Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The suitability of triazolam for oral premedication was evaluated in comparison to flunitrazepam. 65 consenting female patients scheduled for gynaecological surgery took part in the trial, were randomly allocated in two groups and were given 0.5 mg triazolam or 2 mg of flunitrazepam as oral premedication 90 min preoperatively. No difference was found in the anxiolytic potency (possible difference d = 0.65 standard deviation, less than 3 points on the anxiety score). Both drugs significantly reduced anxiety (alpha less than 0.01). Anxiolysis depended on the initial anxiety; the higher the initial anxiety score, the better the anxiolytic effect. Triazolam was found to have an antidepressant effect (alpha less than 0.05) and asthenic affects decreased (n.s.). Flunitrazepam had a tendency to increase depression (n.s.) and asthenic effects increased (alpha less than 0.05). No differences were found in the degree of sedation and in the amnestic effect. Systolic pressure remained unchanged in both groups, whereas values of diastolic pressure increased to the same extent in both groups. While heart rate increased after triazolam, it decreased after flunitrazepam. Both groups had comparable initial heart rates. Possible mechanisms to explain this discordance of heart rate-changes are discussed. Triazolam is comparable to flunitrazepam as an oral premedicant and is a suitable drug for short surgical procedures if rapid postoperative recovery is required.
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PMID:[Premedication with triazolam]. 217 87

The respiratory-depressant effect of the benzodiazepine-derived hypnotic triazolam was investigated with a single oral dose at two and three times the usual dosage in 62 awake normal subjects. A randomized, double-blind protocol compared the following groups: (1) placebo, (2) triazolam, 1.0 mg, (3) triazolam, 1.5 mg, and (4) morphine, 0.15 mg/kg. Differences between predrug and postdrug administration were compared. Minute ventilation (Ve), end-tidal PCO2, and the ventilatory response to CO2 (Ve/PCO2) were preserved with both 1.0 mg and 1.5 mg triazolam compared with placebo. Triazolam caused an increase in breathing frequency (+21% to 50%; p less than 0.05) as a result of a shortening of inspiratory time. Triazolam was associated with a higher Ve corrected for CO2 production and Ve/PCO2 compared with morphine. We concluded that a single dose of triazolam at two and three times the usual level does not cause respiratory depression in awake, normal subjects but does alter respiratory cycle timing causing an increase in breathing frequency.
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PMID:Ventilatory effects of single, high-dose triazolam in awake human subjects. 319 67

Abnormal circadian rhythms have been linked to at least some forms of depression and to disturbances in the sleep-wake cycle. In addition, mental and physical disorders associated with rapid travel across time zones (i.e. the jet-lag syndrome) and with rotating shift-work schedules, are thought to involve a disruption of normal circadian rhythmicity. It might be possible to alleviate some of the adverse effects associated with abnormal circadian rhythms if pharmacological agents could be used to manipulate the central circadian pacemaker(s) that regulates these rhythms. Recent findings indicate that treatment with a short-acting benzodiazepine, triazolam, can induce major shifts in the circadian clock of golden hamsters. In the absence of a synchronizing light-dark cycle (i.e. during exposure to constant light or constant dark), a single injection of triazolam can induce a permanent phase shift in the circadian rhythm in locomotor activity. In addition, following a shift in the light-dark cycle, a single injection of triazolam can facilitate the time it takes for the activity rhythm to be resynchronized to the new lighting schedule. Triazolam, or drugs with similar phase-shifting effects on the mammalian circadian system, might be useful in the treatment of various sleep and mental disorders that have been associated with a disorder in circadian time-keeping in humans.
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PMID:Manipulation of the circadian clock with benzodiazepines: implications for altering the sleep-wake cycle. 336 62

The triazolobenzodiazepine triazolam, applied iontophoretically onto rat cerebral cortical neurons, potentiated the magnitude and duration of adenosine-elicited depressions of spontaneous activity. Triazolam did not enhance the depressions evoked by adenosine 5'-N-ethylcarboxamide, an uptake resistant analog of adenosine, suggesting that potentiation of adenosine resulted from an inhibition of adenosine uptake. With larger application currents, triazolam depressed the firing of cortical neurons. This action was blocked by the adenosine antagonist caffeine (20 mg/kg, i.v.) implying that the depression resulted from an accumulation of endogenously released adenosine.
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PMID:Potentiation of adenosine-evoked depression of rat cerebral cortical neurons by triazolam. 337 Apr 71

A 71-year-old man was found dead in a car into which exhaust fumes had been introduced. His wife who was in the same car recovered consciousness following hospitalization. She claimed that they had both attempted suicide by taking a large number of sleeping pills. Autopsy revealed no significant external injuries or medical disorders that would have led to the husband's death. The concentrations of alcohol and carbon-monoxide hemoglobin in his whole blood were 0.26 mg/ml and < 10%, respectively. Therefore, poisoning by carbon monoxide from the exhaust fumes was ruled out, and further toxicological examinations were undertaken. Triazolam, pentobarbital, amitriptyline and bromazepam were all detected in the tissues of the victim; whole blood concentrations were 45.60, 386.4, 521.2 and 166.7 ng/g, respectively. Triazolam (7.350 ng/g) and pentobarbital (288.2 ng/g) were also detected in the whole blood of the wife, collected 17 h after admission to hospital. When evaluating these results in the light of existing literature, we concluded that the victim and his wife had indeed attempted suicide by taking triazolam and pentobarbital. However, only the man had died of triazolam poisoning due to its apparently lethal combination with amitriptyline and other psychotropic drugs which had been prescribed to treat his depression.
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PMID:Death attributed to the toxic interaction of triazolam, amitriptyline and other psychotropic drugs. 915 80

One hundred sixty-six patients suffering from major depressive disorders were treated for 8 weeks with nefazodone in an open study in dosage ranges from 200 to 600 mg. This report focuses primarily on the first week of therapy and on the concomitant use of several benzodiazepines, one of which is not metabolized by the cytochrome system (temazepam). Triazolam response was further evaluated as a function of two nefazodone dosage regimens provided during the first week of therapy, one group receiving nefazodone 200 mg/day for 7 days, and another group receiving nefazodone 200 mg/day for 3 days, followed by 4 days with 400 mg/day. Finally, a comparison of three different nefazodone dosages, the third being 400 mg from day 1 on, was also carried out. Outcome measures included Hamilton Rating Scale for Depression total and the total of the three Hamilton Rating Scale for Depression insomnia items, as well as global improvement, a daily completed sleep questionnaire, and adverse event assessment. A combination of nefazodone with a benzodiazepine (BZ) caused more sedation than nefazodone alone; triazolam, the BZ with the shortest half-life and the highest dependence on the cytochrome 450 system for its metabolism, caused the least amount of sedation, and alprazolam and diazepam, the two daytime benzodiazepines, caused the most sedation. Triazolam caused significant and identical reduction of insomnia in both nefazodone groups. Compared with nefazodone 200 mg given as monotherapy, insomnia was significantly improved--not only by triazolam, but also alprazolam and diazepam, but not temazepam. The addition of nefazodone raised triazolam plasma levels to almost 500%, the plasma level of desmethyl-diazepam 87%, and that of alprazolam 34%. Temazepam plasma levels remained unchanged. When prescribing nefazodone with a benzodiazepine, one should expect an improved sleep pattern initially, but at the cost of clinically relevant daytime sedation. The prediction that temazepam, the only BZ not dependent on the cytochrome mechanism for metabolism, should be the least sedating, and triazolam, because of its cytochromic metabolism interference with nefazodone should be the most sedating, could not be confirmed. In fact, triazolam 0.25 mg capsules seem to be the safest treatment of choice when one has to combine a benzodiazepine with nefazodone in initial stages of therapy, at least of the four benzodiazepines tested in this study.
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PMID:Nefazodone in major depression: adjunctive benzodiazepine therapy and tolerability. 958 Mar 69

Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4mg caused euphoria-related effects as measured by increases in ARCI-MBG and "high" scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential.
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PMID:Abuse liability of flunitrazepam among methadone-maintained patients. 988 25

The case of a 77-year-old woman who was found dead in her bathtub with her head clearly above the water line is presented. The decedent had a medical history of depression, liver disease, spinal stenosis, and diabetes mellitus. An empty medication bottle of triazolam was found in the trashcan. At autopsy, no injury or evidence of drowning was found. Toxicological analysis identified triazolam at a concentration of 0.12 mg/L in the heart blood. Triazolam and alpha-hydroxytriazolam were quantitated in the specimens received. The medical examiner ruled that the cause of death was triazolam intoxication and the manner of death was suicide.
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PMID:Distribution of triazolam and alpha-hydroxytriazolam in a fatal intoxication case. 1188 17

Previous work described the pharmacokinetics and clinical effects of multidose sublingual triazolam (Halcion; Pharmacia & Upjohn Co, Kalamazoo, Mich). This laboratory study evaluated the hypothesis that incremental dosing of triazolam produces dose-dependent central nervous system depression that is profound and long lasting. Forty-nine healthy adults between the ages of 21 and 39 years, not receiving dental treatment, were randomly assigned to placebo (n = 12) or 1 of 3 triazolam groups (0.25-mg single dose, n = 12; 0.5 mg divided between 2 equal doses for 60 minutes, n = 12; or 0.75 mg divided among 3 doses for 90 minutes, n = 13). Plasma triazolam concentrations were determined. Bispectral index (BIS) and the Observer Assessment of Alertness/Sedation scale were used to assess sedation. Plasma triazolam concentrations increased with time in all subjects, with Tmax and Cmax both increasing dose dependently. Compared with placebo, all dosing paradigms produced dose-dependent BIS suppression and sedation. The single dose of 0.25 mg reached its peak BIS suppression at 90 (81 +/- 7) minutes and sedation at 120 (3.6 +/- 0.5) minutes and returned to baseline before 360 minutes. In contrast, incremental dosing of 0.5 and 0.75 mg produced profound and long-lasting BIS suppression and sedation that did not plateau until either 180 or 210 minutes as measured by the BIS index (67 +/- 14 and 60 +/- 16 at 0.5 and 0.75 mg, respectively) and 150 minutes as measured by the Observer Assessment of Alertness/Sedation scale (3.2 +/- 1.0 and 2.7 +/- 0.4 at 0.5 and 0.75 mg, respectively). These data more fully characterize the effects of incremental dosing with sublingual triazolam and provide additional insight for discharge safety recommendations.
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PMID:Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers. 1974 41