Session 12 - Antipsychotics

Question 1

What is the theory for the cause of depression?

Answer 1

Deficiency of production of the monoamine neurotransmitters serotonin and noradrenaline in the brain. This combined with an environmental trigger such as death, divorce or trauma and possibly a genetic susceptibility leads to depression.

Question 2

What are the core symptoms of depression?

Answer 2

Core symptoms (2 of 3 needed to diagnose depression):

Low mood
Anhedonia
Decreased energy

Question 3

What are the secondary symptoms of depression?

Answer 3

Decreased appetite
Sleep disturbance
Hopelessness 
Reduced concentration 
Irritability 
Self harm or suicidal ideas and acts
Reduced libido 
May have psychotic symptoms

Question 4

What tool is used to help diagnose the severity of depression?

Answer 4

Becks depression scale

Question 5

What management is used to treat depression?

Answer 5

1. Assess suicide risk. May need mental health act assessment/sectioning.
2. Psychological therapy e.g. counselling/cognitive behavioural therapy
3. Antidepressants - first line = SSRIs

Question 6

Other than depression, what other indications are there for the use of antidepressants?

Answer 6

Anxiety

Neuropathic pain

Question 7

What are the types of antidepressants?

Answer 7

Serotonin Selective Reuptake Inhibitors (SSRIs) (first line)

Tricyclic Antidepressants (TCAs)

Serotonin/Noradrenergic Reuptake Inhibitors (SNRIs)

Monoamine Oxidase Inhibitors (MAOIs)

Question 8

What is the guidance for changing and stopping antidepressants?

Answer 8

Try one antidepressant for at least 6 weeks before switching to another.

Even if feeling better it is recommended to continue antidepressants for at least a year to reduce relapse risk.

Question 9

Give examples of serotonin selective reuptake inhibitors.

Answer 9

Citalopram

Fluoxetine

Question 10

Explain the mechanism of action of serotonin selective reuptake inhibitors.

Answer 10

Limit reabsorption (reuptake) of serotonin into the presynaptic cell (neurone), which increases the concentration of serotonin in the synaptic cleft. This means there is more serotonin available to bind to the postsynaptic receptors and carry on an action potential.

Question 11

What are the possible side effects of serotonin selective reuptake inhibitors (SSRIs)?

Answer 11

Nausea
Sexual dysfunction
Insomnia

Serotonin syndrome

Question 12

What is serotonin syndrome?

Answer 12

Life threatening presentation which occurs within a few weeks of initiating SSRI or when two SSRIs are used at once.

Symptoms:
Tachycardia 
Sweating
Dilated pupils
Myoclonic
Hyperreflexia
Hyperthermia

Can lead to seizures, muscle breakdown and complication of hyperthermia.

Question 13

Give an examples of a tricyclic antidepressant (TCA).

Answer 13

Amitriptyline

Question 14

What are the indications for amitriptyline?

Answer 14

Depression

Neuropathic pain

Question 15

What is the mechanism of action of tricyclic antidepressants (TCAs)?

Answer 15

They act largely as serotonin noradrenaline reuptake inhibitors (SNRIs).

Question 16

What are the possible adverse drugs reactions caused by tricyclic antidepressants?

Answer 16

Due to antimuscarinic action:
Dry mouth
Dry nose
Blurry vision
Constipation (lowered GI motility)
Urinary retention
Cognitive and/or memory impairment
Increased body temperature 

CARDIOTOXIC - life threatening inhibitors
NEUROTOXIC - seizures, hallucinations, delirium, coma

Question 17

Why should tricyclic antidepressants not be prescribed to patients with suicidal ideation?

Answer 17

Tricyclic are lethal in overdose due to their wide range of toxic effects.

Question 18

Give examples of serotonin noradrenaline reuptake inhibitors (SNRIs).

Answer 18

Venlafaxine

Duloxetine

Question 19

What are the possible adverse drug reactions caused by serotonin noradrenaline reuptake inhibitors (SNRIs)?

Answer 19

Same as SSRIs plus:
Raised blood pressure
Dry mouth
Hyponatraemia

Question 20

Explain the mechanism of action of monoamine oxidase inhibitors (MAOIs).

Answer 20

Monoamine oxidase inhibitors (MAOIs) block the enzyme monoamine oxidase from destroying neurotransmitters.

Question 21

Give examples of illnesses that involve psychosis.

Answer 21

Schizophrenia
Mania
Severe depression with psychosis 
Organic syndromes
Delusional disorder
Delirium
Dementia

Question 22

What does psychosis mean?

Answer 22

A lack of contact with reality.

Question 23

What are the symptoms of paranoia schizophrenia?

Answer 23

Disturbances of thinking 
Hallucinations
Delusions
Unusual speech-thought disorder 
Behavioural changes
Lack of insight 
Negative symptoms

Question 24

What is a hallucination?

Answer 24

A perception in the absence of an external stimulus - auditory, olfactory, visual, gustatory, tactile.

Question 25

What is a delusion?

Answer 25

A fixed false belief that is out of keeping with someone’s culture or religious beliefs.

Question 26

What are the main dopamine pathways?

Answer 26

Mesolimbic - emotional response and behaviour Mesocortical - important in arousal and mood Nigrostriatal - key pathway damaged in Parkinson’s disease Tuberoinfundibular - in hypothalamus and pituitary gland

Question 27

What are the two types of antipsychotics?

Answer 27

Typical (old generation) | Atypical (new generation)

Question 28

Give examples of typical antipsychotics.

Answer 28

Haloperidol | Chlorpromazine

Question 29

What is the mechanism of action of typical antipsychotics?

Answer 29

Act predominantly as dopamine antagonists. More likely to cause extrapyramidal side effects.

Question 30

Give examples of atypical antipsychotics.

Answer 30

``` Risperidone Quetiapine Aripiprazole Clozapine Olanzapine ```

Question 31

What is the mechanism of action of atypical antipsychotics?

Answer 31

Act at serotonin (5HT2) receptors as agonists and also act as dopamine antagonists.

Question 32

Which type of antipsychotic is most effective for reducing symptoms of schizophrenia?

Answer 32

Atypical antipsychotic (serotonin receptor agonists and dopamine receptor antagonists)

Question 33

What are the possible side effects caused by antipsychotic drugs?

Answer 33

Anti cholinergic: dry mouth, urinary retention, blurred vision Serotonergic: nausea, sexual dysfunction, insomnia (also due to anti-adrenergic) Metabolic syndrome: increased blood glucose, obesity, increased cardiovascular risk (most have significantly reduced life expectancy) Anti dopaminergic: extrapyramidal side effects

Question 34

What causes extra-pyramidal side effects?

Answer 34

All dopamine antagonists, however it is more prominent in the typical antipsychotics as these largely act on D2 receptors.

Question 35

What are the extra-pyramidal side effects?

Answer 35

Dystonia - sustained muscle contraction resulting in abnormal fixed posture Akathisia - internal feeling of restlessness Tardive dyskinesia - abnormal, involuntary, repetitive movements, e.g. grimacing, sticking out tongue or smacking lips Pseudo-Parkinsonism - rigidity, tremor and increased tone

Question 36

What is neuroepileptic malignant syndrome?

Answer 36

A life threatening reaction within 2 weeks of initiating antipsychotics. It is characterised by; fever, altered mental status, muscle rigidity and autonomic dysfunction (tachycardia, labile BP, flushing)

Question 37

What group of drugs are anxiolytic?

Answer 37

Benzodiazepines

Question 38

Give examples of benzodiazepines.

Answer 38

Lorazepam Diazepam Midazolam

Question 39

What are the uses of benzodiazepine?

Answer 39

Anxiety - anxiolytic in the short term (orally) Acute seizure - anticonvulsant (IM, IV, buccal) Sedative

Question 40

What is the mechanism of action of benzodiazepines?

Answer 40

Potentiate (increase) the action of GABA (the main inhibitory neurone) by increasing the opening of chloride channels which hyperpolarises the membrane. This decreases overall cortical transmission. It is unclear why this reduces anxiety.

Question 41

Why should benzodiazepines only be used in the short term?

Answer 41

Dependency (withdrawal symptoms if stopped) Tolerance (higher doses needed for same effect) Make patients more likely to act on suicidal impulses and are dangerous in overdose.