Management of schizophrenia 1.5.2

Question 1

What are the principles of antipsychotic treatment?

Answer 1

• drug tx tailored to individual (consider side effects)
• Use lowest effective dose
• Use monotherapy where possible

Question 2

Which are the high potency FGA antipsychotics?

Answer 2

• droperidol
• flupentixol
• haloperidol
• trifluoperazine
• zuclopenthixol

Question 3

What are the features of the high potency FGA?

Answer 3

• ↑EPSE
• ↓ Sedation
• ↓ orthostatic hypotension
• ↓ anticholinergic side effects

Question 4

Which are the low potency FGA?

Answer 4

• chlorpromazine
• pericyazine

Question 5

What are the feautures of the low potency FGA?

Answer 5

• ↓EPSE
• ↑sedation
• ↑ orthostatic hypotension
• ↑ anticholinergic side effects

Question 6

Which antipsychotics have better efficacy on negative symptoms?

Answer 6

• second generation antipsychotics

Question 7

What are the side effects of SGAs?

Answer 7

Question 8

Why do we not use clozapine first line?

Answer 8

• agranulolcytosis
• myocarditis
• cardiomypathy
• gastrointestinal hypomotility
  
  • constipation

Question 9

How are FGA used in schizophrenia?

Answer 9

• Used 2nd line due to side effects – largely extrapyramidal side effects
• Effective for positive symptoms, little effect on negative symptoms
• Haloperidol, droperidol used for acute psychosis (inpatients)
• Use if had previous good response to these agents, or if poor response to several SGAs
• Zuclopenthixol depot used commonly

Question 10

What are examples of EPSE?

Answer 10

• Dystonias - stiffness, uncontrolled muscular spasms
  
  • Treatment: benzatropine (oral, inj), trihexyphenidyl (benzhexol)
• Akathisia - inner restlessness, strong desire or compulsion to move
  
  • Treatment: propranolol, clonazepam
• Parkinsonism - tremor and/or rigidity, mask- like face, shuffling gait, slow movements
  
  • treatment: benzatropine, trihexyphenidyl
• tardive Dyskinesia - involuntary abnormal movements of face, tongue, lips, hands or feet n Can be irreversible. Stop antipsychotic (preferred)
  
  • Treatment poor efficacy – tetrabenazine, Ginkgo biloba
• If EPSE occurs, ideally reduce antipsychotic dose or switch to alternative antipsychotic

Question 11

What do we do if EPSE occurs?

Answer 11

• ideally reduce antipsychotic dose OR
• switch to alternative antipsychotic

Question 12

What treatment for the following EPSE?

A) Dystonias - stiffness, uncontrolled muscular spasms

B) Akathisia - inner restlessness, strong desire or compulsion to move

C) Parkinsonism - tremor and/or rigidity, mask- like face, shuffling gait, slow movements

D) Tardive Dyskinesia - involuntary abnormal movements of face, tongue, lips, hands or feet

Answer 12

A) benzatropine (oral, inj), trihexyphenidyl (benzhexol)

B) propranolol, clonazepam

C) benzatropine, trihexyphenidyl

D) Can be irreversible. Stop antipsychotic (preferred)

Treatment poor efficacy – tetrabenazine, Ginkgo biloba

Question 13

How does cloazapine differ from other side effects of SGAs?

Answer 13

Increased sedation, weight gain and anticholinergic effects

Question 14

Pharmacalogy of aripiprazole? What is it used to agument?

Answer 14

Is a dopamine system stabiliser (increased dopamine output when conc are low and decreased dopamine output when conc. are high)

Less sedation, weight gain and prolactin elevation

Good 1st choice antipsychotic

Doesn’t provide sedation if patient acutely unwell

May cause insomnia, akathisia and/or activation

> Often used to augment other antipsychotics

To reduce weight gain – e.g. clozapine, olanzapine

To reduce prolactin – e.g. risperidone

Question 15

Pharmacology of brexpiprazole

Answer 15

Indicated only in schizophrenia

May have positive effects on mood

Well tolerated – little weight gain, prolactin elevation, akathisia

Question 16

Pharmaclogy of lurasidone

Answer 16

Take with food to increase absorption

Low incidence weight gain, small rise in prolactin

Theorised to improve mood & be useful in bipolar

Reports of increased irritability/rage

Question 17

Pharmacology of olanzapine

Answer 17

Sedating – may be beneficial in acute psychosis

WEIGHT GAIN +++

Metabolic syndrome major concern. For this reason falling out of favour as long term treatment

Question 18

Pharmacology of paliperidone

Answer 18

• 9-hydroxyrisperidone
• Active metabolite of risperidone
• Similar adverse effects to risperidone

Swallow tablets whole –> Cannot be halved, crushed –> Empty tablet may appear in stools

• always with food, or always on an empty stomach
• Oral not commonly used, but depot very common

Question 19

Pharmacology of Quietiapine

Answer 19

Commonly used antipsychotic

• Prone to abuse – watch for doctor shopping and picking up supply earlyn
• More sedating at lower doses
• To get antipsychotic effect, some patients require higher dose

Question 20

Pharmacology of risperidone

Answer 20

Adverse effects:

• Prolactin elevation – can be severe and problematic
• EPSE – dose related

cheaper than most SGAs

Question 21

Pharmacology of Amisulpride? How does its MOA change from low to higher doses?

Answer 21

Indicated for treatment of schizophrenia

• At low doses (50-300mg) it is more effective for negative symptoms
• At higher doses (400-800mg) it is more effective for positive symptoms
• Not metabolised in the liver; reduce dose in renal impairment
• Dose-related EPSE & hyperprolactinemia

Question 22

Pharmacology of Asenapine

Answer 22

Rarely used

Sublingual wafer –> do not eat or drink for 10 minutes after taking –> take after all other medications –> poor absorption if swallowed

• Tastes awful!! Makes mouth numb/tingly up to 1 hour after taking

Question 23

Pharmacology of Ziprasidone

Answer 23

Can cause QT prolongation, increase risk of arrythmia – monitor ECG

Little weight gain, prolactin elevation & sedation

Question 24

Clozapine pharmacology? Why is it not 1st line?

Answer 24

• The most effective antipsychotic
• 50% of non-responders will improve with clozapine
• Particularly effective for negative symptoms

Not 1st line due to serious adverse effects (Immune mediated, rather than dose-dependent)

• Agranulocytosis
• Neutropenia
• Cardiomyopathy
• Myocarditis
• Gastrointestinal Hypomotility – i.e. constipation = highest risk of mortality

Question 25

What is the condition of clozapine being used?

Answer 25

Must have trialled ≥2 antipsychotics prior to clozapine initiation * Not effective or not tolerated * At least 1 must be atypical antipsychotic

Question 26

What is done before treatment of clozapine can be done (monitoring)?

Answer 26

Monitoring systems record WCC and neutrophil count * Clopine Connect * Clozaril Patient Monitoring Service Pre-treatment * FBP, CRP, troponin, ECG, echocardiogram ( pregnancy test) * Desired: LFTs, U&Es, lipids, weight, BSL/HbA1c, weight, waist circumferance,

Question 27

What ongoing monitoring for clozapine?

Answer 27

Ongoing monitoring. Medication only supplied until next blood test * FBP weekly for first 18 weeks * CRP, troponin weekly for 4 weeks * \> Monthly (every 4 weeks) thereafter

Question 28

What is clozapine dosing/drug concentration?

Answer 28

Slow dose titration to avoid/reduce dose dependent adverse effects * Target drug concentration: 350-1000mcg/L

Question 29

For clozapine; A) What to use to treat hypersalivation B) What to use to treat GI hypomotility (constiaption)

Answer 29

A) Atropine 1% eye drops sublingually Hyoscine wafers Ipratropium MDI sublingually Moclobemide, metoclopramide B) Macrogol first line and BE AGGRESSIVE! Docusate/senna first line for prophylaxis

Question 30

Why is medication used in acute agitation and arousal in patients with schizophrenia? What drugs to use?

Answer 30

Medication is used to calm/lightly sedate the patient and reduce the risk to self and/or others \> Verbal de-escalation * Oral benzodiazepine (lorazepam, clonazepam, diazepam) * Oral antipsychotic (olanzapine, risperidone, quetiapine, haloperidol) * IM medication (lorazepam, olanazapine, ziprasidone, haloperidol, droperidol, midazolam, clonazepam) * IV med --\> used in EDs, not used in psychiatric inpatient wards

Question 31

Outline why certain IM medication is not used for acute agitation. Which one is preferred?

Answer 31

IM diazepam not recommended as absorption is poor & erratic IM chlorpromazine not recommended due to risk of abscess formation & catastrophic hypotension IM clonazepam not an approved route of administration – absorption erratic \> IM lorazepam available under SAS – more predictable absorption & effect --\> refrigerate, 3 months shelf life once out of fridge

Question 32

What is needed when benzodiazepines used IM/IV? When to use?

Answer 32

Have flumazenil available when benzodiazepines used IM/IV * Use if respiratory rate falls below 10/minute * Caution in patient with epilepsy & on long term benzos * Has short half life (shorter than diazepam) so respiratory function may recover then deteriorate again

Question 33

Pharmacology of Zuclopenthixol acetate. When are they used?

Answer 33

* NOT a rapid tranquilising agent * Can only be written as a stat dos * Used if other short-acting treatment options for acute agitation and arousal have been ineffective * IM administration. Intermediate-acting injection. * Not for long-term use. Duration of Tx cannot exceed 2 weeks, 400mg or 4 injections * Max conc at about 8 hours. Effects persist for 3 days

Question 34

When is long acting (depot) antipsychotics used? How is it used?

Answer 34

* Antipsychotic long-acting injections (LAIs) used where non-adherence to oral treatment is problematic, or patient prefers this formulation type * Deep intramuscular injection (gluteal or deltoid) * Medication slowly released into bloodstream, providing steady supply of medication. * LAIs do not ensure adherence: they assure awareness of adherence * Allow regular assessment of patient (due to regular injections)

Question 35

Advantages and disadvantages of LAI antipsychotics?

Answer 35

Advantages * Proven reduction in relapse * Improved adherence * Fewer hospitalisations * Less fluctuation in drug concentration * Regular contact with clinicians * Less risk of overdose * Avoids first pass metabolism Disadvantages * Pain at injection site * Cannot be withdrawn quickly (E.g. side effects) * Patient loses control of treatment * Less dosing flexibility * Monitoring required (olanzapine)

Question 36

How is LAI antipsychotics formulated? Where is it injected?

Answer 36

All fomulated in oil Test doses required to test tolerability to antipsychotic and oil --\> Regular dosing commence 4-10 days after test dose • Injected into gluteal muscle sometimes deltoid

Question 37

Pharmacology of paliperidone palmitate? Strengths: 25mg, 50mg, 75mg, 100mg, 150mg

Answer 37

* once monthly (every 4 weeks) --\> IM * Must trial oral risperidone or paliperidone prior to initiation --\> To test tolerability to medication * Two initiation doses, so oral administration not required once injection has commenced. * Deltoid gives approx 28% higher peak concentration

Question 38

What are the effects of smoking and smoking cessation with antipsychotics?

Answer 38

Cigarette smoking induces CYP1A2 * Reduces plasma levels of drugs eg BZD, clozapine, olanzapine * Significant effects with clozapine and olanzapine Smoking cessation --\> increased drug plasma levels --\> consider dose reduction

Question 39

What to use for smoking cessation?

Answer 39

NRT has been used effectively for smoking cessation * But does not affect CYP enzymes \> Varenicline – Champix® - pschiatric adverse effects reported, but can be used with careful monitoring \> Bupropion – Zyban® - not routinely used in psychiatric setting. Lowers seizure threshold

Question 40

What are effects of caffeine on antipsychotic drugs?

Answer 40

Patients with mental illness have been reported to drink large amounts of caffeinated drinks * Caffeine can increase drug levels --\> possibly due to competitive CYP1A2 inhibition

Question 41

Why does NMS occur (Neuroleptic Malignant Syndrome)?

Answer 41

Thought to be due to a sudden over-blockade of dopaminergic function * A very rare life-threatening syndrome that can occur with any antipsychotic medication antipsychotics that act on stronger dopamine receptors

Question 42

Symptoms of NMS (Neuroleptic Malignant Syndrome)?How to treat?

Answer 42

* Characterised by fever, muscle stiffness, altered consciousness and problems with the autonomic nervous system * Can be fatal if left untreated * Treatment is symptomatic and antipsychotic should be ceased

Question 43

Concerns with elderly patients?

Answer 43

* More susceptible to adverse effects including EPSE and TD * Lower starting doses of medications are used * There is some concern that olanzapine and risperidone may increase the chance of a stroke * Elderly patients more likely to have other illness or be on other medications

Question 44

How to deal with side effects A) Akathisia B) Sedation C) nausea D) constipation some more not relate to questions above Weight gain – combination of good diet and exercise – prevention better than treatment metformin can reduce weight gain Augmentation with aripiprazole --\> can reduce weight gain

Answer 44

A) stretching & exercise B) take medication at night (if once daily dose) e.g. clozapine small dose in morning and large dose at night C) take with or after food D) balanced diet, increase fibre and fluid intake Coloxyl & Senna, Movicol