The Challenge of Adding or Switching Antipsychotics - Getting Treatment Just Right Event Type Live Online

Transcription

1 The Challenge of Adding or Switching Antipsychotics - Getting Treatment Just Right Event Type Live Online Expiration Date 3/19/2017 Credits 1 Contact Hour Target Audience Nurses, Pharmacists, Pharmacy Technicians Program Overview Patients with schizophrenia and their health care providers often search for a treatment solution that is just right, often switching or adding an antipsychotics in the long term maintenance to ensure continuation of successful treatment. This program will focus on what health care providers can do to refine and adjust treatment until they get it just right. The science of treating schizophrenia continues to improve; getting the art of treatment right continues to be a challenge. A combination of education, safe prescribing and appropriate monitoring will help us eventually eliminate the consequences of poorly managed schizophrenia. As the bridge between patients and physicians, pharmacists are in the position to play an integral part of a multi-pronged solution to this challenge, and have the potential to ensure that patients switching or adding medication can attain optimal therapeutic outcomes while minimizing the risk of adverse events. Nurse Educational Objectives Outline the current pharmacological approaches to the management of schizophrenia (pharmacologic profiles, efficacy, side effects, & adverse events). Outline the common indications (and contraindications) for adding or switching antipsychotics, strategies for changing medications. Review the challenges with switching or add antipsychotic medications and highlight counseling points to ensure a smooth transition and optimal therapeutic outcomes while minimizing the risk of adverse events. Pharmacist Educational Objectives Outline the current pharmacological approaches to the management of schizophrenia (pharmacologic profiles, efficacy, side effects, & adverse events).

2 Outline the common indications (and contraindications) for adding or switching antipsychotics, strategies for changing medications. Review the challenges with switching or add antipsychotic medications and highlight counseling points to ensure a smooth transition and optimal therapeutic outcomes while minimizing the risk of adverse events. Pharmacy Technician Educational Objectives List symptoms of schizophrenia List medications used to treat schizophrenia Activity Type Knowledge Accreditation Nurse Pharmacist Pharmacy Technician N L01-P L01-T PharmCon, Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. PharmCon, Inc. has been approved as a provider of continuing education for nurses by the Maryland Nurses Association which is accredited as an approver of continuing education in nursing by the American Nurses Credentialing Center s Commission on Accreditation. Faculty Shane Martin, PharmD, RPh, BCCP Chillicothe Veterans Affairs Medical Center Financial Support Received From Pharmaceutical Education Consultants, Inc.

3 Disclaimer PharmCon, Inc. does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced and objective. Occasionally, authors may express opinions that represent their own viewpoint. Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient or pharmacy management. Conclusions drawn by participants should be derived from objective analysis of scientific data presented from this activity and other unrelated sources.

4 Page 1 B. Shane Martin, PharmD, RPh, BCPP Accreditation Faculty Pharmacists: L01-P Pharmacy Technicians: L01-T Nurses: N-878 Shane Martin, PharmD, RPh, BCCP Chillicothe Veterans Affairs Medical Center CE Credit(s) Faculty Disclosure 1 contact hour(s) Dr. Martin has no actual or potential conflicts of interest in relation to this program. Learning Objectives Outline the current pharmacological approaches to the management of schizophrenia (pharmacologic profiles, efficacy, side effects, & adverse events). Outline the common indications (and contraindications) for adding or switching antipsychotics, strategies for changing medications. Review the challenges with switching or add antipsychotic medications and highlight counseling points to ensure a smooth transition and optimal therapeutic outcomes while minimizing the risk of adverse events. Legal Disclaimer The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Learning Objectives Outline the current pharmacological approaches to the management of schizophrenia (pharmacologic profiles, efficacy, side effects, & adverse events). Outline the common indications (and contraindications) for adding or switching antipsychotics, strategies for changing medications. Review the challenges with switching or add antipsychotic medications and highlight counseling points to ensure a smooth transition and optimal therapeutic outcomes while minimizing the risk of adverse events. Pharmacotherapy of Schizophrenia Antipsychotics are the mainstay of pharmacotherapy Second generation (SGA) or atypical (AAP) agents generally preferred over first generation (FGA) or typical (AP) agents With the exception of clozapine for treatment resistant schizophrenia, antipsychotic drug selection is based upon factors other than proven superiority in EFFICACY Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): Tandon R, et al. Schizophrenia, Just the Facts 5. Schizophrenia Research. 2010; 122: Leucht SL, et al. Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacology. 2011; 14(2):

5 Page 2 Reasons for Switching Antipsychotics Inadequate therapeutic response Adherence Dose Duration Drugs of abuse Diagnosis Intolerable side effects/long-term health risks Cost Goals of Switching Improve symptomatic and functional level in unstable patients Maintain symptomatic and functional level in stable patients Improve or, at least, not worsen medication tolerability/overall health Effectiveness of Switching Antipsychotics Reasons NOT to Switch Recent recovery from acute episode and clear benefit with current antipsychotic Presently stable with history of clinical instability (e.g. violence, self-harm/neglect, severe symptoms) during acute exacerbations Presently stable on long-acting injectable (LAI) with history of clinical instability prior to LAI use Essock SM, et al. Am J Psychiatry. 2006; 163:

6 Page 3 Steps in Deciding to Make an Elective Antipsychotic Switch Identify target symptoms and side effects Translate therapeutic targets into outcomes than can be tracked Determine if therapeutic target is amenable to pharmacological intervention Optimize current treatment regimen if possible Evaluate appropriateness of adjunctive interventions Conduct risk/benefit assessment with the patient Steps in Implementing an Elective Antipsychotic Switch Educate the patient about the risk/benefits of the new medication relative to current side effect issues Work with the patient in deciding which medication to try next Make a switching plan with attention to the potential sleep-wake affects of both antipsychotics Monitor more closely during the switch Steps in Implementing an Elective Antipsychotic Switch Be alert for rebound and new-onset side effects Provide short-term medication to manage sleep disturbance, agitation, and anxiety Evaluate efficacy and safety/tolerability outcomes; note that changes in side effects may appear at different times (e.g. short period for changes in lipid or prolactin levels, longer period for weight loss) Switching Strategies No clear algorithmic approach has been established More gradual (conservative) approaches often recommended; less gradual (aggressive) may be more appropriate in certain situations The best strategy will be dependent upon: Evidence (when available) Reason for switch Current illness severity

7 Page 4 Abrupt Switch Cross-Taper Switch Buckley PF, et al. J Clin Psychiatry. 2008; 69(s1): 4-17 Correll CU. J Clin Psychiatry. 2006; 67(1): Buckley PF, et al. J Clin Psychiatry. 2008; 69(s1): 4-17 Correll CU. J Clin Psychiatry. 2006; 67(1): Plateau Cross-Taper Switch Ascending Taper Switch Buckley PF, et al. J Clin Psychiatry. 2008; 69(s1): 4-17 Correll CU. J Clin Psychiatry. 2006; 67(1): Buckley PF, et al. J Clin Psychiatry. 2008; 69(s1): 4-17 Correll CU. J Clin Psychiatry. 2006; 67(1):

8 Page 5 Ascending Plateau Switch Descending Taper Switch Buckley PF, et al. J Clin Psychiatry. 2008; 69(s1): 4-17 Correll CU. J Clin Psychiatry. 2006; 67(1): Buckley PF, et al. J Clin Psychiatry. 2008; 69(s1): 4-17 Correll CU. J Clin Psychiatry. 2006; 67(1): Descending Plateau Switch Side Effect Comparison Four major side effects to consider when choosing between or among FGAs and SGAs EPS (including Tardive Dyskinesia) Prolactin elevation and its effects Weight gain and associated side effects QTc prolongation Buckley PF, et al. J Clin Psychiatry. 2008; 69(s1): 4-17 Correll CU. J Clin Psychiatry. 2006; 67(1):

9 Page 6 EPS TD Side Effect Comparison EPS and TD High potency FGA > Mid Potency FGA=Risperidone* > Low potency FGA Risperidone*=Paliperidone Aripiprazole (mainly akathisia) Asenapine=Iloperidone=Lurasidone Olanzapine=Ziprasidone Quetiapine >/= Clozapine (minimal to none) FGA > SGA > Clozapine Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): Side Effect Comparison Prolactin Elevation and Its Effects Effects of prolactin elevation galactorrhea, amenorrhea, gynecomastia, sexual dysfunction, decreased bone density Risperidone=Paliperidone FGAs Olanzapine Ziprasidone Quetiapine=Clozapine (minimal to none) Aripiprazole (minimal to none) Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): Common Adverse Effects Associated with Receptor Blockade Dopamine (D 2 ) Antagonism Nigrostriatal EPS and akathisia Nigrostriatal Suppression of dyskinetic movements* Tuberoinfundibular Prolactin elevation Mesocortical Secondary negative symptoms Common Adverse Effects Associated with Receptor Blockade Dopamine (D 2 ) Withdrawal Mesolimbic rebound psychosis Nigrostriatal withdrawal dykinesia How to manage? Slow down taper Use of plateau taper strategy See management of Tardive Dyskinesia

10 Page 7 Acute Dystonia: sustained muscle contraction Management of EPS and TD Pseudoparkinsonism: bradykinesia, tremor, cogwheel rigidity, postural instability Akathisia: internal feeling of restlessness Tardive Dyskinesia: late onset strange movements choreiform ( worm-like) Tardive Dystonia Tardive Akathisia < 24 to 96 hrs Few days to few weeks > 6 months to years IM benztropine, diphenhydramine; IM lorazepam Decrease dose; Beta-blocker; Lorazepam Decrease dose; Benztropine, Trihexyphenidyl, Diphenhydramine; Amantadine Decrease dose; FGA to SGA; SGA to lower EPS SGA; Clozapine Management of Prolactin Elevation If significant/bothersome symptoms develop (e.g. galactorrhea, amenorrhea, gynecomastia, sexual dysfunction, decreased bone density) may consider switch: FGA to SGA (other than Risperidone/Paliperidone) Risperione/Paliperidone to lower risk SGA Schizophrenia and Metabolic Syndrome Axis III co-morbidity in Schizophrenia Obesity Cardiovascular Diabetes Higher incidence independent of exposure to SGAs Metabolic Syndrome TG > 150mg/dL HDL < 40mg/dl Men HDL < 50mg/dL Women FBG > 100mg/dL BP > 130/85mmHg Waist circumference > 40 Men > 34 Women Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care. 2004; 27(2): Common Adverse Effects Associated with Receptor Blockade Serotonin (5-HT) Antagonism Increased appetite/weight gain (5-HT 2C )

11 Page 8 Common Adverse Effects Associated with Receptor Blockade Histamine (H 1 ) Antagonism Sedation, sleep induction Increased appetite Weight gain Side Effect Comparison Weight Gain and Other Metabolic Effects Weight Gain Dyslipidemia Hyperglycemia Clozapine Olanzapine Quetiapine Risperidone Paliperidone Illoperidone ++ +/0 +/0 Asenapine +/0 +/0 +/0 Lurasidone +/0 +/0 +/0 Aripiprazole +/0 +/0 +/0 Ziprasidone +/0 +/0 +/0 Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): Dehart M, et. CNS Drugs. 2012; 26(9): Side Effect Comparison Weight Gain and Other Metabolic Effects Weight Gain Dyslipidemia Hyperglycemia LP FGA MP FGA + +/0 +/0 HP FGA +/0 +/0 +/0 Strategies to Prevent or Reverse Weight Gain and Metabolic Side Effects Pharmacotherapy Metformin, Topiramate current evidence is too limited to support their regular use as adjunctive medications Non-pharmacologic Diet, exercise Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): Gardner DM, et al. CMAJ. 2005;172(13): Maayan L, et al. Neuropsychopharmacology. 2010; 35: Maayan L, et al. Neuropsychopharmacology. 2010; 35:

12 Page 9 How effective is switching to reduce metabolic risk for CVD?-Newcomer JW, et al Patients with Schizophrenia or Schizoaffective Randomly assigned to remain on Olanzapine OR switch to Aripiprazole (2-week cross taper) Evaluation duration 16 weeks How effective is switching to reduce metabolic risk for CVD? Newcomer JW, et al Results Metabolic Outcomes Primary outcome mean weight change ARI 1.8 vs OLZ kg (p < 0.001) Clinically relevant weight loss (> 7%): ARI 11.1% vs OLZ 2.6% (p < 0.038) Clinically relevant weight gain (> 7%): ARI 2.5% vs OLZ 9.1% (p < 0.082) Secondary outcomes % Δ in TGs: ARI 14.46% vs OLZ +5.29% (p = 0.002) % Δ in TC, HDL, and non-hdl: statistically significant for ARI No significant differences in Δ in LDL-C, fasting glucose, fasting insulin, fasting C-peptide, or glucose tolerance test at week 16 Newcomer JW, et al. J Clin Psychiatry. 2008; 69: Newcomer JW, et al. J Clin Psychiatry. 2008; 69: How effective is switching to reduce metabolic risk for CVD? Newcomer JW, et al Results Clinical Status CGI-I (lower is better): OLZ 3.09 ± 0.16 vs ARI 3.74 ± 0.15 (p < 0.001; LOCF) CGI-I (lower is better): OLZ 2.63 ± 0.14 vs ARI 3.10 ± 0.14 (p = 0.020; completers) CGI-I for both ARI ad OLZ in the range of minimally improved to no change Results Treatment Discontinuation ARI 36% (32/88) vs OLZ 26% (22/85) How effective is switching to reduce metabolic risk for CVD?-Newcomer JW, et al Results side effects ARI insomnia (21.6%), headache, nausea OLZ insomnia (10.7%), weight increase Similar rates of EPS and use of antimuscarinic agents Newcomer JW, et al. J Clin Psychiatry. 2008; 69: Newcomer JW, et al. J Clin Psychiatry. 2008; 69:

13 Page 10 How effective is switching to reduce metabolic risk for CVD? CAMP Trial Patients with Schizophrenia or Schizoaffective Randomly assigned to remain on Olanzapine, Quetiapine or Risperidone OR switch to Aripiprazole (3-week cross taper) Manualized behavioral intervention diet and exercise to reduce CVD risk Evaluation duration 24 weeks How effective is switching to reduce metabolic risk for CVD? CAMP Trial Results Metabolic Outcomes Primary outcome reduction in non-hdl-c ARI 20.2 vs SGAs 10.8 mg/dl (95% CI 2.2, 16.5, p=0.010) Secondary outcomes Weight loss: ARI 3.6 vs SGAs 0.7 kg (95% CI 1.6, 4.2, p < 0.001) BMI: ARI 1.07 units (p < 0.001) TGs: ARI 25.7 vs SGAs +7.0 mg/dl (95% CI 12.1, 53.4, p=0.002) No statistically significant differences in HDL-C, LDL-C, C- reactive protein, fasting glucose, fasting insulin, A1C, or glucose tolerance test 2-hour insulin level: ARI 31.1 vs SGAs 6.8 mg/dl (p=0.014) Stroup TS, et al. Am J Psychiatry. 2011; 168(9): Stroup TS, et al. Am J Psychiatry. 2011; 168(9): How effective is switching to reduce metabolic risk for CVD? CAMP Trial Results Clinical Status No difference in efficacy failure: ARI N=22, 20.6% vs SGA N=18, 17% (p=0.4872) No difference in time to efficacy failure: hazard ratio for switching (95% CI , p=0.3703) Hospitalized for psychiatric reasons: ARI N=8, 7.5% vs SGA N=5, 4.7% Results Treatment Discontinuation Switch (ARI) more likely to d/c before 1 month (16.5% vs 7.8%) and more likely to d/c before 24 weeks (43.9% vs 24.5%) Stroup TS, et al. Am J Psychiatry. 2011; 168(9): How effective is switching to reduce metabolic risk for CVD? CAMP Trial Results side effects Switchers (ARI): more insomnia Stayers (SGAs): more sleepiness, hypersomnia, nausea, dry mouth, increased appetite, and akinesia Stroup TS, et al. Am J Psychiatry. 2011; 168(9):

14 Page 11 Common Adverse Effects Associated with Receptor Blockade Histamine (H 1 ) Common Adverse Effects Associated with Receptor Blockade Muscarinic (M 1-5 ) Withdrawal Rebound insomnia Increased anxiety Decreased appetite Weight loss How to manage? Hydroxyzine Benzodiazepine Antagonism Deficit in memory and cognition Delirium Anticholinergic effects (blurred vision, dry mouth, constipation, urinary retention, tachycardia) Common Adverse Effects Associated with Receptor Blockade Muscarinic (M 1-5 ) Withdrawal Cholinergic rebound (flu-like symptoms, sleep disturbances, increased sweating) Agitation, fear, hallucinations How to manage? Symptomatic management; possible use of antimuscarinics Slower taper; use of plateau strategy Withdrawal Symptoms and Rebound Symptoms Associated with Atypical Antipsychotic Switching Switching to Switching from Aripiprazole Clozapine Aripiprazole Clozapine Olanzapine Quetiapine Risperidone Ziprasidone Haloperidol Psychosis, insomnia, agitation, anxiety, cholinergic rebound Sedation weight gain, metab, dist. Olanzapine Same as above Weight Gain Quetiapine Reisperidone Ziprasidone Insomnia, agitation No major TEAE reported or to be anticipated Weight Gain, sedation, weight gain, metab. Dist. Sedation, weight gain, metab. Dist. anxiety, agitation Sedation, weight gain, metab. Dist. Sedation, weight gain, metab. Dist. No major TEAE reported or to be anticipated Same as above Prolactin Increase Psychosis, dyskinesia, cholinergic rebound, RR decrease Prolactin increase Psychosis, cholinergic rebound, prolactin increase Insomnia, prolactin increase Prolactin Increase Sedation, prolactin increase Insomnia, agitation, anxiety, cholinergic rebound Same as above Insomnia, agitation Psychosis, dyskinesia, Prolactin Increase Insomnia Same as above Same as above No major TEAE reported or to be anticipated Same as above Haloperidol Psychosis, weight gain, dyskinesia, Dyskinesia

15 Page 12 Switch to Asenapine, Illoperidone, and Lurasidone Why switch to one of these agents? Lower risk for metabolic side effects and EPS; likely switching FROM a medication with GREATER risk of metabolic side effects or EPS; similar concerns regarding withdrawal symptoms Any special considerations for tapering? Illoperidone titrate slowly to avoid postural hypotension; plateau strategy may be most appropriate QTc Prolongation Pfizer 054 Study measured QTc prolongation (msec) Ziprasidone 15.9 (10.6 to 21.2) Risperidone 3.9 ( 0.3 to 7.5) Olanzapine 1.7 ( -3.8 to 7.1) Quetiapine 5.7 ( 1.8 to 9.7) Thioridazine 30.1 (24.8 to 35.5) Haloperidol 7.1 ( 1.8 to 12.4) Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): QTc Prolongation Immediate-release Paliperidone (8mg daily) QTc prolongation of 12.3 msec Iloperidone (12mg BID) QTc prolongation of 9 msec Low risk for QTc prolongation: Aripiprazole, Asenapine, Clozapine, Lurasidone, Olanzapine, Quetiapine, Risperidone QTc Prolongation Management Avoid concomitant use of other QTc prolonging medications Avoid use of higher risk medications in patients at increased for ventricular dysrhythmias Normalize electrolytes (potassium, magnesium) Switch to low risk medication Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): Buchanan RW, et al. Schizophrenia Bullentin. 2010; 36(1): 71-93

16 Page 13 Notes: Notes: Notes: Notes:

17 3/27/2014 Withdrawal Symptoms and Rebound Symptoms Associated with Atypical Antipsychotic Switching Switching to Switching from Aripiprazole Clozapine Olanzapine Quetiapine Risperidone Ziprasidone Haloperidol Aripiprazole Sedation weight gain, metab, dist. (same as for clozapine) Sedation, weight gain, metab. Dist. Prolactin Increase Sedation, prolactin increase Prolactin Increase Clozapine Psychosis, insomnia, agitation, anxiety, cholinergic rebound anxiety, agitation No major TEAE reported or to be anticipated Psychosis, dyskinesia, cholinergic rebound, RR decrease Prolactin increase Insomnia, agitation, anxiety, cholinergic rebound Insomnia Olanzapine Same as above Weight Gain Same as above Psychosis, cholinergic rebound, prolactin increase Same as above Insomnia Quetiapine Insomnia, agitation Weight Gain Weight Gain Insomnia, prolactin increase Insomnia, agitation Insomnia Reisperidone, sedation, weight gain, metab. Dist. (same as for clozapine) (same as for clozapine) Psychosis, dyskinesia, No major TEAE reported or to be anticipated Ziprasidone No major TEAE reported or to be anticipated Sedation, weight gain, metab. Dist. Sedation, weight gain, metab. Dist. (same as for olanzapine) Prolactin Increase Same as above Haloperidol Psychosis, weight gain, dyskinesia, (same as for olanzapine) Dyskinesia Dyskinesia 1