Antidepressants (PSYCH DRUGS) Flashcards
First-line antidepressant
SSRI - selective serotonin receptor inhibitor (few SE because selective action on serotonin alone)
SSRI
1. Full name
2. MOA
Selective Serotonin Reuptake Inhibitor
- MOA: block serotonin reuptake by transmitting neurons -> elevated serotonin levels in synaptic space -> prolonged action on receiving neuron
SSRI side effects - common AND uncommon
Common
1. Anxiety
2. Insomnia
3. Headache
4. Nausea
5. Diarrhea
6. Sexual dysfunction
Uncommon
1. Antidepressant-induced hypoNa (common in old people, manifestations: lethargy, muscle ache, nausea, more severe- cardiac failure, confusion, seizure)
2. GI bleed/GI ulcer
3. Serotonin syndrome (applies to antidepressants as a class)
SSRI indications
- Depression with anxiety/obsessional symptoms
- Depression in elderly (due to benign SE profile)
- Suicidal pt (safe in OD)
- (conditions with serotonin deficiency) Panic disorder, social anxiety disorder, PTSD, OCD, bulimia nervosa
SSRI examples AND dose
x5
1. Fluoxetine (20 mg OM)
2. Fluvoxamine (50 mg OM to 50 mg BD)
3. Paroxetine (20mg OM)
4. Sertraline (50mg OM)
5. Escitalopram (10mg OM)
SNRI Full name + MOA
Serotonin noradrenaline reuptake inhibitor
MOA: dual action - block serotonin and noradrenaline reuptake transporters
SNRI side effects
Similar to SSRI PLUS adrenergic SE
- Anxiety
- Nausea
- # Sexual dysfunction
- Tachycardia, HTN, mydriasis, diaphoresis
- Dry mouth
- Constipation
SNRI example and dose
- Venlafaxine (75mg/day)
- Desvenlafaxine (50mg/day)
- Duloxetine (60mg/day)
SNRI indications
- Depression
- Generalised anxiety disorder
- Pain symptoms in depression
Duloxetine added benefits
Effect on pain symptoms in depression eg. Back ache
Which SNRI has Discontinuation symptom?
Venlafaxine
TCA MOA
MOA: dual action - block both serotonin and noradrenaline transporters PLUS block cholinergic, histamine, alpha-adrenergic receptor, sodium channel ***dirty drug!! broad spectrum
TCA side effect
- Dry mouth, tachycardia, memory impairment (bad for elderly), acute closed angle glaucoma [muscarinic M1 receptor blockade]
- Sedation, weight gain [block histamine receptor]
- Postural hypotension [block alpha adrenergic receptor]
- Arrythmia ***overdose + wide QRS complex = TCA OD seizure [block Na channel]
TCA efficacy, safety
Efficacy: superior to other antidepressants
Safety: highly lethal in OD (VF, seizure 2’ to Na channel blockade)
TCA indication
- Severe depression (superior to newer agents)
- Specific dx (chronic pain, fibromyalgia, migraine, insomnia) - use amitriptyline
- Specific dx (OCD) - use clomipramine
Avoid TCA in
- Elderly
- Physically ill
- The suicidal (if really need to prescribe, do safety advice - family keep drugs for pt)
TCA examples and dose
x4
1. Amitriptyline (25-150mg)
2. Imipramine (25-150mg)
3. Dothiepin (25-150mg)
4. Clomipramine (25-100mg)
Noradrenaline Dopamine Reuptake Inhibitor MOA
MOA: block both dopamine and noradrenaline reuptake transporters
Noradrenaline dopamine reuptake inhibitor example AND dose
Bupropion 150mg/day
Noradrenaline dopamine reuptake inhibitor/Bupropion Side effects
- Insomnia, agitation, anxiety (as a result of overstimulation ***rmb that bupropion can be used in ADHD!)
- Seizures (due to effects of elevated dopamine levels on seizure threshold)
Has NO effect on sexual dysfunction
Noradrenaline dopamine reuptake inhibitor Indications
- Depression with anhedonia
- Depression with fatigue
- Smoking cessation
- ADHD (child psych)
Avoid noradrenaline dopamine reuptake inhibitor (bupriopion) in
- Anxiety disorders
- Panic attacks
- Seizures
NaSSA full name + MOA
Noradrenergic and Specific serotonergic antidepressant **diff from SNRI (block reuptake transporter) VS NaSSA (block receptors)
MOA: x3
1. Block presynaptic alpha 2 receptors of noradrenergic AND serotonergic pathways (which are normally responsible for -ve feedback) -> increases noradrenergic and serotonergic neurotransmission
2. Block postsynaptic serotonin 5HT2 AND 5HT3 receptors
3. block histamine 1 receptor -> sedating effect
Side effects of NaSSA (Mirtazapine)
- Sedation, weight gain (antihistaminergic effects)
***NO insomnia, nausea, sexual dysfunction (due to selective activity; increased serotonin binds to desired 5HT receptor ie. 5HT1A to exert therapeutic effect
NaSSA indications
- Antidepressant, anxiolytic effect
- Depression with anxiety, insomnia, weight loss
- Commonly used in elderly
- No CYP450 inhibition -> less likely for drug drug interaction
NaSSA example AND dose
Mirtazapine (30mg/day)
Agomelatine MOA
Melatonin receptor agonist (active melatonin 1&2 receptors in suprachiasmatic nucleus of hypothalamus -> restore circadian rhythms -> resynchronise disturbed sleep/wake cycle in depressed pt
Agomelatine side effects
- Common: dizziness
- Rare: hepatitis
No daytime sedation, sexual dysfunction, weight gain
Safe in overdose
Indications for agomelatine
- Depression with sleep disturbance
- Depression with fatigue
Agomelatine dose
25-50mg/day
MOAI full name + MOA
Monoamine oxidase inhibitors (MAOI)
MOA: irreversibly inhibit monoamine oxidase -> both serotonergic AND noradrenergic pathways involved
**THIRD LINE (extensive SE profile)
MAOI side effect
- Hypertensive crisis
- Serotonin syndrome (interaction with serotonergic drugs)
MAOI examples
X4
1. Selegiline
2. Isocarboxazid
3. phenelzine
4. Tranylcypromine
RIMA full name + MOA
Reversible inhibitor of monoamine oxidase A (RIMA)
- MOA: reversibly and selectively inhibit the enzyme MOA
RIMA side effect
- Insomnia
Reduced risk of hypertensive crisis compared to MAOI
Multimodal drugs examples AND dose
- Vortioxetine (10mg/day)
- SARI (serotonin antagonist/reuptake inhibitor)
Vortioxetine MOA
- multimodal drug
MOA: x2
1. Block serotonin receptor
2. Multiple actions on serotonin receptor -> downstream effect of adrenaline and acetylcholine in specific area of brain (pro-cognitive effect too)
Vortioxetine side effect
Generally q tolerable
1. Nausea
2. Low sexual dysfunction
No insomnia or weight gain
Vortioxetine indication
Depression with cognitive dysfunction (rumination, indecision, inattention, poor conc)
SARI full name + MOA
Serotonin antagonist/reuptake inhibitor
MOA: x4 it is a serotonin modulator
1. Blocks post synaptic serotonin 5HT2A receptors robustly
2. Blocks presynaptic serotonin reuptake transporter weakly
3. Blocks histamine 1 receptor (-> sedating effect)
4. Blocks alpha adrenergic receptors (-> orthostatic hypotension, priapism)
SARI side effects
- Sedation
- Orthostatic hypotension and priapism
- Cardiac arrhythmias
SARI indications
- Hypnotic for insomnia in depression (lower dose as hypnotic: 25-150mg)
- Antidepressant dose higher 150-600ng (but hard to tolerate cause too sedated)
Serotonin syndrome symptoms
- Tremor
- Agitation (mental state)
- Hyperreflexia, clonus (Neuromuscular hyperactivity)
- HTN, tachycardia, diaphoresis, mydriasis (Autonomic hyperactivity)
Dangerous complication of combination SSRI use?
Serotonin syndrome
Strong inhibitors of CYP450 2D6
Bupropion, fluoxetine, paroxetine
Concern with propranolol (beta blocker) and fluoxetine (SSRI)?
Fluoxetine: strong CYP2D6 inhibitor
Beta blocker: major substrate of CYP2D6
Thus beta blocker in body system will increase due to inhibition of metabolism of propranolol
Concerns with fluoxetine and phenytoin
Fluoxetine: moderate inhibitor CYP2C19
Phenytoin: major substrate of CYP2C19
Although fluoxetine moderate inhibitor, phenytoin has narrow therapeutic index
Antidepressant discontinuation symptoms onset and symptoms
Onset: 3-5 days of stopping half-life antidepressant
Symptoms: x4
1. Dizziness
2. Headache
3. Insomnia
4. Irritability
Antidepressants prone to discontinuation symptoms
- Fluvoxamine
- Paroxetine
Why the need to recognise discontinuation symptoms?
May mistaken for new physical illness
What is the Black box warning?
Antidepressant for first few weeks: Increased risk of suicidality (for children and adults up to 24 years of age)
Antidepressants that cause MINIMAL sexual dysfunction
- Mirtazapine
- Bupropion
SARI examples of drug
- Trazodone
- Nefazodone
Key symptom: anxiety
Preferred antidepressant?
SSRI or SNRI
Eg. Setraline (SSRI)
Key symptom: cognitive difficulties (learning, memory, decision-making)
Preferred antidepressant?
- Duloxetine
- Vortioxetine
Key symptom: sleep disturbances eg insomnia
Preferred antidepressant?
- Mirtazapine
- Agomelatine
Key symptom: fatigue
Preferred antidepressant?
Bupropion
Key symptom: pain
Preferred antidepressant?
Duloxetine, TCA
Key symptom: melancholia (psychomotor retardation, diurnal mood variation)
Preferred antidepressant?
TCA