Presentation is loading. Please wait.

Presentation is loading. Please wait.

Schizophrenia: An overview of diagnosis and treatment

Similar presentations

Presentation on theme: "Schizophrenia: An overview of diagnosis and treatment"— Presentation transcript:

1 Schizophrenia: An overview of diagnosis and treatment
This slide presentation briefly reviews clinical features of schizophrenia, its costs, and considerations in selection of therapy. The role of ZYPREXA for the treatment of schizophrenia is described through a summary of the clinical studies documenting the efficacy and safety of ZYPREXA as a first-line therapy for treatment of schizophrenia.

2 Epidemiology of Schizophrenia
A disease process with multiple signs and symptoms involving thoughts, perceptions, emotions, and behavior1 Most catastrophic mental illness1,2 Peak incidence in males at 15 to 25 years of age and in females at 25 to 35 years of age1 Global incidence: 1% in all societies3 Course of illness is extremely variable, often chronic, and sometimes episodic1 Florid symptoms may diminish with age, although years of dysfunction are rarely overcome1 Schizophrenia is a disease process.1 The peak incidence of schizophrenia occurs in young adults.1 It rarely strikes before puberty. It is likely that both genetic and environmental factors play a role in the development of schizophrenia.1 The clinical course of schizophrenia is variable, but often chronic. Years of disability associated with schizophrenia are rarely overcome.1 Positive symptoms may diminish with age, but negative symptoms tend to persist.1

3 Epidemiology of Schizophrenia
Associated with heavy emotional burden4 Often requires long-term caregiving4 50% of patients exhibit comorbid substance abuse Economic impact 22% of all mental illness costs in the United States5 Annual direct and indirect costs estimated at $65 billion (1991)5 Annual treatment costs may range from $10,000 to $70,000 per patient6-9 Schizophrenia is associated with considerable indirect and direct costs: The annual direct and indirect costs of schizophrenia in the United States are an estimated $32.5 billion.5 Direct costs include physicians’ bills, drugs, nursing home care, and services of mental health organizations and professionals. Indirect costs include morbidity, premature mortality, costs incurred by the criminal justice system, and family care giving. The annual per-patient treatment costs of schizophrenia may be $10,000 to $70,

4 Behavioral Symptoms Positive Symptoms Negative Symptoms Mood
Delusions Hallucinations Disorganized speech Suspiciousness Exaggerated thoughts Negative Symptoms Affective flattening Alogia / Avolition Anhedonia Social withdrawal Mood Depression Mania Anxiety / Aggression Cognition Attention / Memory Organized Thinking Judgment / Insight Positive symptoms: Delusions, hallucinations, suspiciousness and conceptual disorganization Negative symptoms: Flat affect, lack of motivation, social withdrawal Alogia= decrease in speech Avolition= decrease in activities Anhedonia= decrease in ability to experience pleasure Hostile behavior: Anger, belligerence Cognitive symptoms: Poor attention, disorganized thinking, lack of judgment and insight. Executive functioning …. Daily living skills

5 Impact of Mood Symptoms
Depressive symptoms present in up to 65% of patients Affect all other core symptoms Affect all outcomes, including compliance Higher suicide rate 40% Attempt / 10% Completion Depressive and anxious symptoms: Are observed in up to 65% of patients with schizophrenia.10 Affect core symptoms of schizophrenia.10 Are associated with a higher suicide rate.11

6 Interplay of Depressive and Other Symptoms of Illness in Schizophrenia
Clinical Issues Interplay of Depressive and Other Symptoms of Illness in Schizophrenia Negative Symptoms Illness Related Symptoms Positive Symptoms Cognitive Dysfunction Mood Symptoms EPS Depressive symptoms associated with schizophrenia: Affect both positive and negative symptoms. Are interrelated with: Cognitive dysfunction Functional impairment EPS Prolactin effects Prolactin Effects Functional Impairment Medication Related Side Effects

7 Causes of Psychosis Dopamine Hypothesis Neurotransmitter Interaction
Structural Abnormalities Prenatal or Perinatal Trauma

8 Brain Pathways From:Risch SC. Pathophysiology of schizophrenia and the role of newer antipsychotics. Pharmacotherapy 1996;15(1 pt 2):12S


10 Dopamine Activity Overview
Psychotic Symptoms: Caused by too much Dopamine activity in the limbic system Extrapyramidal Symptoms: Not enough Dopamine activity

11 Efficacy = Dopamine Blockade
All Anti-psychotic medications MUST: BLOCK DOPAMINE RECEPTORS For Superior Efficacy: SELECTIVE DOPAMINE BLOCKING Degree of dopamine blocking Activity in selective areas of the brain (A9, A10)

12 Degree of Blockade Agent must block 50% of D2 receptors to begin controlling positive symptoms Blocking > 70% of D2 receptors may cause dose-dependant EPS PUBLISHED DATA SHOWS: Zyprexa & Clozaril 50-60% D2 Blockade Risperdal & Haldol 80-90% D2 Blockade

13 Selective Dopamine Blockade
A-10 (Mesolimbic) PATHWAY The "Efficacy Pathway" ZYPREXA is theorized to have strong activity here A-9 (Nigral Striatal) PATHWAY The "EPS Pathway" Typicals and Risperdal are theorized to be more active here (vs.. A-10) A-10 = GOOD A-9 = BAD

14 Patient Care The "Team Approach"
Pharmacologic Psychiatrist Psychiatric Nurse / DON Psychologist Medical Director Primary care physician Physician Assistant (PA) Nurse Practitioner (NP) Consultant / Clinical Pharmacist Case Manager / Social worker Family and friends Psychological Rehabilitation Psychosocial

15 Considerations in Choosing Antipsychotics: Acute vs.Continuation
Time to response: significant response may take 4 to 5 weeks of therapy with conventional agents12 Symptom control/level of function: persistence of positive, negative, cognitive, or affective symptoms may indicate need to switch Incidence of adverse effects: EPS/TD, sedation, cognitive impairment, hypotension, sexual dysfunction (Risks vs. Benefits) Cost of therapy, including acquisition price and cost of necessary adjunctive meds or inpatient treatment Available formulations: Dosing Flexibility Previous experience with an agent or class OBJECTIVES OF THERAPY: Acute/inpatient goals: Initial control of acute psychotic symptoms beginning week 1 (positive symptoms, agitation, hostile behavior, mood symptoms) Outpatient goals: Maintain and improve clinical effect over time, Improvement in negative symptoms, Improve depression-anxiety symptoms, Patient acceptance of therapy (minimize adverse effects such as EPS, prolactin effects) Several factors contribute to the ultimate choice of antipsychotic agent: Onset of action and whether rapid control of symptoms is needed Efficacy in symptom control, including positive and negative symptoms as well as mood, cognition, and behavioral symptoms Side effect profile Total cost of therapy Formulations and their suitability for the individual patient Clinician’s and patient’s past experience with a particular medication

16 Chemical Structures Clozapine Olanzapine Quetiapine Haloperidol
OH N N O N O N N N Cl N N N N N S S CH3 H H Clozapine Olanzapine Quetiapine CH3 N N HO Cl O F N N Newer antipsychotic agents have been developed in an attempt to retain positive aspects of older agents, while minimizing drawbacks. In general, atypicals have 2 major advantages compared with typical antipsychotics: Efficacy in both positive and negative symptoms Lower potential for certain side effects, including extrapyramidal side effects O N Haloperidol Risperidone O F

17 Receptor Binding Profiles
Olanzapine Clozapine Haloperidol Aripiprazole D1 D2 D4 5-HT2A 5-HT2C Musc a 1 Risperidone Quetiapine Ziprasidone a 2 H1 Bymaster FP, et al. Neuropsychopharmacology. 1996;14(2):87-96. Schotte A, et al. Psychopharmacology (Berl). 1996;124(1-2):57-73.

18 Anti-Psychotic Side Effects:
Extrapyramidal Symptoms (EPS) Akathisia: Severe inner restlessness Dystonia: Involuntary muscle spasms Parkinsonism: Rigidity of the muscles, Tremor, Shuffling of feet "It can be argued that EPS are the most troublesome side effects… a major reason why patients discontinue their drug therapy"* *Source: Casey DE. International Clinical Psychopharmacology. 1997;12 (suppl 1):S19-S27

19 Anti-Psychotic Side Effects:
TD (Tardive Dyskinesia) Involuntary muscle movements of the face, body and/or trunk Often Irreversible: Patient is disfigured, "looks like a psych patient" Typicals carry 5% risk of developing TD per year of exposure 85% risk after 25 years of continuous exposure *Source: Casey DE. International Clinical Psychopharmacology. 1997;12 (suppl 1):S19-S27

20 Anti-Psychotic Side Effects:
Prolactin Related Side-Effects Short Term Amenorrhea Galactorrea Gynecomastia Sexual Dysfunction Long Term Increased risk for Osteoporosis Increased risk for Breast Cancer

21 Other Limitations of Conventional Anti-Psychotics:
Extrapyramidal symptoms (EPS) Tardive dyskinesia (TD) Prolactin elevation Sedation QTc prolongation Cognitive impairment Orthostatic hypotension Compliance / Relapse Conventional antipsychotics may carry a substantial list of limitations both in terms of side effect profile as well as the potential for poor compliance and inadequate response. Among the most troublesome side effects of conventional antipsychotics are EPS, tardive dyskinesia, and cardiovascular toxicity. According to IMS Health data, conventional antipsychotics account for more than half of all antipsychotics currently prescribed by PCPs.

22 Typical Antipsychotics Haldol, Mellaril, Thorazine, Prolixin, etc.
Perceived Advantages Perceived Disadvantages Available since the mid - '50s Proven positive symptom efficacy Formulations: Short acting ( I.M.) Long acting (Depot) Generics available ($) Incomplete symptom efficacy (compared to atypicals) Negative Mood Cognition High incidence of EPS Increased risk for TD Prolactin-related side effects

23 The Bipolar patient... “My thoughts ran with lightning-like rapidity from one subject to another. All the problems of the universe came crowding in my mind, demanding instant discussion and solution--- mental telepathy, hypnotism, women’s right, all the problems of medical science, religion and politics Months later……...

24 Bipolar Patient cont….. “I seem to be in a perpetual fog and darkness. I cannot get my mind to work. Instead of associations clicking into place, everything is an inextricable jumble. I could not feel more ignorant, undecided or inefficient. It is appallingly difficult to concentrate, and writing is a pain and grief to me”

25 Classifications of Bipolar
Bipolar I 1 or more manic or mixed episodes May be followed by 1 or more depressive episodes Bipolar II 1 or more depressive episodes accompanied by at least 1 hypomanic episode mania not severe enough to cause “marked impairment”

26 Subtypes: Rapid Cycling
4 or more mood episodes in 1 year Occurs in 12-20% of bipolar patients Occurs later in the illness Difficult to treat More common in women Inducible by antidepressants Upon Treatment, more susceptible to pole flipping.

27 Symptom Domains in Bipolar I Disorder
Manic Mood and Behavior Dysphoric Mood and Behavior Euphoria Grandiosity Pressured Speech Impulsivity Excessive Libido Recklessness Diminished Need for Sleep Depression Anxiety Irritability Hostility Violence or Suicide Cognitive Symptoms Racing Thoughts Distractibility Poor Insight Disorganization Inattentiveness Confusion Psychotic Symptoms Delusions Hallucinations Sensory Hyperactivity

28 Symptom Descriptors for Bipolar
Manic Episodes inflated self-esteem or grandiosity decreased need for sleep excessive talkativeness racing thoughts distractibility increased physical activity pursuit of pleasurable but risky activities psychotic features Depressive Episodes depressed mood diminished interests or pleasure fatigue worthlessness or guilt poor concentration suicidal thoughts Increase or decrease in: weight/appetite physical activity sleep

29 Classifications of Bipolar
Depressive Episode Manic Episode BIPOLAR I Mixed Episode Mood Within Normal Range Rapid Cycling Hypomanic Episode BIPOLAR II Subtypes of Bipolar Classifications of Bipolar

30 Epidemiology of Bipolar Disorder
Psychotic symptoms occur in 47-75% of all patients at some point in the disease cycle 2/3 of bipolar episodes present as depression No differences in race or gender 50% have a family history Women with postpartum depression at higher risk Symptoms usually first appear between the ages of 15-24 Prevalence rates from 1.2% - 1.6% • Prevalence is similar between men and women • Women appear more likely to be depressed at the first episode and more likely to develop rapid cycling 47-75% of pts hospitalized with bipolar disorder experience psychotic symptoms *Compared to an 18% rate for those without bipolar

31 Effect on Social Functioning
Ability to work declines in 66% of patients Social functioning declines in 50% of patients Represents a high divorce rate 60% suffer from substance abuse issues May be self medicating Masks illness in early stages Predictor of early onset (before age of 20) Significant impact on expected life span and personal health

32 Morbidity of Bipolar Disorder
Recurrent illness in 85-95% of patients Functional recovery often lags behind symptomatic and syndrome recovery Recurrent episodes may lead to progressive deterioration in functioning Number of episodes may affect subsequent treatment response and prognosis Patients with Bipolar Disorder usually suffer long-term disruption of their lives. Symptomatic episodes can persist for months or longer if not treated

33 Mortality in Bipolar Disorder
25%-50% attempt suicide Suicide completion rate ~19% 50% suicidal ideation in mixed mania Bipolar Disorder is a high mortality illness % of patients attempt at least once. Studies estimate that at least 11% kill themselves, this is 25X the rate of the general population effective treatment of Bipolar Disorder can literally be life- saving. Other features that may carry higher suicide risk include: presence of psychosis First onset of illness Rapid cycling Recent switch in mood state

34 Schizophrenia vs. Bipolar
Schizophrenia Bipolar Thinking Disorder which can affect mood Primarily a mood disorder that can affect thinking & judgment Schizophrenia is primarily a thought disorder which can effect mood whereas Bipolar disorder is primarily a mood disorder which can effect thought. Schizoaffective disorder falls in-between the two. Psychotic disorder Affective Disorder

35 Contrasts of Schizophrenia and Bipolar Disorder
Key Similarities Generally treated by psychiatrists Psychotic symptoms are frequent during mania Antipsychotics were drugs of choice through 1960s lithium as a "mood stabilizer" Awareness of TD risk (greater risk in bipolar ?) High utilization of health care system Problems with treatment compliance Key Differences Different core symptoms Different courses of illness Bipolar patients are less consistently "sick" and outcomes get closer to "well” Bipolar patients are more likely to commit suicide Treatment paradigms therapeutic setting treatment goals medication choices While some similarities exist, mostly a different patient population with different treatment paradigms

36 Related Disease Outcomes
level of functioning This slide looks at the differences of progression of schizophrenia , schizoaffective disorder and bipolar disorder. Patients with bipolar are able to get back to a higher level of functioning, close or at the level prior to and episode, where as patients with schizophrenia experience a slow steady downward drift. Patients with schizoaffective disorder are similar to patients with bipolar disorder in that they do experience some improvement during asymptotic periods, yet outcomes do deteriorate over time. Bipolar Schizoaffective Schizophrenia Schizoaffective: has features of both schizophrenia and mood disorders. Best diagnosis for patients whose clinical syndrome would be distorted if it were considered as only schizophrenia or only a mood disorder. (Kaolin and Sadock, 1996)

37 Diagnosis of Bipolar Disorder
High rates of misdiagnosis - Important to determine longitudinal course May be diagnosed as unipolar depression May be mischaracterized as adolescent behavior May be masked by substance abuse A psychiatrist is most often the one who ultimately makes the correct diagnosis Involvement from various members of the health care team (Psychologist, Psych Nurse, etc.) 84% of Bipolar Patients are initially diagnosed with something else.

38 Olanzapine Data Suggest Effects Across Multiple Neurotransmitter Systems
Olanzapine Action Relevance to Bipolar Dopamine Direct DA receptor antagonist DA antagonists reduce psychotic symptoms Serotonin Multiple, balanced 5HT receptor antagonist 5HT may affect mood, violence, suicide Acetylcholine Indirect Ach agonist Cholinomimetics may reduce mania, improve cognition While knowledge is not conclusive regarding the mechanism of action,Zyprexa's effect on several neurotransmitter systems corresponds to those postulated to be beneficial to Bipolar Disorder Blockade of Dopamine helps to reduce psychotic symptoms, but may also have anti-manic properties and help with mood-stabilization. Serotonin (particularly the 5HT2 antagonism may suggest antidepressant/ antianxiety potential) GABA= Gamma-Amino Butyrate , a primary inhibitory neurotransmitter, found to inhibit dopamine secreting neurons. Glutamate the brains most prevalent neurotransmitter.. Some evidence that lithium and valproic acid enhance glutamate as well . Role is not understood. GABA Indirect GABA agonist May help reduce manic symptoms Glutamate Modulates and stabilizes glutamate transmission May help regulate mood stability

39 Current Treatment Paradigm for Psychiatrists
(For psychosis associated with acute mania) A/P M/S A/P Maintenance Treatment MOOD STABILIZER A/D For recurrent psychotic features For recurrent depressive features A/D M/S Antipsychotics are currently not considered a standard therapy for long term treatment of bipolar

40 Attributes of Ideal Mood Stabilizer for Mania
Rapid efficacy for mania Favorable cognitive effects Treats psychotic symptoms of mania Long-term usefulness Broad efficacy (e.g., mixed, rapid cycling) Safe & well-tolerated Reduces depressive elements in mania Ease of use Adapted from Keck Jr. PE, McElroy SL. In: Nathan PE, Gorman JM, eds. A Guide to Treatment that Works. New York: Oxford University Press, 1997

41 Young Mania Rating Scale (Y-MRS)
Elevated mood Hypersexuality Irritability Racing thoughts / flight of ideas Disruptive behavior Increased activity Decreased sleep Abnormal thought content Rapid/pressured speech Inappropriate appearance Poor insight Y-MRS scale widely used in mania trials to quantitate the 11 symptoms listed on the slide. This scale captures most of the core manic symptoms 11 items are scored 0-4 or 0-8, min score = 0 ; max score =60 To be eligible to enroll in study, a Y-MRS as at least 20 was required, This would correlate to a moderately severe score , that reflects a general need for hospitalization. Response was defined as a greater than or equal to 50%v improvement in the Y-MRS score Euthymia was defined prior to the study as a Y-MRS score < 12. This definition was also used in the studies for Lithium and Valproic Acid. Y-MRS was the primary efficacy variable for both studies

42 Psychosis in Bipolar Disorder
Prevalence 55% of patients had at least one psychotic symptom by clinician evaluation 90% of patients had at least one psychotic symptom by self-report More common in mania than in depression Stabilized bipolar patients with history of psychotic features have relapse rates two to three times those without history of psychosis Over half of acutely manic patients have psychotic features, most commonly delusions. Psychotic symptoms are likely to reoccur in subsequent manic episodes Patients with psychotic symptoms appear capable of full recovery, there are studies that suggest they are less able to sustain remission and may relapse more sooner than stabilized manic pts who were free of psychosis Goodwin FK, Jamison KR, 1990; Keck Jr. PE et al, 1998; Pope HG, Lipinski JF, 1978; Tohen et al, 1990

43 Reasons for Non-Compliance
Symptoms of the illness Patients don't want to “lose the high” Feelings of Grandiosity Blood monitoring Stigma of a medication Fear of taking an “antipsychotic” Unwanted Side Effects Higher functioning pts - more sensitive? Co-morbid substance abuse Considered the most consistent predictor of poor compliance Partial efficacy Multiple daily dosing More unique to bipolar disorder Stigma: Bipolar Consumers: I can be a contributing member of society, Family Members: stigma gets in the way of resources Insight into Illness: Bipolar Consumers: Denial, Enjoy Mania, Family Member: Denial of affect on their family "The System“: lack access to medication, multiple MD switches: impacts med changes In lithium treatment studies, 18-53% of subjects are non-compliant with medications* Patient survey reveals that cognitive dulling (memory problems) is the side effect most likely to provoke drug discontinuation against medical advice* Olanzapine does not worsen and may improve cognitive functioning in mania

44 Symptom Domains in Bipolar I Disorder
Manic Mood and Behavior Dysphoric Mood and Behavior Euphoria Grandiosity Pressured Speech Impulsivity Excessive Libido Recklessness Diminished Need for Sleep Depression Anxiety Irritability Hostility Violence or Suicide Cognitive Symptoms Racing Thoughts Distractibility Poor Insight Disorganization Inattentiveness Confusion Psychotic Symptoms Delusions Hallucinations Sensory Hyperactivity

Download ppt "Schizophrenia: An overview of diagnosis and treatment"

Similar presentations

Ads by Google