Week 2 - Schizophrenia and Antipsychotics Flashcards
What are the risk factors, symptoms and age of onset for schizophrenia
RISKS:
- Genetics i.e. suceptibility genes
- Environemntal i.e. life events, drug abuse, prenatal problems
The more risks you have = ↑ risk of development
SYPMTOMS:
- Positive - adds something to person’s personality
- Negative - takes something away from person’s personality
- Cognitive - affects brain
AGE of ONSET:
- late teens / early adulthood (majority cases)
- hormones may affect development as there are 2 peak increases in its diagnosis for women ( teen / adult+ post-menopausal)
OTHER INFO:
- have other comorbidities with schizophrenia e.g. mental ilness, substance misuse
- die 15-20 years earlier than those without schizophrenia due to suicide or other physcial health disease
Explain the 3 types of symptom groups
- Positive
- hallucinations e.g. hear voices
- delusions
- disordered thoughts, speech and behaviour e.g. not their own thoughts
NOTE: - most treatment targets these symptoms
- symptoms linked to excessive dopamine released in associative striatum (of brain)
- Negative
- alogia (reduced quantity of words spoken / lack of speech)
- avoliation (reduced motivation)
- anhedonia (lack of interest, enjoyment or pleasure)
- affective flattening (reduced / no change in expressions)
NOTE: - symptoms linked to prefrontal cortex of brain
- Cognitive
- attention deficit e.g. can’t concentrate, irritable
- memory difficulties
- executive functioning e.g. problem solving
NOTE: - symptoms linked to reduced dopamine in prefrontal cortex of brain
How are signs / symptoms used to diagnose schizophrenia
other ppt
Diagnosed via: DSM-5, ICD-11 or presence of positive symptoms
- picks up on altered behaviour, cognition and emotion
- need to have symptoms present for approx 1 month (some say 6 months)
- need to be careful as many other conditions can present with psychosis
Prodromal state (state before diagnosis of schizophrenia) is important
- may recieve treatment during this phase, typically CBT before antipsychotics
What are the 4 dopamine pathways
- Nigrostriatal
- nigra to striatum (associative striatum is affected in schizophrenia)
- Mesolimbic
- mid brain (VTA) to the limbs
- includes VTA and nucleus accumbens
- a.k.a. reward pathway
- Mesocortical
- mid brain (VTA) to frontal cortex
- if have schizophrenia + cognitive symptoms = do NOT have enough dopamine in this pathway
- Tuberinfundibular
- tuberal region to infundibular region
- this pathway is isn’t linked to schizophrenia BUT schizophrenia treatment affects pathway
- USUALLY dopamine binds to D2 receptors inhibiting prolactin release
- BUT tretament prevnts dopamine binding = prolacton release = hyperprolactermia
List the current treatments for schizophrenia
- Antipsychotics (D2 receptor antagonist)
- Partial agonist
- behaves like dopamine BUT as it is partial = will partially activate receptor = dampens down signal = ↓ inhibition
- Non-pharmacological treatment
NOTE:
D2 receptor = inhibitory
D1 receptor = excitatory
What causes schizophrenia and how does antipsychotic treat it
CAUSE:
- excess dopamine in synapse of associative striatum
- dopamine binds to D2 receptors = over-activation = positive symptoms
TREATMENT:
- D2 receptor antagonist binds to receptor preventing dopamine from binding
- at least 65% blockage = effective
- works best when taken regulalry, poor adherance = ↑ risk of relapse
- have poor recovery rate, not many remain in remission
- body still has excess dopamine but as it can’t bind it looks like normal levels are present
- BUT once stop taking antipsychotics = relapse
- as antispychotics does NOT CURE schizophrenia just alleviates symptoms
What are the 3 Phases when treating with antispychotics
- Early phase (6 months to 1 year)
- earlier its diagnosed + treated = better respone
- usually have a high response in 1st epsiode
- Next phase (2-3 years)
- many remain remission BUT many also relapse
- Late phase (>5 years)
- may still relapse despite being on antipsychotics
What are the options for treating schizophrenia + how might they be used
other ppt
- Pharmacological
- includes typcial and atypical antipsychotics
- can be oral
- can be depot injections (convenient, dont have to take meds daily)
- partial agonsits
- includes typcial and atypical antipsychotics
- Non-pharmacological
- CBT
- Arts therapy (improve negative symptoms)
Depot (long acting) Antipsychotic Injections
can be used for either typical or atypical
- More effective than oral therapy
- level doesnt fluctuate in body over time (has steady state)
- more stability = fewer relapse - Considered if patient has adherance issues
- Have more atypical drug options
- need to ensure they have tried the oral version of the injection first (ensures they can tolerate drug / have no ADRs)
- start on low dose and taper up slowly
- use longest dose interval possible e.g. every 3 months - If use typical option need to prescribe a test dose
- dose less than normal dose to treat illness
- tests for SE and allergic r5eactions
NOTE: need to visiti clinic / home visits for injections
may need to remain in clinic after inejction to be monutored for few hours
How to treat 1st schizophrenia episode in adults - NICE GUIDELINES
Prodromal phase (phase before achizophrenia episode):
- offer CBT
- do NOT offer antipsychotics
1st Episode:
- do a full assessment + rule out other possible causes for symptoms
- offer antipsychotics + CBT
- when deciding drug ~ shared decision making consider patient history, side effects, which likely to tolerate more
Maintenance Treatment:
- continue treatment for 1-2 years if effective
- be careful when stopping due to withdrawal + high relapse risk
- need to taper dose down slowly when wanting to come off
- dramatic reductions = symptoms reappear + side effects
What are the core principles when using antipsychotic therapy
- Theraoy is prescribed on trial basis (4-6 weeks)
- takes 4-6 weeks to see full effects
- Inform patient it takes at least 2-3 weeks to start working
- Start at lower dose then titrate up (toleranc/efficacy)
How to treat subsequent schizophrenia episode in adults - NICE GUIDELINES
when patient recovers / in remission then have another episode
Subsequent acute episode:
- treat as 1st episode
- review diagnsois + existing meds
- i.e. adherance, dose
- may need to switch to another antispychotic
- e.g. if on typical switch to atypical
Maintenace treatment:
- continue with treatment if its effective
- inform patient about high risk of relapse
Treatment resisitnace schizophrenia:
- offer clozapine if uresponsive to other treatment
- need to have tried at least 2 diff. antispychotics (inc. 1 atypical drug)
NOTE: with each episode patient has their abiltiy to function drops = may need more help
Whats the difference between typical and atypical antipsychotics
Typical:
- Have very ↑ affinity for D2 receptors (ONLY)
- these are first gen. antipsychotics
Atypical:
- Have ↑ affinity for serotonin (5-HT2) AND many OTHER receptors BUT still have affinity for D2
- As they can bind to many other receptors = have many diff. side effects
- e.g. dry mouth, sedation, weight gain
- these are second gen. antipsychotics
- NOTE: not classed as antipsychotic if doesnt bind to D2 receptor
Efficacy vs side effects
- There’s NO difference in efficacy between typical and atypial antipsychotics
- BUT there ARE differences in side effects / SE profiles of each
- atypicals have less EPSE and hyperprolactaemia
- atypicals hace more metabolic side effects e.g. weight gain, diabetes
-
Evaluate the side effect profiles, dosing and delivering of antipsychotics AND how this links to monitoring of drug therapy
Doses required to reach threshold varies depending on antipschyotic + patient (inter-individual variability)
What is the therapeutic window for CNS drugs
Window is: % of blockage of a certain no. of receptors
- If block a certain % / amount of receptors = ↑ changce of seeing efficacy
- when reach 65% blockage start seeing clinical effects
- when ↑ to 70% = still good efficacy BUT other dopamine pathways affected e.g. tuberinfundbular (prolactin release not inhibited) = hyperprolactemia SE
- when ↑ to 80% = still see efficacy BUT blocking dopamine motor pathway = motor SE - BUT if go over this % = ↑ chance of seeing side effects (SE)
- as beginning to block receptors that shouldn’t be blocked
- window for efficacy and side effects is very small (5%)
Atypical drugs less likely to cause EPS side effects as they block to other receptors too = OTHER SE causes
What are potential side effects of antipsychotics
- EPSE
- Metabolic syndrome
- Hyperprolactinaemia
- QT Prolongation
OTHER:
- anticholinergic (with atypicals)
- blurred vision. constipation
- sexual dysfunction
- sedation
- lower seizure threshold
- photosensitivity
- postural hypotension + tachycardia
- neutropenia
- neuroleptic malignant syndrome
- stop antipsychotic + initiate specialist treatment
Explain EPS side effects
EPS - Extrapyramidal Symptoms
EPSE are caused when dopamine pathway in dorsal striatum (nigrostriatum) is affected
- causes motor SE
- In schizophrenia there is nothing wrong with dopamine release in motor pathway BUT antipsychotics can affect this
- EPSE are dose related (high dose)
- see SE with 80% blockage ~ lose normal regulation of dopamine
- MAINLY seen with TYPICALS (atypicals dont bind strongly to D2 receptors)
How to treat EPSE
- Use anticholinergic
- NOT in tardive dyskinesia (makes i worse) - Reduce dose of typical OR switch to atypical antipsychotic
EPSE:
- muscle spasms
- tremor
- inner restlesness
- lip smacking / chewing
Explaine “metabolic syndrome”
metabolic side effects
Side effects that cause ↑ weight, blood glucose and lipid profile
- these can lead to obesity, diabetes, macro/microvascular complications etc.
TREATMENT:
- use statins
- use T2DM medication
- metformin + orlistat (for obesity ~ lose weight)
- Monitor carefully
- Switch drugs if neccesary
- Caused mainly by atypicals e.g. clozapine, olanzapine, risperidone
- induce insulin resistance = diabetes, hyperlipidaemia
- increase histamine and serotnin activity = weight gain
Explain hyperprolactaemia
Cause when ↑ to 70% D2 receptors are blocked
- blockage causes other dopamine pathways unrelated to schizophrenia to be affected
- causes -ive effects on sexual function
Tuberinfundbular pathway affected = prolactin release is not inhibited = hyperprolactemia SE
- dopamine inhibits prolactin release when it binds to D2 receptor
- antipsychotic binds to receptor preventing dopamine from binding
TREATMENT:
- Switch drug
- Add ariprprazole (partial dopamine agonist = ↓ prolactin release)
- use alongisde antipsychotic
NOTE: monitor prolactin at base line + every 6 months as its often asymptomatic
Explain QT interval prolongation
prolongation in de/repolarising of heart
This puts you at ↑ risk of TdP and arrhythmias
- SE: palipitations, fainting
CAUSE:
- drugs: dose related
- may have prolongation symptom from birth
Ca2+ channels are blocked
TREATMENT:
- Reduce dose or switch drug
- Refer to cardiology
NOTE: ECG at baseline and monitor when dose changes / drug switches occur
How to monitor antipsychotic therapy
- Record changes in symptoms / behaviours
- Screen + record any side effects from antipsychotics
- Avoid smoking can increase emtabolism of antipsychotic
- Avoid alcohol can increase risk of hypotension + sedation
Investigate treatment:
- weight, waist circumference
- BP, pulse
- prolactin levels (at baseline + every 6 months)
- FBC, lipids
- Fasting BM and HbA1c
- ECG (at baseline + when dose / drug changes are made)
Describe the role of Clozapine in treatment of schizophrenia
cloazapine = atypical / secon gen. antipsychotic
Offered in subsequent acute episode if patient hasn’t responded adequately to other treatment
- need to have tried at least 2 diff. antispychotics (inc. 1 atypical drug)
NOTE:
If miss a dose may expereince relapse / withdrawal due to sudden decline of clozapine plamsa conc.
- clozapine has short half life (12 hrs)
Non-adherance + constant dose missing can lead to treatment resistance
What are the 3 adverse effects of Clozapine treatment
- GI effects
- inc. constipation, N&V, weight gain, problems swallowing, excess saliva, pancreatitis
- Cardiac effects
- inc. arrythmia, QT interval prolongation, hypotension
- Immune effects
- inc. fever, flu like symptoms, hypersensitivity reactions
How do you manage adverse effects of Clozapine treatment
- GI effects
- drink plenty of fluids, high fibre diet, stool softners / laxatives = alleviate constipation
- regular physical activity, probiotics = promotes digestive health
- quit smoking as tobacco exacerbates GI symptoms
- take clozapine with food to prevent GI irritation
- Cardiac effects
- tailor cloazapine dose (indiviualised)
- start with low dose then titrate slowly
- regular follow ups to assess response to treatment
- if have high CV risk use alternative treatment with lower risk of cardiac effects
- Immune effects
- if life-threatening ADRs = have to stop medication
What are the monitoring requirements of Clozapine treatment
CARDIAC:
- Baseline cardiac evaluation (inc. ECG, assessing CV risk factors) before beginning treatment
- Routine BP, heart rate and ECG checks throughout treatment
- Monitor serum electrolytes
IMMUNE:
- Baseline tests inc. FBC,
- Regular blood monitoring throughout treatment (inc. WBC and neutrophils)
- weekly monitoring initally
- then when reach stable therapeutic level = less frequent monitoring
What is the Impact of smoking on Clozapine
When STOP Smoking:
- decreased metabolism / enzyme activity
- resulting in clozapine + its metabolite conc. levels increasing (past therapeutic level = toxic = ADRs)
- Dose adjustments required + moitnoring for trewatment response
- Stopping shpuld be done gradually with medical supervision
When START Smoking:
- Smoking induces enzyme (CYP1A2) activity = increased metabolism of clozapine
- Plasma conc. of clozapine + its metabolite decrease significantly = reduced therapeutic effects
- Dose adjustments required + moitnoring for trewatment response
