Innovations In Clinical Neuroscience

MAR-APR 2018

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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24 ICNS INNOVATIONS IN CLINICAL NEUROSCIENCE March-April 2018 • Volume 15 • Number 3–4 R E T R O S P E C T I V E S T U D Y L Little data support or refute the claim that statins or low serum cholesterol increase a patient's risk of aggression. Therefore, it is imperative that we, as healthcare professionals, contribute to best practices to ensure that we do not inadvertently worsen a patient's preexisting psychiatric condition. Behavioral changes can be provoked by a variety of medications. Recent literature has linked 3-hydroxy-3-methyl- glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, to central nervous system (CNS) neuropsychiatric adverse effects, including aggression, agitation, irritability, mood changes, violent ideation, sleep problems, suicidality, and additional behavioral disturbances. 1–5 These adverse effects have also been reported in the setting of low cholesterol and with lower omega-3 fatty acid levels. 6–9 Several mechanisms have been proposed to explain the association between lowered cholesterol and behavioral changes. Lipids play an important role in brain functioning and are critical in the formation of neuron cell membranes, myelin sheath, and nerve synapses. It has been hypothesized that decreased serum lipid levels in the brain can reduce obtainable cholesterol by neurons, which can lower serotonergic activity by decreasing serotonin receptor expression. Serotonin plays a vital role in behavioral control, and alterations to the serotonergic pathway or serotonin availability can result in changes in behavioral control and psychiatric adverse effects. 3 Connections between mitochondrial dysfunction and psychiatric adverse effects have been previously documented. Statins might lead to mitochondrial dysfunction and oxidative stress; while the precise mechanism is unknown, there is evidence that statins lead to depletion of coenzyme Q10 (CoQ10), a mitochondrial nutrient needed to transport fatty acids to and within the mitochondria. During cholesterol synthesis, various metabolites, including CoQ10, are produced. Plasma levels of CoQ10 would therefore be lowered during treatment with HMG-CoA reductase inhibitors. It has also been documented that lower CoQ10 plasma levels could possibly be a result of decreased low- density lipoprotein (LDL), as CoQ10 is mainly transported by LDL. 10 Statins might secondarily cause behavioral changes through their impact on a variety of different factors, including impaired sleep, reduced testosterone, and effects on oxidative stress. Impaired or decreased sleep has been linked to irritability, aggression, and violence. However, behavioral changes associated with statin therapy might also be protective, as lower testosterone levels have been linked to reduced aggressive behavior. 1 In a 2015 case series, Cham et al 1 found that cholesterol-lowering therapy was A B S T R A C T Overview: Psychiatric adverse effects, including aggression, have been reported with the use of statin medications; however, there is little data to support or refute the theory that statins or low serum cholesterol do in fact increase a patient's risk of aggression. Objective: This study examined 1) statin use and increased aggression, measured by the requirement of either emergent psychiatric intervention referred to as "Code Green" (CG) or "Restraint and Seclusion" (RS) and 2) cholesterol level and increased aggression in psychiatric inpatients. Materials and Methods: Patient charts from January 1, 2011, to December 31, 2015 were reviewed. Statin therapy, lipid panel, and requirement of a psychiatric emergency code CG or RS were noted. Inpatients who did not receive cholesterol-lowering therapy were used as controls. Analyses of variance (ANOVAs) were used to examine the relationship between statin use and increased aggression. Results: Eleven (9.6%) patients receiving statins required a total of 57 CGs, and five (4.4%) required 27 RSs. Conversely, 33 (28.9%) patients not receiving statins required a total of 64 CGs, and 14 (12.3%) required 27 RSs. No statistically significant relationship between statin therapy and agitation was found as evidenced by a CG (F=0.068; p=0.795) or RS (F=0.001; p=1.000). A statistically significant relationship was found between total cholesterol level and requirement of a CG (F=1.435; p=0.029) or RS (F=2.89; p=0.000). Conclusion: It is evident that psychiatric inpatients with lower total cholesterol levels are at an increased risk for loss of behavioral control. Keywords: Statins, cholesterol, aggression, agitation, violence, psychiatric inpatients Effects of Statins and Cholesterol on Patient Aggression: Is There a Connection? by EMILY LEPPIEN, PharmD, BCPS; KIMBERLY MULCAHY, PharmD, BCPS, BCPP; TAMMIE LEE DEMLER, BS, PharmD, MBA, BCGP, BCPP; EILEEN TRIGOBOFF, RN, PMHCNS-BC, DNS, DABFN; and LEWIS OPLER, MD, PhD Drs. Leppien, Mulcahy, Demler, and Trigoboff are with Buffalo Psychiatric Center, New York State Office of Mental Health, and State University of New York, University at Buffalo School of Pharmacy and Pharmaceutical Sciences in Buffalo, New York. Drs. Demler and Trigoboff are with State University of New York, University at Buffalo School of Medicine, Department of Psychiatry. in Buffalo, New York. Dr. Opler is affiliated with Long Island University in Long Island, New York. Innov Clin Neurosci. 2018;15(3–4):24–27 FUNDING: None DISCLOSURES: The authors declare no conflicts of interest relevant to the content of this article. CORRESPONDENCE: Tammie Lee Demler, BS, PharmD, MBA; Email:

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