Management of schizophrenia 1.5.2 Flashcards
What are the principles of antipsychotic treatment?
- drug tx tailored to individual (consider side effects)
- Use lowest effective dose
- Use monotherapy where possible
Which are the high potency FGA antipsychotics?
- droperidol
- flupentixol
- haloperidol
- trifluoperazine
- zuclopenthixol
What are the features of the high potency FGA?
- ↑EPSE
- ↓ Sedation
- ↓ orthostatic hypotension
- ↓ anticholinergic side effects
Which are the low potency FGA?
- chlorpromazine
- pericyazine
What are the feautures of the low potency FGA?
- ↓EPSE
- ↑sedation
- ↑ orthostatic hypotension
- ↑ anticholinergic side effects
Which antipsychotics have better efficacy on negative symptoms?
- second generation antipsychotics
What are the side effects of SGAs?
Why do we not use clozapine first line?
- agranulolcytosis
- myocarditis
- cardiomypathy
- gastrointestinal hypomotility
- constipation
How are FGA used in schizophrenia?
- 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
What are examples of EPSE?
- 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
What do we do if EPSE occurs?
- ideally reduce antipsychotic dose OR
- switch to alternative antipsychotic
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
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
How does cloazapine differ from other side effects of SGAs?
Increased sedation, weight gain and anticholinergic effects
Pharmacalogy of aripiprazole? What is it used to agument?
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
Pharmacology of brexpiprazole
Indicated only in schizophrenia
May have positive effects on mood
Well tolerated – little weight gain, prolactin elevation, akathisia
Pharmaclogy of lurasidone
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
Pharmacology of olanzapine
Sedating – may be beneficial in acute psychosis
WEIGHT GAIN +++
Metabolic syndrome major concern. For this reason falling out of favour as long term treatment
Pharmacology of paliperidone
- 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
Pharmacology of Quietiapine
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
Pharmacology of risperidone
Adverse effects:
- Prolactin elevation – can be severe and problematic
- EPSE – dose related
cheaper than most SGAs
Pharmacology of Amisulpride? How does its MOA change from low to higher doses?
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
Pharmacology of Asenapine
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
Pharmacology of Ziprasidone
Can cause QT prolongation, increase risk of arrythmia – monitor ECG
Little weight gain, prolactin elevation & sedation
Clozapine pharmacology? Why is it not 1st line?
- 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
What is the condition of clozapine being used?
Must have trialled ≥2 antipsychotics prior to clozapine initiation
- Not effective or not tolerated
- At least 1 must be atypical antipsychotic
What is done before treatment of clozapine can be done (monitoring)?
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,
What ongoing monitoring for clozapine?
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
What is clozapine dosing/drug concentration?
Slow dose titration to avoid/reduce dose dependent adverse effects
- Target drug concentration: 350-1000mcg/L
For clozapine;
A) What to use to treat hypersalivation
B) What to use to treat GI hypomotility (constiaption)
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
Why is medication used in acute agitation and arousal in patients with schizophrenia? What drugs to use?
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
Outline why certain IM medication is not used for acute agitation. Which one is preferred?
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
What is needed when benzodiazepines used IM/IV? When to use?
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
Pharmacology of Zuclopenthixol acetate. When are they used?
- 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
When is long acting (depot) antipsychotics used? How is it used?
- 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)
Advantages and disadvantages of LAI antipsychotics?
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)
How is LAI antipsychotics formulated? Where is it injected?
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
Pharmacology of paliperidone palmitate?
Strengths: 25mg, 50mg, 75mg, 100mg, 150mg
- 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
What are the effects of smoking and smoking cessation with antipsychotics?
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
What to use for smoking cessation?
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
What are effects of caffeine on antipsychotic drugs?
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
Why does NMS occur (Neuroleptic Malignant Syndrome)?
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
Symptoms of NMS (Neuroleptic Malignant Syndrome)?How to treat?
- 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
Concerns with elderly patients?
- 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
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
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
