Research

The Use of Valeriana officinalis (Valerian) in Improving Sleep in Patients Who Are Undergoing Treatment for Cancer: A Phase III Randomized, Placebo-Controlled, Double-Blind Study (NCCTG Trial, N01C5)

Publish date: February 13, 2011

Table 5. Self-Reported Side Effects: Change from Baseline—Higher Numbers Are Better

SIDE EFFECT	WEEK	VALERIAN	PLACEBO	P
Nausea	Week 4	3.0	–2.1	0.07
	Week 8	3.4	0.0	0.06
Headache	Week 4	4.8	1.5	0.09
	Week 8	6.7	4.6	0.27
Trouble waking	Week 4	8.8	4.3	0.42
	Week 8	9.5	5.7	0.36
Drowsiness	Week 4	21.0	9.7	0.04
	Week 8	24.0	14.0	0.03
Sleep problems	Week 4	18.7	4.3	<0.01
	Week 8	24.0	13.0	0.03

Discussion

This study failed to identify any significant improvements in sleep as measured by the overall PSQI or the FOSQ in this population. This corroborates data from a recent study by Taibi and colleagues,⁴⁹ who evaluated 300 mg of valerian, taken half an hour before bed. They reported that valerian did not improve any self-reported or polysomnographic sleep outcomes significantly more than placebo. The Taibi et al. study has several possible limitations, including a small sample size (n = 16), a dose lower than that used in the majority of pilot trials with promising results, and a duration of only 15 days on the study agent.

The current study is one of the few randomized placebo-controlled trials evaluating pharmacological treatment of insomnia complaints among cancer patients. Most randomized trials of treatments directed at insomnia in cancer patients compare CBT with usual care or wait-list care and find it of substantial benefit.^[50]^,^[51]^,^[52]^,^[53]^,^[54]^,^[55]^,^[56]^,^[57]^,^[58]^and ^[59] One prior trial in terminal cancer patients evaluated intravenous agents for effectiveness, and another controlled trial found mirtazapine to be effective at improving sleep complaints in cancer patients with depression.^[51]^and ^[60] Otherwise, there are no other controlled trials assessing pharmacologic agents to primarily address sleep-related complaints in cancer patients.

While there was no significant improvement in sleep quality as assessed by the PSQI, there were consistent improvements in the secondary fatigue outcomes as measured by both the BFI and the POMS Fatigue-Inertia subscale. Although caution is required in interpreting these secondary results, the raw differences in change scores between the two arms are fairly large, often over 10 points (on a 100-point scale). In addition, several other secondary end points—change from baseline related to sleep latency, amount of sleep per night, improvement in sleep problems, and less drowsiness—all support the valerian arm outperforming placebo.

There are several hypotheses related to the inconsistencies in the results. The PSQI may measure different dimensions of well-being from the BFI or POMS, the former concentrating on sleep-quality measures, while the latter two concentrate on daytime symptoms. The correlation between sleep-quality and daytime symptoms may not be very strong in this study's population. Another possibility is that there was a beta-error. Some of the data were incomplete due to the patients' inability to complete the questionnaires appropriately. The power analysis suggested 100 patients per arm were required, and only about 60 per group provided data for analysis. Another hypothesis is that the effects of valerian were too modest and limited to one aspect, perhaps sleep latency, that were not detectable with multidimensional scales such as the PSQI or the FOSQ that look at impact on activity.

There were more patients who withdrew from the placebo arm early compared to the valerian arm. The reasons for this are not known. However, patients on this trial were getting active treatment for cancer, so numerous and varied reasons could explain early withdrawals including complications from treatment, increased fatigue, and worsening sleep problems.

In summary, this trial did not provide data to support that valerian is helpful in improving sleep during cancer treatment in this population. It is not clear whether valerian may have helpful physiologic activity supporting research in oncology symptom management related to fatigue. Perhaps further exploration is warranted.

Acknowledgments

This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-124477 (Mentorship Grant), CA-35431, CA-63848, CA-35195, CA-35133, CA-35267, CA-35269, CA-35103, CA-35101, CA-63849, CA-35119, CA-52352, CA-35448, CA-35103, CA-03011, CA-107586, CA-35261, CA-67575, CA-95968, CA-67753, and CA-35415. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institutes of Health.

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The Use of Valeriana officinalis (Valerian) in Improving Sleep in Patients Who Are Undergoing Treatment for Cancer: A Phase III Randomized, Placebo-Controlled, Double-Blind Study (NCCTG Trial, N01C5)

Discussion

Acknowledgments

References

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