Psychosis

Question 1

Definition

Answer 1

Clinical state of mind characterised by loss of contact with reality

Question 2

Clinical signs

Answer 2

Patients might experience perceptual disturbances e.g. hallucinations that are generally auditory as well as disturbances of thought content i.e. delusions
Negative symptoms- blunting of affect, avolition, alogia
Social or occupational dysfunction
clear sensorium

Question 3

Delirium with acute confusion and aggression - clinical signs

Answer 3

Impaired awareness, confusion, disorientation

Others : restlessness, agitation and hallucinations, ANS symptoms, aggressiveness etc

Question 4

Causes of delirium can be due to

Answer 4

DIMTOP (drugs, infection, metabolic, trauma, oxygen, psychological)

Question 5

Pathogenesis of psychosis

Answer 5

UNKNOWN
Dopamine hypothesis of schizophrenia
Excessive dopaminergic activity

Question 6

Neuroanatomy of psychosis

Answer 6

Mesolimbic-mesocortical - behaviour
Nigrostrial-coordination of voluntary movement
Tuberoinfindibular-inhibition of prolactin secretion

Question 7

Causes of psychosis

Answer 7

Functional psychosis (Schizophrenia, Bipolar mood disorder)

Psychotic disorders due to medical conditions (Medical conditions e.g. epilepsy, Alzheimer’s dementia, HIV, neurosyphilis and Drugs - Illicit drugs –cannabis, mandrax, cocaine, amphetamines; prescription drugs- steroids, antiparkinsonism drugs, atropine)

Other- e.g. postpartum psychosis

Question 8

Management depends on…

Answer 8

Aetiology

Onset of the psychosis

Question 9

Acute management (agitated or acutely disturbed pt)

Answer 9

Goals of therapy is to calm pt down and achieve containment

Antipsychotic and/or benzodiazepine of your choice

Question 10

Chronic management

Answer 10

Goal of therapy is to prevent relapse of acute psychotic symptoms i.e. delusions, hallucination so as to maintain functionality
Antipsychotic drugs
Supportive psychotherapy for patient and family

Question 11

Classes of classical neuroleptics

Answer 11

Dopamine 2 receptor antagonists

Tendency to cause extrapyramidal side effects

Question 12

Classes of atypical neuroleptics

Answer 12

D2 & D3 receptor antagonists

D2 & serotonin receptor antagonist

Question 13

Primary indications for neuroleptics

Answer 13

Schizophrenia
Mania
Organic psychosis

Question 14

Other indications for neuroleptics

Answer 14

Nausea and vomiting
Intractable hiccups
Tourette’s syndrome
Behaviour disorders
Anaesthesia

Question 15

name 3 classes of Traditional neuroleptics

Answer 15

Phenothiazines (side chain)
Butyrophenones
Thioxanthenes

Question 16

3 classe of phenothiazines and examples of each

Answer 16

Aliphatic e.g. chlorpromazine
Piperazine e.g. prochloperazine, fluphenazine
Piperidine e.g. thioridazine*, pericyazine

Question 17

name 2 examples of Butyrophenones

Answer 17

Haloperidol, droperidol

Question 18

name 2 examples of thioxanthenes

Answer 18

Flupenthixol, zuclopenthixol

Question 19

Formulations

Answer 19

oral
Injectables- usually IM (Short acting- acute management; long acting depot preparations- preferred if compliance a problem)

Question 20

MOA of typical antipsychotics

Answer 20

Blocks D2 and D1, preventing dopamine-receptor interaction

Question 21

MOA of adverse effects of typical antipsychotics

Answer 21

Blocks H1 and 5-HT2 receptors

Question 22

MOA of atypical antipsychotics

Answer 22

block D1

Question 23

MOA of adverse effects atypical antipsychotics

Answer 23

Block 5-HT2 and alpha adrenergic receptors

Question 24

Oldest neuroleptic of low potency

Answer 24

Chlorpromazine (Piperazine phenothiazine)

Question 25

Indications for chlorpromazine

Answer 25

Schizophrenia Mania Organic psychosis etc Tranquillization in emergency aggressive behavioural disturbances

Question 26

Onset of action of Chlorpromazine

Answer 26

Onset 30-60min after oral ingestion and 15min after injection

Question 27

Half-life of Chlorpromazine

Answer 27

30 hrs

Question 28

Contraindications for Chlorpromazine

Answer 28

coma, severe mental depression, severe liver impairment, significant cardiac disorders, glaucoma, bone marrow depression

Question 29

Adverse effects of chlorpromazine

Answer 29

EPSEs, sedation, postural hypotension, anticholinergic side effects, epileptogenic, photosensitivity ,jaundice, agranulocytosis

Question 30

Drug interactions Chlorpromazine

Answer 30

anticholinergics, antiepileptics, antihypertensives, antiparkinsonism drugs, CNS depressants , enzyme inducers

Question 31

Doses: Chlorpromazine

Answer 31

initially 25mg tds but maintenance range 75-300mg. IM 25-50mg ,can be repeated 3-4 times in 24hrs as necessary USE THE LOWEST EFFECTIVE DOSE

Question 32

EPSE-complications of antipsychotics

Answer 32

``` Acute dystonic reaction Parkinsonism akathisia Tardive dyskinesia Neuroleptic malignant syndrome ```

Question 33

Explain acute dystonic reaction

Answer 33

Acute dystonic reaction- spasm of muscles of tongue, face, neck, and back (torticollis, protrusion of the tongue, facial grimacing, oculogyric crisis, opisthotonus, truncal dystonia and laryngeal spasm) vs seizure Onset 24-48hrs Risk factor- young male Rx –biperiden 2mg IM/IV, benzodiazepine if necessary, if c/o pain analgesia Stop neuroleptic until symptoms full resolution

Question 34

Explain parkinsonism

Answer 34

Parkinsonism –bradykinesia, rigidity, tremor Onset-weeks or months Common in older pts Rx - reduce dose- lowest effective dose Prescribe anticholinergic orphenadrine 50-150mg

Question 35

Explain akathisia

Answer 35

Akathisia-motor restlessness vs anxiety Onset days-weeks Rx - Reduce dose, Add anticholinergic if necessary

Question 36

Explain tardive dyskinesia

Answer 36

Tardive dyskinesia- syndrome of choreoathetoid and or other involuntary movements, usually of face, lips and tongue +/- arms legs and trunk Onset-usually >6/12 MOA-? Excess dopamine Rx- PREVENTION N.B. lowest effective dose for the shortest time - Gradually withdraw , Consider changing to atypical antipsychotics (less tendency for EPSEs)

Question 37

explain Neuroleptic malignant syndrome

Answer 37

Neuroleptic malignant syndrome-Rare BUT mortality >10% Aetiology unknown-?dopamine blockade in hypothalamus Onset –usually weeks but can occur after 1st dose Risk- ↑ambient temp, dehydration, intercurrent mildly febrile illness, catatonia Presents with -Hyperpyrexia -Sweating -Unstable blood pressure -Changes in LOC (stupor or catatonia like state) -Muscle rigidity Lasts 5-7 days, longer if depot prep used

Question 38

Advantages and disadvantage of atypical neuroleptics & uses

Answer 38

Newer and expensive Less EPSEs (not devoid of EPSEs), prolactin effects, ↑weight gain Clozapine EDL- reserved for treatment resistant psychosis Major s/e agranulocytosis & neutropenia Associated with QT prolongation

Question 39

Special populations

Answer 39

Pregnancy or lactation - No randomised controlled trials - All neuroleptics cross the placenta - Phenothiazines are excreted in breast milk-behavioural changes in infants Children - Use only if necessary as EPSEs can occur after first dose Elderly - More susceptible to cardiovascular side effects and anticholinergic side effects Hepatic diseases - dose adjustment may be needed

Question 40

Causes of treatment failure

Answer 40

Low efficacy rate!!!!! 40-60% Inter and intraindividual variability Under dosing- lowest EFFECTIVE dose Malabsorption- change to depot preparation Drug interactions Wrong diagnosis- Rx underlying cause e.g. brain tumours Non-compliance - Lack of insight-consider depot preparation vs tablets - Adverse effects- consider changing classes