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This may be a period where negative symptoms dominate and patients may become isolated and withdrawn.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.
