Update on Atypical Antipsychotics in Schizophrenia

Views:
 
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

Update on Atypical Antipsychotics in Schizophrenia : 

Walid Sarhan F.R.C.Psych. Amman-Jordan The First International Congress of Jordanian Association of Psychiatrists 6-9 April 2010 3/20/2011 sarhan-AstraZeneca Update on Atypical Antipsychotics in Schizophrenia 1

Overview : 

Overview 3/20/2011 sarhan-AstraZeneca Schizophrenia is characterized by a progressive decline in patients’ functioning and relationship with the outside world The ultimate goal of long-term treatment is symptomatic relief, full remission and successful reintegration into society via functional recovery There remain significant barriers that can prevent these goals from being achieved 2

Features of schizophrenia : 

Features of schizophrenia 3/20/2011 sarhan-AstraZeneca Positive symptoms Delusions Hallucinations Disorganised speech Catatonia Social / occupational dysfunction Work Interpersonal relationships Self care Negative symptoms Affective flattening Alogia Avolition Anhedonia Social withdrawal Cognitive deficits Attention Memory Executive functions (eg abstraction) Comorbid substance abuse Mood symptoms Depression Hopelessness Suicidality Anxiety Agitation Hostility 3

Schizophrenia: an underestimated and disabling condition : 

Schizophrenia: an underestimated and disabling condition 3/20/2011 sarhan-AstraZeneca 4

Mortality and cardiovascular disease risk factors in schizophrenia : 

Mortality and cardiovascular disease risk factors in schizophrenia 3/20/2011 sarhan-AstraZeneca 40% increased risk of death from medical causes 20- to 30-year shorter lifespan, primarily due to cardiovascular disease 5

The importance of early diagnosisand treatment initiation : 

The importance of early diagnosisand treatment initiation 3/20/2011 sarhan-AstraZeneca Advantages of early treatment Patient challenges Improves likelihood of remission Reduces elapse risk Impacts positively on long-term morbidity Limits brain tissue loss High risk of relapse Adherence to treatment 6

Partial adherence: a primary treatmentchallenge in schizophrenia : 

Partial adherence: a primary treatmentchallenge in schizophrenia 3/20/2011 sarhan-AstraZeneca 7

Schizophrenia Why poor adherence is a major issue : 

Schizophrenia Why poor adherence is a major issue 3/20/2011 sarhan-AstraZeneca Denial of illness (anosognosia) Cognitive impairment – memory functions – executive (frontal) functions Negative symptoms – lack of initiative – lack of motivation Side effects of medications Dosing complexity of medications Poor therapeutic alliance Chaotic lifestyle with substance abuse Lack of family support Beliefs about the illness or treatment Partial adherence is HUMAN NATURE (even in people with chronic pain)! 8

Level and consistency of medication adherence in nonpsychiatric disorders : 

Level and consistency of medication adherence in nonpsychiatric disorders 3/20/2011 sarhan-AstraZeneca 9

Perceived degree of difficulty toachieve sufficient adherence : 

Perceived degree of difficulty toachieve sufficient adherence 3/20/2011 sarhan-AstraZeneca 10

Partial adherence is a major problemin patients with schizophrenia : 

Partial adherence is a major problemin patients with schizophrenia 3/20/2011 sarhan-AstraZeneca Begins within days of discharge and increases with time 11

Schizophrenia – a relapsing illness : 

Schizophrenia – a relapsing illness 3/20/2011 sarhan-AstraZeneca After 24 months, more than 50% of patients with new-onset schizophrenia relapse 80% relapse within 4 years – of these, 85% experience a second relapse Strongest predictor of relapse: antipsychotic discontinuation 12

Relapse rates in schizophrenia : 

Relapse rates in schizophrenia 3/20/2011 sarhan-AstraZeneca 13

Further consequences of inconsistentadherence in schizophrenia : 

Further consequences of inconsistentadherence in schizophrenia 3/20/2011 sarhan-AstraZeneca Medical Forensic Economic Biological Psychotic relapse and self neglect, more important residual symptoms Harm to self / others during relapse Rehospitalisation costs Neurotoxicity - progressive loss of grey matter with each psychotic relapse leads to further clinical and functional deterioration 14

Rate of grey matter loss in schizophrenia : 

Rate of grey matter loss in schizophrenia 3/20/2011 sarhan-AstraZeneca 15

Possible mechanisms of brain tissue loss in schizophrenia : 

Possible mechanisms of brain tissue loss in schizophrenia 3/20/2011 sarhan-AstraZeneca Apoptosis Inflammation Glutamate neurotoxicity Oxidative damage 16

Antipsychotics and neuroprotection : 

Antipsychotics and neuroprotection 3/20/2011 sarhan-AstraZeneca Unlike conventional antipsychotics, atypical antipsychotics have been shown to be neuroprotective Atypical antipsychotics can prevent progressive brain tissue loss associated with psychosis and stimulate neurite extension, neurogenesis and cell survival, and induce neurotropic factors 17

Effects of olanzapine or haloperidol on brainmorphology in first-episode psychosis : 

Effects of olanzapine or haloperidol on brainmorphology in first-episode psychosis 3/20/2011 sarhan-AstraZeneca 18

Atypical antipsychotics may provide neuroprotection byaugmenting NGF levels in patients with schizophrenia : 

Atypical antipsychotics may provide neuroprotection byaugmenting NGF levels in patients with schizophrenia 3/20/2011 sarhan-AstraZeneca 19

Challenges in schizophrenia : 

Challenges in schizophrenia 3/20/2011 sarhan-AstraZeneca Reducing mortality rates Promoting functional recovery Challenges Reducing the risk of relapse and associated brain tissue loss Ongoing need for novel treatments that offer additional advantages, eg neuroprotection Improving adherence to antipsychotic medication 20

The rationale for developing newformulations of antipsychotics : 

The rationale for developing newformulations of antipsychotics 3/20/2011 sarhan-AstraZeneca Improved efficacy Convenient dosing regimen Faster onset of action Better side-effect profile More treatment options All lead to improvement in Prognosis and outcome Adherence Overall satisfaction with treatment 21

Challenges in schizophrenia : 

Challenges in schizophrenia 3/20/2011 sarhan-AstraZeneca Reducing mortality rates Promoting functional recovery Challenges Reducing the risk of relapse and associated brain tissue loss Ongoing need for novel treatments that offer additional advantages, eg neuroprotection Improving adherence to antipsychotic medication Do we need more treatment options? YES !!! 22

Why is there a need for newformulations of atypical antipsychotics? : 

Why is there a need for newformulations of atypical antipsychotics? 3/20/2011 sarhan-AstraZeneca Nonadherence to medication in patients with schizophrenia is a significant concern – each patient is an individual – patients and doctors need choice New formulations provide a greater choice of treatment options 23

Adherence to medication improves witha less frequent dosing regimen : 

Adherence to medication improves witha less frequent dosing regimen 3/20/2011 sarhan-AstraZeneca 24

Medication choice and consentGiven the option, most patients prefer oral medications : 

Medication choice and consentGiven the option, most patients prefer oral medications 3/20/2011 sarhan-AstraZeneca 25

Partial adherence and hospitalization : 

Partial adherence and hospitalization 3/20/2011 sarhan-AstraZeneca 26

Medication choice and consentGiven the option, most patients prefer oral medications : 

Medication choice and consentGiven the option, most patients prefer oral medications 3/20/2011 sarhan-AstraZeneca 27

Route of medication received in the acute setting : 

Route of medication received in the acute setting 3/20/2011 sarhan-AstraZeneca 28

New formulations of atypical antipsychotics : 

New formulations of atypical antipsychotics 3/20/2011 sarhan-AstraZeneca In 2003, long-acting injectable Risperidone was approved by the FDA for the long-term treatment of schizophrenia IM formulations have been developed for Aripiprazole, Olanzapine and Ziprasidone Recently, new oral extended-release formulations of atypical antipsychotics have been developed – paliperidone ER: 9-OH-risperidone, metabolite of risperidone – Quetiapine XR: extended release Quetiapine fumarate 29

Paliperidone ER6-week study in acute schizophrenia : 

Paliperidone ER6-week study in acute schizophrenia 3/20/2011 sarhan-AstraZeneca 30

Clinical rationale for the developmentof Quetiapine XR : 

Clinical rationale for the developmentof Quetiapine XR 3/20/2011 sarhan-AstraZeneca Once-daily dosing Initiate therapy at higher doses Reach a therapeutic dose range earlier Provide patients with improved convenience of use Improve adherence 31

Seroquel XR delivers: : 

Seroquel XR delivers: 3/20/2011 sarhan-AstraZeneca Acute efficacy On the core symptoms of Schizophrenia Maintenance of efficacy Prevention of relapse Significantly reduced risk of relapse Trusted tolerability In the acute setting and over longer term treatment Ease of use Once daily dosing 2–3 day-dose escalation Effective dose range by Day 2 Clear target dose Same dose for initiation and maintenance 32

Clinical Rationale for Developmentof Seroquel XR : 

Clinical Rationale for Developmentof Seroquel XR To provide physicians and patients with enhanced convenience of use and potentially improve adherence by: Once daily dosing Simplifying dose initiation Initiating therapy at a higher dose Reaching therapeutic dose range earlier 3/20/2011 sarhan-AstraZeneca 33

Acute Efficacy Seroquel XR Studies in Schizophrenia : 

Acute Efficacy Seroquel XR Studies in Schizophrenia 3/20/2011 sarhan-AstraZeneca 34

Seroquel XR Studies in Schizophrenia : 

Seroquel XR Studies in Schizophrenia Seroquel XR has been approved for the treatment of Schizophrenia in some markets, and is currently under regulatory review in others – Please check local prescribing information before use 3/20/2011 sarhan-AstraZeneca 35

Quetiapine XRStudy 132: 6-week study in acute schizophrenia : 

Quetiapine XRStudy 132: 6-week study in acute schizophrenia 3/20/2011 sarhan-AstraZeneca Design: 6-week, double-blind, double-dummy, randomized, placebo-controlled study in acutely ill patients with schizophrenia Primary endpoint: mean change from baseline to Week 6 in PANSS total score Other efficacy assessments included: PANSS response, CGI-S, CGI-I Objective: to demonstrate superior efficacy of Quetiapine XR compared with placebo 36

Study 132: 6-week study in acute schizophrenia Dosing schedule : 

Study 132: 6-week study in acute schizophrenia Dosing schedule 3/20/2011 sarhan-AstraZeneca 37

Study 132: 6-week study in acute schizophreniaPANSS total score change from randomization to Day 42 : 

Study 132: 6-week study in acute schizophreniaPANSS total score change from randomization to Day 42 3/20/2011 sarhan-AstraZeneca 38

Study 132: 6-week study in acute schizophreniaPANSS response rate at Day 42 : 

Study 132: 6-week study in acute schizophreniaPANSS response rate at Day 42 3/20/2011 sarhan-AstraZeneca 39

Study 132: 6-week study in acute schizophreniaCGI Global Improvement: score ≤3 at Day 42 : 

Study 132: 6-week study in acute schizophreniaCGI Global Improvement: score ≤3 at Day 42 3/20/2011 sarhan-AstraZeneca 40

Study 132: 6-week study in acute schizophrenia Withdrawals from study : 

Study 132: 6-week study in acute schizophrenia Withdrawals from study 3/20/2011 sarhan-AstraZeneca 41

Quetiapine XRStudy 146: 6-week switching study : 

Quetiapine XRStudy 146: 6-week switching study 3/20/2011 sarhan-AstraZeneca Design: 6-week international, multicentre, double-blind, randomized, parallel group, double-dummy trial in clinically stable outpatients with schizophrenia Primary endpoint: proportion of patients who discontinued treatment due to lack of efficacy defined as – ‘lack of therapeutic response’ listed as primary reason for discontinuation on case report form – PANSS total score increased by ≥20% from baseline at any visit Objective: to determine the feasibility of switching from Quetiapine IR twice daily to Quetiapine XR once daily 42

Study 146: 6-week switching study : 

Study 146: 6-week switching study Patients were directly switched to the same total daily dose of quetiapine XR Dose at randomization (and through to Day 42) 3/20/2011 sarhan-AstraZeneca Quetiapine XR 400 mg/day Quetiapine IR 400 mg/day Quetiapine XR 600 mg/day Quetiapine IR 600 mg/day Quetiapine XR 800 mg/day Quetiapine IR 800 mg/day Quetiapine IR 400 mg/day Quetiapine IR 600 mg/day Quetiapine IR 800 mg/day 43

Study 146: 6-week switching studyDifference in lack of efficacy : 

Study 146: 6-week switching studyDifference in lack of efficacy 3/20/2011 sarhan-AstraZeneca 44

Study 146: 6-week switching studyPANSS total score over time : 

Study 146: 6-week switching studyPANSS total score over time 3/20/2011 sarhan-AstraZeneca 45

Quetiapine XRStudy 147: 12-week switching study : 

Quetiapine XRStudy 147: 12-week switching study 3/20/2011 sarhan-AstraZeneca Design: 12-week, multicentre, open-label, non-comparative trial in patients with schizophrenia who, in their own or the investigator’s opinion, considered their ongoing antipsychotic treatment inadequate because of insufficient efficacy (residual symptoms) or intolerability Primary endpoint: proportion of patients who achieved an improved clinical benefit based on assessment of clinical efficacy combined with assessment of tolerability using the CGI-CB score Objective: to evaluate the clinical benefit of switching from current antipsychotics to a flexible dose of quetiapine XR 46

Study 147: 12-week switching study : 

Study 147: 12-week switching study 3/20/2011 sarhan-AstraZeneca 47

Study 147: 12-week switching studyPrimary endpoint results: CGI-CB at Week 12 : 

Study 147: 12-week switching studyPrimary endpoint results: CGI-CB at Week 12 3/20/2011 sarhan-AstraZeneca 48

Study 147: 12-week switching studyPANSS total and subscale scores at Week 12 : 

Study 147: 12-week switching studyPANSS total and subscale scores at Week 12 3/20/2011 sarhan-AstraZeneca 49

Risperidone: Clinical Evidence of Dose-Related EPS Risk : 

Risperidone: Clinical Evidence of Dose-Related EPS Risk Mean Change in Maximum ESRSScore from Baseline Risperidone Haloperidol Owens 1994; Peuskens, et al. 1995. P < 0.05 vs 1 or 4 mg/day risperidoneP < 0.05 vs 1, 4, 8, or 12 mg/day risperidone

Olanzapine: Clinical Evidence of Dose-Related EPS Risk : 

BACK Olanzapine: Clinical Evidence of Dose-Related EPS Risk Olanzapine prescribing Information. * P < 0.05 vs placebo

Quetiapine: Placebo-Level EPS Across the Full Dose Range : 

75 (n = 53) 150(n = 48) 600(n = 51) Quetiapine Dose (mg/day) Patients(%) 300(n = 52) 750(n = 54) Placebo(n = 51) Arvanitis, et al. 1997; Data on file: AstraZeneca. Quetiapine: Placebo-Level EPS Across the Full Dose Range Data from a 6-Week Trial

Prolactin Concentrations Mean Changefrom Baseline to Week 8 and Week 28 : 

Prolactin Concentrations Mean Changefrom Baseline to Week 8 and Week 28 3/20/2011 sarhan-AstraZeneca nmol/L * * Tran, et al. 1997. Mean Prolactin Concentration 53

Effect of Antipsychotic Drugs on QTc (Steady State) : 

-5 0 5 10 15 20 25 30 35 40 Ziprasidone160 mg Risperidone16 mg Olanzapine20 mg Quetiapine750 mg Thioridazine300 mg Haloperidol15 mg (n = 24) (n = 25) (n = 27) (n = 27) (n = 31) (n = 30) Mean QTcChange from Baselinea (msec) aPfizer Study 54 baseline correctionDoses are highest total daily doses evaluated. FDA Psychopharmacological Drug Advisory Committee. Pfizer Study 54;19th July 2000. Effect of Antipsychotic Drugs on QTc (Steady State) 3/20/2011 sarhan-AstraZeneca 54

Clinically Significant (7%) Weight GainDuring Antipsychotic Treatment : 

Incidence ( %) Data US labels. Clinically Significant (7%) Weight GainDuring Antipsychotic Treatment 3/20/2011 sarhan-AstraZeneca 55

Seroquel - efficacy in positivesymptoms : 

Seroquel - efficacy in positivesymptoms 3/20/2011 sarhan-AstraZeneca 56

Seroquel improves positive symptomsawithin 1 week : 

Seroquel improves positive symptomsawithin 1 week 3/20/2011 sarhan-AstraZeneca 57

Seroquel is as effective as haloperidolin improving positive symptoms : 

Seroquel is as effective as haloperidolin improving positive symptoms 3/20/2011 sarhan-AstraZeneca 58

Seroquel is as effective as Risperidone in improving the positive symptoms of schizophrenia : 

Seroquel is as effective as Risperidone in improving the positive symptoms of schizophrenia 3/20/2011 sarhan-AstraZeneca 59

Improvements in positive symptomsamong atypical agents : 

Improvements in positive symptomsamong atypical agents 3/20/2011 sarhan-AstraZeneca 60

Seroquel - similar response to haloperidol inreducing positive symptoms within 12weeks : 

Seroquel - similar response to haloperidol inreducing positive symptoms within 12weeks 3/20/2011 sarhan-AstraZeneca 61

Negative symptoms of schizophrenia : 

Negative symptoms of schizophrenia 3/20/2011 sarhan-AstraZeneca Primary negative symptoms Direct causality Primary manifestation of schizophrenia Enduring symptoms Deficit schizophrenia Secondary negative symptoms Consequence of EPS Depressive symptoms Disorganized or paranoid withdrawal Non-deficit schizophrenia 62

Consequences of the negative symptoms of schizophrenia : 

Consequences of the negative symptoms of schizophrenia 3/20/2011 sarhan-AstraZeneca Evaluation of the effectiveness of treatments should differentiate primary and secondary symptomatology Current treatment largely addresses secondary symptoms Primary and secondary negative symptoms ↓ Quality of life and level of functioning 63

Negative symptoms improve in more patients on Seroquel compared with placebo : 

Negative symptoms improve in more patients on Seroquel compared with placebo 3/20/2011 64 sarhan-AstraZeneca

Seroquel - efficacy in negativesymptoms : 

Seroquel - efficacy in negativesymptoms 3/20/2011 65 sarhan-AstraZeneca

Seroquel significantly improves negative symptoms(SANS total score) among patients with prominentsymptoms† at baseline : 

Seroquel significantly improves negative symptoms(SANS total score) among patients with prominentsymptoms† at baseline 3/20/2011 66 sarhan-AstraZeneca

Effects of Seroquel and placebo on negative symptom domains of SANS global summary score : 

Effects of Seroquel and placebo on negative symptom domains of SANS global summary score 3/20/2011 67 sarhan-AstraZeneca

Seroquel improves negative symptoms from Week 1 : 

Seroquel improves negative symptoms from Week 1 3/20/2011 68 sarhan-AstraZeneca

Seroquel - maintenance of negativesymptom improvement over 52 week : 

Seroquel - maintenance of negativesymptom improvement over 52 week 3/20/2011 69 sarhan-AstraZeneca

Seroquel - as effective as Risperidone in improving the negative symptoms of schizophrenia : 

Seroquel - as effective as Risperidone in improving the negative symptoms of schizophrenia 3/20/2011 70 sarhan-AstraZeneca

Seroquel - reduction in negative symptoms appears similar to other atypicals : 

Seroquel - reduction in negative symptoms appears similar to other atypicals 3/20/2011 71 sarhan-AstraZeneca

Seroquel – greater improvements innegative symptoms than haloperidol : 

Seroquel – greater improvements innegative symptoms than haloperidol 3/20/2011 72 sarhan-AstraZeneca

Improvements in negative symptomsamong atypical agents : 

Improvements in negative symptomsamong atypical agents 3/20/2011 73 sarhan-AstraZeneca

Affective symptoms : 

Affective symptoms Commonly occur in patients with schizophrenia but are often under-recognised and inadequately treated May occur during any phase of schizophrenia 3/20/2011 74 sarhan-AstraZeneca

Impact of depressive symptoms on patientswith schizophrenia : 

Impact of depressive symptoms on patientswith schizophrenia 3/20/2011 sarhan-AstraZeneca Increased rate of relapse Increased rate of suicide Reduced quality of life Increased risk of substance abuse problems Poor social and family relationships Greater use of mental health services Increased logistical and financial burden on mental health and criminal justice systems 75

Prevalence of depressive symptoms inpatients with schizophrenia : 

Prevalence of depressive symptoms inpatients with schizophrenia Reported to be between 13 and 80%, depending on whether assessments are performed in acute or chronic phase Variation in prevalence may relate to – different assessment methods / rating scales – illness stage and chronicity – different diagnostic criteria 3/20/2011 76 sarhan-AstraZeneca

Aetiology of depressive symptomsin schizophrenia : 

Aetiology of depressive symptomsin schizophrenia 3/20/2011 77 sarhan-AstraZeneca

Impact of depressive symptoms severity on quality of life in patients with schizophrenia : 

Impact of depressive symptoms severity on quality of life in patients with schizophrenia 3/20/2011 78 sarhan-AstraZeneca

Impact of depression on QoL infirst-episode schizophrenia : 

Impact of depression on QoL infirst-episode schizophrenia 3/20/2011 sarhan-AstraZeneca 79

Impact of depressive symptoms : 

Impact of depressive symptoms 3/20/2011 80 sarhan-AstraZeneca

Depression as an early indicator of relapse : 

Depression as an early indicator of relapse Research has demonstrated that the onset of depression often signals imminent relapse Anxiety, withdrawal, guilt and shame commonly accompany dysphoria during this time Depression as a prodrome of a new psychotic episode is short lived 3/20/2011 81 sarhan-AstraZeneca

Depression as an indicator of suicide risk : 

Depression as an indicator of suicide risk Depression in schizophrenia is related to an increased risk of suicide Recent meta-analysis estimates a lifetime risk for completing suicide of 5.6% Between 25 and 50% of patients make a suicide attempt Suicide is the leading cause of premature death in patients with schizophrenia 3/20/2011 82 sarhan-AstraZeneca

Detection of depressive symptoms : 

Detection of depressive symptoms 3/20/2011 83 sarhan-AstraZeneca

Effect of Ziprasidone in patients withschizophrenia and a MADRS score ≥14 : 

Effect of Ziprasidone in patients withschizophrenia and a MADRS score ≥14 3/20/2011 84 sarhan-AstraZeneca

Effect of olanzapine and ziprasidone on CDSS score in patients with schizophrenia : 

Effect of olanzapine and ziprasidone on CDSS score in patients with schizophrenia 3/20/2011 85 sarhan-AstraZeneca

Effect of Quetiapine IR and Risperidone onHAM-D score in patients with schizophrenia : 

Effect of Quetiapine IR and Risperidone onHAM-D score in patients with schizophrenia 3/20/2011 86 sarhan-AstraZeneca

Effect of switching to Quetiapine IR on depressive symptoms in patients with schizophrenia : 

Effect of switching to Quetiapine IR on depressive symptoms in patients with schizophrenia De Nayer J et al. Int J Psychiatry Clin Pract 2003; 7: 59-66 3/20/2011 87 sarhan-AstraZeneca

Effect of Quetiapine XR on PANSSdepression cluster : 

Effect of Quetiapine XR on PANSSdepression cluster Kahn RS et al. J Clin Psychiatry 2007; 68: 832-842 3/20/2011 88 sarhan-AstraZeneca

How significant is a long-term change in depressed status? : 

How significant is a long-term change in depressed status? Conley RR et al. Schizophr Res 2007; 90 (1-3): 186-97 3/20/2011 89 sarhan-AstraZeneca

Change in depressed status: rate ofsuicidal thinking : 

Change in depressed status: rate ofsuicidal thinking Conley RR et al. Schizophr Res 2007; 90 (1-3): 186-97 3/20/2011 90 sarhan-AstraZeneca

Effect of change from depressed tonon-depressed status : 

Effect of change from depressed tonon-depressed status Conley RR et al. Schizophr Res 2007; 90 (1-3): 186-97 3/20/2011 91 sarhan-AstraZeneca

Slide 92: 

5HT 6 5HT 7 quetiapine Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 92 Stephen Stahl

Slide 93: 

Quetiapine Pearls Some patients respond to Quetiapine who have failed to respond to other atypicals. Anecdotal reports of usefulness for bipolar, for treatment-refractory cases, and for positive symptoms of psychosis in disorders other than schizophrenia Useful and well tolerated for psychosis in Alzheimer’s patients Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 93

Slide 94: 

Never say never, but essentially no EPS or Prolactin elevation at any dose Early studies support use in adolescents, elderly patients, and for hostility/aggression, cognition, and affective symptoms in schizophrenia. Quetiapine Pearls Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 94

Slide 95: 

Quetiapine may be the drug of choice for patients with Parkinson’s disease who require treatment with an antipsychotic. No dose-related prolongation of QT interval Less weight gain in long-term treatment than with many antipsychotics Quetiapine Pearls Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 95

Slide 96: 

Clinical trials suggest effective dose range for schizophrenia is 150-750 or 800 mg/day (75-400 mg bid; 375 bid in some countries), except for lower doses in the elderly: 25-100 mg bid. Clinical practice suggests that Quetiapine is often underdosed, then switched prior to adequate trials. An initial target daily dose of 400-600 mg/day should be reached in most cases to optimize the chances of success. Trials of 800 mg/d or more may be justified and helpful in some cases. Quetiapine Dosing Tips Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 96

Slide 97: 

At 200 mg bid, may be one of the lower cost atypical antipsychotics. Higher doses may make it one of the more expensive antipsychotics, but this may be justified in severe or treatment-resistant cases. Quetiapine Dosing Tips Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 97

Slide 98: 

Quetiapine: Greater Efficacy with Higher Dose Small, et al. Arch Gen Psychiatry 1997. Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 98

Slide 99: 

Quetiapine Dosing Tips Twice-daily regimen Titration recommended to an initial target dose of 200 mg twice daily achieved within 4-6 days (200 mg bd) Can be administered with or without food Dose adjustment not required in renal impairment (but may be in hepatic impairment) Dose not dependent on gender, race, or smoking status Stahl. J Clin Psychiatry 2002 3/20/2011 sarhan-AstraZeneca 99

Slide 100: 

3/20/2011 sarhan-AstraZeneca Summary There are five first-line atypical antipsychotics (Risperidone, Olanzapine, Quetiapine, Ziprasidone, and aripiprazole) that all reduce psychosis with a low incidence of EPS. Every agent has some distinctive properties as well. Knowledge of the differences among these agents allows a prescriber to best match a drug to an individual patient. Stahl. J Clin Psychiatry 2002 Comparison of First-Line Atypical Antipsychotics 100

Seroquel XR Dosing : 

Seroquel XR Dosing 3/20/2011 sarhan-AstraZeneca Single dose at night Rapid titration Less side effects 101

Conclusions-1 : 

Conclusions-1 3/20/2011 sarhan-AstraZeneca New oral extended release formulations of the atypical antipsychotics are an important development for patients with schizophrenia The efficacy of Quetiapine XR and Paliperidone ER in this indication is demonstrated by data from clinical trials Quetiapine XR can be increased up to 800 mg/day in 3 days without increasing adverse events compared with Quetiapine IR 102

Conclusions-2 : 

Conclusions-2 Seroquel XR once daily demonstrates significant efficacy across a broad range of symptoms including core symptoms of acute schizophrenia Seroquel XR once daily is effective in preventing relapse in stable patients with chronic schizophrenia Seroquel XR once daily is well tolerated across the dose range and over longer term treatment (up to 9 months) Seroquel XR once daily can be prescribed at the therapeutically effective dose range by Day 2 and does not need to be adjusted for maintenance treatment 3/20/2011 sarhan-AstraZeneca 103

Conclusions-3 : 

Conclusions-3 The PK profile of Seroquel XR provides smoother, more stable plasma concentrations than Seroquel IR Once daily Seroquel XR at doses of 400–800 mg/day is effective in the treatment of acute schizophrenia The therapeutic dose range is reached by Day 2 with once daily Seroquel XR Seroquel XR is effective in preventing relapse in patients with chronic stable schizophrenia 3/20/2011 sarhan-AstraZeneca 104

Conclusion-4 : 

Conclusion-4 3/20/2011 sarhan-AstraZeneca 105 Patients can be easily switched from Seroquel IR to Seroquel XR without deterioration of clinical condition Patients can be easily switched from other antipsychotics to Seroquel XR using a 4-day cross-titration period Once daily Seroquel XR is well tolerated and the overall safety profile is similar to Seroquel IR

References-1 : 

References-1 3/20/2011 sarhan-AstraZeneca American Psychiatric Association. Am J Psychiatry 1997; 154: 1-63. Bai O et al. J Neurosci Res 2003; 71: 127-131. Bergiannaki JD et al. Eur Psychiatry 2001; 16: 90-98. Birkenaes AB et al. J Clin Psychiatry 2007; 68: 917-923. Chlan-Fourney J et al. Brain Res 2002; 954: 11-20. DeQuardo JR et al. J Clin Psychiatry 1998; 59 (Suppl 19): 9-17. Docherty J et al. Poster presented at the annual meeting of the ACNP, San Juan, Puerto Rico, December 2002. Fenton WS et al. Schizophr Bull 1997; 23: 637-651 Raton, FL, USA, June 2002. 106

References-2 : 

References-2 3/20/2011 sarhan-AstraZeneca Fumagalli F et al. NeuroReport 2004; 15: 2109-2112. Gitlin M et al. Am J Psychiatry 2001; 158: 1835-1842. Harris EC, Barraclough B. Br J Psychiatry 1998; 173: 11-53. Kane J. J Clin Psychiatry 1983; 44: 3-6. Keith SJ, Kane JM. J Clin Psychiatry 2003; 64: 1308-1315. Kissling W. Br J Psychiatry Suppl 1992; 133-139. Kyngas HA. Nurs Health Sci 1999; 1: 195-202. Lam D et al. Poster presented at the 42nd Annual NCDEU Meeting, Boca 107

References-3 : 

References-3 3/20/2011 sarhan-AstraZeneca Lieberman JA et al. Biol Psychiatry 2001; 60: 884-897. Lieberman JA et al. Arch Gen Psychiatry 2005; 62: 361-370. Lubman DI, Sundram S. Med J Aust 2003; 178 Suppl: S71-S75. Luo C et al. Brain Res 2005; 1063: 32-39. Maguire GA. Am J Health Syst Pharm 2002; 59: S4-11. Newcomer J. J Clin Psychiatry 2006; 67 (Suppl 9): 25-30. Parikh V et al. Schizophr Res 2003; 60: 117-123. Parikh V et al. Neurosci Lett 2004; 356: 135-139. Perkins DO. J Clin Psychiatry 2002; 63: 1121-1128. 108

References-3 : 

References-3 3/20/2011 sarhan-AstraZeneca Pillai A et al. Schizophr Res 2006; 82: 95-106. Prince M et al. Lancet 2007; 370: 859-877. Robinson DG et al. Am J Psychiatry 1999; 156; 544-549 Thompson PM et al. Proc Natl Acad Sci U S A 2001; 98: 11650-11655. Valenstein M et al. Med Care 2002; 40: 630-639. Viller F et al. J Rheumatol 1999; 26: 2114-2122. Weiden PJ et al. Psychiatr Serv 2004; 55: 886-891. Weiden PJ, Zygmunt A. J Pract Psychiatry Behav Health 1997; 106. 109

References-1 : 

References-1 3/20/2011 sarhan-AstraZeneca Lacro et al. J Clin Psychiatry 2002; 63: 892-909. Fleischhacker et al. J Clin Psychiatry 2003; 64 (Suppl 16): 10-13. Sun et al. Curr Med Res Opin 2007; 23: 2305-12. Claxton et al. Clin Ther 2001; 23: 1296-310. Allen et al. J Psychiatr Pract 2003; 9: 39-58. Kane. J Clin Psychiatry 2006; 67 (Suppl 5): 9-14. Citrome. J Clin Psychiatry 2007; 68: 1876-85. Davidson et al. Schizophr Res 2007; 93: 117-30. Kahn et al. J Clin Psychiatry 2007; 68: 832-42. Möller et al. Int Clin Psychopharmacol 2008; 23: 95-105. Ganesan et al. Curr Med Res Opin 2008; 24: 21-32. 110

References-2 : 

References-2 3/20/2011 sarhan-AstraZeneca Allen MH et al Postgrad Med 2001; Spec. No.: 1-88 [page 52] Allen MH et al. J Psychiatr Pract 2003; 9: 39-58. Allen MH et al. Psychiatr Pract 2005; 11 (Suppl 1): 5-25. Arango C & Bobes J. Curr Med Res Opin 2004; 20: 619-26. Arango C et al. Eur Psychiatry 2004; 19: 21-26. Bryson G, Bell MD. J Nerv Ment Dis 2003; 191: 87-92. Conley RR et al. Schizophr Res 2007; 90: 186-97 [Epub 2006]. Elgie R, Morselli PL. Bipolar Disord 2007; 9: 144-157. Fenton WS et al. Schizophr Bull 1997; 23: 637-51. Gerlach J. J Clin Psychiatry 1999; 60 (Suppl 23): 20-24. Weissman EM et al. Psychiatr Serv 2006; 57: 724-5. Wykes T et al. Br J Psychiatry 2007; 190: 421-427. 111

References-3 : 

References-3 3/20/2011 sarhan-AstraZeneca Green MF et al. Schizophr Bull 2000; 26: 119-36. Hansen L. Hum Psychopharmacol 2001; 16: 495-505. Haut et al submitted. Lacro JP et al. J Clin Psychiatry 2002; 63: 892-909. Lay B et al. Schizophr Bull 2000; 26: 801-16. Leong GB, Silva JA. J Forensic Sci 2003; 48: 187-9. MacDonald AW et al. Am J Psychiatry 2005; 162: 475-484. McGurk SR et al. Ment Health Serv Res 2004; 6: 185-8. McGurk SR. Am J Psychiatry 2007; 164: 437-441. Rössler W et al. Eur Neuropsychopharmacol 2005; 15: 399-409. Sim K et al. Psychiatry Res 2004; 129: 141-7. Velligan DI et al. Schizophr Res 1997; 25: 21-31 112

References-4 : 

References-4 3/20/2011 sarhan-AstraZeneca Harvey PD, Keefe RS. Am J Psychiatry 2001; 158:176-84. Maguire GA. Am J Health Syst Pharm 2002; 59 (17 Suppl 5): S4-11. Conley RR et al. Schizophr Res 2007; 90 (1-3): 186-97. Mulholland C, Cooper S. Advances in Psychiatric Treatment 2000; 6: 169-77. Zisook S et al. Am J Psychiatry 1999;156 (11): 1736-43. Hausmann A and Fleischhacker WW. CNS Drugs 2000; 14(4): 289-99. Caldwell CB, Gottesman II. Suicide Life Threat Behav 1992; 22: 479-93. Meltzer HY. Ann N Y Acad Sci 2001; 932: 44-58. Mullen J et al. Clin Ther. 2001; 23 (11): 1839-54. . 113

References-5 : 

References-5 3/20/2011 sarhan-AstraZeneca Levinson DF et al. Am J Psychiatry 1999; 156 (8): 1138-48. Siris SG. Am J Psychiatry 2000; 157 (9): 1379-89. Jin H et al. J Clin Psychiatry 2001; 62 (10): 797-803. Plasky P. Schizophr Bull 1991; 17 (4): 649-57. Kim SW et al. Psychiatry Res 2006 30; 144 (1): 57-63. Palmer BA et al. Arch Gen Psych 2005; 62: 247-53. Harkavy-Friedman JM et al. Am J Psychiatry 1999; 156 (8): 1276-8. Mazeh D et al. J Clin Psychopharmacol 2004; 24 (6): 653-5. 114

References-6 : 

References-6 3/20/2011 sarhan-AstraZeneca Kinon BJ et al. J Clin Psychopharmacol 2006; 26 (2): 157-62. Daniel DG et al. Neuropsychopharmacology 1999; 20 (5): 491-505. Muller MJ et al. Can J Psychiatry 2006; 51 (6): 387-92. Collaborative Working Group on Clinical Trial Evaluations. J Clin Psychiatry 1998; 59 (Suppl 12): 41-5. De Nayer J et al. Int J Psychiatry Clin Pract 2003; 7: 59-66. Kahn RS et al. J Clin Psychiatry 2007; 68: 832-842 115

THANK YOU : 

THANK YOU 3/20/2011 sarhan-AstraZeneca www.walidsarhan.net 116

authorStream Live Help