Clinical Study of the Effectiveness of Pluralist Homeopathy in Generalized Anxiety Disorder

Introduction and objectives: Generalized anxiety disorder (GAD) is mainly observed in the primary care setting and may reach a prevalence of 5%. This retrospective study was conducted with the aim of assessing the results obtained using a therapeutic method based on pluralistic homeopathy. Material and Methods: An observational study of a cohort of 220 patients treated by a pluralistic homeopathic physician was performed. A total of 460 medical records were reviewed, among which 220 patients who met DSMIV-TR criteria for the diagnosis of GAD were selected. In relation to homeopathic remedies, remedy of temperament was prescribed in all cases. A complementary remedy, a remedy of autonomic regulation, causal remedy, constitution remedy and remedy of terrain or diathesis was prescribed when necessary. Criteria for grouping patients according to response to treatment were defined. On the basis of this response, levels of cure or lack of response were grouped. A specific database was designed for the purpose of the study. Results: The mean age of patients was 38 years. Women accounted for 78% of the cases. Associated general pathologic conditions were found in only 16% of patients. The duration of symptoms exceeded 12 months in 45% of the cases. At presentation, 31% of patients were taken conventional treatment (anxiolytics and/or antidepressants). The remedy of temperament was prescribed to all 220 cases. Starting of improvement was already observed at the first control visit in 73% of cases (158 patients) after 30 days of the baseline visit. In 157 of the 220 cases (71%), patients considered to be cured due to resolution of all symptoms. In 56.4% of cases (n=124), the length of follow-up was shorter than 2 years, and in 38.2% of cases (n=84) the follow-up ranged between 2 to 6 years. Nine cases (4%) have been followed between 6 and 10 years, and in 3 cases the follow-up was longer than 10 years. Cure achieved by means of homeopathic treatment was significantly associated with younger age, shorter duration of symptoms and absence of conventional pharmacologic treatment prior to consultation with the homeopath. Conclusions: Data of this retrospective review shows that the applied homeopathic treatment may be effective in the management of patients with GAD. The scope of treatment may include both somatic manifestations of anxiety and deepest vital discomfort affecting the subject.


Introduction
Generalized anxiety disorder (GAD) is mainly observed in the primary care setting and may reach a prevalence of 5% [1,2]. It is an underdiagnosed condition, the chronicity and severity of which is frequently underestimated. It is known that the disorder is influenced by personality, genetic, environmental and biological factors [3]. This retrospective study was carried out with the aim of evaluating the results obtained over the years with a therapeutic approach used in a single consultation and based on pluralistic homeopathy.

Material and Methods
In order to assess the results of homeopathic treatment in GAD, an observational study of a cohort of 220 consecutive patients treated by a single clinician, a pluralistic homeopath doctor, was performed. All patients evaluated had consulted a homeopath because they were not convinced of taking medication proposed by a conventional physician (anxiolytics, antidepressants) and sought another treatment option, or because they were not satisfied with the result obtained with the drugs they were taking or complained of side effects related to these agents.
All 220 patients fulfilled DSM-IV-TR criteria [4] for the diagnosis of GAD. Also, a distinction was made between patients with panic attacks, depressive symptoms or traits, and/or obsessive symptoms or traits, and acute or post-traumatic stress. Patients already diagnosed and with an established conventional pharmacological treatment were included in the study, as well as patients without a previous diagnosis but seeking immediate medical care because anxiety symptoms prevented them from normal daily living.
Patients were selected as rigorously as possible. After the first visit, the medical record of each new patient was classified according to a diagnostic code based on the main diagnosis or the reason for consultation, always according to diagnostic classification of academic medicine. A total of 460 medical histories were reviewed among which 220 fulfilling criteria of DSM-IV-TR required for the diagnosis of GAD were selected. A series of data that were considered to be important to obtained relevant conclusions were chosen.
It was considered that a patient had GAD when presented excessive worrying and anxiety hard enough to be controlled, with an important effect on a wide range of activities or events (such as work or school performance) that lasted for more than 6 months. This anxiety and worries was accompanied by muscular tension (tremor, fatigue, pain), increased autonomic activity (sweating, palpitations, dry mouth, nausea, diarrhea, nocturia), hypervigilance (difficulty concentrating, sleep problems, irritability) and these symptoms followed a sustained and oscillating pattern. It was considered that a patient had GAD associated with depressive symptoms in the presence of mild traits of depressive symptoms, such as: important weakness (lack of energy or fatigue), early awakening in addition to poor restful sleep, sadness, guilty ideation, low self-esteem, fear to economic ruin, etc.
Cases of GAD with obsessive traits, excluding an obsessivecompulsive disorder (OCD), were characterized by punctual symptoms, such as: repetitive thoughts or behaviors (recurrent and persistent) beyond usual manifestations of GAD (compulsive eating, washing hands, verifications, etc.). In some cases, recurrent thoughts had a relation with traumatic events (post-traumatic stress) or acute stress: unable to avoid reliving the traumatic life experience that can appear even in dreams awakening.
Patients with GAD and panic attacks were defined as cases that referred a sudden, temporal (isolated) episode of intense fear, with four or more of the following symptoms: intense palpitations, sweating, tremor or shaking, shortness of breath, chest pain or discomfort, nausea or abdominal complains, instability, fainting or dizziness, feeling of unreality and fear of losing control (to go crazy), fear of dying, paresthesia, chills or hot flushes. With regard to homeopathic remedies, as a pluralistic homeopath, the patient's remedy of temperament (main remedy of background remedy) was prescribed in all cases. Also, when it was considered necessary a complementary remedy, a remedy of autonomic regulation, a causal remedy, a remedy of terrain or a constitution remedy was prescribed.
Also, complementary therapies including psychotherapy, nutritherapy and phytotherapy were indicated in selected cases. Homeopathic treatment was associated to nutritherapy based on trace elements (lithium, magnesium, potassium, phosphorus, manganese, cooper, cobalt, chromium); vitamins (group B particularly B6); amino acids (taurine, tyrosine); and omega-3 essential fatty acids. Nutrients were prescribed especially during the first months of treatment usually as multi nutrient formulas available in the market. In all cases, it was systematically recommended to excluded excitants (coffee, coke) and sweet aliments (sugar, cookies, pastries) from the diet. Phytotherapy has been also used as a complementary therapy in the form of dry extracts or pharmaceutical specialties (formulae already available in the market), being the most indicated plants: Passiflora, valeriana, Melissa, Crataegus oxycantha, Lupulus, Griffonia simplicifolia, Eschscholzia californica, Hypericum perforatum (Saint John's wort). In some cases, we recommended to start psychotherapy or to continue psychotherapy if this therapeutic modality has been previously instituted.
In relation to assessment of results, criteria for grouping patients according to response to treatment in a pre-established period that was considered adequate for expecting response, were defined. On the basis of response to treatment, patients were grouped into levels of cure or lack of response. A patient was considered completely cured when symptoms recorded in the first interview had totally disappeared, and the patient could continue with normal daily activities, stating that well-being prior to the onset of symptoms has been restored, or a wellbeing level previously unknown has been achieved, without the need of any type of treatment.
A specific database was designed in which data of interest of the patient's medical record to meet the objectives of the study were registered. The following data were recorded: demographic variables (age, sex, education level); associated medical conditions (diabetes, arthritis, thyroid diseases, asthma, heart diseases, Crohn's disease, celiac disease, congenital abnormalities, etc.); duration of symptoms and reasons for consultation to the homeopathic physician. All homeopathic remedies were recorded and grouped according to categories of remedy of temperament, complementary remedy, remedy of autonomic regulation, causal remedy, and remedy of terrain and/or constitution. In order to evaluate the results, the time elapsed from the beginning of response to treatment and the end of treatment due to symptomatic improvement was registered. It was considered that the patient was cured when all symptoms had disappeared and no continuous treatment was needed. Patients were divided into two groups: A) total remission of symptoms without the need of any treatment, and B) total remission of symptoms but requiring some kind of treatment. The possible association between some demographic and clinical factors (age, duration of symptoms, previous treatment and GAD-related traits) with the outcome of cure was assessed with the Pearson's correlation coefficient.

Demographic data
The mean age of the patients was 38 years, with a range of 8 to 67 years. Almost half of the patients aged between 31 and 45 years of age ( Figure 1). A total of 78% of patients were women and only one third was menopausal women. Also, 47% of men and 51% of women were married or lived with a partner. Thirty-six percent of women and 37% of men had university education and 34% of both sexes had secondary education, which demonstrates the high education level of the population attended by the homeopathic physician. Only 16% of patients (36 cases) presented some type of general associated pathologic conditions (diabetes, arthritis, thyroid diseases, asthma, heart diseases, gastrointestinal disorders, congenital abnormalities). In all cases, these chronic diseases were well controlled by the corresponding specialist.
In 45% of cases, the duration of symptoms exceeded 12 months. In 31% of cases, the duration of symptoms ranged between 6 and 12 months, and only in 24% of cases, the duration of symptoms was less than 6 months.

Homeopathic remedies
In relation previous or current pharmacological treatments, only 69 of the 220 patients (31%) were currently on conventional pharmacological treatment at the time of consultation. Treatments included anxiolytics in 55% of cases, antidepressants in 9%, and a combination of anxiolytics and antidepressants in 36%. Benzodiazepines (alprazolam, bromazepam, ketazolam, lorazepam, diazepam, etc.) were the most common anxiolytics. In relation to antidepressants, most patients were treated with selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, paroxetine, etc.).
The remedy of temperament (main remedy of background remedy) was prescribed to all 220 patients and in only 3 cases was the only homeopathic remedy prescribed. The distribution of patients according to the combinations of homeopathic remedies is shown in Figure 2. A complementary remedy was prescribed in 66% of cases (n=145), remedy of autonomic regulation in 172 cases (78%), causal remedy in 86 patients (39%), remedy of terrain in 58 cases (28%) and constitution remedy in only 27 patients (12%). In 100% of patients a remedy of temperament was prescribed, and under this concept (main or background remedy) a total of 29 remedies were used. The frequency of mostly prescribed remedies is shown in Figure 3. Seventy-one percent of cases (n=157) were covered with 6 remedies, which have been usually prescribed in Korsakovian dilution, from 200 K or 1000 K increasing up to 50,000 K, even reaching CMK in some occasion. The remedy of temperament was the only homeopathic remedy used in 3 cases: Natrum Muriaticum in 1, Actea Racemosa in 1 and Nux Vomica in 1. Also, in 1 case Argentum Nitricum with Gelsemium, both at 30CH, together, twice a day, was the only treatment prescribed. In these 4 cases, a good response to treatment was obtained.
In 86 cases, a causal remedy was prescribed. The most commonly prescribed remedies were Arnica and Opium (remedy for posttraumatic stress) in 10% of cases; Staphysagria (remedy for offense) in 10%; Opium (remedy for blocking fear) in 9%; Causticum (remedy for the feeling of abandonment) in 3%, and Alumine (remedy for the feeling of betrayal) in 2%. Other remedies as causal remedies were also used: Arnica montana (mental or psychic trauma), Phophoricum acidum (exhaustion for repeated griefs or long vigils), Nitricum acidum (hate and mistrust at their maximal expression), Capsicum (nostalgia for the lost paradis), Apis mellifica (possessive jealousy, only filters what causes pain) and Colocynthis (in a case of acute anger). These remedies were usually prescribed as a single dose of 10,000 K, 50,000 K or 100,000 K.
In 85 cases (39%), a remedy of terrain or a constitution remedy was prescribed besides the aforementioned remedies: T.K. (Koch tuberculin) in 11% of cases (MK or XMK); Calcarea fluorica in 10% (50 MK), which has been used as a remedy for excellence in recurrent thoughts and ruin syndrome; Thuya occidentalis in 6% of cases, Luesinum in 5% (MK or XMK), Psorinum in 4% (XMK), Calcarea phosphorica and Calcarea carbonica in 1%. Sulphur was used in a single case. Nutritherapy (micronutrition) was indicated as a complementary therapy in 173 patients (79%) and phytotherapy in 99 cases (45%). In 23% of cases, we recommended to start psychotherapy or to continue psychotherapy if the patient was previously visited by a psychotherapist.

Starting of clinical improvement
Beginning of clinical improvement was observed in 73% of cases (158 patients) in the first control visit, at 30 days from the first visit, although it should be noted that all these patients stated having feeling an improvement of their symptoms at 10 days to 15 days after the start of homeopathic treatment. In 23 cases (11%) in which improvement occurred at 60 days, the remedy prescribed at the first visit has been changed at the 30-day control visit. When improvement was observed at 90 days (33 cases, 15%), the remedy that was effective had been prescribed at the third control visit. In only 2 cases (1%), the remedy that was effective for controlling symptoms had been prescribed at the fourth control visit (at 120 days). A transient improvement was observed in 4 cases but there was a relapse and for this reason, these cases were not considered as improvement.

Cure
In 157 cases (71%), patients were considered to be cured because of disappearance of all symptoms and no need of continued treatment. Of these 157 cases, 122 which accounted for 55% of the total number of cases, patients felt to be cured without requirement of any treatment, and 35 cases (16% of the total) felt to be cured and only required to take homeopathic remedies occasionally, usually during certain seasons, Spring and Autumn or situations of greater professional or familial stress (Figures 4 and 5). Only 31 patents (14%) felt to be cured but needed continuing taking homeopathic remedies. Homeopathic remedies and anxiolytics were needed in 8 cases, and 11 patients continued taking homeopathic remedies together with antidepressants and anxiolytics for the control of GAD symptoms. In 13 of the 220 cases (6%) neither cure nor improvement could be obtained.

Changes of previous pharmacological treatment
Of the 38 patients treated with anxiolytics, 29 (76.3%) were able to discontinue this medication. Of the 6 cases treated with antidepressants, 4 (66.7%) stopped this medication. Of the 25 patients treated with a combination of anxiolytics and antidepressant, treatment would be withdrawn in 9 (36%), although 6 (24%) were able to discontinue anxiolytics (but not antidepressants) and 3 were able to discontinue antidepressants (but not anxiolytics). In 7 cases (28%), neither anxiolytics nor antidepressant could be discontinued.

Follow-up of patients
In 56.4% of cases (n=124), the length of follow-up was shorter than 2 years because the patient felt well and was discharged. In 38.2% of cases (n=84) the follow-up ranged between 2 and 6 years. Nine cases (4%) have been followed between 6 and 10 years, and in 3 cases the follow-up was longer than 10 years. The long-term follow-up in some of the cases was explained by the highly unfavorable circumstances of the patients, who required be controlling and accompanying to be able to face difficulties.

Analysis of factors associated with complete cure
Cure achieved by means of homeopathic treatment was significantly associated with younger age, shorter duration of symptoms and absence of conventional pharmacologic treatment prior to consultation with the homeopathic physician (Tables 1-3).    This analysis only shows a simple association. The association between cure with the presentation of GAD with other traits and/or panic crises was not statistically significant. Cure was observed in the group without associated traits (73/117, 62%) and with associated traits (49/103, 48%) (P>01).

Discussion
Anxiety disorders are a group of diseases that affect 25% of the population and it has been estimated that account for 10% of new diagnoses established in the primary care setting [1]. These disorders involve a significant impairment of the social and family functioning of patients with a notable decrease in the quality of life. Conventional treatments, anxiolytics and/or antidepressants not always are successful to resolve satisfactorily the symptomatology, and it is logical to search for alternatives to help patients to solve their difficulties and to improve their ability to adapt to the environment. Changes in lifestyle and diet are an increasingly used approach for treating anxiety disorders [5]. Recent studies in experimental animals have shown that some homeopathic remedies have an anxiolytic effect comparable to conventional pharmacological treatments [6][7][8].
This article reports the results of a retrospective analysis of homeopathic treatment for GAD in a cohort of consecutive patients treated by a single professional, a pluralistic homeopath, who tries to recognize the origin of the disorder to help patients to regain their personal balance that has been lost.
A question, is why we have prescribed 29 different homeopathic remedies if GAD is supposedly the same in all cases? Well, because for example, GAD of Natrum muriaticum has its nucleus (or origin) in affective frustration and the existential angst comes back from the lack of a real training love that parents did not know how or were unable to give, blocking the harmonic integration in the environment and each new frustrating experience reactivates the primal experience, which aggravates resentment and increases irritability and, consequently, anxiety symptoms [9]. In Lachesis, for example, anxiety comes from what is expected to get from the world, and this primary anxiety is projected aggressively demanding active participation of the environment to the projects …if projects are coherent and stimulate enthusiasm in the environment, then their passion pulls along this environment, which in addition may establish order and terminates what she does not finish because of their characteristics, but when this does not occur is when Lachesis deforms reality being unable to convince the environment and goes into anxiety (10). Whilst in Silicea, on the other hand, the nucleus or origin remains in the weakness of the ego, with consciousness of such weakness, due to constitutional (genetic) factors aggravated by affective indifference or overprotection by progenitors, which is frequent given the constitutional characteristics, and this produces great insecurity and vulnerability against the world. In front of these fears, there is an obsessive and aggressive reaction putting emotional distance between himself and the others (to prevent suffering), which in turn generates increasing anxiety [10].
Sepia for example, often is for me, the night of Natrum muriaticum, a wonderful complement that helps precisely Natrum either not to evolve into Sepia or to achieve the balance, which is the purpose of our therapeutic intervention.
Pulsatilla is also a wonderful complement to Natrum, which are also the day and the night of some personalities, and many times after prescribing Natrum, Pulsatilla appears, and the introverted, distant, resentful Natrum reappears abandoned, made a sea of tears looking for contact and relief. When complementary prescribed, once again, we have the purpose to achieve balance, which is the object of our intention.
It is interesting to note that Ignatia Amara, as a remedy of autonomic regulation, covers a large part of GAD symptoms: spasmodic pain (abdominal, precordial), the ball in the throat or in the stomach, nauseas, headaches, paresthesias, Tuberculinism remedy helps well to N. mur., Silicea, Pulsatilla, Lycopodium… However, we know that Gelsemium cover to a greater extent the physical weakness, dizziness, tremors, frequent micturitions, anticipation and Nux Vomica, impatience, marked irritability, muscle spasms, hypersensitivity to noise, light, intolerance to cold air is a remedy of the psoric series and helps Sulfur, Sepia, Lycopodium [11].
With regard to causal remedy [12], it should be noted that it is prescribed when there is a cause or it is possible to find out the cause or a precipitating factor (the deep of anxiety lies on the personality) but some vital events may trigger the appearance of the full range of symptoms. This precipitating circumstance may be recent or might have been present in the remote past and be immersed in the subconscious, and homeopathy and the word may help to arouse the feeling and the causal remedy contributes to its dilution.

Conclusions
This review shows the results of the practice of pluralist homeopathy used by the same professional. Based on this retrospective review it was demonstrated that the homeopathic remedies applied can be effective in the treatment of GAD. It was found that treatment can cover both somatic manifestations of anxiety as vital deeper discomfort that affects the individual, which frequently is the source of their anxiety and that often he does not know where it comes from.
However, all methodological limitation for the assessment of results should be considered, the presence of multiple variables that intervene in GAD as well as the medicines or homeopathic remedies.
The purpose of this study is to contribute to the challenge of the evaluation of complementary medicines, and as physicians who are practicing we are not reluctant to be evaluated, as has been stated in some media, although we believe that certain methods of evaluation are relatively reductionist and do not take into account the holistic nature of our practice.