Atomoxetine (Strattera) is a norepinephrine reuptake inhibitor that crosses the blood brain barrier. Its main action is to increase norepinephrine within the synaptic cleft in noradrenergic synapses.
Droxidopa is a norepinephrine precursor that also crosses the BBB and is metabolized to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (AAAD). Unlike atomoxetine, droxidopa has a more systemic effect "AAAD is ubiquitously expressed in tissues, including the kidney, gastrointestinal tract and liver. Strong evidence indicates that norepinephrine production after droxidopa administration occurs in non-neuronal tissues." (ref
Additionally, "Droxidopa may convert into norepinephrine within sympathetic terminals and the newly synthesized norepinephrine is then released as a neurotransmitter upon neuronal activation." This is thought to prolong the effect of droxidopa as the presynaptic neuronal stores of norepinephrine are replenished. (ref
This paper details the mechanism and pharmacokinetics of droxidopa: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509799/#!po=12.3762
Differences between (as experienced by me)
I am using these primarily for blood pressure. Droxidopa was developed to treat neurogenic hypotension and it is FDA approved for that purpose. Atomoxetine is approved for treatment of ADHD and its use for hypotension would be off label.
My experience with droxidopa is that it gives me a more consistent, longer-lasting, and natural feel than atomoxetine (as long as I don't take too much). However, it is less mentally stimulating and mood elevating, so I will often use a very small amount of atomoxetine in the morning to help with focus and motivation, in addition to the droxidopa.
- Quick onset and short acting
- Have to dose frequently and feel I am going up and down. I think this might go away if I could tolerate a higher dose, such as 10mg at once. I have seen others comment that they could take 10mg once a day and they were good all day.
- Greater impact on concentration, cognition, and mood, secondary impact on blood pressure
Availability of Meds:
- Slower onset and effects last longer
- Effect can be cumulative- after taking it for a few days, I needed less frequent dosing and amount (this may have to do with building norepinephrine reserves in the nerves). Has a more even, consistent effect
- Greater impact on blood pressure, secondary impact on concentration and mood
- More natural feel. At the right dose, I can practically feel 'normal'
Atomoxetine is relatively inexpensive and available from alldaychemist and buypharma.
Droxidopa is available as a generic in Japan and can be purchased here: https://www.mimaki-family-japan.com/item/list?keyword_pc=droxidopa&x=0&y=0
The Japanese version is a tablet that is sweet and literally dissolves in your mouth. I much prefer it to the US generic prescription in a capsule as it can be cut into pieces for dosing rather than parsing out capsule powder, but the US prescription is covered by my insurance, so that is what I am using.