In this study, depressed outpatients were randomly assigned to a double-blind treatment with individualized homeopathic Q-potencies or fluoxetine. The non-inferiority analysis indicated that the homeopathic Q-potencies were not inferior as compared to fluoxetine in treatment of this sample of outpatients with moderate to severe depression.
This is the first randomized controlled double-blind trial with a reasonable number of subjects to draw conclusions about the homeopathic treatment of depression, to the best of our knowledge. In fact, a recent systematic review found only two randomized controlled trials examining the use of homeopathy to treat depression, one of low methodological quality (non-blinded) and the other with recruitment‘s difficulties: eleven participants were included and only three completed the study [30
The current sample was not recruited by advertisement and it was not composed by “consumers of alternative medicine” [33
], but by help-seeking patients referred to clinic of Homeopathy and Depression of Jundiaí Medical School by health care professionals within the public health system. The predominance of women participants in a proportion greater than normally expected may be partially explained by men's relatively limited use of public health services in Brazil, a trend that has been associated with representation of caring as a female task, work-related issues, difficult access to services and lack of services specifically targeting men's health [34
The need of individual prescriptions in classical homeopathy has been considered as “a severe obstacle for any double-blind trial” by experienced researchers [17
]. In fact, a study design in which the selection of a suitable, individualized homeopathic medicine occurs during the double-blind randomized phase evaluates not only the efficacy of homeopathy, but also the efficiency of the homeopath in selecting and managing that medicine. A placebo substitution design (with an open-label phase preceding the randomization) would be recommendable, but in depression studies such a design is used for continuation or maintenance trials [35
] and not to assess the treatment of the acute episode.
Primary efficacy measure results indicated mean MADRS scores differences were neither significant at the 4th week (P
= .654), nor at the 8th week (P
= .965). There were also no significant differences between response or remission rates in the two treatment groups, which were over 70% and in some degree superior to those found in primary care settings for active antidepressant interventions, favoring the hypothesis that “the homeopathic consultation is in itself a therapeutic intervention working independently or synergistically with the prescribed remedy” [36
A placebo-arm was not included in the present study because it was not authorized by the National Ethic Council. Although placebo interventions are associated with mean response or remission rates of ~
], a placebo effect cannot be ruled out, since the homeopathic Q-potencies were compared with an antidepressant and “it is becoming more and more difficult to prove that antidepressants—even well-established antidepressants—actually work better than placebo in clinical trials” [39
]. Nevertheless, it also has to be taken into consideration that the antidepressant-placebo difference seems to be smaller in the trials aiming at mild to moderate depression [40
] and the present sample consisted of patients suffering from moderate to severe depression. Placebo-controlled studies would be recommendable to clarify these findings.
Fluoxetine and homeopathy patients showed differences, although not significant, in exclusion profiles and tolerability. There was trend toward greater treatment interruption for adverse effects in the fluoxetine group, what is in line with the higher percentage of troublesome adverse effects reported by patients receiving fluoxetine. On the other hand, more patients randomized to homeopathy than to fluoxetine were excluded due to worsening of their depressive symptoms. Possible explanations are that casual differences can occur in small samples, or that homeopathy was not effective in protecting against stressful situations or even that the medicines selected were non-homeopathic, that is, not adequately individualized to match the peculiar symptoms of each case. There is no data about the efficacy of homeopathy in protecting against depression relapse or recurrence, but it's known that stressful life events can cause recurrence of depression even in conventionally medicated patients [42
The current study has other limitations besides the lack of a placebo control, such as dependence on a single homeopathic practitioner, a relatively small sample and a short period of treatment—the acute phase of depression. A multicenter trial could include a larger number of participants, from different homeopathic research centers, increasing the generalizability of the results. Nevertheless, larger or multicenter trials aiming at repeating these results should take in account the need for properly training the physicians in the homeopathic methodology used (6th edition of the Organon), as well as the use of high quality, exactly prepared Q-potencies.
A recent meta-analysis of homeopathic trials concluded that the results were “compatible with the notion that clinical effects of homeopathy are placebo effects” [43
]. However, as demonstrated by Lüdtke and Rutten, this conclusion was based on an arbitrarily chosen subset of eight trials, out of 21 high-quality trials and the results favor homeopathy, if another threshold to define a “large trial” is used [44
]. Moreover, the homeopathic interventions were grouped in classical, clinical, complex or isopathy, without any further reference to the specific homeopathic clinical or pharmaceutical methodology used in each one of these groups. Defining the homeopathic methodology being analyzed would have been essential to avoid biased or generalized conclusions. In an analogous way, the efficacy of psychotherapeutic interventions in depression is assessed within their specific approaches: behavioral, cognitive-behavior, interpersonal, and so forth, [45
This study, in spite of its limitations, illustrates the feasibility of randomized controlled double-blind trials of homeopathy for depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in the acute treatment of outpatients with moderate to severe depression. Further studies are needed to confirm these results, as well as studies aiming at the continuation and maintenance phases of depression treatment with homeopathy.