ADHD and Migraine Flashcards
What is the efficacy of stimulants as a treatment of ADHD?
Treatment with medication or in combination with medication + behavioral therapy is significantly better than behavioral therapy alone (or no intervention either).
However, in the long-term, there is no significant difference in outcomes, and kids tend to function worse than their peers.
What are two stimulants used in the treatment of ADHD and how do they work?
Methylphenidate (Ritalin) and amphetamine (Adderall)
Work by reversing VMAT-2 as well as DAT/NET to cause increase in NE/DA in the synapse
Does D-amphetamine have similar effects in normal people as those with ADHD?
Actually yes - so it’s unlikely to be due to a DAT transporter overexpression problem
Reduces activity, inattention, and impulsivity
What is meant by double-pulse administration of stimulants and why does this need to be done?
Short-acting formulation with a long-acting / extended release capsule inside.
Half-life is only 3-5 hours so you would normally need multiple doses in the day
Take in the morning for instant therapeutic effect early in the day, which lasts throughout the day due to XR
What are the adverse effects of the stimulants?
Decreased appetite / weight loss (diet pills)
Delayed sleep onset, insomnia
Anxiety / irritability
Stomach aches / headaches
What is a side effect of concern for children with stimulants?
May cause long-term growth retardation
What drug was originally marked as an antidepressant but is now used less efficaciously against ADHD?
Atomoxetine
Norepinephrine reuptake inhibitor (NRI)
How is Atomoxetine metabolized?
CYP2D6
What are the adverse effects of Atomoxetine?
Nausea, vomiting, and sleepiness
Important warning: Increased suicide risk
What are the alpha-2 agonists which are used for treatment of ADHD and how does this work?
- Guanfacine
- Clonidine
Works by inhibiting NT release, thereby strengthening regulation pathways in the prefrontal cortex
What is the last class of drugs used to treat ADHD?
Antidepressants - i.e. bupropion
How is migraine distinguished from other types of headache? What are the other features of migraine?
Presence of prodrome or aura
Generally unilateral
Associated with nausea and vomiting
Intense enough to interrupt daily activities
Can last up to three days untreated
What is the most important way to prevent migraines and who does it disproportionately affect?
Recognize the triggers
Affects women 3x as much as men
What causes the aura in migraine?
Cortical spreading depression (CSD) which is a slowly propagating wave of depolarization across the cortex
-> happens in only a fraction migraines
What is the consensus today about what triggers migraine?
Sensitization of the trigeminal afferents, especially those which supply the area around the cranium. This leads to the activation of nociceptive neurons
What are the drugs of choice for mild-moderate migraine?
NSAIDs or combinations of NSAIDs with codeine / hydrocodone
What are the drugs of choice for moderate-severe migraine? Their mechanism of action?
Triptans - they act as 5-HT1 B/D agonists which are targeted towards presynaptic terminals
- > inhibit neurotransmitter release
- > Inhibit synaptic transmission
When should treatment with triptans begin? Is it a monotherapy?
As early as possible -> prevent the development of full migraine episode, not good for stopping one in full force
Use in combination with an NSAID
What is the prototype triptan and when are they contraindicated?
Sumatriptan
-contraindicated in arterial disease / uncontrolled hypertension, though there are few side effects
Can triptans cause serotonin syndrome? Why aren’t they always used?
Yes, because they are a serotonin receptor agonist
Aren’t always used because they are very expensive
What drugs are used to prevent migraine currently?
- Beta-blockers
- Anti-epileptics
- Antidepressants
- Behavioral therapies (Relaxation, cognitive therapy)
What future drug target might entirely stop migraines from developing?
CGRP - either an anti-CGRP or an antagonist
Calcitonin Gene Related Peptide - Important in development of migraine
