Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

all patients

1st line – specialist multidisciplinary care

Back
ONGOING
|
all patients
1st line – 

specialist multidisciplinary care

Treatment of PSP is mainly focused on symptomatic management and rehabilitation, with the objective to avoid complications and to delay disability and perhaps death.[10]

  • Despite multiple clinical trials, there is as yet no disease-modifying treatment available for PSP.[10][97]​ Note that high-quality evidence is lacking for most treatment options, hence many treatment recommendations are based on clinical experience.

PSP is best managed by a multidisciplinary team, including a social worker or a case manager, with care based on a case management approach drawing on the expertise of multiple specialties. Other key team members are a neurologist (ideally a movement disorder specialist), a physiotherapist, an occupational therapist, a speech-swallow therapist, and, if available, a neuropsychologist and a nurse.[10]

  • The goal is to address the whole spectrum of symptoms including parkinsonism, gait and balance problems, swallowing and speech impairments, behavioural changes, and cognitive impairment. Physiotherapy, occupational therapy, and speech therapy are important aspects of care.

  • Ensure the initial treatment plan for any patient with a diagnosis of PSP includes referral to a movement disorder specialist.

  • Full neuropsychological evaluation is usually necessary to determine the degree and pattern of cognitive impairment, evaluate decision-making capacity, and inform the treatment plan.[10]​

  • Carer education is recommended. Advise the carer/family that a false or exaggerated impression of dementia can be created by the patient’s apathy, depression, dysarthria, fixed expression, and poor eye contact.[10]​ Resources for carers are available from various organisations including the PSP Association in the UK, and CurePSP and the Association for Frontotemporal Degeneration in the US. PSP Association Opens in new window CurePSP Opens in new window Association for Frontotemporal Degeneration Opens in new window

  • Advice on lifestyle modifications might include aerobic exercise where feasible and safe, healthy diet advice, ensuring adequate sleep, and encouraging social and cognitive engagement.[10]

  • Palliative care is important to consider from the point of diagnosis, with discussions around advance care planning started within the first year and regularly reviewed thereafter.[10]

A clinical rating scale can be used to evaluate disease progression and as an indicator of prognosis.

  • The European Reference Network for Rare Neurological Diseases recommends the use of the Progressive Supranuclear Palsy Rating Scale (PSPRS) developed by Golbe and colleagues.[98][99]

As a general rule, avoid polypharmacy and discontinue any medications that are found to be ineffective or are causing significant adverse effects.[100]

  • Anecdotal evidence suggests that medications for dementia, motor parkinsonism, and bladder dysfunction are especially likely to be continued past their limit of utility.[10]

Plus – trial of levodopa

Back
ONGOING
|
all patients
|
with parkinsonism
Plus – 

trial of levodopa

Treatment recommended for ALL patients in selected patient group

A therapeutic trial of levodopa (in the form carbidopa/levodopa) for at least 1 month is recommended in any patient with PSP with bradykinesia, rigidity, or tremor affecting daily activities.[10]

  • Parkinsonism in patients with PSP does not show a sustained benefit from levodopa therapy, in contrast with the response seen in Parkinson’s disease (PD).[3][30][31][32] Any benefit in PSP tends to be minimal or transient although, by definition, patients with the parkinsonian subtype of PSP (PSP-P) are initially better levodopa-responders than those with other PSP phenotypes.[10][44]

  • However, because in retrospective studies up to 40% of patients with PSP showed some response to levodopa and also because of the difficulty in distinguishing the early stages of PSP-P and PSP-Richardson's syndrome (PSP-RS) from PD, it is worthwhile initiating a levodopa trial for any patient diagnosed with PSP who has parkinsonism.[100]

  • In PSP, a response tends to occur only early in the disease course and persist for only a few months.[10]

  • The dose of levodopa is up-titrated over a 4-week period from a low starting dose to the therapeutic dose (or maximum tolerated dose, if lower).[10] Based on findings from PD studies, a noticeable effect might take weeks to become evident so treatment should be continued for at least 1-3 months before any judgement on effectiveness is made.[101]​ If no effect is observed, levodopa can be tapered off over at least 2 weeks and discontinued.[10] If the patient does show benefit and adverse effects are minimal, in practice it is worth continuing the levodopa but with frequent re-evaluation so that tapering and discontinuation can be undertaken as soon as the benefit disappears.

The carbidopa component of carbidopa/levodopa is a decarboxylase inhibitor that inhibits peripheral plasma breakdown of levodopa, thereby increasing availability of levodopa at the blood-brain barrier.

Avoid other dopaminergic treatments such as dopamine receptor agonists, monoamine oxidase type B inhibitors, and catecholamine-O-methyltransferase inhibitors. Also avoid anticholinergics.[10]

  • These medications have no clinical utility in PSP.[10][102]

Primary options

carbidopa/levodopa: 25 mg (carbidopa)/100 mg (levodopa) orally (immediate-release) three times daily initially, increase gradually according to response, maximum 2000 mg/day (levodopa)

More

Plus – physical and occupational therapy

Back
ONGOING
|
all patients
|
with gait and balance problems
Plus – 

physical and occupational therapy

Treatment recommended for ALL patients in selected patient group

A daily physiotherapy home exercise programme, started early in the disease course and complemented by occupational therapy, is recommended for all patients with PSP who have gait and balance problems.[10]

  • Gait and balance impairments in PSP are not responsive to dopaminergic treatments.[10]

  • Physiotherapy can improve gait and balance, thereby reducing the risk of falls. Falls are a major cause of morbidity and a predictor of mortality among all parkinsonian patients but are especially more frequent and occur earlier in the course of PSP.[103][104]​ Patient and carer education on falls prevention is essential.[10]

  • One systematic review of 11 small studies evaluating physiotherapy and exercise in PSP showed a small to moderate effect on gait and walking but this did not reach statistical significance.[105]​ A subsequent uncontrolled but larger study of 117 patients with PSP found that a multiple therapeutic exercise programme that included a customised mix of resistance training, balance training, and walking exercises was effective in improving gait and balance scores.[106]​ The programme was administered for 60-80 minutes daily, 5 days per week for 4 weeks.

Interventions that address visual impairment (including gaze shifting and eye movement training) may provide additional benefit when coupled with gait and balance therapy.[10]​​

Use of a weighted, wide-based walking stabiliser that has a reverse braking mechanism (e.g., a U-Step® walker) is very helpful.[10]​ A wheelchair may be needed as the condition progresses and mobility declines but this requires shared decision-making with the patient and carer.[10]​​

Non-pharmacological measures can be helpful for patients with freezing of gait.

  • Freezing of gait is a significant symptom in some patients with PSP and is difficult to treat because it does not respond to levodopa, and other medications have a minimal or modest effect.

  • The use of an auditory or visual cue to show the patient the next step can help decrease the frequency and duration of freezing episodes (e.g., a device to make a click sound before every step or a line projected on the floor where the next step should be, using a laser device on the shoe or the walker). The evidence to support this comes mainly from patients with Parkinson’s disease, because studies involving patients with PSP are scarce.[107][108]

Consider – trial of pharmacotherapy

Back
ONGOING
|
all patients
|
with gait and balance problems
Consider – 

trial of pharmacotherapy

Additional treatment recommended for SOME patients in selected patient group

Evidence about amantadine, an NMDA-receptor antagonist, is very scarce and that which is available is contradictory. An expert consensus group has suggested that a 1-month trial may be worthwhile in patients with PSP who have significant gait impairment.[10]​ However, the evidence to support this is extremely weak and opinions differ on this point.

  • One crossover study that tested amantadine on 7 patients with PSP reported a decrease in the freezing of gait score. However, a retrospective study of 310 patients with PSP showed no effect on gait.[109][110]​ Another study reported a general subjective improvement in a subset of patients with PSP.[111]

  • An expert consensus group recommends a 1-month trial of amantadine in patients with PSP with significant gait impairment, with the dose titrated upwards at intervals of at least 2 weeks and careful monitoring for psychosis, confusion, and constipation.[10] In practice, patients aged <60 years are more likely to report benefits from amantadine whereas those >75 years are more likely to experience serious adverse effects.[42]

Coenzyme Q10 may also improve gait (based on expert opinion). Although only a few patients will respond, the adverse effects are minimal; therefore, a 2-month trial is recommended.[10] Discontinue if no benefit is seen after 2 months.[10]

Based on expert opinion, rasagiline (a monoamine oxidase type B inhibitor) may also improve freezing of gait but is less effective than amantadine.[10]

Primary options

amantadine: 100 mg orally once or twice daily initially, increase gradually according to response, maximum 300 mg/day

Plus – speech and language therapy

Back
ONGOING
|
all patients
|
with dysphagia
Plus – 

speech and language therapy

Treatment recommended for ALL patients in selected patient group

Oropharyngeal dysphagia occurs earlier and is more severe in PSP compared with other parkinsonian disorders. Evaluation and treatment of dysphagia is an important part of management.

  • Complications include sialorrhoea (excessive drooling), malnutrition, and aspiration pneumonia. Pneumonia is the leading cause of death in PSP.[113]

Dysphagia must be evaluated at every visit of a patient with PSP.

  • This can be done through history, oral motor examination, a water swallow test, and/or a swallowing questionnaire.[114]​ If any sign of dysphagia is noted, including coughing on liquids or sialorrhoea, a full evaluation by a speech-language pathologist (SLP) is essential.[10]

  • The SLP will perform a clinical swallow evaluation. If silent aspiration, which is common in PSP, cannot be excluded then a modified barium swallow test is indicated.[10]

Interventions that can improve swallowing include:[10]

  • Postural manoeuvres such as chin-tuck and head turns

  • Alternating bite and sip or taking multiple swallows

  • Thickening liquid consistency and optimising soft/pureed food consistency

  • Early speech and language therapy. Evidence is scarce for PSP but a benefit for dysphagia was demonstrated for patients with Parkinson's disease who had a speech and language therapy programme specifically designed for patients with Parkinson's disease (Lee Silverman Voice Treatment® or LSVT).[10] A small uncontrolled pilot study of LVST in patients with PSP suggested improvements in swallowing function.[115][116][117]

Consider – tube feeding via percutaneous endoscopic gastrostomy

Back
ONGOING
|
all patients
|
with dysphagia
Consider – 

tube feeding via percutaneous endoscopic gastrostomy

Additional treatment recommended for SOME patients in selected patient group

Percutaneous endoscopic gastrostomy (PEG) for tube feeding can be considered in severe cases of swallowing impairment.[10]

It may be appropriate when a modified barium swallow has shown aspiration or laryngeal penetration of all textures that cannot be improved by feeding modification or therapy and there is one or more of:[10]

  • A significant (>10%) weight loss

  • Increased work of eating (>1 hour)

  • A first episode of aspiration pneumonia

  • Fever of unknown origin.

However, there are no studies that evaluate whether PEG increases survival.

Consider – botulinum toxin injection

Back
ONGOING
|
all patients
|
with drooling
Consider – 

botulinum toxin injection

Additional treatment recommended for SOME patients in selected patient group

Management of excessive drooling in PSP is similar to in other neurological disorders except that in patients with PSP it is important to avoid anticholinergics with blood-brain barrier penetrance because of their detrimental effect on cognition.

Botulinum toxin injection is effective in decreasing sialorrhoea in parkinsonian patients, including those with PSP, with botulinum toxin type A and type B both being good options.[10][119][120]​ It is important to note that dysphagia is a potential side effect of botulinum toxin injection.[10][121]

Primary options

botulinum toxin type A: consult specialist for guidance on dose

OR

botulinum toxin type B: consult specialist for guidance on dose

Consider – glycopyrronium

Back
ONGOING
|
all patients
|
with drooling
Consider – 

glycopyrronium

Additional treatment recommended for SOME patients in selected patient group

Glycopyrronium is an anticholinergic agent with no significant blood-brain barrier penetration. It has been shown to be effective in decreasing sialorrhoea in patients with Parkinson's disease in a double-blind clinical trial and is an option in PSP (based on expert opinion).[10][118]

Primary options

glycopyrronium bromide: consult specialist for guidance on dose

Plus – speech and language therapy

Back
ONGOING
|
all patients
|
with speech impairment
Plus – 

speech and language therapy

Treatment recommended for ALL patients in selected patient group

Evidence is scarce regarding therapeutic options to improve speech impairment in PSP.

  • Referral for speech therapy is recommended for any patient with decreased speech intelligibility.[10]​ A small uncontrolled study suggested that Lee Silverman Voice Treatment® (LSVT) improves voice quality and articulation in patients with PSP.[123]

  • As the disease progresses, use of augmentative and alternative communication strategies (e.g., alphabet board, text-to-speech system, eye-gaze speech-generating device) might be necessary for most patients with PSP.[10] Early referral to a speech-language pathologist can ensure advance planning and preparation for this stage.[124]

  • If palilalia (involuntary repetition of words and phrases) is a significant problem, pacing techniques may be helpful.[10]

Consider – selective serotonin-reuptake inhibitor

Back
ONGOING
|
all patients
|
with behavioural symptoms
Consider – 

selective serotonin-reuptake inhibitor

Additional treatment recommended for SOME patients in selected patient group

It is important to differentiate apathy from depression in patients with PSP.[10]

  • Apathy is not usually amenable to treatment.[10]

  • Treat depression using a standard dose of an antidepressant such as a selective serotonin-reuptake inhibitor (SSRI). Avoid tricyclic antidepressants due to possible detrimental effects on cognition.[10]

  • Non-pharmacological measures such as cognitive behavioural therapy can also be offered.

Impulsivity is a very difficult symptom to treat effectively.[10]

  • If significant impulsivity is present, it may be necessary to discontinue levodopa and other drugs with a dopaminergic effect.[10] Non-dopaminergic SSRIs (e.g., escitalopram, sertraline) can be tried, although they are often ineffective.[10][125]

An SSRI is also sometimes used to treat emotional lability, based on anecdotal evidence and expert opinion.[10] However, dextromethorphan/quinidine is the most effective treatment for emotional lability in PSP.

Primary options

citalopram: 20-40 mg orally once daily

OR

escitalopram: 10-20 mg orally once daily

OR

fluoxetine: 20-80 mg orally (immediate-release) once daily

OR

paroxetine: 20-50 mg orally (immediate-release) once daily

OR

sertraline: 50-200 mg orally once daily

Consider – dextromethorphan/quinidine

Back
ONGOING
|
all patients
|
with behavioural symptoms
Consider – 

dextromethorphan/quinidine

Additional treatment recommended for SOME patients in selected patient group

Pseudobulbar affect (PBA) with labile emotions might be encountered in some patients.[10]

  • Dextromethorphan/quinidine is the most effective treatment for PBA with emotional lability in PSP although its use may be limited by cost.[10] Multiple clinical trials in different neurological disorders have confirmed its effectiveness and safety in the treatment of PBA.[126][127][128]

Primary options

dextromethorphan/quinidine: 20 mg (dextromethorphan)/10 mg (quinidine) orally once daily for 7 days, followed by 20 mg (dextromethorphan)/10 mg (quinidine) twice daily

Consider – occupational therapy

Back
ONGOING
|
all patients
|
with cognitive impairment
Consider – 

occupational therapy

Additional treatment recommended for SOME patients in selected patient group

Executive dysfunction and verbal fluency deficits are the predominant symptoms of cognitive impairment in PSP. No symptomatic therapy is available for these.[37][58]

  • Occupational therapy input can include advice to manage executive dysfunction (e.g., structured daily routine, daily planners).[10]

Consider – botulinum toxin injection

Back
ONGOING
|
all patients
|
with dystonia
Consider – 

botulinum toxin injection

Additional treatment recommended for SOME patients in selected patient group

Limb dystonia can severely impair patients’ daily functioning. Facial/neck dystonias are sometimes painful and can prevent eating/feeding.

  • Botulinum toxin injection is probably the best treatment option for localised dystonias.[133]​ Treatment can be repeated every 3 months to maintain effect.[10] For use in cervical dystonia, the American Academy of Neurology assigns level A efficacy rating to abobotulinumtoxinA and rimabotulinumtoxinB, and level B efficacy rating to onabotulinumtoxinA and incobotulinumtoxinA (abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA are types of botulinum toxin type A, and rimabotulinumtoxinB is a type of botulinum toxin type B).[133]

  • The utility of anticholinergics and muscle relaxants is limited in PSP due to the adverse effects of worsening cognitive function and gait. Muscle relaxants such as baclofen or clonazepam can be tried at low doses as a last resort, but are not routinely used in practice.[10]

Botulinum toxin injection is recommended for blepharospasm.[10]

  • Eyelid-opening apraxia, which can co-exist with blepharospasm in the same patient, is more difficult to treat and requires the input of a neuro-ophthalmologist.

  • If decreased blink rate leads to dry eye, blepharitis, and exposure keratitis, conservative treatment with humidifiers, warm wet compresses, and protective eyewear is recommended. Tear volume can be improved by using artificial tear drops and preservative-free lubricants.[10]

Refer to an ophthalmologist if eye movement problems cause diplopia or significant visual impairment.

Primary options

botulinum toxin type A: consult specialist for guidance on dose

OR

botulinum toxin type B: consult specialist for guidance on dose

Plus – symptomatic management

Back
ONGOING
|
all patients
|
with sleep disturbance
Plus – 

symptomatic management

Treatment recommended for ALL patients in selected patient group

Sleep issues are common. Pharmacological and non-pharmacological management options exist but evidence for efficacy specific to PSP is scarce. Standard sleep hygiene advice is recommended.[10]

  • Insomnia can be treated with melatonin. This is also an effective and well-tolerated option if REM sleep behaviour disorder is present.[10]

  • Modafinil, armodafinil, or methylphenidate can be considered at low dosages if excessive daytime sleepiness is a problem.[10]

  • Great caution is required regarding benzodiazepines in patients with PSP because of the risk of falls.[10] In addition, retrospective analysis of 305 patients with PSP-Richardson's syndrome (PSP-RS) suggested that those who were prescribed benzodiazepines (lorazepam, clonazepam, alprazolam, diazepam) experienced an increased worsening of their PSP compared with those not prescribed benzodiazepines, as measured by the PSP Rating Scale (PSPRS) during the 1-year follow-up period.[135]​ The effect persisted after adjusting for indications for benzodiazepine administration (including insomnia, anxiety, and sleep disturbance). Benzodiazepines were the only drug class being taken by ≥10% of the participants that was found to be associated with this more rapid worsening of PSP.

  • Obstructive sleep apnoea is managed with advice on lateral decubitus positioning, weight loss if obesity is present, and elevation of the head of the bed, together with standard approaches such as continuous positive airway pressure (CPAP), surgical removal of obstructive tissue, or implantation of a hypoglossal nerve stimulator.[10]

  • Similar treatment approaches can be used for periodic limb movement disorder and restless legs syndrome. The medications indicated for these problems in the setting of other conditions (e.g., gabapentin, pregabalin, cabergoline) require great caution in PSP because of the adverse effects of sedation and psychosis. If iron deficiency or low ferritin levels are present, a trial of oral iron replacement is recommended.[10] See Iron-deficiency anaemia.

Primary options

melatonin: consult specialist for guidance on dose

OR

modafinil: 200-400 mg orally once daily in the morning

OR

armodafinil: 150-250 mg orally once daily in the morning

OR

methylphenidate: 10-60 mg/day orally (immediate-release) given in 2-3 divided doses

Plus – symptomatic management

Back
ONGOING
|
all patients
|
with constipation
Plus – 

symptomatic management

Treatment recommended for ALL patients in selected patient group

Constipation occurs frequently and is managed using standard approaches. Initial treatment centres on non-pharmacological measures including increased hydration, physical activity (where feasible), and fibre supplementation.[10]

  • First-line pharmacological treatment is a stool softener such as docusate. Osmotic laxatives (e.g., polyethylene glycol, magnesium citrate, lactulose) can then be used if needed. Stimulant laxatives (e.g., bisacodyl, sennosides) should only ever be used short-term and sparingly. Bowel stimulants such as linaclotide or prucalopride were found to be effective in a small cohort of patients with parkinsonism but should be reserved for those with refractory constipation as their long-term safety requires further evaluation.[10]

For more information see the recommendations for non-opioid-induced chronic constipation in Constipation.

Plus – symptomatic management

Back
ONGOING
|
all patients
|
with urinary symptoms
Plus – 

symptomatic management

Treatment recommended for ALL patients in selected patient group

Urinary symptoms affect more than half of people with PSP and generally require input from a urologist.[10]

  • Behavioural advice on avoiding caffeine and alcohol is the first-line treatment for overactive bladder. If nocturia is a problem, daytime use of compression stockings and elevation of the lower limbs in the late afternoon can be advised. Bladder training and pelvic floor exercises with biofeedback may improve symptoms but are often difficult for patients with PSP to perform.[10]

  • An alpha-blocker (e.g., terazosin, doxazosin, tamsulosin) is the first-line pharmacological option for bladder outlet obstruction.[10]

  • A 5-alpha reductase inhibitor (e.g., finasteride, dutasteride) may improve urinary dysfunction in men with PSP.[10]

  • A beta-3 adrenergic agonist (e.g. mirabegron) can be helpful for overactive bladder.[10]

  • Avoid the use of non-selective antimuscarinic agents (e.g., oxybutynin, tolterodine, fesoterodine) due to their central anticholinergic adverse effects.[10]

Primary options

terazosin: 1 mg orally once daily at bedtime initially, increase gradually according to response, maximum 20 mg/day

OR

doxazosin: 1 mg orally once daily at bedtime initially, increase gradually according to response, maximum 8 mg/day

OR

tamsulosin: 0.4 mg orally once daily initially, increase gradually according to response, maximum 0.8 mg/day

OR

finasteride: 5 mg orally once daily

OR

dutasteride: 0.5 mg orally once daily

OR

mirabegron: 25-50 mg orally once daily

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer