Schizophrenia Flashcards
1
Q
Diagnostic Criteria: Duration of Symptoms?
A
- 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)
2
Q
When diagnosing schizophrenia, what should be ruled out?
A
- Schizoaffective disorder (depression or bipolar with psychotic features)
- Medical disorder (organic causes)
- Substance abuse
3
Q
What are the 3 Main Symptom Clusters in Schizophrenia?
A
- Positive - tend to relapse and remit
- Cognitive
- Negative - tend to be chronic
4
Q
3 Main Symptom Clusters in Schizophrenia -
- What are Positive Symptoms?
- Can they be treated?
A
- Can treat well with medications
- Hallucinations
- Delusions
- Suspiciousness
- Disorganisation
5
Q
3 Main Symptom Clusters in Schizophrenia - What are Cognitive Symptoms?
A
- Impaired planning
- Impaired memory
- Impaired social cognition
- Impaired mental flexibility
6
Q
3 Main Symptom Clusters in Schizophrenia -
- What are Negative Symptoms?
- Can they be treated with meds?
A
- Medications don’t always treat well
- Lack of motivation
- Blunted affect
- Reduced speech
- Social withdrawal
- Poor self-care
7
Q
What are the 3 main factors underlying the pathophysiology of Schizophrenia?
A
- 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
8
Q
What are the Advantages of Atypical Antipsychotics (2nd gen) over Typical A/P (1st gen)?
A
- 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)
9
Q
- What are the Goals of Therapy of Schizophrenia?
- What about for acute positive symptoms?
- What about for negative symptoms?
A
- 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
10
Q
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?
A
- 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
11
Q
Behavioural Emergencies
Treatment objectives and recommendations differ based on what?
A
- Treatment objectives and recommendations differ based on setting
- Acute medical settings = IV preferred
- Acute Psychiatric Settings = Oral preferred
12
Q
Behavioural Emergencies
In the acute psychiatric setting, PRN A/P should be considered if patient already taking or?
A
- 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
13
Q
Changing
Before you make change:
A
- Make sure patient adhering
- No substance abuse
14
Q
Changing:
When can a drug be changed?
A
- If unacceptable partial response after 12 weeks
- No response after 1st 4 weeks
- Severe EPSE even with dose adjustments
15
Q
Changing:
What are the Options for Drug Change?
A
- Alternative second generation A/P
- First generation A/P
16
Q
Switching from One Drug to Another
What is the Target Dose for the new drug?
A
Target dose for the new drug should be therapeutically comparable to the dose of the drug being stopped
17
Q
Switching from One Drug to Another
- Speed of changeover?
- What is recommended?
A
- 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
18
Q
When switching from depot to oral formulation what should be considered?
A
- 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
19
Q
Switching from One Drug to Another
What are 5 PK and PD related problems when switching?
A
- 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
20
Q
Maintenance Treatment
- How long should patient be on maintenance treatment?
- At the end of this period?
A
- 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
21
Q
When is Refractory Schizophrenia diagnosed?
A
Diagnosed after adequate drug trial of 6-12 weeks duration on optimal doses of at least two different antipsychotics
22
Q
Who should have TDM done? – Clozapine
A
- 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
23
Q
If a patient doesn’t respond to clozapine, what are the options?
A
- Augmenting strategies with clozapine
- ECT
24
Q
If a patient doesn’t respond to clozapine
Augmenting strategies with clozapine, what are the options?
A
- Amisulpride
- Haloperidol
- Lamotrigine
- Omega 3 fatty acids
25
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
26
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
27
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
28
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
29
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
30
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
31
Adverse Effect Profile of Antipsychotics: Extrapyramidal side effects (**D**ystonia **A**kathisia **P**arkinsonism **T**ardive 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
32
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
33
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
34
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
35
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
36
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
37
Lifelong Treatment Considered for:
* History of violent behaviour
* History of suicide attempts
* Residual psychotic symptoms
