Fluoxetine Flashcards
Fluoxetine - Mechanism of action
- SSRI - increases serotonergic neurotransmission which results in desensitisation of serotonin receptors (1A)
- has an antagonist effect a serotonin 2C-R which increases norepinephrine/dopamin neurotransmission
FDA and OGYEI approved use in pediatric population
FDA:
- MDD (8+)
- OCD (7+)
- Bipolar depression (in combination with olanzapine)
OGYEI:
- MDD (8+)
How long does it take for fluoxetine to work?
2-8 weeks
Notable side effects of fluoxetine:
- CNS (insomnia/sedation/agitation/tremor/headache/dizziness)
- TEAS
- GI (dry mouth/decreases appetite/nauseaconstipation/diarrhea/weight loss)
- Sexual dysfunction (delayed ejaculation/erectile dysfunction/decreased sexual desire/anorgasmia)
- Sweating
- Bruising/rare bleeding (in combination with NSAID/aspirin/anticouagulants)
- SIADH
Dangerous side effects of fluoxetine
- Rare seizures
- Rare induction of mania
- Rare activation of suicidality
What is TEAS?
Treatment-emergent activation syndrome:
- hypomania
- agitation
- anxiety
- panic attacks
- hostility/aggression
- impulsivity
- insomnia
- suicidality
What can TEAS represent?
bipolar mania or the onset of suicidality
What to do upon detecting TEAS?
- decreasing the dose
- discontinuation (and switching)
- adding of another agent
Fluoxetine may be one of the […] activating agents in its class.
most
What to do if fluoxetine causes activation?
- administer dose in the morning
- consider temporary dose reduction (or a more gradual up-titration)
- consider adding a 5HT2A antagonist (trazodone or mirtazapine)
- consider adding a benzodiazepine short-term
- consider switching to another antidepressant
- optimize behavioral interventions
What is the rule of thump in augmentation vs. mono-therapy (antidepressants)?
Often best to try another mono-therapy prior resorting to augmentation strategies to treat side effects.
For insomnia (fluoxetine):
- consider adding melatonin
2. consider addig trazodone/mirtazapine
For GI upset (fluoxetine):
- try giving medication with a meal (or after the meal)
For sexual dysfunction (fluoxetine):
- reduce dose or try another agent
- daytime exercise
- (bupropion/buspirone)
- (cyproheptadine/mirtazapine)
For emotional flattening, apathy (fluoxetine)
- try adding bupropion with caution
When side effects are expected? (fluoxetine)
- In the first 2-3 weeks of starting or increasing the dose.
- They go away about the same time that therapeutic effects start.
How does fluoxetine cause side effects?
- increases serotonin concentrations in unwanted areas (e.g. sleep center, gut)
- increased serotonin cc. cause diminished dopamine release which contribute to emotional flattening, cognitive slowing, and apathy
- fluoxetine’s 5HT2C antagonist properties could contribute to agitation, anxiety, activation
Contraindications of fluoxetine:
Patient is taking:
- MAO inhibitor
- thioridazine
- pimozide
- tamoxifen
- has proven allergy to fluoxetine
Overdose of fluoxetine:
- rarely lethal in monotherapy overdose
- causes resp. depression/ataxia/sedation/seizures
Usual dose range and how to dose (fluoxetine):
- usual dose range: 10-80 mg/day
- doses higher than 20 mg/day may best administered in divided doses twice daily (morning and noon).
Pharmacokinetics of fluoxetine:
- norfluoxetine is the active metabolite (2 week half life)
- parent drug has 2-3 day half-life
- Inhibits CYP450 2D6/3A4/2C19
Drug interactions (fluoxetine):
- tramadol increases seizures in patients taking antidepressants
- can increase TCA levels
- may displace highly protein bound drugs (e.g. warfarin)
- in combination with sumatriptan (or other triptans) can rarely cause weakness, hyperreflexia, incoordination
- increased risk of bleeding when combined with anticoagulants (NSAID!!!)
- NSAID may impair the effectiveness of SSRIs
- CYP450 2D6 inhibition: can interfere with codein analgesic action/increase the plasma levels of beta blockers and atomoxetine/increase the cc. of thioridazine/may increase aripiprazole levels (!!!)
- may reduce the clearance of trazodone/diazepam
- CYP450 3A4 inhibition: could theoretically increase the cc. of HMG COA reductase inhibitors/pimozide
