1. Adapted from: Treatment of Schizophrenia (and Related Psychotic Disorders) Scott Stroup, MD, MPH 2004

2. Psychosis Generally equated with positive symptoms and disorganized or bizarre speech/behavior Impaired “reality testing” A syndrome present in many illnesses –remove known cause or treat underlying illness –treat symptomatically with antipsychotic medications

3. Schizophrenia is a heterogeneous illness Defined by a constellation of symptoms, including psychosis Multifactorial etiology, variable course Social/occupational dysfunction a required diagnostic criterion Good treatment must address symptoms and social/occupational dysfunction

4. DSM-IV Schizophrenia 2 or more of the following for most of 1 month: –Delusions –Hallucinations –Disorganized speech –Grossly disorganized or catatonic behavior –Negative symptoms Social/occupational dysfunction Duration of at least 6 months Not schizoaffective disorder or a mood disorder with psychotic features Not due to substance abuse or a general medical disorder

5. Features of Schizophrenia Positive symptoms Delusions Hallucinations Cognitive deficits Attention Memory Verbal fluency Executive function (eg, abstraction) Functional Impairments Work/school Interpersonal relationships Self-care Negative symptoms Anhedonia Affective flattening Avolition Social withdrawal Alogia Mood symptoms Depression/Anxiety Aggression/Hostility Suicidality Disorganization Speech Behavior

6. Common needs of people with schizophrenia Symptom control Housing Income Work Social skills Treatment of comorbid conditions

7. Challenges in the Treatment of Schizophrenia Stigma Impaired “insight”– no agreement on problem Treatment “compliance” Substance abuse very common Violence risk Suicide risk Medical problems common, often unrecognized

8. Schizophrenia Treatment Therapeutic Goals minimize symptoms minimize medication side effects prevent relapse maximize function “recovery” Types of Treatment pharmacotherapy psychosocial/psychotherapeutic

9. Treatments for schizophrenia: Strong evidence for effectiveness Antipsychotic medications Family psychoeducation Assertive Community Treatment (ACT teams)

10. The First Modern Antipsychotic Chlorpromazine (Thorazine) Antipsychotic properties discovered in 1952 Studied originally for usefulness as a sedative Found to be useful in controlling agitation in patients with schizophrenia Introduced in U.S. in 1953

11. Show Video Tape Augustine

12. The Dopamine Hypothesis of Schizophrenia All conventional antipsychotics block the dopamine D 2 receptor Dopamine enhancing drugs can induce psychosis (e.g., chronic amphetamine use)

13. Conventional Antipsychotics FDA approval Generic Name Brand Name 1953 chlorpromazine (Thorazine) 1958 trifluoperazine (Stelazine) 1958 perphenazine (Trilafon) 1959 fluphenazine (Prolixin) 1959 thioridazine (Mellaril) 1967 haloperidol (Haldol) 1967 thiothixene (Navane) 1970 mesoridazine (Serentil) 1975 loxapine (Loxitane) 1977 molidone(Moban) 1984 pimozide(Orap)

14. “Typical” antipsychotic medications (aka first-generation, conventional, neuroleptics, major tranquilizers) High Potency (2-20 mg/day) (haloperidol, fluphenazine) Mid Potency (10-100 mg/day) (loxapine, perphenazine) Low Potency (300-800+ mg/day) (chlorpromazine, thioridizine)

15. Dopamine blockade effects Limbic and frontal cortical regions: antipsychotic effect Basal ganglia: Extrapyramidal side effects (EPS) Hypothalamic-pituitary axis: hyperprolactinemia

16. Typical Antipsychotic limitation: Extrapyramidal side effects (EPS) Parkinsonism Akathisia Dystonia Tardive dyskinesia (TD)-- the worst form of EPS-- involuntary movements

17. Parkinsonian side effects Rigidity, tremor, bradykinesia, masklike facies Management: –Lower antipsychotic dose if feasible –Change to different drug (i.e., to an atypical antipsychotic) –Anticholinergic medicines: benztropine (Cogentin) trihexylphenidine (Artane)

18. Akathisia Restlessness, pacing, fidgeting; subjective jitteriness; associated with suicide Resembles psychotic agitation, agitated depression Management: –lower antipsychotic dose if feasible –Change to different drug (i.e., to an atypical antipsychotic) –Adjunctive medicines: propanolol (or another beta-blocker) benztropine (Cogentin) benzodiazepines

19. Acute dystonia Muscle spasm: oculogyric crisis, torticollis, opisthotonis, tongue protrusion Dramatic and painful Treat with intramuscular (or IV) diphenhydramine (Benadryl) or benztropine (Cogentin)

20. Tardive Dyskinesia (TD) Involuntary movements, often choreoathetoid Often begins with tongue or digits, progresses to face, limbs, trunk Etiologic mechanism unclear Incidence about 3% per year with typical antipsychotics –Higher incidence in elderly

21. Show Tardive Dyskinesia Videotape Abnormal Involuntary Movement Scale (AIMS) training tape

22. Neuroleptic Malignant Syndrome (NMS) Fever, muscle rigidity, autonomic instability, delirium Muscle breakdown indicated by increased CK Rare, but life threatening Risk factors include: –High doses, high potency drugs, parenteral administration Management: –stop antipsychotic, supportive measures (IV fluids, cooling blankets, bromocriptine, dantrolene)

23. Typical Antipsychotic limitation: Other common side effects Anticholinergic side effects: dry mouth, constipation, blurry vision, tachycardia Orthostatic hypotension (adrenergic) Sedation (antihistamine effect) Weight gain “Neuroleptic dysphoria”

24. Typical Antipsychotic limitation: Treatment Resistance Poor treatment response in 30% of treated patients Incomplete treatment response in an additional 30 % or more