Adult Psychiatry 1.2 Flashcards
What did Kendell show in his 1996 study?
Pregnancy induced hypertension increased the risk of psychosis almost 9 fold
What obstetric events are linked to schizophrenia?
Low birth weight, small for gestational age
Perinatal factors e.g. PIH
Hypoxic events e.g. PROM
What is used to measure obstetric complications during childbirth?
Lewis-Murray scale
Which study started research into cannabis and schizophrenia?
Swedish study in 1960s by Andreassen
What did the Dunedin cohort show re cannabis and schizophrenia?
Exposure at 15 to cannabis compared to 26 showed there was an association with psychosis
What did Bauml et al divide psychosocial interventions into?
Obligatory
Voluntary
What is basic level competency?
Process of empowerment of patients and relatives to understand and accept the illness and cope with it in a successful manner
Examples of voluntary psycho-social interventions
Individual behavioural therapy
Communication training
Family therapy
What is the most basic and important part of psychosocial intervention for schizophrenia?
Psychoeducation
Who first employed the term psychoeducation?
ANderson
What did psychoeducation first consist of?
Briefing patient about their illness
Problem solving
Communicatino training
Self-assertiveness training
What does Cochrane review of psychoeducation for schizophrenia show?
Reduction in relapse
Improved compliance
Who did studies into high expressed emotion in families of schizophrenia?
Brown & Rutter
What did Brown & Rutter show in families with schizophrenia?
Patients in families with high expressed emotion were more likely to experience a relapse during the following year despite medication
Impact of family therapy on schizophrenia?
Reduces relapse rate from 64% to 24% when there is high expressed emotion
When is family therapy for schizophrenia more effective?
If baseline risk of relapse is increased
NNT for family therapy for relapse prevention in schizophrenia?
6
Who created the framework for social skills training?
Bellack and Mueser
What are the forms of social skills training?
Basic Model
Social problem-solving model
Cognitive remediation model
What is the basic model of social skills training?
Complex social repertoires are broken down into simpler steps, practiced through role playing and applied in natural settings.
What is the social problem-solving model?
Focuses on improving impairments in information processing that are assumed to be the cause of social skills deficits.
Targets things like medication and sx management, self-care.
What is the cognitive remediation model in social skills training?
Corrective learning process begins by targeting fundamental cognitive impairments like attention & planning.
What did Birchwood say re CBT for schizophrenia?
Target is emotional dysfunction that accompanies psychotic experience and not the sx themselves.
What did Turkington describe re the elements of CBT for psychosis?
Therapeutic alliance - validation
Improving medication adherence
Providing alternate explanations to unusual experiences
Decreasing impact of positive sx
Graded reality testing using peripheral questioning and inference chaining
What did a meta-analysis for CBT in psychosis show?
34 trials concluded positive beneficial effects for target sx
No effect on hopelessness
Competitive employment rate for those with SMI?
<20%
Elements of supported employment?
Goal of permanent competitive employment Minimal screening for employability Avoidance of preoccupational training Individualized placement Time-unlimited support Consideration of preferences
Unweighted mean of patients in supported employment programs for obtaining competitive employment?
65% vs 26% in controls
Relapse rate of psychosis in one year irrespective of treatment
27%
Relapse rate of psychosis in one year if not on treatment
61%
Relapse rate of psychosis regardless of treatment if patient has 5 or more episodes in one year?
48%
Relapse rate of psychosis if no treatment of patient who has had 5 or more episodes in one year?
87%
Relapse rate of psychosis in one year regardless of treatment for patients living in stressful environments?
62%
Relapse rate of psychosis in one year if receiving antipsychotics and family education?
19%
Relapse rate of psychosis in one year if receiving antipsychotics and social skills training?
20%
Definition of recovery for schizophrenia
GAF>60
Recovery rate of schizophrenia at 15 years
37% with schizophrenia
54% with other psychoses
Who did a meta-analysis into schizophrenia and suicide?
Palmer et al
Lifetime prevalence of suicide in schizophrenia?
5.6%
Self-harm rates in people with schizophrenia
38% had at least one episode in 2-12 year follow up period
Median standardised mortality rate for schizophrenia?
2.58
Is standardised mortality rate increasing or decreasing for schizophrenia?
Increasing
Which subtypes of schizophrenia have the best outcome?
Paranoid
Catatonic
Which subtype of schizophrenia has the worst outcome?
Hebephrenic
Which study looked into prognosis of schizophrenia?
187 schizophrenic patient study from Chestnut Loge over 19 years
What did Chestnut Lodge study show re prognosis of paranoid schizophrenia?
Paranoid patients had older age of onset, developed rapidly in people with good functioning, was intermittent during first 5 years and associated with good recovery.
What did Chestnut Lodge study show re prognosis of hebephrenic schizophrenia?
Earlier age of onset
Poor premorbid functioning
Continuous illness
Poor long-term prognosis
What did Chestnut Lodge study show re undifferentiated schizophrenia and its prognosis?
Poorly distinguished from patients premorbid state
Early hx of behavioural difficulties
Continuous but stable disability
Factors suggestive of good prognosis for schizophrenia
Late onset Obvious precipitating factors acute onset Good premorbid adjustment Affective sx Married FHx of affective disorders Good social support Positive sx only Good initial response to Rx
What is the best predictor of a good prognosis of schizophrenia?
Good initial response to treatment
Poor prognostic factors for schizophrenia
Early onset No precipitating factors Insidious onset Poor premorbid adjustment Social withdrawal Single/divorced/widowed FHx of schizophrenia Poor social network/High EE families Negative sx Poor compliance Neurological sx Hx of perinatal trauma No remissions in 3 years Many relapses Hx of violence
Best predictors of poor short-term outcome in acute psychosis
Stressful live events
High EE
Non-compliance
Predictors of good medium (2-5 years) outcome in
psychosis?
Females
Married
Social contacts outside home
Acute onset
Best predictor of course of schizophrenia?
Course of illness n first 2 years
Which antipsychotics show an effect size difference from first generation antipsychotics?
Clozapine
What did CATIE and CUtLASS studies show?
Second generation drugs are no better than first in terms of efficacy and cost
Olanzapine better than other atypicals for attrition
Who did a meta-analysis into dose comparison of antipsychotics for psychoses?
Davis & Chen, 2003
What did Davis & Chen 2002 find re doses for antipsychotics for psychoses?
Maximal effective dose of Haloperidol ranges from 3.3-10mg/day
No evidence that higher doses more effective
Best doses for atypical antipsychotics
Aripiprazole 10mg/day
Clozapine >400mg/day
Olanzapine 5mg/day
Risperidone 2mg/day
Guidelines for Chlorpromazine dose/day
100mg.day
Guidelines for Quetiapine dose/day
75mg/day
Guidelines for Ziprasidone dose/day
60mg/day
Guidelines for Aripiprazole dose/day
7.5mg/day
What did Essock et al. 2007 do with the CATIE study?
Used data to find out whether switching or staying with same medication was useful
What did Essock et al 2002 find?
People who stayed on same medication did better, particularly for Olanzapine.
Best medication for aggression?
Clozapine
Olanzapine
Haloperidol
(in that order)
What are primary negative sx?
Sx that are intrinsic to schizophrenia
What are secondary negative sx?
Sx that occur in association with or are caused by positive sx, affective sx, medication SE, environment, illness-related.
What % of schizophrenic patients have primary negative sx?
20-30% (clinical)
14-17% (population)
First criteria of deficit schizophrenia?
At least 2 of 6 of the following present and of clinical severity: Restricted affect Diminished emotional range Poverty of speech Curing of interest Diminished sense of purpose Diminished social drive
Second criteria of deficit schizophrenia
2 or more of these features present for preceding 12 months and present during periods of clinical stability.
Third criteria of deficit schizophrenia
2 or more of these enduring features are idiopathic i.e. not secondary to factors other than the disease.
Fourth criteria of deficit schizophrenia
Patient meets DSM V criteria for schizophrenia.
Difference between DSM IV and V re schizophrenia
DSM V has no special attribution to bizarre delusions of first-rank auditory hallucinations.
Associations with deficit schizophrenia
Frontal atrophy Familial pattern Summer birth Increased eye tracking dysfunctions More tardive dyskinesia Poor functional outcome Lower suicide and depression rates
Best antipsychotic for negative sx?
Amisulpride
What augmentation medication can be used for negative sx?
D-cycloserine; partial agonist at glycine modulatory site of glutamatergic N-methyl-d-aspartate receptor.
Selegiline
Impact of glycine on negative sx?
30% reduction
Which study looked into suicide prevention in schizophrenia?
Intersept study?
What did Intersept study show?
Suicidal behaviour significantly less in patients treated with clozapine or olanzapine
Which antipsychotics lead to improvement in neurocognition?
Second generation
What was Goldberg et al. 2007’s RCT?
Risperidone v Olanzapine in patients with first episode schizophrenia
Finding of Goldberg et al. 2007?
Effect size for cognitive change in patients exposed to 2nd gen antipsychotic was similar to healthy control group.
NICE recommendations for first line Rx of psychosis
PO atypical antipsychotic as per patient choice
NICE guidelines if good effect with typical PO antipsychotic but SEs
Consider PO atypical antipsychotic
Which antipsychotic to use if more than one atypical antipsychotic is considered appropriate?
Drug with lowest purchase cost should be prescribed
Which treatment should be given for psychosis if discussion between patient and clinician is not possible?
PO atypical - lower potential risk of EPSEs
How long should monotherapy be trialled for schizophrenia?
4-6 weeks
IPAP recommendation for initial monotherapy for schizophrenia?
Amisulpride Aripiprazole Olanzaine Quetiapine Risperidone Ziprasidone
IPAP recommendation if initial monotherapy fails for schizophrenia?
4-6 week trial of second atypical
IPAP recommendation if 2nd monotherapy fails for schizophrenia?
6 month trial of clozapine up to 900mg.day
IPAP recommendation if persistent sx of psychosis despite 6 months of clozapine?
Optimize clozapine and/or augment with ECT or adjuvant medication
Alternate strategies
What should the clinician consider each time they review antipsychotics for schizophrenia for a patient?
Major suicide risk Metabolic risk - especially with Olanzapine Severe agitation/violence Non-compliance Depression/mood sx Substance abuse Prodromal/first episode Catatonia
What does treatment of future episodes of psychosis depend on?
Compliance Therapeutic responde Side effects Cause of relapse Treatment resistant
What % of patients with psychosis relapse despite on treatment?
20%
What % of patients with psychosis relapse if they do not take their medications?
60%
Risk of relapse if one stops medication for psychosis
Five fold increase
Duration of maintenance treatment recommended for psychosis
1-2 years
Duration of maintenance treatment for multiple episodes of psychosis
At least 5 years
What medications to change to if EPSEs?
Atypicals; avoid high doses, especially of Risperidone
Which medications to avoid for metabolic syndrome?
Clozapine
Olanzapine
Best medications to avoid metabolic syndrome?
Amisulpride
Aripiprazole
Which medications are safe for high prolactin?
Aripiprazole
Olanzapine
Quetiapine
Which medications to switch to if problems with sedation?
Haloperidol
Aripiprazole
Amisulpride
Which medications have fewer SE of tardive dyskinesia?
Clozapine
Atypicals
Better profile for sexual dysfunction re medications?
Aripiprazole
Quetiapine
Who did a meta-analysis into depot for schizophrenia?
Adams et al.
What did Adams et al. find re depot use for schizophrenia?
Global improvement among patients given depot compared to those on PO and similar rate of SEs
Who did a survey of OP with depot for schizophrenia?
Pereira & Pinto 1997
What did Pereira & Pinto 1997 find re depot and schizophrenia?
Patients who were receiving depots prefered to continue on them.
60% of patients converted to depot and said they felt better on it.
Patients felt when on depot they were able to live normal lives and the depot protected them from relapses
Characteristic features of Zuclopenthixol depot
More effective in aggressive patients
Better at relapse prevention
High EPSE burden
Characteristic features of Flupentixol
Antidepressant effect
Characteristic features of haloperidol depot
Useful in prevention of manic relapse
May need 3-6 months to reach steady state
Characteristic features of Pipotiazine depot
Fewer EPSEs
Characteristic features of Fluphenazine depot
May induce depressed mood
Characteristic features of Risperidone depot
Needs aqueous suspension before injection.
Needs to be stored in fridge
Test dose not required
Risk of NMS with depot vs PO meds?
Same risk
Risk of TD for depot vs PO meds>
Same
Evidence of high dose prescribing for antipsychotics
No evidence that high dose prescribing provides sx relief in those who have not responded at lower doses
Guidelines for high dose prescribing
Consider alternative approaches such as adjuvant therapy, newer antipsychotics such as Clozapine
When are risk factors such as metabolic effects more pronounced in high dose prescribing of antipsychotics?
> 70 years of age
Guidelines of increasing dose for high dose px
Increase dose no more than weekly
ECG
Regular physical examination, obs and hydration status
Duration guidance for high dose px
For 3 months only; no use in continuing after 3 months if no response
Who provided evidence of Clozapine for treatment-resistant schizophrenia?
Kane et al. 1998
Wahlbeck et al. 1999 - meta-analysis
Describe structure of Kane et al. 1998’s study
Multicentre clinical where schizophrenia patients failed to respond to 3 meds, underwent a prospective, single-blind trial of high dose haloperidol for 6 weeks.
Patients who didn’t improve on haloperidol where double-blinded and given clozapine or chlorpromazine for 6 weeks.
Results of Kane 1998’s study?
Out of 268 patients, 30% of clozapine patients responded compared to 4% of chlorpromazine patients.
Meltzer’s conclusino of clozapine?
30% of clozapine patients would respond in 6 weeks, 20% by 3 months, 10-20% by 6 months.
Relationship between clozapine plasma levels and clinical response?
None
What plasma level of clozapine should be reached before patient can be considered non-respondent to clozapine?
350-450ng/ml
Who reproduced the methodology of Kane 1998 and what did they find?
Conley et al 1998
Olanzapine no better than chlorpromazine in treatment resistance
NICE’s definition of treatment resistance of schizophrenia
Lac of satisfactory clinical response to sequential use of at least two antipsychotics for 6-8 weeks; at least one must be atypical.
What medications have been used to augment clozapine?
Risperidone
Fluoxetine
Anticonvulsants
Amisupride - high potency D2 blockade
Studies of augmentation of clozapine with lamotrigine?
Improvement in positive sx
No effect on negative sx
Studies of augmentation of clozapine with risperidone?
Low risperidone dosage (4.5mg/day) and long duration of trial is associated with good outcome
Non-pharmacological adjuvant to clozapine?
Fish omega oil - ethyl-eicoaspentanoate
What does CATIE stand for?
Clinical Antipsychotic Trials of Intervention Effectiveness
What type of study was CATIE?
Double-blind pragmatic RCT
Patients in CATIE?
1493 patients with chronic schizophrenia across 57 sites from 2001-2004
Medications used in CATIE?
Olanzapine Quetiapine Risperidone Ziprasidone (added later) Perphanazine
How many patients discontinued treatment in 18 months in CATIE?
74%
Which medication had lowest discontinuation rate in CATIE?
Clozapine - 10 months
Olanzapine - 64%
Which medication had highest SE burden in CATIE?
Olanzapine
Which medication caused most anticholinergic sx in CATIE?
Quetiapine
Which medication caused most EPSes in CATIE?
Perphenazine
What happened in phase 2 of CATIE?
Those who terminated phase 1 due to SEs (444 participants) were tested with Olanzapine, Risperidone, Quetiapine or ZIprasidone.
Effectiveness of medications in phase 2 of CATIE?
Olanzapine and Risperidone had equal effectiveness and both better than the others
Problems with CATIE
Perphenazine only used in one randomized phase
Double-blind treatment decreased resemblance to clinical case
Mean doses used is controversal
What is CUtLASS?
Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study
What type of study was CUtLASS?
Unblinded randomised control trial comparing first and second generation antipsychotics
Primary outcome of CUtLASS?
QoL at 1 year
Secondary outcome of CUtLASS?
Sx measures at 1 year
Participants in CUtLASS?
1,227 patients with schizophrenia assessed by their clinical team for medication review because of poor response or adverse effects were randomised
Second generation drugs used in CUtLASS?
Amisulpride
Olanzapine
Quetiapine
Risperidone
Rate of follow-up at 1 year in CUtLASS?
81%
Results of CUtLASS?
No advantage of 2nd generation drugs
Those on 1st generation drugs did relatively better
Patients had no clear preference
What was the second phase of CUtLASS?
Compared clozapine with other 2nd gen antipsychotics in 136 patients
Results of 2nd phase of CUtLASS?
Significant advantage for clozapine in sx improvement in 1 year
Patients preferred Clozapine
Treatment of Delusional Disorders
Fluoxetine 80mg/day; effect at 8-12 weeks
Who conducted a systematic review into post schizophrenic depression?
Levinson
What did Levinson find re post schizophrenic depression?
Antidepressants are beneficial for patients stable re psychotic sx
Which antipsychotics have antisuicidal effects in schizophrenia?
Clozapine
Olanzapine
Main treatment for schizoaffective disorder
Mood stabiliser
Which medication is best for depressive type of schizoaffective disorder?
Carbamazepine
Who did a meta analysis of 10 RCTs into psychotic depression?
Wijkstra et al.
What did Wijkstra et al. find re medication treatment for psychotic depression?
Combination of antidepressant and antipsychotic is no better than antidepressant monotherapy.
Which combination is superior for psychotic depression compared to monotherapy?
Antidepressant + antipsychotic compared to antipsychotic alone
What do NICE guidelines recommend re treatment for psychotic depression?
Combination strategy
