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Twenty-year effects of antipsychotics in schizophrenia and affective psychotic disorders

Published online by Cambridge University Press:  08 February 2021

Martin Harrow*
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
Thomas H Jobe
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
Liping Tong
Affiliation:
Advocoate Aurora Health, Downers Grove, IL, USA
*
Author for correspondence: Martin Harrow, E-mail: mharrow@uic.edu

Abstract

Background

Studies that examine course and outcome in psychosis have reported considerable heterogeneity in terms of recovery, remission, employment, symptom presentation, social outcomes, and antipsychotic medication effects. Even with demonstrated heterogeneity in course and outcome, prophylactic antipsychotic maintenance therapy remains the prominent practice, particularly in participants with schizophrenia. Lack of efficacy in maintenance antipsychotic treatment and concerns over health detriments gives cause to re-examine guidelines.

Methods

This study was conducted as part of the Chicago follow-up study designed as a naturalistic prospective longitudinal research study to investigate the course, outcome, symptomatology, and effects of antipsychotic medication on recovery and rehospitalization in participants with serious mental illness disorders. A total of 139 participants with 734 observations were included in the analysis. GEE logistic models were applied to adjust for confounding factors measured at index hospitalization and follow-ups.

Results

Our data show that the majority of participants with schizophrenia or affective psychosis experience future episodes of psychosis at some point during the 20-year follow-up. There was a significant diagnostic difference between groups showing an increase in the number of future episodes of psychosis in participants with schizophrenia. Participants with schizophrenia not on antipsychotics after the first 2 years have better outcomes than participants prescribed antipsychotics. The adjusted odds ratio of not on antipsychotic medication was 5.989 (95% CI 3.588–9.993) for recovery and 0.134 (95% CI 0.070–0.259) for rehospitalization. That is, regardless of diagnosis, after the second year, the absence of antipsychotics predicted a higher probability of recovery and lower probability of rehospitalization at subsequent follow-ups after adjusting for confounders.

Conclusion

This study reports multiple findings that bring into question the use of continuous antipsychotic medications, regardless of diagnosis. Even when the confound by indication for prescribing antipsychotic medication is controlled for, participants with schizophrenia and affective psychosis do better than their medicated cohorts, strongly confirming the importance of exposing the role of aiDSP and antipsychotic drug resistance.

Type
Original Article
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Agnati, L. F., Guidolin, D., Cervetto, C., Borroto-Escuela, D. O., & Fuxe, K. (2016). Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes. Reviews in the Neurosciences, 27(1), 125.CrossRefGoogle ScholarPubMed
Amato, D., Kruyer, A., Samaha, A. N., & Heinz, A. (2019). Hypofunctional dopamine uptake and antipsychotic treatment-resistant schizophrenia. Frontiers in Psychiatry, 10, 314.CrossRefGoogle ScholarPubMed
Ashok, A. H., Marques, T. R., Jauhar, S., Nour, M. M., Goodwin, G. M., Young, A. H., & Howes, O. D. (2017). The dopamine hypothesis of bipolar affective disorder: The state of the art and implications for treatment. Molecular Psychiatry, 22(5), 666679.CrossRefGoogle ScholarPubMed
Bergström, T., Taskila, J. J., Alakare, B., Köngäs-Saviaro, P., Miettunen, J., & Seikkula, J. (2020). Five-year cumulative exposure to antipsychotic medication after first-episode psychosis and its association with 19-year outcomes. Schizophrenia Bulletin Open, 1(1), sgaa050.CrossRefGoogle Scholar
Bland, R. C., & Parker, J. H. (1978). Prognosis in schizophrenia: Prognostic predictors and outcome. Archives of General Psychiatry, 35(1), 7277.CrossRefGoogle ScholarPubMed
Bowtell, M., Eaton, S., Thien, K., Bardell-Williams, M., Downey, L., Ratheesh, A., … O'Donoghue, B. (2018). Rates and predictors of relapse following discontinuation of antipsychotic medication after a first episode of psychosis. Schizophrenia Research, 195, 231236.CrossRefGoogle ScholarPubMed
Carone, B. J., Harrow, M., & Westermeyer, J. F. (1991). Posthospital course and outcome in schizophrenia. Archives of General Psychiatry, 48(3), 247253.CrossRefGoogle Scholar
Catts, S. V., & O'Toole, B. I. (2017). Reducing long-term antipsychotic use: A therapeutic dead end? The British Journal of Psychiatry, 210(5), 368.CrossRefGoogle ScholarPubMed
Centorrino, F., Cincotta, S. L., Talamo, A., Fogarty, K. V., Guzzetta, F., Saadeh, M. G., … Baldessarini, R. J. (2008). Hospital use of antipsychotic drugs: Polytherapy. Comprehensive Psychiatry, 49(1), 6569.CrossRefGoogle ScholarPubMed
Charron, A., El Hage, C., Servonnet, A., & Samaha, A. N. (2015). 5-HT2 Receptors modulate the expression of antipsychotic-induced dopamine supersensitivity. European Neuropsychopharmacology, 25(12), 23812393.CrossRefGoogle ScholarPubMed
Chouinard, G., & Chouinard, V. (2008). Atypical antipsychotics: CATIE study, drug-induced movement disorder and resulting iatrogenic psychiatric-like symptoms, supersensitivity rebound psychosis and withdrawal discontinuation syndromes. Psychotherapy and Psychosomatics, 77(2), 6977.CrossRefGoogle ScholarPubMed
Chouinard, G., Samaha, A., Chouinard, V., Peretti, C., Kanahara, N., Takase, M., & Iyo, M. (2017). Antipsychotic-induced dopamine supersensitivity psychosis: Pharmacology, criteria, and therapy. Psychotherapy and Psychosomatics, 86(4), 189219.CrossRefGoogle ScholarPubMed
Citrome, L. (2013). A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: An evidence-based medicine approach. CNS Drugs, 27(11), 879911.CrossRefGoogle Scholar
Cohen, C. I., & Iqbal, M. (2014). Longitudinal study of remission among older adults with schizophrenia spectrum disorder. The American Journal of Geriatric Psychiatry, 22(5), 450458.CrossRefGoogle ScholarPubMed
Correll, C. U., Rubio, J. M., & Kane, J. M. (2018). What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry, 17(2), 149160.CrossRefGoogle ScholarPubMed
De Lafuente, V., & Romo, R. (2011). Dopamine neurons code subjective sensory experience and uncertainty of perceptual decisions. Proceedings of the National Academy of Sciences, 108(49), 1976719771.CrossRefGoogle ScholarPubMed
Demjaha, A., Murray, R. M., McGuire, P. K., Kapur, S., & Howes, O. D. (2012). Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. American Journal of Psychiatry, 169(11), 12031210.CrossRefGoogle ScholarPubMed
Endicott, J., & Spitzer, R. L. (1978). A diagnostic interview: The schedule for affective disorders and schizophrenia. Archives of General Psychiatry, 35(7), 837844.CrossRefGoogle ScholarPubMed
Endicott, J., Spitzer, R. L., Fleiss, J. L., & Cohen, J. (1976). The global assessment scale: A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry, 33(6), 766771.CrossRefGoogle ScholarPubMed
Escamilla, R., Camarena, B., Saracco-Alvarez, R., Fresán, A., Hernández, S., & Aguilar-García, A. (2018). Association study between COMT, DRD2, and DRD3 gene variants and antipsychotic treatment response in Mexican patients with schizophrenia. Neuropsychiatric Disease and Treatment, 14, 2981.CrossRefGoogle ScholarPubMed
Fallon, P., & Dursun, S. M. (2011). A naturalistic controlled study of relapsing schizophrenic patients with tardive dyskinesia and supersensitivity psychosis. Journal of Psychopharmacology, 25(6), 755762.CrossRefGoogle ScholarPubMed
Fallon, P., Dursun, S., & Deakin, B. (2012). Drug-induced supersensitivity psychosis revisited: Characteristics of relapse in treatment-compliant patients. Therapeutic Advances in Psychopharmacology, 2(1), 1322.CrossRefGoogle ScholarPubMed
Fernandes, B. S., Williams, L. M., Steiner, J., Leboyer, M., Carvalho, A. F., & Berk, M. (2017). The new field of ‘precision psychiatry’. BMC Medicine, 15(1), 80.CrossRefGoogle ScholarPubMed
Glick, I. D., Davis, J. M., Zamora, D., Ballon, J., & Nuthi, M. (2017). Should antipsychotic medications for schizophrenia be given for a lifetime?: A naturalistic, long-term follow-up study. Journal of Clinical Psychopharmacology, 37(2), 125130.CrossRefGoogle ScholarPubMed
Glick, I. D., Zamora, D., Kamis, D., & Davis, J. M. (2019). Should antipsychotic medications for schizophrenia be given for a lifetime? Replication of a naturalistic, long-term, follow-up study of antipsychotic treatment. CNS Spectrums, 24(5), 557563.CrossRefGoogle ScholarPubMed
Goff, D. C., Falkai, P., Fleischhacker, W. W., Girgis, R. R., Kahn, R. M., Uchida, H., … Lieberman, J. A. (2017). The long-term effects of antipsychotic medication on clinical course in schizophrenia. American Journal of Psychiatry, 174(9), 840849.CrossRefGoogle Scholar
Goldberg, J. F., & Harrow, M. (2011). A 15-year prospective follow-up of bipolar affective disorders: Comparisons with unipolar nonpsychotic depression. Bipolar Disorders, 13(2), 155163.CrossRefGoogle ScholarPubMed
Grinker, S. R., Roy Richard, E. D., & Harrow, M. E. (1987). Clinical research in schizophrenia: A multidimensional approach. Springfield, Ill. : Charles C Thomas, Publisher.Google Scholar
Harrison, G., Hopper, K., Craig, T., Laska, E., Siegel, C., Wanderling, J., … Der Heiden, W. A. (2001). Recovery from psychotic illness: A 15-and 25-year international follow-up study. The British Journal of Psychiatry, 178(6), 506517.CrossRefGoogle ScholarPubMed
Harrow, M., Goldberg, J. F., Grossman, L. S., & Meltzer, H. Y. (1990). Outcome in manic disorders: A naturalistic follow-up study. Archives of General Psychiatry, 47(7), 665671.CrossRefGoogle ScholarPubMed
Harrow, M., Grossman, L. S., Herbener, E. S., & Davies, E. W. (2000). Ten-year outcome: Patients with schizoaffective disorders, schizophrenia, affective disorders and mood-incongruent psychotic symptoms. The British Journal of Psychiatry, 177(5), 421426.Google ScholarPubMed
Harrow, M., Grossman, L. S., Jobe, T. H., & Herbener, E. S. (2005). Do patients with schizophrenia ever show periods of recovery? A 15-year multi-follow-up study. Schizophrenia Bulletin, 31(3), 723734.CrossRefGoogle ScholarPubMed
Harrow, M., & Jobe, T. H. (2007). Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: A 15-year multifollow-up study. The Journal of Nervous and Mental Disease, 195(5), 406414.CrossRefGoogle Scholar
Harrow, M., & Jobe, T. H. (2013). Does long-term treatment of schizophrenia with antipsychotic medications facilitate recovery? Schizophrenia Bulletin, 39(5), 962965.CrossRefGoogle ScholarPubMed
Harrow, M., & Jobe, T. H. (2018). Long-term antipsychotic treatment of schizophrenia: Does it help or hurt over a 20-year period? World Psychiatry, 17(2), 162.CrossRefGoogle ScholarPubMed
Harrow, M., Jobe, T. H., & Faull, R. N. (2012). Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychological Medicine, 42(10), 21452155.CrossRefGoogle ScholarPubMed
Harrow, M., Jobe, T. H., & Faull, R. N. (2014). Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. Psychological Medicine, 44(14), 30073016.CrossRefGoogle ScholarPubMed
Harrow, M., Jobe, T. H., Faull, R. N., & Yang, J. (2017). A 20-year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia. Psychiatry Research, 256, 267274.CrossRefGoogle Scholar
Hegelstad, W. T. V., Larsen, T. K., Auestad, B., Evensen, J., Haahr, U., Joa, I., … Opjordsmoen, S. (2012). Long-term follow-up of the TIPS early detection in psychosis study: Effects on 10-year outcome. American Journal of Psychiatry, 169(4), 374380.CrossRefGoogle ScholarPubMed
Huhn, M., Leucht, C., Rothe, P., Dold, M., Heres, S., Bornschein, S., … Leucht, S. (2020). Reducing antipsychotic drugs in stable patients with chronic schizophrenia or schizoaffective disorder: A randomized controlled pilot trial. European Archives of Psychiatry and Clinical Neuroscience. Published online February 15, 2020. doi:10.1007/s00406-020-01109-y.Google ScholarPubMed
Iyo, M., Tadokoro, S., Kanahara, N., Hashimoto, T., Niitsu, T., Watanabe, H., & Hashimoto, K. (2013). Optimal extent of dopamine D2 receptor occupancy by antipsychotics for treatment of dopamine supersensitivity psychosis and late-onset psychosis. Journal of Clinical Psychopharmacology, 33(3), 398404.CrossRefGoogle ScholarPubMed
Jauhar, S., Nour, M. M., Veronese, M., Rogdaki, M., Bonoldi, I., Azis, M., … Howes, O. D. (2017). A test of the transdiagnostic dopamine hypothesis of psychosis using positron emission tomographic imaging in bipolar affective disorder and schizophrenia. JAMA Psychiatry, 74(12), 12061213.CrossRefGoogle ScholarPubMed
Jauhar, S., Veronese, M., Nour, M. M., Rogdaki, M., Hathway, P., Natesan, S., … Kapur, S. (2019). The effects of antipsychotic treatment on presynaptic dopamine synthesis capacity in first-episode psychosis: A positron emission tomography study. Biological Psychiatry, 85(1), 7987.CrossRefGoogle ScholarPubMed
Keck, P. E., Perlis, R. H., Otto, M. W., Carpenter, C. D., Ross, R., & Docherty, J. P. (2004). The expert consensus guideline series: Treatment of bipolar disorder.Google Scholar
Kesby, J. P., Eyles, D. W., McGrath, J. J., & Scott, J. G. (2018). Dopamine, psychosis and schizophrenia: The widening gap between basic and clinical neuroscience. Translational Psychiatry, 8(1), 112.CrossRefGoogle Scholar
Kirkbride, J. B., Fearon, P., Morgan, C., Dazzan, P., Morgan, K., Tarrant, J., … Leff, J. P. (2006). Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: Findings from the 3-center AeSOP study. Archives of General Psychiatry, 63(3), 250258.CrossRefGoogle ScholarPubMed
Kotov, R., Fochtmann, L., Li, K., Tanenberg-Karant, M., Constantino, E. A., Rubinstein, J., … Carlson, G. (2017). Declining clinical course of psychotic disorders over the two decades following first hospitalization: Evidence from the Suffolk county mental health project. American Journal of Psychiatry, 174(11), 10641074.CrossRefGoogle ScholarPubMed
Lally, J., & MacCabe, J. H. (2015). Antipsychotic medication in schizophrenia: A review. British Medical Bulletin, 114(1), 169179.CrossRefGoogle ScholarPubMed
Leff, J. P., & Wing, J. K. (1971). Trial of maintenance therapy in schizophrenia. British Medical Journal, 3(5775), 599604.CrossRefGoogle Scholar
Leucht, S., Cipriani, A., Spineli, L., Mavridis, D., Örey, D., Richter, F., … Geddes, J. R. (2013). Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple-treatments meta-analysis. The Lancet, 382(9896), 951962.CrossRefGoogle ScholarPubMed
Leucht, S., & Davis, J. M. (2017). Do antipsychotic drugs lose their efficacy for relapse prevention over time? The British Journal of Psychiatry, 211(3), 127129.CrossRefGoogle ScholarPubMed
Leucht, S., Tardy, M., Komossa, K., Heres, S., Kissling, W., & Davis, J. M. (2012a). Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database of Systematic Reviews (5) :CD008016. doi: 10.1002/14651858.CD008016.pub2.CrossRefGoogle Scholar
Leucht, S., Tardy, M., Komossa, K., Heres, S., Kissling, W., Salanti, G., & Davis, J. M. (2012b). Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: A systematic review and meta-analysis. The Lancet, 379(9831), 20632071.CrossRefGoogle Scholar
Levenstein, S., Klein, D. F., & Pollack, M. (1966). Follow-up study of formerly hospitalized voluntary psychiatric patients: The first two years. American Journal of Psychiatry, 122(10), 11021109.CrossRefGoogle ScholarPubMed
Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., … Lebowitz, B. D. (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine, 353(12), 12091223.CrossRefGoogle ScholarPubMed
Lindenmayer, J. (2000). Treatment refractory schizophrenia. Psychiatric Quarterly, 71(4), 373384.CrossRefGoogle ScholarPubMed
Moilanen, J., Haapea, M., Miettunen, J., Jääskeläinen, E., Veijola, J., Isohanni, M., & Koponen, H. (2013). Characteristics of subjects with schizophrenia spectrum disorder with and without antipsychotic medication – a 10-year follow-up of the northern Finland 1966 birth cohort study. European Psychiatry, 28(1), 5358.CrossRefGoogle ScholarPubMed
Moncrieff, J. (2006). Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse. Acta Psychiatrica Scandinavica, 114(1), 313.Google ScholarPubMed
Moncrieff, J., Crellin, N. E., Long, M. A., Cooper, R. E., & Stockmann, T. (2019). Definitions of relapse in trials comparing antipsychotic maintenance with discontinuation or reduction for schizophrenia spectrum disorders: A systematic review. Schizophrenia Research, 225, 4754. doi: 10.1016/j.schres.2019.08.035.Google ScholarPubMed
Moos, R. H., McCoy, L., & Moos, B. S. (2000). Global assessment of functioning (GAF) ratings: Determinants and role as predictors of one-year treatment outcomes. Journal of Clinical Psychology, 56(4), 449461.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Morgan, C., Lappin, J., Heslin, M., Donoghue, K., Lomas, B., Reininghaus, U., … Murray, R. M. (2014). Reappraising the long-term course and outcome of psychotic disorders: The AESOP-10 study. Psychological Medicine, 44(13), 27132726.CrossRefGoogle ScholarPubMed
Murray, R. M., & Di Forti, M. (2018). Increasing expectations and knowledge require a more subtle use of prophylactic antipsychotics. World Psychiatry, 17(2), 161.CrossRefGoogle ScholarPubMed
Murray, R. M., Quattrone, D., Natesan, S., van Os, J., Nordentoft, M., Howes, O., ... Taylor, D (2016). Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?. The British Journal of Psychiatry, 209(5), 361365.CrossRefGoogle ScholarPubMed
Nakahara, H. (2014). Multiplexing signals in reinforcement learning with internal models and dopamine. Current Opinion in Neurobiology, 25, 123129.CrossRefGoogle ScholarPubMed
Nakata, Y., Kanahara, N., & Iyo, M. (2017). Dopamine supersensitivity psychosis in schizophrenia: Concepts and implications in clinical practice. Journal of Psychopharmacology, 31(12), 15111518.Google ScholarPubMed
Oda, Y., Kanahara, N., & Iyo, M. (2015). Alterations of dopamine D2 receptors and related receptor-interacting proteins in schizophrenia: The pivotal position of dopamine supersensitivity psychosis in treatment-resistant schizophrenia. International Journal of Molecular Sciences, 16(12), 3014430163.CrossRefGoogle ScholarPubMed
Oda, Y., Kanahara, N., Kimura, H., Watanabe, H., Hashimoto, K., & Iyo, M. (2015). Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in schizophrenia. Neuropsychiatric Disease and Treatment, 11, 1845.Google ScholarPubMed
Oishi, K., Kanahara, N., Takase, M., Oda, Y., Nakata, Y., Niitsu, T., … Iyo, M. (2018). Vulnerable combinations of functional dopaminergic polymorphisms to late-onset treatment resistant schizophrenia. PLoS ONE, 13(11), e0207133.CrossRefGoogle ScholarPubMed
Rajkumar, R. P. (2014). Supersensitivity psychosis and its response to asenapine in a patient with delusional disorder. Case Reports in Psychiatry, 2014, Article ID 215732. https://doi.org/10.1155/2014/215732.CrossRefGoogle Scholar
Samaha, A. N., 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(11), 29792986.CrossRefGoogle Scholar
Seeman, P. (2011). All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2High receptors. CNS Neuroscience & Therapeutics, 17(2), 118132.CrossRefGoogle Scholar
Shin, C., Han, C., Pae, C., & Patkar, A. A. (2016). Precision medicine for psychopharmacology: A general introduction. Expert Review of Neurotherapeutics, 16(7), 831839.CrossRefGoogle ScholarPubMed
Stephens, J. H., Richard, P., & McHugh, P. R. (1997). Long-term follow-up of patients hospitalized for schizophrenia, 1913 to 1940. The Journal of Nervous and Mental Disease, 185(12), 715721.Google ScholarPubMed
Strålin, P., Skott, M., & Cullberg, J. (2019). Early recovery and employment outcome 13 years after first episode psychosis. Psychiatry Research, 271, 374380.CrossRefGoogle ScholarPubMed
Suzuki, T., Kanahara, N., Yamanaka, H., Takase, M., Kimura, H., Watanabe, H., & Iyo, M. (2015). Dopamine supersensitivity psychosis as a pivotal factor in treatment-resistant schizophrenia. Psychiatry Research, 227(2–3), 278282.CrossRefGoogle ScholarPubMed
Tadokoro, S., Okamura, N., Sekine, Y., Kanahara, N., Hashimoto, K., & Iyo, M. (2012). Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis. Schizophrenia Bulletin, 38(5), 10121020.CrossRefGoogle ScholarPubMed
Takase, M., Kanahara, N., Oda, Y., Kimura, H., Watanabe, H., & Iyo, M. (2015). Dopamine supersensitivity psychosis and dopamine partial agonist: A retrospective survey of failure of switching to aripiprazole in schizophrenia. Journal of Psychopharmacology, 29(4), 383389.CrossRefGoogle Scholar
Tiihonen, J., Mittendorfer-Rutz, E., Majak, M., Mehtälä, J., Hoti, F., Jedenius, E., … Taipale, H. (2017). Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with schizophrenia. JAMA Psychiatry, 74(7), 686693.CrossRefGoogle Scholar
Tiihonen, J., Tanskanen, A., & Taipale, H. (2018). 20-year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. American Journal of Psychiatry, 175(8), 765773.CrossRefGoogle ScholarPubMed
Turkheimer, F. E., Selvaggi, P., Mehta, M. A., Veronese, M., Zelaya, F., Dazzan, P., & Vernon, A. C. (2020). Normalizing the abnormal: Do antipsychotic drugs push the cortex into an unsustainable metabolic envelope? Schizophrenia Bulletin, 46(3), 484495.CrossRefGoogle ScholarPubMed
Vaillant, G. E. (1962). The prediction of recovery in schizophrenia. The Journal of Nervous and Mental Disease, 135(6), 534543.CrossRefGoogle Scholar
Vaillant, G. E. (1978). A 10-year followup of remitting schizophrenics. Schizophrenia Bulletin, 4(1), 78.CrossRefGoogle ScholarPubMed
Velthorst, E., Fett, A. J., Reichenberg, A., Perlman, G., van Os, J., Bromet, E. J., & Kotov, R. (2017). The 20-year longitudinal trajectories of social functioning in individuals with psychotic disorders. American Journal of Psychiatry, 174(11), 10751085.CrossRefGoogle ScholarPubMed
Vita, A., Minelli, A., Barlati, S., Deste, G., Giacopuzzi, E., Valsecchi, P., … Gennarelli, M. (2019). Treatment-resistant schizophrenia: Genetic and neuroimaging correlates. Frontiers in Pharmacology, 10, 402.Google ScholarPubMed
Westermeyer, J. F., & Harrow, M. (1984). Prognosis and outcome using broad (DSM-II) and narrow (DSM-III) concepts of schizophrenia. Schizophrenia Bulletin, 10(4), 624637.CrossRefGoogle ScholarPubMed
Whitaker, R. (2002). Mad in America: Bad science, bad medicine, and the enduring mistreatment of the mentally ill. New York, NY: Perseus Publishing.Google Scholar
Whitaker, R. (2010). Anatomy of an epidemic. New York. NY: Crown Publishers.Google Scholar
Wils, R. S., Gotfredsen, D. R., Hjorthøj, C., Austin, S. F., Albert, N., Secher, R. G., … Nordentoft, M. (2017). Antipsychotic medication and remission of psychotic symptoms 10 years after a first-episode psychosis. Schizophrenia Research, 182, 4248.CrossRefGoogle Scholar
Wunderink, L. (2019). Personalizing antipsychotic treatment: Evidence and thoughts on individualized tailoring of antipsychotic dosage in the treatment of psychotic disorders. Therapeutic Advances in Psychopharmacology, 9, 2045125319836566.CrossRefGoogle ScholarPubMed
Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., & Nienhuis, F. J. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: Long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry, 70(9), 913920.CrossRefGoogle ScholarPubMed
Yin, J., Barr, A. M., Ramos-Miguel, A., & Procyshyn, R. M. (2017). Antipsychotic induced dopamine supersensitivity psychosis: A comprehensive review. Current Neuropharmacology, 15(1), 174183.CrossRefGoogle ScholarPubMed
Zigler, E. F., & Glick, M. (2001). A developmental approach to adult psychopathology. Hoboken, NJ: John Wiley & Son.CrossRefGoogle Scholar
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