Transcript Managing Treatment-resistant Schizophrenia

Managing Treatmentresistant Schizophrenia
What is treatment-resistant
schizophrenia?
 A substantial minority of patients
show a poor response to
antipsychotics
 Identifiable during the first episode
 Often identified within the first two
years
 Effect on functioning due to positive
and negative symptoms
Clinical characteristics
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Negative symptoms
Neurocognitive function deficits
Depressive features
Associated substance misuse
Other medical conditions can
complicate the picture
Negative symptoms
 Deficit Syndrome - Smaller frontal
lobes, lower frontal metabolism,
executive performance deficits etc.
 Type I/Type II model (Crow 1980)
 Fluctuating nature
 Atypicals more effective in general,
but less so in chronic cases
Neurocognitive function
 The degree of cognitive impairment
key predictor of overall treatment
response
 Can be seen as early as during the
first episode
 Some improvement with atypical
antipsychotics
 Even with treatment, impairment may
be permanent
Demographic variables
 Earlier age of onset associated with
poor outcome
 Duration of untreated psychosis
(DUP) key factor
 Gender a robust predictor
 Poor pre-morbid function
 Presence of neurological soft signs
 Cognitive impairment also points to
relatively poor outcome
Findings in Neuroimaging
 Structural abnormalities very
common
 Literature inconsistent on association
between structural abnormalities and
treatment response
 Progressive brain changes
 Differential cerebral blood flow in
patients receiving risperidone (Honey
et al. 1999)
Predictors of treatment
response
 Plasma levels – good indicator of
treatment response with Clozapine
 Aim for low doses, unless clinically
poor response
 Plasma levels above 350 – 400 ng/mL
associated with improved response
Management
 Pharmacological treatment
 Psychological and social approaches
 Rehabilitation and Recovery
Psychosocial approaches
 CBT for psychotic symptoms
 Cognitive rehabilitation and
compensation strategies
 Family work
 Psychosocial programmes for daily
living skills and social skills
Pharmacological treatment
 High doses of typical antipsychotics
ineffective in most cases
 Atypical antipsychotics and Clozapine
have largest evidence base
 Combinations of antipsychotics
 Adjunctive pharmacological
treatments
 Treat co-morbid conditions
Clozapine
 Kane et al (1988)
 Suicide rates may be lower
 Adverse effects: salivation,
constipation, weight gain, enuresis,
lower seizure threshold, and fatal
agranulocytosis
 Plasma levels useful if poor clinical
response
Adjunctive treatments
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Clozapine and Sulpiride
Mood stabilisers
Benzodiazepines
Antidepressants
ECT
Working towards recovery
 Psychiatric rehabilitation
 Assertive community treatment
 Specific interventions, such as alcohol
and drug misuse interventions
 Community support
Rehabilitation
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Social learning programmes
Skills enhancement
Cognitive remediation
Environmental modification
Compensating for deficits
Psycho-education for carers