Venkata Kolli, MBBS, Julie Dickson, MD; Mojgan Amani, MD; John Tan
Drs. Kolli and Amani are Residents,Creighton-Nebraska Psychiatry Residency Program, Omaha, Nebraska; Dr. Dickson is Contributed Services Assistant Professor, Department of Psychiatry, Creighton University, and Staff Psychiatrist, VA Medical Center, Omaha, Nebraska; Mr. Tan is M4 Medicval Student, Creighton University, Omaha, Nebraska.

Innov Clin Neurosci. 2013;10(9–10):10–14

Funding/financial disclosures: No funding was received for the preparation of this article. The authors have no conflicts relevant to the content of this article.

Dear Editor:

We report a case of posttraumatic stress disorder (PTSD) exacerbation with donezepil, a cholinesterase inhibitor.

Case report. An 80-year-old Korean War veteran with combat trauma-related PTSD presented with progressive memory loss. He was diagnosed with PTSD 18 years ago. His symptoms included distressing and intrusive recollection of events and images from the Korean War and avoidance of any reminders of the war. He experiences hyperarousal and nightmares up to five times a month. He presented again to the outpatient clinic with complaints of progressive memory loss, word finding difficulties, getting lost while driving, and occasionally forgetting to turn the stove off. He scored 18 out of 30 on a Montreal Cognitive Assessment. He lost points prominently on delayed recall, abstraction, and concentration. A subsequent neuropsychological testing was consistent with a diagnosis of mixed dementia. He was started on a donezepil 5mg every morning. Within 2 weeks of starting the cholinesterase inhibitor, he experienced an exacerbation of PTSD symptoms, with increased intrusive thoughts, worsening of anxiety, and nightmares every night. Donezepil was subsequently discontinued and PTSD symptoms reverted back to their baseline in seven days.

Discussion. PTSD has a life-time prevalence of eight percent.1 It is a chronic illness afflicting patients across the life span including late life. PTSD increases the risk of dementia by two-fold.[2] Donezepil is a reversible cholinesterase inhibitor, and acts via increasing acetylcholine concentration in the brain. Cholinesterase inhibitors have been used in the treatment of dementia, delirium, traumatic brain injury, schizophrenia, and bipolar disorder.[3] A Pubmed search reveals a contrasting effects of cholinesterase inhibitors on PTSD symptoms. Two cases report emergence of PTSD symptoms related to prior war trauma in patients with cognitive dysfunction without any prior PTSD diagnosis, with cholinesterase inhibitors.[4,5] The onset of PTSD symptoms in both these patients was attributed to a dose increase of donezepil from 5mg to 10mg. Another case series of four patients without cognitive dysfunction reported improvement in nightmares with donezepil.[6] However, in our case, existing PTSD symptoms worsened with donezepil 5mg initiation.

The role of cholinergic pathways in anxiety disorders is not clear. Anxiety related to dementia improves with cholinesterase inhibitors. However, the mechanism of PTSD exacerbation with cholinesterase inhibitors is not known. Chronic PTSD is associated with smaller hippocampal volume.[7] Hippocampus plays a key role in integrating memory elements from primary sensory and secondary association areas.[7] It is possible that cholinergic stimulation might have an inadvertent activation of the circuits encoding for the suppressed traumatic experiences making them prominent. Cholinergic projections promote both wakefulness and REM sleep, and modulating these pathways possibly impacts nightmares.

We recommend close monitoring of patients for any exacerbation of PTSD-related symptoms when started on cholinesterase inhibitors.

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