Effectiveness of donepezil in the treatment of musical hallucinations: evidence from case reports and pathophysiological considerations

Musical hallucinations are a rather rare but distressing neuropsychiatric condition occurring in patients with hypoacusis, psychiatric disorders, focal brain lesions, epilepsy and intoxications suggesting a heterogeneous etiology and pathophysiology. However, hearing loss and higher age seem to be the most frequent conditions for the emergence of musical hallucinations, suggesting that this phenomenon is a consequence of deafferentiation similar to the occurrence of visual hallucinations in Charles Bonnet syndrome. Despite the spatial dissociation of the underlying brain areas, these “deafferentiation syndromes” may share a common pathophysiology leading to complex visual and musical hallucinations. There are now several case reports of successful drug treatment with the acetylcholinesterase inhibitor donepezil in mostly elderly but non-demented patients with hypoacusis. Donepezil exerts a dose-dependent inhibitory effect on AChE activity in the cerebral cortex thus increasing extracellular acetylcholine levels. Also beyond this evidence ex juvantibus, there is some rationale for the assumption of a cholinergic deficit as pathomechanism in these syndromes. Thus, at least for the “prototypical” group of elderly patients with hypoacusis, acetylcholinesterase inhibitors should definitely be regarded as treatment option also in absence of dementia. Besides pharmacological treatment, consultation of an otolaryngologist and thorough somatic diagnostics should be mandatory.