DDIs (antidepressants), Special Populations DOC Flashcards
[PD drug interactions]
CNS depression
Increase CNS depressant effects with alcohol and other CNS depressants (excessive sedation, drowsiness, toxicity)
- Space 4-6h apart with alcohol
[PD drug interactions]
Serotonin syndrome
- symptoms
- onset
- risk (drug examples)
Symptoms:
- Mental status change
- Neuromuscular changes
- Autonomic instability
Mild: insomnia, anxiety, nausea, diarrhea, hypertension, tachycardia, hyperreflexia (tendon knee jerk reflex)
Moderate: agitation, myoclonus, tremor, mydriasis, flushing, diaphoresis, fever <38.5
Severe: severe hyperthermia, confusion, rigidity, respiratory failure, coma, death
Onset: acute (within 6-8h)
Risk: coadministration of high-dose serotonergic drugs
- Triptans
- Opioids (Tramadol, Fentanyl, Pethidine)
- Dextromethorphan (moderate serotonin reuptake inhibitor)
- Linezolid, Ritonavir
- MAOi + serotonergic antidepressant (*importance of wash out when switching b/w them)
[PD drug interactions]
- Bleeding risk
SSRI increases the risk of bleeding by 1-2 folds
- higher risk in: elderly on NSAIDs, warfarin, steroids
- consider adding PPI
- consider stopping serotonergic antidepressant 2 weeks before surgery if high bleeding risk
- agomelatine is safest in terms of bleeding risk; may also consider bupropion, mirtazapine
FYI: SSRIs inhibit the serotonin transporter, which is responsible for the uptake of serotonin into platelets. It could thus be predicted that SSRIs would deplete platelet serotonin, leading to a reduced ability to form clots and a subsequent increase in the risk of bleeding
[PD drug interactions]
- Anticholinergic agents
Anticholinergic effects
[PK interactions]
- CYP1A2
Fluvoxamine is a CYP1A2 inhibitor
Ciprofloxacin (Quinolones), Macrolides, Isoniazid, Ketoconazole, are also CYP1A2 inhibitors
CYP1A2 substrates (incr AUC, serum conc.):
- Theophylline
- Amiodarone
- Warfarin (incr bleeding)
- Agomelatine (incr level, incr risk of transaminitis)
- Clozapine
- Phenothiazines (FGA)
[PK interactions]
- CYP2C19
Fluvoxamine is a CYP2C19 inhibitor
(also Fluoxetine, Moclobemide)
CYP2C19 substrate: Warfarin
[PK interactions]
- CYP2D6
CYP2D6 inhibitors:
- Fluoxetine
- Paroxetine
- Bupropion (also a substrate of CYP2B6)
- Duloxetine
CYP2D6 substrates:
- Metoprolol
- Codeine, hydrocodone, oxycodone, tramadol
- Risperidone, Olanzapine, Aripiprazole, Brexpiprazole
[PK interactions]
- CYP3A4
CYP3A4 inhibitors: Grapefruit juice, Macrolides, Azoles, PI (Ritonavir), Fluvoxamine (weak CYP3A4 inhibitor), Norfluoxetine, TCAs
CYP3A4 inducers: Rifampicin, CBZ, PHT, St Johns Wort
CYP3A4 substrates:
- simvastatin, lovastatin, nifedipine, amlodipine, diltiazem
- Risperidone, Quetiapine, Aripiprazole, Brexpiprazole
- mirtazapine
[PK interactions]
In general, which antidepressants have minimal CYP interaction?
- Mirtazapine - CYP3A4 substrate (major), CYP1A2, CYP2C9, CYP2D6 substrate, weak inhibitor of CYP2D6
- Escitalopram - substrate of CYP3A4 (minor), CYP2C19 (major)
- Venlafaxine/Desvenlafaxine - note that Venlafaxine is metabolised by CYP2D6 to desvenlafaxine
- Vortioxetine - substrate of CYP2D6 (major)
Pregnancy
Consider Nortriptyline in late pregnancy
Avoid Paroxetine and Bupropion
Breastfeeding
Consider Sertraline or Mirtazapine in breastfeeding
Postpartum depression
Brexanolone (GABA-A modulator)
Bipolar depression
Lithium
Lamotrigine
SGAs:
- Quetiapine
- Olanzapine + Fluoxetine (Symbyax capsule)
- Others (FYI): Lurasidone, Cariprazine
Renal impairment
Avoid Duloxetine, also Bupropion, Venlafaxine, Mirtazapine, Escitalopram, TCAs
May use: Vortioxetine, Paroxetine with caution
Hepatic impairment
Avoid Duloxetine and Agomelatine
Mild-mod: Vortioxetine
May also use: Paroxetine, Escitalopram with caution
