Browsing by Subject "BENZODIAZEPINES"

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  • Puustinen, Juha; Lähteenmäki, Ritva; Nurminen, Janne; Vahlberg, Tero; Aarnio, Pertti; Partinen, Markku; Räihä, Ismo; Neuvonen, Pertti J.; Kivelä, Sirkka-Liisa (2018)
    Background: Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications. Methods: 92 outpatients (>= 55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9.9 +/- 6.2 years), and willingness to withdraw from BZDAs each received either melatonin or a placebo nightly for one month. During this period, BZDAs were meant to be gradually withdrawn. Sleep hygiene counselling and psychosocial support were provided. Three years later, use of BZDAs and other medications was determined by interview and confirmed from medical records. Results: Of the original 92 outpatients, 83 (90%) participated in the 3-year survey (mean follow-up 3.3 +/- 0.2 years). The number of BZDA-free participants decreased from 34 (37%) at 6 months to 26 (28%; intention-to-treat) at 3 years, that of irregular BZDA users decreased from 44 (48%) at 6 months to 27 (29%) at 3 years, while that of regular users increased from 11 (12%) at 6 months to 30 (33%) at 3 years (P = 0.001). Those who were regular BZDA users at 3 years had at baseline (before withdrawal) higher BMI (P = 0.001) than did other participants. At 3 years, the total number of medications remained unchanged for non-users (P = 0.432), but increased for the irregular (P = 0.011) and regular users (P = 0.026) compared to baseline. At 3 years, compared to baseline, use of antidepressants, dopamine agonists, melatonin, and NSAIDs/paracetamol was significantly more common in the whole cohort, but their use did not differ between the BZDA-user subgroups. Randomization to melatonin or placebo during BZDA withdrawal was unrelated to BZDA-withdrawal result. Conclusions: At 3 years after withdrawal, the number of BZDA-free participants had decreased, but still one-third of the subjects remained BZDA-free, and one-third had reduced their use. Successful BZDA withdrawal did not lead to any increase in total number of medications; use of symptomatic medications in the whole cohort, however, did increase.
  • Amaghnouje, Amal; Bohza, Serhii; Bohdan, Nathalie; Es-Safi, Imane; Kyrylchuk, Andrii; Achour, Sanae; El Fatemi, Hinde; Bousta, Dalila; Grafov, Andriy (2021)
    We report the design and synthesis of a new diazepine derivative, 4-(4-methoxyphenyl)-2,3,4,5-tetrahydro-2,3-benzodiazepin-1-one (VBZ102), and the evaluation of its anxiolytic-like profile, memory impairment effect, and toxicity in Swiss mice. VBZ102 was evaluated for central nervous system effects in an open field, light-dark box, and novel object recognition tests under oral administration for acute and sub-acute treatment. We tested the VBZ102 toxicity in mice through a determination of LD50 values and examination of the biochemical and histopathological parameters. The VBZ102 induced an anxiolytic effect at different doses both in the light-dark box and open field tests. Unlike other benzodiazepines (e.g., bromazepam), a sedative effect was noted only after administration of the VBZ102 at 10.0 mg/kg.
  • Ketola, Raimo A.; Ojanperä, Ilkka (2019)
    Concentration distributions for 183 drugs and metabolites frequently found in post-mortem (PM) femoral venous blood were statistically characterized based on an extensive database of 122 234 autopsy cases investigated during an 18-year period in a centralized laboratory. The cases represented all causes of death, with fatal drug poisonings accounting for 8%. The proportion of males was 74% with a median age of 58 years compared with 26% females with a median age of 64 years. In 36% of these cases, blood alcohol concentration was higher than or equal to 0.2 parts per thousand, the median being 1.6 parts per thousand. The mean, median, and upper percentile (90th, 95th, 97.5th) drug concentrations were established, as the median PM concentrations give an idea of the "normal" PM concentration level, and the upper percentile concentrations indicate possible overdose levels. A correspondence was found between subsets of the present and the previously published PM drug concentrations from another laboratory that grouped cases according to the cause of death. Our results add to the knowledge for evidence-based interpretation of drug-related deaths.
  • Kronholm, Erkki; Jousilahti, Pekka; Laatikainen, Tiina; Lallukka, Tea; Peltonen, Markku; Seppänen, Johanna; Virta, Lauri (2019)
    Purpose: Whether the association between hypnotic and increased mortality risk is created by causation or confounding, has been long debated. We further examined the possibility of confounding by indication with a comprehensive approach. Methods: The National FINRISK Study cohorts of 1997, 2002, and 2007 (25,436 participants aged 25-74) were followed up until July 2012. There were 1822 deaths, and at least one gender, baseline age and cohort matched 'control' was found for 1728 'cases' yielding a final analytical sample of 3955 individuals. An index age, equivalent to the age at death of their respective cases' was set for each control. Hypnotic drug purchases were followed from the Finnish nationwide register during a 36-month run-up period before the date of death/index date. The prevalence and incidence of hypnotic purchases were compared between cases and matched controls. Moreover, latent developmental trajectories of purchases were modelled and their relations with specific and all-cause death risks were analysed. Results: An increasing difference between cases and controls was observed as regards the use of hypnotic drugs. During the last 30 months before the date of death/index date, the rate ratio of incident purchases between cases and controls was 2.37 (95% CL, 1.79-3.12) among older and 3.61 (95% CL, 2.37-5.89) among younger individuals. The developmental trajectories of hypnotic drug purchases were differently and by interpretation plausibly associated with specific mortality risks. Conclusions: In most cases the association between hypnotics and mortality risk is created by symptomatic treatment when death is approaching. (c) 2018 Elsevier B.V. All rights reserved.
  • Pajunen, Tuulia; Vuori, Erkki; Vincenzi, Frank F.; Lillsunde, Pirjo; Smith, Gordon; Lunetta, Philippe (2017)
    Background: Alcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates. Methods: Drowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75.1. The data were narrowed to unintentional drowning, using the ICD-10 external-injury codes V90, V92, and W65-74. Each drowning case had its blood alcohol concentration (BAC) and concentrations of other drugs recorded. Evaluation of the contribution of psychotropic drugs to drowning was based on their blood concentration by means of a 6-grade scale. Results: Among victims >= 15 years old, unintentional drownings numbered 1697, of which, 303 (17.9%) were boating-related and 1394 (82.1%) non-boating-related. Among these, 65.0% of boating-related and 61.8% of non-boating-related victims were alcohol-positive (=BAC >= 50 mg/dL). The male-to-female ratio in alcohol-positive drownings was 7.3. At least one psychotropic drug appeared in 453 (26.7%) drowning cases, with some victims' bodies showing up to 7 different drugs. Overall 70 different psychotropic drugs were detectable, with 134 (7.9%) cases both alcohol-negative and psychotropic-drug-positive, of these, 59 (3.5%) were graded 4 to 6, indicating a possible to very probable contribution to drowning. Our findings suggest that psychotropic drugs may play a significant role in drowning, in up to 14.5% of cases, independently or in association with alcohol. Conclusions: Psychotropic drugs alone or in association with alcohol may be an overlooked risk factor in drowning, due to their effects on psychomotor function and cognition. Future studies should also address other mechanisms-for instance drug-induced long-QT syndrome-by which drugs may contribute to drowning.