Table 8.
Interventions to treat autonomic dysfunction in PD
| Symptom | Drug/intervention | Efficacy | Safety | Practice implications |
|---|---|---|---|---|
| Orthostatic hypotension | Fludrocortisone | Insufficient evidence | Insufficient evidence | Possibly useful a |
| Midodrine | Insufficient evidence | Insufficient evidence | Possibly useful b | |
| Domperidone | Insufficient evidence | Acceptable risk with specialized monitoring c | Investigational | |
| Yohimbine | Nonefficacious | Insufficient evidence | Investigational | |
| Droxidopa d | Efficacious (short term) | Acceptable risk without specialized monitoring (short term)e | Possibly useful | |
| Sexual dysfunction | Sildenafil | Efficacious | Acceptable risk without specialized monitoring | Clinically useful |
| Constipation | Macrogol | Likely efficacious | Acceptable risk without specialized monitoring | Possibly useful |
| Lubiprostone | Likely efficacious | Acceptable risk without specialized monitoring | Possibly useful | |
| Probiotics and prebiotic fiber | Efficacious | Acceptable risk without specialized monitoring | Clinically useful | |
| Abdominal massages | Insufficient evidence | Insufficient evidence | Investigational | |
| Anorexia, nausea and vomiting associated with levodopa and/or dopamine agonist treatment | Domperiodone | Likely efficacious | Acceptable risk with specialized monitoring c | Possibly useful |
| Drooling | Ipratropium Bromide Spray | Insufficient evidence | Insufficient evidence | Investigational |
| Glycopyrrolate | Efficacious | Insufficient evidence | Possibly useful | |
| Botulinum Toxin B | Efficacious | Acceptable risk with specialized monitoring | Clinically useful | |
| Botulinum Toxin A | Efficacious | Acceptable risk with specialized monitoring | Clinically useful | |
| Urinary frequency, urgency, and/or urge incontinence | Solifenacin f | Insufficient evidence | Acceptable risk without specialized monitoring g | Possibly useful h |
RCTs, randomized controlled trials.
Although there is insufficient evidence for fludrocortisone to be rated for the treatment of orthostatic hypotension (OH) in PD, it provided some significant benefits in 1 RCT.2 Therefore, the practice implication is “possibly useful.”
Although there is insufficient evidence for midodrine to be rated for the treatment of OH in PD, it provided some significant benefits on measures of OH in RCTs in a mixed population of patients in which only a subgroup had PD.1 Therefore, the practice implication is “possibly useful.”
As a result of the risk of QT interval prolongation and the association with ventricular tachyarrhythmia/sudden cardiac death in PD patients with preexisting cardiac disease.96
Recommendations are for the very short‐term treatment of OH in PD, while there is insufficient evidence to conclude on the efficacy and safety of droxidopa for the treatment of OH in PD for the long term.
A recent systematic review evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic OH who participated in RCTs (short‐term RCTs: 1 to 2 weeks, n = 444; intermediate RCTs: 8 to 10 weeks, n = 222) and long‐term open‐label studies (n = 422).97 Adjusting for exposure time, cardiovascular adverse events rates were 0.30 events/patient‐year in the short‐ and intermediate‐term studies, and 0.15 events/patient‐year in the long‐term open‐label studies, and most evident in patients with preexisting cardiac disorders. Moreover, the risk for supine hypertension has to be considered. Indeed, in the postmarketing surveillance, 1 case with intracranial hemorrhages has been reported.98
For the treatment of overactive bladder.
A systematic review including 4,188 participants (3,952 participants in placebo‐controlled trials; 650 of them randomized to solifenacin) aged 65 or older randomized to antimuscarinic medications for 4 to 12 weeks and 3,026 randomized to placebo, revealed that treatment for overactive bladder using antimuscarinics in adults aged 65 or older resulted in significant increased risk of several adverse events when compared with placebo including both anticholinergic (eg, dry mouth, constipation) and nonanticholinergic (eg, dyspepsia, dizziness, headaches) adverse events.101 Moreover, incidence of urinary tract infections with solifenacin was significantly higher when compared with placebo.
There were some significant benefits in the active arm and as such the practice implications for solifenacin for the treatment of overactive bladder is “possibly useful” because of the established efficacy and license of solifenacin in this indication outside PD.