Antidepressants Flashcards
2 major types of depression
- Unipolar (swing in same direction): reactive or endogenous
- Bipolar depression or affective disorder (alternate depression and mania): strongly familial
What is monoamine theory?
Deficits in monoamine neurotransmitters (noradrenaline and 5-HT) cause depression
What are the 2 major forms of monoamine oxidase?
MAO-A and MAO-B
- 5-HT mainly broken down by MAO-A
- Both act on noradrenaline and dopamine
What is the MOA of MAOIs?
Inhibit monoamine oxidase to increase biological availability of monoamines
Characteristics of phenelzine?
Non-selective and irreversible MAOI
ADRs of MAOIs
Postural hypotension: sympathetic block by dopamine accumulation (inhibitory transmitter) in cervical ganglia
Restlessness and insomnia
Serotoninergic (esp if combined with similar effect drugs): hyperexcitable, increased muscular tone, myoclonus, loss of consciousness
What is the cheese reaction with MAOIs?
Drug-food interaction with cheese and concentrated yeast products
Causes acute hypertension which leads to severe headache and even intercranial haemorrhage
What type of MAOIs are less likely to cause the cheese reaction?
Reversible, MAO-A selective MAOIs (e.g. moclobemide)
How do MAOIs cause the cheese reaction?
- MAOIs prevent breakdown of (tyr)amines in intestine and liver
- Tyramine accumulates and is taken up into adrenergic terminals
- Sympathomimetic effect: compete with NA for vesicles -> release of NA into synapse
What are the 4 tricyclic antidepressants and their selectivity?
Non-selective for SERT/NET: imipramine, amitriptyline, nortriptyline
Selective for NET: desipramine
(serotonin/norepinephrine transporter: SERT/NET)
Why is nortriptyline preferred as choice of TCA?
2nd gen TCA
Milder side effects than amitriptyline and imipramine
Improved compliance
List 4 ADRs for TCAs
Sedation: H1 histamine receptor antagonism, tolerance in 1-2 weeks
Postural hypotension: a-adrenoceptor sympathetic block
Dry mouth, blurred vision, constipation: muscarinic receptor antagonism
DDI: plasma protein bound, mainly hepatic metabolised
What are the main differences between SSRIs and TCAs?
SSRIs: fluoxetine and citalopram
50-1000-fold selectivity for 5-HT over NA
Fewer adverse effects: safer in overdose -> better compliance
List 3 advantages of SSRIs
- Lack cardiovascular effects: low affinity for a-adrenoceptor
- Reduced sedation: lack effect at histamine receptors
- Minimal anticholinergic effects: low affinity for muscarinic receptors
Adverse effects of SSRIs
Nausea, insomnia: withdrawal symptoms when plasma levels drop between doses
Sexual dysfunction: increased stimulation of 5HT2 receptors
Sedation: citalopram (histamine antagonism)
What drug can be given to prevent SSRI-induced sexual dysfunction?
5HT2 blocker e.g. Cyproheptadine
What is serotonin syndrome?
DDI with concomitant use of multiple serotoninergic drugs
Effects: tremor, hyperthermia, cardiovascular collapse
List one noradrenaline reuptake inhibitor (NARI)
Reboxetine or maprotiline
What differentiates NARIs from other antidepressants?
Reboxetine: 1000-fold selectivity for NA
Fewer adverse effects than SSRIs and TCAs
ADRs of reboxetine
Dry mouth, constipation: anticholinergic
Insomnia: increase NA activity in CNS
Tachycardia: increase NA availability at sympathetic synapses
What is the MOA of venlafaxine?
SNRI (dual serotonin and noradrenaline reuptake inhibitor): similar reuptake inhibition profile to TCA
Advantages of venlafaxine
Fewer side effects than TCA due to change in structure
Works slightly faster
Better in treatment-resistant patients
ADRs of venlafaxine
Similar to SSRIs: nausea, insomnia, sexual dysfunction
DDI: serotonin syndrome
Withdrawal effects more common and stronger than SSRIs or TCAs
List 4 other antidepressants and their MOA
- Mirtazapine: NE and specific serotonin antidepressant (NaSSA)
- Bupropion: NE-dopamine reuptake inhibitor (NDRI)
- Agomelatine: agonist melatonin MT1 and MT2, antagonist 5HT2C receptor; less TCA/SSRI effects, also for sleep disorders
- Ketamine: glutamate NMDA receptor antagonist; rapid-onset antidepressant
Why is vortioxetine a multimodal serotonergic antidepressant?
5-HT1a receptor agonist
5-HT1b receptor partial agonist
5-HT1d, 5-HT7, 5-HT3 antagonist
Increase extracellular serotonin, dopamine, NE, ACh, histamine in depression-related brain areas
How efficacious and safe is vortioexetine compared to other antidepressants?
Efficacious in treatment-resistant patients
Pro-cognitive effects
ADRs: similar to others but increase suicidal ideation in children and teens -> require close monitoring
