Cholinesterase inhibitors and affective symptoms

Bipolar Disorder and Manic-Like Symptoms in Alzheimer’s, Vascular and Frontotemporal Dementia: A Systematic Review

“…Six cases of manic episodes associated to the use of acetylcholinesterase inhibitors (AChEIs) in patients with probable AD have been reported (Table 2 ) [ 27 - 31 ], two of which also had vascular alterations [ 29 , 30 ]. Three of these subjects had been previously diagnosed with BD type I [ 27 , 29 ], one of which had a late-onset [ 29 ], and two subjects had previous depressive symptoms [ 30 , 31 ], in one case arising during treatment with AChEIs, just before the occurrence of mania [ 31 ]. Only one patient had no personal history of psychiatric disorders [ 28 ].…”

“…In five out of six cases manic symptoms started from 3 days to 2 weeks after the initiation/optimization of AChEI treatment, supporting the existence of a relationship between the onset of mania and treatment [ 27 - 30 ]. The latter patient developed mood elevation many months after donepezil introduction [ 31 ]. At the onset of mania, three patients were simultaneously taking an antidepressant therapy [ 27 , 30 ].…”

“…Despite antidepressants are generally known to increase the risk for mania, each of these subjects had received the antidepressant drug for a relatively long period (1 to 8 years) without showing the emergence of clinically relevant manic symptoms, supporting the possibility of an AChEI-induced mania. In all cases AChEIs and, whenever present, antidepressants were discontinued [ 27 - 31 ]. The remission of mania was observed after a period ranging from 2 days to 4 weeks, either spontaneously [ 27 , 28 , 31 ] or following treatment with antipsychotic and/or antiepileptics [ 29 , 30 ].…”

“…In all cases AChEIs and, whenever present, antidepressants were discontinued [ 27 - 31 ]. The remission of mania was observed after a period ranging from 2 days to 4 weeks, either spontaneously [ 27 , 28 , 31 ] or following treatment with antipsychotic and/or antiepileptics [ 29 , 30 ]. In one patient, who initially developed mania on rivastigmine, no additional manic symptoms were reported after re-challenging with donepezil 2.5 mg/day, possibly as a consequence of the lower dose administered [ 28 ].…”