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Pharmacotherapeutics Theory 2 > Schizophrenia > Flashcards

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)
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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
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3
Q

What are the 3 Main Symptom Clusters in Schizophrenia?

A
  • Positive - tend to relapse and remit
  • Cognitive
  • Negative - tend to be chronic
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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
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5
Q

3 Main Symptom Clusters in Schizophrenia - What are Cognitive Symptoms?

A
  • Impaired planning
  • Impaired memory
  • Impaired social cognition
  • Impaired mental flexibility
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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
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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
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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)
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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
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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
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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
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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
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13
Q

Changing

Before you make change:

A
  • Make sure patient adhering
  • No substance abuse
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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
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15
Q

Changing:

What are the Options for Drug Change?

A
  • Alternative second generation A/P
  • First generation A/P
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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
Q

If a patient doesn’t respond to clozapine - ECT

  • Will patients relapse?
  • What is essential?
  • Is ECT effective?
A
  • 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
Q

Combined Antipsychotics

  • Is there evidence supporting combining A/P?
A
  • 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
Q

What are General Prescribing Principles of A/Ps?

A
  • 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
Q

What are the Adverse Effect Profile of Antipsychotics?

A
  • Movement disorder (e.g. EPSE)
  • Rapid weight gain
    • More common with atypicals
  • Undue sedation
  • Hyper-prolactinoma
  • Sexual dysfunction
29
Q

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?
A
  • 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
Q

Adverse Effect Profile of Antipsychotics: Agranulocytosis

  • What drug is it common with?
  • What monitoring is required?
  • What is the mechanism?
A
  • 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
Q

Adverse Effect Profile of Antipsychotics: Extrapyramidal side effects (Dystonia Akathisia Parkinsonism Tardive dyskinesia)

  • Common with?
  • Least likely with?
  • Management?
A
  • Common with all 1st gen
  • Akathisia and tardive dyskinesia may occur with 2nd
  • Least likely = clozapine
  • Management
    • Non-selective beta blockers
    • Benzos
32
Q

Adverse Effect Profile of Antipsychotics: Sedation

  • Can occur with?
  • Most pronounced when?
  • Minimise by?
A
  • 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
Q

Adverse Effect Profile of Antipsychotics: Weight gain and hyperglycaemia

  • What is it common with?
  • What is it least likely with?
  • How is it managed?
A
  • Common with all 1st gen, cloazapine and olanzapine
  • Least likely amisulpride and aripiprazole
  • Management:
    • Metformin
    • Non pharm: PA, diet restriction
34
Q

Adverse Effect Profile of Antipsychotics: Dyslipidaemia

  • Common with?
  • Least likely with?
  • How is it managed?
A
  • 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
Q

Adverse Effect Profile of Antipsychotics: Hyperprolactinaemia

  • Common with?
  • Least likely with?
  • How is it managed?
A
  • 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
Q

How and When to Stop Treatment?

Abrupt withdrawal leads to?

A
  • 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
Q

Lifelong Treatment Considered for:

A
  • History of violent behaviour
  • History of suicide attempts
  • Residual psychotic symptoms

Pharmacotherapeutics Theory 2 (17 decks)

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