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