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At least 1,009 records · Page 56Linked to original sources
PubMed1982

Plasma levels, psychophysiological variables, and clinical response to amitriptyline.

Hamilton depression scale ratings and physiological measurements were made for 37 patients with primary depression before treatment with amitriptyline (150 mg/day) and again after 2 and 4 weeks of treatment; plasma drug levels were determined weekly. Improvement was maximal at mean amitriptyline + nortriptyline concentrations of 125-200 ng/ml (14 patients), while at lower levels the outcome was significantly poorer (12 patients). Highly variable results were seen in 11 patients with levels between 200 and 301 ng/ml, with lesser improvement occurring in those patients who exhibited poor habituation of the skin resistance response before treatment. Other psychophysiological variables showed significant changes during treatment, but no correlation with clinical results or drug levels.

Adult↗
PubMed1987

Open-trial response to antidepressant treatment in elderly patients with mixed depression and cognitive impairment.

We report open-trial antidepressant response in 16 inpatients with mixed symptoms of depression and cognitive impairment, compared to 16 elderly depressives without cognitive impairment. Criteria for adequate treatment specified a steady-state plasma nortriptyline level of 50-150 ng/ml for 4 consecutive weeks or a minimum of six treatments with electroconvulsive therapy. Ten of 16 mixed-symptom patients showed a drop in Hamilton depression ratings greater than or equal to 50% during treatment. Similarly, Blessed dementia ratings declined significantly; the % change in Blessed dementia ratings was significantly correlated with improvement in Hamilton depression ratings. By contrast, Folstein mini-mental state scores did not change significantly during treatment. Six of 16 (37.5%) patients showed resolution of cognitive impairment with adequate treatment of depression. Mixed-symptom patients diagnosed as suffering from major depression (with cognitive impairment) showed more robust pre-post treatment differences, particularly in Hamilton, Folstein, and Blessed dementia scores, than did mixed patients diagnosed as having primary degenerative dementia (with depression). In cognitively intact elderly depressives, the mean % change in Hamilton ratings was 72% (4.3), not significantly different from mean % change in mixed-symptom patients (57.4 +/- 29.9). The proportion of intact depressives showing a reduction greater than or equal to 50% in Hamilton depression ratings was significantly greater (93.8%) than in the mixed group (62.5%). In both groups, 81.3% of patients (13 of 16 in each cell) had a final Hamilton rating less than or equal to 10. These data suggest that elderly patients with mixed depression and cognitive impairment respond to treatment similar to that used in cognitively intact elderly depressives. A controlled study of antidepressant treatment in mixed-symptom patients is warranted.

Aged↗
PubMed1995

T-lymphocyte cholecystokinin-8 and beta-endorphin concentrations in eating disorders: I. Anorexia nervosa.

Baseline concentrations of cholecystokinin-8 (CCK-8) and beta-endorphin (beta-EP) were measured in T-lymphocytes from 33 restricting patients with anorexia nervosa (AN-R), 23 binging/purging patients with anorexia nervosa (AN-BP), and 24 healthy volunteers. CCK-8 basal values were significantly lower and beta-EP values significantly higher in AN-R and AN-BP patients than in normal volunteers. Levels of the peptides were measured three more times during a 4-month combined cognitive-behavioral/psychopharmacological treatment (nortriptyline or fluoxetine in AN-R, fluoxetine or amineptine in AN-BP). CCK-8 values fluctuated (nonsignificantly) during each treatment, while beta-EP values decreased (to a significant degree only in fluoxetine-treated AN-R patients).

Adolescent↗
PubMed1996

Quality of life in elderly patients with recurrent major depression: a factor analysis of the General Life Functioning Scale.

Quality of life profiles measured by the General Life Functioning (GLF) Scale were examined in elderly patients with recurrent major depression, before and during combined treatment with nortriptyline and interpersonal psychotherapy. The study group included 110 patients, 91 recovered and 19 nonrecovered, aged 60 to 80 years, suffering from at least their second lifetime episode of major depression. Repeated measures analysis of covariance (with Hamilton and Beck depression scores as time-dependent covariates) was used to compare the temporal course of overall GLF scores for the recovered and the nonrecovered groups. Factor analysis was used to examine whether the GLF Scale yielded an overall score and measured specific aspects of well-being and coping. There were significant differences in the overall GLF scores between recovered and nonrecovered patients, with the differences increasing from week 8 of treatment onward. Analysis revealed significant improvements in quality of life, as measured by overall GLF scores, over the course of treatment in both recovered and nonrecovered patients. Even when changes in Hamilton and Beck depression ratings were controlled for in the statistical analysis, improvements in GLF scores were found to be greater in recovered than in nonrecovered patients. Thus, the GLF measures more than change in level of depression. Its overall score also has high internal reliability.

Adaptation, Psychological↗
PubMed1990

The pupil response to E-10-hydroxynortriptyline in rabbits with ocular sympathetic paresis.

E-10-hydroxynortriptyline, a metabolite of nortriptyline with half the norepinephrine re-uptake blocking potency of the parent drug, but only 5% of its anticholinergic effect, was as effective as cocaine in demonstrating ocular sympathetic paresis. In five rabbits with unilateral superior cervical ganglionectomies, bilateral 5% cocaine HCl or E-10-hydroxynortriptyline maleate eye drops increased (P less than 0.001) the mean +/- SE anisocoria at 1 h by 1.84 +/- 0.03 mm or 2.16 +/- 0.33 mm, respectively. A single drop of E-10-hydroxynortriptyline did not alter corneal thickness or endothelial cell count.

Animals↗
PubMed1989

Protective effect of flavonoids on drug-induced hepatotoxicity in vitro.

Primary cell cultures of neonatal hepatocytes were used to examine the protective effect of flavonoids in the presence of hepatotoxins. Catechin (CAT) and silybin (SIL) protected the hepatocytes against cell injury produced by erythromycin estolate (EE), amitriptyline (AT), nortriptyline (NT), and tert-butylhydroperoxide (TBOOH). Leakage of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as morphological parameters, were used as indices of hepatotoxicity. Hepatocytes were exposed to EE (1 X 10(-4) M and 2 X 10(-4) M), AT, NT, and TBOOH (1 X 10(-4) M and 1 X 10(-3) M) for a 2-h period. These hepatotoxins caused significant LDH, AST, and ALT leakage (P less than 0.05) when compared to untreated control groups. NT was less toxic than its parent compound, AT. Changes in morphology were evident after 1 h of treatment with the toxicants, including: vacuole formation, size deformation and cell necrosis. As the concentration of hepatotoxins was increased, the changes were more pronounced. Pretreatment of the cultures with either CAT or SIL resulted in less enzyme leakage and morphological alterations by the hepatotoxins. The results of this study suggest that CAT and SIL may act by stabilizing the plasma membrane against toxic insult.

Alanine Transaminase↗
PubMed1996

Plasma and brain pharmacokinetics of amitriptyline and its demethylated and hydroxylated metabolites after one and six half-life repeated administrations to rats.

The purposes of the present study were as follows: 1. After an acute intraperitoneal (IP) administration of amitriptyline (AMI) to male Sprague-Dawley rats we found that: (i) its absorption rate is rapid; (ii) its elimination half-life is much shorter than in humans; and (iii) its levels largely exceeded those of its metabolites. The most important metabolites being 10-hydroxynortriptyline and nortriptyline in plasma and brain, respectively. 2. After six (every half-life) repeated IP administrations: (i) AMI kinetic parameters were unchanged; and (ii) amounts of metabolites were significantly increased and the levels of AMI were lowered both in plasma and brain.

Amitriptyline↗
PubMed1979

Metabolic interaction between amitriptyline and perphenazine in psychiatric patients.

1. Steady-state plasma level samples of sixty-five schizophrenic patients from two psychiatric hospitals assigned to three treatment groups (amitriptyline 150 mg/day, perphenazine 20 mg/day and a combination of amitriptyline and perphenazine at 150 mg and 20 mg/day) were assayed for amitriptyline (AT), endogenous nortriptyline (NT) and perphenazine (PPZ) using gas-liquid chromatography. 2. Results reveal that AT and NT levels are independent of sex and hospital environment. 3. PPZ significantly increased the steady-state NT plasma levels, probably through inhibition of the hydroxylation biotransformation pathway, but had no effect on AT levels, thus indicating that PPZ has no influence on the desmethylation pathway, or alternatively, the hydroxylation of AT.

Adult↗
PubMed1992

Determination of fluvoxamine in human plasma by high-performance liquid chromatography with fluorescence detection.

Fluvoxamine and nortriptyline, the assay internal standard, were extracted from plasma with ethyl acetate, then reacted with dansyl chloride. The derivatives were quantitated by isocratic reversed-phase high-performance liquid chromatography with fluorescence detection. The assay calibration range for fluvoxamine was 10-1000 ng/ml using a 1-ml plasma sample. Pooled plasma quality control sample relative recoveries at 25 and 250 ng/ml were 103 and 105%, respectively. Estimates of quality control inter-day precision during validation were less than or equal to 3% relative standard deviation. The assay was cross-validated with a gas chromatographic method and has been employed in therapeutic drug level monitoring.

Chromatography, High Pressure Liquid↗
PubMed1993

Dual ultraviolet wavelength high-performance liquid chromatographic method for the forensic or clinical analysis of seventeen antidepressants and some selected metabolites.

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.

Amitriptyline↗
PubMed2006

Aggressive behavior in patients with stroke: association with psychopathology and results of antidepressant treatment on aggression.

OBJECTIVE: To examine, in a post hoc analysis of an antidepressant treatment trial, correlates of irritability and aggression after stroke and changes in irritability scores associated with antidepressant treatment. DESIGN: Aggressive patients (n=23) were compared with nonaggressive patients (n=69) on numerous measures of psychopathology, poststroke impairment, and neuroimaging findings. SETTING: All patients were hospitalized at the time of the initial evaluation for acute stroke or for rehabilitation therapy. PARTICIPANTS: Ninety-two patients from the Iowa City Stroke Study were classified as aggressive or nonaggressive, based on symptoms elicited by the Present State Examination (PSE) and from family or caretaker reports. INTERVENTION: All patients were randomized to receive nortriptyline, fluoxetine, or placebo using a double-blind methodology. MAIN OUTCOME MEASURE: The change in aggression score as elicited by the PSE at the beginning and the end of a 12-week treatment trial. RESULTS: Twenty-five percent (23/92) of patients reported irritability or aggression. Irritable and aggressive patients had higher total PSE scores, Hamilton Depression Rating Scale scores, Hamilton Anxiety Rating Scale (HAMA) scores, and lower Mini-Mental State Examination scores. They also had lesions that were more proximal to the frontal pole. Stepwise regression analysis showed that HAMA scores and proximity of lesion to the frontal pole were significant independent predictors of irritability. Among irritable and aggressive patients with depression who responded to antidepressants, there was a significantly greater reduction in irritability after treatment, compared with patients whose depression did not lessen with treatment. CONCLUSIONS: Several factors, such as severity of impairment, other psychopathology, and neurobiologic factors, appear to contribute to irritable and aggressive behavior in stroke patients. If depression accompanies aggression, the results of this small study suggest that successful treatment of depression may reduce aggressive behavior.

Aged↗
PubMed2006

Pharmacologic interventions for smoking cessation.

According to the US Public Health Service, all patients attempting to quit smoking should be encouraged to use one or more effective pharmacotherapy agents for cessation except in the presence of special circumstances. This article provides an overview of the pharmacologic agents for acute and critical care nurses to consider when intervening with tobacco-dependent patients. Medications addressed in this article include (1) first-line agents (nicotine replacement therapy, sustained-release bupropion) that have proven efficacy and are approved by the Food and Drug Administration (FDA) for smoking cessation, (2) second-line agents (nortriptyline, clonidine) that have proven efficacy but no FDA indication for smoking cessation, (3) approaches that use of combination or high-dose therapy, (4) herbal therapies, and (5) emerging therapies that are currently under investigation.

Administration, Cutaneous↗
PubMed2005

Tissue distribution of mirtazapine and desmethylmirtazapine in a case of mirtazapine poisoning.

An ingestion of an unknown quantity of mirtazapine in a suicide attempt leading to death is described. Sertraline and amitriptyline have been co-ingested. Because mirtazapine is reported to be relatively safe in overdose, body fluids and tissues were investigated for both mirtazapine and desmethylmirtazapine by high-pressure liquid chromatography/tandem mass spectrometry following liquid-liquid extraction. The limit of detection was sufficiently low to also apply the assay in pharmacokinetic studies. The levels of amitriptyline and nortriptyline were very low (38 and 19 ng/mL femoral venous blood) and the amount of sertraline in blood taken from the femoral vein (880 ng/mL) was considerably lower than those seen in overdosage. Accumulation of mirtazapine and N-desmethylmirtazapine was evident in fluids and tissues involved in enterohepatic circulation and excretion. The concentration determined in a brain sample suggests a contribution of the metabolite to the drug's pharmacodynamic activity. Based on literature data, significant adverse or synergistic effects among the drugs detected as well as adverse reactions such as a serotonin reaction appeared less probable. Mirtazapine exhibits alpha(1)-antagonistic properties on the cardiac-vascular system and may cause hyponatraemia. In the face of the cardiac findings at autopsy and the lack of an apparent cause of death, these effects of mirtazapine may have initiated a process leading to death.

Aged↗
PubMed2006

Rheological studies on pressure-sensitive silicone adhesives and drug-in-adhesive layers as a means to characterise adhesive performance.

Pressure-sensitive adhesives are viscoelastic polymers used in the formulation of transdermal patches that allow attachment of a patch onto the skin. Established criteria exist that correlate viscoelastic parameters with adhesive performance. In this study, fulfillment of the adhesive performance criteria was examined using two silicone adhesives with different tack properties. The viscoelastic parameters of high and low tack silicone adhesives (BIO-PSA High Tack 7-4302 and BIO-PSA Low Tack 7-4102) were determined and compared with the criteria described by Chu and Dahlquist. Drug-in-adhesive layers were prepared using the high tack adhesive combined with nortriptyline HCl or paracetamol. The effect of drug addition on the viscoelastic properties of the adhesive was examined. The high tack adhesive showed congruence with the established criteria although with a modified range of viscoelastic moduli to that described by Chu. Examination of the low tack adhesive showed that it did not possess the appropriate viscoelastic properties for bonding onto the skin. The addition of the drugs into the high tack adhesive caused a concentration-dependent increase in its cohesive strength. This effect was independent of the physicochemical properties of the drugs tested.

Acetaminophen↗
PubMed2005

Application of solid-phase microextraction in the investigation of protein binding of pharmaceuticals.

Protein-drug interactions of seven common pharmaceuticals were studied using solid-phase microextraction (SPME). SPME can be used in such investigations on the condition that no analyte depletion occurs. In multi-compartment systems (e.g. a proteinaceous matrix) only the free portion of the analyte is able to partition into the SPME fiber. In addition if no sample depletion occurs, the bound drug-free drug equilibria are not disturbed. In the present study seven pharmaceuticals (quinine, quinidine, naproxen, ciprofloxacin, haloperidol, paclitaxel and nortriptyline) were assayed by SPME. For quantitative purposes SPME was validated first in the absence of proteins. Calibration curves were constructed for each drug by HPLC-fluorescence and HPLC-UV analysis. SPME was combined to HPLC off-line, desorption occurring in HPLC inserts filled with 200 microL methanol. Binding of each drug to human serum albumin was studied independently. Experimental results were in agreement with literature data and ultrafiltration experiments, indicating the feasibility of the method for such bioanalytical purposes.

Binding, Competitive↗
PubMed2005

Non-nicotine pharmacotherapies for smoking cessation.

International chronic obstructive pulmonary disease guidelines recommend that smokers be strongly advised to quit, and should be offered help in doing so. The most effective smoking-cessation interventions combine behavioural support with pharmacotherapies. For smokers who do not wish to use nicotine replacement treatments, bupropion is a safe and effective non-nicotine alternative first-line treatment. Nortriptyline and clonidine have demonstrated efficacy in aiding smoking cessation, but are regarded as second-line therapies. A number of other non-nicotine treatments show promise, but more data are required before these can be recommended in assisting smokers to stop.

Adrenergic alpha-Agonists↗
PubMed2001

Endogenous concentrations of DHEA and DHEA-S decrease with remission of depression in older adults.

BACKGROUND: Clinical studies of endogenous concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate DHEA-S in depression are limited. This study was designed to evaluate the influence of successful pharmacological treatment of late-life depression on concentrations of DHEA, DHEA-S and cortisol. METHODS: We determined endogenous concentrations of DHEA, DHEA-S and cortisol in elderly control subjects (n = 16) and in elderly depressed patients who remitted (n = 44) or failed to remit (n = 16) with pharmacological treatment. Depressed patients were treated for 12 weeks with either nortriptyline or paroxetine. RESULTS: In remitters, DHEA and DHEA-S concentrations were lower at week 12 than at week 0 (p =.002 and p =.0001, respectively). In the nonremitters and control subjects, neither DHEA nor DHEA-S concentrations changed. Decreases in hormone concentrations were associated with improvement in mood and functioning in depressed patients. Although cortisol concentrations decreased in remitters and nonremitters, the change was not significant. CONCLUSIONS: Our data suggest that the decrease in DHEA and DHEA-S in remitters is related to remission of depression rather than to a direct drug effect on steroids, as nonremitters had no change in hormone concentrations.

Aged↗