Antipsychotics Flashcards
What are the domains of psychosis
- Positive symptoms: hallucinations, delusions, thought disorder
- Negative symptoms: alogia, apathy, avolition, associalty, affective blunting
- Disorganisation symptoms: bizarre, chaotic and agitated behaviours
What is the dopamine theory
Dopamine release from the mesolimbic pathway into the nucleus accumbens regulates motivation and facilitates reinforcement and reward
Excessive dopamine → positive symptoms of psychosis
What are the four dopamine pathways in the brain
Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular
What is the role of the mesolimbic dopamine pathway in psychosis
Ventral tegmental area → dopaminergic neurons → ventral striatum of basal ganglia
Responsible for positive symptoms
What is the role of the mesocortical dopamine pathway in psychosis
Ventral tegmental area → dopaminergic neurons → prefrontal cortex
Cognitive control, motivation, emotional response
Negative symptoms
What is the role of the nigrostriatal dopamine pathway in psychosis
Substantia nigra → dopaminergic neurons → striatum/basal ganglia
Extrapyramidal nervous system, controls motor movement
EPSE
What is the role of the tuberoinfundibular dopamine pathway in psychosis
Hypothalamus → dopaminergic neurons → anterior pituitary gland
Normally active and inhibits the release of prolactin
Hyperprolactinaemia
Which area of the brain is associated with aggressive and impulsive symptoms
Orbitofrontal cortex and connections to the amgydala
What receptors do typical antipsychotics act on and give examples
Widely acts on D2 dopamine receptors
Chlorpromazine (first)
Haloperidol
Zuclopenthixol
Flupentixol
What receptors do atypical antipsychotics act on and give examples
Selectively acting for dopamine, serotonin and 5-HT2A
Clozapine
Olanzapine
Quetiapine
Risperidone
Aripiprazole
Why are atypical antipsychotics preferred to typical antipsychotics
Antagonist of the 5HT-2A receptor
Reduces antipsychotic receptor occupancy from 80-60% in the nigrostriatal pathway → reduces risk of EPSEs
Which antipsychotics have partial agonist activity
aripiprazole
cariprazine
furasidone
What are the side effects of antipsychotics
Hyperprolactinaemia
QTc prolongation
Extra-pyramidal side effects:
- Parkinsonism
- Dystonia
- Tardive dyskinesia
- Akathisia
Metabolic syndromes
Neuroleptic malignant syndrome
What are the differentials for hyperprolactinaemia
Physiological: pregnancy, lactation, stress
Antipsychotics - amisulpride, risperidone
Antidepressants
Organic: prolactinoma
What are the symptoms of hyperprolactinaemia
Often asymptomatic, clinically significant >1000
Women: reduced libido, amenorrhoea, galactorrhoea, osteoporosis, increase breast Ca risk
Men: reduced libido, erectile dysfunction, gynaecomastia, galactorrhoea
What is the management for hyperprolactinaemia caused by antipsychotics
Switch to a prolactin sparing agent e.g. quetiapine, aripiprazole (dopamine agonist)
Add in aripiprazole
Avoid dopamine agonists e.g. cabergoline, bromocriptine
What does the QT segment represent, what is classified as prolongation, and why is prolongation a risk
Ventricular depolarisation and repolarisation
Corrected fro heart rate (QTc)
>500ms - risk increases significantly
Increases risk of cardiac arrhythmias e.g. polymorphic ventricular tachycardia (Torsade de Pointes) → loss of cardiac output → unconsciousness → death
What is the management for QTc prolongation caused by antipsychotics
Switch to a more QTc sparing agent e.g. aripiprazole
Describe parkinsonism EPSEs from antipsychotics
Occurs when 80-90% of the neurons are lost
Classic symptoms: bradykinesia, rigidity, pill rolling tremor, postural instability
Stooped posture
Shuffling gate, reduced arm swing
Hypomimia
Generally bilateral
What investigations and management should be done for parkinsonism EPSEs from antispychotics
dopamine transporter (DAT) scan
Management: switch medication, add procyclidine (anti-muscarinic)
What is tardive dyskinesia as an EPSE of antipsychotics
Involuntary orofacial dyskinesia associated with long term antipsychotic use
Develops after months/years of treatment
Typically seen as continuous mouth and tongue movements e.g. lip smacking, eye closing, jaw clenching, trunk/extremity movement
What are the the risk factors for developing tardive dyskinesia from antipsychotics
Typical antipsychotics
High dose
Elderly
What is the management for tardive dyskinesia caused by antipsychotics
May be permanent, even when the medication is stopped
Stop the causative agent
Consider tetrabenazine
What is dystonia as an EPSE of antipsychotics
Involuntary muscle spasm/contractions
Develops within hours of starting antipsychotics
Specific types:
- Oculogyric crisis (eyes rolling upward)
- Torticollis (head and neck twisted to one side)
- Laryngeal dystonia (can compromise airway and be life threatening)
What are the risk factors for developing dystonia from antipsychotic use
Antipsychotics naive
young males
High dose typical antipsychotics
What is the management for dystonia caused by antipsychotics
Anticholinergics e.g. procyclidine
What is akathisia as an EPSE of antipsychotics
A sense of internal restlessness.
Occurs within days to weeks of starting/increasing an antipsychotic
The patient feels compelled to constantly move, rock, fidget or pace around.
Associated with an increased risk of suicide
What is the management for akathisia caused by antipsychotics
Change medication
Diphenhydramine
Propranolol
Low dose benzodiazepines
Describe metabolic syndrome
Schizophrenia reduces life expectancy by 15-20 years, partly mediated by the metabolic side effects:
Weight gain
Dyslipidaemia
Insulin insensitivity
Leads to heart disease, lipid problems, HTN, T2DM, dementia, PCOS, cancer, NAFLD
What is the management for metabolic syndrome caused by antipsychotics
Monitor weight, BP, lipid profile, and HbA1c
Treat any complications on their merits e.g. statins, anti-glycaemics, anti-hypertensives
Promote health eating and exercise
How long does it take for antipsychotic effects to be apparent
Sedation: minutes-hours
Antipsychotic effect: 1-2 weeks, max benefit within 6 weeks
What is high dose antipsychotic treatment (HDAT)
total antipsychotic dose >100% BNF maximum dose
What antipsychotics can be used for rapid tranquilisation
IM olanzapine
IM haloperidol
What cautions should be taken for antipsychotic use as tranquilisation
Pre-treatment ECG needed with haloperidol due to risk of QTc prolongation
IM olanzapine not to be given within 1 hr of IM lorazepam due to risk of respiratory depression
No more than 3 days of IM olanzapine to be given in a row due to risk of post-injection syndrome
What is treatment resistance and what can be used
Treatment resistance = If two antipsychotics have been given an adequate trial (6 weeks at a therapeutic dose including one atypical)
→ consider clozapine (i.e. treatment resistance pathway)
Which medication has evidence towards negative symptoms
Clozapine
What needs to be done before clozapine is started in a patient
FBC and ECG prior
Register with national clozapine monitoring service
How often does a patient need to be monitored while on clozapine
Weekly → fortnightly → monthly (after 1 year of treatment)
What is the traffic light system for clozapine monitoring
Green: continue
Amber: continue but FBC monitoring increased to twice weekly
Red: stop immediately
What are the side effects of clozapine
Lowering of seizure threshold
Constipation
Agranulocytosis/Neutropenia/leucopenia → regular FBC test monitoring
Myocarditis, cardiomyopathy, tachycardia, hypotension
Hypersalivation
Prothrombotic → DVT/PE
Sedation, increased appetite → weight gain (Blocks histamine-H1 receptors)
What are the symptoms of agranulocytosis caused by clozapine
Ulcer development in mucous membranes that line the mouth and GI tract
Susceptible to bacterial infections
Sepsis occurs to bacterial contamination
How should clozapine be started and stopped
Start at a low dose and titrate slowly
Re-titrate if stopped >48 hours
Stop slowly - if abruptly stopped there is a high risk of rebound psychosis
What monitoring is done for patients on antipsychotics
6 weeks: weight
12 weeks: weight, pulse, BP, HbA1c//glucose, lipids
1 year: weight, pulse, BP, HbA1c//glucose
Annually:
- Weight, pulse, BP, waist circumference
- HbA1c, U&Es, FBC, lipids, prolactin, LFTs, CK
Describe neuroleptic malignant syndrome
Acute potentially life threatening complication of antipsychotic treatment, seen in <1% of patients
A disorder of thermoregulation and neuromotor control
Within hours to days of starting an antipsychotic:
agitated delirium with confusion
pyrexia
muscle rigidity
Hyporeflexia
autonomic lability: hypertension, tachycardia and tachypnoea
Diaphoresis
Raised CK, AKI, leukocytosis
Mortality 10%
What is the management for neuroleptic malignant syndrome
- stop antipsychotic
- Admit/transfer to MEDICAL ward
- IV fluids (prevent renal failure) ± dantrolene ± bromocriptine
