Table 5

Treatment suggestions for some non-motor symptoms

Non-motor symptomsCommonly 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 sleepinessSleep 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)
 InsomniaSleep 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 disorderSleep in a safe environment while in bed, (remove all sharp and breakable objects)
Clonazepam (usually used first line)
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
 FatigueMethylphenidate—recommended by American Academy of Neurology, although considerable side effect profileModafinil (weak evidence base)
 PainNo 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
 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 dysfunctionPhosphodiesterase-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 hypotensionNon-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.