Antidepressants Flashcards
What medications are associated with prolonged QTc?
TCAs Lithium SSRIs Venlafaxine (SNRI) Macrolides e.g. erythromycin and clarithromycin Sotalol Methadone
Name the different types of antidepressants
MAOIs TCAs SSRIs SNRIs NaSSA - NA and specific serotonergic antidepressant (Lithium)
Which patient groups should you be more cautious with prescribing antidepressants?
Renal or hepatic impairment - excretion and metabolism Cardiac problems - prolong QTc Epilepsy - increased risk of seizures Pregnant or breastfeeding Elderly or children
How should antidepressant switching occur?
Cross-tapering: reduction of old antidepressant whilst increasing the new antidepressant.
Aim is to minimise the fluctuation of serum antidepressant levels to reduce the risk of side effects and behavioural changes.
Name 2 MAOIs
Isocarboxazid
Phenelzine
Describe the mechanisms of action of MAOIs
Irreversible inhibition of MAO-A and MAO-B ➔ accumulation of monoamines (particularly dopamine and serotonin) in the synaptic cleft
Why has Phenelzine been discontinued?
‘Cheese reaction’
Hypertensive crisis due to accumulation of tyramine which is found in cheese, wine, and other foods.
Avoid indirect sympathomimetics.
Name 3 side effects of MAOIs
Risk of hypertensive crisis Postural hypotension and dizziness Euphoria Antimuscarinic effects Hepatotoxicity Insomnia Anxiety
List 2 cautions for MAOIs
Poorly controlled hypertension
Hyperthyroidism
List 2 contraindications for MAOIs
Pheochromocytoma
Stroke
What should be monitored if taking a MAOI?
Blood pressure - postural hypotension and HTN crisis
Name 2 TCAs
Amitriptyline - also used for neuropathic pain
Clomipramine - 2nd line OCD Tx
Imipramine
Trimipramine
Describe the mechanism of action of TCAs
Serotonin and NA reuptake inhibition
Name 3 side effects of TCAs
Sedation Impaired psychomotor function Antimuscarinic effects CVS: tachycardia, postural hypotension, prolonged QTc sudden cardiac death Lowers seizure threshold Weight gain
Why is TCA toxicity dangerous?
TCAs are cardiotoxic in overdose.
Most: Amitriptyline
Least: Lofepramine
What monitoring is advised when taking TCAs?
Cardiac and liver function
Longterm: U&Es, FBC, weight
Name 3 SSRIs
Sertraline
Fluoxetine
Paroxetine
Citalopram - prolongs QTc
Describe the mechanism of action of SSRIs
Inhibit the reuptake of serotonin ➔ accumulation in the synaptic cleft
Name 3 side effects of SSRIs
Nausea GI upset Agitation - early onset Sexual dysfunction Anorexia Vivid dreaming Prolonged QTc SIADH ➔ dilution hyponatraemia
Rare: Mania, increased suicidal ideation and self-harm (under 30s), EPSP
What are the extrapyramidal side effects?
Akathisia - restlessness
Tardive dyskinesia - involuntary twisting of facial muscles, late onset, can involve extremities (hands > feet)
Acute dyskinesias and dystonic reactions
Parkinsonism - rigidity, pill rolling tremor, bradykinesia
Akinesia
What is neuroleptic malignant syndrome?
Life-threatening reaction (10% mortality) in response to neuroleptic medication (within 1 month of starting).
Characterised by tetrad of: fever*, muscle rigidity, altered mental state, and autonomic dysfunction. Typically develops over a few days.
Tx: stop causative drug + ICU care
What is the consequence of SSRI toxicity
Serotonin syndrome:
Restlessness, XS sweating, tremor, shivering, myoclonus, confusion, convulsions, death
Which SSRI has the highest risk of Serotonin syndrome and why?
Paroxetine due to its short half life.
What should be monitored when taking SSRIs?
Risk of suicide, as SSRIs can increase the risk.
Name 2 SNRIs
Venlafaxine
Duloxetine
Describe the mechanism of action of SNRIs
Inhibits reuptake of serotonin and noradrenaline
Name 3 side effects of SNRIs
Same SE as SSRIs: Nausea, GI upset, sexual dysfunction, anorexia, vivid dreams, prolonged QTc
Additional: Sleep disturbances, hypertension, dry mouth, hyponatraemia
What are the indications for Duloxetine?
Major depression
GAD
Diabetic neuropathy
Stress urinary incontinence (moderate-severe)
What are the indications for Venlafaxine?
Major depression
GAD
Social phobia
What are the indications for Sertraline?
Depression
OCD
Panic disorder, PTSD, Social phobia
What are the indications for Fluoxetine?
Major depression
Bulimia nervosa
OCD
What are the indications for Paroxetine?
Major depression
OCD
Social phobia, PTSD, GAD, Panic disorder
What are the indications for Citalopram?
Depression
Panic disorder
Name 1 NaSSa
Mirtazapine
What are the indications for Mirtazapine?
Major depression
PTSD
Describe the mechanism of action for NaSSa
5-HT and alpha receptor antagonist
*Mirtazapine also blocks histamine receptors
Name 3 side effects of NaSSa
Common: Sedation (greater at lower dose)
Increased appetite and weight gain
Uncommon: Transaminase elevation, jaundice, postural hypotension, closed angle glaucoma
Rare: Agranulocytosis
Name 2 contraindications of NaSSa
Renal impairment
Hepatic impairment
Jaundice
Pregnancy
What is the benefit of Mirtazapine’s mechanism of action?
It differs from other antidepressant mechanisms. Therefore it can be used in combination with SSRIs or Venlafaxine, without increasing the risk of serotonin syndrome.
Which situation would most benefit from the action and side effects of Mirtazepine?
Depression with insomnia - sedation side effect
Depressive reduced appetite - weight gain and increased appetite side effect
Which medication is used for treatment-resistant depression?
Lithium
What are the indications of Lithium?
Treatment resistant depression (Tx and prophylaxis)
Bipolar affective disorder (gold standard Tx)
Mania (Tx and prophylaxis)
Aggressive or self-harming behaviour
What property of Lithium is especially useful in depression?
Lithium decreases suicidal ideation
List 3 side effects of Lithium
NaV
GI disturbances - diarrhoea
Fine tremor
Diabetes insipidius - polyuria and polydipsia
Weight gain
Thyroid problems (Female 8:1)
Teratogenic - Ebstein’s anomaly (cardiac)
Mild renal impairment ➔ risk of chronic renal failure
Describe the presentation of Lithium toxicity
Seizures Dysarthria Reduced consciousness, coma Ataxia Coarse tremor Acute kidney injury
What ECG changes are seen with Lithium?
Flattened T wave
Wide QRS
Prolonged QTc
What drugs increase lithium plasma concentration?
ACEi/ARBs NSAIDs SSRIs and other antidepressants Diuretics (and dehydration) Haloperidol and other antipsychotics
What drugs decrease lithium plasma concentration?
Antacids - neutralise stomach acid
Theophylline - COPD and Asthma
What is the DDI between SSRIs and NSAIDs?
Increased risk of GI bleed.
If using both, give a PPI.
Which TCA has the highest risk of antimuscarinic side effects?
Imipramine
Which SSRI is first line treatment for children and adolescents?
Fluoxetine
What monitoring is required when taking Lithium?
Blood monitoring taken 12h after each dose change
ECG
TFT (6 monthly)
U&E (6 monthly)
How long should antidepressants be continued once depression (1st episode) has enter remission?
Continue for 6 months after remission
How long should antidepressants be continued once depression (2nd episode) has enter remission?
Continue for 2 years after remission
What is the effect of hyponatraemia on lithium?
Hyponatraemia can reduce renal excretion of lithium -> increased risk of lithium toxicity
