Understanding Parkinson’s - Timing of - Evidence base list (from course review on 8 December 2020) Topic Relevant excerpt Original source of excerpt Link to original evidence Relevant excerpt within identified (ie Parkinson’s UK source/reference internal/ external resource or external source resource?)

The Why is it important that people Get it on Time report (page ​ importance of with Parkinson’s get their 4) medication medication on time, every https://www.nice.org.uk/gu NICE quality standard - timing Section: Importance of idance/qs164/chapter/Qua statement 4 time? If people with medication lity-statement-4-Levodopa Adults with Parkinson's Parkinson’s are unable to take -in-hospital-or-a-care-hom disease who are in their Parkinson’s medication at If people with Parkinson’s e hospital or a care home the right time, the balance of don’t get their medication on take levodopa within 30 chemicals in their body can be time it can seriously impact minutes of their their health. They may not be individually prescribed severely disrupted. This leads able to move, get out of bed, administration time. to their Parkinson’s becoming swallow, walk or talk. Some uncontrolled – increasing their people may never recover Rationale: Serious ​ care needs considerably. This and may permanently lose complications can will mean that staff will need to their ability to walk, talk or develop if levodopa is worse. Even a delay in taking not taken on time. These do more for the person with medication of 30 minutes can include acute akinesia Parkinson’s than would lead to serious health and, if delays are otherwise have been implications for someone significant, neuroleptic necessary. It can take living with Parkinson’s. In malignant syndrome. someone with Parkinson’s a 2017, NICE recognised the These complications can importance of levodopa lead to increased care long time to get back to normal admission as an area for needs and increased after this. Understandably, quality improvement within length of stay in hospital people with Parkinson’s may the Parkinson’s NICE quality or a care home. standard.2 be very anxious about getting ​ their on time. These times will differ from person to person and may not fit in easily with rounds.

Parkinson’s UK run a campaign called ‘Get It On Time’ to highlight the importance of people with Parkinson’s getting their medication on time, every time. Further information is available on the Parkinson’s UK Get It ​ On Time webpage

If any of the drugs used for Berman B. D. (2011). https://www.ncbi.nlm.nih.g Causative Agents Neuroleptic treating Parkinson’s need to be Neuroleptic malignant ov/pmc/articles/PMC3726 The abrupt cessation or stopped, it is important this is syndrome: a review for 098/ reduction in dose of malignant done gradually. Abrupt neurohospitalists. The ​ syndrome withdrawal of certain drugs can Neurohospitalist, 1(1), 41–47. such as ​ ​ ​ result, albeit rarely, in https://doi.org/10.1177/19418 levodopa in Parkinson neuroleptic malignant 75210386491 disease may also

syndrome. This is a very precipitate NMS.27 The ​ ​ serious condition that may rapid switching from one cause death from type of complications of the to respiratory, cardiovascular or another in such patients renal system. This is rare, but has also been it does emphasise the associated with NMS,28 ​ importance of the Get It On and there may be some Time message. risk of NMS associated with the abrupt withdrawal of Parkinson medications that are not known to have direct dopaminergic activity such as amantadine29 ​ and .30 ​ Neuroleptic malignant syndrome has also been rarely associated with a number of other medications not known to have any central antidopaminergic activity such as lithium,31 ​ desipramine, , dosulpin,32 ​ and phenelzine (Table 2 ​ ).33 ​

Prognosis

Initial reports of mortality rates from NMS were over 30%, but increased physician awareness and introduction of newer neuroleptic medications over the last few decades have helped reduce them to closer to 10%.71 When ​ ​ recognized early and treated aggressively, NMS is usually not fatal and a majority of patients will recover completely between 2 and 14 days.3,7 But if diagnosis ​ ​ ​ ​ ​ and treatment are delayed, resolution can require several weeks or longer, and surviving patients may have residual catatonia or , or significant morbidity secondary to renal or cardiopulmonary complications.10,13,34 ​ ​ ​ ​ ​ When death does occur, it is usually attributable to arrhythmias, DIC, or cardiovascular, respiratory, or renal failure. Thus, early recognition and initiation of therapeutic measures by physicians remain paramount to reducing the number of severe cases of NMS and limiting this significant source of morbidity and mortality among patients receiving .

Dopamine agonist Rabinak CA, Nirenberg MJ. https://pubmed.ncbi.nlm Abstract (results): Dopamine withdrawal syndrome Dopamine agonist withdrawal .nih.gov/20065130/ Symptoms of DAWS (DAWS) happens when a syndrome in Parkinson resembled those of other agonist ​ disease. Arch Neurol. 2010 person’s dopamine agonist withdrawal Jan;67(1):58-63. doi: syndromes and included treatment is stopped or syndrome 10.1001/archneurol.2009.294 anxiety, panic attacks, reduced. This could be when a . PMID: 20065130. agoraphobia, person is experiencing , ,

impulsive or compulsive diaphoresis, fatigue, pain, orthostatic behaviour as a and , and drug needs to stop taking (or reduce cravings. the amount of) the medication causing the behaviour. Stopping or reducing treatment should always take place in consultation with the person’s specialist.

Symptoms of DAWS can include anxiety, panic attacks, depression, , irritability and drug cravings. To avoid this, people with Parkinson’s must get help from a healthcare professional and withdrawal must be done gradually.

Dopamine dysregulation 1 Averbeck BB https://www.ncbi.nlm.nih.g Abstract syndrome is an impulsive and &O’Sullivan SS et al ov/pmc/articles/PMC3465 DDS is characterised by Dopamine ​ compulsive behaviour when (2014) 'Impulsive and 018/ an addictive or dysregulation compulsive behaviors in compulsive overuse of people start taking more syndrome Parkinson’s disease ' dopamine replacement medication than they need to Annu Rev Clin Psychol; therapies. Patients with control their Parkinson’s. 10:553–80 DDS take larger amounts of their If someone is taking too much dopaminergic medication than are necessary to levodopa, this can lead to adequately control their further side effects, such as motor symptoms in order severe involuntary movements to avoid “off” periods. (dyskinesia). If this is The excessive use often ​ ​ suspected, you should get help leads to adverse consequences such as from a healthcare professional. dyskinesia, which is accompanied by dysphoria accompanied by dysphoria.