Berk 2019.
| Study characteristics | ||
| Methods | Double‐blind, randomised, placebo‐controlled trial | |
| Participants |
Diagnosis: DSM‐IV‐TR bipolar disorder (I, II, or not otherwise specified) on MINI, MADRS score ≥ 20; current acute depressive episode
N: 181 Age: N‐acetylcysteine (NAC) group M = 44.9 (SD = 12.5), NAC+ combination of nutraceutical agents (CT) group M = 46.3 (SD = 12.7), placebo group M = 45.4 (SD = 11.9) Sex: NAC group = 61% female, NAC+CT group = 63.9% female, placebo group = 65.6% female Baseline depression severity: N‐acetylcysteine (NAC) group M = 28.8 (SD = 5.2), NAC+ combination of nutraceutical agents (CT) group M = 29.5 (SD = 5.6), placebo group M = 29.4 (SD = 5.6) |
|
| Interventions | 16 weeks treatment adjunctive to usual treatment (medications not specified) with 2000 mg/day NAC, 2000 mg/day NAC with the combination nutraceutical treatment, or placebo |
|
| Outcomes | MADRS HAM‐A BDRS YMRS CGI‐improvement CGI‐severity PGI‐I SOFAS LIFE‐RIFT Q‐LES‐Q‐SF |
|
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: “Participant number allocation to treatment arm was randomly assigned using permutated block randomisation. The computer‐generated randomisation plan was developed by an independent researcher utilising four‐to‐a‐block design. Participant numbers were sequentially allocated by trial clinicians.” (p2) |
| Allocation concealment (selection bias) | Low risk | Quote:“To facilitate the double‐blinding process, the trial medications (CT, NAC only, and placebo) were packed in the medicopacks and dispensed by an independent pharmacist in sealed containers. Medicopacks and capsules in all arms were identical, to conceal treatment allocation and blinding.” (p2) |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote:“Medicopacks and capsules in all arms were identical, to conceal treatment allocation and blinding. The consultant statistician (SC), investigators, and participants were blinded to the group allocation.” (p2) |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote:“The consultant statistician (SC), investigators, and participants were blinded to the group allocation”. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | CONSORT diagram included (p7) |
| Selective reporting (reporting bias) | Low risk | Protocol published, outcomes reported as expected. |
| Other bias | Unclear risk | None identified. |