Skip to main content Accessibility help
Hostname: page-component-7ccbd9845f-w45k2 Total loading time: 0.418 Render date: 2023-01-31T19:55:01.782Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study

Published online by Cambridge University Press:  17 February 2012

M. Harrow*
Department of Psychiatry, University of Illinois College of Medicine, Chicago, IL, USA
T. H. Jobe
Department of Psychiatry, University of Illinois College of Medicine, Chicago, IL, USA
R. N. Faull
Department of Psychiatry, University of Illinois College of Medicine, Chicago, IL, USA
*Address for correspondence: M. Harrow, Ph.D., University of Illinois at Chicago, Department of Psychiatry, 1601 W. Taylor (M/C 912), PI, Rm. 445, Chicago, IL 60612, USA. (Email:



The prevailing standard of care in the field involves background assumptions about the importance of prolonged use of antipsychotic medications for all schizophrenia (SZ) patients. However, do all SZ patients need antipsychotics indefinitely? Are there factors that help to identify which SZ patients can enter into prolonged periods of recovery without antipsychotics? This 20-year longitudinal research studied these issues.


A total of 139 early young psychotic patients from the Chicago Follow-up Study, including 70 patients with SZ syndromes and 69 with mood disorders, were assessed, prospectively, at the acute phase and then followed up six times over the next 20 years. Patients were assessed with standardized instruments for major symptoms, psychosocial functioning, personality, attitudinal variables, neurocognition and treatment.


At each follow-up, 30–40% of SZ patients were no longer on antipsychotics. Starting at the 4.5-year follow-ups and continuing thereafter, SZ patients not on antipsychotics for prolonged periods were significantly less likely to be psychotic and experienced more periods of recovery; they also had more favorable risk and protective factors. SZ patients off antipsychotics for prolonged periods did not relapse more frequently.


The data indicate that not all SZ patients need treatment with antipsychotics continuously throughout their lives. SZ patients not on antipsychotics for prolonged periods are a self-selected group with better internal resources associated with greater resiliency. They have better prognostic factors, better pre-morbid developmental achievements, less vulnerability to anxiety, better neurocognitive skills, less vulnerability to psychosis and experience more periods of recovery.

Original Articles
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


American DiabetesAssociation (2004). Consensus development conference on antipsychotic drugs and obesity. Diabetes Care 27, 596601.CrossRefGoogle Scholar
Bland, R, Parker, J, Orn, H (1978). Prognosis in schizophrenia: prognostic predictors and outcome. Archives of General Psychiatry 35, 7277.CrossRefGoogle ScholarPubMed
Bleuler, M (1978). The Schizophrenic Disorders: Long-Term Patient and Family Studies. Yale University Press: New Haven.Google Scholar
Bola, J, Mosher, L (2002). At issue: predicting drug-free treatment response in acute psychosis from the Soteria project. Schizophrenia Bulletin 28, 559575.CrossRefGoogle ScholarPubMed
Bonner-Jackson, A, Harrow, M, Rosen, C (2010). Neurocognition in schizophrenia: a 20-year multi-follow-up of the course of processing speed and stored knowledge. Comprehensive Psychiatry 51, 471479.CrossRefGoogle ScholarPubMed
Bosveld-van Haandel, L, Slooff, C, van den Bosch, R (2001). Reasoning about the optimal duration of prophylactic antipsychotic medication in schizophrenia: evidence and arguments. Acta Psychiatrica Scandinavica 103, 335346.CrossRefGoogle ScholarPubMed
Buchanan, R, Kreyenbuhl, J, Kelly, D, Noel, J, Boggs, D, Fischer, B, Himelhoch, S, Fang, B, Peterson, E, Aquino, P, Keller, W (2010). The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophrenia Bulletin 36, 7193.CrossRefGoogle ScholarPubMed
Burdick, K, Harrow, M, Goldberg, J (2006). Neurocognition as a stable endophenotype in bipolar disorder and schizophrenia. Journal of Nervous and Mental Disease 194, 255267.CrossRefGoogle Scholar
Carone, J, Harrow, M, Westermeyer, J (1991). Posthospital course and outcome in schizophrenia. Archives of General Psychiatry 48, 247253.CrossRefGoogle Scholar
Carpenter, Jr. WT, Appelbaum, PS, Levine, RJ (2003). The Declaration of Helsinki and clinical trials: a focus on placebo-controlled trials in schizophrenia. American Journal of Psychiatry 160, 356362.CrossRefGoogle Scholar
Chouinard, G, Jones, BD (1980). Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics. American Journal of Psychiatry 137, 1621.Google ScholarPubMed
Cohen, P, Cohen, J (1984). The clinician's illusions. Archives of General Psychiatry 41, 11781182.CrossRefGoogle Scholar
Cornblatt, BA, Carrión, RE, Addington, J, Seidman, L, Walker, EF, Cannon, TD, Cadenhead, KS, McGlashan, TH, Perkins, DO, Tsuang, MT (2011). Risk factors for psychosis: impaired social and role functioning. Schizophrenia Bulletin. Published online: 10 November 2011. doi:10.1093/schbul/sbr136.Google ScholarPubMed
Dibben, C, Rice, C, Laws, K, McKenna, P (2009). Is executive impairment associated with schizophrenic syndromes? A meta-analysis. Psychological Medicine 39, 381392.CrossRefGoogle ScholarPubMed
Endicott, J, Spitzer, R (1978). A diagnostic interview. Archives of General Psychiatry 35, 837844.CrossRefGoogle ScholarPubMed
Fenton, W, McGlashan, T (1987). Sustained remission in drug-free schizophrenic patients. American Journal of Psychiatry 144, 13061309.Google ScholarPubMed
Gilbert, PL, Harris, MJ, McAdams, LA, Jeste, DV (1995). Neuroleptic withdrawal in schizophrenic patients: a review of the literature. Archives of General Psychiatry 52, 173188.CrossRefGoogle ScholarPubMed
Goldberg, J, Harrow, M (eds) (1999). Bipolar Disorders: Clinical Course and Outcome. American Psychiatric Press: Washington, DC.Google Scholar
Gorham, D (1956). A proverbs test for clinical and experimental use. Psychological Reports 2, 112.CrossRefGoogle Scholar
Gottesman, I, Shields, J (1982). Schizophrenia: The Epigenetic Puzzle. Cambridge University Press: New York.Google Scholar
Grinker, R, Harrow, M (eds) (1987). Clinical Research in Schizophrenia: A Multidimensional Approach. Charles C. Thomas: Springfield, IL.Google Scholar
Gur, RE, Calkins, ME, Gur, RC, Horan, WP, Nuechterlein, KH, Seidman, LJ, Stone, WS (2007). The Consortium on the Genetics of Schizophrenia: neurocognitive endophenotypes. Schizophrenia Bulletin 33, 4968.CrossRefGoogle Scholar
Harding, C, Brooks, G, Ashikiga, T, Strauss, J, Breier, A (1987). The Vermont longitudinal study of persons with severe mental illness: II. Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. American Journal of Psychiatry 144, 727735.Google Scholar
Harrison, G, Hopper, K, Craig, T, Laska, E, Siegel, C, Wanderling, J, Dube, K, Ganev, K, Giel, R, an der Heiden, W, Holmberg, SK, Janca, A, Lee, PW, Leon, CA, Malhotra, S, Marsella, AJ, Nakane, Y, Sartorius, N, Shen, Y, Skoda, C, Thara, R, Tsirkin, SJ, Varma, VK, Walsh, D, Wiersma, D (2001). Recovery from psychotic illness: a 15- and 25-year international follow-up study. British Journal of Psychiatry 178, 506517.CrossRefGoogle ScholarPubMed
Harrow, M, Goldberg, J, Grossman, L, Meltzer, H (1990). Outcome in manic disorders: a naturalistic follow-up study. Archives of General Psychiatry 47, 665671.CrossRefGoogle ScholarPubMed
Harrow, M, Grossman, L, Herbener, E, Davis, E (2000). Ten-year outcome: patients with schizoaffective disorders, schizophrenia, affective disorders, and mood-incongruent psychotic symptoms. British Journal of Psychiatry 177, 421426.CrossRefGoogle ScholarPubMed
Harrow, M, Grossman, L, Jobe, T, Herbener, E (2005). Do patients with schizophrenia ever show periods of recovery? A 15-year multi-follow-up study. Schizophrenia Bulletin 31, 723734.CrossRefGoogle ScholarPubMed
Harrow, M, Hansford, B, Astrachan-Fletcher, E (2009). Locus of control: relation to schizophrenia, to recovery, and to depression and psychosis – a 15-year longitudinal study. Psychiatry Research 168, 186192.CrossRefGoogle ScholarPubMed
Harrow, M, Jobe, T (2007). Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: a 15-year multi-follow-up study. Journal of Nervous and Mental Disease 195, 406414.Google ScholarPubMed
Harrow, M, Jobe, T (2010). How frequent is chronic multiyear delusional activity and recovery in schizophrenia: a 20-year multi-follow-up. Schizophrenia Bulletin 36, 192204.CrossRefGoogle ScholarPubMed
Harrow, M, Jobe, T, Astrachan-Fletcher, E (2008). Prognosis of persecutory delusions in schizophrenia: a 20-year longitudinal study. In Persecutory Delusions: Assessment, Theory and Treatment (ed. Freeman, D., Garety, P. and Bentall, R.), pp. 7390. Oxford University Press: Oxford.CrossRefGoogle Scholar
Ho, BC, Andreasen, NC, Ziebell, S, Pierson, R, Magnotta, V (2011). Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry 68, 128137.CrossRefGoogle ScholarPubMed
Jobe, T, Harrow, M (2005). Long-term outcome of patients with schizophrenia: a review. Canadian Journal of Psychiatry 50, 892900.CrossRefGoogle ScholarPubMed
Jobe, T, Harrow, M (2010). Schizophrenia course, long-term outcome, recovery, and prognosis. Current Directions in Psychological Science 19, 220225.CrossRefGoogle Scholar
Jones, P, Murray, R, Rodgers, B, Marmot, M (1994). Child developmental risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344, 13981402.CrossRefGoogle ScholarPubMed
Katz, M, Lyerly, S (1963). Methods for measuring adjustment and social behavior in the community: I. Rationale, description, discriminative, validity and scale development. Psychological Reports 13, 503535.CrossRefGoogle Scholar
Kendler, K, Neale, M (2010). Endophenotype: a conceptual analysis. Molecular Psychiatry 15, 789797.CrossRefGoogle ScholarPubMed
Kreyenbuhl, J, Buchanan, R, Dickerson, F, Dixon, L (2010). The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophrenia Bulletin 36, 94–103.CrossRefGoogle ScholarPubMed
Lehtinen, V, Aaltonen, J, Koffert, T, Räkköläinen, V, Syvälahti, E (2000). Two-year outcome in first-episode psychosis treated according to an integrated model. Is immediate neuroleptisation always needed? European Psychiatry 15, 312320.CrossRefGoogle Scholar
Levenstein, D, Klein, D, Pollack, M (1966). Follow-up study of formerly hospitalized voluntary psychiatric patients: the first two years. American Journal of Psychiatry 122, 11021109.CrossRefGoogle ScholarPubMed
Lieberman, J, Stroup, S, McEvoy, J, Swartz, M, Rosenheck, R, Perkins, D, Keefe, R, Davis, S, Davis, C, Lebowitz, B, Severe, J, Hsiao, J (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine 353, 12091223.CrossRefGoogle ScholarPubMed
Marengo, J, Harrow, M, Rogers, C (1980). A Manual for Scoring Abstract and Concrete Responses to the Proverbs Test. ASIS/NAPS No. 03646. Microfiche Publications: New York.Google Scholar
Menezes, N, Arenovich, T, Zipursky, R (2006). A systematic review of longitudinal outcome studies of first-episode psychosis. Psychological Medicine 36, 13491362.CrossRefGoogle ScholarPubMed
Moncrieff, J (2009). A critique of the dopamine hypothesis of schizophrenia and psychosis. Harvard Review of Psychiatry 17, 214225.CrossRefGoogle ScholarPubMed
Moncrieff, J, Leo, J (2010). A systematic review of the effects of antipsychotic drugs on brain volume. Psychological Medicine 40, 14091422.CrossRefGoogle ScholarPubMed
Owens, DC, Johnstone, EC, Miller, P, Macmillan, JF, Crow, TJ (2010). Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk. British Journal of Psychiatry 196, 296301.CrossRefGoogle ScholarPubMed
President's New Freedom Commission on Health (2003). Achieving the Promise: Transforming Mental Health Care in America. University of Michigan Library: Ann Arbor, MI.Google Scholar
Reed, R, Harrow, M, Herbener, E, Martin, E (2002). Executive function in schizophrenia: is it linked to psychosis and poor life functioning? Journal of Nervous and Mental Disease 190, 725732.CrossRefGoogle ScholarPubMed
Remington, G, Kapur, S (2010). Antipsychotic dosing: how much but also how often? Schizophrenia Bulletin 36, 900903.CrossRefGoogle Scholar
Samaha, AN, Seeman, P, Stewart, J, Rajabi, H, Kapur, S (2007). ‘Breakthrough’ dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. Journal of Neuroscience 27, 29792986.CrossRefGoogle ScholarPubMed
Stephens, J, Pascal, R, McHugh, P (1997). Long-term follow-up of patients hospitalized for schizophrenia, 1913 to 1940. Journal of Nervous and Mental Disorders 185, 715721.CrossRefGoogle ScholarPubMed
Strauss, J, Carpenter, W (1972). The prediction of outcome in schizophrenia: I. Characteristics of outcome. Archives of General Psychiatry 27, 739746.CrossRefGoogle Scholar
Tandon, R, Belmaker, R, Gattaz, WF (2008). World Psychiatric Association Pharmacopsychiatry Section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia. Schizophrenia Research 100, 2038.CrossRefGoogle ScholarPubMed
Vaillant, G (1978). A 10-year follow-up of remitting schizophrenics. Schizophrenia Bulletin 4, 7885.CrossRefGoogle ScholarPubMed
Ventura, J, Subotnik, KL, Guzik, LH, Hellemann, GS, Gitlin, MJ, Wood, RC, Nuechterlein, KH (2011). Remission and recovery during the first outpatient year of the early course of schizophrenia. Schizophrenia Research 132, 1823.CrossRefGoogle ScholarPubMed
Webber, MA, Marder, SR (2008). Better pharmacotherapy for schizophrenia: what does the future hold? Current Psychiatry Reports 10, 352358.CrossRefGoogle ScholarPubMed
Wechsler, D (1955). Weschler Adult Intelligence Scale Manual. Psychological Corporation: New York.Google Scholar
White, C, Stirling, J, Hopkins, R, Morris, J, Montague, L, Tantam, D, Lewis, S (2009). Predictors of 10-year outcome of first-episode psychosis. Psychological Medicine 39, 14471456.CrossRefGoogle ScholarPubMed
Zigler, E, Glick, M (2001). The developmental approach to adult psychopathology. Clinical Psychologist 54, 2–11.Google Scholar
Zigler, E, Levine, J (1983). Hallucinations vs. delusions: a developmental approach. Journal of Nervous and Mental Disease 171, 141146.CrossRefGoogle ScholarPubMed
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study
Available formats

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study
Available formats

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *