Schizophrenia Flashcards
Diagnostic Criteria: Duration of Symptoms?
- Continuous signs for at least 6 months
- At least 1 month of symptoms that meet ACTIVE PHASE SYMPTOMS
- May include prodromal (early signs) or residual symptoms (recurrence)
When diagnosing schizophrenia, what should be ruled out?
- Schizoaffective disorder (depression or bipolar with psychotic features)
- Medical disorder (organic causes)
- Substance abuse
What are the 3 Main Symptom Clusters in Schizophrenia?
- Positive - tend to relapse and remit
- Cognitive
- Negative - tend to be chronic
3 Main Symptom Clusters in Schizophrenia -
- What are Positive Symptoms?
- Can they be treated?
- Can treat well with medications
- Hallucinations
- Delusions
- Suspiciousness
- Disorganisation
3 Main Symptom Clusters in Schizophrenia - What are Cognitive Symptoms?
- Impaired planning
- Impaired memory
- Impaired social cognition
- Impaired mental flexibility
3 Main Symptom Clusters in Schizophrenia -
- What are Negative Symptoms?
- Can they be treated with meds?
- Medications don’t always treat well
- Lack of motivation
- Blunted affect
- Reduced speech
- Social withdrawal
- Poor self-care
What are the 3 main factors underlying the pathophysiology of Schizophrenia?
- Brain structure
- Ventricles much larger and changes in grey and white matter compared to person without schizophrenia
- Dopamine
- Increased dopamine synthesis, release and increased concentration within synaptic cleft during acute phase
- Brain imaging
- Increase in dopamine activity
What are the Advantages of Atypical Antipsychotics (2nd gen) over Typical A/P (1st gen)?
- Better efficacy in treating positive symptoms
- Clozapine with overall efficacy advantage
- First line in treating negative and cognitive symptoms
- Preference for amisulpride or clozapine
- Risk of EPSE (dystonia, akathisia, parkinsonism) is lower (risk increased if beyond recommended dose)
- Reduced potential to elevate prolactin levels (with the exception of risperidone and amisulpride in some cases)
- What are the Goals of Therapy of Schizophrenia?
- What about for acute positive symptoms?
- What about for negative symptoms?
- Treat acute symptoms and reduce risk of subsequent relapse by ensuring patient carries on with maintenance treatment
- Using minimum effective dose to avoid unwanted side effects – monotherapy
- For acute positive symptoms: response onset may be within the first week, but a longer period may be required for full effect
- Negative symptoms are less responsive than positive symptoms to medication. Excessive doses of medication can augment negative symptoms
For someone’s first psychotic episode
- How is this managed?
- When should a response be expected?
- How should anxiety, agitation, insomnia or the activation syndrome be treated?
- Increasing the dose in staged increment unless patient requires fast uptitration
- Response within 1-2 weeks
- If no response in first 2 weeks, then dose needs to be increased
- If response inadequate after the 4th week, increase dose
- Particularly for less-sedating antipsychotics, treat anxiety, agitation, insomnia or the activation syndrome with short term benzodiazepine therapy
Behavioural Emergencies
Treatment objectives and recommendations differ based on what?
- Treatment objectives and recommendations differ based on setting
- Acute medical settings = IV preferred
- Acute Psychiatric Settings = Oral preferred
Behavioural Emergencies
In the acute psychiatric setting, PRN A/P should be considered if patient already taking or?
- PRN A/P should be considered if patient already taking an antipsychotic, or if any of the following are present:
- Psychotic symptoms
- Intense agitation
- A high risk of severe and immediate physical danger
- Inadequate tranquilisation with a benzo alone
Changing
Before you make change:
- Make sure patient adhering
- No substance abuse
Changing:
When can a drug be changed?
- If unacceptable partial response after 12 weeks
- No response after 1st 4 weeks
- Severe EPSE even with dose adjustments
Changing:
What are the Options for Drug Change?
- Alternative second generation A/P
- First generation A/P
Switching from One Drug to Another
What is the Target Dose for the new drug?
Target dose for the new drug should be therapeutically comparable to the dose of the drug being stopped
Switching from One Drug to Another
- Speed of changeover?
- What is recommended?
- Speed of changeover affects likelihood of adverse effects with the new drug
- Crossover phase of at least 1-2 weeks is recommended
- Drop dose of 1st drug gradually and then increase 2nd drug gradually
When switching from depot to oral formulation what should be considered?
- Long washout period
- Excessive amount of A/P in system = patient may present with EPSE or any other S/Es due to long washout period of depot
- Once it completely washes out, A/Es should settle
- Once you stop depot, will then initiate oral formulation
- Once patient completely switched to oral formulation and symptoms return in 2-5 months, they return due to the new drug – drug not adequately controlling symptoms for patient or not suitable
Switching from One Drug to Another
What are 5 PK and PD related problems when switching?
- Emergent of movement disorders
- Change in level of dopaminergic blockade
- Should settle quickly
- Increased risk of pregnancy
- Loss of contraceptive effect of hyperprolactinaemia
- Cholinergic rebound syndrome
- Presents itself as flu like symptoms
- Activation syndrome
- Depends on activation potential of drug (Some increase and some decrease)
- Patient going to be agitated and restlessness
- Can initiate short course of diazepam if stressful for patient
- Changes in QTc interval
- Monitor
- All A/P has potential to prolong QT interval depending on dose you’ve given them
Maintenance Treatment
- How long should patient be on maintenance treatment?
- At the end of this period?
- Emphasise the need for continuing A/P treatment after recovery from first psychotic episode for at least 2 years
- At the end of 2 years:
- If there has been full remission, the A/P can be cautiously tapered and discontinued over a period of at least 3 months
- If relapse occurs after cessation of maintenance therapy, longer-term treatment (e.g. at least 5 years) is required
- Go back on treatment you were initially on
When is Refractory Schizophrenia diagnosed?
Diagnosed after adequate drug trial of 6-12 weeks duration on optimal doses of at least two different antipsychotics
Who should have TDM done? – Clozapine
- Treatment failure with adequate treatment time
- Significant adverse effects in a responder
- Complicating physical disease
- Concurrent administration of other drugs (CYP1A2)
- Advanced age
- Suspicion of poor treatment adherence
If a patient doesn’t respond to clozapine, what are the options?
- Augmenting strategies with clozapine
- ECT
If a patient doesn’t respond to clozapine
Augmenting strategies with clozapine, what are the options?
- Amisulpride
- Haloperidol
- Lamotrigine
- Omega 3 fatty acids
If a patient doesn’t respond to clozapine - ECT
- Will patients relapse?
- What is essential?
- Is ECT effective?
- Safe and tolerable
- Relapse rate is high after ceasing acute course of ECT
- Maintenance antipsychotic drug treatment is essential
- Maintenance ECT has limited evidence
Combined Antipsychotics
- Is there evidence supporting combining A/P?
- Little evidence supporting the efficacy of combining non-clozapine A/P
- Associated with substantially increased mortality
- Clozapine augmentation strategies is the sole therapeutic area that’s supported
What are General Prescribing Principles of A/Ps?
- Lowest possible dose should be used
- No evidence that high doses are of any benefit
- Use of single A/P is recommended
- Combinations of A/P should only be used where response to a single A/P has been demonstrated to be inadequate
- A/P shouldn’t be used as ‘prn’ sedatives
- Those receiving A/P should undergo close monitoring of physical health and regular assessment of adverse effects
What are the Adverse Effect Profile of Antipsychotics?
- Movement disorder (e.g. EPSE)
- Rapid weight gain
- More common with atypicals
- Undue sedation
- Hyper-prolactinoma
- Sexual dysfunction
Adverse Effect Profile of Antipsychotics: Neuroleptic malignant syndrome
- What is it caused by?
- Is it common?
- What is the Treatment?
- Notes:
- How long to wait?
- What should be different?
- Commence on?
- Reaction to neuroleptic drugs as a result of inhibition of D2 receptor – rare but life threatening
- Relatively common with all antipsychotics
- Treatment
- Cease drug that causes NMS or initiate DA agonist (e.g. bromocriptine)
- Notes:
- Wait 5 days
- Use a different A/P – pick A/P that’s structurally different to drug that causes problem or drug that has low affinity for DA e.g. quetiapine or clozapine = won’t cause problems again in patients with previous bad experiences
- Commence on low dose and titrate upwards until desired effect is achieved
Adverse Effect Profile of Antipsychotics: Agranulocytosis
- What drug is it common with?
- What monitoring is required?
- What is the mechanism?
- Clozapine
- Highest agranulocytosis risk
- Monitoring of WBC is required
- Mechanism
- Clozapine metabolised to N-desmetylclozapine
- Metabolised to nitrenium ion in leukocytes
- Genetics may play a role
Adverse Effect Profile of Antipsychotics: Extrapyramidal side effects (Dystonia Akathisia Parkinsonism Tardive dyskinesia)
- Common with?
- Least likely with?
- Management?
- Common with all 1st gen
- Akathisia and tardive dyskinesia may occur with 2nd
- Least likely = clozapine
- Management
- Non-selective beta blockers
- Benzos
Adverse Effect Profile of Antipsychotics: Sedation
- Can occur with?
- Most pronounced when?
- Minimise by?
- Can occur with all but more pronounced with low-potency 1st gen and clozapine
- Most pronounced on starting therapy (likely to decline over 1-2 weeks) or with upward dose titration (start low and uptitrate slowly)
- Minimise by dose reduction or changing to a less sedating drug
Adverse Effect Profile of Antipsychotics: Weight gain and hyperglycaemia
- What is it common with?
- What is it least likely with?
- How is it managed?
- Common with all 1st gen, cloazapine and olanzapine
- Least likely amisulpride and aripiprazole
- Management:
- Metformin
- Non pharm: PA, diet restriction
Adverse Effect Profile of Antipsychotics: Dyslipidaemia
- Common with?
- Least likely with?
- How is it managed?
- Common with chlorpromazine (unknown with other 1st) and most 2nd
- Least likely: aripiprazole and ziprasidone
- Management:
- Pharmalogical: use antipsychotics with lower risk; may consider a statin
- Non pharm: PA
Adverse Effect Profile of Antipsychotics: Hyperprolactinaemia
- Common with?
- Least likely with?
- How is it managed?
- Common: all 1st gen, amisulpride and risperidone
- Least likely: aripiprazole and quetiapine
- Management:
- Non-pharm: monitor prolactin levels
- Avoid in patients under 25 years, or patients at high risk of breast cancer
How and When to Stop Treatment?
Abrupt withdrawal leads to?
- Requires a thorough risk-benefit analysis
- Withdrawal of A/P drugs after long-term treatment should be gradual and closely monitored
- Abrupt withdrawal leads to:
- Double the rate of relapse
- More discontinuation symptoms
Lifelong Treatment Considered for:
- History of violent behaviour
- History of suicide attempts
- Residual psychotic symptoms
