A Primer on Psychotropic Medications. Michael Flaum, MD
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1 The Iowa Mental Health System and Employment for Individuals with Psychiatric Conditions Iowa Vocational Rehabilitation Services Conference Des Moines, IA, September 18, 2006 A Primer on Psychotropic Medications Michael Flaum, MD Director, Iowa Consortium for Mental Health Department of Psychiatry, University of Iowa Carver College of Medicine
2 Broad Classes of Psych Drugs Antipsychotics Antidepressants Mood Stabilizers Antianxiety Agents Psychostimulants
3 Costs of Mental Health and All Other Drugs Iowa Medicaid: Drop Page Fields Here $450,000,000 $400,000,000 $350,000,000 $300,000,000 $250,000,000 $200,000,000 Drug Class All Other Drugs Total MH $150,000,000 $100,000,000 $50,000,000 $0 Sum of SFY2001 Sum of SFY2002 Sum of SFY2003 Sum of SFY2004 Sum of SFY2005 Data
4 Mental Health Drug Costs by Category Iowa Medicaid: FY Drop Page Fields Here $180,000,000 $160,000,000 $140,000,000 $120,000,000 $100,000,000 $80,000,000 $60,000,000 Drug Class Antianxiety Agents / Hypnotics Psychostimulants Anticonvulsants Antidepressants Antipsychotics (Total) $40,000,000 $20,000,000 $0 Sum of SFY2001 Sum of SFY2002 Sum of SFY2003 Sum of SFY2004 Sum of SFY2005
5 Psychoactive Costs by Category Iowa Medicaid Data $60,000,000 $50,000,000 $40,000,000 $30,000,000 $20,000,000 $10,000,000 $0 Antidepressants Antipsychotics Mood Stabilizers Sedative/Hypnotics Stimulants
6 Antipsychotic Drug Costs by Category Iowa Medicaid: FY Drop Page Fields Here $80,000,000 $70,000,000 $60,000,000 $50,000,000 $40,000,000 $30,000,000 Drug Class Antipsychotics (Typical) Antipsychotics (Atypical) $20,000,000 $10,000,000 $0 Sum of SFY2001 Sum of SFY2002 Sum of SFY2003 Sum of SFY2004 Sum of SFY2005 Data
7 Terms used to categorize Antipsychotics First Generation vs. Second Generation Old vs. New Typical vs. Atypical Novel vs. Conventional Cheap vs. Expensive
8 New Antipsychotics Marketed in U.S. Generic Clozapine Risperidone Olanzapine Quetiapine Ziprasidone Brand Clozaril Risperdal Zyprexa Seroquel Geodon Company Year Novartis 89 Janssen 94 Eli Lilly 96 Astra-Zeneca 97 Pfizer 01 Aripiprazole Abilify Bristol Myers Squibb 02
9 Introduction of Antipsychotics Introduction of Antipsychotics in the US Chlorpromazine 54 Fluphenazine 59 Thioridazine 59 Haloperidol 67 Clozapine 89* Risperidone 94 Olanzapine 96 Quetiapine 97 Ziprasidone 01 Many others Aripiprazole ? 2000 Era of Typical Antipsychotics *developed in 58
10 Reputed Advantages of Newer vs. Older Antipsychotics Less Extrapyramidal Side Effects (EPS) Including Tardive Dyskinesia More effective Broader spectrum of action Mood symptoms Negative symptoms
11 Motor side effects (Extrapyramidal Symptoms or EPS) Parkinsonism Tremor, slowing (zombie-like) Dystonia Muscle spasms Akathesia Restless Leg Syndrome Tardive Dyskinesia
12 Dealing with EPS Side Effects Parkinsonism, Dystonia, Akathesia Short term, time limited - Go away with lower doses or when meds are stopped Often respond to treatment with side effect meds,, (e.g., Cogentin, Inderal) Tardive Dyskinesia Long term; can be irreversible (i.e., persist or worsen even after meds are stopped) No good treatment may respond to Vit E.
13 Literature Review: % of Patients with Tardive Dyskinesia in 1 Year with Conventional Antipsychotics
14 Reported Rates (% per year) of TD with New Antipsychotics (non- elderly) Risp. (1) Olanz (2) Quet. (3) Source: (1) Csernansky J, et al. ECNP poster. 1999;London. (2) Beasely et al, Br J Psychiatry 1999;175:391-2 (3) Astra-Zeneca Pharmaceuticals, 1999 (data on file)
15 Rate of Tardive Dyskinesia Among Elderly Patients % of patients with TD N = 61 in each group Months Haloperidol Risperidone Matched on major TD risk factors: 1) Age; 2) Dx; 3) Duration of neuroleptic exposure at study entry Jeste et al, JAGS 47: , 1999
16 EPS - Conclusion A major problem Compliance issue in younger patients Tardive dyskinesia in older patients Newer agents definitely better than older
17 Disadvantages of Newer Antipsychotics Metabolic effects Weight gain Diabetes (type II) High Triglyceride levels Costs Few available in long acting injectible forms
18 Average weight change over 10 weeks on Atypical Antipsychotics Wt change (lbs.) Placebo Zipras. Risp. Olanz. Quet.* Cloz. *Quetiapine estimate is extrapolated from 6 week data to 10 weeks (assuming linear gain) From: Allison et al Am J Psychiatry 1999;156:1686
19 Weight Gain after 8 weeks in Risperidone vs. Olanzapine study (RIS-112) Risperidone Olanzapine Percent of Patients >7% >10% >15% >20% Percent of initial body weight gained
20 Excessive Weight May Have Serious Consequences Increased risk of morbidity and mortality Cardiovascular disease Diabetes Cancer Breast, ovarian, endometrial, gallbladder and cervical cancers in women Colorectal and prostate cancers in men Diminished self-esteem esteem Noncompliance
21 Comparative Efficacy of New Antipsychotics Are all new antipsychotics equal in efficacy? Don t t yet know Differing neurotransmitter profiles suggest differential efficacy (positive, negative, mood, etc.)
22 In Vitro Receptor Activity of Antipsychotics 5-HT 2 α 1 D D1 1 D 1 D 2 Muscarinic D 2 5-HT 2 α 1 α 2 D 1 D 2 α 1 D 2 α 2 Haloperidol Clozapine H 1 Risperidone 5-HT 2 D 1 Muscarinic D 2 α 2 D 1 D 2 5-HT 2 α 1 D 1 D 2 5-HT 2 α 2 α 1 Olanzapine 5-HT 2 α 1 Quetiapine Ziprasidone
23 CATIE Clinical Antipsychotic Trial of Intervention Effectiveness National Institute of Mental Health
24 CATIE: Participants 57 sites in US N = 1493 (randomized) Age: Dx: Schizophrenia (DSM-IV) No history of treatment resistance Non-1 st episode
25 CATIE: Medications Compared Generic Name Trade Name FDA Approval Risperidone Risperdal 1994 Olanzapine Quetiapine Ziprasidone* Perphenazine Zyprexa 1996 Seroquel 1997 Geodon 2001 Trilafon 1957
26 Outcome Measures Primary: Discontinuation of treatment for any cause Secondary: Specific reasons for discontinuation Symptom ratings (PANSS, CGI) Side effects / tolerability / adverse events EPS, Weight gain, lab values, EKG
27 CATIE Trial: % Discontinued before 18 months (for any reason) Overall Quetiapine Ziprasidone Perphenazine Risperidone Olanzapine
28 CATIE: Symptom Ratings Positive and Negative Symptom Scale (PANSS) Ratings Clinical Global Impression (CGI) Ratings
29 CATIE Trial: Mean Change in Fasting Blood Glucose Levels Olanzapine Risperidone Perphenazine Ziprasidone Quetiapine
30 CATIE Trial: Mean Change in Triglycerides Olanzapine Risperidone Perphenazine Ziprasidone Quetiapine
31 People who take antipsychotics tend to prefer newer agents to older because of less acute EPS Probably leads to better compliance
32 Is the term antipsychotic still appropriate? Are psychotic symptoms the primary target symptoms? Psychotic symptoms Delusions, hallucinations Disorganized Speech, disorganized, agitated behavior Broader spectrum of action? Negative symptoms Cognitive impairment Mood symptoms Aggressivity/impulsivity
33 Year of Approved FDA Indications for Second Generation Antipsychotics Brand Name Abilify Geodon Seroquel Zyprexa Chemical Name Acute mania Schizo- phrenia Bipolar I Maint- enance Aripiprozole Ziprazidone Quetiapine Olanzapine Risperdal Risperidone Clozaril Clozapine 89
34 Mood Stabilizers (other than antipsychotics) Chemical Name Lithium Brand Name Year of FDA approval 1970 Divalproex Depakote 1995 Carbamazepine Tegretol 2000 Lamotragine Lamictal 2003
35 Lithium First observed behavioral effects in 1950 s FDA approved for acute mania ~1970 A salt of the earth (no profit for industry) May be best for pure or euphoric mania, less effective in mixed or rapid cycling Main drawback: VERY LOW THERAPEUTIC INDEX (i.e., toxic dose close to therapeutic dose) Non-response 20 25%
36 Lithium: Main side effects and Short term limitations Tremor, weight gain, GI (nausea), increased urination Long term hypothyroidism, renal insufficiency Teratogenicity Category D Highly lethal on overdose
37 Drugs to worry about in overdose Lithium Tricyclic Antidepressants Imiprimine, Nortryptyline, etc Aspirin, Tylenol
38 Drugs that rarely cause fatalities in overdose Antipsychotics (all) Newer antidepressants SSRI s SNRI s Anti-anxiety agents Including benzodiazepines Psychostimulants
39 Antidepressants :: Indications and Uses Mood Disorders MDD, dysthymia, BPAD (adjunctive) Anxiety Disorders GAD, Panic, OCD, PTSD Attention Deficit Disorders Second line to stimulants Pain Tricyclics
40 Antidepressants Tricyclics (TCA s) Mono Amine Oxidase Inhibitors (MAOI s) Selective Serotonin Reuptake Inhibitors (SSRI s) Selective serotonin and norepinephrine reuptake inhibitors (SNRI s) Others
41 Anticonvulsants as Mood Stabilizers Examples: Depakote (Valproate), Tegretol (Carbamazepine), Lamictal (Lamotragine), Topomax (Topiramate) Similar efficacy to Lithium Generally less side effects, less toxic in overdose May be quicker acting
42 Tricyclic Antidepressants Examples: nortriptyline, imiprimine, amitryptyline, Elavil Developed in the 1950 s Gold standard for decades Main drawback: High lethality and morbidity potential in OD Cheap and effective
43 Monoamine Oxidase Inhibitors Examples: Parnate, Nardil Also developed in the 1950 s Effective and cheap Rarely used because of potentially dangerous interactions with many other drugs and dietary products If used, strict dietary restrictions
44 Selective Serotonin Reuptake Inhibitors (SSRI s) Examples: Prozac, Paxil, Zoloft, Celexa, Lexapro Developed in 1980 s Dominated the market since Low lethality potential in OD Main side effects: sexual? Side effect of increased suicidality, especially in children
45 SSRI s (cont) Many generics available, more coming Prozac fluoxetine Zoloft sertraline Paxil Paroxatine All equally effective?
46 Costs of Antidepressants
47 Other Antidepressants SNRI s: Selective serotonin and norepinephrine reuptake inhibitors Effexor Cymbalta Remeron Good for people who can t t sleep Weight gain Wellbutrin may have less sexual side effects; may be stimulating
48 Anti-anxiety Agents Benzodiazepines E.g., Valium, Librium, Ativan, Xanax, Klonopin Can be addictive, and abused Tolerance often develops Lower potential for OD than most people think
49 Meds used to treat ADHD Psychostimulants Examples: ritalin; adderall, concerta Amphetamine or amphetamine-like 1 st line treatment for childhood ADHD Adult ADHD? Strettera (Atamoxatine) Non-stimulant Antidepressants
50 Meds used to treat Borderline Personality Disorder Target the predominant symptom pattern, not the Dx Antidepressants Mood stabilizers Antipsychotics Anti-anxiety agents
51 Polypharmacy Medication use is part evidence-based science, part industry-driven, driven, part art My opinion: we are in an era of over- utilization of psychotropic medications in general Polypharmacy is the norm rather than the exception We (psychiatry) will not look back on this era proudly
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