The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies sometimes used by patients with cancer. In this installment, Yen Nien (Jason) Hou, PharmD, DiplOM, LAc, and Jyothirmai Gubili, MS, focus on the use of the multiherb formulation known as Suan Zao Ren Tang, because it is widely used in traditional Chinese medicine for improving sleep health.

Yen Nien (Jason) Hou, PharmD, DiplOM, LAc

Jyothirmai Gubili, MS

Scientific Name: Suan Zao Ren Tang

Common Names: Suanzaoren, Semen Ziziphi Spinosae, Ziziphus, Sour Jujube Decoction, Ziziphus Decoction Formula, Tabellae Suanzaoren Tang

Overview

Insomnia is highly prevalent among patients with cancer and can have a significant negative impact on their quality of life. It may also increase the risk of infections¹ and psychological distress.² Standard treatments offer relief but may be associated with undesirable effects, including performance problems, memory disturbance, falls, and driving accidents.³

Suan Zao Ren Tang (SZRT) is a traditional Chinese medicine formulation comprising five herbs. Historically used to address sleep issues, it continues to be used by practitioners to treat insomnia and is often prescribed for sleep disorders in Taiwan.⁴

The Science

In a randomized controlled trial, 240 adults with chronic insomnia were assigned to receive SZRT (150 mL twice daily) plus the benzodiazepine lorazepam (0.5 mg/d) or lorazepam (0.5 mg/d) alone for 12 weeks. The reductions in Insomnia Severity Index (ISI) were greater in the intervention arm than in the control group at 4, 8, and 12 weeks (P = .008, .001, and .001, respectively). Improvements were also reported in anxiety, a secondary outcome (P < .01), although there were no between-group differences in depression. Of note, subjects in the intervention group reported greater physical functioning at 12 weeks. Compared with the controls, those treated with the intervention also experienced fewer side effects, including loss of appetite, constipation, dizziness, headache, abnormal liver function, and sexual dysfunction (P < .05 or .01).⁵

Similar findings were reported in another trial of 90 patients being maintained on methadone. Participants received SZRT (4 g, thrice daily) or placebo for 4 weeks. At the end of the study period, sleep quality improved significantly in the SZRT group, with mean total Pittsburgh Sleep Quality Index (PSQI) scores decreasing by 3.8 vs 1.9 points (P = .007) and the average diary sleep efficiency increasing by 11% vs 5% (P = .017). However, there were no between-group differences in heroin craving or anxiety and depression scores.⁶

Additionally, in an observational study of 67 climacteric women,⁷ 4-week treatment with SZRT (4 g, thrice daily) yielded significant improvements in sleep quality (mean PSQI scores fell from 13 [± 2.9] to 9 [± 3.2; 95% confidence interval (CI) = −4.93 to −3.10; P < .001]). Of note, women with severe Menopause Rating Scale (MRS) scores had greater improvements in daytime functioning compared with those who had mild or moderate MRS scores.

Preliminary findings also suggest benefits of SZRT in cancer settings. In a 2-week, pilot study of 30 patients with different cancer diagnoses, those who received a modified SZRT formula (3.75 g, thrice daily) had greater improvements in ISI scores than did the waitlist arm (–5.5 ± 4.4 vs 0.1 ± 1.1, P < .001). The formula also affected improvements in fatigue levels (–0.8 ± 0.8 vs 0.0 ± 0.3, P = .002).⁸ In a second trial involving 22 patients with cancer, a modified SZRT formula (once daily between meals) taken for 4 weeks was as effective as cognitive behavioral therapy for insomnia (CBT-I) in mitigating insomnia along with affecting significant reductions in anxiety symptoms compared with CBT-I (P < .001).⁹

The safety and benefits of the short-term use of SZRT were confirmed in a systematic review/­meta-analysis (9 trials, 905 patients with sleep disturbance or insomnia). Study authors reported significant improvements in subjective sleep quality in participants who took SZRT compared with those in the placebo arm (standard mean difference, –0.58, 95% CI = –1.04 to –0.11; P < .01). Furthermore, SZRT affected notable reductions in insomnia severity when compared with benzodiazepines or CBT (mean difference –2.68 points, 95% CI = –5.50 to –0.22; P = .03).¹⁰

Although the mechanisms by which SZRT exerts its effects are not fully known, pharmacologic studies revealed that the bioactive components of SZRT, including jujubogenin, jujuboside A, and jujuboside B, enhance sleep activity by stimulating serotonin and gamma-aminobutyric acid (GABA) receptors.^11-14 Spinosin, another compound, was shown to increase total sleep time while reducing sleep latency in rats treated with pentobarbital.¹⁵

GUEST EDITOR

Jun J. Mao, MD, MSCE

Dr. Mao is the Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.

Adverse Reactions

Clinical studies of SZRT have reported sleep disruption, dizziness, dry mouth, facial skin rash, urinary urgency, constipation, diarrhea, fatigue, lethargy, and sweating.^6,16-19

Herb-Drug Interactions

Concurrent use of SZRT with serotonin reuptake inhibitors²⁰ or monoamine oxidase inhibitors²¹ may amplify the sedative effects of these medications.

Summary

Available evidence indicates that Suan Zao Ren Tang has a positive impact on individuals with sleep issues. More research is needed to determine its benefits in diverse populations and to assess its long-term effects. Also, the heterogeneity of trial participants (eg, those with insomnia or inconsistently defined sleep disturbance) should be decreased to better define the effects of this formula. Cognitive behavioral therapy for insomnia is still the first-line treatment, but SZRT may be appropriate for patients with cancer who may want to try nonpharmaceutical and non–habit-forming options.

To ensure appropriate use of SZRT, it is important to guide patients to seek licensed traditional Chinese medicine practitioners experienced in working with cancer populations (https://www.nccaom.org/find-a-practitioner-directory/). 

DISCLOSURE: Dr. Hou and Ms. Gubili reported no conflicts of interest.

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