Optimizing Care for Patients With Schizophrenia

Transcription

1 Optimizing Care for Patients With Schizophrenia (page 217 in syllabus) Andrew J. Cutler, MD Courtesy Assistant Professor, Department of Psychiatry University of Florida CEO and Medical Director, Florida Clinical Research Center, LLC Sponsored by the Neuroscience Education Institute Additionally sponsored by the American Society for the Advancement of Pharmacotherapy This activity is supported by an educational grant from Lilly USA, LLC. For further information concerning Lilly grant funding visit,

2 Individual Disclosure Statement Faculty Editor / Presenter Andrew J. Cutler, MD, is a courtesy assistant professor in the department of psychiatry at the University of Florida in Gainesville, and the CEO and chief medical officer of Florida Clinical Research Center, LLC in Maitland. Grant/Research: Alkermes, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dainippon Sumitomo, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Lilly, Lundbeck, Merck, Ortho-McNeil, Otsuka America, Quintiles Transnational, Roche, Shionogi, Shire, Sunovion, Supernus, Takeda, Targacept Consultant/Advisor: AstraZeneca, Bristol-Myers Squibb, Cypress, Dainippon Sumitomo, Forest, Janssen, Labopharm, Lilly, Merck, Ortho-McNeil, Otsuka America, Pamlab, PharmaNeuroBoost N.V., Quintiles Transnational, Shionogi, Shire, Sunovion, Supernus, Takeda, Targacept Speakers Bureau: AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo, Forest, GlaxoSmithKline, Janssen, Labopharm, Lilly, Merck, Ortho-McNeil, Otsuka America, Pamlab, Shionogi, Shire, Sunovion

3 Learning Objectives Implement evidence-based treatment strategies that are aligned with recovery goals set by the patient Integrate novel treatment approaches into clinical practice according to best practices guidelines Include strategies for monitoring and addressing adherence as part of the treatment plan for all patients

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5 Pretest Question 1 Theresa is a 49-year-old patient with schizophrenia and a history of nonadherence. She does not want to try a depot formulation due to a fear of needles. Given that complexity of dosage regimen may adversely affect treatment adherence, which atypical antipsychotic would you consider for Theresa? 1. Asenapine 2. Iloperidone 3. Quetiapine XR 4. Ziprasidone

6 Pretest Question 2 Joel is a 23-year-old patient with schizoaffective disorder. He is currently taking a relatively low dose of clozapine but is considering stopping his medication due to side effects, especially daytime sedation. Based on receptor binding profiles, which antipsychotic has the least risk of causing sedation? 1. Aripiprazole 2. Olanzapine 3. Quetiapine 4. Asenapine

7 Pretest Question 3 Henry is a 34-year-old patient with schizophrenia. Results from the Positive and Negative Syndrome Scale (PANSS) reveal numerous symptoms, especially in the General Psychopathology subscale. Imaging of Henry s brain would likely reveal loss of gray matter in which brain region? 1. Temporal lobe 2. Frontal lobe 3. Anterior cingulate gyrus

8 What Should Ideal Care Provide for Patients With Schizophrenia?

9 Recovery Recovery from illness Cure of illness, absence of illness vs Recovery in illness: being in recovery Process of managing illness more effectively Having a meaningful life in the community Moving ahead with one s life despite illness Davidson L et al. Schizophr Bull 2008;34:5-8.

10 Symptom management Physical health Reduced hospitalization Reduced criminal activity Reduced substance abuse Stable housing Employment Community involvement Family involvement Treatment alliance Cognitive ability Empowerment RECOVERY

11 Schizophrenia PORT Patient Outcomes Research Team Makes conservative recommendations based solely on substantial scientific evidence From systematic literature reviews Includes psychopharmacological and psychosocial treatment recommendations Kreyenbuhl et al. Schizophr Bull 2010;36(1):

12 2009 Updated PORT Psychopharmacological Treatment Recommendations First and Foremost Conventional or atypical antipsychotics as first-line treatments Clozapine and olanzapine should not be used first line More Is More Higher doses of antipsychotics for patients with multiple episodes Don t Stop Continuous antipsychotic maintenance treatment Not Just a Pain in the Long-acting injectable formulations Shake It Up Antiparkinson medications to prevent EPS Be Cloz-Minded Clozapine for treatment-resistant cases Chillax! Benzodiazepines for acute agitation Quitters Win Smoking cessation assistance A Little Shocking Repetitive transcranial magnetic stimulation (rtms) for treatment-resistant auditory hallucinations Buchanan et al. Schizophr Bull 2010;36(1):71-93.

13 2009 Updated PORT Psychosocial Treatment Recommendations Get Your ACT Together Assertive Community Treatment Hi-Ho, Hi-Ho, It s Off To Work We Go Supported employment Out of the Frying Pan and Into the Skill-et Skills training Think About It Cognitive psychotherapy You Can Do It! Positive reinforcement It s a Family Affair Family intervention Drugs Are Bad, Mmkay? Substance abuse treatment Be a Loser Weight management Dixon et al. Schizophr Bull 2010;36(1):48-70.

14 Symptom Management

15 Least Squares Mean Change in PANSS Total Score Early Risperidone Responders Show Early and Consistent Improvement: Clinical Outcomes Early Responders (ER) (n = 144) Early Non-Responders (ENR) (n = 192) * * * * * * Weeks Kinon B et al. Schizophr Res 2010;118: *P < 0.001

16 Least Squares Mean Change in SOFI Baseline to Endpoint Early Risperidone Responders Show Early and Consistent Improvement: Functional Outcomes * * * * ER Group ENR Group * Overall Living Situation Instrumental Activity Productive Activity Social Functioning *P < SOFI: Schizophrenia Objective Functioning Instrument Kinon B et al. Schizophr Res 2010;118:

17 Duration and Severity of Untreated Psychosis and Outcome in First-Episode Schizophrenia Meta-analysis of 43 publications Prolonged duration of untreated psychosis prior to the initiation of treatment was associated with poorer symptomatic and functional recovery in initial episodes Global Functional Outcome Negative Symptom Severity Positive Symptom Severity Global Psychopathology Effect Size (95% CI) Perkins DO et al. Am J Psychiatry 2005;162(10):

18 FIN-11 Study Long-term antipsychotic use associated with lower mortality compared to no antipsychotic use in patients with schizophrenia Favors antipsychotic Favors no antipsychotic Risk of death from any cause vs cumulative use of any antipsychotic drug *Mortality = unadjusted absolute risk per 1000 person-years No antipsychotic drug = patients (18,914) who had not used any antipsychotic drugs during follow-up Tiihonen et al. Lancet 2009;374(9690):620-7.

19 Efficacy of Antipsychotics on Positive and Negative Symptoms of Schizophrenia Potkin SG et al. Int J Neuropsychopharmacol 2009;12:

20 Efficacy of Antipsychotics on Symptoms of Schizophrenia Guo X et al. Psychopharmacology 2011; Epub ahead of print.

21 Efficacy of Antipsychotics on Negative Symptoms of Schizophrenia n = 227 n = 221 n = 151 * P < 0.05 vs HAL; ** P < 0.01 vs HAL Stahl S et al. J Clin Psychopharmacol 2010;30:

22 Efficacy of Antipsychotics on Cognitive Symptoms of Schizophrenia Harvey PD et al. J Neuropsychiatry Clin Neurosci 2006;18:54-63.

23 Antipsychotics Can Improve Illness Insight Guo X et al. Psychopharmacology 2011; Epub ahead of print.

24 The Bottom Line For many patients Antipsychotic treatments may ameliorate symptoms of schizophrenia if they are maintained for an extended period of time Continuous maintenance antipsychotic medication results in ~70% reduction in risk of relapse Lindenmayer et al. J Clin Psychiatry 2009;70(7):990-6; Marder. J Clin Psychiatry 2003;64(Suppl):3-9.

25 Treatment Adherence Antipsychotics Don t Work At All If They Aren t Taken

26 How Common Is Nonadherence? Nonadherence is estimated to be as high as 60% 40% of annual costs for rehospitalization are due to nonadherence 75% of patients who discontinue their medication experience significant symptom exacerbation over 1 year compared to 25% of those who adhere to their medication Treatment nonadherence is associated with up to a 7-fold increased risk of suicide attempt Lindenmayer et al. J Clin Psychiatry 2009;70(7):990-6; Marder. J Clin Psychiatry 2003;64(Suppl):3-9.

27 Assessing Nonadherence Nope, Doc, I haven t missed a single dose She seems like an adherent patient Patient self-report Unreliable Physician report Overly optimistic Feasibility Pill counts Easily manipulated Rx renewals Medication must be obtained from a single source Accuracy Rx Microelectric monitoring of pill caps Expensive Physiological monitoring Invasive Ouch! llorca et al. Psychiatry Res 2008;161:235-47; Marder. J Clin Psychiatry 2003;64(Suppl):3-9; Velligan et al. Psychiatr Serv 2007;58(9): Copyright 2011 Neuroscience Education. Institute. All rights reserved.

28 Why Don t Patients Take Their Medicine?

29 Factors That May Affect Medication Adherence Poor illness insight Cognitive deficits Positive symptoms Doctor/patient relationship Treatment efficacy Side effects Treatment regimen Drug abuse Lieberman et al. N Engl J Med 2005;353(12): ; Piette et al. Arch Intern Med 2005;165(15): ; Novick et al. Psychiatry Res 2010;176:

30 Relationship Between Symptoms and Adherence

31 Consequences of Nonadherence

32 Progressive Gray Matter Loss in Adolescent Patients With Schizophrenia Over 5 Years Normal Subjects Subjects With Schizophrenia Difference P-Value Thompson PM et al. PNAS 2001;98(20):

33 Gray Matter Loss in Adult Patients With Schizophrenia at Baseline and 5-Year Follow-Up Baseline 5-year Follow-Up Talairach coordinate (axial): z=3 Talairach coordinate (axial): z=3 Excessive gray matter loss was related to an increased number of hospitalizations (increased psychotic episodes) van Haren NE et al. Neuropsychopharmacology 2007;32(10):

34 Psychosis and Brain Volume Changes During the First 5 Years of Schizophrenia Gray Matter Lateral Ventricle Volume 3rd Ventricle Volume Duration of Psychosis (months) Duration of Psychosis (months) Duration of Psychosis (months) Cahn W et al. Eur Neuropsychopharm 2009;19: N = 48

35 Reduced Gray Matter Volume in Antipsychotic-Naïve Patients With First-Episode Schizophrenia Correlates With Functional Deficits Temporal Lobe Abnormalities Anterior Cingulate Gyrus Abnormalities Correlate with: Global Assessment of Functioning (GAF) Scale PANSS Positive Symptoms PANSS General Psychopathology PANSS Thought Disturbance PANSS Activation PANSS Paranoia PANSS Impulsive Aggression Lui S et al. Am J Psychiatry 2009;166: Correlate with: Global Assessment of Functioning (GAF) Scale PANSS Positive Symptoms PANSS Thought Disturbance PANSS Activation PANSS Paranoia PANSS Impulsive Aggression

36 Gray Matter Loss Is Worse in Patients With a Longer Duration of Untreated Psychosis Colored voxels depict brain areas of significantly greater gray matter loss in patients with a long duration of untreated psychosis (>18 wks) compared to those with a short duration (<18 wks) Malla AK et al. Schizophr Res 2011;125(1):13-20.

37 Antipsychotic Treatment Improves Cerebral Functioning Baseline untreated patients with first-episode schizophrenia have decreased amplitude of low-frequency fluctuations Patients treated for 6 wks with antipsychotics have increased amplitude of low-frequency fluctuations compared to baseline Patients treated for 6 wks with antipsychotics have increased amplitude of low-frequency fluctuations compared to controls Lui S et al. Arch Gen Psychiatry 2010;67(8):

38 Consequences of Nonadherence on Functional Outcomes Nonadherence is associated with: Alcohol-related problems Reduced mental functioning Reduced satisfaction with life Psychiatric hospitalizations Use of emergency psychiatric services Arrests Violence Victimizations Substance use Ascher-Svanum et al. J Clin Psychiatry 2006;67(3):

39 Nonadherence Is Associated With Increased Hospitalization % of Patients Hospitalized >30 Total Maximum Gap in Therapy (days within one year) Weiden et al. Psychiatr Serv 2004;55:

40 Partial Nonadherence Patient reduces dose of drug or fails to take drug from time to time Can lead to unexplained and unanticipated adverse events Suboptimal treatment increases risk of relapse A 20% reduction in treatment compliance predicts a 3.1 point increase in PANSS total score Perkins et al. J Clin Psychiatry 2008;69(1):106-13; Docherty et al. American College of Neuropsychology 41st Annual Meeting. Abstract 2002:154.

41 Even Partial Nonadherence Is Detrimental Nonadherent patients defined here are those who miss <50% of their medication for 2 weeks or more Missing even <25% of medication for >2 weeks increases the risk for psychotic relapse Subotnik KL et al. Am J Psychiatry 2011;168:

42 Improving Treatment Adherence

43 How to Improve Adherence Minimize side effects and increase drug efficacy By switching to another antipsychotic Utilize long-term depot formulations Psychosocial interventions Maximize cognitive functioning

44 Strategies to Improve Adherence Basic communication Take the patient's preferences into account Explain the benefits and hazards of treatment options Strategy-specific interventions Adjusting medication timing and dosage for least intrusion Minimize adverse effects and maximize effectiveness Reminders (psychosocial interventions) Evaluate adherence regularly Mitchell, Selmes. Adv Psychiatr Treatment 2007;13:

45 Maximize Treatment Efficacy While Minimizing Side Effects for the Individual Patient

46 Long-Acting Depot Formulations

47 Long-Acting Injectable (LAI) Antipsychotics to Improve Medication Adherence Advantages Assured medication delivery Continuous antipsychotic coverage No need to remember to take medication every day Drug remains in system for 1-2 weeks after a missed dose Reduced risk of relapse and rehospitalization Avoidance of first-pass metabolism Peak plasma level is lower and occurs less often (less side effects?) More frequent contact with treatment team Increasing number of options available Disadvantages Cost/insurance coverage More appointments Oral to LAI conversion Perceived stigma Negative perceptions by clinicians Gerlach. Int Clin Psychopharmacol 1995;9(5):17-20.

48 Atypical Antipsychotics With Long-Acting Depot Formulations iloperidone 4 wk in trials aripiprazole 4 wk in trials paliperidone 4 wk 12 wk in trials risperidone 2 wk 4 wk in trials olanzapine 2 wk 4 wk

49 Depot Injections Are Associated With a 50-65% Lower Risk of Rehospitalization Compared to Their Oral Counterparts Tiihonen J et al. Am J Psychiatry 2011;168:603-9.

50 Not All Studies Show Superiority of Depot Antipsychotics Rosenheck RA et al. N Engl J Med 2011;364:

51 Characteristics That May Affect Adherence Morrissette D, Stahl S. Neuroscience Education Institute. Accessed Sept 2010.

52 Psychosocial Intervention

53 Psychosocial Interventions Supported employment Cognitive behavioral therapy (CBT) Cognitive adaptation therapy (CAT) Cognitive remediation therapy (CRT)

54 Pharmacy-Based Intervention Valenstein et al. Schizophr Bull 2009; Epub ahead of print.

55 Effect Size Cognitive Remediation Therapy McGurk et al. Am J Psychiatry 2007;164:

56 ACT Now! Recovery Is Going Fast!

57 Elements of ACT Developed in the 1970s Goal Replace crisis-oriented clinical care with intensive community-based intervention Design Integrative care is continuous and offered for as long as it is needed Care is available 24/7 Team approach to care Dixon L. Psychiatr Serv 2000;51(6):

58 The ACT Team ACT leader Psychiatrists Psychiatric nurses Employment specialist Substance abuse specialist Peer specialist Additional mental health professionals Program assistant The team meets regularly to discuss each case At least one team member visits the patient on a regular basis to assess medication efficacy, treatment adherence, medication side effects, physical health, and other issues that could potentially affect recovery Dixon L. Psychiatr Serv 2000;51(6):

59 ACT Services Medication prescription, administration, and monitoring Illness management and recovery skills Continuous assessment and intervention Medication prescription, administration, and monitoring Continuous assessment and intervention Medical care Crisis assessment and intervention Illness management and recovery skills Medication prescription, administration, and monitoring Illness management and recovery skills Medication prescription, administration, and monitoring Individual supportive therapy Substance abuse treatment Illness management and recovery skills Individual supportive therapy Housing support services Employment-support services Transportation Intervention with support networks Transportation Intervention with support networks Individual supportive therapy Frequent interaction with ACT team members Integration of patient s wishes in treatment planning Individual supportive therapy Assistance with activities of daily living Case management Integration of patient s wishes in treatment planning Incorporation of recovering patients as peer specialists on ACT team Element of Recovery Symptom management Physical health Reduced hospitalization Reduced criminal activity Reduced substance abuse Stable housing Employment Community involvement Family involvement Treatment alliance Cognitive ability Empowerment RECOVERY

60 Is ACT Worth It? Direct and indirect costs of treating schizophrenia are ~$60 billion 2/3 of these costs are from hospitalizations Increased cost of ACT-based care is offset by: Reduced hospitalizations Reduced use of emergency services Reduced criminal activities and justice system use Increased engagement in the workforce Decreased use of welfare services Reduced death from suicide May be most cost-effective for patients who are severely disabled by their illness, have numerous hospitalizations, or are at high risk for relapse Rosen A et al. J Rehab Res Dev 2007;44(6):813-26; Gilmer TP et al. 2010;67(6):645-52; McCrone P et al. Br J Psychiatr 2010;196:

61 Summary Symptom management is just a portion of what is necessary for optimizing outcomes for patients with schizophrenia Antipsychotic treatments ameliorate symptoms of schizophrenia for many patients and should be initiated early in the disease course Treatment nonadherence greatly increases the risk of poor functional outcomes in schizophrenia; even partial nonadherence increases the risk for relapse Minimization of treatment side effects may help to maximize treatment adherence; establishing a strong treatment alliance and optimizing treatment for the individual patient can increase adherence Long-acting depot formulations of antipsychotics offer the benefit of better ensuring treatment adherence Psychosocial interventions and the mediation of cognitive deficits should also be integral parts of treatment for schizophrenia