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Treatment resistance and other complicating factors in the management of schizophrenia

Published online by Cambridge University Press:  20 November 2014

Martin T. Strassnig  and
Philip D. Harvey
Martin T. Strassnig
Affiliation:
Department of Psychiatry, University of Miami, Miami, Florida, USA
Philip D. Harvey*
Affiliation:
Department of Psychiatry, University of Miami, Miami, Florida, USA Research Service, Bruce W. Carter VA Medical Center, Miami, Florida, USA
*
*Address for correspondence: Dr. Philip D. Harvey, Department of Psychiatry, University of Miami, Miami, FL, USA. (Email: harveyp@med.miami.edu)
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Abstract

Treatment resistance, along with its sibling partial response, remains a common phenomenon in schizophrenia, complicating the disability burden inherent in the disease. Antipsychotic medications are the mainstay of treatment, and treatment resistance has mainly been defined in terms of poor response to antipsychotic medication. At the same time, clozapine, the most effective antipsychotic, remains underutilized at the expense of exposing patients to polypharmacy. We review known causes of disability in schizophrenia, how they impact various areas of everyday functioning, and discuss potential treatment options including but not limited to pharmacological approaches aimed at maximizing treatment response and reducing treatment resistance.

Keywords

Chroniccognitionhealthrefractoryschizophrenia
Type
CME Review Article
Information
CNS Spectrums , Volume 19 , Issue S1: CME SUPPLEMENT , December 2014 , pp. 13 - 24
Copyright
© Cambridge University Press 2014 

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Footnotes

This activity is supported by an educational grant from Jazz Pharmaceuticals, Inc.

References

1.Murray, CJ, Lopez, AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet. 1997; 349(9064): 1498–1504.CrossRefGoogle ScholarPubMed
2.Harvey, PD. Cognitive functioning and disability in schizophrenia. Current Directions in Psychological Science. 2010; 19(4): 249–254.CrossRefGoogle Scholar
3.Henry, BL, Minassian, A, Perry, W. Everyday functional ability across different phases of bipolar disorder. Psychiatry Res. 2013; 210(3): 850–856.CrossRefGoogle ScholarPubMed
4.Suzuki, T, Remingon, G, Mulsant, BH, et al. Treatment resistant schizophrenia and response to antipsychotics: a review. Schizophr Res. 2011; 133(1–3): 54–62.CrossRefGoogle ScholarPubMed
5.Hellewell, JS. Treatment-resistant schizophrenia: reviewing the options and identifying the way forward. J Clin Psychiatry. 1999; 60(Suppl 23): 14–19.Google ScholarPubMed
6.Harvey, PD, Strassnig, M. Predicting the severity of everyday functional disability in people with schizophrenia: cognitive deficits, functional capacity, symptoms, and health status. World Psychiatry. 2012; 11(2): 73–79.CrossRefGoogle ScholarPubMed
7.Strassnig, M, Harvey, PD. Treatment of obesity and disability in schizophrenia. Innov Clin Neurosci. 2013; 10(7–8): 15–19.Google ScholarPubMed
8.Emsley, RA. Partial response to antipsychotic treatment: the patient with enduring symptoms. J Clin Psychiatry. 1999; 60(Suppl 23): 10–13.Google ScholarPubMed
9.Bowie, CR, Twamley, EW, Anderson, H, Halpern, B, Patterson, TL, Harvey, PD. Self-assessment of functional status in schizophrenia. J Psychiatr Res. 2007; 41(12): 1012–1018.CrossRefGoogle ScholarPubMed
10.Green, MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996; 153(3): 321–330.Google ScholarPubMed
11.Carpenter, WT Jr, Arango, C, Buchanan, RW, Kirkpatrick, B. Deficit psychopathology and a paradigm shift in schizophrenia research. Biol Psychiatry. 1999; 46(3): 352–360.CrossRefGoogle Scholar
12.Miyamoto, S, Miyake, N, Jarskog, LF, Fleischhacker, WW, Lieberman, JA. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Mol Psychiatry. 2012; 17(12): 1206–1227.CrossRefGoogle ScholarPubMed
13.Kopelowicz, A, Liberman, RP, Mintz, J, Zarate, R. Comparison of efficacy of social skills training for deficit and nondeficit negative symptoms in schizophrenia. Am J Psychiatry. 1997; 154(3): 424–425.Google ScholarPubMed
14.Kurtz, MM, Mueser, KT. A meta-analysis of controlled research on social skills training for schizophrenia. J Consult Clin Psychol. 2008; 76(3): 491–504.CrossRefGoogle ScholarPubMed
15.Wyatt, RJ. Neuroleptics and the natural course of schizophrenia. Schizophr Bull. 1991; 17(2): 325–351.CrossRefGoogle ScholarPubMed
16.Davis, KL, Buchsbaum, MS, Shihabuddin, L, et al. Ventricular enlargement in poor outcome schizophrenia. Biol Psychiatry. 1998; 43(11): 783–793.CrossRefGoogle ScholarPubMed
17.Gur, RE, Cowell, P, Turetsky, BI, et al. A follow-up magnetic resonance imaging study of schizophrenia: relationship of neuroanatomical changes to clinical and neurobehavioral measures. Arch Gen Psychiatry. 1998; 55(2): 145–152.CrossRefGoogle ScholarPubMed
18.Harvey, PD, Bertisch, H, Friedman, JI, et al. The course of functional decline in geriatric patients with schizophrenia: cognitive-functional and clinical symptoms as determinants of change. Am J Geriatr Psychiatry. 2003; 11(6): 610–619.Google ScholarPubMed
19.Harvey, PD, Reichenberg, A, Bowie, CR, Patterson, TL, Heaton, RK. The course of neuropsychological performance and functional capacity in older patients with schizophrenia: influences of previous history of long-term institutional stay. Biol Psychiatry. 2010; 67(10): 933–939.CrossRefGoogle ScholarPubMed
20.DeLisi, L, Sakuma, M, Tew, W, Kushrer, M, Hoff, A, Grimson, R. Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of psychosis. Psychiatry Res Brain Imaging. 1997; 74(3): 129–140.CrossRefGoogle Scholar
21.DeLisi, LE. Defining the course of brain structural change and plasticity in schizophrenia. Psychiatry Res. 1999; 92(1): 1–9.CrossRefGoogle ScholarPubMed
22.van Haren, NE, Schnack, HG, Cahn, W, et al. Changes in cortical thickness during the course of illness in schizophrenia. Arch Gen Psychiatry. 2011; 68(9): 871–880.CrossRefGoogle ScholarPubMed
23.van Haren, NE, Hulshoff, Pol HE, Schnack, HG, et al. Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology. 2007; 32(10): 2057–2066.CrossRefGoogle ScholarPubMed
24.Cahn, W, van Haren, NE, Hulshoff Pol, HE, et al. Brain volume changes in the first year of illness and 5-year outcome of schizophrenia. Br J Psychiatry. 2006; 189(4): 381–382.CrossRefGoogle ScholarPubMed
25.Davis, KL, Buchsbaum, MS, Shihabuddin, L, et al. Ventricular enlargement in poor-outcome schizophrenia. Biol Psychiatry. 1998; 43(11): 783–793.CrossRefGoogle ScholarPubMed
26.Boonstra, G, Cahn, W, Schnack, HG, et al. Duration of untreated illness in schizophrenia is not associated with 5-year brain volume change. Schizophr Res. 2011; 132(1): 84–90.CrossRefGoogle Scholar
27.Bowie, CR, Leung, WW, Reichenberg, A, et al. Predicting schizophrenia patients’ real-world behavior with specific neuropsychological and functional capacity measures. Biol Psychiatry. 2008; 63(5): 505–551.CrossRefGoogle ScholarPubMed
28.Harvey, PD, Raykov, T, Twamley, EW, Vella, L, Heaton, RK, Patterson, TL. Validating the measurement of real-world functional outcomes: phase I results of the VALERO study. Am J Psychiatry. 2011; 168(11): 1195–2201.CrossRefGoogle ScholarPubMed
29.Gould, F, Sabbag, S, Durand, D, Patterson, TL, Harvey, PD. Self-assessment of functional ability in schizophrenia: milestone achievement and its relationship to accuracy of self-evaluation. Psychiatry Res. 2013; 207(1–2): 19–24.CrossRefGoogle ScholarPubMed
30.Harvey, PD, Putnam, KM, Davidson, M, et al. Brief neuroleptic discontinuation in Kraepelinian and non-Kraepelinian chronic schizophrenic patients. Psychiatr Res. 1991; 38(3): 285–292.CrossRefGoogle ScholarPubMed
31.Harvey, PD, Davidson, M, Powchik, P, et al. Time course and clinical predictors of treatment response in schizophrenia. Schizophr Res. 1991; 5(2): 161–166.CrossRefGoogle ScholarPubMed
32.Lieberman, JA, Sheitman, B, Chakos, M, Robinson, D, Schooler, N, Keith, S. The development of treatment resistance in patients with schizophrenia: a clinical and pathophysiologic perspective. J Clin Psychopharmacol. 1998; 18(2 Suppl 1): 20S–24S.CrossRefGoogle ScholarPubMed
33.Lieberman, J, Stroup, TS, McEvoy, JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005; 353(12): 1209–1223.CrossRefGoogle ScholarPubMed
34.Jones, PB, Barnes, TR, Davies, L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CutLASS 1). Arch Gen Psychiatry. 2006; 63(10): 1079–1087.CrossRefGoogle Scholar
35.Agid, O, Foussias, G, Singh, S, Remington, G. Where to position clozapine: re-examining the evidence. Can J Psychiatry. 2010; 55(10): 677–684.CrossRefGoogle ScholarPubMed
36.Conley, RR, Buchanan, RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull. 1997; 23(4): 663–674.CrossRefGoogle ScholarPubMed
37.Stroup, TS, Lieberman, JA, McEvoy, JP, et al. Results of phase 3 of the CATIE schizophrenia trial. Schizophr Res. 2009; 107(1): 1–12.CrossRefGoogle ScholarPubMed
38.Taylor, DM, Young, C, Paton, C. Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review. J Clin Psychiatry. 2003; 64(1): 30–34.CrossRefGoogle ScholarPubMed
39.Wheeler, AJ. Treatment pathway and patterns of clozapine prescribing for schizophrenia in New Zealand. Ann Pharmacother. 2008; 42(6): 852–860.CrossRefGoogle ScholarPubMed
40.Goren, JL, Meterko, M, Williams, S, et al. Antipsychotic prescribing pathways, polypharmacy, and clozapine use in treatment of schizophrenia. Psychiatr Serv. 2013; 64(6): 527–533.CrossRefGoogle ScholarPubMed
41.Stroup, TS, Gerhard, T, Crystal, S, Huang, C, Olfson, M. Geographic and clinical variation in clozapine use in the United States. Psychiatr Serv. 2014; 65(2): 186–192.CrossRefGoogle ScholarPubMed
42.Glazer, WM. The depot paradox. Behav Healthc. 2007; 27(5): 44–46.Google ScholarPubMed
43.Kane, JM, Kishimoto, T, Correll, CU. Assessing the comparative effectiveness of long-acting injectable vs. oral antipsychotic medication in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry. J Clin Epidemiol. 2013; 66(8 Suppl): S37–S41.CrossRefGoogle ScholarPubMed
44.Taylor, M, Ng, KY. Should long-acting (depot) antipsychotics be used in early schizophrenia? A systematic review. Aust N Z J Psychiatry. 2013; 47(7): 624–630.CrossRefGoogle ScholarPubMed
45.Kane, JM, Garcia-Ribera, C. Clinical guideline recommendations for antipsychotic long-acting injections. Br J Psychiatry Suppl. 2009; 52: S63–S67.CrossRefGoogle ScholarPubMed
46.Velligan, DI, Weiden, PJ, Sajatovic, M, et al. Expert Consensus Panel on Adherence Problems in Serious and Persistent Mental Illness. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry. 2009; 70(Suppl 4): 1–46.Google ScholarPubMed
47.Kishimoto, T, Robenzadeh, A, Leucht, C, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014; 40(1): 192–213.CrossRefGoogle ScholarPubMed
48.Leucht, C, Heres, S, Kane, JM, Kissling, W, Davis, JM, Leucht, S. Oral versus depot antipsychotic drugs for schizophrenia—a critical systematic review and meta-analysis of randomized long-term trials. Schizophr Res. 2011; 127(1–3): 83–92.CrossRefGoogle ScholarPubMed
49.Kane, JM, Aguglia, E, Altamura, AC, et al. Guidelines for depot antipsychotic treatment in schizophrenia. Eur Neuropsychopharmacol. 1998; 8(1): 55–66.CrossRefGoogle ScholarPubMed
50.Jin, H, Folsom, D, Sasaki, A, et al. Increased Framingham 10-year risk of coronary heart disease in middle-aged and older patients with psychotic symptoms. Schizophr Res. 2011; 125(2–3): 295–299.CrossRefGoogle ScholarPubMed
51.Vargas, G, Strassnig, M, Sabbag, S, et al. The course of vocational functioning in patients with schizophrenia: re-examining social drift. Schizophr Res Cogn. 2014; 1(1): 41–46.CrossRefGoogle ScholarPubMed
52.Fett, AK, Viechtbauer, W, Dominguez, MD, Penn, DL, van Os, J, Krabbendam, L. The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev. 2011; 35(3): 573–588.CrossRefGoogle ScholarPubMed
53.Bowie, CR, McGurk, SR, Mausbach, B, Patterson, TL, Harvey, PD. Combined cognitive remediation and functional skills training for schizophrenia: effects on cognition, functional competence, and real-world behavior. Am J Psychiatry. 2012; 169(7): 710–718.CrossRefGoogle ScholarPubMed
54.Keefe, RS, Buchanan, RW, Marder, SR, et al. Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? Schizophr Bull. 2013; 39(2): 417–435.CrossRefGoogle ScholarPubMed
55.Harvey, PD, Koren, D, Reichenberg, A, Bowie, CR. Negative symptoms and cognitive deficits: what is the nature of their relationship? Schizophr Bull. 2006; 32(2): 250–258.CrossRefGoogle ScholarPubMed
56.Bowie, CR, Reichenberg, A, Patterson, TL, Heaton, RK, Harvey, PD. Determinants of real-world functional performance in schizophrenia subjects: correlations with cognition, functional capacity, and symptoms. Am J Psychiatry. 2006; 163(3): 418–425.CrossRefGoogle ScholarPubMed
57.Bowie, CR, Depp, C, McGrath, JA, et al. Prediction of real-world functional disability in chronic mental disorders: a comparison of schizophrenia and bipolar disorder. Am J Psychiatry. 2010; 167(9): 1116–1124.CrossRefGoogle ScholarPubMed
58.an der Heiden, W, Könnecke, R, Maurer, K, Ropeter, D, Häfner, H. Depression in the long-term course of schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2005; 255(3): 174–184.CrossRefGoogle ScholarPubMed
59.Harvey, PD. Mood symptoms, cognition, and everyday functioning: in major depression, bipolar disorder, and schizophrenia. Innov Clin Neurosci. 2011; 8(10): 14–28.Google ScholarPubMed
60.Kollias, CT, Kontaxakis, VP, Havaki-Kontaxaki, BJ, et al. Association of physical and social anhedonia with depression in the acute phase of schizophrenia. Psychopathology. 2008; 41(6): 365–370.CrossRefGoogle ScholarPubMed
61.Siris, SG. Depression in schizophrenia: perspective in the era of "atypical" antipsychotic agents. Am J Psychiatry. 2000; 157(9): 1379–1389.CrossRefGoogle ScholarPubMed
62.Zisook, S, Kasckow, JW, Golshan, S, et al. Citalopram augmentation for subsyndromal symptoms of depression in middle-aged and older outpatients with schizophrenia and schizoaffective disorder: a randomized controlled trial. J Clin Psychiatry. 2009; 70(4): 562–571.CrossRefGoogle ScholarPubMed
63.Friedman, JI, Ocampo, R, Elbaz, Z, et al. The effect of citalopram adjunctive treatment added to atypical antipsychotic medications for cognitive performance in patients with schizophrenia. J Clin Psychopharmacol. 2005; 25(3): 237–242.CrossRefGoogle ScholarPubMed
64.Hennekens, CH, Hennekens, AR, Hollar, D, Casey, DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005; 150(6): 1115–1121.CrossRefGoogle ScholarPubMed
65.McEvoy, JP, Meyer, JM, Goff, DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005; 80(1): 19–32.CrossRefGoogle ScholarPubMed
66.Homel, P, Casey, D, Allison, DB. Changes in body mass index for individuals with and without schizophrenia, 1987–1996. Schizophr Res. 2002; 55(3): 277–284.CrossRefGoogle ScholarPubMed
67.Newcomer, JW. Metabolic risk during antipsychotic treatment. Clin Ther. 2002; 26(12): 1936–1946.CrossRefGoogle Scholar
68.Casey, DE, Haupt, DW, Newcomer, JW, et al. Antipsychotic-induced weight gain and metabolic abnormalities: implications for increased mortality in patients with schizophrenia. J Clin Psychiatry. 2004; 65(Suppl 7): 4–18.Google ScholarPubMed
69.Newcomer, JW. Metabolic syndrome and mental illness. Am J Manag Care. 2007; 13(7 Suppl): S170–S177.Google ScholarPubMed
70.Druss, BG, Newcomer, JW. Challenges and solutions to integrating mental and physical health care. J Clin Psychiatry. 2007; 68(4): e09.CrossRefGoogle ScholarPubMed
71.Morrato, EH, Druss, B, Hartung, DM, et al. Metabolic testing rates in 3 state Medicaid programs after FDA warnings and ADA/APA recommendations for second-generation antipsychotic drugs. Arch Gen Psychiatry. 2010; 67(1): 17–24.CrossRefGoogle ScholarPubMed
72.Strassnig, M, Brar, JS, Ganguli, R. Low cardiorespiratory fitness and physical functional capacity in obese patients with schizophrenia. Schizophr Res. 2011; 126(1–3): 103–109.CrossRefGoogle ScholarPubMed
73.Strassnig, M, Brar, JS, Ganguli, R. Health-related quality of life, adiposity, and sedentary behavior in patients with early schizophrenia: preliminary study. Diabetes Metab Syndr Obes. 2012; 5: 389–394.Google ScholarPubMed
74.Vancampfort, D, Probst, M, Scheewe, T, Knapen, J, De Hert, A, De Hert, M. The functional exercise capacity is correlated with global functioning in patients with schizophrenia. Acta Psychiatr Scand. 2012; 125(5): 382–387.CrossRefGoogle ScholarPubMed
75.Vancampfort, D, Knapen, J, Probst, M, Scheewe, T, Remans, S, De Hert, M. A systematic review of correlates of physical activity in patients with schizophrenia. Acta Psychiatr Scand. 2012; 125(5): 352–362.CrossRefGoogle ScholarPubMed
76.Heggelund, J, Hoff, J, Helgerud, J, Nilsberg, GE, Morken, G. Reduced peak oxygen uptake and implications for cardiovascular health and quality of life in patients with schizophrenia. BMC Psychiatry. 2011; 11: 188.CrossRefGoogle ScholarPubMed
77.Hillman, CH, Erickson, KI, Kramer, AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci. 2008; 9(1): 58–65.CrossRefGoogle ScholarPubMed
78.Cotman, CW, Berchtold, NC, Christie, LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007; 30(9): 464–472.CrossRefGoogle Scholar
79.van Praag, H, Christie, BR, Sejnowski, TJ, Gage, FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999; 96(23): 13427–13431.CrossRefGoogle ScholarPubMed
80.Fabel, K, Toda, H, Fabel, K, Palmer, T. Copernican stem cells: regulatory constellations in adult hippocampal neurogenesis. J Cell Biochem. 2003; 88(1): 41–50.CrossRefGoogle ScholarPubMed
81.Kronenberg, G, Bick-Sander, A, Bunk, E, Wolf, C, Ehninger, D, Kempermann, G. Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging. 2006; 27(10): 1505–1513.CrossRefGoogle ScholarPubMed
82.Strassnig, M, Caceda, R, Newcomer, JW, Harvey, PD. Cognitive deficits, obesity and disability in schizophrenia. Translational Neuroscience. 2012; 3(4): 345–354.CrossRefGoogle Scholar
83.Lieberman, JA, Drake, RE, Sederer, LI, et al. Science and recovery in schizophrenia. Psychiatr Serv. 2008; 59(5): 487–496.CrossRefGoogle ScholarPubMed
84.McGurk, SR, Twamley, EW, Sitzer, DI, McHugo, GJ, Mueser, KT. A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry. 2007; 164(12): 1791–1802.CrossRefGoogle ScholarPubMed
85.Torrent, C, Bonnin, C, del, M, Martínez-Arán, A, et al. Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study. Am J Psychiatry. 2013; 170(8): 852–859.CrossRefGoogle ScholarPubMed
86.Twamley, EW, Savla, GN, Zurhellen, CH, Heaton, RK, Jeste, DV. Development and pilot testing of a novel compensatory cognitive training intervention for people with psychosis. Am J Psychiatr Rehabil. 2008; 11(2): 144–163.CrossRefGoogle ScholarPubMed
87.Cook, JA, Leff, HS, Blyler, CR, et al. Results of a multisite randomized trial of supported employment interventions for individuals with severe mental illness. Arch Gen Psychiatry. 2005; 62(5): 505–512.CrossRefGoogle ScholarPubMed