Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients’ awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women) treated with clozapine and 23 patients (16 men and 7 women) treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD). Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds. 1. Introduction Schizophrenia is a serious and disabling mental disorder usually associated with a decline in social and occupational functioning, and deficits in communication, control of behavior, the ability to feel pleasure, will, and initiative. The disease affects approximately 1% of the world’s population, or around 1–12 adults in every 1,000, mostly in the 15–35 year-old group [1–3]. Yearly incidence is 16–40 cases per 100,000 according to the ICD-9 criteria and 7–14 cases per 100,000 using more restrictive criteria [4, 5]. The risk of developing schizophrenia during a lifetime is around 0.7% (95% confidence interval (CI): 0.3%–2.0%) . The longitudinal course of schizophrenia is characterized by recurrent episodes of illness, periods of complete or partial remission, and often chronicity. Schizophrenia is linked to functional and social disability, it impacts the patients’ ability to engage in productive work and social relationships, and it is associated with a reduced life expectancy as a result of accidents, high comorbidity with medical conditions, and suicide [6–17]. Furthermore, depression in schizophrenic
A. Jablensky, N. Sartorius, G. Ernberg et al., “Schizophrenia manifestations, incidence and course in different cultures. A World Health Organization ten-country study,” Psychological Medicine, vol. 22, no. 20, pp. 1–97, 1992.
M. T. Tsuang and R. F. Woolson, “Excess mortality in schizophrenia and affective disorders. Do suicides and accidental deaths solely account for this excess?” Archives of General Psychiatry, vol. 35, no. 10, pp. 1181–1185, 1978.
M. T. Tsuang, R. F. Woolson, and J. A. Fleming, “Premature deaths in schizophrenia and affective disorders. An analysis of survival curves and variables affecting the shortened survival,” Archives of General Psychiatry, vol. 37, no. 9, pp. 979–983, 1980.
D. A. Casey, M. Rodriguez, C. Northcott, G. Vickar, and L. Shihabuddin, “Schizophrenia: medical illness, mortality, and aging,” International Journal of Psychiatry in Medicine, vol. 41, pp. 245–251, 2011.
M. Shepherd, D. Watt, I. Falloon, and N. Smeeton, “The natural history of schizophrenia: a five-year follow-up study of outcome and prediction in a representative sample of schizophrenics,” Psychological Medicine, vol. 19, no. 15, pp. 1–46, 1989.
Y. Conwell, P. R. Duberstein, C. Cox, J. H. Herrmann, N. T. Forbes, and E. D. Caine, “Relationships of age and axis I diagnoses in victims of completed suicide: a psychological autopsy study,” The American Journal of Psychiatry, vol. 153, no. 8, pp. 1001–1008, 1996.
J. H. Kim, J. H. Ann, and M. J. Kim, “Relationship between improvements of subjective well-being and depressive symptoms during acute treatment of schizophrenia with atypical antipsychotics,” Journal of Clinical Pharmacy and Therapeutics, vol. 36, no. 2, pp. 172–178, 2011.
J. Bobes, A. Ciudad, E. álvarez, L. San, P. Polavieja, and I. Gilaberte, “Recovery from schizophrenia: results from a 1-year follow-up observational study of patients in symptomatic remission,” Schizophrenia Research, vol. 115, no. 1, pp. 58–66, 2009.
G. D. Tollefson and S. W. Andersen, “Should we consider mood disturbance in schizophrenia as an important determinant of quality of life?” The Journal of Clinical Psychiatry, vol. 60, no. 5, pp. 23–30, 1999.
K. Sim, R. Mahendran, S. G. Siris, S. Heckers, and S. A. Chong, “Subjective quality of life in first episode schizophrenia spectrum disorders with comorbid depression,” Psychiatry Research, vol. 129, no. 2, pp. 141–147, 2004.
J. M. Narvaez, E. W. Twamley, C. L. McKibbin, R. K. Heaton, and T. L. Patterson, “Subjective and objective quality of life in schizophrenia,” Schizophrenia Research, vol. 98, no. 1–3, pp. 201–208, 2008.
R. Dutta, R. M. Murray, M. Hotopf, J. Allardyce, P. B. Jones, and J. Boydell, “Reassessing the long-term risk of suicide after a first episode of psychosis,” Archives of General Psychiatry, vol. 67, no. 12, pp. 1230–1237, 2010.
T. C. Manschreck, D. A. Redmond, S. F. Candela, and B. A. Maher, “Effects of clozapine on psychiatric symptoms, cognition, and functional outcome in schizophrenia,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 11, no. 4, pp. 481–489, 1999.
M. Bourin, B. Guitton, E. Dailly, P. Hery, and P. Jolliet, “A follow-up study of a population of schizophrenic patients treated with clozapine,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol. 25, no. 8, pp. 1481–1495, 2001.
J. A. Lieberman, G. Tollefson, M. Tohen et al., “Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol,” The American Journal of Psychiatry, vol. 160, no. 8, pp. 1396–404, 2003.
National Collaborating Centre for Mental Health, The NICE Guideline on Core Interventions in the Treatment and Management of Schizophrenia in Adults in Primary and Secondary Care, The British Psychological Society and the Royal College of Psychiatrists, London, UK, 2010.
M. Dossenbach, C. Arango-Dávila, H. S. Ibarra et al., “Response and relapse in patients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol: 12-month follow-up of the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study,” The Journal of Clinical Psychiatry, vol. 66, no. 8, pp. 1021–1030, 2005.
M. Dossenbach, A. Erol, M. E. M. Kessaci et al., “Effectiveness of antipsychotic treatments for schizophrenia: interim 6-month analysis from a prospective observational study (IC-SOHO) comparing olanzapine, quetiapine, risperidone, and haloperidol,” The Journal of Clinical Psychiatry, vol. 65, no. 3, pp. 312–321, 2004.
D. Novick, J. M. Haro, D. Suarez, E. Vieta, and D. Naber, “Recovery in the outpatient setting: 36-month results from the Schizophrenia Outpatients Health Outcomes (SOHO) study,” Schizophrenia Research, vol. 108, no. 1–3, pp. 223–230, 2009.
J. Geddes, N. Freemantle, P. Harrison, and P. Bebbington, “Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis,” British Medical Journal, vol. 321, no. 7273, pp. 1371–1376, 2000.
S. Leucht, G. Pitschel-Walz, D. Abraham, and W. Kissling, “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,” Schizophrenia Research, vol. 35, no. 1, pp. 51–68, 1999.
M. Riedel, N. Müller, M. Stradding, I. Spellmann, E. Severus, and H. J. M？ller, “Quetiapine in the treatment of schizophrenia and related disordes,” Neuropsychiatric Disease and Treatment, vol. 3, no. 2, pp. 219–235, 2007.
S. Leucht, C. Corves, D. Arbter, R. R. Engel, C. Li, and J. M. Davis, “Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis,” The Lancet, vol. 373, no. 9657, pp. 31–41, 2009.
D. Naber and M. Lambert, “Aripiprazole: a new atypical antipsychotic with a different pharmacological mechanism,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol. 28, no. 8, pp. 1213–1219, 2004.
S. A. M. K. Houthoofd, M. Morrens, and B. G. C. Sabbe, “Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder,” Clinical Therapeutics, vol. 30, no. 9, pp. 1565–1589, 2008.
L. P. Henry, G. P. Amminger, M. G. Harris et al., “The EPPIC follow-up study of first-episode psychosis: longer-term clinical and functional outcome 7 years after index admission,” The Journal of Clinical Psychiatry, vol. 71, no. 6, pp. 716–728, 2010.
A. Karow, S. Moritza, M. Lambert, D. Sch？ttle, and D. Naber, “Remitted but still impaired? Symptomatic versus functional remission in patients with schizophrenia,” European Psychiatry, vol. 27, no. 6, pp. 401–405, 2012.
B. J. Kinon, L. Chen, H. Ascher-Svanum et al., “Predicting response to atypical antipsychotics based on early response in the treatment of schizophrenia,” Schizophrenia Research, vol. 102, no. 1–3, pp. 230–240, 2008.
H. Ascher-Svanum, A. W. Nyhuis, D. E. Faries, B. J. Kinon, R. W. Baker, and A. Shekhar, “Clinical, functional, and economic ramifications of early nonresponse to antipsychotics in the naturalistic treatment of schizophrenia,” Schizophrenia Bulletin, vol. 34, no. 6, pp. 1163–1171, 2008.
S. Miyamoto, G. E. Duncan, C. E. Marx, and J. A. Lieberman, “Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs,” Molecular Psychiatry, vol. 10, no. 1, pp. 79–104, 2005.
J. A. Lieberman, “Effectiveness of antipsychotic drugs in patients with chronic schizophrenia: efficacy, safety and cost outcomes of CATIE and other trials,” The Journal of Clinical Psychiatry, vol. 68, no. 2, p. e04, 2007.
J. A. Lieberman, T. Scott Stroup, J. P. McEvoy et al., “Effectiveness of antipsychotic drugs in patients with chronic schizophrenia,” The New England Journal of Medicine, vol. 353, no. 12, pp. 1209–1223, 2005.
J. M. Haro, D. Suarez, D. Novick, J. Brown, J. Usall, and D. Naber, “Three-year antipsychotic effectiveness in the outpatient care of schizophrenia: observational versus randomized studies results,” European Neuropsychopharmacology, vol. 17, no. 4, pp. 235–244, 2007.
G. B. Cuyún Carter, D. R. Milton, H. Ascher-Svanum, and D. E. Faries, “Sustained favorable long-term outcome in the treatment of schizophrenia: a 3-year prospective observational study,” BMC Psychiatry, vol. 11, p. 143, 2011.
A. Farahani and C. U. Correll, “Are antipsychotics or antidepressants needed for psychotic depression? A systematic review and meta-analysis of trials comparing antidepressant or antipsychotic monotherapy with combination treatment,” The Journal of Clinical Psychiatry, vol. 73, pp. 486–496, 2012.
G. D. Tollefson, T. M. Sanger, Y. Lu, and M. E. Thieme, “Depressive signs and symptoms in schizophrenia: a prospective blinded trial of olanzapine and haloperidol,” Archives of General Psychiatry, vol. 55, no. 3, pp. 250–258, 1998.
G. D. Tollefson, T. M. Sanger, C. M. Beasley, and P. V. Tran, “A double-blind, controlled comparison of the novel antipsychotic olanzapine versus haloperidol or placebo on anxious and depressive symptoms accompanying schizophrenia,” Biological Psychiatry, vol. 43, no. 11, pp. 803–810, 1998.
M. C. Mauri, D. Moliterno, M. Rossattini, and A. Colasanti, “Depression in schizophrenia: comparison of first- and second-generation antipsychotic drugs,” Schizophrenia Research, vol. 99, no. 1–3, pp. 7–12, 2008.
J. H. Kim, J. H. Ann, and J. Lee, “Insight change and its relationship to subjective well-being during acute atypical antipsychotic treatment in schizophrenia,” Journal of Clinical Pharmacy and Therapeutics, vol. 36, pp. 687–694, 2011.