Depression Flashcards
What is the DSM-5 diagnostic criteria for MDD?
At least 5 symptoms of IN SAD CAGES have to be present during the same 2-week period, causing significant distress or functional impairment.
Symptoms not caused by an underlying medical condition or substance
What does the acronym “IN SAD CAGES” stand for?
INterest - decreased interest and pleasure in normal activities
Sleep - insomnia or hypersomnia
Appetite - decreased appetite, weight loss
Depressed mood
Concentration - impaired concentration and decision making
Activity - psychomotor retardation or agitation
Guilt - feelings of guilt or worthlessness
Energy - decreased energy or fatigue
Suicidal thoughts or attempts
What is the treatment for mild depression?
Non-pharmacological management.
Antidepressants are NOT indicated in mild depression
What are the non-pharmacological management options for depression?
Sleep hygiene to improve sleep habits
Psychotherapy
Neurostimulation (electroconvulsive treatment (ECT) or rTMS for severe/refractory cases)
When are anti-depressants indicated?
For moderate-severe depression
How is treatment usually initiated for patients with moderate to severe depression?
Antidepressants + Adjunctive meds (+ non-pharm)
How are antidepressants selected?
Select antidepressant based on target symptoms, comorbid conditions, drug interactions, prior response, preference
What are adjunctive medications, why are they needed and what are examples of them?
Prescribed short course of PRN hypnotics/anxiolytics as antidepressants do not work very fast; some symptoms such as insomnia may require more rapid relief and so patients may benefit from a short course of sleeping pills
First line antidepressant monotherapy
SSRI, SNRI, Mirtazipine or bupropion (1st 3 are subsidised → affordable)
What are the phases of treatment for depression?
Initiation
Acute phase treatment
Continuation phase
How long does acute phase treatment last and why does it require this length of treatment?
4-8 weeks; there is delayed onset due to down-regulation of pre-synaptic autoreceptors
What is the definition of adequate trial in acute phase treatment?
Adequate dose and adequate duration
During the acute phase, when can patients start to see improvements in symptoms?
1-2 weeks for physical symptoms (eg sleep, appetite)
4-6 weeks for mood symptoms
What is the continuation phase?
Continuation of the drug dose from acute phase for at least 4-9 months more
What is the total duration of treatment before we take a patient off antidepressants?
6-12 months (1-2 months to titrate dose, then 4-9 months to continue treatment)
What are the classes of antidepressants?
TCA (amitriptyline, clomipramine)
SSRI (fluoxetine, fluvoxamine, escitalopram)
SNRI (venlafaxine, duloxetine)
SMS - serotonin modulators and simulators (vortioxetine)
NaSSA (mirtazipine)
RIMA - reversible inhibitor of monoamine oxidase A (moclobemide)
NDRI (bupropion)
Melatonin receptor agonist (agomelatine)
Which class of antidepressants can also be used to treat anxiety disorders?
Drugs that oromote serotonin
Examples of SSRIs
fluoxetine, fluvoxamine, escilatopram, citalopram, paroxetine, sertraline
Examples of SNRIs
venlafaxine, desvenlafaxine, duloxetine
Which drug is almost identical in structure to venlafaxine?
Tramadol (and thus many SNRIs have pain relief properties as well)
What are the other indications of duloxetine?
Diabetic neuropathy, stress urinary incontinence, fibromyalgia, chronic musculoskeletal pain
Why are tricyclic antidepressants not good for elderly?
Very anticholinergic - can cause delirium, constipation and urinary retention
Very sedating and hypotensive
What are examples of TCAs?
Amitriptyline
Nortriptyline
Clomipramine
Imipramine
What is an advantage of TCAs?
Track record of efficacy and safety for anxiety and depressive disorders
Relatively safe for use in pregnancy
MOA of TCAs?
Inhibit reuptake of noradrenaline and serotonin but also antagonise the cholinergic, histaminic, alpha adrenergic receptors
Side effects of TCAs
GI and sexual dysfunction (due to serotonin)
Anticholinergic: constipation, dry mouth, urinary retention, blurred vision, delirium in elderly
Antihistaminic: sedation and weight gain
Alpha1 adrenergic antagonism: orthostatic hypotension
Arrythmias, seizures, can be fatal on overdose
MOA of SSRIs?
Blocks reuptake of 5HT selectively
Which SSRI has concerns for QTc prolongation?
Escitalopram and citalopram
Which SSRI leads to the most weight gain and sedation?
Paroxetine
What black box warning does venlafaxine have?
Increased high blood pressure
What are the side effects of SNRIs?
GI and sexual dysfunction
Increased blood pressure
What are the side effects of vortioxetine?
Sexual dysfunction and GI
What additional agonism does vortioxetine provide?
5HT1A receptors
What is the MOA of mirtazipine?
It antagonises the presynaptic autoreceptors which directly induces downregulation and also increases the release of serotonin and NE.
Does mirtazipine have the side effect of sexual dysfunction and N/V?
They reverse the sexual side effects of serotonergic agents, as they antagonise the 5HT2 and 5HT3 receptors.
Receptor activity of mirtazipine
Antagonises presynaptic autoreceptors
Antagonises 5HT2 and 5HT3 receptors
Antihistaminic activity - sedation and weight gain
Side effects of mirtazipine
increased appetite, weight gain
What is the MOA of buproprion?
It is a noradrenaline and dopamine reuptake inhibitor.
What other indications for buproprion are there?
Smoking cessation (increase in dopamine in the brain tells the brain to reduce craving for substances)
What are the adverse effects of buproprion?
Seizures → do not give to those with epilepsy or prone to seizure.
Not suitable for eating disorders or psychosis
NO sexual dysfunction or GI effects as it avoids the serotonergic pathway.
Name the classes of antidepressants with sexual dysfunction and GI related side effects.
SSRIs, TCA, SNRI, SMS
What is the mechanism of action for mocloblemide?
Reversible MAO A inhibitor
Adverse effect related to irreversible non-selective MAO inhibitors such as phenelzine?
Hypertensive crisis
How long are benzodiazepines typically given for as adjunct therapy for depression?
2 weeks ; need to counsel to prevent dependency
MOA of benzodiazepines
Potentiates GABA
Side effects of benzodiazepines
Sedation, drowsiness, amnesia
Examples of Z-Hypnotics
Zolpidem, Zopiclone
SE of Z-hypnotics
Taste disturbance, complex sleep behaviors (sleep walking)
Advantage of Z-hypnotics over benzodiazepines?
Binds preferentially to gamma and alpha1 subunits that causes sedation but does not bind to other subunits that causes anxiolysis, muscle relaxant, cognitive impairment
Females take the same dose as males for zolpidem, true or false?
False.
Females need half dose
What are antihistamines used for? What side effects do they have?
Its sedating properties
Anticholinergic → dry mouth, constipation
What antihistamines are used for adjunctive therapy?
Promethazine or hydroxyzine
Which second generation antipsychotics are used for adjuncts to antidepressants?
Aripiprazole, brexipiprazole, quetiapine XR
What is esketamine used for?
Nasal spray. treatment resistant depression
Adjunct to SSRI/SNRI
Which herbs should be avoided in depression?
St Johns Wort - significant drug interactions with antidepressant
What are the ways of switching to alternative antidepressants?
Direct switching - one SSRI is stopped totally and the next serotonergic agent initiated
Cross-titration - Decreasing one drug while increasing the new drug (watch out for serotonin syndrome if combining two agents)
When do you switch to alternative antidepressants?
If it is ineffective or patient is intolerable of adequate dose in 1-4 weeks
What should you do when switching from a serotonergic antidepressant to a non-serotonergic agent?
Gradual cross-tapering over several weeks to reduce the risk of Antidepressant Discontinuation Syndrome
What are the approaches to managing partial/no response?
Switch antidepressants
Augmentation (combining a 2nd antidepressant with different MOA)
For TRD: neurostimulation (ECT or rTMS), spravato nasal spray, symbax oral capsule
What agents are typically used when combining to an existing antidepressant with a partial response?
Augmentation - use mirtazipine, bupropion, quetiapine XR, aripiprazole, brexpiprazole (avoids serotonin syndrome)
What antidepressant can be used in late pregnancy?
Nortriptyline
What antidepressant can be used during breastfeeding?
Sertraline or mirtazipine
Which antidepressants should be avoided in elderly?
TCAs and anticholinergic, CNS, hypotensive or other cardiac SE
Why must we monitor serum sodium at baseline, 2nd week, 4th week then 3 monthly for elderly?
Due to risk of hyponatremia (SIADH) that is associated with all antidepressants, mostly reported for SSRI
Association to suicidality in patients at less than how many years old?
Association to suicidality in patients <24 years old
require counselling to patients and caregivers for close monitoring, regular review
What are examples of PD DDIs seen with antidepressants?
- Serotonergic + serotonergic = serotonin syndrome
- SSRIs: increase risk of bleeding, with NSAIDs, warfarin, steroids
- Increased CNS depressant effects with alcohol and other CNS depressants
- Anticholinergic agents cause excessive anticholinergic effect
What is the onset of serotonin syndrome
Acute (6-8 hours)
What should you do for a patient with high bleeding risk going for surgery?
Consider stopping serotonergic antidepressant 2 weeks before surgery
Agomelatine safest
Counselling points for CNS depressant effects?
Do not take medication at the same time as alcohol, seperate them 4-6 hours apart
Avoid taking benzodiazepines together with opioids (increased mortality)
Which antidepressant is a CYP1A2 inhibitor?
Fluvoxamine
Which antidepressant is a 2C19 inhibitor?
Fluvoxamine
Which antidepressants are cyp2d6 inhibitors?
Fluoxetine, paroxetine, bupropion
Which antidepressants have fewer CYP interactions?
Mirtazipine, escitalopram, venlafaxine, dexvenlafaxine, vortioxetine
Antidepressant discontinuation syndrome is an example of a withdrawal syndrome - t/f?
False.
There is no craving involved
Symptoms of antidepressant discontinuation syndrome?
Within 36-72 hours: FINISH Flu-like symptoms (fatigue, muscle aches, headache) Insomnia Nausea Imbalance - dizziness Sensory - 'electric shock' sensations Hyperarousal - anxiety, agitation
Which drugs tend to lead to antidepressant discontinuation syndrome?
Short half life antidepressants - paroxetine, venlafaxine
What should you do when you need to stop a long-term antidepressant therapy to minimise antidepressant discontinuation syndrome?
Gradually taper over at least 4 weeks
Which drugs do not require tapering to prevent antidepressant discontinuation syndrome?
Long half lives - fluoxetine, bupropion
How should someone come off benzodiazepines?
Gradual discontinuation of long term high dose use
What are counselling points for patients with antidepressant therapy?
- Antidepressants may take at least a couple of weeks to help with symptoms of low mood, poor sleep and appetite
- Do not take at the same time as alcohol (space 4-6 hours apart)
- Tell your Drs, nurses and pharmacists the medicines you are using
- If you feel your condition is worsening, or feeling suicidal, agitated, or experiencing bothersome and persistent side effects, contact Dr asap
- Possible side effects -drowsy, insomnia, dizzy/light-headedness, stomach upset, changes in sexual function
Which drugs are less likely to cause sexual dysfunction?
Mirtazapine, bupropion, agomelatine (does not work on serotonin)
What are the treatment goals for MDD?
Remission of symptoms, treatment adherence, suicide prevention.
Non-pharmacological therapy for MDD
Psychotherapy, sleep hygiene, severe MDD may require neurostimulation (ECT)
Order of antidepressants
SSRI, SNRI, NaSSA, Bupropion > agomelatine, vortioxetine > TCA > MAOIs
