Antidepressants and Antipsychotics Flashcards
What are some common effects of adrenergic receptor agonism?
Sweating
Tremor
Headaches
Nausea
Dizziness
What are some common effects of muscarinic receptor agonism?
Dry mouth + thirst (+dysphagia)
Urinary retention/difficulty urinating
Hot and flushed skin
Dry skin
What are some common effects of histamine receptor agonism?
Dry mouth
Drowsiness
Dizziness
N+V
What neurotransmitter system do most anti-depressants act on?
Serotonin
What do most serotonin related anti-depressants aim to do?
Increase serotonin activity at post-synaptic receptors
How long can it take for most anti-depressants to begin working?
2-3 weeks
What is the most commonly used type of anti-depressant?
SSRI’s (Selective serotonin re-uptake inhibitors)
What are some other types of ant-depressant’s?
NSRI’s (noradrenaline and serotonin re-uptake inhibitors)
Mirtazapine
Tricyclics
MAOI’s (Mono-amine oxidase inhibitors)
How doe SSRI’s exert their effects?
By increasing serotonin activity at post-synaptic receptors
How do SSRI’s increase serotonin activity?
Reducing the pre-synaptic re-uptake of serotonin after its release
What does the reduction of the pre-synaptic re-uptake of serotonin result in?
More serotonin sitting in the nerve junction
Other than increased serotonin in the nerve junction, what effect do SSRI’s have on the nerve junction?
Down regulates post-synaptic serotonin receptors
What are some common side-effects of SSRI’s?
Restlessness and agitation on initiation Nausea/GI disturbances Headaches Weight changes Sexual dysfunction
Bleeding and suicidal ideation (less common and usually age related)
What are some examples of SSRI’s?
Sertraline
Citalopram
Escitalopram
Fluoxetine
Paroxetine
What is the dose range for sertraline?
50 - 200mg
In the context of what group of non-psychiatric conditions is sertaline considered the safest?
Cardiac disease
What is the dose range for citalopram?
20 - 40mg
What is the dose range for escitalopram?
10 - 20mg
What must be considered when prescribing citalopram/escitalopram?
QTc prolongation
What is the dose range for fluoxetine?
20 - 60mg
What must be considered when switching from fluoxetine?
Serotonin syndrome
What is the dose range for paroxetine?
20 - 60mg
What must be considered when stopping paroxetine?
Discontinuation syndrome
What does NSRI stand for?
Noradrenaline and serotonin re-uptake inhibitors
How do NSRI’s work?
The same way as SSRI’s but by binding to noradrenaline re-uptake receptors as well
What other symptom are NSRI’s indicated for besides depression?
Neuropathic pain
In what way do the side-effects differ from those of SSRI’s?
Have a greater potential for sedation, nausea and sexual dysfunction
What are the two NSRI’s?
Duloxetine
Venlafaxine
What is the dose range for duloxetine?
60 - 120mg
What is the dose range for venlafaxine?
75 - 375mg
Why is venlafaxine generally better than duloxetine?
More efficacious
Can go to a higher dose
When can high dose duloxetine be problematic?
Heart disease
What must be done regularly in patients on venlafaxine at doses higher than 225mg?
Blood pressure monitoring
What class does mirtazapine belong to?
A unique class
How does mirtazapine work?
By acting as a 5HT-2 and 5HT-3 antagonist
Through what pathway does mirtazapine exert it’s main side effect of sedation?
H1 (histamine) activity
What are the two major side effects of mirtazapine?
Sedation and weight gain
Are the side-effects of mirtazapine always negative?
No - can be used to therapeutic advantage
Are tricyclics antidepressants commonly used?
Not as a first line treatment
When are tricyclics antidepressants usually used?
In patient’s who do not respond to SSRI’s
What are some newer tricyclics antidepressants?
Lofepramine and nortriptyline
What is an older tricyclic antidepressant?
Amitriptyline
What sort of side-effects can tricyclic antidepressants have?
Muscarinic and histamine
Why must caution be taken when prescribing tricyclic antidepressants?
They can be fatal in an overdose
How can tricyclic antidepressants cause death?
QTc prolongation and arrhythmias
What other condition can tricyclic antidepressants be used to treat?
Neuropathic pain
What does MAOI stand for?
Monoamine oxidase inhibitor
What are the two types of MAOI?
MAOI-A and MAOI-B
What pathway do MAOI-A’s work more on?
Serotonin
What pathways do MAOI-B’s work more on?
Dopamine
What type of depression are MAOI’s more useful in?
Atypical depression
What other way can MAOIs be categorised?
Reversible and irreversible
Which category of MAOI’s (reversible or irreversible) are more dangerous?
Irreversible
What are two examples irreversible MAOI’s?
Phenelzine
Isocarboxazid
What are two examples of reversible MAOI’s?
Moclobamide
Tranylcypromine
Why must MAOI’s be prescribe with caution?
Potential for dangerous interactions with other drugs
Potential for tyramine reaction
Requires a wash-out period before changing to another antidepressant
What can a tyramine reaction lead to?
Hypertensive crisis
What foods should be avoided to prevent a tyramine crisis?
Cheese
Picked meats
Wine
Other tyramine products
How long must the wash-out period be when switching from an MAOI?
Up to 6 weeks
What is vortioxetine?
A new type of antidepressant?
How does vortioxetine exert its effects?
By having all sorts of serotonergic activity
What is the most common side-effect of vortioxetine?
Nausea
When deciding which antidepressant to use what should be considered?
What has been used before and was it effective/tolerated?
Are there comorbidities that also need to be addressed?
What comorbidities can be addressed when treating depression?
Weight loss
Insomnia
Neuropathic pain
What should be used to treat new depression with no previous treatment?
SSRI
With an exception
What is the exception to using an SSRI for treating previously untreated depression?
In major weight loss or sleep difficulty
What should be used instead of an SSRI if its use is contraindicated in new depression?
Mirtazapine
When treating depression, if a drug has no benefit at a typical dose, should it be increased?
No
When treating depression, if a drug has no benefit at a typical dose, what should be done?
Switch to a different antidepressant
When treating depression, if a drug has only partial benefit at a typical dose, should it be increased?
Yes
When treating anxiety, if an antidepressant has no benefit at a typical dose, should it be increased?
Consider as an option
Should an antidepressant be switched immediately if it has significant side-effects within a couple of week?
Not always, these can get better
When should antidepressants be switched if they’re causing significant side-effects in the first couple of weeks?
If they cause a big problem for the patient
What is discontinuation syndrome?
A syndrome occurring upon discontinuation of antidepressants that is characterised by:
Sweating
Shakes
Agitation
Insomnia
Headaches
Irritability
Nausea and vomiting
Paraesthesia
Clonus
What is the severity of discontinuation syndrome influenced by?
Half-life
What antidepressants are the trickiest to stop?
Paroxetine and venlafaxine
What methods can be used to ease discontinuation of antidepressants?
Alternate days of taking and not taking
Snap tablets in half
Switch to fluoxetine and then reduce that instead
What is serotonin syndrome?
A potentially life threatening condition with a very vague presentation with three groups of symptoms
What are the three groups of symptoms seen in serotonin syndrome?
Cognitive
Autonomic
Somatic
What are the cognitive symptoms of serotonin syndrome?
Headaches
Agitation
Hypomania
Confusions
Coma
What are the autonomic symptoms of serotonin syndrome?
Shivering
Sweating
Hyperthermia
Tachycardia
Nausea and diarrhoea
What are the somatic symptoms of serotonin syndrome?
Myoclonus
Hyper-reflexia
Tremor
What causes serotonin syndrome?
Occurs sometimes in the use of drugs affecting the serotonin system and causing excessive serotonin
How is serotonin syndrome treated?
Supportively with fluids and monitoring
What is another name for antipsychotics?
Neuroleptics
What do all current antipsychotics do?
Reduce the level of dopamine activity at D2 receptors
What are the targeted dopaminergic pathways in antipsychotic mechanism?
Mesocortical
Mesolimbic
What pathways are not meant for targeting (but often are) in antipsychotic mechanism?
Nigrostriatal
Tuberoinfundibular
What is the nigrostriatal pathway involved in?
Movement
Deficiency of dopamine in the nigrostriatal pathway occurs in what non-psychiatric condition?
Parkinson’s Disease
What is the tuberoinfundibular pathway involved in?
HPA axis
What do all antipsychotics have the potential to cause?
Sedation
Extrapyramidal side-effects (EPSE’s)
Weight gain
QTc prolongation
What can all antipsychotics cause acutely?
Dystonia - including oculogyric crisis
What are the two main groups of antipsychotics?
Typical
Atypical
What are typical antipsychotics?
Older drugs that are more likely to cause extrapyramidal side-effects
Tend to bind more to muscarinic and histamines receptors
Other than dopamine, what other system do atypical antipsychotics tend to affect?
Serotonin
What are some typical antipsychotics?
Haloperidol
Flupenthixol
Zuclopenthixol
Chlorpromazine
Sulpride
What are some atypical antipsychotics?
Clozapine
Olanzapine
Risperidone
Quetiapine
Amisulpride
Aripiprazole
What is another name for atypical antipsychotics?
Second generation antipsychotics
What side-effects are typical antipsychotics more likely to cause?
EPSE’s
Dizziness
Sexual dysfunction
What are some EPSE’s?
Bradykinesia
Muscle stiffness
Tremor
Tardive dyskinesia
Akathisia
What is akathisia?
Inner feeling of restlessness - particularly affects the legs, can also present as rocking back and forth or pacing
What side-effects are atypical antipsychotics more likely to cause?
Weight gain
Dyslipidaemia
Diabetes
What types of monitoring must patients on antipsychotics undergo?
Baseline
Weekly
Three monthly
Yearly
What are some baseline observations taken before prescribing antipsychotics?
FBC
Lipids
LFT
HbA1C
Weight
ECG
Blood pressure and pulse
What weekly observations must a patient on antipsychotics undergo?
Weight
What three monthly observations must a patient on antipsychotics undergo?
FBC
Lipids
LFT
HbA1C
Weight
ECG
Blood pressure and pulse
What yearly observations must a patient on antipsychotics undergo?
FBC
Lipids
LFT
HbA1C
Weight
ECG
Blood pressure and pulse
What was the first atypical antipsychotic?
Clozapine
What receptors does clozapine act as an antagonist at?
D2
5HT-2
What is special about clozapine?
The most efficacious antipsychotic
How long can it take for clozapine to exert its full effects?
Months
When should clozapine be used to treat schizophrenia?
When two other antipsychotics have not worked
What does clozapine have significant potential to cause?
Agranulocytosis (severe leukopenia)
Gastrointestinal hypomobility
What must be done to avoid agranulocytosis in clozapine use?
Close FBC monitoring.
Weekly for first 18 weeks, then fortnightly then monthly
What can gastrointestinal hypomobility cause?
Constipation
Potentially fatal bowel obstruction
What are some other side-effects of clozapine?
Hypersalivation
Urinary incontinence
How should clozapine dosage be increased?
Titrated slowly over two weeks with monitoring of vital signs
Why should vital signs be monitored when titration clozapine upwards?
Due to the potential for autonomic dysregulation
What is neuroleptic malignant syndrome?
A rare life threatening reaction to antipsychotics
What are the symptoms of neuroleptic malignant syndrome?
Fever
Confusion
Muscle rigidity
Sweating
Autonomic instability
What usually causes death in neuroleptic malignant syndrome?
Rhabdomyolysis
Renal failure
Seizures
What are the risk factors for neuroleptic malignant syndrome?
High potency dopamine antagonists (typical antipsychotics) in antipsychotic naive
High doses
Young men
What is the treatment for neuroleptic malignant syndrome?
Emergency referral to A & E
Stop antipsychotic
Fluid resuscitation
Reduce temperature
What are anticholinergics used for in psychiatry?
To treat the EPSE’s of antipsychotics
What quality of dopamine and acetylcholine is important in the nigrostriatal pathway?
The ratio between the two
What happens if there is too much acetylcholine in relation to dopamine?
Get EPSE’s
As antipsychotics aim to reduce dopamine activity, dopamine cannot be increased (or will reverse antipsychotic treatment). So how are EPSE’s treated?
By simultaneously reducing acetylcholine activity to restore the normal ratio
What is the most commonly used drug for treating EPSE’s?
Procyclidine
What does procyclidine have the potential for?
Misuse
What are two other anticholinergics?
Benzatropine
Trihexphenidyl
What are anticholinergics not effective at treating?
Tardive dyskinesia
What effect can anticholinergics have on tardive dyskinesia?
Exacerbation
