The Concepts of Remission and Recovery in Schizophrenia

Objective: To examine the past and current research into the concepts of remission and recovery in schizophrenia. Data Sources: An electronic literature search of studies published between January 1990-April 2005 examining the concepts of remission and recovery in schizophrenia and the treatment of schizophrenia with antipsychotic agents was performed using Medline and EMBASE. Primary research parameters were ‘schizophrenia’, ‘remission’, ‘recovery’, ‘meta-analysis’, ‘antipsychotics’, ‘atypicals’, ‘conventional’, ‘cognition’, ‘function’ and ‘quality of life’. Study selection: English language articles, original research articles, reviews and other articles of interest were reviewed. Data extraction: Data quality was determined by publication in the peer-reviewed literature and the most important information was identified. Data synthesis: A number of different definitions of remission and recovery have been previously used, which has made comparison of study results problematic. Recently, the first operational definition of remission, based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria (DSM-IV) for schizophrenia, was developed. It is hoped that this will provide a standard tool for assessing the effectiveness of treatments for schizophrenia. Recovery, which encompasses both symptom remission and more functional aspects of patient's well being, such as cognition, social functionality and quality of life, is still to be satisfactorily defined. Although recent studies on new generation antipsychotics have examined some proxy outcomes related to recovery, further research is required. Conclusions: Until the definition for ‘recovery’ is further elucidated, factors such as symptom control and remission, and functional aspects of recovery such as improvements in cognition and social functioning, which are quantifiable, should be used as measures of treatment outcome and markers of recovery.

References

• 1 Amminger GP, Resch F, Mutschlechner R, Friedrich MH, Emst E. Premorbid adjustment and remission of positive symptoms in first-episode psychosis.  Eur Child Adolesc Psychiatry. 1997;  6 212-218
• 2 Andreasen N, Carpenter W, Kane J, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus.  Am J Psychiatry. 2005;  162 441-449
• 3 Andresen R, Oades L, Caputi P. The experience of recovery from schizophrenia: towards an empirically validated stage model.  Aust N Z J Psychiatry. 2003;  37 586-594
• 4 Angermeyer MC, Kuhn L, Goldstein JM. Gender and course of schizophrenia: differences in treated outcomes.  Schizophr Bull. 1990;  16 293-307
• 5 Auslander LA, Jeste DV. Sustained remission of schizophrenia among community-dwelling older outpatients.  Am J Psychiatry. 2004;  161 1490-1493
• 6 Bouchard RH, Merette C, Pourcher E, Demers MF, Villenueve J, Roy-Gagnon MH. et al . Longitudinal comparative study of risperidone and conventional neuroleptics for treating patients with schizophrenia. The Quebec Schizophrenia Study Group.  J Clin Psychopharmacol. 2000;  20 295-304
• 7 Brenner H, Dencker S, Goldstein M, Hubbard JW, Keegan DL, Kruger J. et al . Defining treatment refractoriness in schizophrenia.  Schizoph Bull. 1990;  16 551-561
• 8 Ciompi L. Catamnestic long-term study on the course of life and aging of schizophrenics.  Schizophr Bull. 1980;  6 606-618
• 9 Cohen D. Atypical antipsychotics and new onset diabetes mellitus: An overview of the literature.  Pharmcopsychiatry. 2004;  37 1-11
• 10 Cole JO. Evaluation of drug treatments in psychiatry.  Proc Annu Meet Am Psychopathol Assoc. 1964;  52 14-31
• 11 Colonna L, Saleem P, Dondey-Nouvel L, Rein W. Long-term safety and efficacy of amisulpride in subchronic or chronic schizophrenia. Amisulpride Study Group.  Int Clin Psychopharmacol. 2000;  15 13-22
• 12 Correll CU, Leucht S, Kane JM. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies.  Am J Psychiatry. 2004;  161 414-425
• 13 Curtis CE, Calkins ME, Lacono WG. Saccadic disinhibition in schizophrenia patients and their first-degree biological relatives. A parametric study of the effects of increasing inhibitory load.  Exp Brain Res. 2001;  137 228-236
• 14 Davis J, Matalon L, Watanabe M, Blake L. Depot antipsychotic drugs. Place in therapy.  Drugs. 1994;  47 741-773
• 15 Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics.  Arch Gen Psychiatry. 2003;  60 553-564
• 16 Dolder CR, Lacro JP, Dunn LB, Jeste DV. Antipsychotic medication adherence: is there a difference between typical and atypical agents?.  Am J Psychiatry. 2002;  159 103-108
• 17 Doyle AC, Pollack MH. Establishment of remission criteria for anxiety disorders.  J Clin Psychiatry. 2003;  64 ((Suppl 15)) 40-45
• 18 Eaton WW, Thara R, Federman E, Tien A. Remission and relapse in schizophrenia: the Madras Longitudinal Study.  J Nerv Ment Dis. 1998;  186 357-363
• 19 Ferrier IN. Characterizing the ideal antidepressant therapy to achieve remission.  J Clin Psychiatry. 2001;  62 ((Suppl 26)) 10-15
• 20 Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse and recurrence.  Arch Gen Psychiatry. 1991;  48 851-855
• 21 Freedman R. Schizophrenia.  N Engl J Med. 2003;  349 1738-1749
• 22 Geddes J, Freemantle N, Harrison P, Bebbington P. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis.  BMJ. 2000;  321 1371-1376
• 23 Gerlach J. Oral versus depot administration of neuroleptics in relapse prevention.  Acta Psychiatr Scand Suppl. 1994;  382 28-32
• 24 Godleski LS, Goldsmith LJ, Vieweg WV, Zettwoch NC, Stikovac DM, Lewis SJ. Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia.  J Clin Psychiatry. 2003;  64 119-122
• 25 Green MF, Marder SR, Glynn SM, McGurk SR, Wirshing WC, Wirshing DC. The neurocognitive effects of low-dose haloperidol: a two-year comparison with risperidone.  Biol Psychiatry. 2002;  51 972-978
• 26 Green MF, Marshall JrBD, Wirshing WC, Ames D, Marder SR, McGurk S. Does risperidone improve verbal working memory in treatment-resistant schizophrenia?.  Am J Psychiatry. 1997;  154 799-804
• 27 Hamilton M. A rating scale for depression.  J Neurol Neurosurg Psychiatry. 1960;  23 56-62
• 28 Harding CM, Brooks GW, Ashikaga T, Strauss JS, Breier A. The Vermont longitudinal study of persons with severe mental illness, II: Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia.  Am J Psychiatry. 1987;  144 727-735
• 29 Harrison G, Hopper K, Craig T, Laska E, Siegel C, Wanderling J. Recovery from psychotic illness: a 15- and 25-year international follow-up study.  Br J Psychiatry. 2001;  178 506-517
• 30 Hartung B, Wada M, Laux G. et al . Perphenazine for schizophrenia.  Cochrane Database Syst Rev. 2005;  25 CD003443
• 31 Ho BC, Andreasen NC, Flaum M, Nopoulos P, Miller D. Untreated initial psychosis: its relation to quality of life and symptom remission in first-episode schizophrenia.  Am J Psychiatry. 2000;  157 808-815
• 32 Huber G, Gross G, Schuttler R, Linz M. Longitudinal studies of schizophrenic patients.  Schizophr Bull. 1980;  6 592-605
• 33 Keefe RS, Silva SG, Perkins DO. et al . The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis.  Schizophr Bull. 1999;  25 201-222
• 34 Kelly DL, Conley RR, Tamminga CA. Differential olanzapine plasma concentration by sex in a fixed-dose study.  Schizophr Res. 1999;  40 101-104
• 35 Kraepelin E. Dementia Praecox and Paraphrenia. Translated and edited by RB Barclay. Edinburgh; ES Livingston 1919
• 36 Lambert M, Schimmelmann B, Karow A. et al . Subjective well-being and initial dysphoric reaction under antipsychotic drugs - concepts, measurement and clinical review.  Pharmacopsychiatry. 2003;  36 181-190
• 37 Larsen NE, Hansen LB. Prediction of the optimal perphenazine decanoate dose based on blood samples drawn within the first three weeks.  ThermDrug Monit. 1989;  11 642-646
• 38 Lasser R, Bossie C, Gharabawi G, Baldessarini RJ. Clinical improvement in 336 stable chronically psychotic patients changed from oral to long-acting risperidone: a 12-month open trial.  Int J Neuropsychopharmacol. 2005;  8 1-12
• 39 Lasser R, Bossie C, Gharabawi G, Turner M. Patients with schizophrenia previously stabilized on conventional depot antipsychotics experience significant clinical improvements following treatment with long-acting risperidone.  Eur Psychiatry. 2004;  19 219-225
• 40 Lasser RA, Bossie CA, Gharabawi GM, Kane JM. Remission in schizophrenia: Results from a 1-year study of long-acting risperidone injection.  Schizophr Res. 2005;  77 215-227
• 41 Leucht S, Barnes TR, Kissling W, Engel RR, Correll C, Kane JM. Relapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials.  Am J Psychiatry. 2003;  160 1209-1222
• 42 Leucht S, Pitschel-Walz G, Abraham D, Kissling W. Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials.  Schizophr Res. 1999;  35 51-68
• 43 Leucht S, Wahlbeck K, Hamann J, Kissling W. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis.  Lancet. 2003;  361 1581-1589
• 44 Leucht S, Pitschel-Walz G, Engel RR. et al . Amisulpride, an unsual atypical antipsychotic: a meta-analysis of randomised controlled trials.  Am J Psychiatry. 2002;  159 180-190
• 45 Liberman R, Kopelowicz A, Ventura J, Gutkind D. Operational criteria and factors related to recovery from schizophrenia.  Int Rev Psychiatry. 2002;  14 256-272
• 46 Lieberman J, Jody D, Geisler S, Alvir J, Loebel A, Szymanski S. Time course and biologic correlates of treatment response in first-episode schizophrenia.  Arch Gen Psychiatry. 1993;  50 369-376
• 47 Lieberman JA, Phillips M, Gu H, Stroup S, Zhang P, Kong L. Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine.  Neuropsychopharmacology. 2003;  28 995-1003
• 48 Lieberman JA, Stroip TS, McEvoy. et al . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.  N Engl J Med. 2005;  353 1209-1223
• 49 Lindenmayer JP, Eerdekens E, Berry SA, Eerdekens M. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics.  J Clin Psychiatry. 2004;  65 1084-1089
• 50 Loebel AD, Lieberman JA, Alvir JM, Mayerhoff DI, Geisler SH, Szymanski SR. Duration of psychosis and outcome in first-episode schizophrenia.  Am J Psychiatry. 1992;  149 1183-1188
• 51 Meltzer HY, Burnett S, Bastani B, Ramirez LF. Cognitive factors in schizophrenia: causes, impact, and treatment.  CNS Spectr. 2004;  9 ((10 Suppl 11)) 15-24
• 52 Mishara AL, Goldberg TE. A meta-analysis and critical review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: opening a closed book.  Biol Psychiatry. 2004;  55 1013-1022
• 53 Molina V, Sanz J, Sarramea F, Benito C, Palomo T. Lower prefrontal gray matter volume in schizophrenia in chronic but not in first episode schizophrenia patients.  Psychiatry Res. 2004;  131 45-56
• 54 Muller N. Mechanisms of relapse prevention in schizophrenia.  Pharmacopsychiatry. 2004;  37 141-147
• 55 Naber D. A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables.  Int Clin Psychopharmacol. 1995;  10 ((Suppl 3)) 133-138
• 56 Nasrallah H, Duchesne I, Mehnert A, Janagap C, Eerdekens M. Health-related quality of life with schizophrenia during treatment with long-acting risperidone injection.  J Clin Psychiatry. 2004;  65 531-536
• 57 Ogawa K, Miya M, Watarai A, Nakazawa M, Yuasa S, Utena H. A long-term follow-up study of schizophrenia in Japan with special reference to the course of social adjustment.  Br J Psychiatry. 1987;  151 758-765
• 58 Penn DL, Mueser KT. Research update on the psychosocial treatment of schizophrenia.  Am J Psychiatry. 1996;  153 607-617
• 59 Revicki DA, Genduso LA, Hamilton SH, Ganoczy D, Beasley Jr CM. Olanzapine versus haloperidol in the treatment of schizophrenia and other psychotic disorders: quality of life and clinical outcomes of a randomized clinical trial.  Qual Life Res. 1999;  8 417-426
• 60 Robinson DG, Woerner MG, McMeniman, Mendelowitz A, Bilder RM. Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder.  Am J Psychiatry. 2004;  161 473-479
• 61 Rosenheck R, Cramer J, Xu W, Thomas J, Henderson W, Frisman L. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.  N Engl J Med. 1997;  337 809-815
• 62 Rosenheck R, Perlick D, Bingham S, Liu-Mares W, Collins J, Warren S, Leslie D, Allan E, Campbell EC, Caroff S, Corwin J, Davis L, Douyon R, Dunn L, Evans D, Frecska E, Grabowski J, Graeber D, Herz L, Kwon K, Lawson W, Mena F, Sheikh J, Smelson D, Smith-Gamble V. Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia - A randomized controlled trial.  JAMA. 2003;  290 2693-2702
• 63 Schooler N, Rabinowitz J, Davidson M, Emsley R, Harvey PD, Kopala L, McGorry PD, Van Hove I, Eerdekens M, Swyzen W, De Smedt G. Risperdione and haloperidol in first-episdoe psychosis: a long-term randomsied trial.  Am J Psychiatry. 2005;  162 947-953
• 64 Sernyak MJ, Leslie DL, Alarcon RD, Losonczy MF, Rosenheck R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia.  Am J Psychiatry. 2002;  159 561-566
• 65 Sethuraman G, Taylor CC, Enerson M, Dunayevich E. A retrospective comparison of cumulative time spent in remission during treatment with olanzapine or risperidone among patients with schizophrenia.  Schizophr Res. 2005;  79 337-340
• 66 Tollefson GD. Cognitive function in schizophrenic patients.  J Clin Psychiatry. 1996;  57 ((Suppl 11)) 31-39
• 67 Turkoz I, Lasser R, Rodriguez S, Locklear J, Mahableshwarkar A, Gharabawi G. Functioning and quality of life during long-acting risperidone maintenance treatment. In: American Psychiatric Association, May 22-26 2005 Atlanta, USA; Abstract N205
• 68 Valenstein M, Copeland LA, Owen R, Blow FC, Visnic S. Adherence assessments and the use of depot antipsychotics in patients with schizophrenia.  J Clin Psychiatry. 2001;  62 545-551
• 69 van Os J, Bossie C, Lasser R. Improvements in stable patients with psychotic disorders switched from oral conventional antipsychotics therapy to long-acting risperidone.  Int Clin Psychopharmacol. 2004;  19 229-232
• 70 Velligan DI, Mahurin RK, Diamond PL, Hazleton BC, Eckert SL, Miller AL. The functional significance of symptomatology and cognitive function in schizophrenia.  Schizophr Res. 1997;  25 21-31
• 71 Wahlbeck K, Cheine M, Essali A. et al . Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomised trials.  Am J Psychiatry. 1999;  156 990-999
• 72 Weiden P, Zygmunt A. Medication noncompliance in schizophrenia. Part I. Assessment.  J Prac Psychiatry Behav Health. 1997;  3 106-110
• 73 Weiss U, Marksteiner J, Kemmler G. et al . Effects of age and sex on olanzapine plasma concentrations.  J Clin Psychopharmacol.. 2005;  25 570-574
• 74 Woodward ND, Purdon SE, Meltzer HY, Zald DH. A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia.  Int J Neuropsychopharmacol. 2005;  8 457-472
• 75 Wyatt R. Neuroleptics and the natural course of schizophrenia.  Schizophr Bull. 1991;  17 325-351
• 76 Yen CF, Chen CS, Yeh ML, Yen JY, Ker JH, Yang SJ. Comparison of insight in patients with schizophrenia and bipolar disorder in remission.  J Nerv Ment Dis. 2002;  190 847-849
• 77 Zygmunt A, Olfson M, Boyer CA, Mechanic D. Interventions to improve medication adherence in schizophrenia.  Am J Psychiatry. 2002;  159 1653-1664

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