Common Medications for PTSD Tied to Increased Dementia Risk

Nancy A. Melville

May 18, 2017

Psychotropic medications commonly used to treat posttraumatic stress disorder (PTSD) are associated with increased risk for dementia in older veterans, new research shows.

"Patients diagnosed with PTSD using SSRIs [selective serotonin reuptake inhibitors], NA [novel antidepressants], or AA [atypical antipsychotics] were significantly more likely to be diagnosed with dementia compared to both those with and without a PTSD diagnosis but without any identified psychotropic medication use at baseline," the authors, led by Francis Mawanda, PhD, University of Iowa, Iowa City, report.

The study was published in the May issue of the Journal of the American Geriatrics Society.

Risk Varies by Drug Type

Previous research has linked PTSD with an increased risk for dementia. However, few studies have evaluated the role of medications for the disorder in the dementia risk.

To evaluate possible effects, the investigators turned to a nationwide sample of 417,172 US veterans aged 56 years or older who had not been diagnosed with dementia or mild cognitive impairment at baseline in 2003 and for whom data were available for one or more clinical encounters every 2 years in the follow-up period through 2012. The veterans were mostly men and 82% were white.

Among the veterans, 22,674 (5.4%) had a PTSD diagnosis at baseline, and 25,639 (6.15%) were diagnosed with dementia during the follow-up period.

After adjustment for demographic, medical comorbidities, and various psychiatric comorbidities associated with PTSD, patients with PTSD showed a significantly increased risk of being subsequently diagnosed with dementia compared to those who did not have PTSD (hazard ratio [HR], 1.35).

Patients with PTSD who were not treated with psychotropic medications were at increased risk of being diagnosed with dementia compared to those without PTSD (HR, 1.55).

However, dementia risk was significantly higher among veterans with PTSD who were treated with psychotropic medications compared to their counterparts with PTSD but who were not treated with psychotropics. The risk varied according to drug type, with the highest risk being associated with use of atypical antipsychotics: SSRIs, HR = 1.99 (P < .001); novel antidepressants, HR = 1.30 ( P = .01); atypical antipsychotics, HR = 2.71 (P < .001).

The investigators also found that patients who were undergoing treatment with benzodiazepines or selective norepinephrine reuptake inhibitors (SNRIs) at baseline were at significantly higher risk for dementia whether they had been diagnosed with PTSD or not (HR, 1.36 and 1.34, respectively).

The authors note that the findings regarding benzodiazepines are consistent with previous research linking long-term use of that drug class with an increased risk for dementia.

They speculate that the increased dementia risk could be the result of various factors, including PTSD symptom severity. It is possible that PTSD was more severe among those who underwent treatment with a psychotropic medication compared to those who did not receive medication.

They note a lack of previous studies regarding a potential association between PTSD severity and a risk for dementia.

The authors point to other studies that support the idea that medications themselves increase the risk for dementia, including a study linking SSRI use with an increased risk for dementia.

Other research implicates neural mechanisms, including serotonergic and noradrenergic neuronal degeneration, decreased serotonin and norepinephrine levels, and serotonergic receptor depletion in the dementia process, the authors note.

"Thus, because SSRI and SNRI sustain higher extracellular activity of serotonin, and serotonin and noradrenaline, respectively, these medications could possibly affect cognitive function and the risk of dementia among PTSD patients," they speculate.

More research is needed to better understand the relationship, they note.

"Although our results showed significant independent and effect modifying impacts, the association between psychotropic medication use and the risk of dementia remains an area for further inquiry," the authors conclude.

"Thus, we recommend further research accounting for dosage, duration, and indications for use to determine whether the independent and the effect modifying impacts of psychotropic medication use on the risk for dementia are due to differences in PTSD severity and symptomatology, other psychiatric comorbidity, or whether they represent independent and direct effects on dementia neuropathogenesis."

Valuable Insight

The findings raise important questions and provide valuable insight into the factors associated with the development of dementia after PTSD, commented Malaz Boustani, MD, MPH, chief innovation and implementation officer with the Sandra Eskenazi Center for Brain Care Innovation and Richard M. Fairbanks Professor of Aging Research at Indiana University School of Medicine, in Indianapolis.

"This is a high-quality pharmacoepidemiological study with very significant and clinically relevant brain health research questions related to the survivors of severe physical or psychological trauma," he told Medscape Medical News.

"It is the first study to untangle the complex relationship among dementia risk and the severity of PTSD, the coexisting psychiatric comorbidities, and exposure to psychotropic medications."

Dr Boustani noted that consideration should be given to the effects that the anticholinergic properties of psychotropic drugs may have on cognition.

His laboratory has developed the Anthicholinergic Cognitive Burden Scale, which specifies the level of anticholinergic properties of various medications, including several psychotropics, he explained.

"Several studies across the world used our scale to identify anticholinergic burden as a risk factor for future development of dementia.

"Medications with anticholinergic properties, such as olanzapine, quetiapine, and paroxetine, are psychotropics that block the muscarinic receptors in the brain and disrupt the activities of acetylcholine, a very important neurotransmitter involved in memory and attention, leading to neurodegeneration."

Elspeth Cameron Ritchie, MD, MPH, chief of mental health for community-based outpatient clinics with the US Department of Veterans Affairs in Washington, DC, said the findings are "disconcerting" and agreed that more studies are needed.

"I think the findings warrant further study, because the ramifications of this are pretty major," she told Medscape Medical News.

"I don’t think this article is enough to warrant a change in practice, but clinicians should perhaps be thinking about alternative treatments for PTSD, especially if the patient has other risk factors for dementia."

The study received funding from the Department of Veterans Affairs Health Services Research and Development Service. Dr Boustani and Dr Ritchie have disclosed no relevant financial relationships.

J Am Geriatr Soc. 2017;65:65,1043-1050. Full text

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