Fatigue - a one patient case study

Updated Information of Modafinil (Provigil) From ASCO 2007

 

Abstract 9004(a) presented results of using Modafinil for cognitive functioning in breast cancer patients.  The results suggested a positive effect on cognitive impairment.  The study also was reported to have shown a positive effect on fatigue, with the results to be published in the near future (by Gary Marrow, MD).

 

The study had an open label portion for 4 weeks where everyone received modafinil (200mg once/day); then those who reported a beneficial effect on fatigue (which was 68 of the 76 patients) were randomized to receive modafinil or placebo for 8 more weeks.  Attention and speed of memory were improved in the modafinil group.

 
Thus, there is the possibility of a dual benefit from using Modafinil.

 

The cognitive effects of modafinil in breast cancer survivors: A randomized clinical trial, Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 9004.
 

Howard Hansen 26th July 2007

Fatigue management during HRPCa (hormone-refractory prostate cancer) chemotherapy: a comparative evaluation of Modafinil and Methylphenidate by one patient


SUMMARY

One HRPCa patient, in a self-managed trial, compared the efficacy of two drugs used to control fatigue resulting from extensive and repeated chemotherapy treatments. He used a subjective, personal performance scale to measure his energy level (EPS-1= lowest energy; EPS-5= normal energy). With appropriate professional medical guidance, he dosed modafinil (Provigil) at 200 mg q.d. for 8 days and methylphenidate (Ritalin) at 5 mg q.i.d. for 6 days. RESULTS. Modafinil raised the energy level from EPS-2 to 3 over a period of 5 days, before it failed. Following a rest period of 2 days, he dosed methylphenidate, which raised the energy level from EPS-2 to 2.5 over a period of 4 days before it failed. CONCLUSIONS. It appears that the drugs, like methamphetamines, borrow energy from future reserves, which are depleted after several days. After the effective period, the drugs had no further effect on raising the energy level. Thus, it would appear that a self-determined rest period, perhaps 2-4 days, is required between effective dosing periods of up to 5 days, depending on the individual. The modafinil was significantly more effective than the methylphenidate in this application.

INTRODUCTION

Fatigue can be a devastating side effect of chemotherapy used to treat HRPCa, destroying the individual’s quality of life. Two drugs were evaluated to assess their efficacy in raising the energy level, i.e., reducing fatigue. Both drugs had been suggested as possibly useful in this application.

It was also recognized that both drugs would likely have the methamphetamine-type effect of drawing on future energy reserves (the “upper”), followed by the need for rest (the “downer”. However, the much more powerful methamphetamine was considered too dangerous for this application.

No effect on the cancer was anticipated; nor was any observed.

THE DRUGS AND DOSAGES

Modafinil is a wakefulness-promoting agent. The dose listed in the PDR [PDR 2004a] is 200 mg, although larger doses are safe to 400 mg. The dose should be taken first thing in the morning, with or without food. This trial indicated that 400 mg would be an excessive dose, with no benefit achieved. No side effects were noted, although many are listed in the PDR.

Methylphenidate is a mild central nervous system stimulant [PDR 2004b]. It was dosed at 5 mg q.i.d. The patient chose to take a pill at 8 a.m., 10 a.m., noon, and 2 p.m. He found it inconvenient to have to remember to take the pills four times daily. The PDR refers to doses up to 60 mg q.d.; however, the decision was made not to increase the dose for two reasons. First, a published trial [Bruera 2003] did not increase the dose beyond 5 mg q.i.d. Second, there was a potential drug interaction with Coumadin, which the patient was already using; so it was felt better to stay with the conservative dose. The methylphenidate may be more effective at the higher dose, but that question cannot be answered from this trial.

MEASUREMENT OF ENERGY LEVEL

An ad hoc scale was created by the patient to measure his energy level. The subjective scale is shown below:

Energy Performance Scale

1. Little energy to the point of doing no physical work. Spend much of the day resting.

2. Climbing a flight of stairs is fatiguing. Do 2 hours of office work; some walking.

3. Regain desire to work. Walks, longer shopping trips. Some swimming.

4. More frequent physical exercise. Light physical jobs.

5. No energy limitations.

The patient’s baseline energy level was EPS-2.

RESULTS

The modafinil was dosed for 8 days; the effect of the pill was slow, nearly 2 hours in taking noticeable effect. The energy level increased from EPS-2 to EPS-3 for the first 5 days; then it fell back to the baseline EPS-2.

The effect of the drug lasted well into the evenings. The first night, the patient was unable to sleep until he took an Ambien at 4:00 a.m. On subsequent nights he was able to sleep.

During the first 5 days, the drug prevented him from sleeping at all during the day. By the sixth day, however, the diminishing energy level enabled him to sleep during the day. The energy level gradually returned to EPS-2, the baseline.

Before taking methylphenidate, the patient discontinued the drugs for 2 days to restore his energy reserve. Depending on the individual user, more or less recovery time may be required.

The methylphenidate was dosed for 6 days. The energy level increased from the baseline EPS-2 to an estimated EPS-2.5. At that time it was clear that this drug—at the designated dose—was not having the same effect as the modafinil. The drug effect was less and the duration was shorter, so the trial was discontinued.

DISCUSSION

It was clear that, in the case of this patient, Modafinil was more effective in increasing his energy level.

The starting energy level was EPS-2 due to extensive chemotherapy. This level served as the baseline for evaluation of both drugs. The modafinil-induced increase from EPS-2 to EPS-3 was significant to the patient, who plans to continue using the drug. The methylphenidate-induced increase from EPS-2 to EPS-2.5 was slight, but still noteworthy. If the methylphenidate had been the only choice, he would have used that drug.

With modafinil, the patient reported a clear feeling of wakefulness, even to the point of not being able to sleep the first night of usage. During the first 5 days, he could not fall asleep for a nap in the afternoon, even though he felt tired.

No side effects were experienced with either drug. However the PDR [PDR 2004a, PDR 2004b] lists many possible side effects that should be reviewed prior to use.

Given the pretrial expectation that “every upper has a corresponding downer,” the patient recorded his energy levels over a period long enough to outlast the energizing effects of the drugs. The stronger modafinil failed after 5 days, and his energy level returned to the baseline EPS-2. A rest of 2-3 days was needed to restore the energy reserve necessary to allow the drug to work again. The rest period was not severe, with the energy level dropping back no lower than the original baseline.

It is likely that the period of efficacy and the period of recovery will be determined by the individual user’s condition. This patient’s expected usage of 200 mg q.d. modafinil for 5 days, followed by a recovery period of 2-3 days would be a reasonable starting point for someone determining a suitable dosing regimen.

As a final point of the discussion, the patient was asked, “Is modafinil (Provigil) worth the bother to gain a limited amount of additional energy temporarily.” His response was affirmative and that he would continue to use the drug.
 

By Bob Benson
Date: 6-24-04

REFERENCES

Bruera E, Driver L, Barnes EA, Willey J, Shen L, Palmer JL, Escalante, C, (Dec. 1, 2003) “Patient-Controlled Methylphenidate for the Management of Fatigue in Patients with Advanced Cancer: A Preliminary Report,” J Clin Oncol, 21 (3): 4439-4443.

PDR: Physicians’ Desk Reference (2004a), “Provigil,” 58th edition, Thomson PDR, 1160-63.

PDR: Physicians’ Desk Reference (2004b), “Ritalin Hydrochloride,” 58th edition, Thomson PDR, 2297-98.

 

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