Homeopathy for Major Depressive Disorder: Protocol for N-of-1 Studies

Abstract

<b><i>Background:</i></b> N-of-1 studies allow the formal assessment of a patient’s treatment. A single participant receives different interventions the same number of times in a crossover, double-blind, randomized design. Using this methodology, we will investigate the effectiveness and safety of a standardized homeopathy protocol in treating 10 cases of major depression. <b><i>Methods:</i></b> The method is described below: Design: crossover double-blind placebo-controlled randomized N-of-1 studies, with at most 28 weeks of duration per participant. Participants: women and men at age over 18 years with a diagnosis of a major depressive episode given by a psychiatrist, who have presented a therapeutic response, i.e., a reduction ≥50% of the baseline depressive symptoms, self-assessed by the Beck Depression Inventory – Second Edition (BDI-II), and sustained for at least 4 weeks during an open homeopathic treatment following the protocol of the sixth edition of the <i>Organon</i>, with or without concomitant use of psychotropic drugs. Interventions: individualized homeopathy following the same protocol, one globule of the fifty-millesimal potency diluted in 20 mL of 30% alcohol; placebo – 20 mL of 30% alcohol, in the same posology as homeopathy. Crossover study: the participant will go through three consecutive treatment blocks, with two random and masked treatment periods (A or B), corresponding to homeopathy or placebo. Treatment periods will have 2, 4, and 8 weeks in the first, second, and third blocks, respectively. A clinically significant worsening (characterized by an augmentation in BDI-II inclusion score ≥30%) will result in the termination of study participation and resumption of the open treatment. Primary measure: progression of the depressive symptoms, self-assessed by the participant using the BDI-II scale at weeks 0, 2, 4, 8, 12, 16, 20, 24, 28 and analyzed throughout the study concerning homeopathy and placebo partitions. Secondary measures: score of the Clinical Global Impression Scale; mental and physical health scores assessed by the 12-Item Short-Form Health Survey; participant’s blind preference for treatment A or B at each block; clinical worsening; and adverse events. Data analysis: the participant, assistant physician, evaluator, and statistician will remain blinded for the study treatments until the completion of data analysis of each study. We will follow a 10-step procedure for analyzing N-of-1 observational data of each participant and conduct a meta-analysis of the combined results. <b><i>Discussion:</i></b> We understand that each N-de-1 study will be a chapter with its teachings in a book of ten, allowing a broader view of the effectiveness of the homeopathy protocol of the sixth edition of the <i>Organon</i> in treating depression.