Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia Hiroyoshi Takeuchi a,b,n, Takefumi Suzuki a,c, Gary Remington b,d, Koichiro Watanabe e, Masaru Mimura a, Hiroyuki Uchida a,f a
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8 c Department of Psychiatry, Inokashira Hospital, Tokyo, Japan d Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada e Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan f Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, ON, Canada b
art ic l e i nf o
a b s t r a c t
Article history: Received 6 November 2013 Received in revised form 24 February 2014 Accepted 6 April 2014
Sixty-one patients with schizophrenia stably treated with risperidone or olanzapine were randomly assigned to dose-reduction-by-half group or dose maintenance group. Subjective experiences were assessed at baseline and 28 weeks using three different self-rating scales. No significant differences in changes of subjective experiences were observed between the two groups. & 2014 Published by Elsevier Ireland Ltd.
Keywords: Antipsychotics Dose reduction Subjective experiences
1. Introduction
2. Methods
Recent neuroimaging studies indicate an association between excessive dopaminergic blockade with antipsychotics and negative subjective experiences (de Haan et al., 2003; Mizrahi et al., 2007). Accordingly, it is imperative that clinicians seek the lowest possible antipsychotic dose for long-term treatment to minimize negative subjective experiences. To our knowledge, however, no clinical trial to date has specifically evaluated the effects of atypical antipsychotic dose reduction on subjective experiences in patients with schizophrenia. Recently, we conducted a 28-week, randomized controlled trial to examine the clinical impact of risperidone and olanzapine dose reduction in stable patients with schizophrenia, and found that atypical antipsychotic dose reduction improved cognitive function and extrapyramidal symptoms in the absence of worsening psychopathology (Takeuchi et al., 2013). In this article, we specifically focused on subjective experiences following antipsychotic dose reduction.
2.1. Study design This study was an open-label, 28-week, randomized controlled trial to investigate the clinical impact of dose reduction of risperidone and olanzapine. Details of the study procedures have been described elsewhere (Takeuchi et al., 2013). Briefly, patients with schizopohrenia were included if they were receiving a stable dose of risperidone or olanzapine for at least three months which was considered a proxy for clinical stabilization, and in remission with regard to representative positive symptoms. Patients who met inclusion criteria were randomly assigned to either the reduction or maintenance groups. In the reduction group, risperidone or olanzapine was reduced by 25% at baseline and week four, followed by treatment with half the original dose over the next 24 weeks. In the maintenance group, patients received the same regimen for the entire 28 weeks. The trial protocol was approved by the institutional review board at each participating site. After full description of the study, all participants provided written informed consent. This trial was registered at UMIN Clinical Trials Registry (UMIN000001834).
2.2. Outcome measures
n
Corresponding author at: Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Tel.: þ 1 416 535 8501x30547; fax: þ 1 416 979 4292. E-mail address: [email protected] (H. Takeuchi).
In an effort to broadly capture subjective experiences, the following assessments were performed at baseline and 28 weeks: the Subjective Well-being under Neuroleptic treatment Short form (SWNS) (Naber, 1995), Drug Attitude Inventory (DAI-10) (Hogan et al., 1983), and Profile of Mood States – Short Form (POMS-SF) (Yokoyama, 2005). In addition, the EuroQol (The EuroQol Group, 1990) and Schedule for Assessment of Insight (SAI) (David, 1990) were administrated.
http://dx.doi.org/10.1016/j.psychres.2014.04.019 0165-1781/& 2014 Published by Elsevier Ireland Ltd.
Please cite this article as: Takeuchi, H., et al., Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.019i
H. Takeuchi et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
2
2.3. Statistical analyses Statistical analyses were performed on an intention-to-treat basis. Betweengroup differences in changes from baseline to endpoint for the assessment scales were tested by the Student's t-test using a last observation carried forward (LOCF) method. A two-tailed P-value of o0.05 was considered statistically significant for all tests. All statistical analyses were conducted using the IBM SPSS Statistics version 19 (IBM Corporation, Armonk, NY).
3. Results Sixty-one patients were enrolled and randomly assigned to the reduction group (N ¼ 31) or the maintenance group (N ¼30). Two and five patients prematurely withdrew from the study in the reduction and maintenance groups, respectively. Patients' demographic backgrounds did not differ between the two groups (Takeuchi et al., 2013). The mean doses at baseline and 28 weeks in the two groups are shown in Table 1. No significant differences in any baseline scores were found between the reduction and maintenance groups (Table 1). There were no significant differences in changes regarding the SWNS total, DAI-10 total, or POMS total mood disturbance score between the two groups. Similarly, changes in the EuroQol Health-Related Quality of Life and Visual Analogue Scale, and SAI total scores did not differ between the two groups (Table 1).
4. Discussion To our knowledge, this is the first study to systematically investigate the impact of atypical antipsychotic dose reduction on subjective experiences in stabilized patients with schizophrenia. Contrary to our expectations, subjective experiences did not improve after dose reduction, suggesting that atypical antipsychotic dose reduction may not specifically counteract negative subjective experiences. One possible explanation for this finding is that baseline dopamine D2 receptor blockade with risperidone or olanzapine in this study may have been already optimal in terms of subjective experiences (i.e. 60–70%) (de Haan et al., 2003). In fact, the estimated baseline D2 occupancy levels according to the formulation by Lataster et al. (2011) were 72% for risperidone and
65% for olanzapine. In addition, the lack of improvement may be, at least in part, explained by a ceiling effect as baseline subjective experiences were already good with the mean SWNS total score as high as over 70 (Lambert et al., 2009), which is compatible with the reported favorable effect of risperidone and olanzapine on subjective well-being (van Nimwegen et al., 2008). Nonetheless, irrespective of whether subjective experiences depend on antipsychotic doses, clinicians should be cognizant of the substantial benefits in minimizing antipsychotic exposure, for these agents, even the atypicals, can induce extrapyramidal symptoms as well as cognitive impairment (Takeuchi et al., 2013) in a dose-dependent fashion. There are limitations that warrant comment. First, the openlabel design could have biased results. Second, the sample size was relatively small, which may contribute to the non-significant differences found between the two groups (i.e., type II errors). Finally, the stability of remission in positive symptoms before enrollment was not evaluated in a longitudinal fashion. In conclusion, reducing the dose of risperidone or olanzapine by half did not result in improvement in subjective experiences in stabilized patients with schizophrenia. Our findings are specific to these two drugs at modest doses, and this preliminary contention should be tested further.
Conflicts of interest Dr. Takeuchi has received fellowship grants from the Japanese Society of Clinical Neuropsychopharmacology and Astellas Foundation for Research on Metabolic Disorders, speaker's honoraria from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKlein, Janssen Pharmaceutical, Meiji Seika Pharma, and Otsuka Pharmaceutical, and manuscript fees from Dainippon Sumitomo Pharma within the past 5 years. Dr. Suzuki has received fellowship grants from the Japanese Society of Clinical Neuropsychopharmacology, the Government of Canada Post-Doctoral Research Fellowships, Kanae Foundation, and Mochida Memorial Foundation, speaker's honoraria from Eli Lilly, Shionogi, and Yoshitomiyakuhin, Novartis Pharma, Meiji Seika Pharma, Astellas Pharmaceutical, and Otsuka Pharmaceutical, and manuscript fees from Dainippon Sumitomo Pharma, Elsevier Japan, Weily Japan, and Kyowa Hakko Kirin within the past 5 years.
Table 1 Doses of risperidone and olanzapine, subjective experiences, quality of life, and insight in reduction and maintenance groupsa. Reduction group (N ¼31)
Maintenance group (N¼ 30)
Baseline
Baseline
Change
Group difference in changeb
Change
Mean
S.D.
Mean
S.D.
Mean
S.D.
Mean
S.D.
P
Dose (mg/day) Risperidone Olanzapine
3.7 13.8
1.0 5.2
1.5 6.7
0.7 2.9
4.5 14.1
2.8 4.3
0.0 0.0
0.0 0.0
o 0.001 o 0.001
Subjective experiences SWNS total DAI-10 total POMS-SF total mood disturbance
74.8 4.3 15.0
12.4 4.2 13.6
3.9 0.8 1.0
10.1 3.5 12.6
78.4 4.7 12.5
16.3 4.7 17.1
3.8 0.3 4.6
7.6 3.4 8.0
0.953 0.215 0.194
Quality of life EuroQol-HRQOL EuroQol-VAS
0.825 70.7
0.227 13.7
0.008 1.1
0.178 12.1
0.864 76.5
0.189 18.5
0.006 1.5
0.122 16.3
0.718 0.927
Insight SAI total
13.8
4.2
0.7
4.7
13.4
3.5
0.6
5.3
0.993
Abbreviations: S.D.; standard deviation, SWNS; Subjective Well-being under Neuroleptic treatment Short form, DAI-10; Drug Attitude Inventory, POMS-SF; Profile of Mood States – Short Form, HRQOL; Health-Related Quality of Life, VAS; Visual Analogue Scale, SAI; Schedule for Assessment of Insight. a b
Last observation carried forward (LOCF) data. No significant differences in all baseline values between the two groups by Student's t-test.
Please cite this article as: Takeuchi, H., et al., Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.019i
H. Takeuchi et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Dr. Remington has received research support from Novartis, Medicure, and Neurocrine Bioscience, consultant fees from Roche, and speaker's fees from Novartis. He holds no commercial investments in any pharmaceutical company within the past 5 years. Dr. Watanabe has served on the advisory board of Dainippon Sumitomo Pharma, Eli Lilly, Janssen Pharmaceutical, Otsuka Pharmaceutical, and Tanabe Pharma, received grants from Dainippon Sumitomo Pharma, GlaxoSmithKline, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, and Pfizer Japan, and speaker's honoraria or manuscript fees from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Otsuka Pharmaceutical, Pfizer Japan, Shionogi, and Yoshitomiyakuhin within the past 5 years. Dr. Mimura has received grants or consultant fees from Astellas Pharma, GlaxoSmithKline, Eisai, and Meiji Seika Pharma, and speaker's honoraria from Astellas Pharma, Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji Seika Pharma, Otsuka Pharmaceutical, Pfizer Japan, and Yoshitomiyakuhin within the past 5 years. Dr. Uchida has received grants from Astellas Pharma, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji Seika Pharma, Mochida Pharmaceutical, Otsuka Pharmaceutical, Pfizer Japan, Shionogi, and Yoshitomiyakuhin, and speaker's honoraria from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Novartis Pharma, Otsuka Pharmaceutical, Shionogi, and Yoshitomiyakuhin within the past 5 years. Acknowledgments This study was supported by research funds from Inokashira Hospital and Research Group for Schizophrenia. The authors thank Drs. Y. Imasaka, Y. Kimura, S. Nakajima, J. Hirano, A. Nagata, Y. Fujita, M. Nishimoto, K. Funaki, H. Ataka, and T. Suzuki for their continuous keen support.
3
References David, A.S., 1990. Insight and psychosis. British Journal of Psychiatry 156, 798–808. de Haan, L., van Bruggen, M., Lavalaye, J., Booij, J., Dingemans, P.M., Linszen, D., 2003. Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. American Journal of Psychiatry 160, 303–309. The EuroQol Group., 1990. EuroQol—a new facility for the measurement of healthrelated quality of life. Health Policy 16, 199-208. Hogan, T.P., Awad, A.G., Eastwood, R., 1983. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychological Medicine 13, 177–183. Lambert, M., Schimmelmann, B.G., Schacht, A., Karow, A., Wagner, T., Wehmeier, P. M., Huber, C.G., Hundemer, H.P., Dittmann, R.W., Naber, D., 2009. Long-term patterns of subjective wellbeing in schizophrenia: cluster, predictors of cluster affiliation, and their relation to recovery criteria in 2842 patients followed over 3 years. Schizophrenia Research 107, 165–172. Lataster, J., van Os, J., de Haan, L., Thewissen, V., Bak, M., Lataster, T., Lardinois, M., Delespaul, P.A., Myin-Germeys, I, 2011. Emotional experience and estimates of D2 receptor occupancy in psychotic patients treated with haloperidol, risperidone, or olanzapine: an experience sampling study. Journal of Clinical Psychiatry 72, 1397–1404. Mizrahi, R., Rusjan, P., Agid, O., Graff, A., Mamo, D.C., Zipursky, R.B., Kapur, S., 2007. Adverse subjective experience with antipsychotics and its relationship to striatal and extrastriatal D2 receptors: a PET study in schizophrenia. American Journal of Psychiatry 164, 630–637. Naber, D., 1995. A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables. International Clinical Psychopharmacology 10 (3), 133–138. Takeuchi, H., Suzuki, T., Remington, G., Bies, R.R., Abe, T., Graff-Guerrero, A., Watanabe, K., Mimura, M., Uchida, H., 2013. Effects of risperidone and olanzapine dose reduction on cognitive function in stable patients with schizophrenia: an open-label, randomized, controlled, pilot study. Schizophrenia Bulletin 39, 993–998. van Nimwegen, L.J., de Haan, L., van Beveren, N.J., van der Helm, M., van den Brink, W., Linszen, D, 2008. Effect of olanzapine and risperidone on subjective wellbeing and craving for cannabis in patients with schizophrenia or related disorders: a double-blind randomized controlled trial. Canadian Journal of Psychiatry 53, 400–405. Yokoyama, K., 2005. Guide Book of POMS Short Form Japanese Version With Case Study. Kanekosyobou, Tokyo.
Please cite this article as: Takeuchi, H., et al., Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.019i
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia Hiroyoshi Takeuchi a,b,n, Takefumi Suzuki a,c, Gary Remington b,d, Koichiro Watanabe e, Masaru Mimura a, Hiroyuki Uchida a,f a
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8 c Department of Psychiatry, Inokashira Hospital, Tokyo, Japan d Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada e Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan f Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, ON, Canada b
art ic l e i nf o
a b s t r a c t
Article history: Received 6 November 2013 Received in revised form 24 February 2014 Accepted 6 April 2014
Sixty-one patients with schizophrenia stably treated with risperidone or olanzapine were randomly assigned to dose-reduction-by-half group or dose maintenance group. Subjective experiences were assessed at baseline and 28 weeks using three different self-rating scales. No significant differences in changes of subjective experiences were observed between the two groups. & 2014 Published by Elsevier Ireland Ltd.
Keywords: Antipsychotics Dose reduction Subjective experiences
1. Introduction
2. Methods
Recent neuroimaging studies indicate an association between excessive dopaminergic blockade with antipsychotics and negative subjective experiences (de Haan et al., 2003; Mizrahi et al., 2007). Accordingly, it is imperative that clinicians seek the lowest possible antipsychotic dose for long-term treatment to minimize negative subjective experiences. To our knowledge, however, no clinical trial to date has specifically evaluated the effects of atypical antipsychotic dose reduction on subjective experiences in patients with schizophrenia. Recently, we conducted a 28-week, randomized controlled trial to examine the clinical impact of risperidone and olanzapine dose reduction in stable patients with schizophrenia, and found that atypical antipsychotic dose reduction improved cognitive function and extrapyramidal symptoms in the absence of worsening psychopathology (Takeuchi et al., 2013). In this article, we specifically focused on subjective experiences following antipsychotic dose reduction.
2.1. Study design This study was an open-label, 28-week, randomized controlled trial to investigate the clinical impact of dose reduction of risperidone and olanzapine. Details of the study procedures have been described elsewhere (Takeuchi et al., 2013). Briefly, patients with schizopohrenia were included if they were receiving a stable dose of risperidone or olanzapine for at least three months which was considered a proxy for clinical stabilization, and in remission with regard to representative positive symptoms. Patients who met inclusion criteria were randomly assigned to either the reduction or maintenance groups. In the reduction group, risperidone or olanzapine was reduced by 25% at baseline and week four, followed by treatment with half the original dose over the next 24 weeks. In the maintenance group, patients received the same regimen for the entire 28 weeks. The trial protocol was approved by the institutional review board at each participating site. After full description of the study, all participants provided written informed consent. This trial was registered at UMIN Clinical Trials Registry (UMIN000001834).
2.2. Outcome measures
n
Corresponding author at: Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Tel.: þ 1 416 535 8501x30547; fax: þ 1 416 979 4292. E-mail address: [email protected] (H. Takeuchi).
In an effort to broadly capture subjective experiences, the following assessments were performed at baseline and 28 weeks: the Subjective Well-being under Neuroleptic treatment Short form (SWNS) (Naber, 1995), Drug Attitude Inventory (DAI-10) (Hogan et al., 1983), and Profile of Mood States – Short Form (POMS-SF) (Yokoyama, 2005). In addition, the EuroQol (The EuroQol Group, 1990) and Schedule for Assessment of Insight (SAI) (David, 1990) were administrated.
http://dx.doi.org/10.1016/j.psychres.2014.04.019 0165-1781/& 2014 Published by Elsevier Ireland Ltd.
Please cite this article as: Takeuchi, H., et al., Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.019i
H. Takeuchi et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
2
2.3. Statistical analyses Statistical analyses were performed on an intention-to-treat basis. Betweengroup differences in changes from baseline to endpoint for the assessment scales were tested by the Student's t-test using a last observation carried forward (LOCF) method. A two-tailed P-value of o0.05 was considered statistically significant for all tests. All statistical analyses were conducted using the IBM SPSS Statistics version 19 (IBM Corporation, Armonk, NY).
3. Results Sixty-one patients were enrolled and randomly assigned to the reduction group (N ¼ 31) or the maintenance group (N ¼30). Two and five patients prematurely withdrew from the study in the reduction and maintenance groups, respectively. Patients' demographic backgrounds did not differ between the two groups (Takeuchi et al., 2013). The mean doses at baseline and 28 weeks in the two groups are shown in Table 1. No significant differences in any baseline scores were found between the reduction and maintenance groups (Table 1). There were no significant differences in changes regarding the SWNS total, DAI-10 total, or POMS total mood disturbance score between the two groups. Similarly, changes in the EuroQol Health-Related Quality of Life and Visual Analogue Scale, and SAI total scores did not differ between the two groups (Table 1).
4. Discussion To our knowledge, this is the first study to systematically investigate the impact of atypical antipsychotic dose reduction on subjective experiences in stabilized patients with schizophrenia. Contrary to our expectations, subjective experiences did not improve after dose reduction, suggesting that atypical antipsychotic dose reduction may not specifically counteract negative subjective experiences. One possible explanation for this finding is that baseline dopamine D2 receptor blockade with risperidone or olanzapine in this study may have been already optimal in terms of subjective experiences (i.e. 60–70%) (de Haan et al., 2003). In fact, the estimated baseline D2 occupancy levels according to the formulation by Lataster et al. (2011) were 72% for risperidone and
65% for olanzapine. In addition, the lack of improvement may be, at least in part, explained by a ceiling effect as baseline subjective experiences were already good with the mean SWNS total score as high as over 70 (Lambert et al., 2009), which is compatible with the reported favorable effect of risperidone and olanzapine on subjective well-being (van Nimwegen et al., 2008). Nonetheless, irrespective of whether subjective experiences depend on antipsychotic doses, clinicians should be cognizant of the substantial benefits in minimizing antipsychotic exposure, for these agents, even the atypicals, can induce extrapyramidal symptoms as well as cognitive impairment (Takeuchi et al., 2013) in a dose-dependent fashion. There are limitations that warrant comment. First, the openlabel design could have biased results. Second, the sample size was relatively small, which may contribute to the non-significant differences found between the two groups (i.e., type II errors). Finally, the stability of remission in positive symptoms before enrollment was not evaluated in a longitudinal fashion. In conclusion, reducing the dose of risperidone or olanzapine by half did not result in improvement in subjective experiences in stabilized patients with schizophrenia. Our findings are specific to these two drugs at modest doses, and this preliminary contention should be tested further.
Conflicts of interest Dr. Takeuchi has received fellowship grants from the Japanese Society of Clinical Neuropsychopharmacology and Astellas Foundation for Research on Metabolic Disorders, speaker's honoraria from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKlein, Janssen Pharmaceutical, Meiji Seika Pharma, and Otsuka Pharmaceutical, and manuscript fees from Dainippon Sumitomo Pharma within the past 5 years. Dr. Suzuki has received fellowship grants from the Japanese Society of Clinical Neuropsychopharmacology, the Government of Canada Post-Doctoral Research Fellowships, Kanae Foundation, and Mochida Memorial Foundation, speaker's honoraria from Eli Lilly, Shionogi, and Yoshitomiyakuhin, Novartis Pharma, Meiji Seika Pharma, Astellas Pharmaceutical, and Otsuka Pharmaceutical, and manuscript fees from Dainippon Sumitomo Pharma, Elsevier Japan, Weily Japan, and Kyowa Hakko Kirin within the past 5 years.
Table 1 Doses of risperidone and olanzapine, subjective experiences, quality of life, and insight in reduction and maintenance groupsa. Reduction group (N ¼31)
Maintenance group (N¼ 30)
Baseline
Baseline
Change
Group difference in changeb
Change
Mean
S.D.
Mean
S.D.
Mean
S.D.
Mean
S.D.
P
Dose (mg/day) Risperidone Olanzapine
3.7 13.8
1.0 5.2
1.5 6.7
0.7 2.9
4.5 14.1
2.8 4.3
0.0 0.0
0.0 0.0
o 0.001 o 0.001
Subjective experiences SWNS total DAI-10 total POMS-SF total mood disturbance
74.8 4.3 15.0
12.4 4.2 13.6
3.9 0.8 1.0
10.1 3.5 12.6
78.4 4.7 12.5
16.3 4.7 17.1
3.8 0.3 4.6
7.6 3.4 8.0
0.953 0.215 0.194
Quality of life EuroQol-HRQOL EuroQol-VAS
0.825 70.7
0.227 13.7
0.008 1.1
0.178 12.1
0.864 76.5
0.189 18.5
0.006 1.5
0.122 16.3
0.718 0.927
Insight SAI total
13.8
4.2
0.7
4.7
13.4
3.5
0.6
5.3
0.993
Abbreviations: S.D.; standard deviation, SWNS; Subjective Well-being under Neuroleptic treatment Short form, DAI-10; Drug Attitude Inventory, POMS-SF; Profile of Mood States – Short Form, HRQOL; Health-Related Quality of Life, VAS; Visual Analogue Scale, SAI; Schedule for Assessment of Insight. a b
Last observation carried forward (LOCF) data. No significant differences in all baseline values between the two groups by Student's t-test.
Please cite this article as: Takeuchi, H., et al., Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.019i
H. Takeuchi et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Dr. Remington has received research support from Novartis, Medicure, and Neurocrine Bioscience, consultant fees from Roche, and speaker's fees from Novartis. He holds no commercial investments in any pharmaceutical company within the past 5 years. Dr. Watanabe has served on the advisory board of Dainippon Sumitomo Pharma, Eli Lilly, Janssen Pharmaceutical, Otsuka Pharmaceutical, and Tanabe Pharma, received grants from Dainippon Sumitomo Pharma, GlaxoSmithKline, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, and Pfizer Japan, and speaker's honoraria or manuscript fees from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Otsuka Pharmaceutical, Pfizer Japan, Shionogi, and Yoshitomiyakuhin within the past 5 years. Dr. Mimura has received grants or consultant fees from Astellas Pharma, GlaxoSmithKline, Eisai, and Meiji Seika Pharma, and speaker's honoraria from Astellas Pharma, Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji Seika Pharma, Otsuka Pharmaceutical, Pfizer Japan, and Yoshitomiyakuhin within the past 5 years. Dr. Uchida has received grants from Astellas Pharma, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji Seika Pharma, Mochida Pharmaceutical, Otsuka Pharmaceutical, Pfizer Japan, Shionogi, and Yoshitomiyakuhin, and speaker's honoraria from Dainippon Sumitomo Pharma, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Novartis Pharma, Otsuka Pharmaceutical, Shionogi, and Yoshitomiyakuhin within the past 5 years. Acknowledgments This study was supported by research funds from Inokashira Hospital and Research Group for Schizophrenia. The authors thank Drs. Y. Imasaka, Y. Kimura, S. Nakajima, J. Hirano, A. Nagata, Y. Fujita, M. Nishimoto, K. Funaki, H. Ataka, and T. Suzuki for their continuous keen support.
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Please cite this article as: Takeuchi, H., et al., Lack of effect of risperidone or olanzapine dose reduction on subjective experiences in stable patients with schizophrenia. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.019i
