treating schizophrenia

the importance of treating first episode psychosis quickly

• improves long term prognosis

• reduces symptom severity

• limits duration of untreated psychosis

• reduces risk of relapse, hospitalisation or social decline

What are common first choice drugs for schizophrenia?

risperidone and quietapine

classification of antipsychotics

• 1st generation - typical

• 2nd and 3rd generation - atypical

characteristics of atypical antipsychotic drugs

High affinity at 5HT2A receptors compared to D2 receptors

High affinity at 5HT2C receptors compared to D2 receptors

A rapid dissociation rate from D2 receptors

Lower rate of EPS

Possibly better efficacy against negative symptoms

chlorpromazine

• typical 1st generation drug

• first effective antipsychotic

• not used frequently now

side effects of chlorpromazine

• Very sedating

• Moderate extrapyramidal

• Moderate muscarinic

• Moderate galactorrhea

• Neuroleptic malignant syndrome (rare)

examples of 1st generation drugs

• chlorpromazine

• haloperidol

haloperidol

• used in tourettes syndrome

• still widely used unlike chlorpromazine

side effects of haloperidol

• Less sedating – can cause agitation in some patients

• High risk of extrapyramidal

• Lower muscarinic side effects than chlorpromazine

• Moderate galactorrhea

• Neuroleptic malignant syndrome (rare)

risperidone

• atypical 2nd generation

• improves pos and neg symptoms

• oral formulation out of patent so very cheap

  • available IM and depot

side effects of risperidone

moderate sedation

moderate weight gain

galactorrhea

EPS at higher doses

quietapine atypical side effects

very sedating

causes drowsiness/tiredness

moderate muscarinic effects

moderate weight gain

moderate hypotension

no EPS, no galactorrhea

olanzapine

• atypical 2nd generation antipsychotic

• available in oral and IM

side effects of olanzapine

• weight gain

• dizziness

• fatigue

• GI tract problems

Which antipsychotics were implicated with diabetes risk?

• atypical

• quietapine and olanzapine

aripiprazole

• atypical 3rd generation

• D2 partial agonist and partial agonist at 5HT1A, 2A-C

side effects of aripiprazole

• lower tendency to produce weight gain

• can inc impulsive behaviour eg shopping, binge eating

clozapine

• atypical

• initially withdrawn due to - agranulocytosis, reintroduced with blood tests

• most effective antipsychotic

• used for treatment resistant schizo disorders

side effects of clozapine

• agranulocytosis

• cardiac effects

• muscarinic effects

• highly sedating

• weight gain/diabetes

agranulocytosis from clozapine

• loss of white blood cells due to suppression of immune system

• causes infection which can be treated with antibiotics

• untreated leads to death - 4-16% of cases

clozapine monitoring

• WBC count

• regular intervals

• if more than 2 days missed then the treatment has to restart

muscarinic side effects of clozapine

–Constipation (can be fatal)

–hypersalivation

–?agonist M4 ?metabolite agonist M1

which antipsychotics induce extra pyramidal side effects?

• haloperidol

• risperidone

• olanzapine, aripiprazole

which antipsychotics produce galactorrhea

• risperidone

• haloperidol

• olanzapine

which antipsychotics have anti muscarinic side effects

• olanzapine

• quietapine

• clozapine

• haloperidol

which antipsychotics are highly sedating

• olanzapine

• quietapine

• clozapine

risperidone acts on which receptors

• D2, D3 and 5HT2A receptors.

dirty atypical drugs act at which receptors

Olanzapine, quetiapine and aripiprazole act on

D2 ,D3 5HT2A, M4, M3, α2, BDNF, H1, 5HT7, 5HT1A and 5HT2C

clozapine acts on which additional receptors

GlyT

M1

mood stabilising drugs prescribed in addition to antipsychotic in schizophrenia and schizoaffective disorder

• valproate

• lithium

• lamotrigine

• may not improve how the antispsychotics work

What are the reasons for antipsychotic non compliance?

lack of belief in illness side effects cognitive problems, disorganized life-style

drug formulations

• oral

• sustained release

• intramuscular injection

• IM depot injections

Which medications can be administered in a psychiatric emergency?

• olanzapine

• risperidone

• haloperidol

IM depot injections advantages

• involuntary

• good for diagnosed patient

  • injection frequency not as much as IM

  • eliminates covert non compliance

IM depot injection limitations

• effects are sometimes delayed

• not all drugs available as depots

Drugs available as depot?

Risperidone (Risperdal consta - monthly)

Haloperidol (monthly)

Aripiprazole (up to 2 months)

non pharmacological interventions for schizo disorders

• CBT can improve symptoms

• PADs: medication reminder, signal behaviour issues, waking

• Physical support.

• ESAs: provide comfort and security, provide a buffer,

• Increase social interactions, exercise benefits