Abstract(resumo):

Objective: Many depressed patients opt for complementary integrative medicine (CIM). We aim to evaluate whether there is an association between the severity of depressive symptoms and CIM Methods: a cross-sectional study using the Brazilian National Survey (PNS, 2019), a population-based study. A sample of 4,792 participants (15-107 years old) reporting a current treatment of depression was categorized into 3 groups: 1 (N=4,307, Yes Psychotherapy/Medication-No CIM), 2 (N=148, Yes CIM-No Psychotherapy/Medication) and 3 (N=337, Yes Psychotherapy/Medication-Yes CIM). Participants answered a sociodemographic questionnaire and the Patient Health Questionnaire-9. We used three categories of depression: no depression (score ?9), mild (score 10-14) and moderate/severe (?15). Multinomial logistic regression estimated crude/adjusted odds ratios and 95% confidence intervals Results: Among participants who reported using at least one type of CIM, 3.2% and 7.0% used CIM exclusively or associated with conventional treatments, respectively. The higher the intensity of depressive symptoms, the lower the chance of using CIM exclusively Conclusion: In Brazil only a minority of depressed people use CIM exclusively. These users showed a lower intensity of depressive symptoms

Keywords(palavra-chave):

integrative medicine; complementary medicine; depression; therapeutics; cross-sectional survey.

Content(conteúdo):

Introduction
Depression is the most common mental illness in the world 1 with around 280 million people affected. From 1990 to 2017, there was an increase of almost 50% in cases of depression worldwide 2, worsened recently by the COVID-19 pandemic and social distancing measures 3. In Brazil, in 2019, the prevalence of depression among the population aged 18 or older was 10%, which means an increase of 36% compared to 2013 4. According to data from the Global Burden of Disease Study 2017 (GBD-2017), major depressive disorder ranks 4th as the leading cause of years lived with disability and disability-adjusted life-years. The recent increase in the number of people with disabilities due to depression will probably result in increased spending to fund prevention and treatment programs 5. Depressive disorders have an important impact on several outcomes, such as quality of life, increased morbidity, suicide risk and mortality 6,7,8.
Psychotherapies and pharmacological therapies are effective in the treatment of adult depression 9. Moreover, different classes of antidepressants, such as serotonin reuptake inhibitors and tricyclic antidepressants are proven to be effective in managing depression 10. Nevertheless, the acceptability of antidepressants may be lower due to side effects, or because many patients prefer psychotherapy over pharmacotherapy 11,12. Other reasons why depressed people avoid mental health treatments are fear, misinformation and uncertainty about the treatment’s effectiveness. Therefore, many patients with depression symptoms may opt for integrative and complementary treatments. Complementary and Integrative Medicine (CIM) has been largely defined as therapies that coexist alongside conventional biomedicine. CIM therapies that are used instead of conventional medicine are known as "alternative” medicines. CIM therapies used alongside conventional medicine are said to be "complementary." "Integrative medicine" results from the thoughtful incorporation of concepts, values, and practices from integrative, complementary, and conventional medicines 13. Since 2018, 170 WHO member states have acknowledged their use of CIM, and 97 of these countries have a national policy regarding CIM therapies 14. In Brazil, Integrative and Complementary Practices were regulated and implemented in the Unified Health System (SUS, in its Brazilian acronym) in 2006. A recent population data study reported that 5.3% of the population use different types of CIM, with medicinal plants and phytotherapy (57,2%), acupuncture (26,3%) and homeopathy (17.0%) being the most frequently used 15. Nevertheless, there are limited data about their use for treating depression in Brazil. In contrast, in the US, CIM therapies have been largely used among those with severe depression 16 and this use has been increasing worldwide. Specifically, depressed patients are more likely to seek and use CIM therapies than those with other health conditions17,18,19. Evidence has also shown that several types of CIM have been used concurrently with conventional medications for the treatment of depression. Nevertheless, it is not clear whether the intensity of depression varies according to the type of treatment, especially among those patients that opted to use CIM exclusively. We hypothesized that the higher the severity of depressive symptoms the lower the chance of treatment with CIM. Finally, it is relevant to establish this relationship considering the conflicting evidence about the efficacy of CIM for the treatment of depression20,21.
The aim of the present study is to evaluate whether there is an association between the severity of symptoms and CIM use in the treatment of depression among a population-based sample of Brazilians.
Material and Methods
Design and sample
We used data from the Brazilian National Health Survey (PNS) of 2019, a cross-sectional study that comprised a representative sample of residents in private households in Brazil. The sample studied by the PNS is a sub-sample of the Master Sample of the Integrated Household Survey System from IBGE, whose geographic coverage is comprised by the census sector from the Geographic Operational Base of the Demographic Census 2010, except for those with very small numbers of households and special sectors such as barracks and long-term institutions. The sample size was calculated to enable the estimation of precise prevalence rates and 95% confidence interval for several outcomes such as diabetes, hypertension, depression, violence, use of health services, having health insurance, tobacco use disorder, practice of physical activities and alcohol consumption, taking into account also the clustered sample in multiple stages. The objective of PNS 2019 was to provide the country with information on the health determinants and needs of the Brazilian population 22. The questionnaire had three parts, covering: (i) characteristics of the household; (ii) all residents of the household, focusing on collecting socioeconomic and health information; and (iii) the selected resident (15 years or older) for whom lifestyle, chronic disease and violence, among other topics were investigated. For the analysis of this study, we selected individuals between 15 and 107 years old who have answered the questionnaire of the Selected Resident of the PNS (N= 8.332). The PNS2019 response rate was 91.9%.
Covariates
On the basis of the PNS 2019 questionnaire data, the following sociodemographic factors were assessed: age (15/19, 20/34,35/49 years of age); self-reported skin color (White or non-white); living with a partner (Yes or No); years of schooling (0-8, 9-11, >11); having a private medical plan (Yes or No), living area (Urban or Rural); country regions (South/Southeast or North/Northeast/Midwest) and minimum wage per person in the family (up to ½, ½ - 1, 1-2, > 2). Health related characteristics evaluated were self-perception of health status (“Very good/Good/Fair; Poor/Very Poor) and depression severity that was measured with the Patient Health Questionnaire-9 (PHQ-9). This screening tool assesses the presence and intensity of each of the nine items in the 2 weeks preceding the interview. The scores range from 0 (“not once”) to 3 (“almost every day”), and the total score can range from 0 to 27. We used three categories of depression: no depression (score ?9), mild depression (score 10-14) and moderate/severe depression (score ? 15). PHQ-9 score ?10 had a sensitivity of 88% and a specificity of 88% for major depression 23. The reliability coefficient, Cronbach's alpha, for the PHQ-9 total score was 0.84.
Main outcome variable
The main outcome variable was current type of treatment for depression. The following questions from PNS 2019 were used for the assessment of type of treatment for depression: "Which type of treatments for depression are you currently using: psychotherapy, medications or any CIM (acupuncture, homeopathy, medicinal plants and phytotherapy, auriculotherapy, meditation, yoga, tai chi chuang and any other)?. Participants who answered “No” for all of the above treatments were excluded from the analysis (N=3.540) and participants who reported “Yes” for any kind of treatment were classified into 3 groups: group 1 (Yes for Psychotherapy/Medication - No for CIM), group 2 (Yes for CIM - No for Psychotherapy/Medication), group 3 (Yes for Psychotherapy/ Medication – Yes for CIM).
Statistical analysis
Exposure variables were summarized and categorized. Multinomial logistic regression was performed using type of depression treatment as a categorical outcome variable and severity of depression as the primary independent variable of interest. We examined the effects of severity of depression on type of depression treatment accounting for potential confounders. Covariates were identified a priori based on previous research on type of depression treatment and severity of depression. The adjusted multivariate model included all covariates which showed a p level <0.20 in the bivariate analysis. We estimated crude and adjusted Odds Ratio (OR) using STATA 16 software and the complexity of the sample was taken into account using the svy command for statistical analysis. We estimated predicted probabilities of type of treatment for depression according to the severity of depression using the predictive margins command in STATA, after running the multivariate multinomial logistic regression model 24. All estimates were weighted to account for PNS-2019 complex survey design and to make the estimates nationally representative (weigthed pooled N= 155,020,634).

Ethical Aspect
Ethics approval and consent to participate The National Survey of Health (PNS-2019) was approved by the National Health Ethics Committee (CONEP) (process n° 3.529.376). Participation was voluntary and participants signed a consent form. The questionnaire could be answered in whole or in part. The PNS dataset is publicly available on the IBGE website without information that could identify individuals.
Results
Of the 8.332 participants (15 to 107 years old) in the PNS 2019 data set who reported a current treatment for depression, 3.540 reported not using any type of treatment and were excluded, leaving a sample of 4.792 participants. Among these there were 4.307 participants in group 1 (Yes for Psychotherapy/Medication - No for CIM), 148, in group 2 (Yes for CIM– No for Psychotherapy/Medication), and 337, in group 3 (Yes for Psychotherapy/ Medication – Yes for CIM).
The characteristics of these 4.792 participants with complete information about depression treatment were: 52.0% female, 42.9% were White, 58.4% reported living with someone, and 22.9% had > 59 years of age. The mean age was 43.3 (SD= 3,1; range 15 to 107). In relation to socioeconomic status, 43.1% had between 0 to 8 years of education and almost half (47.7%) had a family income of >1 minimum wage (270 US Dollars) per person. Nearly one fourth (26.6%) of participants had a private health plan. Most of the participants lived in South/Southeast region of the country (57.4%) and in the urban area (85.9%). Regarding the health characteristics, 5.2% reported a “poor or very poor” perception of health status. The prevalence of type of treatment for depression varied between 10.2% for CIM to 96.8% for medication/ psychotherapy (table 1). Characteristics of participants according to groups of treatment for depression are also presented at table 1. Among participants (n = 485) who reported use of at least one type of CIM, 3.2% (95%CI 2.4% - 4.2%) and 7.0% (95%CI 5.8% - 8.4%) used CIM isolately or associated with conventional treatments, respectively. From these 485 participants who answered “yes” to the use of CIM for depression treatment, 174 (35.9%) participants did not specify which CIM was used (i.e., those participants had missing values on the subsequent questions regarding the types of CIM treatments). The most frequent CIM used (n = 311, 64.1%) were medical plants (61 in Group 2 and 38 Group 3), acupuncture (32 in Group 2 and 29 Group 3), meditation (40 in Group 1 and 12 Group 3) and homeopathy (32 in Group1 and 12 Group 3). A score of types of CIM was created, ranging from 0 to 9 types of CIM treatments, with a mean (SD) = 2.5 (1.7) of CIM used among the 311 participants. The majority of participants reported the use of one type of CIM (n = 119, 24.5%), followed by 2 types of CIM (n = 60, 12.4%), and three types of CIM (n = 46, 9.5%). A total of 85 participants (27.3%) reported the current use of 4 or more types of CIM.
In the bivariate analysis, keeping group 1 as the reference, the following variables were associated with an increased OR of treatment in group 2 (CIM use without medication or psychotherapy): 9-11 (OR:1.86; 1.04-3.33) and >11 (OR: 4.78; 2.74-8.33) years of schooling; 1-2 (OR: 1.91; 1.04-3.49) and >2 (OR: 2.98; 1.54-5.79) minimum wages per person of family income and very good/good/fair perception of health status (OR: 3.95;2.10-7.30). A decreased OR of treatment in Group 2 was found with the highest PHQ-9 score (>14): OR:0.22; 0.13-0.38. In comparison with group 1, the following variables were associated with an increased OR of treatment in group 3 (CIM use with or without medication or psychotherapy): 9-11 (OR: 3.20;1.79-5.71) and >11 (OR: 4.80;3.07-7.49) years of schooling; 1-2 (OR: 2.08;1.09-3.98) and >2 (OR: 2.67;1.54-5.79) minimum wages per person of family income; having a private health insurance (OR: 2.07;1.35-3.19) and living in a rural area (OR: 4.07;2.21-7.49). A decreased OR of treatment in Group 3 was found with the variable living in the North/Central region of the country (OR:0.70;0.49-1.00). (table 2).
In the multivariate analysis the following variables were significantly associated with type of treatment in group 2: >11 years of schooling (OR:3.40;1.81-6.37); 1-2 minimum wage per person (OR: 1.87; 1.02-3.41), living in the North/Central region of the country (OR:1.98;1.10-3.29), having a very good, good, fair perception of health status (OR: 2.27;0.1.16-4.46) and PHQ-9 score of >14 (OR: 0.28; 0.16-0.49). In relation to group 3, the following variables were significant with type of treatment: 9-11 (OR: 2.87; 1.66-4.97) and >11 (OR: 3.67;2.08-6.47) years of schooling and living in a rural area (OR: 2.26; 1.23-4.17) (table 2). Figure 1 and Table S1 show the predicted probability of type of treatment for depression according to the depression severity measured by PHQ-9. The probability of belonging to the group 1 is highest among all groups regardless the depressive severity. There is no difference between the probability of belonging to the group 2 and group 3 when there is no depression or the depressive symptoms are mild. When the depressive symptoms are moderate or severe, the probability of belonging to the group 3 is slightly higher (predicted probability = 0.086, 95% CI 0.040 – 0.133) when compared to belonging to the group 2 (predicted probability = 0.010, 95% CI 0.005 – 0.014).
Discussion
The present study’s main findings confirm that approximately 10% of the Brazilian population uses CIM for the treatment of depression (exclusively or in association with conventional therapies) and the inverse association between the severity of depression and exclusive CIM use even after controlling for covariates. The higher the intensity of depressive symptoms the lower the chance of using CIM exclusively. In comparison with participants who use conventional therapies, participants with moderate/severe depression are almost 4 times less likely to use CIM exclusively.
The prevalence of CIM use among depressed patients varied significantly between studies. A study carried out in Turkey showed that 22.2% of patients with mental disorders were using some form of CIM for treating depression (18.7%) 25. In the US, complementary and alternative medicines were used among 40% of adults with moderate depression and anxiety disorder 26. In contrast, a study assessed national estimates for the use of practitioner-based complementary treatments among 16.038 US residents with mental conditions. They reported that 4.5% of participants were using CIM to treat a mental condition 27. De Jonge et al evaluated CIM use for treating mental health problems among adults in 25 countries (N=138.801), finding that an estimated 3.6% of participants with a past 12-month mental disorder reported having contact with a CIM therapy, which was two times higher in high-income countries (4.6%) than in low and middle-income countries (2.3%) 28. A critical review found that CIM use among sufferers of depressive disorders appears to be approximately in the range of 10–30% 18. Another review reported a prevalence range of CIM use among depressed patients between 17.8% to 54% 19. In our study, the lower prevalence of CIM use (10.7%) in comparison with other countries, can be explained by cultural beliefs, population characteristics, differences in the depression assessment and the type of CIM used for the treatment of depression that has been assessed in the PNS. Of note, a few CIM practices employed in other countries such as prayer, hypnotherapy and spiritual healing have not been evaluated in our study. Regardless differences between studies, the exclusive use of CIM for depression treatment is uncommon in the majority of publications 29.
The association between the severity of depressive symptoms and the lower likelihood of using CIM exclusively can be explained. Firstly, patients with more severe symptomatology of depression may have problems adhering to CIM treatments as they require more sessions/appointments than conventional therapy with psychotropic medications. Secondly, national studies reported that health professionals are unaware of and/or have little experience with CIM practices 30. The majority of healthcare providers, including Family Health Strategy community physicians, are unaware of the National Policy on Complementary and Integrative Practices 31,32. Furthermore, there is great distrust among them about the effectiveness of the CIM, which also occurs in other countries. Healthcare providers showed different attitudes towards these practices, ranging from encouragement to ignorance and even opposition to CIM therapies 32. In the US, there is a lack of CIM training and education for medical students 33. Thirdly, patients’ knowledge and perceptions about CIM use for managing depression may also play a role. It is likely that the controversy about overall CIM efficacy may hamper the possibility of the patient accepting the use of these types of treatment as the primary or even complementary therapy. The belief in the efficacy of treatment (either CIM or conventional) has been shown to influence the pattern of choice exhibited by the participants 34.
Reviewing the literature, we found that studies yielded conflicting evidence about the association between depression intensity and CIM use. In Norway, Hansen et al studied 1.685 participants who reported suffering from anxiety and/or depression and found no association between the receiving treatment with a CIM therapy and the degree of symptomatology 35. Parslow et al reached the same conclusion while comparing two groups of adults that experienced depressive and anxiety symptoms or other mental health problems in the past month: one group used CIMs only and the other group used prescription medications only 29. In the US, Druss & Rosenheck suggested that people reporting transient stress or adjustment disorders rather than chronic and serious conditions were most likely to seek complementary therapies to treat their mental condition. They concluded that CIM treatment is likely to be a substitute for conventional care, particularly in patients with moderate disease 27. In contrast to the above results, a review challenges the idea that CIM contacts are more often used for mild complaints and emphasizes that CIM is a complement to conventional treatment. De Jonge et al found that the contact of participants with CIM increased with increasing mental disorder severity 28. Of note, this review included one Brazilian study carried out in São Paulo, the most developed city in the country, with the best structure for mental care in the country, and used the frequency of visits to a CIM provider as a proxy of CIM treatment. Moreover, this Brazilian study was carried out in 2005 when the CIM practices were not included in Brazilian national health policies. Differently, the present study used a population-based sample and evaluated, directly, the effectiveness of CIM therapies for treating depression. Overall, our data are in line with studies that consider CIM as an option for treating mild or transient depression alongside conventional treatments while the exclusive use of CIM for treating mental health problems is uncommon 19.
A broader view of using CIM to treat depression has been suggested in a study that employed an interesting approach. Berna et al conducted a web-based study including 1.807 participants who were asked to imagine that they had a particular chronic illness based on clinical vignettes (depression was one of them). Participants were invited to rate four determined patterns of treatment: strictly conventional, weak or strong complementary, and alternative. The main result showed that CIM was selected as a complementary treatment option by more than 95% of people who hypothetically faced chronic illness, however, different factors, such as employment status, the severity of illness, age and perceived distress, social stigma and treatability of the illness driven this preference. They concluded that CIM use varied according to the kind of illness faced by the person or by the severity of this illness, which means that CIM exclusive use or alongside conventional care for the treatment of depression depends on the circumstances. Overall, the preference for the alternative option was more frequent for illnesses perceived as less distressful and with low levels of symptoms and low frequency of relapse 36.
Our data have clinical implications. First, CIM treatments are not free of side effects and there should be certain care regarding possible undesirable interactions between conventional and CIM treatments. A retrospective analysis of the Medicare beneficiary population showed that concurrent use of conventional and CIM treatments was common (14.4%) and that 5.8% of the sample were taking combinations considered to have a significant risk of causing an adverse interaction 37. Therefore, clinicians not specialized in CIM therapies should know if their patients are also receiving CIM treatments for mental health problems.
The present study also has some limitations. First of all, the cross-sectional design of our study does not allow the establishment of temporal causality and therefore reverse causality cannot be excluded. Secondly, the assessment of types of therapy for depression including CIM was made with a single direct question. Specifically, the question about CIM treatments included different types of therapies whose efficacies may vary enormously. Unfortunately, we do not have data from medical charts to confirm the type of CIM used. On the other hand, the evaluation of the current use of CIM for depression makes recall or misinformation unlikely. Thirdly, our analysis is based on a small sample of participants who reported exclusive use of CIM and, therefore, a lack of power for detecting differences between groups of comparison is expected.
One strength of our study is the use of data from a large national survey that used a complex sampling method. Participants in the PNS 2019 are from different socioeconomic statuses with access to private or public healthcare. Therefore, we believe that our findings can be generalized to the Brazilian population.
Conclusions
There is a growing interest in alternative/natural treatments in many countries, including for the treatment of depression. Additionally, there is evidence that issues related to the efficacy of CIM for treating depression are not an obstacle for certain groups of patients. Overall, these aspects support the relevance to evaluate the use of CIM for treating depression. Our data showed that, in Brazil, only a minority of depressed people use CIM exclusively. Moreover, they showed a lower intensity of depressive symptoms. Future studies with quantitative and qualitative assessments should evaluate prospectively the relationship between the severity of the depressive symptoms with the use of CIM for treatment, instead of or alongside conventional medication. An integration of CIM with conventional therapies for the treatment of mental health problems has clinical and public health implications and has received support from the WHO 38.

Contributors: All authors participated in the conception, design, analysis, data interpretation and writing of the article, as well as approved the version to be published.
Funding: There was no funding for this article.
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