Using Medications as a Management Strategy for Persons with PWS

Barbara Y. Whitman, PhD, Prof. of Paediatrics, St Louis University School of Medicine.

Often, one of the first questions of parents who have learned that their child has PWS is, "What medications may s/he need?" This simple question requires a very complex answer. As with many genetic syndromes, there is no "cure" for PWS. Medications and other medical interventions are employed to correct specific impacts of the disorder, or for "symptom management" of aspects of the disorder. For example, heart surgery may completely correct a heart defect in a child with Down Syndrome but does not change the character of the syndrome itself.

PWS presents unique management issues on many dimensions. Besides managing the hyperphagia (excessive appetite) and its consequences, cognition, learning and behaviour are additional challenges presented by the person with PWS. Indeed as the young person with PWS matures, managing behaviour difficulties is frequently more problematic than managing food-related issues. Additionally, these evolving behaviour challenges are frequently accompanied by intense emotional disturbances that further complicate management. And all of these issues are further complicated by a little-understood refractivity (unresponsiveness) or, conversely, a toxic reaction to medications effectively used for these "symptoms" in persons without PWS.

Let us briefly review some of these areas.

Hyperphagia and Obesity

A number of medications have long been employed to suppress appetite. Foremost among these are the "amphetamines" such as Dexedrine and Benzedrine. While quite effective, the side effects of long term use of these medications has led to the search for alternatives. In the past two decades, a number of newer compounds have been introduced with variable effectiveness. In addition, other compounds that work to block fat absorption or to "dissolve" fat tissue are in development. Without exception, these medications have been ineffective in addressing the brain signals that drive the person with PWS to seek food and overeat. Until such a medication is discovered, good management depends on environmental protection against overeating, as well as an understanding caregiver who recognises that a constant feeling of being hungry is a natural stimulus for being irritable and occasionally hard to get along with.

Behaviours and Emotions

When the behaviour/emotional aspects become unduly disruptive to daily functioning and resistant to other forms of management, behaviour change medication is often sought to supplement other management strategies. As is the case with appetite suppressing medications, many first-line behaviour change medications commonly used in other circumstances are ineffective for persons with PWS. Additionally, many have been noted to worsen the behaviours being targeted by the medication or to create unacceptable side effects such as further increasing appetite. In an effort to develop a systematic database, Dr Louise Greenswag and I initiated a study of effective behaviour change medications for persons with PWS. Our initial study was conducted in 1988 and 1989. In order to maintain as current a database as possible, we have since repeated the study three additional times. A brief description of how the data was obtained is necessary before discussion the results.

All studies have used essentially the same method. Volunteer parents or caregivers respond to a telephone administered interview that systematically inquires about recent (the past year) and prior (ever in a lifetime) use of medications to suppress appetite, facilitate sleep, alter mood (depression, anxiety), alter behaviour, modify feelings (e.g. anger) and the like. Fifteen separate questions regarding various thoughts, feelings and behaviour are systematically addressed. Several additional questions inquire about the use of counselling or psychotherapy or other forms of behaviour therapy. To fully cover the scope of possible medications, one final question that lists many common behaviour change medications is asked. Often this question jogs a memory of a medication briefly tried that was forgotten in responding to the other questions. Finally, when parents who are willing returned signed release of information forms for doctors who may have prescribed such medications, the medical records are then requested. Thus we try to obtain the best quality information by building in a number of pathways to reliability and validity of the data.

The results of the initial study were startling in a number of aspects. We found that almost every behaviour change medication "known to man" had been tried both singly and in multiple combinations in an effort to help alter severe behaviour problems in persons with PWS. What was startling was the ineffectiveness to absolute toxicity of most of those medications. At the time of that initial report, we were able to document real effectiveness only for Haldol, Melloril, and a then-new medication - Prozac.

As we have repeated the study several times over, we have been encouraged by the addition of many more medications that have successfully been used for persons with PWS. Many of these are the newer generation of the prototype SSRI (Selective serotonin re-uptake inhibitor) medication, Prozac. Several medications that have been successfully used for other conditions such as seizures have in some instances proven helpful in altering difficult behaviour in PWS. So today, there is a larger medication armamentarium that can be employed to help difficult behaviour in persons with PWS.

Considerations and Cautions

Despite the larger number of medications that may be helpful, there are a number of cautions that must be raised and issues considered before initiating any medication or a person with PWS.

First is the issue of necessity. Many persons with PWS who are exhibiting frequent and very difficult behaviours are able to completely turn around when a number of environmental changes are instituted. While requiring a lot of thought and hard work to restructure an environment, this solution is always preferable due to the uncertainty of medication effects in any one person.

Second, no single medicine is universally effective. While many persons with PWS have responded dramatically to Prozac, others (just as in the general population) have had severe negative reactions both behaviourally and medically, so that any medication must be carefully thought through and conservatively approached.

Third, we have learned from many difficult situations that persons with PWS are unique in their dosage needs - many responding to one-forth to one-half the dose normally prescribed, but becoming toxic with worsened behaviour at what would be considered "normal" dosage levels for someone without PWS. Thus, unless an extremely cautious approach to dosages is employed, there is risk of making the situation worse. Low dosages, conservative increases, and monumental patience are needed to select and regulate medication for persons with PWS.

Fourth is what can be addressed with these medications. For instance, many medications have been initiated to alter the frequency of skin-picking. While an occasional parent has reported some positive response on this dimension, most do not. Other medications are given to alter or eliminate "bizarre" thoughts. In the event that a person with PWS is hearing voices or seeing things that aren't there (auditory or visual hallucinations), then these medications may be quite effective. Most parents and caregivers, however, report "bizarre" thoughts that are not hallucinations - such as concern that someone has tampered or stolen their "stuff." In this instance, medication may or may not be helpful.

Finally the question of when to start medication is often raised. For many, this question is based on an assumption of the inevitability of medication use, with the age of starting medication the only uncertainty. There is no evidence to support an assumption that medication use is inevitable. Many never need medication. Many may require medication to get through a difficult time, but with appropriate environmental supports can discontinue its use. Thus, the "when to use" is answered with "when the behaviour is so out of control that all other forms of intervention have failed." This may be sooner for some persons, if it is not possible to adjust their environment effectively, and much later for others.