Consensus Panel Recommendations for the Pharmacological Management of Breastfeeding Women with Postpartum Depression.

INTRODUCTION: Our consensus statement aims to clarify the use of antidepressants and anxiolytics during breastfeeding amidst clinical uncertainty. Despite recent studies, potential harm to breastfed newborns from these medications remains a concern, leading to abrupt discontinuation of necessary treatments or exclusive formula feeding, depriving newborns of benefits from mother's milk. METHODS: A panel of 16 experts, representing eight scientific societies with a keen interest in postpartum depression, was convened. Utilizing the Nominal Group Technique and following a comprehensive literature review, a consensus statement on the pharmacological treatment of breastfeeding women with depressive disorders was achieved. RESULTS: Four key research areas were delineated: (1) The imperative to address depressive and anxiety disorders during lactation, pinpointing the risks linked to untreated maternal depression during this period. (2) The evaluation of the cumulative risk of unfavorable infant outcomes associated with exposure to antidepressants or anxiolytics. (3) The long-term impact on infants' cognitive development or behavior due to exposure to these medications during breastfeeding. (4) The assessment of pharmacological interventions for opioid abuse in lactating women diagnosed with depressive disorders. CONCLUSIONS: The ensuing recommendations were as follows: Recommendation 1: Depressive and anxiety disorders, as well as their pharmacological treatment, are not contraindications for breastfeeding. Recommendation 2: The Panel advocates for the continuation of medication that has demonstrated efficacy during pregnancy. If initiating an antidepressant during breastfeeding is necessary, drugs with a superior safety profile and substantial epidemiological data, such as SSRIs, should be favored and prescribed at the lowest effective dose. Recommendation 3: For the short-term alleviation of anxiety symptoms and sleep disturbances, the Panel determined that benzodiazepines can be administered during breastfeeding. Recommendation 4: The Panel advises against discontinuing opioid abuse treatment during breastfeeding. Recommendation 5: The Panel endorses collaboration among specialists (e.g., psychiatrists, pediatricians, toxicologists), promoting multidisciplinary care whenever feasible. Coordination with the general practitioner is also recommended.

Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases.

Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on "prescription drug use-related software" illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug-device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer's disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx "active ingredients" also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug-device combination products are illustrated by Humira® (adalimumab) facing a "patent-cliff" competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies.

Risk Assessment of Psychotropic Drugs on Mitochondrial Function Using In Vitro Assays.

Mitochondria are potential targets responsible for some drug- and xenobiotic-induced organ toxicities. However, molecular mechanisms of drug-induced mitochondrial toxicities are mostly unknown. Here, multiple in vitro assays were used to investigate the effects of 22 psychotropic drugs on mitochondrial function. The acute extracellular flux assay identified inhibitors of the electron transport chain (ETC), i.e., aripiprazole, phenytoin, and fluoxetine, an uncoupler (reserpine), substrate inhibitors (quetiapine, carbamazepine, buspirone, and tianeptine), and cytotoxic compounds (chlorpromazine and valproic acid) in HepG2 cells. Using permeabilized HepG2 cells revealed minimum effective concentrations of 66.3, 6730, 44.5, and 72.1 µM for the inhibition of complex-I-linked respiration for quetiapine, valproic acid, buspirone, and fluoxetine, respectively. Assessing complex-II-linked respiration in isolated rat liver mitochondria revealed haloperidol is an ETC inhibitor, chlorpromazine is an uncoupler in basal respiration and an ETC inhibitor under uncoupled respiration (IC50 = 135 µM), while olanzapine causes a mild dissipation of the membrane potential at 50 µM. This research elucidates some mechanisms of drug toxicity and provides some insight into their safety profile for clinical drug decisions.

Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders.

INTRODUCTION: The initiative of a consensus on the topic of antidepressant and anxiolytic drug use in pregnancy is developing in an area of clinical uncertainty. Although many studies have been published in recent years, there is still a paucity of authoritative evidence-based indications useful for guiding the prescription of these drugs during pregnancy, and the data from the literature are complex and require expert judgment to draw clear conclusions. METHODS: For the elaboration of the consensus, we have involved the scientific societies of the sector, namely, the Italian Society of Toxicology, the Italian Society of Neuropsychopharmacology, the Italian Society of Psychiatry, the Italian Society of Obstetrics and Gynecology, the Italian Society of Drug Addiction and the Italian Society of Addiction Pathology. An interdisciplinary team of experts from different medical specialties (toxicologists, pharmacologists, psychiatrists, gynecologists, neonatologists) was first established to identify the needs underlying the consensus. The team, in its definitive structure, includes all the representatives of the aforementioned scientific societies; the task of the team was the evaluation of the most accredited international literature as well as using the methodology of the "Nominal Group Technique" with the help of a systematic review of the literature and with various discussion meetings, to arrive at the drafting and final approval of the document. RESULTS: The following five areas of investigation were identified: (1) The importance of management of anxiety and depressive disorders in pregnancy, identifying the risks associated with untreated maternal depression in pregnancy. (2) The assessment of the overall risk of malformations with the antidepressant and anxiolytic drugs used in pregnancy. (3) The evaluation of neonatal adaptation disorders in the offspring of pregnant antidepressant/anxiolytic-treated women. (4) The long-term outcome of infants' cognitive development or behavior after in utero exposure to antidepressant/anxiolytic medicines. (5) The evaluation of pharmacological treatment of opioid-abusing pregnant women with depressive disorders. CONCLUSIONS: Considering the state of the art, it is therefore necessary in the first instance to frame the issue of pharmacological choices in pregnant women who need treatment with antidepressant and anxiolytic drugs on the basis of data currently available in the literature. Particular attention must be paid to the evaluation of the risk/benefit ratio, understood both in terms of therapeutic benefit with respect to the potential risks of the treatment on the pregnancy and on the fetal outcome, and of the comparative risk between the treatment and the absence of treatment; in the choice prescription, the specialist needs to be aware of both the potential risks of pharmacological treatment and the equally important risks of an untreated or undertreated disorder.

In Vivo Sex-Dependent Effects of Perinatal Pb2+ Exposure on Pilocarpine-Induced Seizure Susceptibility and Taurine Neuropharmacology.

Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. This finding suggests that neurodevelopmental Pb2+ exposures may increase the risk of brain excitability and/or seizure susceptibility. Prior studies have suggested that neurodevelopmental Pb2+ exposures may cause excitotoxicity of cholinergic neurons, but little to no research has further investigated these potential relationships. The present study sought to evaluate the potential for perinatal neurodevelopmental Pb2+ exposures of 150 ppm and 1000 ppm on pilocarpine-induced seizures through the M1 receptor. The study also evaluated the potential for sex- and treatment-dependent differences in brain excitability. The study revealed that Control females have elevated cholinergic brain excitability and decreased GABAergic inhibition in response to pilocarpine-induced seizures. At low Pb2+ exposures, males exhibited more cholinergic brain excitability, whereas at higher Pb2+ exposures, females exhibited more cholinergic brain excitability. Further, taurine was able to provide neuroprotection against pilocarpine-induced seizures in males, whereas females did not reveal such observations. Thus, the present study adds new insights into the potential for cholinergic seizure susceptibility as a function of sex and the dosage ofneurodevelopmental Pb2+ exposure and how taurine may provide selective pharmacodynamics to treat or recover cholinergic system aberrations induced by neurotoxicants.

Taurine-Derived Compounds Produce Anxiolytic Effects in Rats Following Developmental Lead Exposure.

Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. Taurine is a well-established neuroprotective and inhibitory compound for regulating brain excitability. Since mechanistically taurine can facilitate neuronal inhibition through the GABA-AR, the present study examined the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1,000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random drug assignments to either saline, taurine, or taurine-derived compound (TD-101, TD-102, or TD-103) to assess the rats' responsivity to each drug in mitigating the developmental Pb2+-exposure and anxiety-like behaviors through the GABAergic system. Long-Evans hooded rats were assessed using an open field (OF) test for preliminary locomotor assessment. Twenty-four hours later, the same rats were exposed to the elevated plus maze (EPM) and were given an i.p. injection of 43 mg/Kg of the saline, taurine, or TD drugs 15 min prior to testing. Each rat was tested using the triple-blind random assignment method for each drug condition. The OF data revealed that Control female rats had increased locomotor activity over Control male rats, and the Pb2+-exposed males and females had increased locomotor activity when compared to the Control male and female rats. However, in the EPM, the Control female rats exhibited more anxiety-like behaviors over Control male rats, and the Pb2+-exposed male and female rats showed selective responsivity to TD drugs when compared to taurine. For Pb2+-exposed males, TD-101 showed consistent recovery of anxiety-like behaviors similar to that of taurine regardless of Pb2+ dose, whereas in Pb2+-exposed females TD-101 and TD-103 showed greater anxiolytic responses in the EPM. The results from the present psychopharmacological study suggests that taurine and its derivatives are interesting drug candidates to explore sex-specific mechanisms and actions of taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for neurodevelopmental Pb2+ exposure.

Percepciones y experiencias de usuarios de benzodiazepinas en la atención primaria de salud en Cuba / Perceptions and experiences of benzodiazepine users in primary health care in Cuba

Resumen A pesar de que son ampliamente conocidos los perfiles de utilización de las benzodiazepinas (BZD) y los riesgos asociados, este conocimiento no ha conducido a visibles transformaciones que mejoren la seguridad de los tratamientos y la salud de los pacientes. Por tanto, es necesaria una mejor compresión del contexto de su utilización, con el fin de implementar acciones educativas eficaces, tomar decisiones clínicas pertinentes y perfeccionar su regulación en los servicios de salud. Este artículo se propone caracterizar el perfil de utilización de benzodiazepinas en un área de salud de Santiago de Cuba y analizar el contexto de consumo a partir de los sentidos construidos por usuarios crónicos. Se realiza un estudio de caso, que describe el perfil de consumo a partir de las recetas dispensadas en la Farmacia Principal Municipal, y se realizan entrevistas a profundidad a los usuarios crónicos. El contenido de las entrevistas fue realizado temáticamente. Los resultados revelan los siguientes temas: poca concientización sobre el beneficio-riesgo del tratamiento, sufrimiento con la dependencia y tolerancia, autonomía en el tratamiento y limitada credibilidad en las terapias alternativas. La proporción de adultos mayores que reciben las BZD es mayor que la identificada en otros estudios. Se concluye que los usuarios perciben aspectos negativos del uso, pero están presos en la dependencia. Se evidencia la importancia de estudiar estrategias para el tratamiento del insomnio y la ansiedad en la atención primaria de salud, así como valorizar las políticas de implementación de terapias naturales y otros abordajes para contribuir al uso racional de las BZD.

Abstract The profiles for the use of benzodiazepines and associated risks are well known. However, this knowledge has not led to visible transformations that improve the safety of treatments and the health of patients. It is therefore necessary to better understand the context of use of these medications in order to implement effective educational actions, make relevant clinical decisions and improve their regulation in health services, especially in primary care. To characterize the profile of use of benzodiazepines in a health area of Santiago de Cuba and to analyze the context of consumption from the senses built by chronic users. Methods: A case study was carried out on the consumption patterns and interviews with chronic users was performed. The content of the interviews was thematically analyzed. The themes revealed were: little awareness of the benefit-risk of treatment; suffering with dependence and tolerance; autonomy in treatment; and limited credibility in alternative therapies. The proportion of older adults receiving benzodiazepines is greater than that identified in other studies. The users perceive negative aspects of use, but they are tied to the dependence. It is evident the importance of studying strategies for the treatment of insomnia and anxiety in primary health care, as well as valuing the policies of implementation of natural therapies and other approaches to contribute to the rational use of benzodiazepines.

Anxiety and Brain Mitochondria: A Bidirectional Crosstalk.

Accumulating data highlight the contribution of brain mitochondria and bioenergetics to psychiatric disorders and stress-related pathologies. Although anxiety has not received much attention in this booming literature, a bidirectional interplay between anxiety and brain mitochondria and metabolism has recently started to emerge. Substantial observations indicate alterations in mitochondria and metabolism in highly anxious individuals and, conversely, anxiety symptoms in humans suffering from mitochondrial disorders. Genetic and pharmacological efforts have made substantial progress at advancing the causal involvement of specific mitochondrial and metabolic factors in anxiety. In this review, we discuss this converging evidence and highlight the relevance of developing a research focused on targeting mitochondria as an approach to alleviate anxiety.

Long-term estrogen deprivation changes the response to antianxiety drugs in mice in the elevated plus maze test.

Estrogen deficiency increases the incidence of female anxiety disorders; however, whether estrogen deficiency alters responses to anxiolytic drugs is unknown. We studied whether long-term estrogen deprivation (ovariectomy, OVX) changes the behavior of mice to anxiolytic drugs (buspirone, diazepam, and venlafaxine), using the elevated plus maze (EPM) test. The percentages of EPM open-arm time and EPM open-arm entries of the OVX mice decreased significantly compared to control, and sham mice 2 months after OVX. The response to buspirone increased in the OVX mice at 1 week, while OVX decreased the response to diazepam at 2 months. Moreover, we found the efficacy of diazepam was significantly decreased, compared to buspirone and venlafaxine, at 2 months. These results suggest that OVX may change responses to different anxiolytic drugs. Not all anti-anxiety drugs appear to be suitable for anxiety caused by estrogen deficiency.

Effects of Repeated Treatment with Midazolam in SHR and SLA16 Rat Strains in the Triple Test.

We exposed male and female rats of SHR (Spontaneously Hypertensive Rats) and SLA16 (SHR.LEW-Anxrr16) strains, in a non-drugged state, for five consecutive days to the Triple Test (experiment 1); or after repeated treatment with midazolam (MDZ), for four consecutive days. The fifth day was performed without treatment (experiment 2). The first experiment showed that males did not avoid and females increased the exploration of the open arms over the days. In experiment 2, SLA16 from both sexes approached more the open arms than SHR rats. The MDZ anxiolytic-like effect was sustained in both strains and sexes over the days. On the fifth day, SLA16 still approached more the open arms than SHR rats. Data suggest an absence of repeated-trial tolerance to MDZ anxiolytic-like effects. Testing the SHR and SLA16 strains, especially females, could be necessary for the future search for the genes and molecular pathways underlying anxiety/emotionality.

Effect of Selank on Spontaneous Synaptic Activity of Rat Hippocampal CA1 Neurons.

Application of anxiolytic drug Selank to hippocampal slices increased the amplitude and discharge rate of spontaneous inhibitory postsynaptic currents in rat hippocampal pyramidal CA1 neurons. In some neurons, Selank-induced up-regulation of spontaneous inhibitory postsynaptic currents was preceded by a transient decrease in this activity. In the examined concentration range (1-8 µM), Selank demonstrated no significant dose-dependence.

Interest of the trajectory method for the evaluation of outcomes after in utero drug exposure: example of anxiolytics and hypnotics.

PURPOSE: The aim of this study was to examine the potential benefit to take into account duration and intensity of drug exposure using the recently published method based on individual drug trajectories. This approach was used to define profiles of exposure to anxiolytics/hypnotics during pregnancy and to evaluate the potential effect on newborn health. METHODS: The study was performed in EFEMERIS database (54 918 mother-children pairs). An estimation of adaptation to extrauterine life was assessed using several criteria especially cardio-respiratory symptoms. A proxy variable called "neonatal pathology" was created. The occurrence of this event was studied using two approaches: The Standard Method comparing exposed and unexposed newborns, The Trajectory Method comparing the different profiles of exposure. RESULTS: Around 5% of newborns (n = 2768) were identified to be exposed to anxiolytics or hypnotics during pregnancy. Using the Standard Method, 6.2% of exposed newborns developed a "neonatal pathology" against 4.8% of unexposed newborns (odds ratios [OR] = 0.9[0.8-1.2], p = 0.7). With the Trajectory Method taking into account evolution of exposure during pregnancy and treatment intensity, four profiles of pregnant women were identified. A significant difference in the rates of "neonatal pathologies" was observed between profiles (p = 0.0002). Newborns of the two profiles exposed in utero to high constant level of anxiolytics or hypnotics were more at risk of developing "neonatal pathology" than unexposed newborns (OR1  = 2.0 [1.0-3.9] and OR2  = 7.6 [2.8-20.5]). CONCLUSIONS: The present study demonstrates the interest of this method based on individual drug trajectories for the evaluation of outcomes in pharmaco-epidemiological studies and more specifically during pregnancy. Copyright © 2017 John Wiley & Sons, Ltd.

A eletrorredução de benzodiazepinas e a sua avaliação matemática / Benzodiazepines' electrochemical reduction and its mathematical evaluation

O processo da eletrorredução de benzodiazepinas, uma ferramenta, capaz de usar-se em pesquisa eletroanalítica, foi analisado dos pontos de vista mecanístico e matemático. O modelo correspondente veio sendo investigado por meio da teoria de estabilidade linear e análise de bifurcações e, por meio da sua análise, pôde-se obter o requisito da melhor eficiência do processo, investigar a pH-dependência do seu desempenho, bem como as condições das instabilidades oscilatória e monotónica. Faz-se uma tentativa de uma análise mecanística sistemática do desempenho de sensores eletroquímicos de benzodiazepinas.

The benzodiazepines' electrochemical reduction process, a tool, capable to be used in electroanalytic investigation, was anaylzed by mechanistic and mathematical means. The correspondent model was analyzed by means of linear stability theory and bifurcation analysis, and by its mean it was possible to get the requisite for the best process efficiency, the pH-dependence of its function, like also of oscillatory and monotonic instability. An effort is made fot the systematic mechanistic analysis of the work of benzodiazepine electrochemical sensors.

Experimental Models of Anxiety for Drug Discovery and Brain Research.

Animal models have been vital to recent advances in experimental neuroscience, including the modeling of common human brain disorders such as anxiety, depression, and schizophrenia. As mice express robust anxiety-like behaviors when exposed to stressors (e.g., novelty, bright light, or social confrontation), these phenotypes have clear utility in testing the effects of psychotropic drugs. Of specific interest is the extent to which mouse models can be used for the screening of new anxiolytic drugs and verification of their possible applications in humans. To address this problem, the present chapter will review different experimental models of mouse anxiety and discuss their utility for testing anxiolytic and anxiogenic drugs. Detailed protocols will be provided for these paradigms, and possible confounds will be addressed accordingly.

Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of antidepressant and anxiolytic drugs in neonatal meconium and maternal hair.

A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of 22 antidepressant and anxiolytic drugs ad metabolites in the three consecutive maternal hair segments representing the pregnancy trimesters and paired neonatal meconium samples. After hair washing with methyl alcohol and diethyl ether and subsequent addition of internal standards, hair samples were treated with 500 µl VMA-T M3 reagent for 1h at 100 °C. After cooling, 100 µl M3 extract were diluted with 400 µl water and a volume of 10 µl was injected into chromatographic system. Meconium samples were firstly treated with 1 ml methyl alcohol and the organic layer back-extracted twice with 1.5 ml of a mixture of ethylacetate:hexane (80:20, v/v). Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization. The method was linear from the limit of quantification (0.05-1 ng/mg hair and 5-25 ng/g meconium depending on analyte under investigation;) to 10 ng/mg hair and 1000 ng/g meconium, with an intra- and inter-assay imprecision and inaccuracy always less than 20% and an analytical recovery between 66.6% and 95.3%, depending on the considered analyte and biological matrix. Using the validated method, 7 mothers were found positive to one or more hair segments and 5 meconium samples were found positive to one or more antidepressant and anxiolytic drugs, assessing prenatal exposure to these drugs following maternal consumption in one or more pregnancy trimesters.

Intrahippocampal infusion of the Ih blocker ZD7288 slows evoked theta rhythm and produces anxiolytic-like effects in the elevated plus maze.

Hippocampal theta rhythm has been associated with a number of behavioral processes, including learning and memory, spatial behavior, sensorimotor integration and affective responses. Suppression of hippocampal theta frequency has been shown to be a reliable neurophysiological signature of anxiolytic drug action in tests using known anxiolytic drugs (i.e., correlational evidence), but only one study to date (Yeung et al. (2012) Neuropharmacology 62:155-160) has shown that a drug with no known effect on either hippocampal theta or anxiety can in fact separately suppress hippocampal theta and anxiety in behavioral tests (i.e., prima facie evidence). Here, we attempt a further critical test of the hippocampal theta model by performing intrahippocampal administrations of the Ih blocker ZD7288, which is known to disrupt theta frequency subthreshold oscillations and resonance at the membrane level but is not known to have anxiolytic action. Intrahippocampal microinfusions of ZD7288 at high (15 µg), but not low (1 µg) doses slowed brainstem-evoked hippocampal theta responses in the urethane anesthetized rat, and more importantly, promoted anxiolytic action in freely behaving rats in the elevated plus maze. Taken together with our previous demonstration, these data provide converging, prima facie evidence of the validity of the theta suppression model.

Evaluation of cage leaving behaviour in rats as a free choice paradigm.

INTRODUCTION: The free exploratory paradigm is regarded as a reliable test for trait anxiety in mice but it may also be useful in rats. Previously, we showed that rat strains differ in their free exploration of novel areas, i.e. the surroundings of their familiar home cage when the lid was removed. AIM: Therefore, the purpose of the present study was to further examine strain, sex, and age differences in animals from different breeders in combination with pharmacological treatment designed to modify anxiety. METHODS: In the present study free exploratory behaviour test was evaluated in Sprague Dawley and Wistar rats from different breeders. We assessed seasonal variation, habituation to the test, and the impact of gender and age on exploration. Furthermore, we monitored exploration following intraperitoneal diazepam, 8-OH-DPAT and caffeine administration. Parameters measured were latency to start exploring the outside of the cage, the percentage of rats that explored the outside, as well as the number of visits. RESULTS: There was no seasonal variability in free exploratory behaviour. However, strains and sexes differed in the test results, though age-related differences had less impact. Diazepam (2mg/kg) and 8-OH-DPAT (30, 100 and 300µg/kg) decreased neophobia while caffeine (50mg/kg) increased the latency to explore the outside the next day. DISCUSSION: The free exploratory behaviour test can be used as a simple and complementary test to study trait anxiety-related behaviour in rats.

Contribuição da homeopatia no controle da ansiedade e do medo, como prevenção das emergências médicas em odontologia: estudo piloto / Contribution of homeopathy in the management of anxiety and fear, and prevention of medical emergencies in dentistry: a pilot study

Sabe-se que a ansiedade do paciente, nos momentos que antecedem um atendimento odontológico, pode interferir significativamente, influenciando nos trabalhos a serem executados. Há estudos que comprovam a eficácia do controle da ansiedade por métodos farmacológicos, que estão dentro do grupo dos agentes ansiolíticos. Com base na necessidade de alguns indivíduos controlar a ansiedade e fazer uso de uma medicação ansiolítica, o objetivo desse trabalho foi comparar o efeito do medicamento homeopático individualizado com o medicamento ansiolítico (benzodiazepínico) nos procedimentos odontológicos.

The patient’s anxiety before a dental procedure can interfere significantly the treatments to be performed. Some studies show the efficacy of the control of anxiety through pharmacological means including anxiolytic drugs. Since some individuals must control anxiety and use anxiolytic medication, this study ought to compare the effect of a benzodiapine and individualized homeopathic treatment on dental anxiety.