Parkinson’s disease is a progressive neurological disorder estimated to affect over 110,000 Australians. While the presentation of Parkinson’s disease can be quite varied, the condition is characterised by bradykinesia plus either muscle rigidity, rest tremor, or both.
Hospitalisation is common among people with a diagnosis of Parkinson’s disease. Each year, around a third of patients with Parkinson’s disease visit an emergency department or are admitted to hospital, with half of these patients going on to have a repeat encounter. Admission to a healthcare facility can be risky for people with Parkinson’s disease. Evidence suggests that these patients have a longer length of stay, more complications, and worse outcomes compared to patients without a diagnosis of Parkinson’s disease. The following factors may contribute to these results:
- Delayed or varied dosing of anti-Parkinson medications;
- Administration of medications contraindicated in Parkinson’s disease; and
- Administration of medications that interact with anti-Parkinson medications.
Levodopa and dopamine agonists are the main medications used to improve motor function in patients with Parkinson’s disease. Anticholinergics, catechol-O-methyl transferase (COMT) inhibitors, monoamine oxidase type B (MAO‑B) inhibitors, and amantadine may also be used. Adherence to prescribed therapy regimens is important as significant deterioration in function can develop when variations from the usual dosing schedule occur.
Levodopa has a relatively short half-life of around 90 minutes. Patients in the early stages of the disease often enjoy a prolonged clinical effect from twice-daily doses which may be due to preserved levodopa storage capacity of presynaptic neurones. However, as the disease progresses, there is a continued loss of these neurones and a reduced duration of levodopa’s clinical effect. It is these patients who are particularly vulnerable to deterioration if doses are delayed or missed. Parkinson’s NSW advises that a delay of just 15 minutes can cause clinical deterioration.
Admission to a healthcare facility may increase the risk of missing or delayed doses for a variety of reasons. The patient may not have brought their own medications in with them, or there may be confusion regarding the patient’s dosing schedule leading to delays in completing the medication chart. One retrospective study found that 76% of patients prescribed medications for Parkinson’s disease had at least one missed dose documented, corresponding to 0.7 missed doses per patient per day. The most common documented reasons for dose omissions were ‘unable to swallow’ (14%), ‘out of stock’ (12%), ‘nil by mouth’ (8%), ‘refused’ (4%), and ‘in theatre’ (4%). However, the majority of omissions had no documented reason.
Acute deterioration can occur when doses are missed. The patient may experience a worsening of tremors, increased rigidity, loss of balance, confusion, agitation, impaired bowel motility, and difficulty swallowing and communicating. This can lead to complications related to falls, aspiration pneumonia, and bowel obstruction as well as causing significant distress for the patient and their family. Parkinsonism-hyperpyrexia syndrome is another potential complication associated with the sudden cessation or reduction in dose of anti-Parkinson medications. This potentially fatal syndrome is characterised by pyrexia, muscle rigidity, reduced consciousness, and autonomic instability. While this condition is rare, the mortality rate is reported to be up to 4% with an additional one-third of patients left with permanent sequelae. Management relies on prompt diagnosis and resumption of anti-Parkinson medications.
Strategies that may reduce the incidence of inadvertent dosing variances include:
- Educate patients prior to an elective admission to bring their own medications, in the original containers, with them to the hospital;
- Educate patients to bring a current medication schedule with them to the hospital;
- Conduct a best possible medication history with each patient as soon as possible after presentation to hospital;
- Ensure medication orders are written for the times the patient normally takes their medications, rather than standard administration times;
- Institute a system to easily identify patients who have Parkinson’s disease; and
- Consider reviewing the availability of common anti-Parkinson medications in imprest and emergency cupboards.
Alternatively, medications may have been deliberately withheld while the patient is nil by mouth e.g. prior to surgery. The Therapeutic Guidelines: Neurology advise that patients with good control of their Parkinson’s disease can miss up to three doses of oral anti-Parkinson therapy if necessary. However, patients with fragile disease control or those expected to miss more than two or three oral doses should receive their anti-Parkinson medication by a non-oral route.
One option that could be considered in a patient who is nil by mouth is the transdermally administered dopamine agonist, rotigotine. An appropriate starting dose can be calculated using the concept of levodopa equivalent doses (LEDs). An LED is the dose of anti-Parkinson medication that provides an equivalent level of symptom control as 100mg of immediate-release levodopa plus a dopa-decarboxylase inhibitor. Another option is to administer the medication via an enteral feeding tube, although not all levodopa formulations are suitable for this route of administration. Any alteration to a patient’s usual medication regimen is ideally supervised by a physician experienced in the management of Parkinson’s disease, especially if the patient has fragile disease control.
It may also be prudent to consider the timing of interventions to minimise interruption to the medication routine. For example, a patient who is nil by mouth prior to surgery can still take prescribed oral medication with a small amount of clear fluid up to two hours before elective surgery. Therefore, placing patients with Parkinson’s disease at the beginning of operating lists and resuming medications as soon as possible after surgery may improve clinical outcomes.
Another issue that can arise during hospitalisation is the administration of medications that are contraindicated in Parkinson’s disease or interact with medications used in the treatment of Parkinson’s disease.
Due to the underlying pathology of Parkinson’s disease, medications that antagonise the effects of dopamine should be avoided as they will impair symptom control. Many medications can reduce the effects of dopamine; some examples are shown in Table 1.
Table 1. Medications to avoid in all patients with Parkinson’s disease
|Medication class||Examples||Mechanism of interaction|
|Typical antipsychotics||Chlorpromazine Flupenthixol Fluphenazine Haloperidol
Pericyazine Trifluoperazine Zuclopenthixol
|Blocks D2 receptors in the brain|
|Blocks D2 receptors in the brain
(effect is less pronounced than with typical agents)
|Blocks D2 receptors in the brain
(domperidone preferred as it does not cross the blood-brain barrier)
|Weak D2 blocking effect|
|Tetrabenazine||Tetrabenazine||Reduces dopamine stores|
|Antihypertensive||Methyldopa||Inhibits dopa decarboxylase to reduce conversion of l-dopa to dopamine|
*If an antipsychotic is required for a patient with Parkinson’s disease, quetiapine or clozapine are less likely to worsen Parkinson’s symptoms
Care is also required to avoid or minimise interactions with anti-Parkinson medications. Drug interactions, such as those shown in Table 2, may result in worsening of symptoms or produce severe adverse effects.
Table 2. Interactions with medications used to treat Parkinson’s disease
|Anti-Parkinson Medication||Interacting medications||Effect|
|MAO-B inhibitors (rasagiline, selegiline, safinamide)||Pethidine||Risk of serotonin syndrome
|Selective serotonin reuptake inhibitors (SSRIs)|
|Tricyclic antidepressants (TCAs)|
|St John’s Wort|
|MAO inhibitors (phenelzine, tranylcypromine)||Non-selective MAO inhibition may lead to hypertensive crisis|
|Moclobemide||Increased risk of hypertensive episodes|
|Apomorphine||Ondansetron||Severe hypotension, loss of consciousness, bradycardia and seizure activity may result|
|Amantadine||Anticholinergic agents||Additive anticholinergic adverse effects|
While it is important for all medications to be administered as prescribed, it is particularly crucial to minimise variations to medications used to treat Parkinson’s disease. Medication regimens for the management of Parkinson’s disease are highly individualised, and the patient’s original dosing schedule should be closely followed during admission. Minimising dosing delays and therapy interruptions may help to improve clinical outcomes by preventing acute deterioration and prolonged length of stay.
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