Feifel 2011.

Methods	Randomised single‐blind trial
Participants	Number of total participants/type of patients: 30 participants randomised. Inpatient study Inclusion criteria: Sex: male and female Age: 18 ‐ 65 years Diagnosis: Bipolar I disorder, most recent episode manic, or bipolar I disorder, most recent episode mixed, with or without psychotic features, as defined by DSM‐IV were recruited. Participants were recruited from among those presenting to the University of California, San Diego (UCSD) Medical Center’s emergency department and deemed needing hospitalisation for their mania, and from those recently admitted to the inpatient psychiatry unit for treatment of acute mania. Consenting participants were enrolled if they scored > 17 on the YMRS as well as receiving a score of 4 (moderate) or higher on the CGI‐S. Exclusion criteria: Treatment with a depot antipsychotic was within 1 treatment cycle.
Interventions	Location: USA, San Diego Medical Center Study duration: Not stated Treatment groups: 1. Valproate extended‐release: Dose initiated at 30 mg/kg/day orally taken at night, rounded up to the nearest 500 mg dose, with adjustments made through the trial to obtain optimal serum valproic acid levels between 85 and 125 mug/mL 2. Quetiapine: Dose given orally at an initial dose of 200 mg/day and titrated up to a target dose of 600 to 800 mg/day, based upon published rapid‐loading regimens Concomitant medications: Lorazepam was provided for agitation and insomnia as needed for rescue only. The maximum dose of lorazepam was 6 mg in the first 7 days, 4 mg for the next 3 days, and 2 mg/day for the remainder of the study. Those who required a greater amount of lorazepam were excluded. Nonpsychotropic medications were allowed as deemed necessary by the participant’s treated physician. Length of study: 21 days Randomisation: 14 patients randomised to valproate extended‐release 16 patients randomised to quetiapine
Outcomes	Primary outcome: Change from baseline to endpoint on the YMRS Secondary outcomes: CGI‐S, CGI‐I, Extra Pyramidal Symptoms Rating Scale (ESRS), MADRS, Behavioural Activity Rating Scale (BARS) Adverse events were reported Study withdrawals were reported
Funding	"The study was supported by a research grant from Abbott Laboratories"
Conflict of interest	"Dr. Feifel has received funding for research, consulting, or speaking from Abbott Labs, Alexa, AstraZeneca, Bristol‐Myers Squibb, Eli Lilly, Forest, Janssen, Merck, Otsuka, Pfizer, Sanofi, Shionogi, Shire, and Sunovion; Dr. MacDonald has received funding for research, consulting, or speaking from Cypress Bioscience, Eli Lilly, Onu Pharmaceuticals, and Pfizer; Ms. Galangue, Cobb, and Dinca and Drs. Becker, Cooper, and Hadley report no conflicts of interest relevant to the content of this article."
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: No comment on randomisation procedure in text. We contacted the authors but received no reply.
Allocation concealment (selection bias)	Unclear risk	Comment: No comment on randomisation concealment in text. We contacted the authors but received no reply.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Raters but not patients or treating physicians were blinded."
Blinding of outcome assessment (detection bias) Efficacy	Low risk	Quote: "Raters but not patients or treating physicians were blinded." Quote: "Independet raters, blind to the subjects' treatments used the following scales to assess efficacy."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: In all groups dropout rate was below 30%.
Selective reporting (reporting bias)	High risk	Comment: Mean change in YMRS scores from baseline to endpoint reported without standard deviations. All other data represented only in graphical form. This leaves us unable to conduct any analysis on any of these data.
Other bias	Low risk	Comment: None identified