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1.
J Clin Psychopharmacol ; 40(4): 391-395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32644323

RESUMO

PURPOSE/BACKGROUND: Attentional bias toward drug-related cues is considered to be an indication of neurocognitive processes associated with drug dependence. While this phenomenon has been shown in other addictive substances, whether hypnotic medication would lead to similar processes remains an issue to be investigated. The present study examined attentional bias toward drug-related cues in long-term hypnotic users and the effect of negative affect on this process. METHODS/PROCEDURES: Thirteen long-term hypnotic users participated in this study. They spent 2 nights in the sleep laboratory: a mood-induction night and a neutral night. Attentional bias was measured through the recording of event-related potentials using a cue-reactivity paradigm; subjective craving for hypnotics was assessed using a single-item rating scale, and negative affect was measured using the Positive and Negative Affect Schedule. FINDINGS/RESULTS: The results showed that the amplitudes of P300 and slow positive wave for hypnotic-related and sleep-related photographs were significantly higher than those for neutral photographs in both conditions. Negative mood induction did not significantly increase attentional bias. IMPLICATIONS/CONCLUSIONS: The findings provide preliminary evidence that long-term hypnotic users do have attentional bias for hypnotic-related photos, suggesting the possibility of neurocognitive processes associated with drug dependence. However, the results did not show higher attentional bias under negative mood, suggesting that the use of hypnotics is not reinforced by the desire to eliminate negative affect. Because of the limited sample size and lack of a control group, the results should be considered as preliminary findings that call for future studies to further investigate this issue.


Assuntos
Afeto/fisiologia , Viés de Atenção/fisiologia , Potenciais Evocados/fisiologia , Hipnóticos e Sedativos/efeitos adversos , Uso Indevido de Medicamentos sob Prescrição , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Adolescente , Adulto , Fissura , Sinais (Psicologia) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Adulto Jovem
2.
Sleep Med Clin ; 15(2): 147-154, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32386690

RESUMO

Patients with chronic insomnia are commonly prescribed hypnotic medications. The long-term effects of chronic hypnotics are not known and discontinuation is encouraged but often difficult to achieve. A gradual taper is preferred to abrupt cessation to avoid rebound insomnia and withdrawal symptoms. Written information provided to the patient about medication discontinuation may be helpful. Cognitive behavioral therapy or behavioral therapies alone can improve hypnotic discontinuation outcomes. There is limited evidence for adjunct medications to assist in hypnotic cessation for insomnia.


Assuntos
Hipnóticos e Sedativos/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Terapia Cognitivo-Comportamental , Humanos , Hipnóticos e Sedativos/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Síndrome de Abstinência a Substâncias/terapia , Suspensão de Tratamento
3.
Chemosphere ; 253: 126762, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32302915

RESUMO

17ß-trenbolone (17ß-TBOH) is one of the dominant metabolites of trenbolone acetate, which is widely applied in beef cattle operations around the globe. The effects of environmental concentrations of 17ß-trenbolone on the early development of zebrafish embryos have received very little attention. Melatonin could regulate sleep-wake cycle and plays a protective role in various adverse conditions. Here, environmentally realistic concentrations of 17ß-trenbolone (1 ng/L, 10 ng/L, 50 ng/L) has been exposure to zebrafish embryos at 2 h postfertilization (hpf). The results showed that 10 ng/L and 50 ng/L 17ß-trenbolone disturbed the distribution of caudal primary motoneurons and downregulated expression of motoneuron development related genes along with locomotion decreasing. While melatonin could recover the detrimental effects caused by 17ß-trenbolone. Interestingly, 17ß-trenbolone exposure increased waking activity and decreased rest even in a low dose (1 ng/L). Moreover, it upregulated hypocretin/orexin (Hcrt) signaling which promotes wakefulness. Melatonin restored the insomnia-like alternation induced by 17ß-trenbolone exposure. Collectively, we conclude that 17ß-trenbolone disturbed motoneuron development and altered sleep/wake behavior, while melatonin could alleviate the deleterious influence on motoneuron development and recover the circadian rhythm.


Assuntos
Comportamento Animal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Melatonina/farmacologia , Atividade Motora/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono/prevenção & controle , Acetato de Trembolona/toxicidade , Peixe-Zebra , Animais , Bovinos , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/genética , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/fisiologia , Desenvolvimento Embrionário/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Orexinas/genética , Fenótipo , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente
4.
J Pharm Pharmacol ; 72(5): 719-727, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32043598

RESUMO

OBJECTIVES: Neuropsychiatric adverse effects (NPAE) related to efavirenz, mainly dizziness, is detrimental to human immunodeficiency virus (HIV) treatment. Our study aims at evaluating if zidovudine use potentiates the risk of dizziness related to efavirenz when used together and whether there are significant differences in over time distribution of this NPAE and others relatively frequents regarding efavirenz regimen without zidovudine. METHODS: Human immunodeficiency virus-infected patients under efavirenz-containing different therapy were enrolled. A retrospective analysis of official medical records was accomplished to collect clinical data regarding NPAE occurrence and severity. Univariate statistic and statistical model based on survival analyses were performed. KEY FINDINGS: One hundred sixty-two patients were included, of these seventy-seven (47.5%) had NPAE reported, such as dizziness (more frequent), depression and insomnia. Univariate statistical analysis demonstrated that the combined use of efavirenz with zidovudine increased the NPAE risk (OR: 2.5; P-value: 0.008), mainly dizziness risk (OR: 3.5; P-value: 0.009) and survival analysis showed that such combination is associated with dizziness occurrence faster (HR: 2.9; P-value: 0.02). CONCLUSIONS: The results may contribute to clarify the dizziness occurrence dynamics in therapy with efavirenz and zidovudine by identifying susceptibilities and assisting in the choice of combined antiretroviral therapy.


Assuntos
Alquinos/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Ciclopropanos/efeitos adversos , Tontura/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/efeitos adversos , Zidovudina/efeitos adversos , Adulto , Brasil , Depressão/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Análise de Sobrevida , Fatores de Tempo
5.
QJM ; 113(1): 31-36, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424520

RESUMO

BACKGROUND: Benzodiazepines (BZD) are associated with adverse effects, particularly in older adults. AIM: This study assesses the association between BZD use and falls, and the impact of sleep quality on this association, in community dwelling adults aged over 50. DESIGN: Cross-sectional analysis of data from wave 1 of The Irish Longitudinal Study on Ageing. METHODS: Participants were classed as BZD users or non-users and asked if they had fallen in the last year, and whether any falls were unexplained. Sleep quality was assessed via self-reported trouble falling asleep, daytime somnolence and early-rising. Logistic regression assessed for an association between BZD use and falls, and the impact of sleep quality on this association was assessed by categorizing based on BZD use and sleep quality variables. RESULTS: Of 8175 individuals, 302 (3.69%) reported taking BZDs. BZD use was associated with falls, controlling for confounders [Odds Ratio (OR) 1.40; 1.08, 1.82; P-value 0.012]. There was no significant association between BZDs and unexplained falls, controlling for confounders [OR 1.41; 95% Confidence Interval (CI) 0.95, 2.10; P-value 0.09]. Participants who use BZDs and report daytime somnolence (OR 1.93; 95% CI 1.12, 3.31; P-value 0.017), early-rising (OR 1.93; 95% CI 1.20, 3.11; P-value 0.007) or trouble falling asleep (OR 1.83; 95% CI 1.12, 2.97; P-value 0.015), have an increased odds of unexplained falls. CONCLUSION: BZD use is associated with falls, with larger effect size in those reporting poor sleep quality in community dwelling older adults. Appropriate prescription of medications such as BZDs is an important public health issue.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Benzodiazepinas/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Sono/efeitos dos fármacos , Idoso , Benzodiazepinas/administração & dosagem , Estudos Transversais , Feminino , Humanos , Vida Independente , Irlanda/epidemiologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/epidemiologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-31526830

RESUMO

OBJECTIVE: To determine the characteristics of the activation syndrome (AS) that predict the emergence or worsening of suicidal ideation (SI) in the first month of antidepressant treatment with tianeptine, as well as the temporal relationship between both conditions. METHOD: A naturalistic sample of 2422 depressed outpatients starting a new antidepressant treatment with tianeptine was assessed at 2, 4 and 6 weeks of follow-up using validated questionnaires. Four main dimensions of AS were examined: impulsivity, sleep problems, anxiety and agitation. RESULTS: The emergence of an AS was more likely in long-lasting depressive episodes, but less likely if the patient responded to the antidepressant or benzodiazepines were added as an add-on treatment. Treatment-emergent SI was strongly associated to the presence of an AS, particularly in case of sleep problems (OR = 8.42) or impulsivity upsurges (OR = 3.89), even after adjustment for all relevant confounding factors. CONCLUSIONS: Our findings suggest a dose-effect mechanism modulating the relationship between treatment-related SI and AS. AS symptoms may need to be monitored closely in the weeks that follow the introduction of an antidepressant treatment.


Assuntos
Antidepressivos Tricíclicos/efeitos adversos , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Comportamento Impulsivo/efeitos dos fármacos , Agitação Psicomotora/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Ideação Suicida , Tiazepinas/efeitos adversos , Antidepressivos Tricíclicos/uso terapêutico , Ansiedade/complicações , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Agitação Psicomotora/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Síndrome , Tiazepinas/uso terapêutico , Fatores de Tempo
7.
Artigo em Inglês | MEDLINE | ID: mdl-31766368

RESUMO

Background: Falls are leading cause of injury among older people, especially for those living in long-term care facilities (LTCFs). Very few studies have assessed the effect of sleep quality and hypnotics use on falls, especially in Chinese LTCFs. The study aimed to examine the association between sleep quality, hypnotics use, and falls in institutionalized older people. Methods: We recruited 605 residents from 25 LTCFs in central Shanghai and conducted a baseline survey for sleep quality and hypnotics use, as well as a one-year follow-up survey for falls and injurious falls. Logistic regression models were applied in univariate and multivariate analysis. Results: Among the 605 participants (70.41% women, mean age 84.33 ± 6.90 years), the one-year incidence of falls and injurious falls was 21.82% and 15.21%, respectively. Insomnia (19.83%) and hypnotics use (14.21%) were prevalent. After adjusting for potential confounders, we found that insomnia was significantly associated with an increased risk of falls (adjusted risk ratio (RR): 1.787, 95% CI, 1.106-2.877) and the use of benzodiazepines significantly increased the risk of injurious falls (RR: 3.128, 95% CI, 1.541-6.350). Conclusion: In elderly LTCF residents, both insomnia and benzodiazepine use are associated with an increased risk of falls and injuries. Adopting non-pharmacological approaches to improve sleep quality, taking safer hypnotics, or strengthening supervision on benzodiazepine users may be useful in fall prevention.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Benzodiazepinas/efeitos adversos , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Hipnóticos e Sedativos/efeitos adversos , Assistência de Longa Duração/estatística & dados numéricos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Razão de Chances
8.
Artigo em Russo | MEDLINE | ID: mdl-31626183

RESUMO

According to modern concepts, sleep disorders are considered as a common geriatric syndrome, which also emphasizes their polyfactorial genesis. One of the important factors inducing sleep disorders is the intake of various drugs, which becomes especially significant with the problems of polymorbidity and polypharmacy occurring in older age groups. The article provides a classification of drug-induced sleep disorders, which presents a wide range of conditions associated with a disturbance of the sleep-wake cycle. The authors present the frequency of insomnia associated with taking drugs from different pharmacological groups according to the literature, and consider mechanisms of insomnia development due to the effect on various receptors and neurotransmitter systems, as well as data on their effect on sleep structure. The article presents risk factors for drug-induced insomnia and discusses preventive measures and management of patients.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Fatores de Risco , Sono/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Transtornos do Sono-Vigília/induzido quimicamente
9.
Sleep ; 42(11)2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31529094

RESUMO

STUDY OBJECTIVES: To asses the long-term safety and efficacy of pitolisant, an histamine H3-receptor antagonist, on narcolepsy. METHODS: This open-label, single-arm, pragmatic study, recruited adult patients with narcolepsy and Epworth Sleepiness Scale (ESS) score ≥12. After a titration period, patients were treated for up to 1 year with oral pitolisant once-a-day at up to 40 mg. Concomitant stimulants and anti-cataplectic agents were allowed. The primary endpoint was safety; secondary endpoints included ESS, cataplexy, and other diary parameters. RESULTS: Patients (n = 102, 75 with cataplexy) received pitolisant, for the first time in 73 of them. Sixty-eight patients (51 with cataplexy) completed the 12-month treatment. Common treatment-emergent adverse events were headache (11.8% of patients), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depressive symptoms (4.9%), and nausea (4.9%). Seven patients had a serious adverse effect, unrelated to pitolisant except for a possibly related miscarriage. One-third of patients stopped pitolisant, mostly (19.6%) for insufficient benefit. ESS score decreased by 4.6 ± 0.6. Two-thirds of patients completing the treatment were responders (ESS ≤ 10 or ESS decrease ≥ 3), and one third had normalized ESS (≤10). Complete and partial cataplexy, hallucinations, sleep paralysis, and sleep attacks were reduced by 76%, 65%, 54%, 63%, and 27%, respectively. Pitolisant as monotherapy (43% of patients) was better tolerated and more efficacious on ESS than on add-on, but efficacy was maintained in this last case. CONCLUSIONS: Long-term safety and efficacy of pitolisant on daytime sleepiness, cataplexy, hallucinations, and sleep paralysis is confirmed.


Assuntos
Estimulantes do Sistema Nervoso Central/uso terapêutico , Antagonistas dos Receptores Histamínicos H3/uso terapêutico , Narcolepsia/tratamento farmacológico , Piperidinas/uso terapêutico , Adulto , Ansiedade/induzido quimicamente , Estimulantes do Sistema Nervoso Central/efeitos adversos , Depressão/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Antagonistas dos Receptores Histamínicos H3/efeitos adversos , Humanos , Masculino , Piperidinas/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Resultado do Tratamento
10.
Chin J Nat Med ; 17(7): 551-560, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514987

RESUMO

Ziziphi Spinosae Semen (ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin (5-HT), glutamic acid (Glu), γ-aminobutyric acid (GABA), noradrenaline (NE) and dopamine (DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESI- MS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 10 min. The method showed a good linearity (R2 > 0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower (P < 0.01) in para-chlorophenylalanine (PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group (P < 0.01). Treatment with ZSS aqueous extract (4 or 8 g·kg-1·d-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.


Assuntos
Encéfalo/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Neurotransmissores/metabolismo , Extratos Vegetais/farmacologia , Distúrbios do Início e da Manutenção do Sono/metabolismo , Ziziphus/química , Animais , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Fenclonina/toxicidade , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/uso terapêutico , Masculino , Medicina Tradicional Chinesa , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Espectrometria de Massas em Tandem
11.
N Engl J Med ; 381(10): 933-944, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31483964

RESUMO

BACKGROUND: Pyruvate kinase deficiency is caused by mutations in PKLR and leads to congenital hemolytic anemia. Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase in red cells. METHODS: In this uncontrolled, phase 2 study, we evaluated the safety and efficacy of mitapivat in 52 adults with pyruvate kinase deficiency who were not receiving red-cell transfusions. The patients were randomly assigned to receive either 50 mg or 300 mg of mitapivat twice daily for a 24-week core period; eligible patients could continue treatment in an ongoing extension phase. RESULTS: Common adverse events, including headache and insomnia, occurred at the time of drug initiation and were transient; 92% of the episodes of headache and 47% of the episodes of insomnia resolved within 7 days. The most common serious adverse events, hemolytic anemia and pharyngitis, each occurred in 2 patients (4%). A total of 26 patients (50%) had an increase of more than 1.0 g per deciliter in the hemoglobin level. Among these patients, the mean maximum increase was 3.4 g per deciliter (range, 1.1 to 5.8), and the median time until the first increase of more than 1.0 g per deciliter was 10 days (range, 7 to 187); 20 patients (77%) had an increase of more than 1.0 g per deciliter in the hemoglobin level at more than 50% of visits during the core study period, with improvement in markers of hemolysis. The response was sustained in all 19 patients remaining in the extension phase, with a median follow-up of 29 months (range, 22 to 35). Hemoglobin responses were observed only in patients who had at least one missense PKLR mutation and were associated with the red-cell pyruvate kinase protein level at baseline. CONCLUSIONS: The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase deficiency, with a sustained response during a median follow-up of 29 months during the extension phase. Adverse effects were mainly low-grade and transient. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02476916.).


Assuntos
Anemia Hemolítica Congênita não Esferocítica/tratamento farmacológico , Hemoglobinas/metabolismo , Piperazinas/administração & dosagem , Piruvato Quinase/deficiência , Erros Inatos do Metabolismo dos Piruvatos/tratamento farmacológico , Quinolinas/administração & dosagem , Administração Oral , Adolescente , Adulto , Anemia Hemolítica Congênita não Esferocítica/sangue , Anemia Hemolítica Congênita não Esferocítica/genética , Catecóis , Esquema de Medicação , Feminino , Seguimentos , Cefaleia/induzido quimicamente , Humanos , Masculino , Mutação , Piperazinas/efeitos adversos , Piruvato Quinase/sangue , Piruvato Quinase/genética , Erros Inatos do Metabolismo dos Piruvatos/sangue , Erros Inatos do Metabolismo dos Piruvatos/genética , Quinolinas/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Tirfostinas , Adulto Jovem
12.
S Afr Med J ; 109(6): 378-381, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31266554

RESUMO

The systemic fluoroquinolones (FQs) have recently been reported to be associated with significant side-effects in susceptible individuals. This has prompted the Food and Drug Administration (FDA) in the USA and the European Medicines Agency (EMA) to issue warnings regarding their use. The FQs should not be used for common bacterial infections, such as urinary tract infections, travellers' diarrhoea and upper and lower respiratory tract infections, unless it is not possible to use another oral agent. There are situations, however, in which these agents are not only effective, but their benefit outweighs the risk. These include the management of conditions such as acute prostatitis, typhoid fever, prosthetic joint infections, multidrug-resistant tuberculosis, certain hospital-acquired infections and situations where the organism is susceptible to FQs, which could then be administered orally. Alternatively, the patient would have to be admitted to hospital for parenteral therapy.


Assuntos
Infecção Hospitalar/tratamento farmacológico , Fluoroquinolonas/efeitos adversos , Prostatite/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Febre Tifoide/tratamento farmacológico , Aneurisma Dissecante/induzido quimicamente , Ansiedade/induzido quimicamente , Fluoroquinolonas/uso terapêutico , Alucinações/induzido quimicamente , Humanos , Prótese Articular , Masculino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Psicoses Induzidas por Substâncias/etiologia , Ruptura/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Síndrome , Tendinopatia/induzido quimicamente
13.
Subst Use Misuse ; 54(10): 1589-1598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131668

RESUMO

Background: Insomnia and excessive daytime sleepiness (EDS) are reported to be common in methadone maintenance treatment (MMT) but much less is known about these symptoms in buprenorphine maintenance treatment (BMT) and in women compared with men. Methods: Cross sectional study of recipients of BMT (n = 113, 47 women), MMT (n = 184, 94 women), people using opioids nonmedically (nonopioid agonist treatment, non-OAT: n = 87, 31 women) and a reference group with no opioid use (RG; n = 105, 53 women) in Australia. Measures included Athens Insomnia Scale, Epworth Sleepiness Scale, the Hospital Anxiety and Depression Scale, and other substance use. Results: Insomnia (Athens Insomnia Scale, total ≥10) was highly prevalent among all people who use opioids (BMT 46.0-68.1%; MMT 55.4-69.6%; non-OAT 58.6-80.5%), did not differ significantly among these groups, and was significantly associated with anxiety and depression. EDS (Epworth score >10) was found in 14.2% of BMT, 22.8% of MMT, 35.6% of non-OAT groups, and 11.4% of the RG, and was significantly associated with depression overall. Fewer people had Epworth score >15 indicating more severe EDS (BMT 4.4%, MMT 6.0%; non-OAT 13.8%; RG 1.9%). Insomnia and EDS did not differ by sex or by opioid dose, nor were they significantly associated with other drug use, housing stress or social security status. Conclusions: Insomnia was common in people receiving OAT and using opioids non-medically, and associated with anxiety and depression. Clinicians should consider the possibility of daytime sleepiness in people receiving BMT and MMT, and in people using opioids nonmedically.


Assuntos
Ansiedade/epidemiologia , Buprenorfina/efeitos adversos , Depressão/epidemiologia , Metadona/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Sonolência , Adulto , Analgésicos Opioides/efeitos adversos , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , New South Wales/epidemiologia , Tratamento de Substituição de Opiáceos/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Prevalência , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Adulto Jovem
14.
Exp Gerontol ; 122: 85-91, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31051199

RESUMO

BACKGROUND: The consumption of caffeine has well known effects on the behavior and sleep of healthy adults. Behavioral symptoms and sleeping difficulties are common in patients with dementia which may be affected by caffeine consumption. This systematic review examines the association between caffeine intake and neuropsychiatric symptoms in patients with dementia. METHODS: In January 2019 an extensive search was conducted in Medline (PubMed), Embase, Emcare, Cochrane, PsychInfo, Web of Science and gray literature. Studies were included when they: i) investigated patients diagnosed with dementia, ii) reported neuropsychiatric symptoms, iii) used caffeine or coffee consumption as an intervention, and iv) reported associations between caffeine or coffee consumption and neuropsychiatric symptoms. Studies were excluded when they also included participants without a diagnosis of dementia, or presented a review or expert opinion. Two reviewers independently rated the studies and reached consensus on the appraisal. RESULTS: Of the seven studies eligible for this review, four reported on sleeping difficulties and five on behavioral symptoms. There was no consistent effect of caffeine administration on neuropsychiatric symptoms: e.g., both high caffeine consumption and eliminating caffeine were associated with less apathy, the total Neuropsychiatric Inventory (Nursing Home) decreased after both coffee therapy and after eliminating caffeine, and both caffeine consumption and eliminating caffeine improved sleep. CONCLUSION: These findings suggest that caffeine can either induce or reduce neuropsychiatric symptoms in individual patients with dementia. Therefore, in these patients, caffeine consumption requires a prudent individualized approach and further research on the effects of caffeine on individual neuropsychiatric symptoms is required.


Assuntos
Cafeína/farmacologia , Demência/psicologia , Apatia/efeitos dos fármacos , Demência/complicações , Humanos , Destreza Motora/efeitos dos fármacos , Casas de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/complicações
15.
Asia Pac Psychiatry ; 11(4): e12356, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31044518

RESUMO

The human population has been witnessing an increase in the number of diseases which are a consequence of progressively increasing physical and mental stress. Insomnia is one such condition whose prevalence is rising all over the world. Apart from the conventional behavioral interventions and use of benzodiazepines, the use of non-benzodiazepine drugs has seen a surge in recent times. The various adverse effects associated with benzodiazepines, dependence potential being one of them, led to an ever increasing use of non-benzodiazepine sedatives like zolpidem and zopiclone all over the world. But with their continuous and ever increasing use, it is seen that even these drugs carry dependence potential. Numerous cases of zolpidem abuse have been reported in literature until now. Here, we are presenting the case of a zolpidem-dependent patient who consumed it in quantities of 2400 mg/day, a quantity not reported anywhere in literature and around 240 times more than its usual prescribed daily dosage.


Assuntos
Clonazepam/uso terapêutico , Hipnóticos e Sedativos/efeitos adversos , Humor Irritável/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Zolpidem/efeitos adversos , Moduladores GABAérgicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade
16.
Aerosp Med Hum Perform ; 90(5): 480-483, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023409

RESUMO

INTRODUCTION: Modafinil is a wakefulness-promoting stimulant that has been approved by the Republic of Singapore Air Force (RSAF) as a fatigue countermeasure medication since 2011. Each RSAF aircrew member must undergo a ground test to exclude operationally relevant adverse drug effects prior to consuming the medication for operational reasons. This study describes the RSAF's modafinil ground testing outcomes over a 7-yr period.METHODS: This is a retrospective case series of 243 RSAF aircrew members who underwent modafinil 100-mg test dosing over the 7-yr period from September 2011 to September 2018.RESULTS: The median age was 31 yr (range, 21-53 yr) and mean age was 31.7 yr ± 6.19 yr. Of the aircrew members, 234 (96.3%) were men and all were of Asian ethnicity. Of the subjects, 237 (97.5%) were medically cleared for the operational use of modafinil. Among the six (2.47%) who failed modafinil ground testing, headache (cumulative incidence, 1.65%), anxiety (cumulative incidence, 0.41%), diarrhea (cumulative incidence, 0.41%), and insomnia (cumulative incidence, 0.41%) were reported as the side effects experienced. None of the aircrew members experienced major adverse drug events.DISCUSSION: Our findings suggest a low occurrence of adverse drug effects among military aircrew members who undergo modafinil test dosing prior to using the drug operationally. To our knowledge, this is the single largest published case series of modafinil ground testing outcomes among Asian military aviators.Ooi T, Wong SH, See B. Modafinil as a stimulant for military aviators. Aerosp Med Hum Perform. 2019; 90(5):480-483.


Assuntos
Medicina Aeroespacial/métodos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Militares , Modafinila/efeitos adversos , Pilotos , Acidentes Aeronáuticos/prevenção & controle , Adulto , Ansiedade/induzido quimicamente , Ansiedade/epidemiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Relação Dose-Resposta a Droga , Fadiga/prevenção & controle , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Estudos Retrospectivos , Singapura , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Vigília/efeitos dos fármacos , Adulto Jovem
17.
Nutrients ; 11(3)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845636

RESUMO

In our previous studies, a standardized phlorotannin (brown seaweed polyphenol) supplement (PS) exhibited sleep-promoting effects via type A γ-aminobutyric acid-benzodiazepine receptors in mice. In addition, in human clinical trials, it decreased wake after sleep onset in adults with sleep disturbance. In this follow-up study, we investigated whether PS attenuates caffeine-induced sleep disruption in mice. The effects of PS were evaluated in a caffeine model by analyzing sleep architecture based on electroencephalogram and electromyogram findings, and were compared with the effects of a well-known sedative-hypnotic drug zolpidem (ZPD). As expected, oral administration of caffeine (25 mg/kg) significantly increased sleep latency and decreased the amount of non-rapid eye movement sleep (NREMS). In the caffeine + PS and caffeine + ZPD groups, PS (500 mg/kg) attenuated caffeine-induced sleep disruption, and its effects were comparable with those of ZPD (10 mg/kg). In particular, PS inhibited the arousal effects of caffeine without change in delta activity during NREMS, whereas ZPD produced a decrease in the delta activity. Considering global trends in coffee and energy drink consumption, our finding suggest that PS may be useful to relieve transitory insomnia symptoms caused by caffeine consumption, unlike the prescription drug ZPD.


Assuntos
Hipnóticos e Sedativos/farmacologia , Fitoterapia , Preparações de Plantas/farmacologia , Polifenóis/uso terapêutico , Alga Marinha/química , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Animais , Cafeína , Eletroencefalografia , Eletromiografia , Seguimentos , Camundongos , Receptores de GABA-A/efeitos dos fármacos , Sono/efeitos dos fármacos , Medicamentos Indutores do Sono/farmacologia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Zolpidem/farmacologia
18.
Cochrane Database Syst Rev ; 3: CD011268, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883669

RESUMO

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Transtorno Afetivo Sazonal/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Diarreia/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Incidência , Náusea/induzido quimicamente , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Transtorno Afetivo Sazonal/epidemiologia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente
19.
Neuropsychopharmacology ; 44(11): 1917-1924, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30822774

RESUMO

F17464, a highly potent preferential D3 antagonist, is a novel compound in development for schizophrenia treatment. This phase II, double-blind, randomized, placebo-controlled, parallel-group study in five European countries evaluated the efficacy and safety of F17464, 20 mg twice daily, versus placebo over 6 weeks in patients with acute exacerbation of schizophrenia. Change from baseline to Day 43 of the Positive and Negative Syndrome Scale (PANSS) total score was the primary outcome. The data from 134 randomized patients (67 per group) were analyzed (efficacy/safety). Using analysis of covariance (ANCOVA) after last observation carried forward (LOCF) imputation (primary analysis), the PANSS total score reduction was statistically significantly greater for F17464 than placebo treated subjects at endpoint (p = 0.014); using ANCOVA with Multiple Imputation (MI) method, the between-group difference was in favor of F17464 but did not reach statistical significance. Differences in PANSS positive and general psychopathology subscale score, Marder positive factor score, PANSS response, and PANSS resolution criteria were also statistically significant in favor of F17464 (p values < 0.05) using the LOCF method, with similar results as for the primary analysis using the MI method. Treatment-related adverse events (AEs) were reported in 49.3% and 46.3% of patients on F17464 and placebo, respectively. The most common AEs in F17464 group: insomnia, agitation, and increased triglycerides; worsening of schizophrenia/drug ineffective was less frequent in F17464. Interestingly, no weight gain, no extrapyramidal disorder except rare akathisia were observed under F17464. This 6-week trial demonstrated therapeutic efficacy of 40 mg/day F17464 in improving symptoms of acute exacerbation of schizophrenia with a favorable safety profile.


Assuntos
Antipsicóticos/uso terapêutico , Antagonistas de Dopamina/uso terapêutico , Receptores de Dopamina D3/antagonistas & inibidores , Esquizofrenia/tratamento farmacológico , Adulto , Acatisia Induzida por Medicamentos , Antipsicóticos/efeitos adversos , Antagonistas de Dopamina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Resultado do Tratamento
20.
Int J Pharm Pract ; 27(3): 264-270, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30768819

RESUMO

OBJECTIVES: Our main aim was to investigate the short-term therapeutic effects, safety/tolerability and potential side effects of the cannabis galenical preparation (Bedrocan) in patients with a range of chronic conditions unresponsive to other treatments. METHODS: In this retrospective, 'compassionate use', observational, open-label study, 20 patients (age 18-80 years) who had appealed to our 'Second Opinion Medical Consulting Network' (Modena, Italy), were instructed to take sublingually the galenical oil twice a day for 3 months of treatment. The usual starting dose was low (0.5 ml/day) and gradually titrated upward to the highest recommended dose (1 ml/day). Tolerability and adverse effects were assessed at baseline and monthly thereafter during the treatment period through direct contact (email or telephone) or visit if required. Patients' quality of life was evaluated at baseline and 3 months using the medical outcome short-form health survey questionnaire (SF-36). KEY FINDINGS: From baseline to 6 months post-treatment, SF-36 scores showed: reductions in total pain (P < 0.03); improvements in the physical component (P < 0.02); vitality (P < 0.03); social role functioning (P < 0.02); and general health state (P < 0.02). No changes in role limitations (P = 0.02) due to emotional state (e.g. panic, depression, mood alteration) were reported. Monthly reports of psychoactive adverse effects showed significant insomnia reduction (P < 0.03) and improvement in mood (P < 0.03) and concentration (P < 0.01). CONCLUSIONS: These data suggest that a cannabis galenical preparation may be therapeutically effective and safe for the symptomatic treatment of some chronic diseases. Further studies on the efficacy of cannabis as well as cannabinoid system involvement in the pathophysiology are warranted.


Assuntos
Doença Crônica/tratamento farmacológico , Emoções/efeitos dos fármacos , Maconha Medicinal/administração & dosagem , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Administração Sublingual , Adulto , Composição de Medicamentos/métodos , Feminino , Humanos , Itália , Masculino , Maconha Medicinal/efeitos adversos , Qualidade de Vida , Estudos Retrospectivos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Inquéritos e Questionários , Resultado do Tratamento
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