Schizophrenia Flashcards
Life expectancy of a patient with schizophrenia:
Schizophrenic patients die on average 15-20 years earlier than the rest of the population
- Very poor awareness and monitoring of physical health
- Risk of death 2.5x rest of population, and increasing over time
- Less likely to seek health care assistance
- More patients smoke etc
SYMPTOMS:
Symptoms of active illness clustered into 3 main areas Positive - Delusions - Hallucinations - Thoughts (interruption/withdrawal)
Negative
- Poverty of speech
- Lack of motivation
- Emotional flattening
Cognitive
- Memory difficulties
- Attention deficit
- Executive functioning
Diagnosis:
Differential diagnosis important:
- The role of family, criminal justice system, educational institutions, employers and friends is vital
- Prognosis variable, poor for some i.e. male
- There are different types of schizophrenia [not examinable]
- ICD-10 and DSM-V diagnostic criteria – see Mike Harte’s lecture
Treating schizophrenia:
Antipsychotics…–>
- Do not CURE schizophrenia, they only ALLEVIATE symptoms
- Have a high response rate in first episode schizophrenia, but may not prompt symptom recovery
- Do not prevent relapse of illness in everyone, as after first episode schizophrenia, only 20-30% are relapse free after 5 years despite treatment
- Work best when taken regularly, poor adherence increases the risk of relapse by 5 times
- -> Non-adherence associated with lots of other problems. 9/10 patients partially adherent to medication. Associated with various problems i.e. poor QoL, self harm, relationship problems etc.
Treating schizophrenia in adults – NICE pathway:
Prodromal phase:
- Offer CBT +/- family intervention
- DO NOT offer antipsychotics
First episode schizophrenia:
- Rule out other causes for symptoms
- Full social, physical, psychiatric, occupational and economical assessment
- Offer antipsychotic therapy in conjunction with psychological interventions (individual CBT & family
Maintenance treatment:
- May continue on treatment for 1-2 years if effective
- Relapse risk high if stopped
- Can withdraw but careful monitoring needed
Considerations when choosing an antipsychotic:
- Partnership between patients and Dr
- Views of patients’ carer also welcome if patient agrees
- Consider metabolic, EPSE, cardiovascular, hormonal and other side effects
- The patient can decide which treatment they might tolerate more
Discuss alcohol/smoking/illicit/OTC use - Dependent on baseline investigations
When using antipsychotic therapy:
- Therapy should be prescribed on a trial basis, for 4-6 weeks at optimum dosage
- Record expected benefits and risks of treatment
- Inform patient that treatment may take 2-3 weeks to work
- Start at lower doses and titrate up according to tolerance/efficacy
- Record the rationale for continuing, changing or stopping medication
- Record the reason if high doses are used
Pathway for treatment resistant schizophrenia and clozapine
Offer clozapine If not responded adequately to treatment deposits the sequential use of adequate doses of at least 2 different antipsychotics one of which is a second generation atypical.
Non-pharmacological options for schizophrenia:
Individual cognitive behavioural therapy (CBT)
- CBT is as effective as antipsychotic treatment, and the combination is synergistic
- Unlike antipsychotics, CBT can be effective for positive, negative & cognitive symptoms of schizophrenia
- Involves multiple sessions with a therapist
- Focus on changing behaviour and ways of thinking, particularly when faced with problems and challenges
- Can be administered with or without family interventions
- Can be used without antipsychotic therapy, but careful review required after 1 month
Arts therapies can be particularly useful for negative symptoms
Pharmacological options for schizophrenia:
First generation ‘typical’ antipsychotics versus second generation ‘atypicals’
- First generation: sulpiride, flupenthixol, haloperidol, chlorpromazine, zuclopenthixol, trifluoperazine, perphenazine
- Second generation: amisulpride, quetiapine, risperidone, olanzapine, clozapine, aripiprazole, paliperidone, lurasidone, asenapine
- LITTLE OR NO DIFFERENCE in efficacy between first and second generation antipsychotics when used appropriately
- Generally less extra-pyramidal side effects (EPSEs) and hyperprolactinaemia for second generation drugs – with notable exceptions
- Metabolic side effects with second generation drugs – ‘metabolic syndrome’
- Antipsychotics have limited effects on negative and cognitive symptoms of schizophrenia
This is important as these symptoms are correlated more closely with impairments in social/occupational functioning than positive symptoms
Extra-pyramidal side effects (EPSEs) to antipsychotics:
- EPSE’s are dose related and more likely to occur with typical antipsychotics
- However, higher doses of risperidone and amisulpride (second gen) can also cause EPSEs
- Generally speaking, there are 3 main treatments depending on the type of EPSE
Dystonia
Muscle spasms in any part of the body, e.g. eye rolling, head/neck twisting swallowing problems
Treat with anticholinergic or switch to atypical antipsychotic drug
Akathisia
Inner restlessness and desire/compulsion to move – shifting feet, pacing, crossing/uncrossing legs
Treat by reducing the antipsychotic dose, or switching to an atypical drug
Anticholinergics are not useful here
Pseudo-Parkinsonism
Characterised by tremor, rigidity, bradykinesia
Treat by reducing the dose of antipsychotic, or by switching to an atypical drug
Can use anticholinergics short term, review 3/12 as pseudo parkinsonism only lasts around 1 month.
Tardive dyskinesia
Lip smacking/chewing, tongue protrusion
Approximately 50% of cases are not reversible
Anti-cholinergic drugs make it worse
Stop anticholinergics, reduce antipsychotic dose, withdraw antipsychotic and switch to atypical drug
What is metabolic syndrome?
- ‘Metabolic syndrome’ describes a collection of side effects to antipsychotics causing increased weight, blood glucose and lipid profile
- If not addressed, these side effects can lead to obesity, diabetes, hyperlipidaemia and associated complications including macro/microvascular diseases and death
Thought to be important contributor to early deaths in population with serious mental illness - Hard to show cause and effect, but all antipsychotics implicated though some present much higher risks than others (see below)
- Must monitor/screen carefully, use education/behavioural change, switch drugs if needed.
- Use statins and treatments for T2DM as required, orlistat and metformin useful for obesity
What is hyperprolactinaemia?
- All antipsychotics increase prolactin
- Some asymptomatic, but should treat regardless due to effects on sexual function, breast growth/milk, amenorrhoea, cancer and BMD
- Treat: switch to alternative or add aripiprazole
- Some evidence for dopamine agonists
QT prolongation as a side effect of antipsychotics:
- QT interval involves de and re-polarising of the heart for pumping action
- QT interval prolongation is a risk factor for ventricular arrhythmias and TdP
Causes
- Some people have QT prolongation syndromes from birth
- Drugs can also cause it:
- -> Can be dose related and additive when >1 drug used
- -> Other psychotropic/non-psychotropics implicated
- ECGs essential, limits 440ms (men), 470ms (women)
- If QT interval prolonged: switch/reduce dose and refer to cardiology
Other side effects to antipsychotics:
- Sedation
- Anticholinergic effects, particularly clozapine and some typicals
- Lowering seizure threshold
- Neutropenia
- Hyponatremia
- Photosensitivity, especially chlorpromazine (use sunscreen)
- Postural hypotension and tachycardia
- Neuroleptic malignant syndrome – rare but could be fatal
Due to rapid changes in dopamine blockade
Watch out for rigidity, hyperthermia, tachycardia, sweating, fluctuating consciousness, raised CK
STOP antipsychotic and initiate specialist treatment
Monitoring antipsychotic therapy – NICE Guideline?
- Regularly record response to treatment including changes in symptoms/behaviour
- Regularly screen for and record management of side effects to antipsychotic treatment
- Investigations for antipsychotic treatment (see also individual drug SmPCs)
- Weight
- Waist circumference
- Pulse and BP
- Fasting BMs and HbA1c
- Lipids
- Prolactin levels
- Assessment of movement disorders, adherence nutrition and exercise
- An ECG at baseline (only if specified in SmPC, personal history of CVD, inpatient admission or physical examination reveals CV risk factor (e.g. HTN))
Depot (long acting) antipsychotics. When to use?
- May be useful in cases where avoiding covert non-adherence is a priority
- If the patient is refusing to take oral medication, explore preventable reasons first
- Some patients may prefer to use depots
BUT we must stress need to visit clinics or have home visits for injections
Zuclopenthixol, flupentixol, haloperidol, fluphenazine (typicals – all decanoate)
Olanzapine embonate, paliperidone palmitate, aripiprazole, risperidone (atypicals)
Little to choose between typical depots in efficacy
- Possibly less EPSE with atypicals, but issues with risperidone and olanzapine
- Start with a test dose for typicals – oily base which may contain allergens and also to test for side effects
- Start dose low and go slow
- Injections into gluteal/deltoid muscle (See individual SmPCs)
- Administer at the longest possible dose interval
What is involved in combined antipsychotic treatment?
- Antipsychotic polypharmacy – more than one agent prescribed
- Approximately 40% of adult inpatients are exposed to combination prescribing
- 50% of schizophrenics prescribed long acting depot injections and oral antipsychotics
NICE 2014: Do not initiate combined antipsychotic medication, except for short periods (for example, when changing medication)
- -> Very limited evidence of any benefit
- -> Large increases in the risk of side effects, drug-drug interactions and non-adherence
Cautious use of two drugs also advocated in treatment resistant illness where clozapine therapy augmented with another antipsychotic (e.g. amisulpride)
HOWEVER – this assumption is now being questioned
Clozapine treatment:
Evidence suggests practitioners are cautious/afraid of using clozapine
BUT clozapine shows superior efficacy than many other antipsychotics when patients are poor responders (in treatment resistant schizophrenia)
Between 30-60% of patients with treatment resistant schizophrenia will respond
NICE guidance for schizophrenia is clear in stating: ‘Offer clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least 2 different antipsychotic drugs. At least 1 of the drugs should be a non-clozapine second-generation antipsychotic.’
Only 30% of eligible patients receive this drug
Clozapine – management of adverse effects:
Myocarditis and cardiomyopathy
- Most common in the first two months of treatment, can be fatal
- Symptoms/signs include fever, fatigue, chest pain, palpitations, low BP, SOB, high pulse
- Related to speed of titration – START LOW GO SLOW
- Can be asymptomatic
- MUST take baseline tests then daily BP/RR/temp/pulse, weekly Trop/ECG/CRP/FBC
- Always ask if symptoms present; if suspected STOP treatment and REFER
Neutropenia and agranulocytosis
- Risk of occurrence actually low (<1%), low death risk
- Generally reversible, not dose related
- Watch out for any sore throat, flu-like symptoms or others indicative of infection
- If infection suspected get blood test immediately, STOP treatment until test result back
Clozapine – management of adverse effects:
Venous thromboembolism
- Rare (1 in 2000-6000) but risk many times higher than rest of the population
- High risk in first few months, ?dose related
- Assess risk factors and use VTE prophylaxis accordingly
Constipation
- Whole system can be affected, rapid fatality possible
- Affects 60% of patients
Risk factors are higher doses and other traditional risk factors for constipation
- Active screening and assertive treatment essential
- Do not delay using laxatives
Sedation
- Could be useful but may also affect adherence
- Most common clozapine ADR
Common in early weeks, tolerance may develop
- Review other medications/comorbidities
- Watchful waiting
- Reduce clozapine dose or move to night time dosing if persistent/troublesome
Hyper salivation
- Common early on in treatment, and source of much social isolation
- Affects 30-80% of patients
- Hyoscine hydrobromide (Kwells) – TRIAL
- Non-drug treatments include chewing sugar free gum during the day and using pillows at night to raise head
- Reducing clozapine dose a later option
Smoking and caffeine in mental health:
- Many mental health patients smoke cigarettes
- -> Nicotine may be a gateway to using other psychoactive substances
- Benefits for mental health if patients do stop smoking, but timing important
Aromatic hydrocarbons (NOT NICOTINE) responsible for drug interactions
- Induction of CYP1A2
- Clozapine, olanzapine, duloxetine, TCAs and benzodiazepine (BZD) levels fall by as much as 50% if smoking (haloperidol 20%)
- On stopping smoking clozapine serum levels can increase by 50-72%
- Levels take time to rise
- Monitor levels and/or adjust dose accordingly
Caffeine also competes with clozapine at CYP1A2, causing clozapine levels to rise by 14-47% (lots of variability between individuals)
- Excessive caffeine intake can cause restlessness, insomnia and may worsen psychosis
- Caffeine also antagonises the effects of BZDs and ‘Z drug’ hypnotics
Medicines optimisation in schizophrenia - summary:
- Patient counselling in those with mental illness can be a challenge
- Non-pharmacological methods important treatment
- Tailor drug treatment for schizophrenia to individual patient
- -> Compare first generation ‘typicals’ with second generation ‘aypicals’
- -> Consider patient age, social history, metabolic and cardiovascular health
- Prescribing advice: selecting and initiating the right treatment, do not delay clozapine if indicated
- Education: depots do not guarantee adherence, minimise dual antipsychotic therapy, importance of monitoring
- Patient counselling: drug choice, initiation and important side effects
