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Adapted from:
Treatment of Schizophrenia (and Related Psychotic Disorders)
Scott Stroup, MD, MPH
2004
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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
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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
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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
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Features of SchizophreniaPositive symptomsDelusionsHallucinations
Cognitive deficitsAttentionMemoryVerbal fluencyExecutive function (eg, abstraction)
Functional ImpairmentsWork/school
Interpersonal relationshipsSelf-care
Negative symptomsAnhedoniaAffective flatteningAvolitionSocial withdrawalAlogia
Mood symptomsDepression/AnxietyAggression/HostilitySuicidality
DisorganizationSpeech
Behavior
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Common needs of people with schizophrenia
• Symptom control• Housing • Income• Work• Social skills• Treatment of comorbid conditions
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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
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Schizophrenia Treatment
• Therapeutic Goals• minimize symptoms• minimize medication side effects• prevent relapse• maximize function• “recovery”
• Types of Treatment• pharmacotherapy• psychosocial/psychotherapeutic
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Treatments for schizophrenia:Strong evidence for effectiveness
• Antipsychotic medications• Family psychoeducation• Assertive Community Treatment
(ACT teams)
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The First Modern AntipsychoticChlorpromazine (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
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Show Video Tape
Augustine
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The Dopamine Hypothesis of Schizophrenia
• All conventional antipsychotics block the dopamine D2 receptor
• Dopamine enhancing drugs can induce psychosis (e.g., chronic amphetamine use)
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“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)
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Dopamine blockade effects
• Limbic and frontal cortical regions: antipsychotic effect
• Basal ganglia: Extrapyramidal side effects (EPS)
• Hypothalamic-pituitary axis: hyperprolactinemia
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Typical Antipsychotic limitation:
Extrapyramidal side effects (EPS)• Parkinsonism• Akathisia• Dystonia• Tardive dyskinesia (TD)-- the worst form
of EPS-- involuntary movements
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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)
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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
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Acute dystonia
• Muscle spasm: oculogyric crisis, torticollis, opisthotonis, tongue protrusion
• Dramatic and painful• Treat with intramuscular (or IV)
diphenhydramine (Benadryl) or benztropine (Cogentin)
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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
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Show Tardive Dyskinesia Videotape
Abnormal Involuntary Movement Scale (AIMS) training tape
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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)
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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”
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Typical Antipsychotic limitation: Treatment Resistance
• Poor treatment response in 30% of treated patients
• Incomplete treatment response in an additional 30% or more