Editor's Note
Insomnia is one of the most common sleep disorders, which can have a significant impact on many facets of mental and physical health. Pharmacotherapies primarily include benzodiazepines and sedating antidepressants which may be associated with side effects.
 
Ziziphus spinosa seeds (ZS) are commonly used in Chinese medicine, and are a potential candidate for the treatment of insomnia.  An early mention of ZS use for sleep was published circa AD 992 in a classical Chinese herbal medicine book, Tai Ping Sheng Hui Fang. Clinical trials using ZS combined with other herbs have also shown promising effects on improving sleep quality and were safe for people with insomnia; to date there have been no rigorously designed, high quality studies of ZS as a stand-alone treatment for insomnia. This feasibility study aimed to explore trial design, eligibility criteria, recruitment, treatment acceptability, outcome measures and provide data to perform a future full-scale randomized controlled trial of ZS for insomnia.

The researchers performed a randomized, double-blind, placebo controlled, cross-over trial of 12 participants with chronic insomnia over 14 weeks including a two-week run-in, four-weeks treatment with ZS or placebo, four-weeks wash out (no treatment given), and four-weeks treatment with the alternate treatment.  Efficacy endpoints were only planned to provide preliminary results as the study was not appropriately powered to determine the efficacy of ZS for insomnia. Yet, the outcomes showed encouraging results for the ZS treatment. Sleep quality measures and subjective sleep parameters such as total sleep time, sleep efficiency and sleep onset latency showed improvement after ZS but not placebo.  This study takes the first steps towards evaluating a promising natural product with known sedative compounds that can be safely used by people with insomnia. The results of the trial support the feasibility and acceptability objectives of conducting a future fully powered randomized controlled trial of ZS for insomnia.
Abstract

Objectives
To evaluate the feasibility of implementing a clinical trial protocol of the herbal seeds Ziziphus spinosa (ZS) for people with insomnia.

Design and setting
A randomized, double-blind, placebo controlled, cross-over feasibility trial in Melbourne, Australia.

Interventions
After two-week run-in participants were randomized to either ZS (encapsulated granules; 2 g daily) or placebo for four weeks. After four-weeks wash-out, participants swapped to the other treatment for four weeks.

Main outcome measures
Sleep quality assessed by the Insomnia Severity Index and Pittsburgh Sleep Quality Index (PSQI). Quality of life, mood, functional impairment and sleep parameters were also assessed.

Results
Twelve participants were randomized and completed both periods of cross-over (six in each sequence). Feasibility endpoints were acceptable. Improvements for sleep quality measured on the PSQI were statistically significant during the ZS treatment periods compared to placebo (t = −2.276, df = 10, 95 % CI −3.3 to −0.04, p = 0.046). There was no evidence of any significant carryover effects. However, there were period effects. Other outcomes showed no statistically significant difference between the treatments. Subjective sleep parameters measured on sleep diaries showed improvements after ZS in terms of total sleep time, sleep efficiency and sleep onset latency, but not after placebo. ZS was well tolerated with only minor adverse events.

Conclusions
ZS is an acceptable and well-tolerated herbal candidate for the treatment of insomnia. The feasibility objectives of this study were achieved and ZS improved both subjective sleep quality and quantity compared to placebo. ZS should be explored in future clinical trials.
2021 Annual Fund Sponsors: