Shell 2012.

Methods	Randomised, double‐bind, 4‐armed, controlled trial
Participants	Insomnia diagnosis criteria (method of diagnosis): history of sleep disturbance lasting > 6 weeks and defined by perceived lack of restorative sleep Other diagnoses: none Number of participants randomised: n = 111 Trazodone: n = 36 Sentra PM: n = 28 Sentra PM + trazodone: n = 22 Placebo: n = 25 Number of participants: n = 110 (the participant who did not complete the trial was carried forward as ITT). Age, range: 18‐75 years. No results on actual age of those recruited or gender. Data not available for each arm Gender: not reported Race/ethnicity: not reported Country: USA Setting: 12 independent sites around the USA Included: men and non‐pregnant and non‐lactating women aged 18‐75 years with history of sleep disturbance lasting > 6 weeks and defined by perceived lack of restorative seep were enrolled by the study physician in each site. Excluded: people currently taking tricyclic antidepressants; who had previously taken Sentra PM, trazodone or another amino acid formulation; with biochemical abnormalities that would put the person at risk or invalidate study findings Withdrawals: n = 1 (included as ITT) Baseline imbalances: uneven randomisation occurred due to higher enrolment rates at some of the clinical sites; however, this did not affect the statistical outcome of the study. Authors state that table 2 demonstrated that the 4 study groups were "statistically comparable" at baseline.
Interventions	Intervention 1: trazodone 50 mg daily at bedtime + 2 capsules Sentra‐like placebo at bedtime Comparator 1: placebo (1 trazodone‐like placebo and 2 Sentra‐like placebo at bedtime Comparator 2: Sentra PM alone (a neurotransmitter based medical food) 2 capsule dose at bedtime + 1 trazodone‐like placebo at home Comparator 3: Sentra PM 2 capsule dose + trazodone 50 mg at bedtime
Outcomes	Primary outcomes Quality of sleep assessed by the sleep latency using the PSQI. reported in tables 2 (baseline) and 3 (14 day). Table 3 had no CI Morning grogginess measured by the LSEQ Hours of sleep Secondary outcomes Latency Hours of sleep
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "randomised," but no further information given. Also reported uneven recruitment between sites caused uneven randomisation (Pg 67‐68).
Allocation concealment (selection bias)	Unclear risk	Data about participants unavailable (Pg 67).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Reported double blind. All participants received identical capsules at the same time.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details given
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 participant did not complete the trial, but data were carried forward as ITT
Selective reporting (reporting bias)	Low risk	Independent biostatistician analysed data. All randomised participants were included, both ITT and completed (Pg 68, statistical analysis section).
Other bias	Low risk	Study was funded by a pharmaceutical company, but the analysis was performed independently.