Antidepressants

Question 1

What are serotonin-selective reuptake inhibitors (SSRIs)?

Answer 1

Citalopram, fluoxetine, paroxetine, sertraline
Selectively inhibit the neuronal uptake of 5-HT, thus enhancing synaptic concentrations of 5-HT and down regulating presynaptic 5-HT receptors
Some are licensed for the treatment of anxiety, panic and obsessive-compulsive disorders

Question 2

Why are SSRIs first line?

Answer 2

Better tolerated than tricyclic antidepressants and are safer in overdose

Question 3

What are tricyclic antidepressants (TCAs)?

Answer 3

Amitriptyline, dothiepin (dosulepin), lofepramine, nortriptyline
Inhibit the neuronal uptake of noradrenaline and 5-HT, leading to augmented concentrations in the synaptic cleft
Increase in catecholamines may lead to down regulation of presynaptic alpha2-adrenoceptors and postsynaptic beta-adrenoceptors
Can be sedating and dangerous in overdose

Question 4

Which receptors do tricyclic antidepressants (TCAs) bind to?

Answer 4

Muscarinic receptors
Histamine receptors
Alpha2-adrenoceptors
5-HT receptors

Question 5

What are the antimuscarinic side effects of TCAs?

Answer 5

Dry mouth
Blurred vision
Constipation
Urinary retention

Question 6

What are the other side effects of TCAs?

Answer 6

Sedation (esp amitriptyline)
Cardiac effects- QT interval prolongation and the potentiation of catecholamines also predisposes to heart block and arrhythmias

Question 7

Who are TCAs not suitable for?

Answer 7

IHD
>70
High risk of suicide

Question 8

What are amitriptyline’s unlicensed uses?

Answer 8

Neuropathic pain
Prophylaxis of migraine
IBS (at low doses)

Question 9

What are noradrenaline reuptake inhibitors (NARIs)?

Answer 9

Reboxetine
Selectively inhibits noradrenaline reuptake
Useful for patients who cannot take TCAs but are resistant to the effects of SSRIs

Question 10

What are serotonin-noradrenaline reuptake inhibitors (SNRIs)?

Answer 10

Venlafaxine
Inhibits serotonin and noradrenaline reuptake but fails to bind to additional receptors- fewer side effects (does cause GI side effects)
Associated with causing hypertension

Question 11

What are noradrenergic and specific serotonergic antidepressants (NaSSAs)?

Answer 11

Mirtazapine
Exhibits alpha2-adrenoceptor antagonist activity, inhibiting negative feedback by these presynaptic receptors and thus producing an increased in noradrenaline and 5-HT transmission
Sedation in early treatment but antimuscarinic side-effects limited

Question 12

What are serotonin receptor modulators (SRMs)?

Answer 12

Nefazodone, trazodone

Inhibition of serotonin reuptake and the selective inhibition of postsynaptic serotonin receptors

Question 13

Whta rae mono-amine oxidase inhibitors?

Answer 13

Isocarboxazid, moclobemide, phenelzine, tranylcypromine
Inhibit monamine oxidases, which increases their concentration
They prevent the breakdown of the indirectly acting sympathomimetic amine, tyramine from the diet- causes the release of catecholamines and leads to hypertension

Question 14

What is tyramine present in?

Answer 14

Yeast extracts
Wines
Beers
Avocado
Banana
Pickled herring
Cheese

Question 15

What do most MAOIs act as?

Answer 15

Irreversibly, effects may persist for 2-3 weeks after the cessation of treatment

Question 16

What is moclobermide?

Answer 16

Selective reversible inhibitor of MAO-A (RIMA) reduces interactions with food since tyramine is metabolised by MAO-B

Question 17

What are the NICE guidelines for prescribing antidepressants?

Answer 17

Mild depression- reassess after 2 weeks, initial treatment not recommended
SSRI first line, TCA preferred if sleep is impaired (take 2 weeks to have an effect)
Psychological therapy (CBT) should be considered

Question 18

What are the rules for withdrawing antidepressants?

Answer 18

Treatment should be considered for at least 6 months after remission
If patient has had 2 recent depressed episodes, treatment should be continued for 2 years
Reduce dose over 4 weeks or longer to stop (especially paroxetine)

Question 19

What is St. John’s wort?

Answer 19

Similar mechanism to SSRI
Shouldn’t be used with conventional antidepressants due to side effects (increased toxicity with SSRIs)
Enzyme inducer

Question 20

What drugs does St John’s wort interact with?

Answer 20

Warfarin
Carbamazepine/phenytoin
Anti-HIV drugs
Ciclosporin 
Oral contraceptives 
(may reduce efficacy)

Question 21

What is the stepped approach for management of depression?

Answer 21

SSRI
If failure use alternative SSRI or mirtazapine or reboxetine or TCS
If remission maintain >6 months
Gradual withdrawal

Question 22

What is used to treat bipolar affective disorder?

Answer 22

Lithium for both acute treatment and prophylaxis of bipolar disorder
Should be avoided in renal impairment
Narrow therapeutic window- range of interactions and requires monitoring

Question 23

What are anticonvulsants?

Answer 23

Carbamazepine and valproate
Used second line as prophylactic mood stabilisers in bipolar disorder
Lamotrigine and gabapentin have an unlicensed role in bipolar affective disorder when other treatments have failed

Question 24

What are neuroleptics (antipsychotics)?

Answer 24

Haloperidol, chlorpromazine

Control psychotic symptoms, may be associated with depression particularly during manic phase of bipolar disorder

Question 25

What drugs offer symptomatic relief for anxiety?

Answer 25

Benzodiazepines

B-blockers

Question 26

Whata are beta-adrenoceptor antagonists?

Answer 26

Propanolol most commonly used to treat sweating, palpitations, tremor and tachycardia

Question 27

What are benzodiazepines?

Answer 27

Diazepam
Reduce anxiety and aggression, induce sleep
Increase activity of GABA in the brain
Tolerance and dependency are problematic
Treatment should be limited to 2-4 weeks

Question 28

What is buspirone?

Answer 28

Anxiolytic
Activates 5-HT1A receptor binds to dopamine receptors
Side effects: dizziness, nausea, headache
Delay of 2-3 weeks prior to effect
Does not cause sedation