Challenge questions
What is the optimal method to titrate droxidopa to achieve the maximal symptomatic
benefit? How should clinicians monitor for supine hypertension?
Case presentation
Mr. E is an 80-year-old male with well-controlled Parkinson disease (PD). He was able
to walk 1 mile daily until he developed occasional episodes of dizziness and syncope
when standing. His nurse practitioner detected a significant fall in blood pressure
(BP) when standing without an adequate heart rate (HR) increase [seated BP of 120/70 mmHg
with a HR of 66 beats per minute (bpm); standing BP of 89/60 mmHg with a HR of 68 bpm].
He was therefore diagnosed with symptomatic neurogenic orthostatic hypotension (nOH).
He was prescribed midodrine [2], fludrocortisone, and pyridostigmine. However, he
reported little or no benefit with any of them. He reported that he continues to suffer
from symptoms of nOH, including fatigue, weakness, lightheadedness, and near syncope
upon standing. He has become wheelchair-ridden many days, and his wife is concerned
that she is unable to care for him because of his dizziness causing falls. His wife
also reported that her husband has been reluctant to engage in previous activities
such as attending worship services, exercise, and bingo games, instead preferring
to sit and watch television. Orthostatic vital signs measured in the office revealed
marked nOH with supine BP of 130/70 mmHg and 3-min standing BP of 90/60 mmHg. Supine
HR was 68 bpm, and standing HR was 64 bpm. It was determined that the patient is a
good candidate for treatment with droxidopa [1].
The patient and his wife were educated on home BP monitoring. They were instructed
to check his BPs in the supine position (at least 15 min after lying down at bedtime
or prior to arising from bed in the morning) and after 3 min of standing (with assistance
as necessary) after arising from bed in the morning. They were instructed that supine
BP measurements are to be performed with a 30° elevation of the head of the bed. If
significant supine hypertension (sHTN) (systolic BP ≥180 mmHg) is recorded, they were
advised to measure and record the BP three times in 1 h to see if this was sustained.
The patient was initiated on 100 mg droxidopa on a modified three times daily (TID)
schedule, with first dose in the morning, second dose at midday, and the last dose
at least 3–4 h prior to bedtime. If significant sHTN (systolic BP ≥180 mmHg) is not
recorded, the patient was instructed to up-titrate droxidopa by 100 mg on the modified
TID schedule (morning, lunchtime, and 3–4 h before bedtime) every 24–48 h based on
symptomatic improvement. They were directed to measure Mr. E’s BPs in the supine position
at least twice daily (morning and before bedtime) while in the titration phase and
measure his BP if he was feeling symptomatic. The patient was otherwise instructed
to continue titration (up to a maximum dose of 600 mg on the modified TID schedule)
until achieving symptomatic improvement in activities, stand time, and overall improvement
in weakness, lightheadedness, and/or near syncope.
Expert commentary (Dr. Karabin)
There are a number of patient characteristics influencing the titration rate; these
may include sHTN, cardiovascular disease, cerebrovascular disease, advanced neurological
disease (e.g., dementia, PD), and elderly with limited home support. In all of these
cases, titration may be slower (e.g., every 72–96 h).
Expert commentary (Dr. Gupta)
Education is key to making the proper decision for titration. If a patient wants to
titrate more slowly, I would advise against this, especially in a very symptomatic
patient with nOH; this is because slowing the titration prolongs the time until the
beneficial impact that droxidopa can play on symptoms of nOH. However, every patient
should be managed based on their comorbidities, ability to tolerate treatment, and
age. Thus, some patients with more comorbidities may require a slower titration.
Case continuation
The patient reported that after receiving 400 mg droxidopa TID, his symptoms were
much improved with very few episodes of dizziness. The patient continued this dosage
schedule until the next follow-up visit, after approximately 4 weeks of starting droxidopa.
At the next follow-up visit 3 months later (supine BP of 134/74 mmHg with a HR of
60 bpm; 3-min standing BP of 115/68 mmHg with a HR of 67 bpm), the wife reported that
her husband had experienced a few episodes of dizziness and had fallen once. At the
visit, the patient was instructed to again up-titrate the dose of droxidopa every
24–48 h up to a maximum dose of 600 mg on the modified TID schedule, as mentioned
above. In addition, they were instructed to monitor his BPs, as before, during the
titration phase.
After achieving the maximum dose of 600 mg TID, the patient and his wife reported
that his symptoms were much improved. He has not had any episodes of falling during
the past 3 months and has only had a couple of episodes of dizziness.