Efficacy was assessed using PSG and patient-reported measures.
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The adsorption of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline onto cholestyramine was demonstrated in vitro with use of 1.2 mol/L HCl at 37 degrees C to simulate gastric fluid. Binding to cholestyramine was approximately 80% for each of the tricyclic antidepressants, and this was about the same degree of binding noted with a nonpharmaceutical, non-ionic resin widely used in the diagnostic toxicology laboratory (Amberlite XAD-2). In contrast, five other non-antidepressants (acetaminophen, chlordiazepoxide, procainamide, quinidine, and theophylline) showed only minimal binding to cholestyramine under these conditions. Activated charcoal completely bound all drugs studied. These findings suggest that cholestyramine should be used with caution in patients receiving tricyclic antidepressants. They also suggest that cholestyramine may be a potentially useful adjunctive therapy in treatment of overdose with the tricyclic antidepressants.
The method is effective, simple, reliable and has been used in real cases.
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The prescribing of anxiolytics is often a hit-and-miss process. Current knowledge is examined to encourage a more rational use of such drugs. Because the common symptoms occur in a great array of illnesses, diagnosis is of first importance. For the transient situational disturbance drugs may be unnecessary or may be used merely for a day or two. If the anxiety state persists for a month or so the illness might be termed an anxiety neurosis and if there is no accompanying depression, a short course of benzodiazepine may be of value. With depression present to more than a mild degree as part of the neurosis the tricyclic antidepressant doxepin usually achieves better results than a benzodiazepine. Imipramine can be helpful for the phobic anxiety syndrome and monoamine-oxidase inhibitors can be of separate utility. If the anxiety and depression occur in the context of alcoholism, thioridazine and amitriptyline have certain advantages. There is very little place for phenothiazines or other antipsychotic agents in low doses in the therapy of anxiety except for thioridazine in the above indication.
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The effects of antidepressants of tricyclic (amitriptyline, nortriptyline, protriptyline, doxepin, imipramine, and desipramine) and atypical (maprotiline, nomifensine, tandamine, viloxazine, CGP 6085A, and YM-08054-1) structures on contractile responses to exogenously applied acetylcholine and (-) noradrenaline were studied in rat isolated anococcygeus muscle previously incubated with 6-hydroxydopamine. Atropine, amitriptyline, protriptyline, doxepin, imipramine, maprotiline and nortriptyline inhibited contractile responses to acetylcholine whereas desipramine, nomifensine, tandamine, viloxazine, CGP 6085A and YM 08054-1 did not. The contractile responses to (-)-noradrenaline were inhibited by low concentrations of tricyclic antidepressants and by higher concentrations of the atypical agents. These results illustrate that, in the preparation, the order of potency of antidepressants as muscarinic and as postsynaptic alpha-adrenoceptor antagonists is similar. The ability of tricyclic, but not atypical agents, to increase the concentration of noradrenaline bound to postsynaptic alpha-adrenoceptors may be severely limited by the antagonistic effect these agents have at this receptor.
A psychiatric study was carried out to seek correct diagnosis and effective therapy for patients with various pain symptoms in ear, nose and throat area, and the unknown cause of pain and invalid treatment. There were 12 patients who coincided with the diagnostic criteria of depression. The therapeutic effect was satisfactory with antidepression medicine. It is suggested that the practicing ENT doctors should have some knowledge of psychiatry, understand the symptoms of depressive state, avoid misdiagnosis and offer correct management.
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To develop a specific, sensitive, reproducible SPE-HPLC method for the determination of 37 drugs in whole blood.
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Forty-four of 48 patients (92%) were asymptomatic. All were single-drug exposures. Forty-three patients (90%) ingested a TCA dose that was less than the normally prescribed pediatric dose (5 mg/kg). Of the five children ingesting >5 mg/kg (range 5-9.4 mg/kg), only one (5.3 mg/kg) was mildly symptomatic (drowsy) prior to admission. Thirty-one of the 48 (65%) were sent to the emergency department (dose range 0.59-9.4 mg/kg). Fourteen of the 31 were admitted for 12-24-hour observation and none subsequently developed symptoms. Twenty-three (74%) received activated charcoal (AC). There was no difference in outcome between the children who did and did not receive AC.
In randomised double-blind comparative trials including patients with major depression, short term (5 to 6 weeks) therapy with mirtazapine was significantly more effective than placebo, as effective as amitriptyline, clomipramine and doxepin, and at least as effective as trazodone. Results from a meta-analysis of 5 comparative trials in which 60% of patients were hospitalised with severe depression [mean baseline 17-item Hamilton Depression Rating Scale (HAMD) score ≥25] revealed no significant differences between mirtazapine and amitriptyline. The responder rates (≥50% decrease in HAMD score from baseline) at 6 weeks and study end-point were 70 and 61 %, respectively, for mirtazapine and 73 and 64%, respectively, for amitriptyline. In a comparative trial in older outpatients (mean age 61 to 63 years), reductions in rating scale scores of depression and the percentage of responders tended to be higher in mirtazapine than in trazodone recipients.
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A sensitive method suitable for the determination of tricyclic and other antidepressants in postmortem and clinical specimens is presented. The procedure, which utilizes reversed-phase HPLC combined with dual ultraviolet wavelength detection, enables the separation of 17 commonly prescribed antidepressants and some selected metabolites in a single extraction. Peak purity was confirmed using absorbance ratios at 220 nm and 254 nm wavelengths and revealed little interference from other eluting analytes. The blood detection limit for most antidepressants was 50 ng/ml. The most commonly observed antidepressants in 281 forensic cases analysed over a two-year period with the described method were dothiepin, amitriptyline, nortriptyline and doxepin.
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The binding potential ratio of mirtazapine in brain cortex was significantly lower than that of fluvoxamine or placebo. Fluvoxamine did not occupy the H₁R, whereas H₁R occupancy (H₁RO) of mirtazapine reached 80-90 % in the cerebral neocortex. In the voxel-by-voxel analysis, the binding potential of mirtazapine was significantly lower than placebo in the dorsolateral prefrontal cortex, lateral temporal cortex, anterior cingulate gyrus, and posterior cingulate gyrus. The H₁RO of mirtazapine depended on the plasma drug concentration (AUC(0-180 min)) and was related to subjective sleepiness.
Three patients taking conjugated estrogens developed akathisia induced by tricyclic antidepressants. The interaction between tricyclic antidepressants and conjugated estrogens could play a role in the development of akathisia.
These data substantiate the view that clinically relevant concentrations of neuroleptics and antidepressants can mediate changes in neuronal pHi, which may contribute to their pharmacological mode of action. Effects on pHi should be taken into account when therapeutic or even harmful effects of these drugs are evaluated.
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Pruritus represents a common and distressing feature of burn wounds. Over the last decades, significant advances in neuroanatomical and neurophysiological knowledge have resulted in the elucidation of the mediators and pathways involved in the transmission of pruritic impulses. A plethora of therapeutic approaches have been evaluated mostly in small-scale studies involving burns patients targeting both the peripheral and the central components of the neurologic pathway. Antihistamines, doxepin, massage therapy, and transcutaneous electrical nerve stimulation are effective strategies to combat pruritus in burns patients. Recent studies have provided preliminary evidence regarding the effectiveness of gabapentin and ondansetron. The area of burns pruritus is under-researched and large-scale studies are required to reinforce the armamentarium of specialists with evidence-based regimens for the treatment of this highly distressing symptom.
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In several cases tobacco smoking fulfills criteria for drug dependence. Withdrawal symptoms after smoking cessation are considered the main cause of relapses. We reviewed results of controlled clinical drug trials (testing nicotine patch, nicotine nasal spray, clonidine, buspirone and doxepin) in smoking cessation. End of treatment quit rates at 3 months with nicotine patch vary between 14% and 39% and one year quit rates between 9% et 26%. Studies with nasal nicotine spray give similar results but nicotine spray is less well tolerated than nicotine patch. The therapeutic effectiveness of nicotine patch seems to be insufficient and there is only one report of long term (> 1 year) results which should be the main goal of treatments used in smoking cessation. A therapeutic approach with psychotropic drugs founded on a better characterization of dependent smokers' psychopathology (depression, anxiety...) may be a more promising research field.
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We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration.The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model.
Employing our novel system we have been able to identify a new class of transfection enhancers, the tricyclic antidepressants (i.e. doxepin, maprotiline, desipramine and amoxapine). All positive drugs enhanced gene transfer in both yeast and human cell lines, but lower concentrations were sufficient for mammalian cells. With a triple combination of doxepin, amoxapine and chloroquine we obtained a transfection efficiency that exceeded that of chloroquine, one of the best-known transfection enhancers of mammalian cells, by nearly one order of magnitude.
The pharmacological effects of three tricyclic antidepressant agents (desipramine, protriptyline and doxepin) are evaluated in rat isolated atria in relation to their accumulation and efflux kinetics. The pharmacological effects studed are: inhibition of 1-3H-noradrenaline uptake, potentiation of 1-noradrenaline chronotropic response, and changes in spontaneous atrial rate. All drugs inhibit noradrenaline uptake and potentiate noradrenaline chronotropic response (desipramine congruent to protriptyline greater than doxepin). Desipramine and protriptyline, at concentrations of 10(-7) -- 10(-6)M stimulate the spontaneous rate; higher concentrations (greater than 10(-6)M) depress it. Doxepin has only a negative chronotropic effect. When the drugs are removed from the incubation medium, the depressing effect starts to disappear immediately for doxepin and desipramine and after 20 min for protriptyline. On the contrary the stimulating effect persists after repeatedly washing the preparations. Desipramine, protriptyline and doxepin extensively accumulate in the myocardial tissue (desipramine larger than or equal to protriptyline greater than doxepin). In the efflux studies doxepin is washed out more rapidly than desipramine and protriptyline. Although the kinetics of uptake and efflux of the three compounds are not sufficient to interpret their different pharmacological activities in isolated atria, they give useful information on the persistance of the sympathomimetic effect and the rapid disappearing of the negative chronotropic effect after washing.
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Cognitive behavioral therapy and sleep hygiene are considered initial therapy for insomnia. Benzodiazepines are discouraged in the geriatric population, especially for long-term use. Although non-BzRAs have improved safety profiles compared with benzodiazepines, their side effects include dementia, serious injury, and fractures, which should limit their use. Ramelteon has a minimal adverse effect profile and is effective for sleep-onset latency and increased total sleep time, making it a valuable first-line option. Although the data on suvorexant are limited, this drug improves sleep maintenance and has mild adverse effects, including somnolence; residual daytime sedation has been reported, however. Sedating low-dose antidepressants should only be used for insomnia when the patient has comorbid depression. Antipsychotic agents, pramipexole, and tiagabine have all been used for insomnia, but none has been extensively studied in an older population, and all have considerable adverse effects. Gabapentin may be useful in patients with restless leg syndrome or chronic neuropathic pain and insomnia. Diphenhydramine should be avoided in the elderly. Valerian and melatonin are unregulated products that have a small impact on sleep latency and can produce residual sedation.
Data on drug safety were not analyzed.
We investigated the possibility that the inflammatory reaction in primary acquired cold urticaria might be associated with the release of platelet-activating factor. Six patients with the disease and five normal controls were subjected to cold-water challenges during which blood samples were obtained for measurement of the release of possible mediators: i.e., histamine, neutrophilic chemotactic activity, and platelet-activating factor-like lipid (PAF-LL). Four of the patients had pronounced experimentally induced cold urticaria with angioedema and release of mediators. Levels of the three mediators were not elevated in five normal controls or in two patients in whom cold challenges induced only mild urticaria and angioedema. The effective suppression of cold-induced urticaria in three patients treated with doxepin correlated with inhibition of PAF-LL release but not inhibition of histamine or neutrophilic chemotactic activity release. These data suggest a positive correlation between PAF-LL release and cold urticaria, although the exact relation between PAF-LL and cutaneous lesions of primary acquired cold urticaria has not yet been established.
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A young nurse was found dead in her flat. In chemical-toxicological analysis the following femoral blood drug concentrations were determined: paroxetine 0.176 mg/l, doxepine 82.12 mg/l, desmethyldoxepine 0.34 mg/l. Additionally the drug concentrations were determined in various body fluids and organs. The results of the described fatality are discussed. For interpretation of toxicologic results in antidepressant fatalities ratios of parent drug to metabolite and postmortem drug redistribution should be taken into account.
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Tricyclic antidepressant plasma levels were measured in nine hospitalized adolescent oversdose patients to define the medical seriousness of the drug ingestion. Seven out of nine of these patients ingested medication prescribed for treatment of their psychiatric symptoms. Indications for tricyclic therapy in adolescents are vague. The more frequent use of these drugs makes the potential for life-threatening ingestions relatively common. The amount of drug ingested is usually poorly documented. Plasma measurements are of value in assessing the efficacy of the various medical treatments of overdose patients. Two of these nine overdoses were medically serious as defined by plasma measurements. Supportive care with cardiac monitoring was adequate in one case; however, a fatality occurred in the other under what could be described as optimal patient management conditions.
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A two-step, randomized, intraindividual parallel-comparative, double-blind, placebo-controlled trial was conducted on the volar side of the forearm. Step 1 was aimed to determine the onset, while step 2 determined the duration of action. The topical AH tested was a single application of 5% doxepin hydrochloride cream, while 10 mg/ml histamine dihydrochloride was used to test the skin responses.
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Cold urticaria is characterized by the development of urticaria, usually superficial and/or angioedematous reaction after cold contact. It was found predominantly in young women. The diagnosis is based on the history and ice cube test. Patients with a negative ice cube test may have represented systemic cold urticaria (atypical acquired cold urticaria) induced by general body cooling. The pathogenesis is poorly understood. Cold urticaria can be classified into acquired and familial disorders, with an autosomal dominant inheritance. Idiopathic cold urticaria is most common type but the research of a cryopathy is necessary. Therapy is often difficult. It is essential that the patient be warned of the dangers of swimming in cold water because systemic hypotension can occur. H1 antihistamines can be used for treatment of cold urticaria but the clinical responses are highly variable. The combination with an H2 antagonists is more effective. Doxepin may be useful in the treatment. Leukotriene receptor antagonists may be a novel, promising drug entity. In patients who do not respond to previous treatments, induction of cold tolerance may be tried.
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Observational study of prescriptions (UK), poisoning deaths involving single antidepressants receiving coroners' verdicts of suicide or undetermined intent (England and Wales) and non-fatal self-poisoning episodes presenting to six general hospitals (in Oxford, Manchester and Derby) between 2000 and 2006. Calculation of fatal toxicity index based on ratio of rates of deaths to prescriptions, and case fatality based on ratio of rates of deaths to non-fatal self-poisonings.
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Which pharmacological and nonpharmacological interventions are associated with improvement in general, physical, or mental fatigue and minimal adverse effects in patients with Parkinson disease (PD)?