Letter to the Editor
Adverse Drug Reactions Associated With Cholinesterase Inhibitors—Sequence Symmetry Analyses Using Prescription Claims Data

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Methods

Sequence symmetry analyses (SSAs)7 were conducted using data from a 10% random sample of dispensing data from the PBS between March 2005 and May 2016. These data comprised patient-level records of all reimbursed medications dispensed by Australian pharmacies. SSA is a signal detection technique used in the postmarketing surveillance of prescription medications that compares the sequence of incident dispensing of an index and marker medication.7 The index medication is considered the exposure,

Results

In total, 11,695 people were initiated on a cholinesterase inhibitor between March 2007 and May 2015. There were 1202 people with incident dispensing for nausea, 1079 for dyspepsia, 389 for seizures, 348 for diarrhea, 261 for urinary incontinence, 1698 for depression, 807 for anxiety, and 963 for insomnia within 52 weeks before or after initiation of the index cholinesterase inhibitor. Incident dispensing was significantly higher for diarrhea (ASR, 1.42; 95% CI, 1.14–1.77), anxiety (ASR, 1.16;

Discussion

The main finding of this study was an increase in first dispensing of medications for seizures, anxiety, insomnia, nausea, and diarrhea following initiation of cholinesterase inhibitors. There was an inverse association between initiation of cholinesterase inhibitors and initiation of medications for dyspepsia and depression.

The WHO database included 247 spontaneous reports of seizures.3 Our data substantiates these ADR reports. Visual inspection of Figure 1 suggests that incident dispensing of

Acknowledgments

The authors thank Dr. Te-yuan Chyou from the University of Otago for his help with R programming. The authors would also like to acknowledge the Australian Government, Department of Human Services for provision of the data.

References (14)

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J.I. was supported by the National Health and Medical Research Council Fellowship (grant number 1072137).

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