[2] Schizophrenia Flashcards
What is the most common psychotic condition?
Schizophrenia
What is schizophrenia characterised by?
Hallucinations, delusions, and thought disorders, which lead to functional impairment
What does schizophrenia occur in the absence of?
Organic disease, alcohol, and drug-related disoders
Can schizophrenia be secondary to an elevation or depression of mood?
No
What factors does the development of schizophrenia involve>
Both biological (including genetic) and environmental factors
What does the dopamine hypothesis of schizophrenia state?
That schizophrenia is secondary to over-activity of the mesolimbic dopamine pathways in the brain
What evidence supports the dopamine hypothesis of schizophrenia?
- Conventional antipyschotics work by blocking dopamine receptors
- Drugs that potentiate the pathway, for example anti-parkinonian drugs, cause psychotic symptoms
What is the stress-vulnerability model of schizophrenia?
The stress-vulnerability model predicts that schizophrenia occurs due to environmental factors interacting with a genetic predisposition (or brain injury). Patients have different vulnerabilities, so different individuals need to be exposed to different levels of environmental factors to become psychotic
What can the risk factors for schizophrenia be categorised into?
Biological, psychological, and social, or predisposing, precipitating, and perputating
What are the biological predisposing risk factors for schizophrenia?
- Genetic predisposition
- Neurodevelopmental problems, including intrauterine infection, premature birth, fetal brain injury, or obstetric complications
- Age 15-35
- Extremes of parental age (<20 years or >35 years)
What are the biological precipitating risk factors for schizophrenia?
Smoking cannabis or using psychostimulants
What are the biological perpetuating risk factors for schizophrenia?
- Substance misuse
- Poor compliance to medication
What are the psychological predisposing risk factors for schizophrenia?
- Family history (due to exposure to the person with schizophrenia)
- Childhood abuse
What are the psychological precipitating risk factors for schizophrenia?
- Adverse life events
- Poor coping style
What are the psychological perpetuating risk factors for schizophrenia?
Adverse life events
What are the social predisposing risk factors for schizophrenia?
- Substance misuse
- Low socioeconmic status
- Migrant population
- Living in an urban area
What are the social precipitating risk factors for schizophrenia?
Adverse live events
What are the social perpetuating risk factors for schizophrenia?
- Lack of social support
- Expressed emotions
What can the symptoms of schizophrenia be divided into?
- The positive symptoms (acute syndrome), where there is appearance of hallucinations and delusions
- Negative symptoms (the chronic syndrome), which refers to loss of function
What do the clinical features of schizophrenia depend on?
The type of schizophrenia
What are the positive symptoms of schizophrenia?
- Delusions
- Hallucinations
- Formal thought disorder
- Passitivity phenomenon
What is a delusion?
A fixed false belief, which is firmly held despite evidence to the contrary, and goes against the individuals normal social and cultural belief system
Of what nature are the delusions in schizophrenia often?
Persecutory, grandiose, nihilistic, or religious
What are ideas of reference?
Thoughts where a person thinks that common events refer to them directly, e.g. personal messages on TV
What are hallucinations?
Perceptions in the absence of an external stimulus
What kind of hallucination is most common in schizophrenia?
Third person auditory hallucinations
What is a formal thought disorder?
An abnormality in the way that thoughts are linked together
What is thought interference?
When the patient thinks that their thoughts are being inserted (thought insertion), removed (thought withdrawal), or heard out loud by others (thought broadcast)
What is meant by passitivity phenomenon?
When patients believe that their actions, feelings, or emotions are being controlled by an external force
What are the negative symptoms of schizophrenia?
- Avolition
- Asocial behaviour
- Anhedonia
- Alogia
- Blunted affect
- Attention deficit
What is avolition?
A reduced ability, or inability, to initiate and persist in goal-directed behaviour
What is asocial behaviour?
Loss of drive for any social engagements
What is anhedonia?
A lack of pleasure in activities which were previously enjoyable to the patient
What is alogia?
A quantitative and qualitative decrease in speech
What is meant by blunted affect?
Diminished or absent capacity to express feelings
What is meant by attention deficit?
Problems with attention, language, memory, and executive function
What are the types of schizophrenia?
- Paranoid schizophrenia
- Post schizophrenic depression
- Hebephrenic schizophrenia
- Catatonic schizophrenia
- Simple schizophrenia
- Undifferentiated schizophrenia
- Residual schizophrenia
What is paranoid schizophrenia?
The most common form of schizophrenia, that is dominated by positive symptoms
What is post-schizophrenia depression?
When depresion predominantes, with a schizophrenic illness in the past 12 months, with some schizophrenia symptoms still present
What is hebephrenic schizophrenia?
When thought disorganisation predominantes
How does hebephrenic schizophrenia differ from other forms?
The onset of illness is earlier (15-25 years) and has a poorer prognosis
What is catatonic schizophrenia?
A rare form of schizophrenia characterised by one or more catatonic symptoms
What is simple schizophrenia?
A rare form where negative symptoms develop without psychotic symptoms
What is undifferentatied schizophrenia?
When the person meets the diagnostic criteria for schizophrenia, but does not conform to any of the other subtypes
What is residual schizophrenia?
When there has been 1 year of chronic negative symptoms, preceded by a clear-cut psychotic episode
What are the ICD-10 diagnostic criteria for schizophrenia?
A person should have at least 1 very clear symptom from group A, and two or more from group B for at least 1 month
Group A;
- Thought echo/insertion/withdrawal/broadcast
- Delusions of control, influence, or passitivity phenomenon
- Running commentary auditory hallucinations
- Bizarre, persistent delusions
Group B;
- Hallucinations in other modalities that are persistent
- Thought disorganisation (loosening of association, neologisms, incoherence)
- Catatonic symptoms
- Negative symptoms
Schizophrenia should not be diagnosed in the presence of an organic brain disease
What is done in the investigation of schizophrenia?
- History
- MSE
- Blood tests to rule out organic cause
- Urine drug test
- ECG - antipsychotics can cause prolonged QT interval
- CT scan, to rule out organic cause
- EEG, to rule out temporal lobe epilepsy
What blood tests are done in schizophrenia?
- FBC
- TFTs
- Glucose/HbA1c
- Serum calcium
- U&E and LFTs
- Cholesterol
- Vitamin B12 and folate
Why is a FBC done in the investigation of schizophrenia?
To look for anaemia and infection
Why are TFTs done in the investigation of schizophrenia?
Thyroid dysfunction can present as psychosis
Why is glucose/HbA1c done in the investigation of schizophrenia?
Atypical antipsychotics can cause metbaolic syndrome
Why is serum calcium done in the investigation of schizophrenia?
Hypercalcaemia can present as psychosis
Why are U&Es and LFTs done in the investigation of schizophrenia?
Should assess renal and liver function before giving antipsychotics
Why is vitamin B12 and folate done in the investigation of schizophrenia?
Deficiencies can cause psychosis
What are the differential diagnoses of schizophrenia?
- Schizotypical disorder
- Acute and transient psychotic disorders
- Schizoaffective disorder
- Persistent delusional disorder
- Induced delusional disorder
- Mood disorders with psychosis
- Post-partum psychosis
- Late paraphrenia
What is schizotypal personality disorder?
A mental disorder characterised by severe social anxiety, thought disorder, paranoid ideation, derealisation, transient psychosis, and often unconventional beliefs
What is schizoaffective disorder?
A mental disorder characterised by abnormal thought processes and deregulated emotions. The diagnosis is made when a person has features of both schizophrenia and a mood disorder, either bipolar or depression, but does not strictly meet the diagnostic criteria alone
What is postpartum psychosis?
A rare psychiatric emergency in which symptoms of high mood and mania, depression, severe confusion, loss of inhibition, paranoid, hallucinations, and delusions set in, beginning suddenly in the first two weeks after childbirth.
What is paraphrenia?
A mental disorder characterised by an organised system of paranoid delusions, with or without hallucinations, and without deterioration of intellect or personality
How is paraphrenia distinguished from schizophrenia?
- Lower heriditary occurence
- Less pre-morbid maladjustment
- Slower rate of progression
How is schizophrenia managed?
- Risk assessment
- Bio-psychosocial approach
When might the Mental Health Act be required in schizophrenia?
For those who are a risk, and refuse informal admission
What are the options in the biological management of schizophrenia?
- Antipsychotics
- ECT
What can the anti-psychotics be broadly divided into?
Typical and atypical
When should a depot formation of anti-psychotics be considered?
- If the patient prefers
- If there are problems with compliance
What is the most effective anti-psychotic?
Clozapine
When should clozapine be used?
In treatment resistant schizophrenia
What is treatment resistant schizophrenia classified as?
Failure to respond to two other antipsychotics
How should the dose of anti-psychotics be determined?
When starting treatment with antipsychotics, you should titrate to the maximum effective dose, adjusting the dose according to response and tolerability, and then assess over 2-3 weeks. If the dose is effective, continue at dose established. If not effective, change the drug and repeat the procedure. If not tolerated or poor compliance, discuss possibility of changing drug with the patient. If compliance is poor related to other factors, consider depot injection
Give two examples of typical antipsychotic drugs
- Haloperidol
- Chlorpromazine
Give 4 examples of atypical antipsychotic drugs
- Olanzapine
- Risperidone
- Quetiapine
- Clozapine
What can all antipsychotic drugs do?
Reduce hallucinations and delusions associated with schizophrenia by blocking dopamine receptors in the mesolimbic system of the brain
How to the negative symptoms of schizophrenia respond to antipsychotics?
They are not as responsive to therapy, particularly with typical antipsychotics
How long should patients who have had two or more psychotic episodes secondary to schizophrenia receive maintenance therapy for?
At least 5 years
What is the mechanism of action of antipsychotics?
All typical and atypical antipsychotics block dopamine receptors in the brain and periphery.
The antipsychotic actions of the drugs appear to reflect a blockade at dopamine and/or serotonin receptors, however many of these agents also block cholinergic, adrenergic, and histaminergic receptors. It is unknown what role, if any, these actions have in alleviating the symptoms of psychosis
What does the clinical efficacy of typical antipsychotics correlate closely to?
Their relative ability to block dopamine receptors in the mesolimbic and mesocortical systems of the brain
What antipsychotic drugs block serotonin receptors as well as dopamine receptors?
Most atypical antipsychotics
Describe the interactions of clozapine with dopamine and serotonin receptors
Clozapine has a high affinity for D1, D2, 5-HT2, muscarinic, and alpha-adrenergic receptors, but is a weak dopamine receptor antagonist
Describe the interations of risperidone with dopamine and serotonin receptors
Risperidone blocks 5-HT2A receptors to a greater extent than it does dopamine receptors
Describe the interactions of olanzapine with serotonin and dopamine receptors
Olanzapine blocks 5-HT2A receptors to a greater extent than it does dopamine receptors
Describe the interactions of quetiapine with dopamine and serotonin receptors
Quetipine blocks dopamine receptors more potently than 5HT2A receptors, but is relatively weak at blocking both
What serotonin receptor is particularly important in atypical anti-psychotics?
5-HT2A
How long do antipsychotic effects of drugs take to occur?
Usually take several days to weeks
What does the antipsychotic effects taking a few days or weeks to occur suggest about the mechanism of action?
It is probably related to secondary changes in the corticostriatal pathway
What are the indications for anti-psychotic drug treatment?
- Treatment of schizophrenia
- Prevention of severe drug-induced nasuea and vomiting
- Use as tranquilisers to manage agitated and disruptive behaviour
- In combination with narcotic analgesics to manage chronic pain with severe anxiety
How efficacious are anti-psychotics in the treatment of schizophrenia?
They are considered to be the only efficacious treatment for schizophrenia, however not all patients respond, and complete normalisation of behaviour is seldom achieved
What symptoms are the typical antipsychotics most effective at treating?
Delusions, hallucinations, thought processing, and agitation
What anti-psychotics might be better for treating patients who are resistant to traditional agents?
Newer agents with 5-HT2A receptor blocking activity
What effect do antipsychotics have on the negative symptoms of schizophrenia?
Newer agents with 5-HT2A receptor blocking activity might be better at treating the negative synmptoms, however even atypical antipsychotics do not consistently improve the negative symptoms more than typical
How many patients do the adverse effects of schizophrenia affect?
Pratically all patients get adverse effects of schizophrenia, and they are significant in approx. 80% patients
What causes the adverse effects of schizophrenia?
The action of antipsychotics on unwanted pathways of the brain, namely the nigrostriatal and tuberoinfundibular pathways
What is the role of the nigrostrial pathway?
Involved in movement
What is the role of the tuberoinfundibular pathway?
Important in hypothalamic-pituitary-adrenal axis
What are the main categories of side effects of anti-psychotics?
- Extrapyramidal side effects
- Metabolic side effects
What is the mechanism of development of the extrapyramidal side effects of antipsychotics?
The inhibitory effects of dopaminergic neurones are normally balanced by the excitatory action of cholinergic neurones in the striatum. Blocking dopamine receptors alters this balance, causing a relative excess of cholinergic influence, which results in extrapyramidal motor effects
What is the risk of the appearance of movement disorders as a side effect of anti-psychotics dependant on?
Time and dose
When do dystonias appear as a side effect of anti-psychotics?
Within a few hours or days of treatment
When does akathisias appear as side effects to anti-psychotics?
Within days to weeks
What is akathisias?
Inability to remain seated due to motor restlessness
What Parkinsonism-like symptoms might develop as a side effect to anti-psychotics?
- Bradykinesia
- Rigidity
- Tremor
When do Parkinsonism-like symptoms appear as a side effect of anti-psychotics?
Within weeks to months of initiating treatment
What can long term treatment (months to years) with anti-psychotics cause?
Tardive dyskinesia
What happens in tardive dyskinesia?
Patients display involuntary movements, including bilateral jaw movements and ‘fly catching’ motions of the tongue.
Can tardive dyskinesia resulting from prolonged antipsychotic treatment be reversed?
A prolonged holiday from the antipsychotics may cause the symptoms to diminish or disappear within a few months, however in many individuals, the disorder is irreversible.
What are the advantages of clozipine?
It is the most efficacious of the antipsychotics, and improvements can continue for several months
What is the problem with clozipine?
It can have very serious side effects
When should clozipine be used in schizophrenia?
Only after two other anti-psychotics have not worked
What are the adverse effects of clozipine?
- Significant potential for agranulocytosis
- Significant potential for gastrointetinal hypomobility, causing constipation and potentially fatal bowel obstruction
- Hypersalivation
- Urinary incontinence
What is the result of the significant potential for agranulocytosis with clozipine?
Close monitoring of FBC is required - weekly for 18 weeks, then fortnightly, then monthly
What should be done when initiating clozipine?
The dose should be slowly titrated upwards over two weeks, and vital signs monitored due to the potential for autonomic dysregulation
What is anti-psychotic malignant syndrome?
A rare, life-threatening reaction to antipsychotics
What are the symptoms of anti-psychotic malignant syndrome?
- Fever
- Confusion
- Muscle rigidity
- Sweating
- Autonomic instability
What causes death in anti-psychotic malignant syndrome?
- Rhabdomyolysis
- Renal failure
- Seizures
What are the risk factors for anti-psychotic malignant syndrome?
- High potency dopamine antagonists (typical antipsychotics) in the antipsychotic naive
- High doses
- Young men
How is anti-psychotic malignant syndrome managed?
- Emergency referral to A&E
- Cessation of anti-psychotics
- Fluid resuscitation
- Temperature reduction
In whom should caution be taken with when considering anti-psychotic treatment?
- Acute agitation accompanying withdrawal from alcohol or drugs
- People with seizure disorders
- Patients with dementia-related behavioural disturbances and psychosis
- Mood disorders
What might happen if anti-psychotics are given to patients with acute agitation accompanying withdrawal from alcohol or drugs?
The agitation may be aggravated by the anti-psychotics
What is the preferred treatment in people with acute agitation accompanying withdrawal from alcohol or drugs?
Stabilisation with a simple sedative, e.g. benzodiazepines
Why should anti-psychotics be used with caution in patients with seizure disorders?
All antipsychotics lower the seizure threshold
Why should anti-psychotics be used with caution in patients in patients with dementia-related behavioural disturbances and psychosis?
Because all atypical antipyychotics have an increased risk of mortality when used in these patients
What should be done when anti-psychotics are given to patients with mood disorders?
Monitoring for worsening of mood and suicidal ideation or behaviours
Describe the absorption of anti-psychotics after oral administration?
They show variable absorption that is unaffected by the food
Can anti-psychotics pass readily into the brain?
Yes
Do anti-psychotics have a large or small volume of distribution?
Large
Do anti-psychotics bind well to plasma proteins?
Yes
What metabolises the anti-psychotics?
Usually the cytochrome P450 system in the liver
What are the antipsychotics metabolised to?
Many different substances, some of which are active
Give three examples of anti-psychotics that have long-acting injectable formulations
- Haloperidol
- Risperidone
- Olanzapine
How are the long-acting injectable formulations of anti-psychotics administered?
Via deep gluteal or deltoid intramuscular injection
What is the therapeutic duration of action of the long-acting injectable formulations of anti-psychotics?
2-4 weeks
What are the long-acting injectable formulations of anti-psychotics used for?
To treat outpatients and individuals who are non-compliant with oral medications
Do anti-psychotics produce tolerance?
Yes. some
Do anti-psychotics produce physical dependance?
A little
How does the efficacy of atypical antipsychotics compare to typical antipsychotics?
The atypical antipsychotics have an efficacy that is equal or greater too the typical
What is the advantage of atypical antipsychotics over typical?
They minimise the risk of debilitating movement disorders associated with typical antipsychotics
What is the advantage of typical antipsychotics over atypical?
Atypical have a higher risk of causing metabolic side effects, such as diabetes, hypercholesterolaemia, and weight gain
What baseline measurements should be done when starting a patient on antipsychotics?
- FBC
- Lipids
- LFTs
- HbA1c
- Weight
- ECG
- Blood pressure
- Pulse
What measurements should be taken weekly when a patient is started on antipsychotics?
Weight
What measurements should be taken 3 months after starting antipsychotic medications?
- FBC
- Lipids
- LFTs
- HbA1c
- Weight
- ECG
- Blood pressure
- Pulse
What measurements should be done yearly when a patient is on antipsychotics?
- FBC
- Lipids
- LFTs
- HbA1c
- Weight
- ECG
- Blood pressure
- Pulse
How can extra-pyramidal side effects of antipsychotics be managed?
Use of anticholinergics
Give three examples of anticholergic medications
- Procyclidine
- Benzatrophine
- Trihexphenidyl
How do antipsychotics reduce the extra-pyramidal side effects of anti-psychotics?
They normalise the ratio of acetylcholine in the nigrostriatal pathway, as antipsychotics cause there to be relatively too much ACh
What is the therapeutic trade off with the use of antimuscarinic drugs to reduce extra-pyramidal side effects of anti-psychotics?
They reduce the extra-pyramidal side effects, but give more side effects from muscarinic receptor blockade
What effects do antimuscarinics have on tardive dyskinesia?
They are not effective for, and may exacerbate, tardive dyskinesia
When might ECT be appropriate in the management of schizophrenia?
In patients who are resistant to pharmacological agents, or have catatonic schizophrenia
What are the options for psychological management in schizophrenia?
- CBT
- Family intervention
Art therapy - Social skills training
What are the options for social management in schizophrenia?
- Support groups, e.g. Rethink and SANE
- Peer support, delivered by peer support worker who has recovered from psychosis or schizophrenia and remains stable
- Supported employment programmes
