NCT01912196.

Trial name or title	Add‐on Study of MSI‐195 (S‐Adenosyl‐L‐Methionine, SAMe) for Patients with Major Depressive Disorder (MDD)
Methods	Double‐blind, randomised, placebo‐controlled trial
Participants	Men and women aged 21 to 70 years DSM‐IV‐TR diagnosis of major depressive disorder with a total score ≥ 16 on the HAM‐D17 at screening and baseline visits, with a score of ≥ 2 on mood item 1, have experienced 1 to 4 prior major depressive episodes, have failed 1 to 3 treatment regimens in the current depressive episode, have received an adequate dose and duration of antidepressant therapy (on antidepressant therapy for at least 6 weeks with a stable dose for at least 3 weeks) Exclusion criteria: failed ≥ 4 adequate treatment regimens in current episode of depression, significant risk for suicidal behaviour, intolerance to SAMe, prior use of MSI‐195; history of any of the following psychiatric disorders: eating disorder within 6 months, obsessive compulsive disorder, psychotic disorder, bipolar disorder, mental retardation, dementia or other forms of cognitive impairment at any time or alcohol‐ or substance‐use abuse; > 3 x ULN alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase; > 1.5 x ULN total bilirubin; pregnant or lactating women; any history of seizures, excluding febrile seizures; known positivity for human immunodeficiency virus
Interventions	Adjunctive MSI‐195: 2 tablets (800 mg) of MSI‐195 plus ongoing antidepressant therapy Adjunctive placebo: 2 tablets placebo plus ongoing antidepressant therapy 8 weeks
Outcomes	HAM‐D17: assessed from baseline to week 8 MADRS: assessed at baseline, weeks 2, 4, 6, 7 and 8 CGI‐Severity: assessed at baseline, weeks 2, 4, 7 and 8 IDS‐Self Rated 30: assessed at baseline, weeks 2, 4, 6 and 8 Adverse events: assessed at baseline, weeks 1, 2, 3, 4, 6, 8 and 9 (follow‐up) Columbia Suicide Severity Rating Scale: assessed at baseline, weeks 2, 4, 6 and 8
Starting date	October 2013
Contact information	Clayton Janik, clayton.janik@ppdi.com; Scott Smith, scott.smith@ppdi.com
Notes

5‐HTP: 5‐hydroxytryptophan; BDI: Beck Depression Inventory; CGI: Clinical Global Impression; DHA: docosahexaenoic acid; DSM: Diagnostic and Statistical Manual of Mental Disorders; ECT: electroconvulsive therapy; EPA: eicosapentaenoic acid; HAM‐A: Hamilton Rating Scale for Anxiety; IDS: Inventory of Depressive Symptomatology; IU: international unit; LSEQ: Leeds Sleep Evaluation Questionnaire; MADRS: Montgomery‐Åsberg Depression Rating Scale; MAOI: monoamine oxidase inhibitor; MINI‐Plus: Mini‐International Neuropsychiatric Interview; SAFER: Massachusetts General Hospital SAFER interview; SAMe: S‐adenosyl methionine; SF‐12: 12‐item Short Form; SNRI: serotonin‐noradrenaline reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant; TMS: transcranial magnetic stimulation; ULN: upper limit of normal.