RESUMO
Esta dissertação objetivou estimar a prevalência, o padrão, e os fatores associados com a incidência de consumo de antidepressivos (AD) e benzodiazepínicos (BDZ) em uma coorte de funcionários de uma universidade. Foi realizado um estudo de coorte concorrente com os dados do Estudo Pró-Saúde, uma investigação longitudinal com funcionários técnico-administrativos do quadro efetivo de uma universidade no Estado do Rio de Janeiro. Os dados foram obtidos utilizando-se questionários autopreenchidos nos anos de 1999 (n=4.030), 2001 (n=3.574), 2006-07 (n=3.058) e 2012 (n=2.933). Foi construído um banco de dados com 5.369 pessoas, abarcando as quatro fases, sendo estimadas prevalências de uso AD e BDZ por fase. Em seguida, foi instituída uma coorte fixa excluindo os indivíduos que entraram no estudo em qualquer fase que não a linha de base (fase 1), e/ou indivíduos que faziam uso de AD e BDZ na fase 1. Modelos de Poisson com estimativa robusta da variância foram utilizados para estimar razões de incidência acumulada (risco relativo) de consumo de AD e BDZ entre 1999 e 2007. Em 1999, as prevalências de uso de AD e de BDZ foram 1,4% (IC 95%: 1,1-1,8) e 4,7% (IC 95%: 4,1-5,4), respectivamente. Em 2012, a prevalência de uso de AD foi de 5,4% (IC 95%: 5,5-6,2) e de BDZ de 6,8% (IC 95%: 6,0-7,8). Os inibidores seletivos da recaptação de serotonina (ISRS) representaram a classe que impulsionou o aumento do consumo dos AD, passando de 17% em 1999 para 67,6% em 2012. As prevalências de consumo de AD e BDZ foram maiores entre as mulheres, assim como entre os entrevistados com pior auto-percepção da saúde geral e mental (mensurada através do GHQ-12). A incidência do consumo de psicofármacos, entre 1999 e 2007, foi de 4,9% (IC 95%: 4,2-5,7) para AD e 8,3% (IC 95%: 7,3-9,3) para BDZ. Quando as fases 2 e 3 foram comparadas, o aumento da incidência de AD foi relativamente maior do que de BDZ. A incidência de uso de AD nas mulheres foi maior do que entre os homens (RR=2,5; IC 95% 1,75-4,04). As mulheres também apresentaram uma incidência de uso de BDZ 58% (IC 95%: 30-110) maior do que a observada para os homens. Aqueles com GHQ-12 positivo mostraram uma incidência 34% maior tanto para o consumo de AD quanto de BDZ. Consistente com a literatura, observou-se um maior risco de iniciar o uso de AD entre os indivíduos consumidores de BDZ na fase 1. Esses resultados sugerem que o aumento na incidência de uso de AD não foi acompanhado de uma queda na incidência do uso de BDZ. É imperativo que as prescrições de AD e BDZ estejam de acordo com as diretrizes atuais de tratamento, principalmente considerando o uso racional dos psicofármacos. Nossos achados apontam para a necessidade de identificar padrões semelhantes aos observados no presente estudo em outras populações, e visam contribuir para as políticas de educação permanente dos profissionais que prestam cuidados em saúde mental
This dissertation aimed to estimate the prevalence, pattern and factors associated with the incidence of antidepressant (AD) and benzodiazepine (BDZ) use in a cohort of university employees. A concurrent cohort study was carried out with data from the Pró-Saúde Study, a longitudinal investigation including all the technical-administrative employees of the actual staff of a university in the State of Rio de Janeiro. Self-administered questionnaires were applied in 1999 (n = 4,030), 2001 (n = 3,574), 2006-07 (n = 3,058) and 2012 (n = 2,933). A database was constructed with 5,369 people covering the four phases, and the prevalence use of AD and BDZ was estimated for each phase. A fixed cohort was defined excluding individuals who entered the study at any phase other than the baseline (phase 1) and/or individuals using AD and BDZ at phase 1. Poisson regression models with robust variance were fitted to estimate the cumulative incidence ratios for the use of AD and BDZ in the period of 1999-2007. The prevalence of use of AD and BDZ in 1999 was 1.4% and 4.7%, respectively. In 2012, the prevalence of use of AD was 5.4% and BDZ was 6.8%. Selective Serotonin Reuptake Inhibitors (SSRI) represented the class responsible for the increase in AD consumption, from 17% in 1999 to 67.6% in 2012. The prevalence use of AD and BDZ were higher among women and those with worse self-perception of general and mental health (measured through GHQ-12). The incidence of psychotropic consumption from 1999 to 2007 was 4.9% (95% CI: 4.2-5.7) for AD and 8.3% (95% CI: 7.3-9.3) for BDZ. When phases 2 and 3 were compared, the increase in the incidence of AD consumption was relatively greater for AD compared to BDZ. The incidence for AD was larger among women compared to men (RR=2.5; 95% CI: 1.75-4.04). Women also had an incidence 58% (95% CI: 30-110) higher for BDZ of use than men. Those with positive GHQ-12 had an incidence 34% greater for both AD and BDZ use. Consistent with the literature, a greater risk of initiating the use of AD was observed among individuals consuming BDZ in phase 1. These results suggest that the increase in the incidence of AD consumption was not followed by a decrease in the incidence of BDZ use. It is imperative that the prescription of AD and BDZ complies with current treatment guidelines, especially considering the rational use of psychotropic drugs. Our findings point to the need to identify patterns similar to those observed in other populations, and aim to contribute to the policies of permanent education of professionals who provide mental health care
Assuntos
Humanos , Psicotrópicos/uso terapêutico , Benzodiazepinonas/uso terapêutico , Saúde Mental , Epidemiologia , Incidência , Prevalência , Antidepressivos/uso terapêuticoRESUMO
Mouse pleurisy induced by carrageenan is used to determine the mechanism of anti-inflammatory action of 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864). Pre-treatment with Ro5-4864 inhibits different inflammatory parameters, such as neutrophil influx, MPO activity and NO levels in the early phase (4 h), as well as mononuclear cells and ADA activity in the late phase (48 h) of pleurisy. dl-Aminoglutethimide, inhibitor of steroidal synthesis, reverted the effect of Ro5-4864 on these different inflammatory parameters. Our results suggest that anti-inflammatory action of Ro5-4864 may be partly due to its capacity to inhibit leukocyte migration, as well as leukocyte activation and formation of NO by a mechanism dependent on glucocorticoids.
Assuntos
Anti-Inflamatórios/uso terapêutico , Benzodiazepinonas/uso terapêutico , Carragenina/toxicidade , Glucocorticoides/uso terapêutico , Pleurisia/tratamento farmacológico , Adenosina Desaminase/metabolismo , Adrenérgicos/farmacologia , Aminoglutetimida/farmacologia , Animais , Movimento Celular , Quimiotaxia de Leucócito , Feminino , Masculino , Camundongos , Neutrófilos/metabolismo , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Pleurisia/induzido quimicamente , Pleurisia/metabolismoRESUMO
The antinociceptive and anti-edematogenic effects of peripheral benzodiazepine receptor (PBR) ligands, Ro5-4864 (7-chloro-5- (4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepine-2) and PK11195 (1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide), were studied in an experimental model of carrageenan/LPS -induced arthritis in rats. These effects were compared with those of indomethacin and dexamethasone. Both pre and post-treatments with PK11195 were found to be anti-edematogenic and antinociceptive. The lower dose (0.01 mg/kg) exhibited the higher anti-edematogenic effect. On the other hand, the higher dose (0.5 mg/kg) produced antinociception, but with a decreased anti-edematogenic effect. Ro5-4864 produced a negligible antinociception and anti-edematogenic effect as pretreatment, but a pro-edematogenic effect when given as post-treatment. Dexamethasone and indomethacin presented parallel and dose-dependent antinociceptive and anti-edematogenic effects. In conclusion, PK11195 can effectively diminish arthritic nociception and edema elicited by LPS, but probably by mechanisms different from those of dexamethasone or indomethacin. RO5-4864 seemed to have opposite effect on this model.
Assuntos
Artrite Experimental/tratamento farmacológico , Benzodiazepinonas/uso terapêutico , Isoquinolinas/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Animais , Carragenina/farmacologia , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/prevenção & controle , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiopatologia , Indometacina/uso terapêutico , Lipopolissacarídeos/farmacologia , Masculino , Dor/tratamento farmacológico , Dor/prevenção & controle , Ratos , Ratos Wistar , Receptores de GABA-A , Resultado do TratamentoRESUMO
Apesar das recomendaçöes contra o uso prolongado de benzediazepínicos em idosos, as pesquisas indicam que o uso desses medicamentos aumenta com a idade. O padräo de uso de benzodiazepínicos e os fatores associados ao uso prolongado destes foram examinados com base em um questionário padronizado, aplicado a 634 mulheres com mais de sessenta anos, participantes de um centro de convivência para idosos no Rio de Janeiro, entre maio de 1992 e dezembro de 1995. A prevalência de uso de benzodiazepínicos na última quinzena foi estimada em 21,3 por cento (IC 95 por cento 1,1-24,5), e a prevalência de uso diário por 12 meses ou mais em 7,4 por cento (IC 95 por cento 5,4-9,4). Em uma análise multivariada, o número de medicamentos consumidos mostrou uma associaçäo importante e progressiva com o uso prolongado de benzodiazepínicos, com OR = 2,77 (IC 95 por cento 1,17-6,57) para aquelas que consomem entre quatro a seis medicamentos e OR = 7,62 (IC 95 por cento 3,18-18,26) para aquelas que consomem mais de sete medicamentos. Questöes de insônia (OR = 8,87 IC 95 por cento 2,53-31,06) e cefaléia (OR = 3,53 IC 95 por cento 1,82-6,89) também estiveram fortemente associadas a este padräo de uso.
Assuntos
Idoso , Benzodiazepinonas/uso terapêutico , Mulheres , UniversidadesRESUMO
Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean=23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, sympromatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range=1 to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean=16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 degrees Celsius, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20 percent) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7 percent), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9 percent), a difference highly significant (p<0.0001). Adverse effects occurred in 10/28 patients (35.7 percent), consisting maily in vomiting, somnolene and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily ocurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to deazepam in the intermittent treatment of FS recurrence.
Assuntos
Criança , Pré-Escolar , Lactente , Feminino , Humanos , Anticonvulsivantes/uso terapêutico , Benzodiazepinonas/uso terapêutico , Convulsões Febris , Anticonvulsivantes , Benzodiazepinonas , Estudos Prospectivos , RecidivaRESUMO
Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean = 23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, symptomatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range = 1 to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean = 16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 degrees C, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20%) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7%), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9%), a difference highly significant (p < 0.0001). Adverse effects occurred in 10/28 patients (35.7%), consisting mainly in vomiting, somnolence and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily occurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to diazepam in the intermittent treatment of FS recurrence.
Assuntos
Ansiolíticos , Anticonvulsivantes/uso terapêutico , Benzodiazepinas , Benzodiazepinonas/uso terapêutico , Convulsões Febris/prevenção & controle , Criança , Pré-Escolar , Clobazam , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , RecidivaRESUMO
New advances in the knowledge on the physiopathogenesis of epilepsy and their relationship with sodium and calcium channels and with the excitatory and inhibitory neurotransmitters actions have recently been developed. These knowledges have produced the research on new antiepileptic drugs which action places have specially based on the known impaired mechanisms. As the conventional drugs, the new therapeutic tool have produced a great advance in the therapy of epileptic events, specially in the refractory seizures, which represent 25-30% of the whole group of epilepsies. In the present work, we review the new drugs, ones have been registered, in order to their pharmacological properties, their efficacy their safety and their clinical indications as first-election or adjuvant drugs. We also discuss their known side adverse effects.