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Schizophrenia: An overview of diagnosis and treatment.

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

1 Schizophrenia: An overview of diagnosis and treatment

2 A disease process with multiple signs and symptoms involving thoughts, perceptions, emotions, and behavior 1 Most catastrophic mental illness 1,2 Peak incidence in males at 15 to 25 years of age and in females at 25 to 35 years of age 1 Global incidence: 1% in all societies 3 Course of illness is extremely variable, often chronic, and sometimes episodic 1 Florid symptoms may diminish with age, although years of dysfunction are rarely overcome 1 Epidemiology of Schizophrenia

3 Associated with heavy emotional burden 4 Often requires long-term caregiving 4 50% of patients exhibit comorbid substance abuse Economic impact 22% of all mental illness costs in the United States 5 Annual direct and indirect costs estimated at $65 billion (1991) 5 Annual treatment costs may range from $10,000 to $70,000 per patient 6-9

4 Behavioral Symptoms Positive Symptoms Delusions Hallucinations Disorganized speech Suspiciousness Exaggerated thoughts Cognition Attention / Memory Organized Thinking Judgment / Insight Negative Symptoms Affective flattening Alogia / Avolition Anhedonia Social withdrawal Mood Depression Mania Anxiety / Aggression

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

6 Clinical Issues Interplay of Depressive and Other Symptoms of Illness in Schizophrenia Negative Symptoms Functional Impairment Prolactin Effects Cognitive Dysfunctio n Positive Symptoms EPS Mood Symptoms Illness Related Symptoms 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 Psychosoci al Pharmacologic Patient Care The "Team Approach" 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 PsychologicalRehabilitation

15 Considerations in Choosing Antipsychotics: Acute vs.Continuation Time to response: significant response may take 4 to 5 weeks of therapy with conventional agents 12 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

16 Chemical Structures CH 3 H Olanzapine Quetiapine Clozapine CH 3 F Risperidone O N N H Cl N N N N N N S O N N N O N N HO Cl O F Haloperidol O N N N S OH

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

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

21 Other Limitations of Conventional Anti-Psychotics: Extrapyramidal symptoms (EPS) Tardive dyskinesia (TD) Prolactin elevation Sedation QTc prolongation Cognitive impairment Orthostatic hypotension Compliance / Relapse

22 Typical Antipsychotics Haldol, Mellaril, Thorazine, Prolixin, etc. 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, womens 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

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

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

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 Prevalence rates from 1.2% - 1.6% *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

33 Mortality in Bipolar Disorder 25%-50% attempt suicide Suicide completion rate ~19% 50% suicidal ideation in mixed mania

34 Schizophrenia vs. Bipolar SchizophreniaBipolar Thinking Disorder which can affect mood Primarily a mood disorder that can affect thinking & judgment 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 level of functioning BipolarSchizoaffective 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) Related Disease Outcomes

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.)

38 Olanzapine Data Suggest Effects Across Multiple Neurotransmitter Systems SYSTEMOlanzapine ActionRelevance 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 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 A/P Antipsychotics are currently not considered a standard therapy for long term treatment of bipolar (For psychosis associated with acute mania) Maintenance Treatment MOOD STABILIZER A/D For recurrent psychotic features For recurrent depressive features A/P M/S A/D M/S

40 Attributes of Ideal Mood Stabilizer for Mania 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 Rapid efficacy for mania Treats psychotic symptoms of mania Broad efficacy (e.g., mixed, rapid cycling) Reduces depressive elements in mania Favorable cognitive effects Long-term usefulness Safe & well-tolerated Ease of use

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 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 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

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

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