International Journal of Psychiatry in Clinical Practice

ISSN: 1365-1501 (Print) 1471-1788 (Online) Journal homepage: http://www.tandfonline.com/loi/ijpc20

Efficacy and tolerability of quetiapine in patients with schizophrenia switched from other antipsychotics A De Nayer, E Windhager, Irmansyah, I Larmo, B Lindenbauer, H Rittmannsberger, T Platz, Am Jones, Jl Whiteford & Ca Altman To cite this article: A De Nayer, E Windhager, Irmansyah, I Larmo, B Lindenbauer, H Rittmannsberger, T Platz, Am Jones, Jl Whiteford & Ca Altman (2003) Efficacy and tolerability of quetiapine in patients with schizophrenia switched from other antipsychotics, International Journal of Psychiatry in Clinical Practice, 7:1, 59-66 To link to this article: http://dx.doi.org/10.1080/13651500310001095

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# 2003 Taylor & Francis

International Journal of Psychiatry in Clinical Practice 2003

Volume 7

59

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Efficacy and tolerability of quetiapine in patients with schizophrenia switched from other antipsychotics A DE NAYER1, E WINDHAGER2, IRMANSYAH3, I LARMO4, B LINDENBAUER5, H RITTMANNSBERGER5, T PLATZ6, AM JONES7, JL WHITEFORD7 AND CA ALTMAN8, ON BEHALF OF THE SPECTRUM STUDY GROUP 1

Hoˆpital Ste-The´re`se, Belgium; 2Psychiatrische Klinik Wels, Austria; 3Department of Psychiatry, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; 4Keskinen Terveyskeskus, Auroran Psykiatrinen Osasto, Helsingin kaupunki, Finland; 5O. O¨. Landesnervenklinik Wagner-Jauregg, Linz, Austria; 6A. O¨. Landes KH Klagenfurt, Austria; 7AstraZeneca, Alderley Park, Macclesfield, UK; 8AstraZeneca Pharmaceuticals, Wilmington, Delaware, USA

The Seroquel Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) study assessed the efficacy and tolerability of quetiapine (SeroquelTM) in patients with schizophrenia switched from treatments providing suboptimal outcomes. OBJECTIVE:

This was an international, open-label, non-comparative study, designed with titration to 400 mg/day quetiapine over 7 days, then flexible dosing (300 750 mg/day) for 11 weeks. Efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS); Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores; and the Calgary Depression Scale for Schizophrenia (CDSS). Clinical benefit and tolerability were also assessed. METHODS:



/

The mean modal dose of quetiapine was 505 mg/day; 509 patients switched to quetiapine from olanzapine (13%), risperidone (11%), conventional antipsychotics (37%) and combinations of antipsychotics (28%), amongst others. Significant decreases in CGI Severity of Illness and PANSS scores and a significant improvement in CDSS score resulted from the switch (all PB 0.001 versus baseline). There were significant reductions in extrapyramidal symptoms (EPS) on the Simpson Angus Scale (SAS) and Barnes Akathisia Scale (BAS) (both PB 0.001 versus baseline) and a low incidence of EPS-related adverse events (4.7%). RESULTS:

/



/

Correspondence Address Dr Andre´ De Nayer, Hoˆpital Ste-The´re`se, Rue Trieu Kaisin 134, 6061 Montignies/Sambre, Belgium Tel: /(32) 712 39275 Fax: /(32) 712 39286 E-mail: [email protected]

Received 29 January 2003; accepted for publication 6 February 2003

/

CONCLUSION: Results indicate that switching to quetiapine was clinically beneficial for patients with poor efficacy or intolerable side effects on their previous antipsychotic medication. (Int J Psych Clin Pract 2003 7: 59 66) /

Keywords schizophrenia atypical antipsychotic tolerability

INTRODUCTION

P

reviously, the primary focus in treating schizophrenia was on controlling positive symptoms. However, there has been a shift in the approach to schizophrenia treatment, with more comprehensive options now aiming to provide relief in all symptom domains, improve compliance and prevent relapse, reduce side effects, and, ultimately, improve functional outcomes.1 The introduction of atypical antipsychotics represented a breakthrough in the treatment of schizophrenia as these drugs cause significantly fewer

quetiapine efficacy

extrapyramidal symptoms (EPS) than conventional agents and are more effective in treating both negative and cognitive symptoms.1,2 However, there are differences in the side-effect profiles of the various atypical antipsychotics currently in use which should be considered when therapy decisions are made.2,3 Patients with schizophrenia can exhibit symptoms that are completely refractory to or are only partially controlled by their antipsychotic medication.4,5 In addition, poor tolerability of antipsychotics, evidenced by EPS and other side effects, can impact upon patients’ quality of life and reduce

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compliance.6,7 Treatment of patients with suboptimal outcomes on their existing medication can be problematic, but there is evidence that they may benefit from switching to a different antipsychotic.8  10 Indications for changing medication in schizophrenia include: persistent positive symptoms, persistent negative symptoms, relapse despite compliance, EPS, tardive dyskinesia, agranulocytosis, elevated prolactin levels, weight gain or other side effects that cause significant distress.5,10 Several factors must be taken into account when a patient switches from one antipsychotic to another, such as withdrawal symptoms on discontinuation of the previous antipsychotic, risk of both medications being given at subtherapeutic doses during any cross-titration phase, compliance problems or medication errors during the switching period, and an increased risk of side effects during any period of concomitant treatment with both drugs.5,11 A switching strategy that minimizes these risks is essential to a successful change from one antipsychotic treatment to another.10,12 The atypical antipsychotic quetiapine (SeroquelTM) has demonstrable efficacy against the positive, negative, affective and cognitive symptoms of schizophrenia.13  15 Quetiapine is well tolerated, with incidence of EPS no greater than with placebo and an absence of sustained prolactin elevation, across the entire dose range, and a minimal long-term effect on weight.13  17 Emsley et al8 have shown that patients with a history of partial response to conventional antipsychotics can benefit from treatment with quetiapine and a recent review has concluded that switching to quetiapine can be achieved without exacerbating patients’ symptoms.12 This paper presents results of the Seroquel Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) study, in which the efficacy, tolerability and clinical benefit of quetiapine were assessed in patients switched to quetiapine due to an inadequate response to, or intolerance of, their previous antipsychotic medication.

pine in the month before study entry; previous non-response to clozapine; a history of noncompliance; a known arrhythmia or QTc ]/500 ms; a known sensitivity to quetiapine; or any of the contraindications detailed in the prescribing information. Patients could be withdrawn from the study for any of the following reasons: treatment noncompliance, protocol deviation, withdrawal of informed consent, lack of efficacy or deterioration in condition, loss to follow-up, or the occurrence of an adverse event (AE).

METHODS

EFFICACY ASSESSMENTS

PATIENTS

The primary endpoint of this study was change in the Index of Clinical Benefit (ICB) from baseline to Week 12. The ICB is derived from the Clinical Global Impression (CGI) efficacy index and is a useful combined measure of both efficacy and side effects. Patients’ scores on the ICB were determined by recording therapeutic effect as follows: marked (complete or nearly complete remission of all symptoms); moderate (partial remission of all symptoms); minimal (does not alter status of care of subject); or none. Side effects were recorded as: none; mild (do not significantly interfere with subject’s functioning); moderate (interfere with subject’s functioning to a moderate degree); or severe (significant interference with subject’s functioning). The ICB is a novel scale: its development and full data obtained using it will be the subject of a separate publication (manuscript in development). This report focuses on more widely recognized measures, which were the secondary endpoints assessing efficacy. These

Male or female patients, aged 18/65 years, with a classification of schizophrenia according to the DSM-IV diagnostic criteria (for any of the subtypes: catatonic, disorganized, paranoid or undifferentiated) were eligible for inclusion in the study. In addition, all patients were required to have shown poor tolerance of, or inadequate response (persistent aggression/hostility, cognitive impairment, negative, positive or general psychopathology symptoms) to, their previous antipsychotic medication. Exclusion criteria were: patients who were pregnant, lactating or at risk of pregnancy; participation in any drug trial or compassionate use programme within 4 weeks of study initiation; evidence of chronic and/or severe disease (e.g. renal or hepatic impairment or cancer); treatment with quetiapine immediately prior to study entry or with cloza-

STUDY DESIGN

AND

TREATMENT

This was an international, multicentre, non-comparative, open-label study conducted in 85 centres across 13 countries. The study assessed the efficacy, safety and tolerability of quetiapine in patients switched from other antipsychotics. A total of 509 patients showing poor tolerance of, or inadequate response to, their previous antipsychotic therapy were recruited to the study. The study design consisted of a 7-day cross-titration period, followed by an 11-week monotherapy phase during which quetiapine could be flexibly dosed. On Days 1 /3, previous antipsychotic medication was to be maintained at the original dose(s), then reduced to 50% of the dose(s) for Days 4 /7 and discontinued on Day 8. Concomitantly, quetiapine was to be introduced at a dose of 50 mg on Day 1, followed by 100, 200 and 300 mg on Days 2, 3 and 4, respectively; on Days 5 /8, 400 mg of quetiapine were to be given. From Day 9 until the end of the study, quetiapine could be dosed between 300 and 750 mg/day at the discretion of the investigator. Depot antipsychotic medication had to be withdrawn at least one dosing interval prior to the study. Antidepressant treatment that had been in place for a minimum of 4 weeks could be continued during the study, but without any alteration of dosage. Prior anticholinergic medication was encouraged to be withdrawn by Week 6 of the study. There were no other restrictions on concomitant medication.

Switching to quetiapine: efficacy and tolerability

included change from baseline to Week 12 in: Positive and Negative Syndrome Scale (PANSS) score; CGI Severity of Illness score; CGI Global Improvement score; and the Calgary Depression Scale for Schizophrenia (CDSS). Assessments of scores on each of these scales were made on Day 1, and at Weeks 6 and 12.

Table 1 Patient demographics

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TOLERABILITY ASSESSMENTS Tolerability of quetiapine during the study was assessed using the Simpson /Angus Scale (SAS), the Barnes Akathisia Scale (BAS), body mass index (BMI) and use of anticholinergic medication. AEs, reported by the patient or observed by the investigator, were documented for each patient throughout the study and during a 7-day follow-up period.

STATISTICAL ANALYSIS As there was no historical estimate of the proportion of patients showing clinical benefit after switching to quetiapine, the sample size (385 patients) was chosen to estimate the true proportion with a 95% confidence interval (CI) of 9/5%. This sample size estimate was increased to a total of 500 patients to compensate for a possible high degree of patient drop-out which has been seen in previous trials in patients with schizophrenia. The analysis of efficacy endpoints was conducted on the intention-to-treat population, consisting of all patients with data for ]/1 post-baseline visit (n/486). Analyses were carried out using the last value carried forward (LVCF) approach and, for a number of variables, analyses were also performed on observed cases at Weeks 6 and 12. Statistical significance was determined using analysis of covariance for the least-square mean (LSM) change from baseline. In addition, 95% CIs were calculated. Assessment of tolerability and safety endpoints was conducted on all patients receiving ]/1 dose of quetiapine during the study (safety population, n /506). As for efficacy endpoints, a LVCF approach was used to analyse SAS and BAS scores and analysis of covariance of the LSM change from baseline was used to determine statistical significance.

RESULTS PATIENTS A total of 509 patients intolerant of, or with an inadequate response to, their existing antipsychotic medication were recruited to the study. Of these patients, 354 (69.5%) switched to quetiapine due to inadequate response and 151 (29.7%) switched due to intolerance of their previous antipsychotic; the reason for switching was not recorded for the remaining four patients (Table 1). Patients’ mean age was 35 years and there were more male than female patients in the study (290 and 219, respectively), a common feature of

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No. patients recruited Male/female, n (%) Mean age (range), years Mean (SD) time since first diagnosis, years Mean weight (SD), kg Mean BMI (SD), kg/m2

509 290/219 (57/43) 35 (17 /68)a 8.7 (9.1) 72.4 (17.7) 25.87 (5.86)

Reason for switching, n (%) Inadequate response Intolerance Not recorded

354 (69.5) 151 (29.7) 4 (0.8)

Previous antipsychotic medication, n (%) Olanzapine monotherapy Risperidone monotherapy Any typical monotherapy Any combination of antipsychotics Low-dose haloperidol ( 5/10 mg/day)b Other

66 (13.0) 55 (10.8) 186 (36.5) 142 (27.9) 43 (8.4) 60 (11.8)

Dose of previous monotherapy antipsychotic, mg/day (range ) Olanzapine 18.1 (2.5 /200) Risperidone 4.4 (1 /12) Low-dose haloperidol 6.2 (1 /10) Response to previous antipsychotic, n (%) Complete Partial Treatment resistant Not recorded

42 (8.3) 399 (78.4) 59 (11.6) 9 (1.8)

a

Two patients outside the eligible age range were recruited to the study but were included in the safety and ITT populations. Written informed consent for the 17-year-old patient was provided by a parent. b The low-dose haloperidol group of patients are a subset of those previously receiving any typical monotherapy.

studies such as this. The majority of patients (78.4%) were classified by the investigators as partial responders to their previous medication. The most common previous treatment regimen providing a suboptimal outcome was any typical monotherapy (36.5% of patients), followed by a combination of typical and/or atypical antipsychotics (27.9%), olanzapine monotherapy (13.0%) and risperidone monotherapy (10.8%) (Table 1). A total of 365 patients (71.7%) completed the study and the mean duration of treatment with quetiapine was 9.6 weeks. The reasons for patients leaving the study were: AEs (5.9%), withdrawal of informed consent (5.1%), lack of efficacy/condition deteriorated (4.9%), protocol noncompliance (4.7%), patient lost to follow-up (4.3%), and other (3.3%).

TREATMENT This study was designed for patients to be switched to quetiapine over a 7-day period, followed by an 11-week period of flexible dosing with quetiapine 300 /750 mg/day. The mean modal dose of quetiapine was 505 mg/day; this

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measure was chosen as it most closely reflects the dose used by patients following the initial titration period. There were no apparent differences in the mean modal dose of quetiapine between subpopulations of patients defined by previous antipsychotic treatment.

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EFFICACY For the primary efficacy endpoint of change in the ICB at Week 12, a response was defined as a decrease of ]/1 points in the ICB, i.e. an improvement in therapeutic effect (e.g. from minimal to moderate) or a reduction in side effects (e.g. from moderate to mild) or both. There was a response in 69% of patients who switched to quetiapine (95% CI 65%, 73%). These data indicate that a major proportion of those switching to quetiapine gained clinical benefit. Analysis of the secondary endpoints relating to efficacy showed that improvements in different symptoms occurred. Switching to quetiapine resulted in significant decreases in PANSS total, positive subscale, negative subscale and general psychopathology scores (all P B/0.001, baseline to Week 12 [LVCF]) (Figure 1). Of those patients who had a PANSS total score ]/60 at baseline, 74% and 49% showed a response of ]/20% and ]/30% decrease in score, respectively. Quetiapine provided significant improvement in symptoms, even in those patients switching due to reasons other than lack of efficacy. Analysis of the PANSS total score for patients grouped according to their reason for switching shows significant improvements in all categories (Table 2). Overall, there was a significant improvement in PANSS total score, from baseline to Week 12 (LVCF), both for those patients who switched due to inadequate response (LSM change /25.3, baseline score 94.2; P B/0.001) and for those who switched due to intolerance (LSM change /19.3, baseline score 75.3; P B/0.001). Furthermore, significant improvement in symptoms on switching to quetiapine was observed irrespective of the medication patients had received previously. The PANSS total score for patients subdivided according to prior antipsychotic treatment improved significantly in all categories (all P B/0.001) (Figure 2). In

Figure 1 Least-square mean (LSM) change from baseline to Week 12 (LVCF) in PANSS total and subscores (ITT population). ***P B/0.001 versus baseline. $Mean score at baseline.

particular, patients who were inadequately treated by the atypical antipsychotics olanzapine and risperidone had a significant decrease in PANSS total score when switched to quetiapine (LSM change /15.4 and /18.5 at Week 12 [LVCF], respectively; both P B/0.001). Patients’ severity of illness was significantly reduced by the end of the study period. Switching to quetiapine resulted in a significant decrease in CGI Severity of Illness score by Week 12 (P B/0.001) (Figure 3). Significant reduction in this score was also evident in each group of patients classified by their prior therapy (P /0.003 for patients switching from olanzapine and P B/0.001 for those switching from other regimens). Moreover, a response in CGI Severity of Illness score, as defined by a score of 1, 2 or 3, was observed at Week 12 (LVCF) in 59.9% of patients switched to quetiapine (95% CI 54%, 63%). In addition, the CGI Global Improvement score at Week 6 was 2.6 and improved further to 2.2 by Week 12 (Figure 3). Depressive symptoms were also significantly improved in patients switching to quetiapine. Patients were classed as depressed on entry to the study if they had a CDSS score /6; within this group, the mean CDSS score fell below 6 within 6 weeks of switching to quetiapine (Figure 4). At Week 12 (LVCF), both those patients with and those without clinically significant depressive symptoms at baseline had a significant reduction in CDSS score, although the change was greater in those initially classed as depressed (P B/0.001) than those not depressed (P /0.002) (Figure 4).

TOLERABILITY Secondary endpoints relating to tolerability included assessments of parkinsonian symptoms (SAS scale) and akathisia (BAS scale). There was a significant reduction in SAS score by Week 12 (LVCF) after the switch to quetiapine (P B/0.001) (Figure 5). Specifically, analysis according to previous medication showed that the subgroups of patients switching from olanzapine or risperidone had a significant reduction in SAS score (both P B/0.001) (Figure 5). A significant reduction in BAS score also occurred in the total population (P B/0.001), although the baseline BAS score for this population was low (0.6). The reduction in EPS occurred irrespective of reason for switching medication; both those patients switching due to intolerance and those switching due to inadequate response had significant decreases in SAS and BAS scores at Week 12 (LVCF) (both P B/0.001). There was also a statistically significant reduction in the number of patients taking anticholinergic medication by Week 12 of the study (P B/0.001). There was a low incidence of AEs relating to EPS, which were reported in only 4.7% of the population. The most frequent EPS-related AEs were extrapyramidal syndrome (nine patients) and akathisia (eight patients) [Table 3]. Overall, the most common AE was somnolence (17% of the population) [Table 3], but this led to withdrawal from the study in only eight patients (1.6%). There was a minimal,

Switching to quetiapine: efficacy and tolerability

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Table 2 LSM change from baseline to Week 12 (LVCF) in PANSS total score analysed by individual reasons for switching

Reason for switching

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Aggression/hostility Cognitive impairment Negative symptoms Positive symptoms Affective symptoms General psychopathology EPS Weight gain

n 79 123 191 189 102 105 67 36

Baseline PANSS score

LSM change in PANSS total score from baseline to Week 12 (LVCF) /30.13 /27.43 /26.61 /22.76 /24.97 /25.95 /18.61 /15.23

105.6 97.5 96.8 96.7 97.5 96.8 76.4 73.8

P value B/0.001 B/0.001 B/0.001 B/0.001 B/0.001 B/0.001 B/0.001 B/0.001

NB some patients had more than one inadequate response reason. LSM /least square mean; LVCF /last value carried forward.

although statistically significant, increase in mean weight during the study (0.69 kg at Week 12 [LVCF]; P /0.003).

DISCUSSION

Figure 2 LSM change from baseline to Week 12 (LVCF) in PANSS total score analysed by previous medication (ITT population). ***P B/0.001 versus baseline. $Mean score at baseline.

Figure 3 Mean CGI scores at baseline, Week 6 and Week 12 (ITT population). ***P B/0.001 versus baseline, based on LSM change of / 1.38. Statistical significance was not calculated for scores at Week 6 or Global Improvement scores.

The results of this open-label study show that patients with schizophrenia who switched to quetiapine experienced significant improvements in positive, negative and general psychopathology symptoms and a significant reduction in severity of illness, as judged by overall clinical impression. In addition, quetiapine was effective in patients switched from either atypical or typical agents and those previously receiving a combination of antipsychotics. Moreover, patients derived benefit from switching to quetiapine irrespective of whether they switched due to intolerance of or an inadequate response to their previous medication. This study, performed under naturalistic conditions, illustrates a successful regimen for switching patients who have been unsuccessfully treated with other antipsychotics to quetiapine. While there is a consensus of opinion that patients with suboptimal outcomes on typical antipsychotics may benefit from switching to an atypical antipsychotic,2,5,8,11 there has been very little investigation of the potential for improvement for patients switching from one atypical antipsychotic to another. Most of the studies that have been undertaken address the question of switching from clozapine to another atypical antipsychotic and focus on patients with treatmentresistant schizophrenia18,19 or clozapine discontinuation symptoms.20 One further study examined switching from risperidone to olanzapine in patients non-responsive to or intolerant of treatment with risperidone. Of the 25 patients who completed the study, a response (an improvement of ]/20% in PANSS total score) was seen in 59% of participants.21 It is difficult to draw any comparisons between these few atypical antipsychotic switching studies. The study presented here is the first of a larger scale to address the question of switching between atypical antipsychotics in a

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Figure 4 Mean CDSS score at baseline, and Weeks 6, 12 and 12 (LVCF) analysed by depressive state on entry to study (ITT population). **P /0.002 versus baseline, based on LSM change of /0.62. ***P 5/0.001 versus baseline, based on LSM changes of /5.43, /6.57, /6.38, /0.57 and /0.83 (patients depressed at baseline, Weeks 6, 12 and 12 [LVCF] and patients not depressed at baseline, Weeks 6 and 12, respectively). CDSS scores 5/6 represent no clinical depression.

Table 3 Most frequent treatment-emergent adverse events (AEs; reported by ]/ 4% of patients) and EPS-related AEs n (%) Treatment-emergent AEs Somnolence Asthenia Dizziness Insomnia Constipation Dry mouth Weight gaina Headache

Figure 5 LSM change from baseline to Week 12 (LVCF) in SAS score (safety population). An SAS score of 10 represents no drug-induced parkinsonian symptoms. ***P B/0.001 versus baseline. $Mean score at baseline.

population of patients with a range of reasons for changing treatment. The data presented here support previous data from a double-blind, randomized trial of 288 patients with a history of partial response to conventional antipsychotics and partial or no response to 4 weeks’ treatment with fluphenazine, in which significantly more patients responded when switched to quetiapine compared with haloperidol (P B/0.05).8 There have been relatively few randomized, parallel-group clinical trials directly comparing the efficacy of atypical antipsychotics, and, whether double-blind22  24 or open-label,25 these have generally demonstrated only small differences between them. While interpretation of the data from this open-label, non-comparative trial must be limited by the nature of the trial’s design, it is clear that switching to quetiapine may provide significant improvement in symptoms and tolerabil-

EPS-related AEs Extrapyramidal syndrome Akathisia Tremor Hypertonia Dystonia a

84 27 24 24 23 22 22 21

(16.6) (5.3) (4.7) (4.7) (4.5) (4.3) (4.3) (4.2)

9 8 6 2 1

(1.8) (1.6) (1.2) (0.4) (0.2)

Defined as a complaint of weight gain.

ity for patients unsuccessfully treated with other atypical antipsychotics, including risperidone and olanzapine. The data described here indicate that quetiapine is clinically effective both in patients whose treatment was changed due to lack of efficacy and in those suffering intolerable side effects with their previous antipsychotic. Incidence of EPS with quetiapine is not significantly different to placebo across the entire dose range13 and it has been shown that patients with a partial response to conventional antipsychotics experience a reduction in EPS on switching to quetiapine.8 In this study, quetiapine provided significant improvements in EPS for patients switched from other

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Switching to quetiapine: efficacy and tolerability

antipsychotics due to intolerance, as well as in those patients with an inadequate response to their previous medication. In addition, reduction in EPS was observed even in patients switching from another atypical agent. Similarly, it has been shown previously that there is a lower incidence of EPS with quetiapine than with risperidone.25 Within a flexible dosing regimen of 300 /750 mg/day, the mean modal dose of quetiapine in this study was 505 mg/ day; this falls within the recommended prescribing range for patients with schizophrenia.26 The reductions in EPS and the low incidence of AEs during the study reinforce the excellent tolerability profile of quetiapine across the dose range.13  15,25 The minimal gain in weight observed in this study is consistent with the results of longer-term studies with quetiapine.17 In conclusion, the results from this study demonstrate that patients with schizophrenia who switched to quetiapine experienced improvements across a range of symptoms as well as a reduction in EPS and other side effects. The fact that these benefits were achieved with a mean modal dose of 505 mg/day (within a range that allowed up to 750 mg/day) supports the excellent tolerability profile of quetiapine across the dose range. These data highlight the successful use of quetiapine in patients unsuccessfully treated by other antipsychotics, whether typical or atypical. Furthermore, these results indicate that rapid switching to quetiapine was clinically beneficial for patients with poor efficacy or

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intolerable side effects on their previous antipsychotic medication.

ACKNOWLEDGEMENTS This research was supported by AstraZeneca Pharmaceuticals, Wilmington, Delaware, USA. The SPECTRUM study investigators were: L Adler; R Aguiar; D Baettig; L Baudewijns; G Beckers; J Boucek; H Calil; J Campos; C Cetti; W Chefarzt; D Chetty; B Daeng; E De Bleeker; A De Nayer; P de Sousa; A Diefenbacher; M Driessen; S Elsner; F Faltus; M Ferla; L Ferreira; M Ferro; C Gagiano; A Gamito; B Gro¨ssl; A Guimara˜es; J Hallak; K Ha¨nninen; G Hart; H-J Haug; M Haushofer; H Hellebuyck; M Herrera; J Horacek; E Iacoponi; Irmansyah; J Ja¨a¨skela¨inen; H Jacobs; P Ko¨nig; H Koponen; I Larmo; M Lourenc¸o; M Louza; N Lumingkewas; E Maura; O-P Mehtonen; F Mesotten; K Meyer; V Muchl; M Mu¨ller; D Nina; M Ortı´z; A Palha; A da Silva; W Pitchot; T Platz; P Ramjee; S Rataemane; I de Oliveira; M Renz; E Revez; H Rittmannsberger; C Robotti; L Roelens; A de la B Sa´nchez; D Sahagun; H Schubert; D Seabra; RG Sepulveda; I Shirakawa; Ph Snauwaert; Z Stankova; M Steyn; C Stuppa¨ck; ATronco; M Versiani; K Vukovic; E Windhager; J Wirtz; D Wynchank; M Xavier; R Zenner.

KEY POINTS . Patients with schizophrenia can exhibit symptoms that are not completely controlled by their antipsychotic medication; these patients may benefit from switching to an alternative antipsychotic . Patients with poor efficacy or intolerable side effects on their existing medication experienced improvement across a broad range of symptoms of schizophrenia when switched to quetiapine . The mean modal dose of quetiapine over the 12-week period of this study was 505 mg/day, which, coupled with a mean reduction in EPS (measured on the SAS and BAS scales) and a low incidence of EPS-related adverse events, reinforces the excellent tolerability profile of quetiapine across the dose range . This study illustrates a clear and successful regimen for rapid switching of patients with suboptimal outcomes on other antipsychotics to quetiapine

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Efficacy and tolerability of quetiapine in patients with schizophrenia switched from other antipsychotics.

OBJECTIVE The Seroquel Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) study assessed the efficacy and tolerability o...
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