PPID: owners and compliance

Pituitary pars intermedia dysfunction (PPID) is a neurodegenerative disorder of the equine pituitary pars intermedia¹. Loss occurs of the normal dopaminergic inhibition of this region of the pituitary by the hypothalamus².

Consequently, continuous stimulation of the pars intermedia melanotropes occurs, resulting in excessive production of their normal hormonal products derived from the cleavage of pro-opiomelanocortin, including a-melanocyte stimulating hormone, corticotropin-like intermediate lobe peptide, b-endorphin, and adrenocorticotrophic hormone¹. Over time, the continued stimulation results in melanocyte hypertrophy and, eventually, adenomatous change³.

Pergolide is a dopaminergic agonist registered for the treatment of clinical signs associated with PPID in horses not intended for human consumption. Pergolide acts as an agonist for both the D1 and D2 receptors located on the melanotropes, and receptor activation reduces hormone production by the pars intermedia and should, therefore, reduce the associated clinical signs⁴. The treatment is aimed at controlling the clinical signs rather than curing the underlying disease, and lifelong daily therapy is required¹.

Daily oral administration of pergolide (initial recommended dose 2mg/kg once daily) should be combined with appropriate dietary management and general wellness care⁵. Improvement in the clinical signs is the most important indicator of response to treatment. If the improvement is insufficient, then the dose of pergolide can be increased by 1mg/kg to 2mg/kg (with doses of more than 4mg/kg considered as extra-label use). If the improvement is still insufficient, then cyproheptadine (0.25mg/kg orally twice daily or 0.5mg/kg orally once daily) can be added⁵.

Cabergoline is an alternative dopamine agonist that has been compounded for administration via once-weekly injection to horses with PPID. This is sometimes suggested for refractory PPID cases or in horses in which daily oral medication administration is not possible (either owner or horse-related reasons), but only limited scientific data is available relating to its efficacy⁶.

Dietary supplements have also been suggested for the management of PPID, but scientific evidence to support their use is lacking⁷.

Compliance

In veterinary medicine, compliance describes the degree to which an owner correctly follows medical advice; most commonly, it refers to medication or drug compliance. Medication compliance equates to the owner or person in charge administering the right medication, at the correct dose, by the correct route, at the right time, in the correct way, to the right patient⁸.

Compliance is vital, as it can significantly affect the success of using these medications and the subsequent health outcomes for the patients. In human medical fields, drug compliance is frequently measured and rates average around 50 per cent, although reports vary between 0 per cent and 100 per cent⁹. Compliance tends to be higher with more severe conditions and lower in situations perceived to be less important¹⁰. Veterinary data predominantly focuses on dogs and cats, and suggests similar short-term compliance rates of between 22 per cent and 80 per cent^11-14. Very little published research exists regarding compliance of horse owners with respect to medication dosing. In one study that evaluated compliance in veterinary medication regimens for horses alongside companion animals, by observing consultations and through questionnaires for the owners and vets¹⁴, veterinarians significantly overestimated the likelihood of clients being compliant, and horse owners were less likely to be compliant compared to companion animal owners (47 per cent versus 55 per cent). Furthermore, the study also found that horse owners were more likely to miss doses, give an incorrect dose or give the medication at the incorrect time compared to companion animal owners¹⁴.

In another study that investigated horse owner compliance with respect to an environmental protocol recommended for the control of severe equine asthma, similarly poor compliance was reported in 51.3 per cent of the cases¹⁵.

PPID and compliance

Treatment with pergolide is orally and daily; therefore, the administration is the responsibility of the owner. As a result, it is possible that owners might forget on some days.

Anecdotally, pergolide palatability has been reported as poor in some animals, meaning owners have to resort to a variety of ingenious methods to disguise the medication. In addition, dosing ponies weighing less than 150kg accurately can be difficult, as tablets have to be split¹⁶. As a result, owners may find administering the medication a difficult process and may not be giving treatment at the dose or the daily interval specified by the attending veterinarian.

Pergolide therapy is also associated with a variety of side effects, with the most common being decreased appetite, lethargy and weight loss. Owners of horses experiencing side effects may also find accurate dosing more difficult.

A single published study exists that estimated pergolide medication compliance in UK horses and ponies from clinical records¹⁷. Overall, 48 per cent of animals were considered as having compliant owners (that is, receiving more than or equal to 90 per cent of the veterinarian-recommended dose of pergolide) and compliance was significantly worse in animals older than 26 years old and in Shetland ponies¹⁷. Interestingly, compliant animals were not more likely to have good laboratory control of their PPID.

Factors affecting owner medication compliance

To maximise compliance, it is important to understand the factors affecting whether a client will comply with the recommendations made by the veterinarian¹⁸. The factors affecting compliance may also vary depending on the specific condition being treated, the duration of treatment required and whether multiple medications are prescribed¹⁸.

A systematic review of factors affecting dog and cat owner compliance with pharmaceutical recommendations revealed that daily dosing frequency, discussion of the dosing regimen in light of owners’ circumstances, consultation time spent with the vet, the specific disease condition being treated, the month of the consultation/treatment, physical risk and social risk were all reported to have affected compliance in at least one of the included studies¹⁸.

Reducing the number of daily doses to once or twice a day has been shown to have a positive effect on compliance in dogs. Multiple dosing schedules demand a rigid schedule from owners, which may be more inconvenient and may impinge upon their lifestyle¹⁹. In addition, frequent administrations of oral medication to animals may be a demanding and frustrating challenge to the owner – especially if the patient is reluctant to swallow the medication and if medication is not able to be given with food. Furthermore, it may seem “excusable” to the owner to omit one or two doses in a high-frequency dosing schedule, as the impact on the clinical signs are not necessarily immediately obvious¹⁹.

In human beings, polypharmacy has been associated with reduced compliance rates in elderly patients, but veterinary evidence relating to this is minimal. A single study in dogs with epilepsy exists in which overall compliance was 56 per cent, but patients on polytherapy actually had significantly higher compliance rates than those on monotherapy¹⁹.

Finally, a potential reason why people fail to administer drugs to their pets is because they simply forget. Most people have fixed daily routines and giving medication to a pet may not fit into it. By giving medication to the pet at a different time each day, we never learn to establish a habit, but if giving the medication is paired with an already established habit (for example, the first cup of coffee in morning), compliance can increase dramatically²⁰.

How to improve compliance in PPID

Clients frequently have a very strong pet bond, and owners essentially want the best possible care for their animals, but they need to be involved in that initial decision-making process and communicated with regularly to maximise compliance²¹. The recommendations need to include not only verbal but also visual and/or written information.

Secondly, compliance can be improved through advanced scheduling of regular follow ups and sending reminders²¹, as owners are busy with life and are likely to forget or postpone their pet care responsibilities.

Finally, compliance can be improved by establishing a standard protocol for the condition and then training the veterinary team to deliver a consistent message in an effective manner²¹.

The following practical strategies that can be employed.

Understand the barriers to owner compliance

Firstly, identify and comprehend the hurdles that the individual owner is facing.

These include inadequate understanding of the advice given due to the use of complex medical jargon or rushed explanations, financial constraints due to the cost of the treatment, and uncooperative patients making administering medication difficult.

Implement strategies to improve compliance

Strategies to enhance understanding include improved communication by using plain language, visual aids and demonstrations, and establishing empathy to help form stronger bonds with clients and increase their trust in the veterinary advice provided and also make them feel more comfortable in discussing their concerns or misunderstandings.

Training is needed to ensure all staff are trained in effective communication techniques, handling difficult situations, and the importance of empathy. If the owner has a better understanding of the animal’s illness and is convinced that treatment can have a positive effect, they will be more willing to follow up prescription instructions. Besides avoiding professional language and repeating yourself, it is necessary to have the owner’s undivided attention. It should be remembered that the owner may have no knowledge of the symptoms or disease progression, or about the therapeutic options and the possible result of treatment. These should be explained alongside the possible side effects. In addition, the owner should be given precise instructions on the exact use of the medication, and the veterinarian must convince the owner of the necessity of using the medication and of the consequences of poor compliance. Written information in combination with verbal instructions on medication use appears to have a positive effect on compliance, whereas written information only, such as that on medicine labels, has no effect on compliance.

Finally, because many owners are often afraid to ask questions, it is important to find out whether or not the owner understands the situation by explicitly asking if the information is understood. Giving owners the opportunity to ask questions has been found to stimulate compliance, and compliance is higher when owners consider that the veterinarian has spent sufficient time on the problem.

Where financial constraints exist, making recommendations more affordable through use of payment plans and prescribing generic medications where possible might help. The use of follow-up systems that generate reminders by text or email for medication administration and scheduling of regular follow ups might be beneficial for those owners that simply forget.

Finally, for patients that are uncooperative, a number of possible solutions exist, some of which might work in an individual animal, including:

Palatability solutions. Mix pergolide tablets with small amounts of water, maple syrup, honey, apple sauce, yoghurt, custard or molasses to syringe directly into the mouth.

Alternative administration. If the horse refuses tablets, try using a compounded paste. If this does not work, then consider changing to injectable cabergoline.

Conclusion

It is vital that equine veterinarians see the value in medication compliance for PPID and the steps that should be taken to maximise it, as non-compliance has a negative impact on the animal due to failure of the clinical signs to improve, and on the owner due to dissatisfaction.

The owner should be involved in developing the treatment protocol and feel empowered, able and confident.

The vet should spend time with the owner to ensure that they fully understand PPID and the need for daily medication, as well as the negative impacts of non-compliance.

Use of pergolide formulations that can be given without a negative reaction, or are associated with a positive reaction, would be expected to result in better compliance.

A generic peppermint-flavoured pergolide tablet that can easily be split as needed has just been approved for use in the US; it is possible that something similar may become available in other countries soon, which might be beneficial in cases where the owner struggles with poor palatability and/or accurate dosing.

Finally, the administration of the medication should be paired with an already established habit, as this will likely increase compliance.

• Use of some of the drugs in this article is under the veterinary medicine cascade.
• This article appeared in Vet Times (2 June issue), Volume 56

Nicola Menzies-Gow qualified from the University of Cambridge in 1997 and, after three years in first opinion equine practice in Essex, joined the RVC, where she completed a residency in equine medicine and a PhD. Now a senior lecturer in equine medicine, Nicola’s clinical interests focus on endocrinology, cardiology and general medicine.