Psychosis and Schizophrenia Flashcards
What is schizophrenia?
What is its prevalence?
Chronic and debilitating neurodevelopmental disorder that affects thinking, emotions and behaviour.
Schizophrenia normally involves periods of acute illness where symptoms can be intense and distressing, followed by more settled periods where symptoms can subside.
It is usual for the first few episodes of psychosis to occur in teenagers and early adulthood, with peaks of diagnoses in the mid-20s. Lifetime prevalence of around 1% of the population worldwide
What are the risk factors for schizophrenia?
- Genetics/Family history
- Environmental stressors, particularly those that occur early in life
- Certain substances, such as cannabis, cocaine, lysergic acid diethylamide (LSD) or amphetamines, can trigger symptoms in susceptible individuals
What are the International Classification of Diseases (ICD-10) requirements for schizophrenia diagnosis?
At least one symptom from the first three below are present most of the time for at least one month:
1. Hallucinations
2. Delusions
3. Specific thought disorder (e.g. thought insertions or withdrawals, or thought broadcasting);
4. At least one symptom from two of the following:
- Catatonic symptoms (e.g. reduced speech and movement, unresponsiveness, agitation or confusion)
- Negative symptoms (e.g. social withdrawal, isolation, apathy or self neglect);
- Thought disorder (e.g. breaks in train of thought, neologisms [i.e. a newly coined word or expression]).
What are positive symptoms?
Something being added that is not normally there (e.g. hallucinations, delusions and specific thought disorder)
What are negative symptoms?
A reduction in functioning (e.g. apathy, self-neglect, withdrawal and lack of drive)
Many people with schizophrenia will experience a prodromal period before a diagnosis is made. What is this?
This may be a period where negative symptoms dominate and patients may become isolated and withdrawn. This may be confused with depression.
People who experience more frequent or longer episodes of untreated schizophrenia can become irreversibly impaired, experiencing long-term problems with cognition and residual symptoms.
True or False?
True
Antipsychotics mainly target what receptors?
How does this differ for newer/atypical antipsychotics?
Antipsychotics mainly target the dopamine D2 receptor because overactivity in the dopaminergic pathways is thought to be involved in the development of schizophrenia
The newer antipsychotics are serotonin 5-hydroxytryptamine receptor 2A (5HT2A) antagonists and affect dopamine receptors to a lesser and varying extent
- less propensity to cause EPSEs
What type of psychotic symptoms do typical (1st gen) antipsychotic drugs relieve?
What are some examples?
Positive symptoms such as thought disorder, hallucination, delusions
- Flupentixol and zuclopentixol
- Haloperidol
- Levomepromazine
- Chlorpromazine and prochlorperazine
- Trifluoperazine
- Sulpiride
What symptoms of psychosis may atypical (2nd or 3rd gen) antipsychotics be better for?
What are some examples?
Negative symptoms such as apathy and withdrawal.
- Amisulpride
- Aripiprazole
- Clozapine
- Olanzapine
- Paliperidone
- Quetiapine
- Risperidone
There is no evidence of any significant benefit of one class of antipsychotics over the other.
True or False?
True
However, there is wide variation in the side effects they can cause. It is, therefore, essential to understand what side effects are most important to the patient and to know which antipsychotic drug is more likely to cause these adverse effects.
What is the treatment pathway for schizophrenia?
How do antipsychotics affect the Alpha 1 adrenergic receptor?
Antagonist
Side effects:
- Dizziness
- Postural hypotension
- Sedation
Antipsychotics MOST likely to cause this effect:
- Clozapine
- Chlorpromazine
- Risperidone
Antipsychotics LEAST likely to cause this effect:
- Amisulpride
- Aripiprazole
How do antipsychotics affect the Alpha 2 adrenergic receptor?
Antagonist
Side effects:
- Hypertension
Antipsychotics MOST likely to cause this effect:
- Risperidone
Antipsychotics LEAST likely to cause this effect:
- Amisulpride
- Aripiprazole
(Same as A1 receptors)
How do antipsychotics affect the Dopamine D2 receptor?
Antagonist
Side effects:
- Extrapyramidal side effects
- Hyperprolactinaemia
Antipsychotics MOST likely to cause this effect:
- First-generation antipsychotics
- Amisulpride
- Risperidone
Antipsychotics LEAST likely to cause this effect:
- Aripiprazole (partial D2 agonist)
- Clozapine
- Olanzapine
- Quetiapine
How do antipsychotics affect the Histamine H1 receptor?
Antagonist
Side effects:
- Sedation
- Weight gain
Antipsychotics MOST likely to cause this effect:
- Clozapine
- Olanzapine
- Chlorpromazine
- Quetiapine
Antipsychotics LEAST likely to cause this effect:
- Amisulpride
- Aripiprazole
- Lurasidone
How do antipsychotics affect the Muscarinic acetylcholine receptor?
Antagonist
Side effects:
- Antimuscarinic s/es (blurred vision, confusion, constipation, dry mouth, urinary retention)
Antipsychotics MOST likely to cause this effect:
- Chlorpromazine
- Clozapine
Antipsychotics LEAST likely to cause this effect:
- Amisulpride
- Aripiprazole
- Lurasidone
How do antipsychotics affect the 5HT2A receptor?
Antagonist
Side effects:
- Sedation
Antipsychotics MOST likely to cause this effect:
- Clozapine
- Olanzapine
- Risperidone
- Lurasidone
Antipsychotics LEAST likely to cause this effect:
- Amisulpride
When is Clozapine indicated?
In resistant schizophrenia when used 2 or more antipsychotics for at least 6-8 weeks each (where at least one was atypical/second gen)
What monitoring is required when patients are taking antipsychotics?
Weight:
Start, weekly for first 6 weeks, at 12 weeks, at 12 months then yearly
Pulse, blood pressure, fasting blood glucose, HbA1C, blood lipids:
at 12 weeks, at 1 year and then annually
ECG: before initiation
- To exclude abnormalities such as prolonged QT interval. - Repeat periodically and reduce dose if QT interval prolongation seen or another cardiac abnormality develops.
FBC, U+Es and LFTs: Start then yearly
What antipsychotics may require higher doses in smokers?
(HOC a lung)
Haloperidol, olanzapine and clozapine
Induced by a chemical found in cigarettes, but not nicotine itself. Tobacco smoke contains aromatic hydrocarbons that are inducers of CYP1A2
How should a patient who stops smoking whilst on haloperidol, olanzapine or clozapine be managed?
Patients who want to stop, or who inadvertently stop, smoking while taking antipsychotics should be monitored for signs of increased adverse effects (e.g. extrapyramidal side effects, weight gain or confusion)
Dose may need reducing
Patients who take clozapine and who wish to stop smoking should be referred to their mental health team for review as clozapine levels can increase significantly when smoking is stopped
Should people with psychosis/schizophrenia be offered bupropion and varenciline to aid smoking cessation?
No
Warn people with psychosis or schizophrenia who are taking bupropion or varenicline that there is an increased risk of adverse neuropsychiatric
symptoms and monitor them regularly, particularly in the first 2 to 3 weeks
What antipsychotics are available as long acting injectables?
Atypicals: olanzapine, risperidone, paliperidone, aripiprazole
Typicals: haloperidol, zuclopenthixol, flupentixol
There is little difference in effectiveness of the antipsychotic LAIs. Side effects are similar to their oral equivalents.
How is treatment resistant schizophrenia defined?
The failure to respond to or tolerate two sequential antipsychotics, where one is a 2nd gen/atypical antipsychotic given at an adequate dose for an adequate length of treatment
What antipsychotic is indicated for treatment resistant schizophrenia?
Clozapine is the only antipsychotic with consistent evidence of superiority in comparison to other antipsychotics.
What psychological treatments can be offered alongside pharmaceutical therapy? Can they be used alone?
- Cognitive behavioural therapy (CBT) aims to challenge unhelpful thinking patterns and help patients understand their symptoms and illness
- Family therapy can help families come together to deal with a diagnosis by looking at causes of stress and finding ways to address these in a positive way
- Arts therapies, such as music, painting/drawing or dance offer different ways for people to express and work through their problems
- Cognitive remediation - the therapeutic process of increasing or improving an individual’s capacity to process and use incoming information, allowing increased functioning in everyday life
Not suitable as a standalone treatment in schizophrenia because it does not prevent relapse
What can be done if there is an inadequate response to clozapine alone?
Combinations of medicines, such as mood stabilisers, other antipsychotics and antidepressants, can be used to augment clozapine or as an alternative to clozapine
How should doses of antipsychotic drugs be increased?
Slowly and not more often than one per week.
Occasionally, high dose antipsychotic therapy is considered for a limited period. When should this be discontinued if no improvement is seen?
After three months, reduce to normal dosage.
Emergency IM doses of antipsychotics are sometimes given. How should the dose given relate to that of the orally administered dose?
The IM dose should be lower to account for the lack of the first pass effect. The dose should be reviewed at least once daily.
What risks are there when an elderly patient with dementia takes antipsychotic drugs?
An increased risk of mortality and stroke or TIA. The elderly are also at an increased risk of postural hypotension and hyper- & hypothermia.
Should antipsychotics be prescribed for mild to moderate cases in the elderly?
No.
What can be done if clozapine has failed to be effective or is not tolerated?
- Review diagnosis/adherence/psychological treatments/interactions with other medicines
- Consider therapeutic drug monitoring
If above fails then consider a second antipsychotic to augment treatment with clozapine. An
adequate trial of may need to be up to 8 to 10 weeks
Or can be tried on doses of single or combined antipsychotics that exceed the licensed maximum doses
The initial dose for antipsychotics in the elderly should be less than that of an adult dose. How much different should they be?
Half the adult dose or less. Treatment should be reviewed regularly.
Which is the only atypical antipsychotic licensed for use in patients over the age of 65? For how long should it be used before review?
Risperidone. It should be used for 6 weeks then reviewed.
What type of side effects are the first gen/typical antipsychotics usually associated with?
Extrapyramidal side effects.
Most common with:
- Group 3 phenothiazines (Fluphenazine, Prochlorperazine, trifluoperazine)
- Haloperidol and Benperidol
What type of side effects are the second gen/atypical antipsychotics usually associated with?
Metabolic side effects
Give some examples of first gen/typical antipsychotics.
Chlorpromazine, haloperidol, flupentixol, fluphenazine.
Give some examples of second gen/atypical antipsychotics.
Amisulpride, aripiprazole, olanzapine, quetiapine, risperidone.
Give some extrapyramidal symptoms.
Acute pseudoparkinsonism, acute dystonia, acute akathisia, chronic tardive dyskinesia.
How is acute pseudoparkinsonism treated?
With antimuscarinics such as procyclidine.
What symptoms are associated with acute pseudoparkinsonism?
Tremor or rigidity.
What symptoms are associated with acute dystonia?
Abnormal face and body movements.
How is acute dystonia treated?
With antimuscarinics such as procyclidine.
What symptoms are associated with acute akathesia?
Inner restlessness.
How is acute akathesia treated?
By either discontinuing antipsychotic treatment or switching to a different antipsychotic.
What is tardive dyskinesia?
Rhythmic, involuntary movements of the tongue, face and jaw. Usually develops on long-term therapy. May be irreversible upon drug withdrawal. Worth switching the patient to an atypical antipsychotic.
What are the symptoms of hyperprolactinaemia?
Sexual dysfunction, reduced bone mineral density, menstrual disturbances, breast enlargement, galactorrhoea (excessive or inappropriate production of milk).
How does hyperprolactinaemia develop?
Both first and second generation antipsychotics increase prolactin concentration because dopamine inhibits prolactin release.
Less dopamine = more prolactin.
Hyperprolactinaemia is more prevalent with which antipsychotics?
Risperidone and amisulpride.
What symptoms of sexual dysfunction are seen with ALL antipsychotic use?
Decreased libido, disorders of arousal, erection/ejaculation problems in men.
Sexual dysfunction is more common with which antipsychotics?
Haloperidol and risperidone.
When is QT interval prolongation more likely to be seen when using antipsychotics?
When exceeding the recommended maximum dose.
What cardiovascular side effects are seen with antipsychotic use?
QT-interval prolongation, tachycardia, arrhythmias, hypotension. Cases of sudden death have been noted.
Which antipsychotics come with a greater risk of hyperglycaemia and diabetes? (CiROQ has the sweetest flavours)
Clozapine
Risperidone
Olanzapine
Quetiapine
Regular monitoring is necessary.
Which antipsychotics come with a greater risk of postural hypotension and syncope?
Clozapine, chlorpromazine, quetiapine.
When are FBC, U&Es and LFTs required when a patient is taking antipsychotic medication?
At the start of therapy and every year thereafter.
When are blood lipids and weight required to be monitored when a patient is on antipsychotic medication?
At baseline, weekly for the first 6 weeks, then at 12 weeks, at 1 year, and then yearly
When should fasting blood glucose, HbA1c, and blood lipids be monitored in patients taking antipsychotic medication?
Baseline, at 12 weeks, at 1 year, and then yearly
Prolactin at baseline.
When should a patients BP be monitored when they are taking antipsychotic medication?
Before starting therapy, at 12 weeks, at 1 year and then yearly
When is ECG monitoring required when a patient is taking antipsychotic medication?
When patients present with CV risk factors or a personal history of CVD.
When should serum prolactin concentration be monitored in patients taking antipsychotic medication?
At the start of therapy, at 6 months, then yearly thereafter.
When should patients with schizophrenia have physical health monitoring?
At least once per year.
Which antipsychotic drug comes with an increased risk of acute dystonic reactions, especially in young children and young women?
Chlorpromazine.
What are the symptoms of the acute dystonic reactions associated with chlorpromazine use?
Facial and skeletal muscle spasms and oculogyric crisis.
Healthcare staff should avoid direct contact with which antipsychotic medication?
Chlorpromazine (contact sensitization). Tablets should not be crushed and solutions should be handled with care.
Can also cause skin photosensitivity.
Patients should be advised on using sunscreen if necessary.
ECG monitoring is required before treatment and anually with which antipsychotic drug? Why?
Pimozide due to risk of sudden unexplained death. Should not be given with other antipsychotics, TCAs, or other drugs which prolong the QT interval.
What should be done if the QT interval is prolonged when a patient is on pimozide?
Review treatment.
There is an increased risk of fatal blood disorder/agranulocytosis with which antipsychotic drug?
Clozapine. Avoid use with other drugs which may exacerbate agranulocytosis/neutropenia (such as carbimazole, carbamazepine or DMARDs)
What specific monitoring should be done prior to clozapine usage?
Blood counts.
Physical examination and full medical history.
Specialist examination if cardiac abnormalities or history of heart disease found.
When on clozapine, what symptoms should patients report immediately?
Symptoms of infection, especially flu-like symptoms.
There is a risk of fatal myocarditis and cardiomyopathy with which antipsychotic drug?
What are the symptoms?
Clozapine
Tends to occur early on in treatment
Symptoms: fever, chest pain, flu-like symptoms, tachycardia and shortness of breath
What course of action should be taken if a patient on clozapine develops tachycardia, especially in the first two months of therapy?
Tachycardia is common at the start of treatment, but tends to improve with continued use
Patients should speak to their doctor or psychiatry team to have their heart rate checked.
If persistent - Stop and observe for other indicators of cardiomyopathy or myocarditis.
If myocarditis or cardiomyopathy are suspected during clozapine use, what course of action should be taken?
Stop clozapine and patient evaluated urgently by cardiologist.
If clozapine-induced myocarditis or cardiomyopathy occurs during clozapine treatment, what course of action should be taken?
Discontinue clozapine permanently.
Which antipsychotic drug is associated with an increased risk of constipation, intestinal obstruction, faecal impaction and fatal paralytic ileus?
Clozapine.
Refer to A+E
With regards to intestinal obstruction, which drugs should be avoided when a patient is taking clozapine?
Drugs that may cause constipation such as antimuscarinics or opioids.
With regards to intestinal obstruction, which patients may not be suitable for treatment with clozapine?
Patients with a history of colonic disease or lower abdominal surgery.
How can the hypersalivation associated with clozapine use be treated? When must extra caution be taken?
Hyoscine hydrobromide as long as the patient is not at risk from the additive anti-muscarinic side-effects of hyoscine and clozapine.
What antipsychotic is specifically licensed for the treatment of psychosis related to Parkinson’s disease?
Clozapine
- also shows particular efficacy in reducing the risk of suicide in those with schizophrenia
What antipsychotics are licensed in children? (HSAC)
- Haloperidol at 12 years
- Sulpiride at 14 years
- Aripiprazole at 15 years
- Clozapine at 16 years.
With which antipsychotic is there an increased risk of CNS and respiratory depression?
Olanzapine.
There is an increased risk of CNS and respiratory depression when olanzapine is used with which class of drugs?
Benzodiazepines.
If administering olanzapine IM, what monitoring is required?
Blood pressure, pulse, and respiratory rate for at least four hours.
How long should be left between administration of IM olanzapine and parenteral benzodiazepines?
At least one hour.
Give examples of first generation/typical antipsychotics
Group 1: ‘-promazine’
Chlorpromazine, levomepromazine, promazine
- Most sedation
- Moderate antimuscarinic and EPSEs
Group 2:
Pericyazine
- Moderate sedation, least EPSEs
Group 3: ‘azine’
Fluphenazine, Prochlorperazine, trifluoperazine
- High EPSEs
- Moderate sedation
Others:
- Haloperidol and Benperidol (same as group 3 - high EPSEs)
- Flupentixol and zuclopenthixol
- Sulpiride, Pimozide (least)
Give examples of second generation/atypical antipsychotics
Amisulpride Aripiprazole (least side effects) Clozapine Olanzapine Quetiapine Risperidone
In what drug is hyperprolactinaemia least common?
Aripiprazole
Which antipsychotics come with a greater risk of weight gain? (COW)
Does stopping them reverse weight gain?
Clozapine and olanzapine
- Weight gain tends to start early in the treatment and is not thought to be dose-related and tends to slow down or plateau with continued therapy
- Stopping the antipsychotic does not reverse the weight gain
- Treatments are available, such as metformin, aripiprazole and orlistat, to help patients with weight loss
How is neuroleptic malignant syndrome treated?
Stop antipsychotic
Give bromocriptine (ergot derived dopamine agonist)
Should resolve in 5-7 days
Specialist reinitiation is needed for clozapine if how many doses are missed?
Two or more days
How often are leucocytes and differential blood counts monitored for clozapine?
Weekly for 18 weeks then
2-weekly until 12 months (i.e. for 34 weeks)
Then monthly until stops taking
And then for an additional month after treatment stops
What is the ‘Care programme approach’ (CPA)?
- One person co-ordinates the patient’s care and is responsible for ensuring they have an up-to-date care plan
- Multidisciplinary approach
- Managed by the patient’s community mental health team
- Not all patients with schizophrenia will require a CPA because it is generally used for those with more complex needs.
What WBC and neutrophil result is classed as green?
How frequently are FBCs monitored for clozapine? (Dependent on treatment length)
WBC (10^9/L) = >3.0
AND
Neutrophils (10^9/L) = >2.0
0–18 weeks = Weekly
18–52 weeks = Fortnightly
>52 weeks = Four-weekly
What WBC and neutrophil result would be classed as Amber for clozapine? How often should the patient be monitored?
WBC (10^9/L) = 3.0 - 3.5
and/or
Neutrophils (10^9/L) = 1.5–2.0
Twice-weekly until green
What WBC and neutrophil result would be classed as Red for clozapine? How often should the patient be monitored?
WBC (10^9/L) = <3.0
and/or
Neutrophils (10^9/L) = <1.5
Monitor daily until green
What platelet level requires discontinuation of clozapine?
If platelet counts fall below 50×10^9/L
What eosinophil level requires discontinuation of clozapine?
Cell counts above 3.0×10^9/L
What advice should be given to patients regarding risk of diabetes?
- This can occur in relation to weight gain but also on its own in the absence of weight gain.
- It can occur early on in treatment where plasma glucose should be measured, rather than haemoglobin A1c
- Provide advice on healthy eating and exercise and refer the patient to their team for further monitoring and advice.
Are clozapine levels required? When are they taken?
Clozapine plasma level are not mandatory, but it is recommended to be completed annually or when clinically indicated (e.g. Non-response to current dose; Concerns about non-concordance; Change in smoking habits; Concerns about toxicity)
Clozapine plasma levels are taken as a trough level and at least 12 hours post-dose where clozapine plasma levels are indicated. Where a patient is taking twice-daily clozapine they should not take their morning dose until the level has been taken
How is sedation as an ADR of clozapine managed?
It is possible to adjust twice-daily dosing so that a greater proportion is taken at night time
Advise the patient to speak to their prescriber.
How should patients be advised to manage constipation due to clozapine?
What treatment is available?
- Offer healthy dietary advice and advise an increase of fluid intake and exercise
- Signs of serious constipation or it is not improving with simple measures, advise the patient to speak to their GP
- Initial treatment should be with a stimulant laxative, but combination of stimulant and osmotic laxative or stool softeners are often required.
What symptoms are indicative of severe constipation and require referral to GP?
- No improvement or bowel movement following laxative use
- Fever
- Stomach pain
- Vomiting
- Loss of appetite and/or diarrhoea (potential faecal impaction overflow)
