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2.
J Altern Complement Med ; 25(6): 613-622, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081672

RESUMO

Objectives: There is an increasing body of literature documenting the efficacy of micronutrients (vitamins and minerals) interventions for the treatment of psychiatric problems in the short term; however, long-term safety is largely unexplored. The goal of this observational study was to investigate the safety of two commercially available broad-spectrum micronutrient formulas (EMPowerplus and Daily Essential Nutrients) given at doses above the Recommended Dietary Allowances for the long-term treatment of individuals with psychiatric symptoms. Design: Participants on long-term treatment with micronutrients (medication-free) for psychiatric problems (attention-deficit hyperactivity disorder [ADHD, n = 21], anxiety/depression [n = 13]) were identified from ongoing research studies and the community through purchasing records. Seventeen children and 17 adults had blood tests to assess their full blood count, coagulation profile, liver and kidney function, fasting glucose, iron studies, key nutrients, and prolactin. Questionnaires assessed psychological/psychiatric functioning. Seventeen of the participants had completed the same measures pretreatment. Results: The average length of consuming micronutrients was 2.66 years (standard deviation = 2.86). Excluding B12 (which was elevated for almost all participants), 94.6% of all blood test results were within the test reference ranges. One participant was diagnosed with hemochromatosis based on iron studies. No other clinically relevant adverse changes in blood results were identified pre- and post-treatment. No clinically significant adverse effects were reported. Post-treatment psychometrics identified that 85% of the participants were in nonclinical ranges for measures of ADHD, depression, anxiety, and stress. Conclusions: We report preliminary evidence for the safety of long-term commercially available micronutrients, although questions remain. Overall, the substantial psychiatric benefits observed appear to outweigh the minimal observed risks in these participants. Screening for potential medical problems is recommended before initiating treatment. Long-term pharmacovigilance monitoring is required to ascertain any rare but significant adverse events.


Assuntos
Ansiedade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Depressão/tratamento farmacológico , Minerais/efeitos adversos , Oligoelementos/efeitos adversos , Vitaminas/efeitos adversos , Adolescente , Adulto , Transtornos de Ansiedade/tratamento farmacológico , Criança , Transtorno Depressivo/tratamento farmacológico , Feminino , Humanos , Masculino , Micronutrientes/efeitos adversos , Micronutrientes/uso terapêutico , Pessoa de Meia-Idade , Minerais/uso terapêutico , Fatores de Tempo , Oligoelementos/uso terapêutico , Vitaminas/uso terapêutico
3.
Phytother Res ; 33(6): 1604-1615, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31006899

RESUMO

This systematic review and meta-analysis aimed to study the efficacy and safety of chamomile for the treatment of state anxiety, generalized anxiety disorders (GADs), sleep quality, and insomnia in human. Eleven databases including PubMed, Science Direct, Cochrane Central, and Scopus were searched to retrieve relevant randomized control trials (RCTs), and 12 RCTs were included. Random effect meta-analysis was performed by meta package of R statistical software version 3.4.3 and RevMan version 5.3. Our meta-analysis of three RCTs did not show any difference in case of anxiety (standardized mean difference = -0.15, 95% CI [-0.46, 0.16], P = 0.4214). Moreover, there is only one RCT that evaluated the effect of chamomile on insomnia and it found no significant change in insomnia severity index (P > 0.05). By using HAM-A scale, there was a significant improvement in GAD after 2 and 4 weeks of treatment (mean difference = -1.43, 95% CI [-2.47, -0.39], P = 0.007), (MD = -1.79, 95% CI [-3.14, -0.43], P = 0.0097), respectively. Noteworthy, our meta-analysis showed a significant improvement in sleep quality after chamomile administration (standardized mean difference = -0.73, 95% CI [-1.23, -0.23], P < 0.005). Mild adverse events were only reported by three RCTs. Chamomile appears to be efficacious and safe for sleep quality and GAD. Little evidence is there to show its effect on anxiety and insomnia. Larger RCTs are needed to ascertain these findings.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Ansiedade/tratamento farmacológico , Camomila/química , Extratos Vegetais/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Sono/efeitos dos fármacos , Adulto , Idoso , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Camomila/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Resultado do Tratamento
4.
Arch Psychiatr Nurs ; 33(2): 211-213, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30927992

RESUMO

Advanced Practice Providers recognize and treat the most common side effects patients bring to our attention with the use of antidepressants, including insomnia, weight gain, emotional flattening, and sexual side effects. (https://www.psychcongress.com/article/top-5-side-effects-psychotropics-and-how-manage-them). We are, however, less intuitive and competent at picking up the high risk and rare, problem prone side effects our patients may experience related to the medications we prescribe, particularly in the more medically complex patients. In addition, the medically complex patient may mask a psychiatric concern as the psychiatric provider finds themselves caught up in the ambiguity of numerous somatic symptoms a patient presents with versus the psychiatric concerns that bear our attention. Autoimmune disorders often blur this line all too well affecting both psychiatric and physical well-being.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Citalopram/uso terapêutico , Depressão/tratamento farmacológico , Edema/etiologia , Doença de Hashimoto/complicações , Adulto , Antidepressivos/uso terapêutico , Transtornos de Ansiedade/diagnóstico , Depressão/diagnóstico , Feminino , Humanos , Vortioxetina/uso terapêutico
5.
J Clin Psychopharmacol ; 39(3): 258-260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30932946

RESUMO

PURPOSE: The time course of adverse events is an important factor for patient management. Clinicians are better able to prepare patients for specific adverse events, which leads to better treatment adherence. METHODS: Adverse events were followed longitudinally for 6 months during the open-label phase of a relapse prevention trial with 264 patients with generalized anxiety disorder. Adverse events were assessed at each treatment visit using a 21-item checklist. Logistic regression modeling, continuation ratio modeling, and hierarchical linear modeling were used to determine whether adverse events led to early attrition and whether adverse events decreased in enrolled patients over time. FINDINGS: Adverse events were found to have decreased highly significantly during treatment. A highly significant race effect was found in that whites had a significantly higher adverse event rate than did nonwhites. Early attrition rates were predicted by presence of nausea and fatigue, late attrition by dizziness, nervousness, and sexual dysfunction. IMPLICATIONS: Our findings provide information for clinicians on the course of adverse events over treatment, useful to prepare patients for treatment adherence.


Assuntos
Antidepressivos de Segunda Geração/administração & dosagem , Transtornos de Ansiedade/tratamento farmacológico , Cloridrato de Venlafaxina/administração & dosagem , Antidepressivos de Segunda Geração/efeitos adversos , Preparações de Ação Retardada , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Fatores de Tempo , Cloridrato de Venlafaxina/efeitos adversos
6.
Biomed Res Int ; 2019: 1037036, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834253

RESUMO

Galphimine-B (G-B), a compound isolated from Galphimia glauca, has been shown to possess important anxiolytic activity. In this study, we evaluated the effectiveness and tolerability of a G-B standardized extract (experimental treatment) that was administered daily for 10 weeks in patients with moderate or severe Generalized Anxiety Disorder (GAD). Alprazolam was used as control treatment and administered under the same conditions. A total of 167 patients were included. At the start of the study, the severe anxiety condition prevailed, with an average on the Hamilton Anxiety Scale of 35.1 ± 8.8 and 35.8 ± 8.1 points in the control and experimental groups, respectively. After the 10 weeks of administration, the average was reduced in the control group to 4.6 ± 6.5 points and in the experimental group to 3.5 ± 5.5 points. Therapeutic success in the control group was 85.7% and in the experimental group, 92.0%. A high proportion of patients (22.2%) treated with Alprazolam manifested daytime sleepiness, while in the group treated with the G-B standardized extract, daytime sleepiness was found in 4.7%. In conclusion, a G-B standardized extract demonstrated therapeutic effectiveness in patients with GAD, without exhibiting significant difference with Alprazolam, but showing fewer cases of daytime sleepiness. The trial was registered at http://clinicaltrials.gov by identifier: NCT03702803.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Galphimia/química , Extratos Vegetais/administração & dosagem , Triterpenos/administração & dosagem , Alprazolam/administração & dosagem , Transtornos de Ansiedade/patologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente/normas , Extratos Vegetais/química , Triterpenos/química
9.
Artigo em Inglês | MEDLINE | ID: mdl-30717435

RESUMO

Mental Disorders and Heroin Use Disorder (HUD) often co-occur and constitute correlated risk factors that the authors believe are best considered from a unitary perspective. In this article we review and discuss data collected by the V.P. Dole Research Group in Dual Disorder (V.P. Dole DD-RG) patients according to the following six discussion points: (1) Treatment of personality disorders during Methadone Maintenance Treatment (MMT); (2) Treatment of Mood Disorders during MMT; (3) Treatment of Anxiety Disorders during MMT; (4) Treatment of Psychotic Disorders during MMT; (5) Treatment of violence during MMT; (6) Treatment of Alcohol Use Disorder (AUD) during MMT. In treating Mood Disorder in HUD patients, we must bear in mind the interactions (potentiation and side effects) between psychopharmacology, used substances and agonist opioid medications; the use of psychiatric medications as an anti-craving drug, and the possible use of agonist and antagonist opioid medications in treating the other mental disorders. In treating chronic psychosis in HUD patients, we must consider the potentiation and side effects of antipsychotic drugs consequent on HUD treatment, worsening addiction hypophoria and inducing a more severe reward deficiency syndrome (RDS) in hypophoric patients. Violence and AUD during MMT can benefit from adequate dosages of methadone and co-medication with Sodium gamma-hydroxybutyrate (GHB). The experience of our V.P. Dole DD-RG suggests the following: (a) DD is the new paradigm in neuroscience in deepening our understanding of mental health; (b) To successfully treat DD patients a double competence is needed; (c) In managing DD patients priority must be given to Substance Use Disorder (SUD) treatment (stabilizing patients); (d) Antidepressant use is ancillary to SUD treatment; antipsychotic use must be restricted to acute phases; mood stabilizers must be preferred; any use of Benzodiazepines (BDZs) must be avoided.


Assuntos
Dependência de Heroína/tratamento farmacológico , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Alcoolismo/tratamento farmacológico , Alcoolismo/epidemiologia , Antidepressivos , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Fissura/efeitos dos fármacos , Interações de Medicamentos , Dependência de Heroína/epidemiologia , Humanos , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Violência/estatística & dados numéricos
10.
Lancet ; 393(10173): 768-777, 2019 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-30712879

RESUMO

BACKGROUND: Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices. METHODS: A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106. FINDINGS: Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias. INTERPRETATION: To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of network analysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy. FUNDING: No funding was received for this research.


Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Meta-Análise em Rede , Antidepressivos/uso terapêutico , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Resultado do Tratamento
11.
BMJ Case Rep ; 12(2)2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30737329

RESUMO

A 21-year-old university student studying abroad in the USA presented to the emergency department with double vision, lower extremity weakness with difficulty ambulating and other neuropsychiatric symptoms. MRI of the brain and spinal cord were normal. Vitamin B12 was 78 pg/mL (58 pmol/L, reference 211-911 pg/mL). The patient had been using nitrous oxide capsules used for whipped cream recharging, which she obtained from other students, a few times daily for a month for the purpose of anxiety relief. The patient was not a vegan or vegetarian. The patient was treated with intramuscular vitamin B12 repletion with partial resolution of neurologic symptoms and discharged on vitamin B12 supplementation.


Assuntos
Óxido Nitroso/efeitos adversos , Transtornos Psicóticos/etiologia , Doenças da Medula Espinal/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/complicações , Deficiência de Vitamina B 12/induzido quimicamente , Vitamina B 12/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Diplopia/induzido quimicamente , Aconselhamento Diretivo , Feminino , Humanos , Óxido Nitroso/administração & dosagem , Transtornos Psicóticos/psicologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Adulto Jovem
12.
J Affect Disord ; 249: 82-89, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30763799

RESUMO

BACKGROUND: This study aimed to explore subtypes of treatment-resistant depression (TRD). METHODS: Latent class analysis (LCA) was performed on clinical and demographic data collected from 375 patients with TRD. Clinical variables were compared across subtypes. Treatment outcomes across subtypes of TRD were compared separately for those within each subtype with anxiety (those with a HRSD-17 anxiety/somatization factor score ≥ 7) and those without anxiety. LCA subtypes were compared using Cochran's and Mantel-Haenszel χ2 test, respectively. Unordered multinomial logistic regression was used to assess clinical correlates of TRD subtypes. RESULTS: Three categories were detected: severe depression (66%), moderate depression with anxiety (9%) and mild depression with anxiety/somatization (25%). Gender, age, age at first onset, family monthly income, number of hospitalizations, HRSD-17 and clinical global impression-severity (CGI) scores were significantly different across the three groups. Remission rates were significantly different among anxious cases with severe (43.75%), moderate (22.73%) and mild (26.25%) depression subtypes. Compared to cases in the mild depression group, those in the severe depression group had a greater likelihood of being male, having a later age of first onset, higher numbers of hospitalization, higher HRSD-17 and CGI total scores, and lower family income. Those in the moderate depression group were more likely to be male and have lower family income than those in the mild depression group. LIMITATIONS: Representative bias, relatively small sample size, unbalanced group size and incomplete indicator variables might have a negative effect on the validity and generalization of the findings. CONCLUSIONS: Depression severity could be a basis for subtype classification of patients with TRD. The classification of latent class of TRD observed in our study was similar to the structure found in MDD. Longitudinal research into the stability of the latent structure of TRD across illness course is merited as is research into treatment outcomes for TRD subtypes.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Transtorno Depressivo Resistente a Tratamento/classificação , Transtorno Depressivo Resistente a Tratamento/etnologia , Adulto , Idoso , Ansiedade/epidemiologia , Transtornos de Ansiedade/tratamento farmacológico , China/epidemiologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Classes Latentes , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Medicine (Baltimore) ; 98(5): e14334, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702618

RESUMO

The aim of the study was to define whether anxiety itself or only the treatment with anxiolytic medication is risk factor for hyponatremia and overhydration.A case-control study of patients with a diagnosis of anxiety who received a selective serotonin reuptake inhibitor (SSRI). Serum sodium, urea to creatinine ratio, and odds ratio (OR) of hyponatremia and overhydration before initiation of treatment were compared to those of a control group of participants. Laboratory tests were also examined for changes following treatment with an SSRI. All blood tests were conducted from January 1, 2001 until December 31, 2017. Subjects were selected from a large electronic database, insuring 2 million Israelis. A total of 7211 patients with a diagnosis of anxiety who have received a prescription for an SSRI were identified; 3634 were excluded mostly due to other conditions that could cause hyponatremia, and 3520 participants were included in the case group. The control group consisted of 6985 age and gender matched participants who did not have a diagnosis of anxiety or any other exclusion criteria.Mean serum sodium levels were elevated in cases before the initiation of SSRIs; sodium: case 139.3 (137.3-141.3), control 139.2 (137.06-141.26) mmol/L (P = .01). The OR of hyponatremia was 0.89 for the case group (P = .004). Treatment with SSRIs decreased mean serum sodium (139.3-139.1 mmol/L; P = .0001) and increased by 50% the rate of hyponatremia (2.6-3.9% P = .024).It is the use of SSRIs and not anxiety itself that causes hyponatremia among anxious patients.


Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/tratamento farmacológico , Hiponatremia/epidemiologia , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Hiponatremia/diagnóstico , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Psychiatr Genet ; 29(2): 51-56, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30681431

RESUMO

OBJECTIVES: Angelman syndrome (AS) is a neurogenetic disorder associated with impaired expression of the ubiquitin-protein ligase E3A gene on chromosome 15. AS results in intellectual disability with limited expressive language, epilepsy, ataxia, sleep impairment, and problematic behavior which may include anxiety. Buspirone is a serotonin (5-HT)1A receptor partial agonist used in the treatment of anxiety disorders and may, therefore, have a treatment role for patients with AS. METHODS: We describe three patients who were given open-label buspirone for the treatment of behaviors thought to be related to anxiety. RESULTS: We found significant improvement in symptoms of anxiety with buspirone. Patients tolerated long-term usage of the medication. CONCLUSION: The findings of this study suggest that buspirone may be effective for the amelioration of behaviors related to anxiety in patients with AS, and well tolerated. Limitations include the open-label nature of these treatments, the small sample size and the absence of a control group.


Assuntos
Síndrome de Angelman/tratamento farmacológico , Ansiedade/tratamento farmacológico , Buspirona/farmacologia , Adulto , Síndrome de Angelman/complicações , Transtornos de Ansiedade/tratamento farmacológico , Feminino , Humanos , Deficiência Intelectual , Masculino , Receptor 5-HT1A de Serotonina , Serotonina , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
17.
J Affect Disord ; 246: 619-626, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609411

RESUMO

BACKGROUND: This study investigated the efficacy of a succulent, Caralluma fimbriata extract (CFE) in reducing anxiety and stress in healthy adults. METHODS: An 8 week double-blind randomised clinical trial, in which 97 adults self-reporting mild to moderate anxiety were given 500 mg b.d. CFE (n = 49), or 500 mg b.d. placebo (n = 48). Anxiety and stress were measured at baseline, week 4, and week 8 to investigate the timing of treatment effect using the GAD-7, Perceived Stress Scale (PSS), Positive and Negative Affect Schedule (PANAS), and salivary cortisol. Data were analysed using mixed ANOVAs on SPSS v.24. RESULTS: Results indicated a significant reduction in anxiety and stress in both groups at week 4 and week 8. The reduction in the CFE group was significantly greater (p < .05) than in the placebo group on the GAD-7 and PSS at week 4 and week 8, and in Negative affect at week 4. Improvement in Positive affect was greater in the CFE group than in the placebo group at week 8. Cortisol analysis indicated that CFE may act through the Hypothalamic-Pituitary-Adrenal (HPA) axis, showing statistically significant changes in males, but not in females. LIMITATIONS: Self-reported instruments involve subjective interpretation thus salivary cortisol was employed as a more objective measure. The study would benefit from a larger sample and longer trial, and the inclusion of a wait-list group to allow comparison between treatment and no treatment. CONCLUSIONS: The findings indicate that CFE is superior to placebo in reducing subclinical anxiety and stress over 8 weeks.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Apocynaceae/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiologia , Estresse Psicológico/fisiopatologia , Adulto Jovem
18.
J Clin Psychopharmacol ; 39(1): 20-27, 2019 Jan/Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30531477

RESUMO

BACKGROUND: Generalized anxiety disorder (GAD) is a common psychiatric disorder, but many patients experience only partial relief of symptoms with existing therapies. Benzodiazepines are effective in many cases but are limited by a number of significant adverse effects. PF-06372865 is a subtype-selective gamma-aminobutyric acid A (GABAA)-positive allosteric modulator lacking in functional activity at alpha 1-containing receptors that are believed to mediate many of these adverse effects. METHODS: PF-06372865 was evaluated as an adjunct to current GAD treatment in a double-blind, placebo-controlled, sequential parallel comparison study in patients with GAD who showed an incomplete response to current standard-of-care pharmacotherapy. A total of 90 subjects (of the planned 384) were randomized into the study before the decision to terminate the study. Two doses of PF-06372865 (2.5 mg twice daily and 7.5 mg twice daily) were compared with placebo. RESULTS: Neither dose of PF-06372865 differentiated from placebo on week 4 Hamilton Anxiety Inventory total (primary end point) or on the Sheehan Disability Scale total score (secondary end point). Adverse events including dizziness, headache, and somnolence were observed, and the 7.5 mg dose demonstrated some impairment on the Digit Symbol Substitution test and the Epworth Sleepiness Scale relative to placebo and the 2.5 mg dose. CONCLUSIONS: Factors contributing to the negative results include the limited sample size and failure to explore a broader range of doses.


Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Imidazóis/uso terapêutico , Piridazinas/uso terapêutico , Adolescente , Adulto , Ansiolíticos/efeitos adversos , Ansiolíticos/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imidazóis/efeitos adversos , Imidazóis/sangue , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Piridazinas/efeitos adversos , Piridazinas/sangue , Padrão de Cuidado , Resultado do Tratamento , Suspensão de Tratamento , Adulto Jovem
19.
Behav Brain Res ; 356: 156-169, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30144460

RESUMO

Depression, a common mood disorder, involves anhedonia and defects in reward circuits and mesolimbic dopamine transmission in the striatum and nucleus accumbens (NAc). Active vitamin-D, (1,25-(OH)2 vitamin-D3), exerts protective and regulatory effects on the brain dopamine system. In this study, key depression-like symptoms were induced in rats by chronic mild-stress (CMS) and the comparative effect of treatment with 1,25-(OH)2 vitamin-D3 (5, 10 µg/kg, or vehicle; i.p., twice weekly) or fluoxetine (5 mg/kg or vehicle, i.p., daily) on anhedonic behavior, locomotor activity and anxiety-like behavior was examined using sucrose preference test (SPT), open field test (OFT) and novel object exploration test (NOT), respectively. We also measured serum corticosterone levels and dopamine transporter-immunoreactivity (DAT-ir) levels in NAc shell and core. CMS exposure for 3 weeks was followed by a SPT and thereafter CMS was continued for 5 weeks, along with vitamin-D or fluoxetine treatment and further testing, which was concluded with another SPT. Vitamin-D treatment enhanced sucrose preference (P < 0.01; an hedonic effect) and increased object exploration (P < 0.01) in CMS rats. CMS significantly reduced the level of DAT-ir in NAc (P < 0.0001). Vitamin-D treatment restored/increased DAT-ir levels (P < 0.0001) in CMS rat NAc (core/ shell), compared to levels in fluoxetine treated and non-treated CMS rats. Vitamin-D did not alter locomotor activity or produce an anxiolytic effect in the OFT. These data suggest that similar to the antidepressant, fluoxetine, regular vitamin-D treatment can improve 'anhedonia-like symptoms' in rats subjected to CMS, probably by regulating the effect of dopamine-related actions in the NAc.


Assuntos
Anedonia/efeitos dos fármacos , Depressão/metabolismo , Vitamina D/fisiologia , Anedonia/fisiologia , Animais , Antidepressivos/farmacologia , Ansiedade/metabolismo , Transtornos de Ansiedade/tratamento farmacológico , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Transtorno Depressivo/tratamento farmacológico , Modelos Animais de Doenças , Dopamina/metabolismo , Dopamina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/efeitos dos fármacos , Masculino , Núcleo Accumbens/metabolismo , Ratos , Ratos Wistar , Estresse Psicológico , Vitamina D/metabolismo , Vitaminas/farmacologia
20.
Methods Mol Biol ; 1916: 99-103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30535687

RESUMO

The open field test is used in studies of the neurobiological basis of anxiety and screening for novel drug targets and anxiolytic compounds. This test uses a camera to measure movement of the test animal in the peripheral and central zones of a 42 × 42 × 42 cm polyvinyl chloride box. This chapter describes a protocol for carrying out the open-field test for assessment of locomotion and anxiety-like behavior in mice.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Comportamento Animal/fisiologia , Locomoção/fisiologia , Biologia Molecular/métodos , Animais , Ansiolíticos/administração & dosagem , Transtornos de Ansiedade/fisiopatologia , Modelos Animais de Doenças , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/fisiologia
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