An update of safety of clinically used atypical antipsychotics

Expert Opinion on Drug Safety

Volumn 15, Issue 10, 2016, Pages 1329-1347

  Orsolini, L ^a,b,c,d   Tomasetti, C ^c,e,f   Valchera, A ^b,c   Vecchiotti, R ^b,c,d   Matarazzo, I ^g,h   Vellante, F ^g,h   Iasevoli, F ^c,f   Buonaguro, E F ^c,f   Fornaro, M ^c,i   Fiengo, A L C ^c   Martinotti, G ^h   Mazza, M ^c,j   Perna, G ^k,l   Carano, A ^m   De Bartolomeis, A ^f   Di Giannantonio, M ⁱ   De Berardis, D ^c,g,h  

^a UNIVERSITY OF HERTFORDSHIRE   (United Kingdom)

^b Hermanas Hospitalarias   (Italy)

^c Polyedra   (Italy)

^d MAASTRICHT UNIVERSITY   (Netherlands)

^e Hospital Maria SS dello Splendore   (Italy)

^f UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^g Mazzini Hospital   (Italy)

^h UNIVERSITY OF CHIETI   (Italy)

ⁱ NEW YORK STATE PSYCHIATRIC INSTITUTE   (United States)

^j UNIVERSITY OF L'AQUILA   (Italy)

^k Albese con Cassano ^*  (Italy)

^l UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^m Psychiatric Service of Diagnosis and Treatment   (Italy)

more..

Author keywords

adverse events; antipsychotic; Atypical antipsychotic; safety; side effects; tolerability

Indexed keywords

ADRENERGIC RECEPTOR; AMISULPRIDE; ARIPIPRAZOLE; ASENAPINE; ATYPICAL ANTIPSYCHOTIC AGENT; CHOLESTEROL; CLOZAPINE; CREATINE KINASE; DOPAMINE RECEPTOR; GLUTAMATE RECEPTOR; HALOPERIDOL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HISTAMINE RECEPTOR; ILOPERIDONE; LITHIUM; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LURASIDONE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; OLANZAPINE; PALIPERIDONE; PLACEBO; PROLACTIN; QUETIAPINE; RISPERIDONE; SEROTONIN RECEPTOR; TRIACYLGLYCEROL; VALPROATE SEMISODIUM; VALPROIC ACID; ZIPRASIDONE; NEUROLEPTIC AGENT;

ABNORMAL LABORATORY RESULT; ACUTE HEART INFARCTION; AGRANULOCYTOSIS; AKATHISIA; AMENORRHEA; ANEMIA; ANXIETY; ARTHRALGIA; ASPIRATION PNEUMONIA; AUDITORY HALLUCINATION; BEHAVIOR DISORDER; BINDING AFFINITY; BIPOLAR DISORDER; BIPOLAR I DISORDER; BLOOD DYSCRASIA; BLURRED VISION; BRADYCARDIA; CARDIOGENIC SHOCK; CARDIOMYOPATHY; CARDIOVASCULAR DISEASE; CARDIOVASCULAR SYMPTOM; CATARACT; CEREBROVASCULAR ACCIDENT; COCHRANE LIBRARY; COGNITIVE DEFECT; COLITIS; CONGESTIVE CARDIOMYOPATHY; CONSTIPATION; COUGHING; CREATINE KINASE BLOOD LEVEL; DELIRIUM; DEPRESSED BLOOD PRESSURE; DIABETES MELLITUS; DIABETIC COMA; DIABETIC KETOACIDOSIS; DIARRHEA; DIZZINESS; DRESS SYNDROME; DROWSINESS; DRUG BLOOD LEVEL; DRUG FORMULATION; DRUG INDICATION; DRUG MECHANISM; DRUG MONITORING; DRUG RECEPTOR BINDING; DRUG SAFETY; DYSPHAGIA; DYSPHONIA; DYSPNEA; DYSTONIA; ECG ABNORMALITY; ELECTROLYTE DISTURBANCE; EMBASE; ENDOCRINE DISEASE; EOSINOPHILIA; ERYTHRODERMA; EXTRAPYRAMIDAL SYMPTOM; FAINTNESS; FATIGUE; FEVER; FLU LIKE SYNDROME; GALACTORRHEA; GLOSSODYNIA; GYNECOMASTIA; HEADACHE; HEART ARREST; HEART ARRHYTHMIA; HEART FAILURE; HEART INFARCTION; HEART PALPITATION; HEART VENTRICLE ARRHYTHMIA; HEAT STROKE; HEPATITIS; HUMAN; HYPERGLYCEMIA; HYPERHIDROSIS; HYPEROSMOLARITY; HYPERPROLACTINEMIA; HYPERSALIVATION; HYPERTENSION; HYPERTHERMIA; HYPERTRANSAMINASEMIA; HYPESTHESIA; HYPOTENSION; INCREASED APPETITE; INJECTION SITE PAIN; INSOMNIA; INTERSTITIAL NEPHRITIS; INTESTINE ISCHEMIA; INTESTINE OBSTRUCTION; INTESTINE PERFORATION; ISCHEMIC HEART DISEASE; KETOACIDOSIS; LEUKOCYTOSIS; LEUKOPENIA; LIVER FAILURE; LUNG EDEMA; LYMPHADENOPATHY; MAJOR DEPRESSION; MALAISE; MANIA; MEDICAL SUBJECT HEADINGS; MEDLINE; MENTAL DISEASE; METABOLIC SYNDROME X; MILD HEPATIC IMPAIRMENT; MIXED MANIA AND DEPRESSION; MODERATE HEPATIC IMPAIRMENT; MUSCLE HYPERTONIA; MYALGIA; MYDRIASIS; MYOCARDITIS; NAUSEA; NEPHRITIS; NEUROLEPTIC MALIGNANT SYNDROME; NEUTROPENIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NOSE OBSTRUCTION; OCULOGYRIC CRISIS; ORAL HYPESTHESIA; OROPHARYNX PAIN; ORTHOSTATIC HYPOTENSION; PANCREATITIS; PARALYTIC ILEUS; PARANOIA; PARANOID SCHIZOPHRENIA; PAROTID GLAND DISEASE; PAROTID GLAND SWELLING; PERICARDITIS; PERIPHERAL EDEMA; PIGMENT DISORDER; PNEUMONIA; PRIAPISM; PROTEINURIA; PSYCINFO; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RESPIRATORY FAILURE; RESTLESSNESS; REVIEW; RHABDOMYOLYSIS; RHINOPHARYNGITIS; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; SEDATION; SEIZURE; SEPSIS; SEXUAL DYSFUNCTION; SIDE EFFECT; SINUS TACHYCARDIA; SOMNOLENCE; SORE THROAT; STUTTERING; SUICIDAL BEHAVIOR; SUICIDAL IDEATION; SWELLING; TACHYCARDIA; TARDIVE DYSKINESIA; THORAX PAIN; THROMBOCYTOPENIA; TOOTH PAIN; TORSADE DES POINTES; TREMOR; URINE RETENTION; VASCULITIS; VOMITING; WEIGHT GAIN; XEROSTOMIA; CHEMICALLY INDUCED; DRUG EFFECTS; ELECTROCARDIOGRAPHY; ELECTROLYTE BALANCE; METABOLIC DISORDER; PATHOPHYSIOLOGY;

ANTIPSYCHOTIC AGENTS; CARDIOVASCULAR DISEASES; ELECTROCARDIOGRAPHY; HUMANS; METABOLIC DISEASES; WATER-ELECTROLYTE BALANCE;

EID: 84988419408     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1080/14740338.2016.1201475     Document Type: Review

References (173)

1. R.Laricchia, I.Sanguinetti Chlorpromazine in mental disorders; indications for its use and limits of its therapeutic efficacy. Encephale. 1956;45(4):1197–1203.
2. WHO. International monitoring of adverse reactions to drugs:adverse reaction terminology. Uppsala (Sweden):WHO Collaborating Centre for International Drug Monitoring; 1992.
3. G.Addonizio, V.L.Susman, S.D.Roth. Neuroleptic malignant syndrome:review and analysis if 115 cases. Biol Psychiatry. 1987;22(8):1004–1020.
4. J.Muench, A.M.Hamer. Adverse effects of antipsychotic medications. American Family Physician. 2010;81(5):617–622.
5. C.R.Dolder, J.P.Lacro, L.B.Dunn, et al. Antipsychotic medication adherence:is there a difference between typical and atypical agents? Am J Psychiatry. 2002;159(1):103–108.
6. S.Bleakley, D.Taylor. The clozapine handbook. London:Lloyd-Reinhold Communications LLP; 2013.
7. J.Idänpään-Heikkilä, E.Alhava, M.Olkinuora, et al. Agranulocytosis during treatment with clozapine. Eur J Clin Pharmacol. 1997;11:193–198.
8. S.R.Marder, R.C.Meibach. Risperidone in the treatment of schizophrenia. Am J Psychiatry. 1994;151:825–835.
9. C.M.Beasley, F.Tollefson, P.Tran, et al. Olanzapine versus placebo and haloperidol:acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology. 1996;14:111–124.
10. L.A.Arvantis, L.A.Miller, Seroquel Trial 13 Study Group. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia:a comparison with haloperidol and placebo. Biol Psychiatry. 1997;42:233–246.
11. C.Prakash, A.Kamel, W.Anderson, et al. Metabolism and excretion of the novel antipsychotic drug ziprasidone in rats after oral administration of a mixture of lac- and 3H-labeled ziprasidone. Drug Metab Dispos. 1997;25:206–218.
12. J.M.Goldstein. The new generation of antipsychotic drugs:how atypical are they? Int J Neuropsychopharmacol. 2000;3(4):339–349.
13. V.Ozdemir, J.Fourie, F.Ozdener. Aripiprazole (Otsuka Pharmaceutical Co). Curr Opin Investig Drugs. 2002;3(1):113–120.
14. L.P.Yang, G.L.Plosker. Paliperidone extended release. CNS Drugs. 2007;21(5):417–425; discussion 426-7.
15. M.Shahid, G.B.Walker, S.H.Zorn, et al. Asenapine:a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009;23(1):65–73. doi:10.1177/0269881107082944.
16. O.Agid, G.Foussias, G.Remington. Long-acting injectable antipsychotics in the treatment of schizophrenia:their role in relapse prevention. Expert Opin Pharmacother. 2010;11:2301–2317.
17. A.Thyssen, S.Rusch, V.Herben, et al. Risperidone long-acting injection:pharmacokinetics following administration in deltoid versus gluteal muscle in schizophrenic patients. J Clin Pharmacol. 2010;50:1011–1021.
18. E.Gilday, H.Nasrallah. Clinical pharmacology of paliperidone palmitate a parenteral long-acting formulation for the treatment of schizophrenia. Rev Recent Clin Trials. 2012;7:2–9.
19. S.Brissos, M.R.Veguilla, D.Taylor, et al. The role of long-acting injectable antipsychotics in schizophrenia:a critical appraisal. Ther Adv Psychopharmacol. 2014;4(5):198–219. doi:10.1177/2045125314540297.
20. 3 receptors. Neuropsychopharmacology. 1994;10:242S.
21. H.J.Mφller. Amisulpride:limbic specificity and the mechanism of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:1101–1111.
22. 7 antagonist:relevance for antidepressant actions in vivo. Psychopharmacology (Berl). 2009;205:119–128.
23. M.P.Curran, C.M.Perry. Amisulpride:a review of its use in the management of schizophrenia. Drugs. 2001;61(14):2123–2150.
24. P.M.Haddad, A.Wieck. Antipsychotic-induced hyperprolactinemia:mechanisms, clinical features and management. Drugs. 2004;64(20):2291–2314.
25. G.K.Isbister, C.R.Balit, D.Macleod, et al. Amisulpride overdose is frequently associated with QT prolongation and torsades de pointes. J Clin Psychopharmacol. 2010;30(4):391–395. doi:10.1097/JCP.0b013e3181e5c14c.
26. M.Bloechliger, S.Rüegg, S.S.Jick, et al. Antipsychotic drug use and the risk of seizures:follow-up study with a nested case-control analysis. CNS Drugs. 2015;29(7):591–603. doi:10.1007/s40263-015-0262-y.
27. P.Rosenzweig, M.Canal, A.Patat, et al. A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpiride in healthy volunteers. Hum Psychopharmacol. 2002;17(1):1–13.
28. D.N.Mendhekar, D.Lohia, P.Kataria. Tardive oculogyric crisis associated with amisulpride monotherapy. J Postgrad Med. 2010;56(4):305–306. doi:10.4103/0022-3859.70947.
29. F.Musshoff, E.Doberentz, B.Madea. Lethal neuroleptic malignant syndrome due to amisulpride. Forensic Sci Med Pathol. 2013;9(2):218–220. doi:10.1007/s12024-013-9410-1.
30. D.A.Shapiro, S.Renock, E.Arrington, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003;28:1400–1411.
31. A.Newman-Tancredi, M.S.Kleven. Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties. Psychopharmacology (Berl). 2001;216:451–473.
32. A.De Bartolomeis, C.Tomasetti, F.Iasevoli. Update on the mechanism of action of aripiprazole:translational insights into antipsychotic strategies beyond dopamine receptor antagonism. CNS Drugs. 2015;29:773–799.
33. T.Hamamura, T.Harada. Unique pharmacological profile of aripiprazole as the phasic component buster. Psychopharmacology (Berl). 2007;191:741–743.
34. R.B.Mailman, V.Murthy. Third generation antipsychotic drugs:partial agonism or receptor functional selectivity? Curr Pharm Des. 2010;16:488–501.
35. A.DeLeon, N.C.Patel, M.L.Crismon. Aripiprazole:a comprehensive review of its pharmacology, clinical efficacy, and tolerability. Clin Ther. 2004;26:649–666.
36. J.M.Kane, S.Assuncao-Talbott, J.M.Eudicone, et al. The efficacy of aripiprazole in the treatment of multiple symptom domains in patients with acute schizophrenia:a pooled analysis of data from the pivotal trials. Schizophr Res. 2008;105:208–215.
37. T.A.Pigott, W.H.Carson, A.R.Saha, et al. Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia:a placebo-controlled 26-week study. J Clin Psychiatry. 2003;64:1048–1056.
38. L.Citrome, I.Kalsekar, R.A.Baker, et al. A review of real-world data on the effects of aripiprazole on weight and metabolic outcomes in adults. Curr Med Res Opin. 2014;30:1629–1641.
39. D.Mamo, A.Graff, R.Mizrahi, et al. Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia:a triple tracer PET study. Am J Psychiatry. 2007;164:1411–1417.
40. S.N.Ghaemi, D.J.Hsu, K.J.Rosenquist, et al. Extrapyramidal side effects with atypical neuroleptics in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:209–213.
41. A.Salmoiraghi, M.Odiyoor. A case of aripiprazole and extra pyramidal side effects. J Psychopharmacol. 2006;20:592–593.
42. J.C.Shim, Y.S.You, D.L.Kelly. Aripiprazole treatment causes extrapyramidal side effects but not prolactin elevation:a disconnect of the striatal D2 occupancy story:case report. J Clin Psychopharmacol. 2008;28:353–354.
43. C.Polcwiartek, B.Sneider, C.Graff, et al. The cardiac safety of aripiprazole treatment in patients at high risk for torsade:a systematic review with a meta-analytic approach. Psychopharmacology (Berl). 2015;232:3297–3308.
44. R.Ries, A.Sayadipour. Management of psychosis and agitation in medical-surgical patients who have or are at risk for prolonged QT interval. J Psychiatr Pract. 2014;20:338–344.
45. S.Leucht, A.Cipriani, L.Spineli, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia:a multiple-treatments meta-analysis. Lancet. 2013;382:951–962.
46. D.De Berardis, M.Fornaro, N.Serroni, et al. Treatment of antipsychotic-induced hyperprolactinemia:an update on the role of the dopaminergic receptors D2 partial agonist aripiprazole. Recent Pat Endocr Metab Immune Drug Discov. 2014;8:30–37.
47. Physician Assistants Prescribing R. New drug information. Saphris. JAAPA. 2010;23:16.
48. M.Shahid, G.B.Walker, S.H.Zorn, et al. Asenapine:a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009;23:65–73.
49. J.Tauscher, T.Hussain, O.Agid, et al. Equivalent occupancy of dopamine D1 and D2 receptors with clozapine:differentiation from other atypical antipsychotics. Am J Psychiatry. 2004;161:1620–1625.
50. O.Franberg, M.M.Marcus, V.Ivanov, et al. Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms. Psychopharmacology (Berl). 2009;204:251–264.
51. K.Jardemark, M.M.Marcus, M.Shahid, et al. Effects of asenapine on prefrontal N-methyl-D-aspartate receptor-mediated transmission:involvement of dopamine D1 receptors. Synapse. 2010;64:870–874.
52. F.I.Tarazi, T.Moran-Gates, E.H.Wong, et al. Asenapine induces differential regional effects on serotonin receptor subtypes. J Psychopharmacol. 2010;24:341–348.
53. H.M.Marston, J.W.Young, F.D.Martin, et al. Asenapine effects in animal models of psychosis and cognitive function. Psychopharmacology (Berl). 2009;206:699–714.
54. S.Snigdha, N.Idris, B.Grayson, et al. Asenapine improves phencyclidine-induced object recognition deficits in the rat:evidence for engagement of a dopamine D1 receptor mechanism. Psychopharmacology (Berl). 2011;214:843–853.
55. M.Kolaczkowski, P.Mierzejewski, P.Bienkowski, et al. Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics:rat profile and implications for behavioral and psychological symptoms of dementia. Naunyn Schmiedebergs Arch Pharmacol. 2014;387:545–557.
56. J.M.Kane, M.Cohen, J.Zhao, et al. Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia. J Clin Psychopharmacol. 2010;30:106–115.
57. L.Citrome. Iloperidone, asenapine, and lurasidone:a brief overview of 3 new second-generation antipsychotics. Postgrad Med. 2011;123:153–162.
58. D.Bishara, D.Taylor. Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder. Neuropsychiatr Dis Treat. 2009;5:483–490.
59. R.S.McIntyre, M.Cohen, J.Zhao, et al. Asenapine for long-term treatment of bipolar disorder:a double-blind 40-week extension study. J Affect Disord. 2010;126:358–365.
60. R.Musil, M.Obermeier, P.Russ, et al. Weight gain and antipsychotics:a drug safety review. Expert Opin Drug Saf. 2015;14:73–96.
61. L.Citrome. Asenapine for schizophrenia and bipolar disorder:a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. Int J Clin Pract. 2009;63:1762–1784.
62. H.Y.Meltzer. An overview of the mechanism of action of clozapine. J Clin Psychiatry. 1994;55(Suppl B):47–52.
63. P.Seeman. Clozapine, a fast-off-D2 antipsychotic. ACS Chem Neurosci. 2014;5(1):24–29.
64. H.Y.Meltzer, B.Bastani, L.Ramirez, et al. Clozapine:new research on efficacy and mechanism of action. Eur Arch Psychiatry Neurol Sci. 1989;238(5–6):332–339.
65. J.Fitzsimons, M.Berk, T.Lambert, et al. A review of clozapine safety. Expert Opin Drug Saf. 2005;4(4):731–744.•• Very interesting review on overall clozapine safety.
66. T.S.Stroup, T.Gerhard, S.Crystal, et al. Comparative effectiveness of clozapine and standard antipsychotic treatment in adults with schizophrenia. Am J Psychiatry. 2016;173(2):166–173.
67. P.De Fazio, R.Gaetano, M.Caroleo, et al. Rare and very rare adverse effects of clozapine. Neuropsychiatr Dis Treat. 2015;11:1995–2003.
68. D.Bishara, D.Taylor. Adverse effects of clozapine in older patients:epidemiology, prevention and management. Drugs Aging. 2014;31(1):11–20.
69. M.Raja, S.Raja. Clozapine safety, 40 years later. Curr Drug Saf. 2014;9(3):163–195.
70. A.M.Williams, S.H.Park. Seizure associated with clozapine:incidence, etiology, and management. CNS Drugs. 2015;29(2):101–111.• Interesting review on clozapine-associated seizures.
71. A.Stark, J.Scott. A review of the use of clozapine levels to guide treatment and determine cause of death. Aust N Z J Psychiatry. 2012;46(9):816–825.
72. S.Varma, D.Bishara, F.M.Besag, et al. Clozapine-related EEG changes and seizures:dose and plasma-level relationships. Ther Adv Psychopharmacol. 2011;1(2):47–66.
73. D.Caetano. Use of anticonvulsants as prophylaxis for seizures in patients on clozapine. Aust Psychiatry. 2014;22(1):78–83.
74. R.Musil, M.Obermeier, P.Russ, et al. Weight gain and antipsychotics:a drug safety review. Expert Opin Drug Saf. 2015;14(1):73–96.
75. J.S.Lamberti, D.Olson, J.F.Crilly, et al. Prevalence of the metabolic syndrome among patients receiving clozapine. Am J Psychiatry. 2006;163(7):1273–1276.•• This study compared the prevalence of the metabolic syndrome among outpatients with schizophrenia and schizoaffective disorder receiving clozapine.
76. L.E.Rojo, P.A.Gaspar, H.Silva, et al. Metabolic syndrome and obesity among users of second generation antipsychotics:A global challenge for modern psychopharmacology. Pharmacol Res. 2015;101:74–85.
77. Z.Whitney, R.M.Procyshyn, D.H.Fredrikson, et al. Treatment of clozapine-associated weight gain:a systematic review. Eur J Clin Pharmacol. 2015;71(4):389–401.
78. A.C.Kelly, B.B.Sheitman, R.M.Hamer, et al. A naturalistic comparison of the long-term metabolic adverse effects of clozapine versus other antipsychotics for patients with psychotic illnesses. J Clin Psychopharmacol. 2014;34(4):441–445.
79. F.M.Werner, R.Coveñas. Safety of antipsychotic drugs:focus on therapeutic and adverse effects. Expert Opin Drug Saf. 2014;13(8):1031–1042.
80. M.Belvederi Murri, A.Guaglianone, M.Bugliani, et al. Second-generation antipsychotics and neuroleptic malignant syndrome:systematic review and case report analysis. Drugs R D. 2015;15(1):45–62.
81. T.L.Demler, N.E.Morabito, C.E.Meyer, et al. Maximizing clozapine utilization while minimizing blood dyscrasias:evaluation of patient demographics and severity of events. Int Clin Psychopharmacol. 2016;31(2):76–83.• This study examined all neutropenic events to identify any potential demographic qualities that may pose increased risk to individuals receiving clozapine treatment in accordance with the FDA guidelines released in 2005.
82. K.Atkin, F.Kendall, D.Gould, et al. Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland. Br J Psychiatry. 1996;169(4):483–488.
83. P.K.Chandrasekaran. Agranulocytosis monitoring with clozapine patients:to follow guidelines or to attempt therapeutic controversies? Singapore Med J. 2008;49(2):96–99.
84. T.L.Demler, E.Trigoboff. Are clozapine blood dyscrasias associated with concomitant medications? Innov Clin Neurosci. 2011;8(4):35–41.• Medications that had a statistically significant impact on the incidence of clozapine-induced blood dyscrasias were reported in this article.
85. Clozapine REMS program. 2015 [cited 2015 Dec20]. Available from: https://www.clozapinerems.com
86. C.R.Young, M.B.Bowers, C.M.Mazure. Management of the adverse effects of clozapine. Schizophr Bull. 1998;24(3):381–390.
87. D.De Berardis, N.Serroni, D.Campanella, et al. Update on the adverse effects of clozapine:focus on myocarditis. Curr Drug Saf. 2012;7(1):55–62.• An interesting narrative review on clozapine-related myocarditis.
88. M.Alawami, C.Wasywich, A.Cicovic, et al. A systematic review of clozapine induced cardiomyopathy. Int J Cardiol. 2014;176(2):315–320.
89. K.J.Ronaldson, P.B.Fitzgerald, J.J.McNeil. Clozapine-induced myocarditis, a widely overlooked adverse reaction. Acta Psychiatr Scand. 2015;132(4):231–240.•• A comprehensive review of the published cases of clozapine-induced myocarditis.
90. K.J.Ronaldson, P.B.Fitzgerald, A.J.Taylor, et al. Clozapine-induced myocarditis and baseline echocardiography. Aust N Z J Psychiatry. 2012;46(10):1006–1007.
91. J.Molina Martín De Nicolás, J.J.Parra Fuertes, E.Gómez Mariscal, et al. Clozapine-associated myocarditis. Med Clin (Barc). 2015;145(9):e19–20.
92. S.C.Cook, B.A.Ferguson, R.O.Cotes, et al. Clozapine-induced myocarditis:prevention and considerations in rechallenge. Psychosomatics. 2015;56(6):685–690.
93. D.M.Coulter, A.Bate, R.H.Meyboom, et al. Antipsychotic drugs and heart muscle disorder in international pharmacovigilance:data mining study. Bmj. 2001;322(7296):1207–1209.
94. K.J.Ronaldson, P.B.Fitzgerald, A.J.Taylor, et al. A new monitoring protocol for clozapine-related myocarditis based on an analysis of 75 cases and 94 controls. Aust N Z J Psychiatry. 2011;45(6):458–465.•• A very useful monitoring protocol for clozapine-related myocarditis.
95. D.De Berardis, D.Campanella, N.Serroni, et al. Clozapine-related pericarditis during titration phase in a patient with resistant schizophrenia and concomitant valproate treatment:a case report. J Clin Psychopharmacol. 2014;34(5):649–651.
96. M.D.Imon Paul, V.Basavaraju, J.C.Narayanaswamy, et al. Clozapine induced pericarditis. Clin Schizophr Relat Psychoses. 2014;1–6.
97. C.A.Paciullo. Evaluating the association between clozapine and venous thromboembolism. Am J Health Syst Pharm. 2008;65(19):1825–1829. doi:10.2146/ajhp070638.
98. B.Cam, M.Z.Tanircan. Clozapine-induced paralytic ileus:a case report. Ther Adv Psychopharmacol. 2014;4(4):170–172.
99. J.P.John, K.N.Chengappa, R.W.Baker, et al. Assessment of changes in both weight and frequency of use of medications for the treatment of gastrointestinal symptoms among clozapine-treated patients. Ann Clin Psychiatry. 1995;7(3):119–125.
100. R.J.Flanagan, R.Y.Ball. Gastrointestinal hypomotility:an under-recognised life-threatening adverse effect of clozapine. Forensic Sci Int. 2011;206(1–3):e31–6.• An interesting paper on clozapine-related gastrointestinal hypomotility.
101. J.Nielsen, J.M.Meyer. Risk factors for ileus in patients with schizophrenia. Schizophr Bull. 2012;38(3):592–598.•• Authors investigated the relative risk of ileus for various psychotropics in schizophrenia patients using the Danish National Registers.
102. N.Galappathie, S.Khan. Clozapine-associated pneumonia and respiratory arrest secondary to severe constipation. Med Sci Law. 2014;54(2):105–109.
103. J.N.Trollor, X.Chen, P.S.Sachdev. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477–492. doi:10.2165/00023210-200923060-00003.
104. M.R.Szeczak, R.Corbett, D.K.Rush, et al. The pharmacological profile of iloperidone, a novel atypical antipsychotic agent. J Pharmacol Exp Ther. 1995;274(3):1404–1413.
105. S.Kongsamut, J.E.Roehr, J.Cai, et al. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996;317(2–3):417–423.
106. P.J.Weiden, A.J.Cutler, M.H.Polymeropoulos, et al. Safety profile of iloperidone:a pooled analysis of 6-week acute-phase pivotal trials. J Clin Psychopharmacol. 2008;28(2Suppl 1):S12–19.
107. Vanda Pharmaceuticals. Fanapt (iloperidone) Tablets [cited 2010 Aug7]. Available from: http://www.pharma.us.novartis.com/product/pi/pdf/fanapt.pdf
108. S.M.Sainati, J.W.Hubbard, E.Chi, et al. Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J Clin Pharmacol. 1995;35(7):713–720.
109. N.Guanci, R.Aggarwal, S.Schleifer. Atypical neuroleptic malignant syndrome associated with iloperidone administration. Psychosomatics. 2012;53(6):603–605. doi:10.1016/j.psym.2012.06.011.
110. S.Caccia, L.Pasina, A.Nobili. New atypical antipsychotics for schizophrenia:iloperidone. Drug Des Devel Ther. 2010;4:33–48.
111. S.G.Potkin, S.Preskorn, M.Hochfeld, et al. A thorough QTc study of 3 doses of iloperidone including metabolic inhibition via CYP2D6 and/or CYP3A4 and a comparison to quetiapine and ziprasidone. J Clin Psychopharmacol. 2013;33(1):3–10. doi:10.1097/JCP.0b013e31827c0314.
112. J.M.Meyer, A.D.Loebel, E.Schweizer. Lurasidone:a new drug in development for schizophrenia. Expert Opin Investig Drugs. 2009;18:1715–1726.
113. L.Citrome, P.J.Weiden, J.P.McEvoy, et al. Effectiveness of lurasidone in schizophrenia or schizoaffective patients switched from other antipsychotics:a 6-month, open-label, extension study. CNS Spectr. 2014;19:330–339.
114. A.V.TerryJr, J.J.Buccafusco, C.Wilson. Cognitive dysfunction in neuropsychiatric disorders:selected serotonin receptor subtypes as therapeutic targets. Behav Brain Res. 2008;195:30–38.
115. L.Citrome, J.Cucchiaro, K.Sarma, et al. Long-term safety and tolerability of lurasidone in schizophrenia:a 12-month, double-blind, active-controlled study. Int Clin Psychopharmacol. 2012;27:165–176.
116. S.Caccia, L.Pasina, A.Nobili. Critical appraisal of lurasidone in the management of schizophrenia. Neuropsychiatr Dis Treat. 2012;8:155–168.
117. Y.S.Woo, H.R.Wang, W.M.Bahk. Lurasidone as a potential therapy for bipolar disorder. Neuropsychiatr Dis Treat. 2013;9:1521–1529.
118. A.Loebel, J.Cucchiaro, K.Sarma, et al. Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia:a randomized, double-blind, placebo- and active-controlled trial. Schizophr Res. 2013;145:101–109.
119. S.G.Potkin, M.Ogasa, J.Cucchiaro, et al. Double-blind comparison of the safety and efficacy of lurasidone and ziprasidone in clinically stable outpatients with schizophrenia or schizoaffective disorder. Schizophr Res. 2011;132:101–107.
120. L.Samalin, M.Garnier, P.M.Llorca. Clinical potential of lurasidone in the management of schizophrenia. Ther Clin Risk Manag. 2011;7:239–250.
121. H.Y.Meltzer, J.Cucchiaro, R.Silva, et al. Lurasidone in the treatment of schizophrenia:a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011;168:957–967.
122. F.P.Bymaster, K.Rasmussen, D.O.Calligaro, et al. In vitro and in vivo biochemistry of olanzapine:a novel, atypical antipsychotic drug. J Clin Psychiatry. 1997;58(Suppl 10):28–36.
123. F.P.Bymaster, D.L.Nelson, N.W.DeLapp, et al. Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro. Schizophr Res. 1999;37(1):107–122.
124. J.Fernø, K.M.Ersland, I.H.Duus, et al. Olanzapine depot exposure in male rats:dose-dependent lipogenic effects without concomitant weight gain. Eur Neuropsychopharmacol. 2015;25(6):923–932. doi:10.1016/j.euroneuro.2015.03.002.
125. R.Meatherall, J.Younes. Fatality from olanzapine induced hyperglycemia. J Forensic Sci. 2002 Jul;47(4):893–896.
126. Z.Sun, X.Wang. Case report of refractory tardive dystonia induced by olanzapine. Shanghai Arch Psychiatry. 2014;26(1):51–53. doi:10.3969/j.issn.1002-0829.2014.01.008.
127. Z.Zhao, H.Zhang, S.Wang, et al. Sudden discontinuation and reinstitution of olanzapine-associated atypical neuroleptic malignant syndrome in a patient undergoing lung surgery. Int J Clin Exp Med. 2015;8(7):11639–11641.
128. S.K.Praharaj, A.K.Jana, S.Sarkar, et al. Olanzapine-induced tardive oculogyric crisis. J Clin Psychopharmacol. 2009;29(6):604–606. doi:10.1097/JCP.0b013e3181c00b08.
129. A.Aggarwal, M.Jain, A.Khandelwal, et al. Tardive Meige’s syndrome associated with olanzapine. Ann Indian Acad Neurol. 2011;14(2):133–134. doi:10.4103/0972-2327.82808.
130. G.P.Singh, R.Kumar, P.Bharti. Tardive dystonia with olanzapine:a rare case report. Indian J Psychol Med. 2012;34(2):187–189. doi:10.4103/0253-7176.101795.
131. K.Malhotra, P.Vu, D.H.Wang, et al. Olanzapine-induced neutropenia. Ment Illn. 2015;7(1):5871. doi:10.4081/mi.2015.5871.
132. S.R.Marder, S.Sorsaburu, E.Dunayevich, et al. Case reports of postmarketing adverse event experiences with olanzapine intramuscular treatment in patients with agitation. Journal of Clinical Psychiatry. 2010;71(4):433–441. doi:10.4088/jcp.08m04411gry.
133. C.J.Bushe, D.Falk, E.Anand, et al. Olanzapine long-acting injection:a review of first experiences of post-injection delirium/sedation syndrome in routine clinical practice. BMC Psychiatry. 2015;15:65.
134. M.Łukasik-Głębocka, K.Sommerfeld, A.Teżyk, et al. Post-injection delirium/sedation syndrome after olanzapine long-acting intramuscular injection – who is at risk? Basic Clin Pharmacol Toxicol. 2015;117(3):213–214. doi:10.1111/bcpt.12394.
135. W.P.Clarke, T.A.Chavera, M.Silva, et al. Signalling profile differences:paliperidone versus risperidone. Br J Pharmacol. 2013;170(3):532–545. doi:10.1111/bph.12295.
136. R.Arakawa, H.Ito, A.Takano, et al. Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology (Berl). 2008;197(2):229–235.
137. C.Álamo, F.López-Muñoz. The pharmacological role and clinical applications of antipsychotics’ active metabolites:paliperidone versus risperidone. Clin Exp Pharmacol. 2013;3:117. doi:10.4172/2161-1459.1000117.
138. A.M.Nussbaum, T.S.Stroup. Paliperidone palmitate for schizophrenia. Schizophr Bull. 2012;38(6):1124–1127.
139. A.Gonzalez-Rodriguez, R.Catalan, R.Penadés, et al. Profile of paliperidone palmitate once-monthly long-acting injectable in the management of schizophrenia:long-term safety, efficacy, and patient acceptability – a review. Patient Prefer Adherence. 2015;9:695–706.
140. E.Spina, R.Crupi. Safety and efficacy of paliperidone extended-release in acute and maintenance treatment of schizophrenia. J Cent Nerv Syst Dis. 2011;3:27–41.
141. S.Gopal, Y.Liu, L.Alphs, et al. Incidence and time course of extrapyramidal symptoms with oral and long-acting injectable paliperidone:a posthoc pooled analysis of seven randomized controlled studies. Neuropsychiatr Dis Treat. 2013;9:1381–1392. doi:10.2147/NDT.S49944.
142. I.Montalvo, L.Ortega, X.López, et al. Changes in prolactin levels and sexual function in young psychotic patients after switching from long-acting injectable risperidone to paliperidone palmitate. Int Clin Psychopharmacol. 2013;28(1):46–49. doi:10.1097/YIC.0b013e32835ba832.
143. A.Rodríguez-Martínez, C.G.Quilo. Paliperidone extended-release:safety and tolerability from a metabolic profile perspective. Clin Drug Investig. 2013;33(12):867–876. doi:10.1007/s40261-013-0100-2.
144. Once-monthly Invega® Sustenna™ (paliperidone palmitate) extended-release injectable suspension [package insert]. Titusville (NJ):Janssen Pharmaceuticals; 2011.
145. G.J.Pandina, J.P.Lindenmayer, J.Lull, et al. A randomized, placebo-controlled study to assess the efficacy and safety of three doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol. 2010;30(3):235–244.
146. S.Gopal, U.Vijapurkar, P.Lim, et al. A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia. J Psychopharmacol. 2011;25(5):685–697.
147. C.F.Saller, A.I.Salama. Seroquel:biochemical profile of a potential atypical antipsychotic. Psychopharmacology. 1993;112:285–292.
148. D.E.Casey. ‘Seroquel’ (quetiapine):preclinical and clinical findings of a new atypical antipsychotic. Exp Opin Invest Drugs. 1996;5:939–957.
149. J.M.Goldstein Preclinical profile of ‘Seroquel’ (quetiapine):an atypical antipsychotic with clozapine-like pharmacology. In:S.G.Holliday, R.J.Ancill, G.W.MacEwan, editors. Schizophrenia:breaking down the barriers. Chichester:John Wiley & Sons Ltd; 1996. p. 177–208.
150. A.F.Schatzberg, C.Nemeroff. The American psychiatric publishing textbook of psychopharmacology. 4th ed. Washington (DC):American Psychoiatric Publishing; 2009.
151. D.Degner. Severe adverse reactions associated with quetiapine. Bmj. 2015;24(350):h1575. doi:10.1136/bmj.h1575.
152. D.D.Miller, S.N.Caroff, S.M.Davis, et al. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Extrapyramidal side-effects of antipsychotics in a randomised trial. Br J Psychiatry. 2008;193(4):279–288. doi:10.1192/bjp.bp.108.050088.
153. R.Shah, S.Grover, U.Maheshwari, et al. Acute akathisia with quetiapine:A case report and review of literature. Indian J Pharmacol. 2010;42(6):416–417. doi:10.4103/0253-7613.71896.
154. M.Brecher, R.W.Leong, G.Stening, et al. Quetiapine and long-term weight change:a comprehensive data review of patients with schizophrenia. J Clin Psychiatry. 2007;68:597–603.
155. J.E.Leysen, P.M.F.Janssen, W.Gommeren, et al. In vitro and in vivo receptor-binding and effects on monoamine turnover in rat-brain regions of the novel antipsychotics risperidone and ocaperidone. Mol Pharmacol. 1992;41(3):494–508.
156. J.E.Leysen, P.M.Janssen, A.A.Megens, et al. Risperidone:a novel antipsychotic balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994;55(Suppl 5):12.
157. J.P.McEvoy, M.Byerly, R.M.Hamer, et al. Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia. A randomized clinical trial. JAMA. 2014;311(19):1978–1986. doi:10.1001/jama.2014.4310.
158. A.González-Rodríguez, R.Catalán, R.Penadés, et al. Profile of paliperidone palmitate once-monthly long-acting injectable in the management of schizophrenia:long-term safety, efficacy, and patient acceptability – a review. Patient Prefer Adherence. 2015;9:695–706. doi:10.2147/PPA.S63948.
159. K.Komossa, C.Rummel-Kluge, S.Schwarz, et al. Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2011;(1):CD006626. doi:10.1002/14651858.CD006626.pub2.
160. K.Gao, M.Mackle, P.Cazorla, et al. Comparison of somnolence associated with asenapine, olanzapine, risperidone, and haloperidol relative to placebo in patients with schizophrenia or bipolar disorder. Neuropsychiatr Dis Treat. 2013;9:1145–1157. doi:10.2147/NDT.S41333.
161. Y.F.Lee, C.K.Tsai, C.S.Liang. High-dose risperidone induced latent syndrome of inappropriate antidiuretic hormone secretion with seizure presentation. Clin Neuropharmacol. 2015;38(4):154–155. doi:10.1097/WNF.0000000000000095.
162. A.Glinka, S.Polak. QTc modification after risperidone administration – insight into the mechanism of action with use of the modeling and simulation at the population level approach. Toxicol Mech Methods. 2015;25(4):279–286. doi:10.3109/15376516.2015.1025346.
163. C.Wong-Anuchit. Clinical management of antipsychotic-induced hyperprolactinemia. Perspect Psychiatr Care. 2015. doi:10.1111/ppc.12111.
164. A.Dos Santos Júnior, T.B.Henriques, M.P.De Mello, et al. Hyperprolactinemia in children and adolescents with use of risperidone:clinical and molecular genetics aspects. J Child Adolesc Psychopharmacol. 2015;25(10):738–748. doi:10.1089/cap.2015.0094.
165. F.Vogel, R.Gansmüller, T.Leiblein, et al. The use of ziprasidone in clinical practice:analysis of pharmacokinetic and pharmacodynamic aspects from data of a drug monitoring survey. Eur Psychiatry. 2009;24(3):143–148. doi:10.1016/j.eurpsy.2008.09.003.
166. P.Seeman. All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2(high) receptors. CNS Neurosci Ther. 2011;17:118–132.
167. L.Citrome. Using oral ziprasidone effectively:the food effect and dose-response. Adv Ther. 2009;26:739–748.
168. D.L.Kelly, R.C.Love. Ziprasidone and the QTc interval:pharmacokinetic and pharmacodynamic considerations. Psychopharmacol Bull. 2001;35(4):66–79.
169. J.S.Gordon, K.M.Neyman, R.D.Wells, et al. Drug rash with eosinophilia and systemic symptoms (DRESS syndrome). Cutis. 2012;89(4):180–182.
170. A.Breier, P.H.Berg, J.H.Thakore, et al. Olanzapine versus ziprasidone:results of a 28-week double-blind study in patients with schizophrenia. Am J Psychiatry. 2005;162(10):1879–1887.
171. C.-H.Li, L.Shi, G.-L.Zhan, et al. A twenty-four-week, open-label study on ziprasidone’s efficacy and influence on glucolipid metabolism in patients with schizophrenia and metabolic disorder. Eur Rev Med Pharmacol Sci. 2013;17(16):2136–2140.
172. N.Campbell, M.Boustani, T.Limbil, et al. The cognitive impact of anticholinergics:a clinical review. Clin Interv Aging. 2009;4:225–233.
173. M.Piersanti, M.Capannolo, M.Turchetti, et al. Increase in mortality rate in patients with dementia treated with atypical antipsychotics:a cohort study in outpatients in Central Italy. Riv Psichiatr. 2014;49(1):34–40. doi:10.1708/1407.15623.