Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-26T10:36:13.319Z Has data issue: false hasContentIssue false
  • English
  • Français

Optimizing Outcomes in Schizophrenia: Long-acting Depots and Long-term Treatment

Published online by Cambridge University Press:  10 December 2012

Debbi A. Morrissette  and
Stephen M. Stahl
Debbi A. Morrissette
Affiliation:
Neuroscience Education Institute, Carlsbad, CA, USA
Stephen M. Stahl*
Affiliation:
Neuroscience Education Institute, Carlsbad, CA, USA Department of Psychiatry, University of California-San Diego, San Diego, CA, USA
*
*Address correspondence to: Stephen M. Stahl, M.D., Ph.D. Neuroscience Education Institute, 1930 Palomar Point Way, Suite 101, Carlsbad, CA 92008. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Antipsychotics are the mainstay of treatment for patients with schizophrenia. However, these medications only work if they are taken and perhaps work best if they are taken for longer periods of time than seen in typical research trials. Here we explore the idea of “time as a drug” by reviewing the data showing the potential benefits of long-term antipsychotic use. We also discuss the utility of depot antipsychotic formulations for improving the chances of attaining long-term therapeutic results.

Type
CME Article
Information
CNS Spectrums , Volume 17 , Issue s1: CME SUPPLEMENT: Optimizing Care for Patients with Schizophrenia , November 2012 , pp. 10 - 21
Copyright
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.)

References

1.Brundtland, GH. From the World Health Organization. Mental health: new understanding, new hope. JAMA. 2001; 286(19): 2391.Google ScholarPubMed
2.Mura, G, Petretto, DR, Bhat, KM, Carta, MG. Schizophrenia: from epidemiology to rehabilitation. Clin Pract Epidemiol Ment Health. 2012; 8: 52–66.CrossRefGoogle ScholarPubMed
3.Manschreck, TC, Boshes, RA. The CATIE schizophrenia trial: results, impact, controversy. Harv Rev Psychiatry. 2007; 15(5): 245–258.CrossRefGoogle ScholarPubMed
4.Mullins, CD, Obeidat, NA, Cuffel, BJ, Naradzay, J, Loebel, AD. Risk of discontinuation of atypical antipsychotic agents in the treatment of schizophrenia. Schizophr Res. 2008; 98(1–3): 8–15.CrossRefGoogle ScholarPubMed
5.Glick, ID, Correll, CU, Altamura, AC, etal. Mid-term and long-term efficacy and effectiveness of antipsychotic medications for schizophrenia: a data-driven, personalized clinical approach. J Clin Psychiatry. 2011; 72(12): 1616–1627.CrossRefGoogle ScholarPubMed
6.Morrissette, DA, Cutler, AJ. Strategies for optimizing medication adherence in schizophrenia. CNS Spectrums. 2012; 17(01): 31–41.CrossRefGoogle Scholar
7.Mitchell, AJ. Adherence behaviour with psychotropic medication is a form of self-medication. Med Hypotheses. 2007; 68(1): 12–21.CrossRefGoogle ScholarPubMed
8.Mitchell, AJ, Selmes, T. Why don't patients take their medicine? Reasons and solutions in psychiatry. Advances in Psychiatric Treatment. 2007; 13(5): 336–346.CrossRefGoogle Scholar
9.Freudenreich, O, Tranulis, C. A prototype approach toward antipsychotic medication adherence in schizophrenia. Harv Rev Psychiatry. 2009; 17(1): 35–40.CrossRefGoogle ScholarPubMed
10.Llorca, PM. Partial compliance in schizophrenia and the impact on patient outcomes. Psychiatry Res. 2008; 161(2): 235–247.CrossRefGoogle ScholarPubMed
11.Robinson, D, Woerner, MG, Alvir, JM, etal. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999; 56(3): 241–247.CrossRefGoogle ScholarPubMed
12.Caseiro, O, Perez-Iglesias, R, Mata, I, etal. Predicting relapse after a first episode of non-affective psychosis: a three-year follow-up study. J Psychiatr Res. 2012; 46(8): 1099–1105.CrossRefGoogle ScholarPubMed
13.Ucok, A, Polat, A, Cakir, S, Genc, A. One year outcome in first episode schizophrenia. Predictors of relapse. Eur Arch Psychiatry Clin Neurosci. 2006; 256(1): 37–43.CrossRefGoogle ScholarPubMed
14.Subotnik, KL, Nuechterlein, KH, Ventura, J, etal. Risperidone nonadherence and return of positive symptoms in the early course of schizophrenia. Am J Psychiatry. 2011; 168(3): 286–292.CrossRefGoogle ScholarPubMed
15.Weiden, PJ, Kozma, C, Grogg, A, Locklear, J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv. 2004; 55(8): 886–891.CrossRefGoogle ScholarPubMed
16.Leucht, S, Tardy, M, Komossa, K, Heres, S, Kissling, W, Davis, JM. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2012; 5: CD008016.Google Scholar
17.Leucht, S, Tardy, M, Komossa, K, etal. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012; 379(9831): 2063–2071.CrossRefGoogle ScholarPubMed
18.Tiihonen, J, Lonnqvist, J, Wahlbeck, K, etal. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009; 374(9690): 620–627.CrossRefGoogle ScholarPubMed
19.Alvarez-Jimenez, M, Gleeson, JF, Henry, LP, etal. Prediction of a single psychotic episode: a 7.5-year, prospective study in first-episode psychosis. Schizophr Res. 2011; 125(2–3): 236–246.CrossRefGoogle ScholarPubMed
20.Harrow, M, Jobe, TH, Faull, RN. Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychol Med. 2012: 1–11.Google Scholar
21.Dell'osso, B, Glick, ID, Baldwin, DS, Altamura, AC. Can Long-Term Outcomes Be Improved by Shortening the Duration of Untreated Illness in Psychiatric Disorders A Conceptual Framework. Psychopathology. 2012.Google ScholarPubMed
22.Stahl, SM, Cucchiaro, J, Simonelli, D, Hsu, J, Pikalov, A, Loebel, A. Long-term safety and tolerability of lurasidone for patients with schizophrenia following 6 weeks of acute treatment with lurasidone, olanzapine, or placebo: a 6-month open-label extension study. Journal of Clinical Psychiatry. 2012; In Press.Google Scholar
23.Addington, DE, Labelle, A, Kulkarni, J, Johnson, G, Loebel, A, Mandel, FS. A comparison of ziprasidone and risperidone in the long-term treatment of schizophrenia: a 44-week, double-blind, continuation study. Can J Psychiatry. 2009; 54(1): 46–54.CrossRefGoogle ScholarPubMed
24.Hirsch, SR, Kissling, W, Bauml, J, Power, A, O'Connor, R. A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. J Clin Psychiatry. 2002; 63(6): 516–523.CrossRefGoogle ScholarPubMed
25.Emsley, R, Rabinowitz, J, Medori, R. Time course for antipsychotic treatment response in first-episode schizophrenia. Am J Psychiatry. 2006; 163(4): 743–745.CrossRefGoogle ScholarPubMed
26.Lieberman, JA, Kane, JM, Safferman, AZ, etal. Predictors of response to clozapine. J Clin Psychiatry. 1994; 55(Suppl B): 126–128.Google ScholarPubMed
27.Schulte, P. What is an adequate trial with clozapine?: therapeutic drug monitoring and time to response in treatment-refractory schizophrenia. Clin Pharmacokinet. 2003; 42(7): 607–618.CrossRefGoogle ScholarPubMed
28.Meltzer, HY, Burnett, S, Bastani, B, Ramirez, LF. Effects of six months of clozapine treatment on the quality of life of chronic schizophrenic patients. Hosp Community Psychiatry. 1990; 41(8): 892–897.Google ScholarPubMed
29.Rosenheck, R, Evans, D, Herz, L, etal. How long to wait for a response to clozapine: a comparison of time course of response to clozapine and conventional antipsychotic medication in refractory schizophrenia. Schizophr Bull. 1999; 25(4): 709–719.CrossRefGoogle Scholar
30.Covell, NH, McEvoy, JP, Schooler, NR, etal. Effectiveness of switching from long-acting injectable fluphenazine or haloperidol decanoate to long-acting injectable risperidone microspheres: an open-label, randomized controlled trial. J Clin Psychiatry. 2012; 73(5): 669–675.CrossRefGoogle ScholarPubMed
31.Essock, SM, Covell, NH, Davis, SM, Stroup, TS, Rosenheck, RA, Lieberman, JA. Effectiveness of switching antipsychotic medications. Am J Psychiatry. 2006; 163(12): 2090–2095.CrossRefGoogle ScholarPubMed
32.Rosenheck, RA, Davis, S, Covell, N, etal. Does switching to a new antipsychotic improve outcomes? Data from the CATIE Trial. Schizophr Res. 2009; 107(1): 22–29.CrossRefGoogle ScholarPubMed
33.Lieberman, JA, Stroup, TS, McEvoy, JP, etal. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005; 353(12): 1209–1223.CrossRefGoogle ScholarPubMed
34.Potkin, SG, Weiden, PJ, Loebel, AD, Warrington, LE, Watsky, EJ, Siu, CO. Remission in schizophrenia: 196-week, double-blind treatment with ziprasidone vs. haloperidol. Int J Neuropsychopharmacol. 2009; 12(9): 1233–1248.CrossRefGoogle ScholarPubMed
35.Stahl, SM, Malla, A, Newcomer, JW, etal. A post hoc analysis of negative symptoms and psychosocial function in patients with schizophrenia: a 40-week randomized, double-blind study of ziprasidone versus haloperidol followed by a 3-year double-blind extension trial. J Clin Psychopharmacol. 2010; 30(4): 425–430.CrossRefGoogle ScholarPubMed
36.Lieberman, JA, Tollefson, G, Tohen, M, etal. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry. 2003; 160(8): 1396–1404.CrossRefGoogle ScholarPubMed
37.Marder, SR, Glynn, SM, Wirshing, WC, etal. Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes. Am J Psychiatry. 2003; 160(8): 1405–1412.CrossRefGoogle ScholarPubMed
38.Addington, DE, Pantelis, C, Dineen, M, Benattia, I, Romano, SJ. Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial. J Clin Psychiatry. 2004; 65(12): 1624–1633.CrossRefGoogle ScholarPubMed
39.Chrzanowski, WK, Marcus, RN, Torbeyns, A, Nyilas, M, McQuade, RD. Effectiveness of long-term aripiprazole therapy in patients with acutely relapsing or chronic, stable schizophrenia: a 52-week, open-label comparison with olanzapine. Psychopharmacology (Berl). 2006; 189(2): 259–266.CrossRefGoogle ScholarPubMed
40.Hsieh, MH, Lin, WW, Chen, ST, etal. A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting. Ann Gen Psychiatry. 2010; 9: 35.CrossRefGoogle ScholarPubMed
41.Kasper, S, Brecher, M, Fitton, L, Jones, AM. Maintenance of long-term efficacy and safety of quetiapine in the open-label treatment of schizophrenia. Int Clin Psychopharmacol. 2004; 19(5): 281–289.CrossRefGoogle ScholarPubMed
42.Kasper, S. Quetiapine is effective against anxiety and depressive symptoms in long-term treatment of patients with schizophrenia. Depress Anxiety. 2004; 20(1): 44–47.CrossRefGoogle ScholarPubMed
43.Loebel, A, Cucchiano, J, Xu, J, Sarma, K, Pikalov, A, Kane, JM. Effectiveness of lurasidone vs. quetiapine XR for relapse prevention in schizophrenia: a 12-month, double-blind study. Paper presented at: American Psychiatric Association Annual Meeting 2012; Philadelphia, PA.CrossRefGoogle Scholar
44.Stahl, SM, Bollu, VK, K. R, Pikalov, A, Hsu, J, Loebel, A. Switching from olanzapine to lurasidone: results from a 6-month open label extension study. Paper presented at: American Psychiatric Association Annual Meeting 2012; Philadelphia, PA.Google Scholar
45.Kissling, W, Heres, S, Lloyd, K, etal. Direct transition to long-acting risperidone--analysis of long-term efficacy. J Psychopharmacol. 2005; 19(5 Suppl): 15–21.CrossRefGoogle ScholarPubMed
46.Gopal, S, Vijapurkar, U, Lim, P, Morozova, M, Eerdekens, M, Hough, D. A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia. J Psychopharmacol. 2011; 25(5): 685–697.CrossRefGoogle ScholarPubMed
47.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 randomised long-term trials. Schizophr Res. 2011; 127(1–3): 83–92.CrossRefGoogle ScholarPubMed
48.Ereshefsky, L, Mascarenas, CA. Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics. J Clin Psychiatry. 2003; 64(Suppl 16): 18–23.Google ScholarPubMed
49.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(6): 603–609.CrossRefGoogle ScholarPubMed
50.Wheeler, A, Vanderpyl, J, Carswell, C, Stojkovic, M, Robinson, E. One-year treatment continuation in patients prescribed risperidone long-acting injection in New Zealand: a retrospective study. Clin Schizophr Relat Psychoses. 2012; 6(2): 61–68.CrossRefGoogle ScholarPubMed
51.Gaebel, W, Schreiner, A, Bergmans, P, etal. Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable vs quetiapine: results of a long-term, open-label, randomized clinical trial. Neuropsychopharmacology. 2010; 35(12): 2367–2377.CrossRefGoogle ScholarPubMed
52.Keks, NA, Ingham, M, Khan, A, Karcher, K. Long-acting injectable risperidone v. olanzapine tablets for schizophrenia or schizoaffective disorder. Randomised, controlled, open-label study. Br J Psychiatry. 2007; 191: 131–139.CrossRefGoogle ScholarPubMed
53.Rosenheck, RA, Krystal, JH, Lew, R, etal. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011; 364(9): 842–851.CrossRefGoogle ScholarPubMed
54.Altamura, AC, Aguglia, E, Bassi, M, etal. Rethinking the role of long-acting atypical antipsychotics in the community setting. Int Clin Psychopharmacol. 2012.CrossRefGoogle ScholarPubMed
55.Carson, WH, Perry, P, Sanchez, R, etal. Effects of long-acting injectable formulation of aripiprazole on secondary efficacy outcomesin maintenance treatment of schizophrenia. Paper presented at: American Psychiatric Association Annual Meeting 2012; Philadelphia, PA.Google Scholar
56.Fleischhacker, WW, Sanchez, R, Perry, P, etal. Long-term safety and tolerability of once-monthly aripiprazole-intramuscular-depot for maintenance treatment in schizophrenia. Paper presented at: American Psychiatric Association Annual Meeting 2012; Philadelphia, PA.Google Scholar
57.Kane, JM, Sanchez, R, Perry, P, etal. Efficacy of aripiprazole-intramuscular-depot for the long-term maintenance treatment of schizophrenia. Paper presented at: American Psychiatric Association Annual Meeting 2012; Philadelphia, PA.CrossRefGoogle Scholar
58.Kane, JM, Sanchez, R, Perry, PP, etal. Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a 52-week, multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012; 73(5): 617–624.CrossRefGoogle ScholarPubMed
59.Peng, X, Ascher-Svanum, H, Faries, D, etal. Decline in hospitalization risk and health care cost after initiation of depot antipsychotics in the treatment of schizophrenia. Clinicoecon Outcomes Res. 2011; 3: 9–14.Google ScholarPubMed
60.Boonstra, G, van Haren, NE, Schnack, HG, etal. Brain volume changes after withdrawal of atypical antipsychotics in patients with first-episode schizophrenia. J Clin Psychopharmacol. 2011; 31(2): 146–153.CrossRefGoogle ScholarPubMed
61.Ho, BC, Andreasen, NC, Ziebell, S, Pierson, R, Magnotta, V. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry. 2011; 68(2): 128–137.CrossRefGoogle ScholarPubMed
62.Leung, M, Cheung, C, Yu, K, etal. Gray matter in first-episode schizophrenia before and after antipsychotic drug treatment. Anatomical likelihood estimation meta-analyses with sample size weighting. Schizophr Bull. 2011; 37(1): 199–211.CrossRefGoogle ScholarPubMed
63.Navari, S, Dazzan, P. Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol Med. 2009; 39(11): 1763–1777.CrossRefGoogle ScholarPubMed
64.Nielsen, MO, Rostrup, E, Wulff, S, etal. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia. Arch Gen Psychiatry. 2012: 1–10.Google ScholarPubMed
65.Shepherd, AM, Laurens, KR, Matheson, SL, Carr, VJ, Green, MJ. Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia. Neurosci Biobehav Rev. 2012; 36(4): 1342–1356.CrossRefGoogle ScholarPubMed
66.Li, M, Chen, Z, Deng, W, etal. Volume increases in putamen associated with positive symptom reduction in previously drug-naive schizophrenia after 6 weeks antipsychotic treatment. Psychol Med. 2012; 42(7): 1475–1483.CrossRefGoogle ScholarPubMed
67.Seeman, P. Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010; 4(1): 56–73.CrossRefGoogle ScholarPubMed
68.Remington, G, Mamo, D, Labelle, A, etal. A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone. Am J Psychiatry. 2006; 163(3): 396–401.CrossRefGoogle ScholarPubMed
69.Remington, G, Kapur, S. Antipsychotic dosing: how much but also how often? Schizophr Bull. 2010; 36(5): 900–903.CrossRefGoogle ScholarPubMed
70.Bushe, C, Taylor, M, Haukka, J. Mortality in schizophrenia. J Psychopharmacol. 2012; 26(9): 1285.CrossRefGoogle ScholarPubMed