Hemoperfusion over cellulose-coated activated charcoal was used to treat a patient with severe doxepin overdose. Noncardiogenic pulmonary edema (NCPE) developed temporally in relation to the procedure. In this case, NCPE may have been from complement activation by the cellulose-coated charcoal column.
Data were collected in pharmacies in Cracow and Gorlice and their vicinity. We analyzed PIPDs as revised by Beers et al. in 1997 and 2002.
Antischizophrenic agents, phenothiazine and nonphenothiazine, inhibit the transformation of the T-lymphocyte in vitro. This inhibition occurs only in the early event and is neither competitive with dopamine, nor appears to involve Na+/K+ adenosine triphosphatase. RNA synthesis is more sensitive to the inhibitory effect than DNA or protein synthesis. This leads to the conclusion that chlorpromazine may act by inhibiting the synthesis of newly formed RNA, and subsequently, transformation, rather than by alteration of the cell membrane.
In a randomized, double-blind safety and efficacy study, 50 patients with chronic pruritus were given either doxepin 10 mg/d or hydroxyzine 25 mg/d for 4 weeks. Pruritic score was calculated for each patient before treatment and 1 month after.
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Examination of the stability of clonazepam, diazepam, alprazolam, haloperidol, and doxepin in basic solutions was performed, together with an assessment of the kinetic (k, t0.1i t0.5) and thermodynamic (Ea, ΔH(++)i ΔS(++)) stability-indicating parameters, which were compared with the lipophilicity (logP) of the studied drugs. It was observed that the calculated values of Ea, ΔH(++) and ΔS(++) for the studied drugs increased from 41.04 kJ/mol to 125.50 kJ/mol, from 37.82 kJ/mol to 122.24 kJ/mol and from -167.09 J/Kmol to 53.02 J/Kmol, respectively, along with an increase of lipophilicity (logP) from 2.12 to 4.30 for the most hydrophilic alprazolam to the most lipophilic haloperidol. The degradation products were identified using UPLC/MS/MS method.
Topically applied doxepin is safe and effective therapy for pruritus.
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A total of 19 women with detrusor overactivity and associated symptoms completed a double-blind placebo-controlled crossover study of doxepin. All patients had previously failed to respond to conventional pharmacotherapy. Doxepin was given at bedtime in a single 50 mg. dose for the first 2 weeks and, if needed, the dose was increased with 25 mg. in the morning for the last week of the 3-week treatment period, which was followed by 2 weeks of washout before crossover. The preference for doxepin to placebo was statistically significant (p less than 0.01). Doxepin caused a significant decrease in the nighttime micturition frequency and the nighttime incontinence episodes (p less than 0.05). Urine loss at the standardized 1-hour pad weighing test decreased significantly during treatment with doxepin although statistical significance (p equals 0.07) was not obtained. Cystometric parameters (first sensation and maximum cystometric capacity) improved significantly during treatment with doxepin (p less than 0.06 and less than 0.04, respectively). Side effects were frequent but mild. Suggestions for use of this tricyclic antidepressant in women with detrusor overactivity and possible mechanisms of action are discussed.
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Using IBOT, the IVeH has successfully established two national programs: one in Kosova and one in Albania. Together, they have connected 16 hospitals. Currently IVeH is in the process of creating such programs in many countries around the world. During the analysis of the first decade, we have identified eight factors that should be considered when establishing telemedicine programs.
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Current techniques of peripheral nerve block have major limitations, including lack of differentiation between motor and sensory fibers and potential toxicity of local anesthetics. Recent studies have suggested that a nociceptive-selective nerve block can be achieved via a transient receptor potential vanilloid type 1 activator (capsaicin) along with local anesthetics. We hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (RTX) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block.
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The perceived intensity of a stimulus may be magnified during depression. Stimulus intensity control can be studied by means of cortical evoked potentials. In a study of 33 depressives, cortical evoked potentials were greater during depression than on recovery. The effect of doxepin on the amplitudes of evoked potentials of depressives was compared with that of amitriptyline. Doxepin reduced amplitudes. Amitriptyline had a similar, but non-significant effect.
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Suicidal self-poisoning with tricyclic antidepressants like doxepin is a major therapeutic problem in emergency medicine with a high fatality rate. Deaths are mainly caused by cardiotoxicity with arrhythmias, intraventricular conduction disturbances and myocardial depression. For treatment, alkalinization and hypertonic saline are recommended. The role of extracorporeal, treatment procedures is not clear. The possible benefit of hemoperfusion/hemodialysis is discussed in a case report with respect to the published literature.
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To analyze the clinical characteristics of children with cyclic vomiting syndrome (CVS), summarize the experience for twelve years, and improve awareness, diagnosis and treatment level of CVS.
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The binding potential ratios of olanzapine and quetiapine in the cerebral cortex were significantly lower than that of the placebo. The H1RO values of olanzapine and quetiapine in the cortex were approximately 61-80 and 56-81%, respectively. The binding potential ratios of the drugs were significantly lower than that of the placebo in the dorsolateral prefrontal and lateral temporal cortices, and anterior and posterior cingulate gyri. The H1RO values in the cortex were significantly correlated with subjective sleepiness but not plasma drug concentrations.
The present study demonstrates a significant contribution of the polymorphic CYP2C19 to the N-demethylation of doxepin. CYP2C9 and CYP1A2 play a minor role and CYP3A4 does not contribute substantially.
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Muscle weakness, neuropathy, and transient rises in hepatic enzyme activity have been reported with the use of the antiarrhythmic agent amiodarone. A 68 year old teetotaller with normal liver function was given amiodarone for resistant supraventricular arrhythmias. He presented 19 months later with vomiting, muscle weakness and wasting, sensory neuropathy, and hepatomegaly. Liver biopsy showed fibrosis and the presence of hyaline. The amiodarone was withdrawn. Three months later he developed ascites. Oesophageal varices were found and he later died. The liver showed micronodular cirrhosis. The large volume of distribution and long half life of amiodarone may explain the persistence of toxicity, which may have been aggravated by simultaneously administered doxepin in this case. Amiodarone should be withdrawn if abnormal liver function or neuropathy develops.
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In the area of Vienna, any person dying under questionable circumstances is examined at the Institute of Forensic Medicine, where the cause of death is determined by means of autopsy and chemical analysis. Our study on fatal intoxications was performed in the period between 1991 and 1997, when selective serotonin reuptake inhibitors (SSRIs) were establishing themselves on the market, reaching the top of prescription statistics. Tricyclic antidepressants (TCAs) were involved in 30 single- and 127 multiple-substance intoxications, with amitriptyline and doxepin being the most frequently used drugs. SSRIs were involved in five multiple-substance intoxications. The f-value, which refers to the number of deaths per million defined daily doses prescribed, was found to be significantly (P=0.001) higher in TCAs than in SSRIs. The f-value for the total group of all antidepressants declined significantly (P=0.05) during the observation period of 7 years. In conclusion, SSRIs turned out to be less toxic than TCAs, and the increasing use of new antidepressants did not coincide with an increased number of deaths caused by these drugs.
The objective of this research was to develop, optimize, and validate a modern, rapid method of preparation of human hair samples, using microwave irradiation, for analysis of eight tricyclic antidepressants (TCADs): nordoxepin, nortriptyline, imipramine, amitriptyline, doxepin, desipramine, clomipramine, and norclomipramine. It was based on simultaneous alkaline hair microwave-assisted hydrolysis and microwave-assisted extraction (MAH-MAE). Extracts were analyzed by high-performance liquid chromatography with diode-array detection (HPLC-DAD). A mixture of n-hexane and isoamyl alcohol (99:1, v/v) was used as extraction solvent and the process was performed at 60°C. Application of 1.0 mol L(-1) NaOH and microwave irradiation for 40 min were found to be optimum for hair samples. Limits of detection ranged from 0.3 to 1.2 μg g(-1) and LOQ from 0.9 to 4.0 μg g(-1) for the different drugs. This enabled us to quantify them in hair samples within average therapeutic concentration ranges.
Paroxetine is generally well tolerated by both younger and older individuals and its adverse event profile is consistent with that expected for an SSRI. The tolerability profile of paroxetine in patients with panic disorder appears to resemble that in patients with depression. Headache, nausea, somnolence, dry mouth and insomnia were the most common adverse events among 469 patients with panic disorder who received paroxetine 10 to 60 mg/day in short term clinical trials. The individual incidences for these events ranged from 18 to 25%; however, the incidence of headache in paroxetine-treated patients was the same as that in placebo recipients. (ABSTRACT TRUNCATED)
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537 TCA recipients and 554 SSRI recipients were compared. TCAs had an increased withdrawal rate (RR: 0.24, CI 1.04, 1.47). A similar result was found when comparing classical TCAs (451 patients) (amitriptyline, clomipramine, doxepin and dothiepin) with SSRIs (466 patients) (RR 1.30 CI: 1.02,1.64). These findings were reflected in the increased TCA prevalence of side effects including dry mouth, drowsiness, dizziness and lethargy. No differences were found when comparing TCA related drugs (mianserin and trazadone) with SSRIs (RR 1.07 CI 0.43, 2.70).
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Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCA) is established in the treatment of depression to optimize outcome and safety. However, there are few reports on TDM under naturalistic clinical conditions. In the present study, we investigated a TDM group (TDM) and a randomly assigned parallel group without TDM (no-TDM) while on TCA treatment. Serum levels were analyzed in both cohorts, but feedback and dose recommendation were only provided for the TDM group. Serum levels of TCA were assessed by high-performance liquid chromatography (HPLC). The outcome was measured weekly using the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions Scale (CGI), and the UKU side-effect scale. 84 patients with depressive disorder according to DSM-IV were recruited in three centers (TDM, n = 43; no-TDM, n = 41; mean age 49.9 +/- 13.2 years, 63.1 % female). Patients were treated with either amitriptyline (n = 69) or doxepin (n = 15); the mean dosage at endpoint was 126 +/- 35 mg and 155 +/- 47 mg, respectively. The mean study duration was 21 +/- 8 days. Both groups improved according to HAMD (from 25.2 +/- 8.4 at baseline to 12.0 +/- 7.4 at endpoint) and CGI scores (68 % responders). Moderately severe or severe side effects occurred in 16 % of patients. Adequate dose adjustment was significantly higher in the TDM group (60 % vs. 46 %, p < 0.05); this led to a significantly higher rate of therapeutic serum levels in the TDM group (58 % vs. 44 %, p < 0.05). Direct effects of TDM were not found for effectiveness. Therapeutic TCA serum levels over weeks one to three, however, were associated with significantly better outcome at endpoint (p < 0.05) as measured with changes in the HAMD or CGI response rates from baseline to endpoint. Finally, considerable side effects occurred significantly more often when serum levels were above the therapeutic range (27 % vs. 11 %; p < 0.01). We conclude that treating depression with TCA can be optimized by early TDM, which is superior to clinical judgment on its own. Since the psychiatrists in charge were less than completely "compliant" to the recommendations provided together with serum levels, the effect could be more pronounced than this study shows. The results encourage further studies in order to optimize antidepressant pharmacotherapy when using TDM appropriately.