The nature of relapse in schizophrenia

Robinson D, Woerner MG, Alvir JM, Bilder R, Goldman R, Geisler S, et al: Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999, 56: 241-247. 10.1001/archpsyc.56.3.241.

Kane JM: Treatment strategies to prevent relapse and encourage remission. J Clin Psychiatry. 2007, 68 (Suppl 14): 27-30.

Wyatt RJ: Research in schizophrenia and the discontinuation of antipsychotic medications. Schizophr Bull. 1997, 23: 3-9. 10.1093/schbul/23.1.3.

Lieberman JA, Alvir JM, Koreen A, Geisler S, Chakos M, Sheitman B, et al: Psychobiologic correlates of treatment response in schizophrenia. Neuropsychopharmacology. 1996, 14: 13S-21S. 10.1016/0893-133X(95)00200-W.

Alvarez-Jimenez M, Priede A, Hetrick SE, Bendall S, Killackey E, Parker AG, et al: Risk factors for relapse following treatment for first episode psychosis: a systematic review and meta-analysis of longitudinal studies. Schizophr Res. 2012, 139: 116-128. 10.1016/j.schres.2012.05.007.

Coldham EL, Addington J, Addington D: Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand. 2002, 106: 286-290. 10.1034/j.1600-0447.2002.02437.x.

Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P: A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011, 168: 603-609. 10.1176/appi.ajp.2011.10081224.

Miller BJ: A review of second-generation antipsychotic discontinuation in first-episode psychosis. J Psychiatr Pract. 2008, 14: 289-300. 10.1097/01.pra.0000336756.65308.83.

Miller BJ, Bodenheimer C, Crittenden K: Second-Generation Antipsychotic Discontinuation in First Episode Psychosis: An Updated Review. Clin Psychopharmacol Neurosci. 2011, 9: 45-53.

Emsley R, Oosthuizen PP, Koen L, Niehaus DJ, Martinez L: Symptom Recurrence Following Intermittent Treatment in First Episode Schizophrenia Successfully Treated for Two Years. In J Clin Psychiatry. 2012, In press

Emsley R, Nuamah I, Hough D, Gopal S: Treatment response after relapse in a placebo controlled maintenance trial in schizophrenia. Schizophr Res. 2012, 138 (1): 29-34. 10.1016/j.schres.2012.02.030. Epub 2012 Mar 23

Emsley R, Oosthuizen PP, Koen L, Niehaus DJ, Martinez L: Comparison of Treatment Response in Second Episode Versus First Episode Schizophrenia. J Clin Psychopharmaco. 2013, 33 (1): 80-83. 10.1097/JCP.0b013e31827bfcc1.

Moller HJ, von Ziersen D, et al: Course and outcome of schizophrenia. Schizophrenia. 1995, Oxford: Blackwell, 127-

Kane JM, Jeste DV, Barnes TR: Tardive dyskinesia: A task force report of the American Psychiatric Association. 1992, Washington, D.C: American Psychiatric Association, Ref Type: Report

Meltzer HY: Neuroleptic withdrawal in schizophrenic patients. An idea whose time has come. Arch Gen Psychiatry. 1995, 52: 200-202.

Newcomer JW: Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007, 68 (Suppl 1): 20-27.

Bostwick JR, Guthrie SK, Ellingrod VL: Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009, 29: 64-73. 10.1592/phco.29.1.64.

Correll CU, Schenk EM: Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry. 2008, 21: 151-156. 10.1097/YCO.0b013e3282f53132.

Perkins DO, Gu H, Weiden PJ, McEvoy JP, Hamer RM, Lieberman JA: Predictors of treatment discontinuation and medication nonadherence in patients recovering from a first episode of schizophrenia, schizophreniform disorder, or schizoaffective disorder: a randomized, double-blind, flexible-dose, multicenter study. J Clin Psychiatry. 2008, 69: 106-113. 10.4088/JCP.v69n0114.

Gilbert PL, Harris MJ, McAdams LA, Jeste DV: Neuroleptic withdrawal in schizophrenic patients. A review of the literature. Arch Gen Psychiatry. 1995, 52: 173-188. 10.1001/archpsyc.1995.03950150005001.

Gitlin M, Nuechterlein K, Subotnik KL, Ventura J, Mintz J, Fogelson DL, et al: Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia. Am J Psychiatry. 2001, 158: 1835-1842. 10.1176/appi.ajp.158.11.1835.

Chen EY, Hui CL, Lam MM, Chiu CP, Law CW, Chung DW, et al: Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial. BMJ. 2010, 341: c4024-10.1136/bmj.c4024.

Boonstra G, Burger H, Grobbee DE, Kahn RS: Antipsychotic prophylaxis is needed after remission from a first psychotic episode in schizophrenia patients: results from an aborted randomised trial. Int J Psychiatry Clin Pract. 2011, 15: 128-134. 10.3109/13651501.2010.534801.

Kane JM, Rifkin A, Quitkin F, Nayak D, Ramos-Lorenzi J: Fluphenazine vs placebo in patients with remitted, acute first-episode schizophrenia. Arch Gen Psychiatry. 1982, 39: 70-73. 10.1001/archpsyc.1982.04290010048009.

Wunderink L, Nienhuis FJ, Sytema S, Slooff CJ, Knegtering R, Wiersma D: Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry. 2007, 68: 654-661. 10.4088/JCP.v68n0502.

Crow TJ, MacMillan JF, Johnson AL, Johnstone EC: A randomised controlled trial of prophylactic neuroleptic treatment. In Br J Psychiatry. 1986, 148: 120-127. 10.1192/bjp.148.2.120.

Gaebel W, Riesbeck M, Wolwer W, Klimke A, Eickhoff M, Von WM, et al: Relapse prevention in first-episode schizophrenia–maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia. J Clin Psychiatry. 2011, 72: 205-218. 10.4088/JCP.09m05459yel.

Takeuchi H, Suzuki T, Uchida H, Watanabe K, Mimura M: Antipsychotic treatment for schizophrenia in the maintenance phase: a systematic review of the guidelines and algorithms. Schizophr Res. 2012, 134: 219-225. 10.1016/j.schres.2011.11.021.

Gefvert O, Eriksson B, Persson P, Helldin L, Bjorner A, Mannaert E, et al: Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia. Int J Neuropsychopharmacol. 2005, 8: 27-36. 10.1017/S1461145704004924.

Moncrieff J: Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse. Acta Psychiatr Scand. 2006, 114: 3-13.

Chouinard G, Jones BD: Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics. Am J Psychiatry. 1980, 137: 16-21.

Birchwood M, Smith J, MacMillan F, Hogg B, Prasad R, Harvey C, et al: Predicting relapse in schizophrenia: the development and implementation of an early signs monitoring system using patients and families as observers, a preliminary investigation. Psychol Med. 1989, 19: 649-656. 10.1017/S0033291700024247.

Yung AR, McGorry PD: The prodromal phase of first-episode psychosis: past and current conceptualizations. Schizophr Bull. 1996, 22: 353-370. 10.1093/schbul/22.2.353.

Bustillo J: Buchanan RW. Carpenter WT Jr: Prodromal symptoms vs. early warning signs and clinical action in schizophrenia. Schizophr Bull. 1995, 21: 553-559.

Norman RM, Malla AK: Prodromal symptoms of relapse in schizophrenia: a review. Schizophr Bull. 1995, 21: 527-539. 10.1093/schbul/21.4.527.

Gaebel W, Riesbeck M: Revisiting the relapse predictive validity of prodromal symptoms in schizophrenia. Schizophr Res. 2007, 95: 19-29. 10.1016/j.schres.2007.06.016.

Gaebel W, Frick U, Kopcke W, Linden M, Muller P, Muller-Spahn F, et al: Early neuroleptic intervention in schizophrenia: are prodromal symptoms valid predictors of relapse?. Br J Psychiatry Suppl. 1993, 21: 8-12.

Herz MI, Melville C: Relapse in schizophrenia. Am J Psychiatry. 1980, 137: 801-805.

Henmi Y: Prodromal symptoms of relapse in schizophrenic outpatients: retrospective and prospective study. Jpn J Psychiatry Neurol. 1993, 47: 753-775.

Tarrier N, Barrowclough C, Bamrah JS: Prodromal signs of relapse in schizophrenia. Soc Psychiatry Psychiatr Epidemiol. 1991, 26: 157-161.

Gleeson JF, Rawlings D, Jackson HJ, McGorry PD: Early warning signs of relapse following a first episode of psychosis. Schizophr Res. 2005, 80: 107-111. 10.1016/j.schres.2005.07.019.

Birchwood M, Spencer E: Early intervention in psychotic relapse. Clin Psychol Rev. 2001, 21: 1211-1226. 10.1016/S0272-7358(01)00105-2.

Emsley R, Medori R, Koen L, Oosthuizen PP, Niehaus DJ, Rabinowitz J: Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study. J Clin Psychopharmacol. 2008, 28: 210-213. 10.1097/JCP.0b013e318167269d.

Wyatt RJ: Neuroleptics and the natural course of schizophrenia. Schizophr Bull. 1991, 17: 325-351. 10.1093/schbul/17.2.325.

Lieberman JA, Jody D, Geisler S, Alvir J, Loebel A, Szymanski S, et al: Time course and biologic correlates of treatment response in first-episode schizophrenia. Arch Gen Psychiatry. 1993, 50: 369-376. 10.1001/archpsyc.1993.01820170047006.

Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T: Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry. 2005, 62: 975-983. 10.1001/archpsyc.62.9.975.

McEvoy JP, Hogarty GE, Steingard S: Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. Arch Gen Psychiatry. 1991, 48: 739-745.

Curson DA, Barnes TR, Bamber RW, Platt SD, Hirsch SR, Duffy JC: Long-term depot maintenance of chronic schizophrenic out-patients: the seven year follow-up of the Medical Research Council fluphenazine/placebo trial. III. Relapse postponement or relapse prevention? The implications for long-term outcome. Br J Psychiatry. 1985, 146: 474-480. 10.1192/bjp.146.5.474.

Glovinsky D, Kirch DG, Wyatt RJ: Early antipsychotic response to resumption of neuroleptics in drug-free chronic schizophrenic patients. Biol Psychiatry. 1992, 31: 968-970. 10.1016/0006-3223(92)90124-I.

Wyatt RJ, Henter ID, Bartko JJ: The long-term effects of placebo in patients with chronic schizophrenia. Biol Psychiatry. 1999, 46: 1092-1105. 10.1016/S0006-3223(99)00227-9.

Levine SZ, Leucht S: Elaboration on the early-onset hypothesis of antipsychotic drug action: treatment response trajectories. Biol Psychiatry. 2010, 68: 86-92. 10.1016/j.biopsych.2010.01.012.

McGlashan TH: Is active psychosis neurotoxic?. Schizophr Bull. 2006, 32: 609-613.

Zipursky RB, Reilly JL, Murray RM: The myth of schizophrenia as a progressive brain disease. Schizophr Bull. 2012, Epub ahead of print

Wiersma D, Nienhuis FJ, Slooff CJ, Giel R: Natural course of schizophrenic disorders: a 15-year followup of a Dutch incidence cohort. Schizophr Bull. 1998, 24: 75-85. 10.1093/oxfordjournals.schbul.a033315.

Kapur S, Mamo D: Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2003, 27: 1081-1090. 10.1016/j.pnpbp.2003.09.004.

Howes OD, Kapur S: The dopamine hypothesis of schizophrenia: version III–the final common pathway. Schizophr Bull. 2009, 35: 549-562. 10.1093/schbul/sbp006.

Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, et al: The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment: Meta-analysis of Imaging Studies. Arch Gen Psychiatry. 2012, 69 (8): 776-786. 10.1001/archgenpsychiatry.2012.169.

Kapur S: Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. 2003, 160: 13-23. 10.1176/appi.ajp.160.1.13.

Agid O, Kapur S, Arenovich T, Zipursky RB: Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and rejected. Arch Gen Psychiatry. 2003, 60: 1228-1235. 10.1001/archpsyc.60.12.1228.

Leucht S, Busch R, Hamann J, Kissling W, Kane JM: Early-onset hypothesis of antipsychotic drug action: a hypothesis tested, confirmed and extended. Biol Psychiatry. 2005, 57: 1543-1549. 10.1016/j.biopsych.2005.02.023.

Emsley R, Rabinowitz J, Medori R: Time course for antipsychotic treatment response in first-episode schizophrenia. Am J Psychiatry. 2006, 163: 743-745. 10.1176/appi.ajp.163.4.743.

Kapur S, Agid O, Mizrahi R, Li M: How antipsychotics work-from receptors to reality. NeuroRx. 2006, 3: 10-21. 10.1016/j.nurx.2005.12.003.

Schwartz TL, Sachdeva S, Stahl SM: Glutamate neurocircuitry: theoretical underpinnings in schizophrenia. Front Pharmacol. 2012, 3: 195-

Leonard BE, Schwarz M, Myint AM: The metabolic syndrome in schizophrenia: is inflammation a contributing cause?. J Psychopharmacol. 2012, 26: 33-41. 10.1177/0269881111431622.

Drzyzga L, Obuchowicz E, Marcinowska A, Herman ZS: Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun. 2006, 20: 532-545. 10.1016/j.bbi.2006.02.002.

Moller M, Du Preez JL, Viljoen FP, Berk M, Emsley R, Harvey BH: Social isolation rearing induces mitochondrial, immunological, neurochemical and behavioural deficits in rats, and is reversed by clozapine or N-acetyl cysteine. Brain Behavior and Immunity. 10.1016/j.bbi.2012.12.011. Epub ahead of print

McAllister CG, van Kammen DP, Rehn TJ, Miller AL, Gurklis J, Kelley ME, et al: Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status. Am J Psychiatry. 1995, 152: 1291-1297.

Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B: Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011, 70: 663-671. 10.1016/j.biopsych.2011.04.013.

Miller BJ, Gassama B, Sebastian D, Buckley P, Mellor A: Meta-Analysis of Lymphocytes in Schizophrenia: Clinical Status and Antipsychotic Effects. Biol Psychiatry. 2012, doi:10.1016/j.biopsych.2012.09.007. doi:pii: S0006-3223(12):00779-2.

Harvey BH, McEwen BS, Stein DJ: Neurobiology of antidepressant withdrawal: implications for the longitudinal outcome of depression. Biol Psychiatry. 2003, 54: 1105-1117. 10.1016/S0006-3223(03)00528-6.

Andreassen OA, Jorgensen HA: Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats, implications for tardive dyskinesia. Prog Neurobiol. 2000, 61: 525-531. 10.1016/S0301-0082(99)00064-7.

Naidu PS, Kulkarni SK: Excitatory mechanisms in neuroleptic-induced vacuous chewing movements (VCMs): possible involvement of calcium and nitric oxide. Behav Pharmacol. 2001, 12: 209-216. 10.1097/00008877-200105000-00006.

Nel A, Harvey BH: Haloperidol-induced dyskinesia is associated with striatal NO synthase suppression: reversal with olanzapine. Behav Pharmacol. 2003, 14: 251-255. 10.1097/00008877-200305000-00010.

Harvey BH, Joubert C, du Preez JL, Berk M: Effect of chronic N-acetyl cysteine administration on oxidative status in the presence and absence of induced oxidative stress in rat striatum. Neurochem Res. 2008, 33: 508-517. 10.1007/s11064-007-9466-y.

Harvey BH, Bester A: Withdrawal-associated changes in peripheral nitrogen oxides and striatal cyclic GMP after chronic haloperidol treatment. Behav Brain Res. 2000, 111: 203-211. 10.1016/S0166-4328(00)00156-X.

Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, et al: N-acetyl cysteine as a glutathione precursor for schizophrenia–a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008, 64: 361-368. 10.1016/j.biopsych.2008.03.004.

van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS: Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curacao Extrapyramidal Syndromes Study III. Am J Psychiatry. 1998, 155: 565-567.

Samaha AN, Seeman P, Stewart J, Rajabi H, Kapur S: "Breakthrough" dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci. 2007, 27: 2979-2986. 10.1523/JNEUROSCI.5416-06.2007.

Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al: Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012, 379: 2063-2071. 10.1016/S0140-6736(12)60239-6.

Konopaske GT, Dorph-Petersen KA, Sweet RA, Pierri JN, Zhang W, Sampson AR, et al: Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biol Psychiatry. 2008, 63: 759-765. 10.1016/j.biopsych.2007.08.018.