Data now exist from which an accurate definition for serotonin toxicity (ST), or serotonin syndrome, has been developed; this has also lead to precise, validated decision rules for diagnosis. The spectrum concept formulates ST as a continuum of serotonergic effects, mediated by the degree of elevation of intrasynaptic serotonin. This progresses from side effects through to toxicity; the concept emphasizes that it is a form of poisoning, not an idiosyncratic reaction. Observations of the degree of ST precipitated by overdoses of different classes of drugs can elucidate mechanisms and potency of drug actions. There is now sufficient pharmacological data on some drugs to enable a prediction of which ones will be at risk of precipitating ST, either by themselves or in combinations with other drugs. This indicates that some antidepressant drugs, presently thought to have serotonergic effects in animals, do not exhibit such effects in humans. Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic antidepressants (other than clomipramine and imipramine) do not precipitate serotonin toxicity and might not elevate serotonin or have a dual action, as has been assumed. 相似文献
Objective Since intoxication with tricyclic antidepressants is common, a supplementary screening method for differentiation between therapeutic and supratherapeutic ranges would be a valuable diagnositc tool, particularly in delirious and unconscious patientsSetting 109 patients treated with amitriptyline, 8 patients treated with doxepin, 10 patients treated with clozapine, and 72 normal control subjects matched for age and sex were tested for heart rate variability while resting.Results Considering time and frequency derived measures, which are rather independent of heart rate, the patients showed significantly decreased heart rate variability parameters (p<0.0001), as compared with the normal subjects. Of the patients presenting delirious symptoms 6 showed coefficients of variation more than 4 standard deviations below the mean control value.Conclusions As heart rate variability can be easily calculated, this measurement is suggested as a useful tool to quickly exclude or support the diagnosis of chronic intoxication with tricyclic antidepressants or clozapine. 相似文献
Rosenthal, Jesse et al. A Preliminary Study of Serotonergic Antidepressants in the Treatment of Dysthymia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 933–941.
1. 1. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents.
2. 2. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone.
3. 3. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on followup at five months.
4. 4. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.
The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4 and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (tmax?2h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F?29 mL min?1; Vz/F?32L); urinary excretion was ~9% of dose, corresponding to a renal clearance of only 3 mL min?1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of 14C-labelled reboxetine, appeared to be dominated by α1-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL?1 (2.8–3.1% unbound with human plasma from three additional volunteers; 1.8–2.0% for 2gL?1 orosomucoid α1-acid glycoprotein, and 46.4–47.4% for 40 gL?1 albumin), whilst the mean Cmax in the current study was much lower (164 ng mL?1 after a 5 mg dose). 相似文献
1. In our series of experiments the role of serotonin in human depression was studied by using animal models of depression.
2. The results of these studies support the hypothesis that some types of human depression may be primarily due to an excessive transmission of serotonin at the synapse. 相似文献
Chronic administration of different antidepressant drugs reduced the number of [3H]imipramine [( 3H]IMI) binding sites in rat cerebral cortex. In the same experimental conditions, fluvoxamine and dothiepin, as well as desmethylimipramine, induced an increase in the maximal velocity of high affinity serotonin (5HT) uptake in cortical slices, whereas citalopram and viloxazine were ineffective in this regard. Our results indicate that even if 5HT uptake and [3H]IMI binding sites are located on the same nerve terminals, they are differently modulated. Increased Vmax of the 5HT uptake process could be due to a rebound phenomenon after withdrawal from drugs that acutely inhibit 5HT uptake. The effect on [3H]IMI sites might be explained through either the agonist properties of the drugs towards these sites or the involvement of mechanisms still unknown. 相似文献