007;37:1883-901.

Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons. Guidelines for the management of severe traumatic brain injury. Steroids. J Neurotrauma 2007;24:S91-S95.