Schizophrenia Flashcards
Which condition has been linked with reductions in small interneurons in cortical layer II in the prefrontal cortex (thought to be involved with the GABA system)?
Schizophrenia
What are the macroscopic features of Schizophrenia?
- Ventricular enlargement
- Reduced brain volume (up to 5%)
- Reduced left planum temporale gray matter, and reversed planum temporale surface area asymmetry (normally left larger than right in a right handed person)
What are the microscopic features of Schizophrenia?
- reduction of the size of the dorsolateral prefrontal cortex
- reduction of the hippocampus
What is the nearest approximation of the lifetime prevalence of schizophrenia in the UK?
15 per 1 000 - mrcpsych mentor
4 per 1 000 - spmm
Which factors result in a higher incidence of Schizophrenia?
- urbanicity
- winter births
- migration
- lower socio economic class
- having a learning disability
- old paternal age
- cannabis use
How much more common is Schizophrenia in migrants?
3-5x
How much more common is Schizophrenia in people with learning disabilities?
3x
What are some factors that indicate poor prognosis in Schizophrenia?
- being male
- younger at time of presentation
- having a positive family history
- length of DUP
- obstetric complications
What’s the SMR all cause mortality in Schizophrenia?
2
What’s the incidence of Schizophrenia in the UK?
1 per 10 000
What is the risk of developing Schizophrenia to the general population?
1%
What is the risk of developing Schizophrenia with a first cousin with the illness?
2%
What is the risk of developing Schizophrenia with a grandparent with the illness?
5%
What is the risk of developing Schizophrenia with a child with the illness?
6%
What is the risk of developing Schizophrenia with a sibling with the illness?
9%
What is the risk of developing Schizophrenia with a parent with the illness?
13%
What is the risk of developing Schizophrenia with a fraternal twin with the illness?
17%
What is the risk of developing Schizophrenia with an identical twin with the illness?
48%
Which obstetric complications increase the risk of Schizophrenia?
- Prenatal nutritional deprivation
- Prenatal brain injury
- Prenatal influenza
What is the SSRI with the lowest known risk in pregnancy?
Fluoxetine
When is tardive dyskinesia worse?
- When patient is distracted
- with emotional arousal
How long after starting antispsychotics does tardive dyskinesia start?
Months to years
What are the risk factors for tardive dyskinesia?
- older age
- women
- higher in black people
- affective disorder
- those who have learning difficulties
- people with substance abuse
Which body parts does tardive dyskinesia affect?
face (3/4 of affected individuals)
the limbs (1/2 of affected)
trunk (1/4 of affected).
What makes tardive dyskinesia better?
- when affected muscles are used for voluntary tasks
- decrease with relaxation
What is the management of tardive dyskinesia?
- stop antipsychotic that has been prescirbed
- switch to quetiapine or clozapine
- stop anticholinergic
- Tetrabenzine
- Benzodiazepines
- vitamin E
- ginkgo biloba
- propranolol
What’s the maximum daily dose of Olanzapine?
20mg/day
What’s the maximum daily dose of Clozapine?
900mg/day
What’s the maximum daily dose of haloperidol?
20mg/day
What’s the maximum daily dose of Quetiapine?
750mg/day in schizophrenia
800mg/day in BPAD
What’s the maximum daily dose of Risperidone?
16mg/day
What’s the maximum daily dose of oral Amisulpride?
1200mg/day
What’s the maximum daily dose of oral Aripiprazole?
30mg/day
What’s the maximum dose of Flupentixol (depot)?
400mg/week
What’s the maximum dose of Zuclopenthixol (depot)?
600mg/week
What’s the maximum dose of Haloperidol (depot)?
300mg every 4 weeks
What’s the male to female ratio of Schizophrenia?
1.4:1
Which typical antipsychotic was selected for use in the CATIE study?
Perphenazine
What was the CATIE study?
Compared the effectiveness of older (first available in the 1950s) and newer (available since the 1990s) antipsychotic medications used to treat schizophrenia.
What happened in phase I of the CATIE study?
Phase I compared old and new antipsychotics.
Which atypical antipsychotics were used in Phase I of the CATIE study?
- olanzapine
- quetiapine
- risperidone
- ziprasidone
What was the outcome of phase I of CATIE study?
- medications were comparably effective but were associated with high rates of discontinuation due to intolerable side effects or failure to adequately control symptoms
- olanzapine, was slightly better than the other drugs but also was associated with significant weight-gain as a side-effect
- perphenazine used in the study generally performed as well as the four newer medications
- movement side effects (rigidity, stiff movements, tremor, and muscle restlessness) were not seen more frequently with perphenazine than with the newer drugs
What happened in phase II of the CATIE study?
Sought to provide guidance on which antipsychotic to try next if the first failed (either due to ineffectiveness or intolerability)
What was the outcome of phase II of the CATIE study?
- Participants who discontinued their first antipsychotic medication because of inadequate management of symptoms were encouraged to enter the efficacy (clozapine) pathway
- participants who discontinued their first treatment because of intolerable side effects were encouraged to enter the tolerability (ziprasidone) pathway
- Clozapine was remarkably effective and was substantially better than all the other atypical medications
What did the CATIE study reveal about cardiometabolic syndrome?
The prevalence of MS at baseline in the CATIE group was 40.9%. By gender this was 51.6% in females and 36% in males. Male patients were twice as likely to have MS than matched controls, and female patients were three times as likely compared to matched controls
What is the criteria for metabolic syndrome?
Central obesity: waist circumference 102 cm or 40 inches (male), 88 cm or 36 inches(female)
Dyslipidaemia: TG 1.7 mmol/L (150 mg/dl)
Dyslipidaemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure 130/85 mmHg
Fasting plasma glucose 6.1 mmol/L (110 mg/dl)
What is the relative risk of developing Schizophrenia as a second generation migrant?
4.5
What is the relative risk of developing Schizophrenia if there are obstetric complications?
2
What is the relative risk of developing Schizophrenia as a first generation migrant?
2.7
What is the only licensed medication for the treatment of tardive dyskinesia in the UK
Tetrabenzine
What mood effect does Tetrabenzine have?
Deprossogenic
What’s the normal therapeutic range for Clozapine?
350-500ug/L
What’s the strongest predictor of relapse for schizophrenia?
Non compliance with medication
What’s the most appropriate medication for individuals with HIV who require treatment for psychosis?
Risperidone first line
Atypicals are ok
What’s a core feature of the oneiroid psychosis?
- Dream like state
- patients are characteristically perplexed and disorientated in time, place, and person
What’s most effective medication for the primary negative symptoms of schizophrenia?
Amisulpride
What are the negative symptoms of schizophrenia?
- Social withdrawal
- Apathy
- Lack of energy
- Poverty of speech (alogia)
- Flattening of affect
- Anhedonia
What are the positive symptoms of schizophrenia?
- Hallucinations
- Delusions
- Thought disorder
How many positive and negative symptoms are on the PANSS?
7
How many general psychopathology symptoms are on the PANSS?
16
How many women experience puerperal psychosis?
1-2 per 1000
What % of women who experience puerperal psychosis have a family history of mood disorders?
50%
Within what period of birth does puerperal psychosis normally beign?
2 weeks
According to ICD10 how long do psychotic symptoms have to be present for a diagnosis of an acute and transient psychotic disorder?
Less than 1 month
According to ICD10 how long must psychotic symptoms have to be present for a diagnosis of Schizophrenia?
More than 1 month
According to DSMV how long must psychotic symptoms have to be present for a diagnosis of Schizophrenia?
At least 6 months with 1 month of active symptoms
According to DSMV if psychotic symptoms are present for >1 month but <6 months what is the diagnosis?
schizophreniform disorder (this is a prodromal phase)
According to DSMV what is the diagnosis if there psychotic symptoms present for less than a month?
Brief psychotic disorder
What is the most effective drug for treating psychosis associated with Parkinson’s?
Clozapine
What type of hallucination are most common in psychosis associated with Parkinson’s?
Visual, but may be auditory or tactile
What’s the cause of psychosis in most patients with Parkinson’s?
Secondary to dopaminergic medication BUT some hallucinations may occur independently of dopaminergic medication
Which Parkinson’s medications are more likely to cause psychosis?
Anticholinergics and dopamine agonists
Which Parkinson’s medications are less likely to cause psychosis?
levodopa or catechol-O-methyltransferase (COMT) inhibitors.
Which antipsychotics should be avoided in patients with Parkinson’s?
Risperidone and the atypicals should be avoided completely (but low dose quetiapine is the best tolerated)
What is the risk with antipsychotics in Parkinson’s?
They may worsen movement problems
What’s the one year prevalence of late onset schizophrenia (aged>60 years)?
0.4%
What’s an adjunctive medication to help with cognitive impairment?
Cholinergic agents
What are some of the likely cardiac complications of prolonged QTc?
- Palpitations
- Sudden cardiac death
- Torsade de pointes
- Ventricular fibrillation
What is a not a feature of pueperal psychosis?
First rank symptoms
What are some of the clinical features of pueperal psychosis?
- odd affect
- being withdrawn
- being distracted by auditory hallucinations
- being confused, incompetent
- lability
- excessive speech
The risk of schizophrenia if both parents have Schizophrenia?
35-50%
The risk of schizophrenia in a child with Digeorge syndrome?
20-24%
The risk of schizophrenia in half-sibling of an affected person?
4%
The risk of schizophrenia in nephews or nieces of an affected person?
3%
The risk of schizophrenia in biological aunt/uncle of an affected person?
3%
The percentage of people with schizophrenia who smoke?
80-85%
smoking lowers antipsychotic levels and reduces side effects
The percentage of people with schizophrenia who do not continue with antipsychotic medication after 1 year?
70-75%
Which drugs must be avoided in Neuroleptic malignant syndrome?
Antipsychotics
The most common presentation seen in women with post partum psychosis is?
Affective symptoms (in 80%)
The most common symptom seen in patients with puerperal psychosis is?
Paranoid ideation
The relapse rate of mood disorders in those who had a past history is when they are pregnant is?
50%
The onset of very early onset schizophrenia is before the age of
13
What has been shown to have some beneficial effects in terms of anhedonia and negative symptoms in patients with treatment resistant schizophrenia taking Clozapine?
Mirtazapine
Which medication has been shown to reduce the incidence of suicide in patients with treatment resistant schizophrenia?
Clozapine
Most common hallucinatory experience in the UK?
Hearing or seeing things no one else could experience
What is the most common feature of Neuroleptic Malignant Syndrome?
Rigidity
Which ethnic groups are more susceptible to dose-dependent side effects of risperidone?
East Asians
Which anti-epileptic may be especially associated with psychosis?
Vibagatrin
Which condition is associated with a clinical picture of schizophrenia-like psychosis?
Huntington’s (6-25%)
Myoclonic seizures have been reported with which of the following antipsychotic medication?
Olanzapine
Which 2 antipsychotics have the greatest risk of orthostatic hypotension?
Risperidone
Clozapine
Which 2 antipsychotics have the lowest likelihood of sedation?
Aripiprazole
Amisulpride
Which antipsychotic is least likely to produce dry mouth?
Amisulpride
A 45-year-old lady with schizophrenia reports hearing the voice of her dead husband every time the tap runs in her house. What special kind of hallucination is this lady experiencing?
Functional (in the same modality as the stimulus)
A 42-year-old male with paranoid schizophrenia describes that he hears people in the bus talking about him. Although he cannot reproduce the exact content of what they are saying he has a rough idea of what the voices are saying about him. He experiences these symptoms on a daily basis.
Self-reference hallucinosis
This disorder presents with abrupt onset of strong sustained or intermittent muscular spasms.
acute dystonia
A 35-year-old female with a diagnosis of acute psychotic episode reports feeling a crawling sensation on her feet every time she hears the sound of a car outside her house.
Reflex hallucinations (stimulus in one modality, hallucination in another)
A 45-year-old female, chairman of a corporate company has been working 14 hours a day with very little sleep to meet her deadlines. Her work colleagues are concerned as she reports an experience of seeing herself and knowing that it is her.
Autoscopy
Akathisia, as a side-effect of drug treatment of schizophrenia usually starts within?
6-10 weeks of treatment
Risk factors for NMS
Younger age Being male Psychosis and mental retardation Physical exhaustion Dehydration or electrolyte imbalance (specifically hyponatremia) Previous and family history of NMS Alcohol Malnutrition Thyrotoxicosis Functional brain disorder (e.g. tumor, delirium, dementia) Low serum iron levels Raised creatine kinase levels Comorbid substance misuse
High loading dose of antipsychotic
Faster rate of loading antipsychotic
Recent or rapid antipsychotic dose increase
High potency antipsychotic use (FGAs)
Sudden withdrawal of antipsychotic
Sudden withdrawal of anticholinergic agents
Antipsychotic polypharmacy
Which meds cause NMS?
It is almost exclusively caused by antipsychotics (but is also associated with antidepressants and lithium)
Management of NMS
The first step is removal of the antipsychotic and the treatment of fever in addition to the use of a benzodiazepine. Other options which may be necessary include ECT, bromocriptine, and dantrolene.
Mortality of NMS
20%
Antipsychotics with low dopamine affinity (therefore useful in NMS for switch)
Clozapine
Quetiapine
Aripiprazole
Therapeutic range for clozapine
Clozapine 350-500 ug/L
What is the minimum effective daily dose of haloperidol in a first episode of schizophrenia?
2mg
In ICD10 which section is disorganised Schizophrenia included under?
Hebephrenic
In the AESOP study, the incidence of schizophrenia was increased in Afro-Caribbeans by what factor?
9
Which drug is known to cause Stevens-Johnson Syndrome?
Carbamezapine
What is the relationship between lamotrigine and valproate?
Valproate increases lamotrigine concentrations more than 2-fold
Which drugs may be used to augment Clozapine?
Amisulpride
Aripiprazole
Haloperidol
Lamotrigine
Omega-3-triglycerides
Risperidone
Sulpiride
Topiramate
Ziprasidone
Which drugs should not be prescribed with clozapine?
Pimozide
Olanzapine
What is not part of an annual check for all patients prescribed antipsychotic medications?
TFT
What is a recognised complication of valproate?
Pancreatitis
What percentage of patients with schizophrenia are treatment resistant?
20%
What percentage of patients with schizophrenia who will respond to clozapine will do so within the first 6 months of therapy?
70%
What is recommended in the management of antidepressant induced hyponatremia?
Demeclocycline
Which antipsychotic is believed to have the lowest effect on seizure threshold?
Haloperidol
What is the risk of developing spina bifida if prescribing Epilim to a pregnant mother?
1 in 100
Clozapine is associated with which biochemical/haematological changes?
Raised ALP
What was Crow’s contribution to schizophrenia?
Divided patients into type 1 (postive symptoms) and type 2 (negative symptoms)
Antipsychotic doses in first episode
Chlorpromazine 200mg Haloperidol 2mg Sulpiride 400mg Trifluoperizine 10mg Amisulpride 400mg Aripiprazole 10mg Olanzapine 5mg Quetiapine 150mg Risperidone 2mg
Antipsychotic doses in relapse
Chlorpromazine 300mg Haloperidol >4mg Sulpiride 800mg Trifluoperizine 15mg Amisulpride 800mg Aripiprazole 10mg Olanzapine 10mg Quetiapine 300mg Risperidone 4mg
Tardive dyskinesia is thought to result from hypersensitivity of which receptor?
D2
Which depot is suggested when EPSEs are a problem?
Pipotiazine palmitate
Which depot is suggested for Prophylaxis of manic illness?
Haloperidol decanoate
Which depot is suggested for Depressed patients?
Flupentixol decanoate
Which depot is suggested for aggressive patients?
Zuclopenthixol decanoate
risk of developing neutropenia if using clozapine?
3%
Drugs not usually associated with hyperprolactinaemia include
Clozapine
Aripiprazole
Quetiapine
Olanzapine
Ziprasidone
Antipsychotics known to cause significant hyperprolactinaemia include
All the typical antipsychotics
Risperidone
Amisulpride
Zotepine
Post acute phase management of Schizophrenia involves
- consoldiation of clinical improvements
- Rationalisation of treatment regimes
- Re-socialisation
The migrants-to-natives prevalence ratio for schizophrenia is estimated to be
1.8:1
Acute EPSEs such as dystonia, parkinsonism are measured using which scale?
Simpson Angus scale
Tardive dyskinesia can be measured using which scale?
AIMS scale
Which antispsychotics are indicated in liver failure?
Haloperidol
Amisulpride
Sulpiride
Management of akathisia
Reduce the dose Switching to alternative antipsychotic Propanolol Clonazepam Mirtazapine Trazodone Mianserin Cyproheptadine Diphenhydramine
% patients who develop akathisia?
Approximately 25%
% patientswho develop tardive dyskinesia?
Approximately 5%
% patients who develop Pseudo-parkinsonism?
Approximately 25%
% patients who develop dystonia?
Approximately 10%
Risk factors for Pseudo-parkinsonism?
- elderly females
- those with pre-existing neuro damage (e.g. stroke)
Risk factors for dystonia?
- young males
- neuroleptic-naive
- high potency drugs (e.g. haloperidol)
When does dystonia occur?
minutes or hours of starting antipsychotics
Management of acute dystonia
Anticholinergic drugs i.e. procyclidine
Switching to alternative antipsychotic
Botulinum toxin
rTMS
When does Pseudo-parkinsonism occur?
Days to weeks after starting antipsychotics
Management of Pseudo-parkinsonism
Reduce the dose
Anticholinergic drugs
Switching to alternative antipsychotic
What is a life-threatening symptom of Neuroleptic Malignant Syndrome?
Dysarthria
What does not have a specific predictive value on the risk of suicide in patients with schizophrenia?
Presence of halllucinations
Risk factors for neutropenia with Clozapine use?
Race (Afro-Caribbean 77% increase in risk)
Age (decrease in risk as age increases)
Low baseline white cell count
Risk factors for agranulocystosis with Clozapine use?
Age (increasing age increases risk)
Ethnicity (Asians are 2.4 times more likely than Caucasians to develop agranulocytosis on clozapine)
What proportion of patients who stop clozapine due to neutropenia or agranulocytosis will develop a blood dyscrasia on rechallenge?
1/3
Which drug used to manage hypersalivation resulting from clozapine use is supported by placebo controlled RCT evidence?
Amisulpride
% of patients on Clozapine that develop hypersalivation
30%
Which depot mediation requires at least 2 hours monitoring after it has been given?
Olanzapine
What is most likely to help rehab schizophrenia patientsreturn to independent living?
Supported employment
Which areasare most likely to be impaired when people with schizophrenia receive cognitive testing?
Working memory
Executive function:
Impaired planning
Speed of processing
What are some factors that indicate good prognosis in Schizophrenia?
- Family history of affective disorder
- having affective symptoms during episodes of illness
- Acute onset
- short duration of untreated symptoms
- older age of onset
- good premorbid functioning
- being in a stable relationship
- having a good support system