Antidepressants Flashcards
What are serotonin-selective reuptake inhibitors (SSRIs)?
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
Why are SSRIs first line?
Better tolerated than tricyclic antidepressants and are safer in overdose
What are tricyclic antidepressants (TCAs)?
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
Which receptors do tricyclic antidepressants (TCAs) bind to?
Muscarinic receptors
Histamine receptors
Alpha2-adrenoceptors
5-HT receptors
What are the antimuscarinic side effects of TCAs?
Dry mouth
Blurred vision
Constipation
Urinary retention
What are the other side effects of TCAs?
Sedation (esp amitriptyline)
Cardiac effects- QT interval prolongation and the potentiation of catecholamines also predisposes to heart block and arrhythmias
Who are TCAs not suitable for?
IHD
>70
High risk of suicide
What are amitriptyline’s unlicensed uses?
Neuropathic pain
Prophylaxis of migraine
IBS (at low doses)
What are noradrenaline reuptake inhibitors (NARIs)?
Reboxetine
Selectively inhibits noradrenaline reuptake
Useful for patients who cannot take TCAs but are resistant to the effects of SSRIs
What are serotonin-noradrenaline reuptake inhibitors (SNRIs)?
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
What are noradrenergic and specific serotonergic antidepressants (NaSSAs)?
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
What are serotonin receptor modulators (SRMs)?
Nefazodone, trazodone
Inhibition of serotonin reuptake and the selective inhibition of postsynaptic serotonin receptors
Whta rae mono-amine oxidase inhibitors?
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
What is tyramine present in?
Yeast extracts Wines Beers Avocado Banana Pickled herring Cheese
What do most MAOIs act as?
Irreversibly, effects may persist for 2-3 weeks after the cessation of treatment
What is moclobermide?
Selective reversible inhibitor of MAO-A (RIMA) reduces interactions with food since tyramine is metabolised by MAO-B
What are the NICE guidelines for prescribing antidepressants?
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
What are the rules for withdrawing antidepressants?
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)
What is St. John’s wort?
Similar mechanism to SSRI
Shouldn’t be used with conventional antidepressants due to side effects (increased toxicity with SSRIs)
Enzyme inducer
What drugs does St John’s wort interact with?
Warfarin Carbamazepine/phenytoin Anti-HIV drugs Ciclosporin Oral contraceptives (may reduce efficacy)
What is the stepped approach for management of depression?
SSRI
If failure use alternative SSRI or mirtazapine or reboxetine or TCS
If remission maintain >6 months
Gradual withdrawal
What is used to treat bipolar affective disorder?
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
What are anticonvulsants?
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
What are neuroleptics (antipsychotics)?
Haloperidol, chlorpromazine
Control psychotic symptoms, may be associated with depression particularly during manic phase of bipolar disorder
What drugs offer symptomatic relief for anxiety?
Benzodiazepines
B-blockers
Whata are beta-adrenoceptor antagonists?
Propanolol most commonly used to treat sweating, palpitations, tremor and tachycardia
What are benzodiazepines?
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
What is buspirone?
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
