Treatment suggestions for some non-motor symptoms
| Non-motor symptoms | Commonly used strategies (where possible based on randomised controlled studies) | Investigational or reported treatment options (based on open label or observational reports) |
|---|---|---|
| Sleep disorders | ||
| Excessive daytime sleepiness | Sleep hygiene (regular daytime exercise, avoiding stimulants at bedtime, regular hours of sleep at night) Modafinil (subjective improvement) | Caffeine intake (contradictory data and tablets may be used) Sodium oxybate—taken at night, only under specialist supervision (potential for abuse) Selective histamine H3 receptor inverse agonist ▸ Pitolisant (in trial) Adenosine receptor antagonists—Istradefylline, Tozadenant (in setup) |
| Insomnia | Sleep hygiene Short-acting benzodiazepines Non-benzodiazepine hypnotics ▸ Zopiclone Tricyclic antidepressants ▸ Amitriptyline | Night-time apomorphine infusion or Rotigotine patch (may help in cases of insomnia due to severe nighttime rigidity, restless legs syndrome and ‘off’ periods) |
| REM sleep behaviour disorder | Sleep in a safe environment while in bed, (remove all sharp and breakable objects) Clonazepam (usually used first line) Melatonin Pramipexole in combination with Clonazepam (one successful trial reported) | Long-acting melatonin (use being investigated) |
| Mood disorders | ||
| Depression | ▸ Pramipexole—recommended by Movement Disorders Society ▸ Selective serotonin reuptake inhibitor – Paroxetine – Citalopram ▸ Serotonin and norepinephrine reuptake inhibitor) – Venlafaxine XR ▸ Tricyclic antidepressants—recommended by Movement Disorders Society – Nortriptyline – Desipramine Awareness of non-motor fluctuation related mood disorders | If as part of non-motor fluctuations ▸ Trial of long acting dopamine agonists ▸ Infusional therapies – Apomorphine infusion – Intrajejunal levodopa infusion |
| Fatigue | Methylphenidate—recommended by American Academy of Neurology, although considerable side effect profile | Modafinil (weak evidence base) |
| Pain | No specific recommendations apart from analgesics and dopaminergic drugs for non motor fluctuation related pain such as off related dystonic pain Baclofen (muscular pain aggravated by rigidity, anecdotal evidence) Opiates (Tramadol) | Central pain: Oxycodone with naloxone (PANDA study, randomised placebo-controlled study completed) |
| Cognitive dysfunction | ||
| Dementia | ▸ Rivastigmine—recommended by the Movement Disorders Society (oral or transdermal patch) ▸ Donepezil | Memantine Galantamine |
| Psychosis (hallucinations/delusions) | ▸ Quetiapine (often used first line, based on clinical experience, despite of unconvincing trial data) ▸ Clozapine (needs specialised monitoring of blood count to monitor for agranulocytosis)– recommended by the Movement Disorders Society ▸ Exclusion of concomitant systemic infection or illness which may precipitate psychosis | Pimavanserin (serotonin 2A receptor inverse agonist)—in clinical trial |
| Autonomic dysfunction | ||
| Dribbling of saliva | ▸ Oral atropine drops—2–3 times/day ▸ Botulinum toxin A and B—parotid and submandibular injections (under specialist supervision in centres with experience in technique)—recommended by the American Academy of Neurology and the Movement Disorders Society | ▸ Glycopyrrolate for short-term treatment—recommended by the Movement Disorders Society ▸ Ipratropium bromide spray (Atrovent)—1–2 doses per day sublingually |
| Constipation | ▸ Diet and lifestyle advise: – Fibre-rich diet – Ensure adequate fluid intake to avoid dehydration ▸ Medications: – Macrogol (Movicol in the UK)—recommended by the American Academy of Neurology and the Movement Disorders Society – Lactulose (Duphalac) – Senna (Senokot) – Avoid constipating opiates for pain | Lubiprostone (Amitiza)—in clinical trial |
| Bladder dysfunction—urgency, nocturia | ▸ Anticholinergic agents (use with caution in patients with hallucinations and cognitive decline) – Oxybutynin – Tolterodine XL ▸ Desmopressin spray for troublesome nocturia (beware of nocturnal hypertension) | ▸ If during off state—adjust PD medications ▸ Exercise-based behavioural therapy |
| Erectile dysfunction | Phosphodiesterase-5 inhibitors (use with caution in patients with postural hypotension) ▸ Sildenafil—recommended by the American Academy of Neurology ▸ Tadalafil (Cialis) | Apomorphine injection may be tried |
| Orthostatic hypotension | Non-pharmacological therapies ▸ Increased salt and water intake ▸ Waist-high support stockings ▸ Physical counter manoeuvres ▸ Avoid volume depleting drugs (diuretics, antihypertensives) Pharmacological therapy ▸ Fludrocortisone ▸ Ephedrine ▸ Midodrine | Pharmacological therapies ▸ Domperidone in addition to fludrocortisone ▸ L-threo-3,4-dihidroxyphenylserine for refractory orthostatic hypotension |
PD, Parkinson's disease.