Treatment of Schizophrenia Flashcards
What is Schizophrenia & its symptoms
- Prolonged, persistent form of psychosis
- “Thought disorder”
- Disorganised bizarre thoughts, hallucinations, delusions, inappropriate effect, impaired psychosocial functioning
Symptoms:
- Hallucinations
- Delusions
- Disorganised thinking
Etiology of Schizophrenia
Possible dysregulation of DA & 5-HT
Predisposing factors:
- Genetics, neurodevelopmental effects
Precipitating factors:
- Drugs (eg. DA agonists)
- Psychosis related to alcohol & psychoactive substance misuse
Perpetuating factors:
- lack of support
- poor adherence to antipsychotics
General Assessment for Schizophrenia
- History of present illness
- Psychiatric, substance use, complete medical & medications misuse, family, social, forensic, occupational hx
- Reassess adherence to meds
- Phy & neurological exam
- MSE
- Labs & other investigations to exclude general med conditions/ substance-induced symptoms
Non pharmacological treatment of Schizophrenia
- Individual CBT (if pt able to go through exercises)
- Electroconvulsive Therapy (ECT) for treatment-resistant Schizophrenia
- Repetitive Transcranial Magnetic Stimulation (rTMS) for reducing auditory hallucinations
- Psychosocial rehabilitation programs to improve pt’s adaptive functioning
Goals for treatment of Schizophrenia
- Minimise threat to self & others
- Minimise acute symptoms
- Minimise/prevent relapse
- Promote med adherence
- Optimise dose vs adverse effects
- Improve functioning & QOL
What do Antipsychotics do?
- Tranquilize w/o impairing consciousness/causing paradoxical excitement
- Short-term: Calm disturbed pts
- Relieve symptoms of psychosis (thought disorders, hallucinations, delusions, prevent relapse)
- long-term treatment often necessary (may relapse if treatment is withdrawn inappropriately)
Why is relapse of Psychosis often delayed for a few weeks after cessation?
- Adipose tissue acts as depot reservoirs
- Antipsychotics stored diffuses back into bloodstream until depletion
Methods to overcome poor adherence of Antipsychotics
- IM long-acting inj
- Patient & caregiver education
- Community psychiatric nurse
MOA of Antipsychotics (Dopamine pathways)
1) Mesolimbic tract
- D2 antagonism in this tract most common MOA
- Overactivity in this region responsible for +ve symptoms
2) Mesocortical tract
- Hypofunction/dopamine blockage in this region results in -ve symptoms
3) Nigrostratial tract
- EPSE (Parkinson-like symptoms)
4) Tuberinfundibular tract
- Hyperprolactinemia
Receptor affinities of Antipsychotics & their implications
D2 antagonism: Improve +ve symptoms
-> SE: EPSE, Hyperprolactinemia
5-HT2A antagonism: Improve -ve symptoms
Algorithm for Treatment of Schizophrenia
1) Single FGA/SGA (NOT clozapine)
2) (+) Single FGA/SGA
If Treatment-resistant…
3) Clozapine (max:900mg)
* only if failed >=2 adequate trials*
4) Clozapine + Augmenting agent (FGA/SGA/ECT)
Notes:
- Individualised
- No intolerable SE
- Compliant to an adequate trial (At least 2-6 weeks @ optimal therapeutic doses)
Precautions for Antipsychotic Use
- CVS Disease
- Parkinson’s disease
- Prostatic hypertrophy
- Angle-closure glaucoma
- Severe respiratory disease
- Blood dyscrasias (esp for Clozapine)
- Elderly with Dementia (increased risks for mortality)
Which Antipsychotics should be given with food?
- Lurasidone
- Ziprasidone
Adjunctive treatment during Acute Agitation (Psychiatric Emergency)
If cooperative:
- PO lorazepam 1-2mg
- PO risperidone 1-2mg
If uncooperative (IM short-acting):
- IM Lorazepam 1-2mg
- IM Olanzapine (immediate release) 5-10mg
- -> Must not give lorazepam & olanzapine within 1h of each other
- IM Haloperidol 2.5-10mg (cheapest) with ECG
- -> Consider + anticholinergics where appropriate
- IM Promethazine 25-50mg
Adjunctive treatment during Catatonia
[Abnormality of movement and behaviour, may involve repetitive or purposeless overactivity, or catalepsy, resistance to passive movement, and negativism]
Benzodiazepines:
- PO/IM Lorazepam
Adjunctive treatment to manage Depressive /Negative Sx of Chronic Schizophrenia
1) Antidepressant
- Some SSRIs has mild-moderate efficacy for managing -ve symptoms
2) SGA
IM Long-Acting Antipsychotics
FGA:
i) Flupenthixol Decanoate
ii) Haloperidol Decanoate
iii) Zuclopenthixol decanoate
SGA:
i) Risperidone long-acting suspension
- Every 2wks
- To supplement with oral dose during 1st 3wks
ii) Paliperidone prolonged-release suspension
- Ivega trinza: Every 3mth
Adverse SE of FGA
- EPSE
- Acute dystonia, tardive dyskinesia, akathisia
*Increased prolactin secretion
- Anticholinergic SE (dry mouth, constipation, urinary retention)
- Hypotension (Alpha-1 antagonism)
- Sedation, weight gain (H1 antagonism)
Adverse SE of SGA
Weight gain, Increase FBG, TG
- Clozapine & Olanzapine especially*
- Ziprasidone, Aripiprazole & Brexpiprazole has less metabolic SE
Sedation (H1 antagonism)
- Clozapine & Olanzapine*
Anticholinergic
- Clozapine* & Olanzapine
Proconvulsant
- Clozapine & Olanzapine*
Monitoring of SE of Antipsychotics
- Clozapine-induced agranulocytosis*
- -> Hematological monitoring weekly for 1st 18weeks, then monthly
BMI: 3mth FBG: 3mth then annually Lipid Panel: BP: 3mth then annually EPSE Exam:
Management of Antipsychotics SE
1) EPSE
- Dystonia: IM anticholinergics (benztropine, diphenhydramine)
- Pseudo-PKS: Decrease dose/Switch to SGA, Anticholinergics PRN (benztropine)
- Akathisia: Decrease dose/Switch to SGA, Clonazepam (low-dose) PRN
- Tardive dyskinesia: Discontinue anticholinergics, Decrease dose/Switch to SGA, Valbenazine 40-80mg/day, Clonazepam PRN
2) Hyperprolactinaemia
- Switch to Aripiprazole
3) Metabolic SE
- Lifestyle modifications, treat diabetes (metformin), switch to lower risk agents (Aripiprazole, Lurasidone)
4) CVS
Orthostatic hypot/s: Get up slowly
VTE/PE: mANAGE EMERGENT dvt
5) CNS
* Neuroepileptic Malignant Syndrome (NMS)*
- Muscle rigidities, fever, autonomic dysfunction (Increase PR, labile BP, diaphoresis), altered consciousness, Increased CK
- Happens with high-potency agents
- > IV Dantrolene 50mg TDS (muscle relaxer), Oral Dopamine Agonist, supportive measures
- Switch to SGA (low-potency)
6) Hematological
Clozapine-induced Agranulocytosis: Discontinue if WBC < 3, ANC < 1.5
To take note of when treating Elderly with Antipsychotics
- Avoid drugs with high propensity to cause orthostatic hypot/s or anticholinergic SE
- Simplify regime
- Elderly with Dementia (increased risks for mortality) when using FGA & SGAs
Clinically significant DDI with Antipsychotics
Fluvoxamine: Increases Clozapine
Carbamazepine: Agranulocytosis with Clozapine
Time course of treatment response with Antipsychotics
1st wk: Decreased agitation
2-4wks: Decreased paranoia, hallucinations
6-12wks: Decreased delusions
3-6mths: Cognitive sxs may improve (with SGAs)
Clinical differences between SGA & FGA
Efficacy
FGA: +ve sxs
SGA: +ve & mood sxs
Toxicity:
FGA: EPSE
SGA:
- More metabolic SE (except Aripiprazole, Brexipiprazole, Lurasidone, Ziprasidone)
- “-ines” relatively > sedating, > weight gain
Acute stabilisation phase of Schizophrenia
Goal: Reduce agitation, aggression, hostility, improve sleep
If acutely agitated/aggressive:
1st: De-escalate
2nd: Consider oral antipsychotic +/- benzodiazepine
- Fast-acting IM alternatives (IM Haloperidol 5mg with ECG + IM Lorazepam 2mg)
If EPSE:
Dystonia/ pseudo-PKS SE: Oral/IM benztropine 2mg
Stabilisation & Maintenance phase of Schizophrenia
Goal: minimise/prevent relapse, maintain baseline functioning
If poor adherence/prefer IM:
- IM long-acting (IM haloperidol Decanoate)
