Episode 11: Sensorium Part 4: Medications, Drugs (THC, Alcohol), Medical Issues, Sleep, and Free Will David Puder, M.D. This PDF is a supplement to the podcast “Psychiatry & Psychotherapy,” found on iTunes or Google Play or YouTube ​ ​ ​ ​ ​ ​ Special thanks to intellectual and research contributions from: Rebeka Sipma, Dr. Amul Shah, Ale-salvo Daniela, Adam Borechy, and Jaime Rudyk ● Optimize medical issues treatment: ○ Diabetes is a common disease that when treated properly has lower rates of depression and cognitive issues. ■ Diabetes has twice the rate of depression than that of nondiabetic comparison groups1 ■ When Type 2 Diabetes was brought under better control through medications, working memory significantly improved2 ○ Hypertensive patients without vascular complications had deficits with speed of ​ cognition, episodic and working memory, and executive function.3 ○ Treat depression and mental health issues ○ Treat seizure disorders ○ Treat OSA ● Medications: ○ Reduce polypharmacy (for example when baclofen and gabapentin were taken ​ together they had cognitive effects but when taken alone did not in one study4 ○ Take off or minimize anticholinergic medications ​ ​ ■ Most commonly used: Hydroxyzine, Amitriptyline, Benztropine, Clozapine, Diphenhydramine, Doxepin, Imipramine, Methocarbamol, Nortriptyline, Olanzapine, Paroxetine, Quetiapine (see full list here) ​ ​ ○ Take off or minimize dose of antihistamine medications5 ​ ​ 1 Anderson, R. J., Freedland, K. E., Clouse, R. E., & Lustman, P. J. (2001). The prevalence of comorbid ​ depression in adults with diabetes: a meta-analysis. Diabetes care, 24(6), 1069-1078. ​ ​ ​ ​ 2 Ryan, C. M., Freed, M. I., Rood, J. A., Cobitz, A. R., Waterhouse, B. R., & Strachan, M. W. (2006). ​ Improving metabolic control leads to better working memory in adults with type 2 diabetes. Diabetes care, ​ ​ 29(2), 345-351. ​ 3 Saxby, B. K., Harrington, F., McKeith, I. G., Wesnes, K., & Ford, G. A. (2003). Effects of hypertension on ​ attention, memory, and executive function in older adults. Health Psychology, 22(6), 587. ​ ​ ​ ​ 4 Salimzade, Asma, Ali Hosseini-Sharifabad, and Mohammad Rabbani. "Comparative effects of chronic administrations of ga​ bapentin, pregabalin and baclofen on rat memory using object recognition test." Research in Pharmaceutical Sciences12.3 ​ ​ (2017): 204. 5 Tannenbaum, C., Paquette, A., Hilmer, S., Holroyd-Leduc, J., & Carnahan, R. (2012). A systematic review of amnestic and no​ n-amnestic mild cognitive impairment induced by anticholinergic, antihistamine, GABAergic and opioid drugs. Drugs & aging, ​ ​ 29(8), 639-658. ​ Copyright: David Puder, M.D., 2018, Please share this without changing any of the content. Episode 11: Sensorium Part 4: Medications, Drugs (THC, Alcohol), Medical Issues, Sleep, and Free Will David Puder, M.D. ○ Taper off benzodiazepines because of issues ​ ​ with psychomotor speed, memory, processing speed, attention, verbal memory, general intelligence, working memory, verbal reasoning (mean effect size -0.74) (xanax, klonopin, ativan, ect).6 Of note, after tapering off patients from chronic benzodiazepine use, there was significant improvement in sensorium. However compared to controls or normative data, there was an incomplete restoration of function at 6 months.7 Of note this could be because people who are on benzodiazepines often have multiple other stressors and things going on which could factor into this discrepancy. Of note, temazepam for sleep might be of less concern.8 Tapering off of these meds can be dangerous if done too fast; specifically there can be issues like having a seizure. Please work with a physician to slowly decrease these medications. ○ Zolpidem if taken 8 hours prior to driving or cognitive tests, it does not cause ​ impairment, whereas if taken 4 hours prior does.9 At 2 hours after ingestion it causes cognitive issues and balance issues.10 ○ Minimize or take off opioids (vicodin, oxycodone)11 ​ ​ ■ In one animal study, opioids reduced neurogenesis by 42% in the hippocampal granule cell layer12 ○ Reduce or eliminate topiramate and valproate13 (of note, sometimes valproate ​ ​ ​ has been helpful in hyperactive delirium with improvement in aggression14) ○ Consider alternatives to carbamazepine15 or zonisomide1617 ​ ​ 6 Melinda J. Barker, Kenneth M. Greenwood, Martin Jackson and Simon F. Crowe. Cognitive Effects of Long-Term Benzodiazepine ​ Use: A Meta-Analysis. CNS Drugs 2004; 18 (1): 37-48 ​ 7 Barker MJ, Greenwood KM, Jackson M, et al. Persistence of cognitive effects after withdrawal from long-term ​ be​ nzodiazepine use: a meta-analysis. Arch Clin Neuropsychol 2004;19:437-454 ​ ​ 8 Morin, C. M., Bastien, C. H., Brink, D., & Brown, T. R. (2003). Adverse effects of temazepam in older adults with chronic insomnia. Hu​ man Psychopharmacology: Clinical and Experimental, 18(1), 75-82. ​ ​ ​ 9 Verster, J. C., Volkerts, E. R., Olivier, B., Johnson, W., & Liddicoat, L. (2007). Zolpidem and traffic safety-the importance of ​ treatment compliance. Current drug safety, 2(3), 220-226. ​ ​ ​ ​ 10 Frey, D. J., Ortega, J. D., Wiseman, C., Farley, C. T., & Wright, K. P. (2011). Influence of Zolpidem and Sleep Inertia on Balance ​ and Cognition During Nighttime Awakening: A Randomized Placebo Controlled Trial. Journal of the American Geriatrics Society, - ​ ​ 59(1), 73-81. ​ 11 Rapeli, P., Fabritius, C., Alho, H., Salaspuro, M., Wahlbeck, K., & Kalska, H. (2007). Methadone vs. buprenorphine/naloxone ​ during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls. BMC ​ clinical pharmacology, 7(1), 5. ​ ​ ​ 12 Eisch, A. J., Barrot, M., Schad, C. A., Self, D. W., & Nestler, E. J. (2000). Opiates inhibit neurogenesis in the adult rat ​ hippocampus. Proceedings of the National Academy of Sciences, 97(13), 7579-7584. ​ ​ ​ ​ 13Gualtieri, C. T., & Johnson, L. G. (2006). Comparative neurocognitive effects of 5 psychotropic anticonvulsants and lithium. Medscape General Medicine, 8(3), 46. ​ ​ ​ 14 Sher Y, Miller AC, Lolak S, Ament A, Maldonado JR. “Adjunctive valproic acid in management-refractory hyperactive delirium: a ​ case series and rationale.” J Neuropsychiatry Clin Neurosci. 2015;27(4):365–370. 15 Mecarelli, Oriano, et al. "Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, ​ oxcarbazepine, and levetiracetam in healthy volunteers." Annals of Pharmacotherapy 38.11 (2004): 1816-1822. ​ ​ 16 Park SP, Hwang YH, Lee HW et al.: Long-term cognitive and mood effects of zonisamide monotherapy in epilepsy patients. ​ Epilepsy Behav 2008; 12(1):102–108 ​ ​ ​ Copyright: David Puder, M.D., 2018, Please share this without changing any of the content. Episode 11: Sensorium Part 4: Medications, Drugs (THC, Alcohol), Medical Issues, Sleep, and Free Will David Puder, M.D. ○ Medications with mild sensorium issues: gabapentin does not cause cognitive changes ​ but does sometimes have occasional sedation issues18 at higher doses19, oxcarbazepine (slight ​ ​ alpha wave slowing and some some issues with sedation)2021, trazodone (mild issues with ​ ​ short-term memory, verbal learning, body sway, muscle endurance)22 ○ Medications without cognitive effects: Lamotrigine23, Keppra (although 20% had ​ ​ ​ complaints of somnolence)24, propranolol.25 ​ ● Sleep issues: ○ Poor sleep leads to decreased memory encoding, mood issues, worse concentration, driving accidents26 ○ Sleep counteracts the effects of chronic stress and allows the body’s immune system to “regenerate”27 ○ Set up patterns of rest (limiting caffeine and electronics at night before bed, consistent bed and wake times, and eliminating napping) ○ Diagnose and treat Obstructive Sleep Apnea and treat with CPAP and weight ​ ​ loss. ■ Uses in CPAP will improve short term memory, episodic memory, processing speed and mental flexibility28 ■ Another study showed that CPAP improved depression scores29 17 Berent S, Sackellares JC, Giordani B et al.: Zonisamide (CI-912) and cognition: results from preliminary study. Epilepsia 1987; ​ ​ 28(​ 1):61–67. ​ 18 Leach JP, Girvan J, Paul A, Brodie MJ. Gabapentin and cognition: a double blind, dose ranging, placebo controlled study in ​ refractory epilepsy. J Neurol Neurosurg Psychiatry 1997;62:372–376. 19 Leach, J. P., Girvan, J., Paul, A., & Brodie, M. J. (1997). Gabapentin and cognition: a double blind, dose ranging, placebo ​ controlled study in refractory epilepsy. Journal of Neurology, Neurosurgery & Psychiatry, 62(4), 372-376. ​ ​ ​ ​ 20 Seo, Jong-Geun, et al. "Comparison of cognitive effects of lamotrigine and oxcarbazepine in epilepsy patients." Journal of Clinical ​ ​ Neurology 3.1 (2007): 31-37. ​ 21 Salinsky, M. C., et al. "Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers." Epilepsy & ​ ​ Behavior 5.6 (2004): 894-902. ​ 22 Roth, A. J., McCall, W. V., & Liguori, A. (2011). Cognitive, Psychomotor, and Polysomnographic Effects of Trazodone in Primary Ins​ omniacs. Journal of Sleep Research, 20(4), 552–558. http://doi.org/10.1111/j.1365-2869.2011.00928.x ​ ​ ​ ​ 23 Pressler, R. M., Binnie, C. D., Coleshill, S. G., Chorley, G. A., & Robinson, R. O. (2006). Effect of lamotrigine on cognition in ​ children with epilepsy. Neurology, 66(10), 1495-1499. ​ ​ ​ ​ 24Mecarelli, Oriano, et al. "Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers." Annals of Pharmacotherapy 38.11 (2004): 1816-1822. ​ ​ 25 Pérez-Stable, E. J.,