Antidepressants Flashcards
How do the MAOIs result in therapeutic effects?
Inhibit monoamine oxidase to increase biological availability of monoamines – counteract deficits in monoamine neurotransmitters
- MAO-A: noradrenaline, dopamine, 5-HT (Serotonin)
- MAO-B: noradrenaline and dopamine only
(moclobemide - reversible antagonism)
What are the adverse effects of MAOIs
- Postural hypotension – likely due to sympathetic block produced by accumulation of dopamine in the cervical (neck) ganglia, where it acts as an inhibitory transmitter
- Restlessness and insomnia – due to CNS stimulation
- Should not be combined with other drugs enhancing serotonergic function (e.g. pethidine) – can result in hyperexcitability, inc muscle tone, myoclonus (jerking, involuntary movements), loss of consciousness
How does the interaction between MAOIs and cheese work?
- Amines (e.g. tyramine) in foods are usually broken down by MAO in the intestines and liver
- Inhibition of MAO allows them to exert sympathomimetic effect – tyramine gets taken into adrenergic terminals , competes w NA for vesicular compartment, ↑NA release to synapses
- Less likely with reversible MAO-A selective MAOIs (e.g. moclobemide)
What is the MOA of the TCAs?
Blocks reuptake of NA and 5-HT
Non-selective for Serotonin and Norepinephrine Transporters: Imipramine, Amitriptyline, Nortriptyline
Selective for Norepinephrine Transporter: Desipramine
What are the adverse effects of the TCAs?
Sedation – due to H1 histamine receptor antagonism
* Tolerance to sedation can develop in 1-2 weeks
Postural Hypotension – due to α-adrenoreceptor sympathetic block
Dry mouth, blurred vision, constipation – due to muscarinic receptor antagonism
What are the advantages of SSRIs?
- Low affinity for α-adrenoreceptors – lack of CV effects, safer in overdose
- Lack of effect at histamine receptors – reduced sedation
- Low affinity for muscarinic cholinergic receptors – minimal anticholinergic SE
- Due to less side effects, able to prescribe more adequate doses (compared to TCAs that are frequently used at subtherapeutic doses due to intolerability of adverse effects)
What is the MOA of SSRIs?
Selectively blocks reuptake of 5-HT
What are the adverse effects of SSRIs?
→ Nausea
→ Insomnia
→ Sexual dysfunction
→ Citalopram still has some histamine receptor antagonism leading to sedation
→ Serotonin Syndrome – DDI with other drugs increasing serotoninergic activity
(Tremor, Hyperthermia, Cardiovascular collapse)
What is the MOA of SNRIs?
Blocks reuptake of NA and 5-HT
What are the adverse effects of SNRIs?
→ Serotoninergic adverse effects similar to SSRIs: nausea, insomnia, sexual dysfunction
→ Serotonin syndrome when combined with other serotoninergic drugs
→ Withdrawal effects may be more common and stronger than for SSRIs and TCAs
What is the MOA of mirtazapine?
→ Norepinephrine and specific serotonin antidepressant
→ Antagonist of adrenergic α2 autoreceptors and 5-HT2C receptors, among others
What is the MOA of bupropion?
Blocks reuptake of NA and DA
What is the MOA of agomelatine?
MT-1, MT-2 agonist
5-HT2C antagonist
↑DA and NA
What is the MOA of ketamine?
Glutamate NMDA agonist used as anaesthetic, currently evaluated for rapid onset antidepressant effect
What is the MOA of vortioxetine?
Multimodal serotonergic antidepressant – novel class
* Agonist activity at 5-HT1A receptor
* Partial agonist activity at the 5-HT1B receptor
* Antagonism at 5-HT1D, 5-HT7, and 5-HT3 receptors
Additional receptor affinities may ↑release of serotonin and release other neurotransmitters
May be efficacious in patients resistant to other antidepressants
May also have pro-cognitive effects
How long is an adequate trial of acute phase treatment?
4-8 weeks, max 12 weeks
How long does it take for treatment response to show up?
- Physical Sx may improve in 1-2 weeks – eg sleep, appetite
- Mood Sx may take longer time to improve eg 4-8 weeks
How long should continuation phase treatment last?
1st episode of uncomplicated MDD – continue for at least another 4-9 months after acute phase Tx
What are the strategies to manage partial/lack of response?
- Switch antidepressant
- Augmentation
Treatment-Resistant Depression – no response to ≥2 adequate trials of antidepressants: ECT, combination therapy
How can antidepressants be switched?
→ If cross-titration – watch for serotonin syndrome if combining serotonergic agents
→ If direct switch, one SSRI can be stopped totally and the next serotonergic agent initiated
→ If switching from a serotonergic antidepressant used daily for the past 2 months to a non-serotonergic agent (eg SSRI/SNRI to bupropion), gradual cross-tapering over several weeks can reduce risk of Antidepressant Discontinuation Syndrome (by half tab Q1-2 weeks)
→ Moclobemide to another antidepressant: 24h washout
→ Another antidepressant to moclobemide: at least 1 week (5 weeks if stopping fluoxetine)
What are the symptoms of Antidepressant Discontinuation Syndrome?
FINISH
Flu-like symptoms – lethargy, fatigue, headache, achiness, sweating
Insomnia – w vivid dreams or nightmares
Nausea – sometimes vomiting
Imbalance – dizziness, vertigo, light-headedness
Sensory disturbances – “burning”, “tingling”, “electric-like” sensations
Hyperarousal – anxiety, irritability, agitation, aggression, mania, jerkiness
How long does Antidepressant Discontinuation Syndrome last for?
3-7 days
How is Antidepressant Discontinuation Syndrome managed?
Typically resolves over 1-2 weeks w/o Tx
(Pt may feel some discomfort, but unlikely to be life threatening)
What are the considerations in pregnancy?
consider nortriptyline in late pregnancy
What are the considerations for breastfeeding?
can consider sertraline or mirtazapine
What are the considerations for post-partum depression?
brexanolone (positive allosteric modulator of GABA)
What are the preferred agents for bipolar depression?
lithium, lamotrigine, lurasidone, quetiapine etc
What are the considerations for renal impairment?
may consider vortioxetine
What are the considerations for hepatic impairment?
Avoid agomelatine. If mild-moderate, can consider vortioxetine
