A comprehensive review of swallowing difficulties and dysphagia associated with antipsychotics in adults

References

• Stahl SM. Antipsychotic agents. In: Stahl SM, editor. Stahl’s essential psychopharmacology. 4th ed. New York: Cambridge University Press; 2013. p. 129–236.
   Google Scholar
• U.S. Food and Drug Administration. Public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. Silver Spring (MD); [cited 2018 Jun 13]. Available from: http://www.fda.gov/drugs/drugsafety/patientsandproviders/ucm053171
   Google Scholar
• U.S. Food and Drug Administration: FDA requests boxed warnings on older class of antipsychotic drugs [news release]. Silver Spring (MD): U.S. Food and Drug Administration; 2008 June 16 [cited 2018 Jun 13]. Available from: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116912.htm
   Google Scholar
• O’Neill JL, Remington TL. Drug-induced esophageal injuries and dysphagia. Ann Pharmacother. 2003;37:1675–1684.
   PubMed Web of Science ®Google Scholar
• Dziewas R, Warnecke T, Schnabel M, et al. Neuroleptic-induced dysphagia: case report and literature review. Dysphagia. 2007;22:63–67.
   PubMed Web of Science ®Google Scholar
• Kulkarni DP, Kamath VD, Stewart JT. Swallowing disorders in schizophrenia. Dysphagia. 2017;32:467–471.
   PubMed Web of Science ®Google Scholar
• Miarons Font M, Rofes Salsench L. Antipsychotic medication and oropharyngeal dysphagia: systematic review. Eur J Gastroenterol Hepatol. 2017;29:1332–1339.
   PubMed Web of Science ®Google Scholar
• Jean A. Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol Rev. 2001;81:929–969.
   PubMed Web of Science ®Google Scholar
• Ertekin C, Aydoglu I. Neurophysiology of swallowing. Clin Neurophysiol. 2003;114:2226–2244.
   PubMed Web of Science ®Google Scholar
• Shaw SM, Martino R. The normal swallow: muscular and neurophysiological control. Otolaryngol Clin North Am. 2013;46:937–956.
   PubMed Web of Science ®Google Scholar
• Bolser DC, Gestreau C, Morris KF, et al. Central neural circuits for coordination of swallowing, breathing, and coughing: predictions from computational modeling and simulation. Otolaryngol Clin North Am. 2013;46:957–964.
   PubMed Web of Science ®Google Scholar
• Bieger D, Neuhuber W. Neural circuits and mediators regulating swallowing in the brainstem. GI Motil Online. 2006. DOI:10.1038/gimo74
   Google Scholar
• Goyal RK, Chaudhury A. Physiology of normal esophageal motility. J Clin Gastroenterol. 2008;42:610–619.
   PubMed Web of Science ®Google Scholar
• McElroy SL, Crow S, Biernacka JM, et al. Clinical phenotype of bipolar disorder with comorbid binge eating disorder. J Affect Disord. 2013;150:981–986.
   PubMed Web of Science ®Google Scholar
• Kaindlstorfer A, Pointner R. An appraisal of current dysphagia diagnosis and treatment strategies. Exp Rev Gastroenterol Hepatol. 2016;10:929–942.
   PubMed Web of Science ®Google Scholar
• Buchholz DW. Oropharyngeal dysphagia due to iatrogenic neurological dysfunction. Dysphagia. 1995;10:248–254.
   PubMed Web of Science ®Google Scholar
• Dantas RO, Nobre Souza MA. Dysphagia induced by chronic ingestion of benzodiazepine. Am J Gastroenterol. 1997;92:1194–1196.
   PubMed Web of Science ®Google Scholar
• Roden DF, Altman KW. Causes of dysphagia among different age groups: a systematic review of the literature. Otolaryngol Clin North Am. 2013;46:965–987.
   PubMed Web of Science ®Google Scholar
• Morris H. Dysphagia in the elderly: a management challenge for nurses. Br J Nurs. 2006;15:558–562.
   PubMedGoogle Scholar
• Kyle G. Managing dysphagia in older people with dementia. Br J Community Nurs. 2011;16:6–10.
   PubMedGoogle Scholar
• Wright D. Medication administration in nursing homes. Nurs Stand. 2002;16:33–38.
   PubMedGoogle Scholar
• Sheppard JJ. Managing dysphagia in mentally retarded adults. Dysphagia. 1991;6:83–87.
   PubMedGoogle Scholar
• Böhmer CJ, Niezen-de Boer MC, Klinkenberg-Knol EC, et al. The prevalence of gastroesophageal reflux disease in institutionalized intellectually disabled individuals. Am J Gastroenterol. 1999;94:804–810.
   PubMed Web of Science ®Google Scholar
• Sheppard JJ, Hochman R, Baer C. The dysphagia disorder survey: validation of an assessment for swallowing and feeding function in developmental disability. Res Dev Disabil. 2014;35:929–942.
   PubMed Web of Science ®Google Scholar
• Sheppard JJ, Malandraki GA, Pifer P, et al. Validation of the choking risk assessment and pneumonia risk assessment for adults with intellectual and developmental disability (IDD). Res Dev Disabil. 2017;69:61–76.
   PubMed Web of Science ®Google Scholar
• Takizawa C, Gemmell E, Kenworthy J, et al. A systematic review of the prevalence of oropharyngeal dysphagia in stroke, Parkinson’s disease, Alzheimer’s disease, head injury, and pneumonia. Dysphagia. 2016;31:434–441.
   PubMed Web of Science ®Google Scholar
• Wirth R, Dziewas R, Beck AM, et al. Oropharyngeal dysphagia in older persons - from pathophysiology to adequate intervention: a review and summary of an international expert meeting. Clin Interv Aging. 2016;11:189–208.
   PubMed Web of Science ®Google Scholar
• Lazenby T. The impact of aging on eating, drinking, and swallowing function in people with Down’s syndrome. Dysphagia. 2008;23:88–97.
   PubMed Web of Science ®Google Scholar
• Rudolph JL, Gardner KF, Gramigna GD, et al. Antipsychotics and oropharyngeal dysphagia in hospitalized older patients. J Clin Psychopharmacol. 2008;28:532–535.
   PubMed Web of Science ®Google Scholar
• Feldman PE. An unusual death associated with tranquilizer therapy. Am J Psychiatry. 1957;113:1032–1033.
   PubMed Web of Science ®Google Scholar
• Hollister LE. Unexpected asphyxia death and tranquilizing drugs. Am J Psychiatry. 1957;114:366–367.
   PubMed Web of Science ®Google Scholar
• Barach E, Dubin LM, Tomlanovich MC, et al. Dystonia presenting as upper airway obstruction. J Emerg Med. 1989;7:237–240.
   PubMedGoogle Scholar
• Sliwa JA, Lis S. Drug-induced dysphagia. Arch Phys Med Rehabil. 1993;74:445–447.
   PubMed Web of Science ®Google Scholar
• McCarthy RH, Terkelsen KG. Esophageal dysfunction in two patients after clozapine treatment. J Clin Psychopharmacol. 1994;14:281–283.
   PubMed Web of Science ®Google Scholar
• Hughes TAT, Shone G, Lindsay G, et al. Severe dysphagia associated with major tranquilizer treatment. Postgrad Med J. 1994;70:581–583.
   PubMed Web of Science ®Google Scholar
• Bashford G, Bradd P. Drug-induced parkinsonism associated with dysphagia and aspiration: a brief report. J Geriatr Psychiatry Neurol. 1996;9:133–135.
   PubMed Web of Science ®Google Scholar
• Leopold NA. Dysphagia in drug-induced parkinsonism: a case report. Dysphagia. 1996;11:151–153.
   PubMed Web of Science ®Google Scholar
• Hayashi T, Nishikawa T, Koga I, et al. Life-threatening dysphagia following prolonged neuroleptic therapy. Clin Neuropharmacol. 1997;20:77–81.
   PubMed Web of Science ®Google Scholar
• Sokoloff LG, Pavlakovic R. Neuroleptic-induced dysphagia. Dysphagia. 1997;12:177–179.
   PubMed Web of Science ®Google Scholar
• Bulling M. Drug-induced dysphagia. Aust N Z J Med. 1999;29:748.
   PubMedGoogle Scholar
• Stewart JT. Reversible dysphagia associated with neuroleptic treatment. J Am Geriatr Soc. 2001;49:1260–1261.
   PubMed Web of Science ®Google Scholar
• Stewart JT. Dysphagia associated with risperidone therapy. Dysphagia. 2003;18:274–275.
   PubMed Web of Science ®Google Scholar
• Sagar R, Varghese ST, Balhara YP. Dysphagia due to olanzapine, an antipsychotic medication. Indian J Gastroenterol. 2005;24:37–38.
   PubMedGoogle Scholar
• Varghese ST, Balhara YP, George SA, et al. Risperidone and dysphagia. J Postgrad Med. 2006;52:327–328.
   PubMed Web of Science ®Google Scholar
• Armstrong D, Ahuja N, Lloyd AJ. Quetiapine-related dysphagia. Psychosomatics. 2008;49:450–452.
   PubMed Web of Science ®Google Scholar
• Kohen I, Lester P. Quetiapine-associated dysphagia. World J Biol Psychiatr. 2009;10:623–625.
   PubMed Web of Science ®Google Scholar
• Brahm NC, Fast GA, Brown RO. Risperidone and dysphagia in a developmentally disabled woman. Prim Care Companion J Clin Psychiatry. 2007;9:315–316.
   PubMedGoogle Scholar
• Tang KT, Hsieh MH. A case of schizophrenia with dysphagia successfully treated by a multidimensional approach. Gen Hosp Psychiatry. 2010;559:e11–3.
   Google Scholar
• Lin TW, Lee BS, Liao YC, et al. High dosage of aripiprazole-induced dysphagia. Int J Eat Disord. 2012;45:305–306.
   PubMed Web of Science ®Google Scholar
• Osman M, Devadas V. Clozapine-induced dysphagia with secondary substantial weight loss. BMJ Case Rep. 2016;bcr2016216445.
   PubMedGoogle Scholar
• Crouse EL, Alastanos JN, Bozymski KM, et al. Dysphagia with second-generation antipsychotics: A case report and review of the literature. Ment Health Clin. 2017;7:56–64.
   PubMedGoogle Scholar
• Stewart JT. Cover dysphagia and recurrent pneumonia related to antipsychotic treatment. J Psychiatry Neurosci. 2018;43:143–144.
   PubMed Web of Science ®Google Scholar
• Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951–962.
   PubMed Web of Science ®Google Scholar
• Robbins JA, Logemann J, Kirshner A. Swallowing and speech in Parkinson’s disease. Ann Neurol. 1986;19:283–287.
   PubMed Web of Science ®Google Scholar
• Casey DE. Neuroleptic-induced acute extrapyramidal syndromes and tardive dyskinesia. Psychiatr Clin North Am. 1993;16:589–610.
   PubMed Web of Science ®Google Scholar
• Jr SC. Drug-induced dystonia. Am J Psychiatry. 1975;132:532–534.
   PubMed Web of Science ®Google Scholar
• Raja M, Azzoni A. Novel antipsychotics and acute dystonic reactions. Int J Neuropsychopharmacol. 2001;4:393–397.
   PubMed Web of Science ®Google Scholar
• Flaherty JA, Lahmeyer HW. Laryngeal-pharyngeal dystonia as a possible cause of asphyxia with haloperidol treatment. Am J Psychiatry. 1978;135:1414–1415.
   PubMed Web of Science ®Google Scholar
• Duggal HS, Mendhekar DN. Risperidone-induced tardive pharyngeal dystonia presenting with persistent dysphagia: a case report. Prim Care Companion J Clin Psychiatry. 2008;10:161–162.
   PubMedGoogle Scholar
• Mendhekar DN, Agarwal A. Paliperidone-induced dystonic dysphagia. J Neuropsychiatry Clin Neurosci. 2010;22:451.
   PubMed Web of Science ®Google Scholar
• Sico JJ, Patwa H. Risperidone-induced bulbar palsy-like syndrome. Dysphagia. 2011;16:340–343.
   Google Scholar
• Nair S, Saeed O, Shahab H, et al. Sudden dysphagia with uvular enlargement following the initiation of risperidone which responded to benztropine: was this an extrapyramidal side effect? Gen Hosp Psychiatry. 2001;23:231–232.
   PubMed Web of Science ®Google Scholar
• Carbon M, Hsieh CH, Kane JM, et al. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78:e264–78.
   PubMed Web of Science ®Google Scholar
• Solmi M, Pigato G, Kane JM, et al. Clinical risk factors for the development of tardive dyskinesia. J Neurol Sci. 2018;389:21–27.
   PubMed Web of Science ®Google Scholar
• Gregory RP, Smith PT, Rudge P. Tardive dyskinesia presenting as severe dysphagia. J Neurol Neurosurg Psychiatry. 1992;55:1203–1204.
   PubMed Web of Science ®Google Scholar
• Feve A, Angelard B, Lacau St Guily J. Laryngeal tardive dyskinesia. J Neurol. 1995;242:455–459.
   PubMed Web of Science ®Google Scholar
• Nieves JE, Stack KM, Harrison ME, et al. Dysphagia: a rare form of dyskinesia? J Psychiatr Pract. 2007;13:199–201.
   PubMedGoogle Scholar
• Bhat PS, Pardal PK, Diwakar M. Dysphagia due to tardive dyskinesia. Indian J Psychiatry. 2010;19:134–135.
   Google Scholar
• Yassa R, Lal S. Respiratory irregularity and tardive dyskinesia: a prevalence study. Acta Psychiatr Scand. 1986;73:506–510.
   PubMed Web of Science ®Google Scholar
• Kruk J, Sachdev P, Singh S. Neuroleptic-induced respiratory dyskinesia. J Neuropsychiatry Clin Neurosci. 1995;7:223–229.
   PubMed Web of Science ®Google Scholar
• Solmi M, Pigato G, Kane JM, et al. Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel. 2018;Ther.12:1215–1238.
   PubMed Web of Science ®Google Scholar
• Zorn SH, Jones SB, Ward KM, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994;269:R1–2.
   PubMed Web of Science ®Google Scholar
• Sur C, Mallorga PJ, Wittmann M,J, et al. N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity. Proc Nat Acad Sci. 2003;100:13674–13679.
   PubMed Web of Science ®Google Scholar
• Davies MA, Compton-Toth BA, Hufeisen SJ, et al. The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine’s actions? Psychopharmacology (Berl). 2005;178:451–460.
   PubMed Web of Science ®Google Scholar
• Asenjo Lobos C, Komossa K, Rummel-Kluge C, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010;11:CD006633.
   Google Scholar
• Ekström J, Godoy T, Riva A. Clozapine: agonistic and antagonistic salivary secretory actions. J Dent Res. 2010;89:276–280.
   PubMed Web of Science ®Google Scholar
• Safferman A, Lieberman JA, Kane JM, et al. Update on the clinical efficacy and side effects of clozapine. Schizophr Bull. 1991;17:247–261.
   PubMed Web of Science ®Google Scholar
• Bird AM, Smith TL, Walton AE. Current treatment strategies for clozapine-induced sialorrhea. Ann Pharmacother. 2011;45:667–675.
   PubMed Web of Science ®Google Scholar
• Schindler JS, Kelly JH. Swallowing disorders in the elderly. Laryngoscope. 2002;112:589–602.
   PubMed Web of Science ®Google Scholar
• Maddalena AS, Fox M, Hofmann M, et al. Esophageal dysfunction on psychotropic medication A case report and literature review. Pharmacopsychiatry. 2004;37:134–138.
   PubMed Web of Science ®Google Scholar
• Shibley H, Pelic C, Pelic A, et al. A case of paranoid schizophrenia complicated by scleroderma with associated esophageal dysmotility. J Psychiatr Pract. 2008;14:126–130.
   PubMed Web of Science ®Google Scholar
• Pearlman C. Clozapine, nocturnal sialorrhea, and choking. J Clin Psychopharmacol. 1994;14:283.
   PubMed Web of Science ®Google Scholar
• Russell SA, Hennes HM, Herson KJ, et al. Upper airway compromise in acute chlorpromazine ingestion. Am J Emergency Med. 1996;14–15:467–468.
   Web of Science ®Google Scholar
• Berzlanovich AM, Fazeny-Dörner B, Waldhoer T, et al. Foreign body asphyxia: a preventable cause of death in the elderly. Am J Prev Med. 2005;28:65–69.
   PubMed Web of Science ®Google Scholar
• Simpson E. How to manage a choking adult. Nurs Stand. 2016;31:42–46.
   PubMedGoogle Scholar
• Duckett SA, Roten RA. Choking. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan [cited 2018 Apr 25]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK499941/PubMed; PMID: 29763116
   Google Scholar
• Craig J. Medication use and deaths attributed to asphyxia among psychiatric patients. Am J Psychiatry. 1980;137:1366–1373.
   PubMed Web of Science ®Google Scholar
• Fioritti A, Giaccotto L, Melega V. Choking incidents among psychiatric patients: retrospective analysis of thirty-one cases from the west Bologna psychiatric wards. Can J Psychiatry. 1997;42:515–520.
   PubMed Web of Science ®Google Scholar
• Corcoran E, Walsh D. Obstructive asphyxia: A cause of excess mortality in psychiatric patients. Irish J Psychol Med. 2003;20:880–890.
   Web of Science ®Google Scholar
• Ruschena D, Mullen PE, Palmer S, et al. Choking deaths: the role of antipsychotic medication. Br J Psychiatry. 2003;183:446–450.
   PubMed Web of Science ®Google Scholar
• Yim PH, Chong CS. Choking in psychiatric patients: associations and outcomes. Hong Kong J Psychiatry. 2009;19:145–149.
   Google Scholar
• Hwang SJ, Tsai SJ, Chen IJ, et al. Choking incidents among psychiatric inpatients: a retrospective study in Chutung veterans general hospital. J Chin Med Assoc. 2010;73:419–424.
   PubMed Web of Science ®Google Scholar
• Allen DE, de Nesnera A, Robinson DA. Psychiatric patients are at increased of falling and choking. J Am Psychiatr Nurses Assoc. 2012;18:91–95.
   PubMed Web of Science ®Google Scholar
• Visser HK, Wigington JL, Keltner NL, et al. Biological perspectives: choking and antipsychotics: is this a significant concern? Perspect Psychiatr Care. 2014;50:79–82.
   PubMed Web of Science ®Google Scholar
• Bock JM, Varadarajan V, Brawley MC, et al. Evaluation of the natural history of patients who aspirate. Laryngoscope. 2017;127(Suppl 8):S1–10.
   PubMedGoogle Scholar
• Kikawada M, Iwamoto T, Takasaki M. Aspiration and infection in the elderly: epidemiology, diagnosis and management. Drugs Aging. 2005;22:115–130.
   PubMed Web of Science ®Google Scholar
• Son YG, Shin J, Ryu HG. Pneumonitis and pneumonia after aspiration. J Dent Anesth Pain Med. 2017;17:1–12.
   PubMedGoogle Scholar
• Knol W, Marum R, Jansen P, et al. Antipsychotic drug use and risk of pneumonia in elderly people. J Am Geriatr Soc. 2008;56:661–666.
   PubMed Web of Science ®Google Scholar
• Trifirò G, Gambassi G, Sen E, et al. Association of community-acquired pneumonia with antipsychotic drug use in elderly patients: a nested case-control study. Ann Intern Med. 2010;152:418–425.
   PubMed Web of Science ®Google Scholar
• Star K, Bate A, Meyboom RH, et al. Pneumonia following antipsychotic prescriptions in electronic health records: A patient safety concern? Br J Gen Pract. 2010;60:e385–94.
   PubMed Web of Science ®Google Scholar
• Huybrechts KF, Schneeweiss S, Gerhard T, et al. Comparative safety of antipsychotic medications in nursing home residents. J Am Geriatr Soc. 2012;60:420–429.
   PubMed Web of Science ®Google Scholar
• Nosè M, Recla E, Trifirò G, et al. Antipsychotic drug exposure and risk of pneumonia: a systematic review and meta-analysis of observational studies. Pharmacoepidemiol Drug Saf. 2015;24:812–820.
   PubMed Web of Science ®Google Scholar
• Gau JT, Acharya U, Khan S, et al. Pharmacotherapy and the risk for community-acquired pneumonia. BMC Geriatr. 2010;10:45.
   PubMed Web of Science ®Google Scholar
• Aparasu RR, Chatterjee S, Chen H. Risk of pneumonia in elderly nursing home residents using typical versus atypical antipsychotics. Ann Pharmacother. 2013;47:464–474.
   PubMed Web of Science ®Google Scholar
• Gambassi G, Sultana J, Trifirò G. Antipsychotic use in elderly patients and the risk of pneumonia. Expert Opin Drug Safety. 2015;14:1–6.
   PubMed Web of Science ®Google Scholar
• Hinkes R, Quesada TV, Currier MB, et al. Aspiration pneumonia possibly secondary to clozapine-induced sialorrhea. J Clin Psychopharmacol. 1996;16:462–463.
   PubMed Web of Science ®Google Scholar
• Schmidinger S, Hofer A. Pulmonary embolism and aspiration pneumonia after reexposure to clozapine: pulmonary adverse effects of clozapine. J Clin Psychopharmacol. 2014;34:385–387.
   PubMed Web of Science ®Google Scholar
• Kaplan J, Schwartz A, Ward MC. Clozapine-associated aspiration pneumonia: case series and review of the literature. Psychosomatics. 2018;59:199–203.
   PubMed Web of Science ®Google Scholar
• Kuo C, Yang S, Liao Y, et al. Second-generation antipsychotic medications and risk of pneumonia. Schizophr Bull. 2013;39:648–657.
   PubMed Web of Science ®Google Scholar
• Yang SY, Liao YT, Liu HC, et al. Antipsychotic drugs, mood stabilizers, and risk of pneumonia in bipolar disorder: a nationwide case-control study. J Clin Psychiatry. 2013;74:e79–86.
   PubMed Web of Science ®Google Scholar
• Hung GC, Liu HC, Yang SY, et al. Antipsychotic reexposure and recurrent pneumonia in schizophrenia: a nested case-control study. J Clin Psychiatry. 2016;77:60–66.
   PubMed Web of Science ®Google Scholar
• Stoecker ZR, George WT, O’Brien JB, et al. Clozapine usage increases the incidence of pneumonia compared with risperidone and the general population: a retrospective comparison of clozapine, risperidone, and the general population in a single hospital over 25 months. Int Clin Psychopharmacol. 2017;32:155–160.
   PubMed Web of Science ®Google Scholar
• Mehta S, Pulungan Z, Jones BT, et al. Comparative safety of atypical antipsychotics and the risk of pneumonia in the elderly. Pharmacoepidemiol Drug Saf. 2015;24:1271–1280.
   PubMed Web of Science ®Google Scholar
• Sultana J, Calabrò M, Garcia-Serna R, et al. Biological substantiation of antipsychotic-associated pneumonia: systematic literature review and computational analyses. PLoS One. 2017;12:e0187034.
   PubMed Web of Science ®Google Scholar
• Marik PE, Kaplan D. Aspiration pneumonia and dysphagia in the elderly. Chest. 2003;124:328–336.
   PubMed Web of Science ®Google Scholar
• Leung JG, Hasassri ME, Barreto JN, et al. Characterization of admission types in medically hospitalized patients prescribed clozapine. Psychosomatics. 2017;58:164–172.
   PubMed Web of Science ®Google Scholar
• Taylor DM, Douglas-Hall P, Olofinjana B, et al. Reasons for discontinuing clozapine: matched, case-control comparison with risperidone long-acting injection. Br J Psychiatry. 2009;194:165–167.
   PubMed Web of Science ®Google Scholar
• Rohde C, Polcwiartek C, Kragholm K, et al. Adverse cardiac events in out-patients initiating clozapine treatment: a nationwide register-based study. Acta Psychiatr Scand. 2018;137:47–53.
   PubMed Web of Science ®Google Scholar
• Raaska K, Raitasuo V, Arstila M, et al. Bacterial pneumonia can increase serum concentration of clozapine. Eur J Clin Pharmacol. 2002;58:321–322.
   PubMed Web of Science ®Google Scholar
• de Leon J, Diaz FJ. Serious respiratory infections can increase clozapine levels and contribute to side effects: a case report. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:1059–1063.
   PubMed Web of Science ®Google Scholar
• Ruan CJ, Zhen XY, Ge XL. Pneumonia can cause clozapine intoxication: a case report. Psychosomatics. 2017;58:652–656.
   PubMed Web of Science ®Google Scholar
• Ruan CJ, de Leon J. Thirty years of both ignorance and clinical experience suggest that clozapine intoxication during co-occurring infections and inflammation may have higher morbidity and mortality than is currently believed. Psychosomatics. 2018 Jul 25:S0033–3182(18)30330-X. DOI:10.1016/j.psym.2018.07.009 Epub ahead of print.
   PubMed Web of Science ®Google Scholar
• Clark SR, Warren NS, Kim G, et al. Elevated clozapine levels associated with infection: A systematic review. Schizophr Res. 2018;192:50–56.
   PubMed Web of Science ®Google Scholar
• Shah RR, Smith RL. Inflammation-induced phenoconversion of polymorphic drug metabolizing enzymes: hypothesis with implications for personalized medicine. Drug Metab Dispos. 2015;43:400–410.
   PubMed Web of Science ®Google Scholar
• Hefner G, Shams ME, Unterecker S, et al. Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels. Psychopharmacology (Berl). 2016;233:1695–1705.
   PubMed Web of Science ®Google Scholar
• Hefner G, Falter T, Bruns K, et al. Elevated risperidone serum concentrations during acute inflammation, two cases. Int J Psychiatry Med. 2015;50:335–344.
   PubMed Web of Science ®Google Scholar
• Song C, Lin A, Kenis G, et al. Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. Schizophr Res. 2000;42:157–164.
   PubMed Web of Science ®Google Scholar
• Cohen D. Clozapine and gastrointestinal hypomotility. CNS Drugs. 2017;31:1083–1091.
   PubMed Web of Science ®Google Scholar
• Palmer SE, McLean RM, Ellis PM, et al. Life-threatening clozapine-induced gastrointestinal hypomotility: an analysis of 102 cases. J Clin Psychiatry. 2008;69:759–768.
   PubMed Web of Science ®Google Scholar
• Galappathie N, Khan S. Clozapine-associated pneumonia and respiratory arrest secondary to severe constipation. Med Sci Law. 2014;54:105–109.
   PubMed Web of Science ®Google Scholar
• de Leon J.de Las Cuevas C. The art of pharmacotherapy: reflections on pharmacophobia. J Clin Psychopharmacol. 2017;37:131–137.
   PubMed Web of Science ®Google Scholar
• Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–245.
   PubMed Web of Science ®Google Scholar
• Gallagher RM, Kirkham JJ, Mason JR, et al. Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool. PLoS One. 2011;6:e28096.
   PubMed Web of Science ®Google Scholar
• de Leon J. Evidence-based medicine versus personalized medicine: are they enemies? J Clin Psychopharmacol. 2012;32:153–164.
   PubMed Web of Science ®Google Scholar
• Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294:1934–1943.
   PubMed Web of Science ®Google Scholar
• Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006;355:1525–1538.
   PubMed Web of Science ®Google Scholar
• Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173:543–546.
   PubMed Web of Science ®Google Scholar
• Chadwick DD, Jolliffe J. A descriptive investigation of dysphagia in adults with intellectual disabilities. J Intellect Disabil Res. 2009;53:29–43.
   PubMed Web of Science ®Google Scholar
• de Leon J. Highlights of drug package inserts and the website DailyMed: the need for further improvement in package inserts to help busy prescribers. J Clin Psychopharmacol. 2011;31:263–265.
   PubMed Web of Science ®Google Scholar