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At least 1,081 records · Page 60Linked to original sources
PubMed1998

Isotope dilution gas chromatographic-mass spectrometric measurement of tricyclic antidepressant drugs. Utility of the 4-carbethoxyhexafluorobutyryl derivatives of secondary amines.

Stable isotope dilution gas chromatographic-mass spectrometric (GC-MS) measurement of tricyclic antidepressants (TCA) is a useful alternative to high-performance liquid chromatography (HPLC) methods when interfering substances prevent accurate quantitation by HPLC. For satisfactory GC-MS analysis, secondary amine TCA must be derivatized. Commonly employed trifluoroacetyl and heptafluorobutyryl derivatives are relatively unstable and cause rapid deterioration of capillary GC columns. Therefore we examined 4-carbethoxyhexafluorobutyryl chloride (CHFB-CI) as an alternative derivatizing agent and developed a stable isotope dilution GC-MS method employing ring-labeled [2H4]-desipramine and [2H4]-imipramine internal standards, which permits measurement of desipramine, nortriptyline, imipramine, and amitriptyline in plasma samples containing one or all of these analytes. The GC-MS assay is linear for each analyte from the lower limit of quantitation (25 ng/mL) up to 1500 ng/mL and correlates well with HPLC measurements. The GC-MS analytic coefficient of variation was 9.7 +/- 1.3% for all analytes considered together. Although interferences are observed in the HPLC assay, thioridazine, perphenazine, cyclobenzaprine, and norcyclobenzaprine do not interfere with GC-MS measurements of the TCA examined here. The stability of the CHFB derivative of secondary amine TCA was found to be superior to that of the trifluoroacetyl derivatives of these compounds.

Amitriptyline↗
PubMedDate not supplied

Determination of tricyclic antidepressants in serum by high pressure liquid chromatography on a silica column.

High pressure liquid chromatography procedures are reported for the determination of amitriptyline and its metabolite, nortriptyline, and for imipramine and its metabolite, desipramine. Separations and quantitations were carried out at ambient temperature using a silica column with a variable wavelength UV detector. The procedures have been used successfully on clinical samples (serum) and on forensic samples (hemolyzed blood). If need be, analysis can be performed on 0.25 mL serum. Several potential interferences, related compounds and drugs, have been evaluated.

Amitriptyline↗
PubMed1994

Postmortem changes in blood amitriptyline concentration.

Detailed toxicological studies were undertaken on two suicides by amitriptyline overdose, one with salicylate also. In the first case, 10 initial blood samples taken 21 h after body discovery and an estimated 28 1/2 h after overdose had drug concentration (mg/L) ranges of 2.5-12 for amitriptyline (AM), 0.7-3.1 for nortriptyline (NOR), and 81-244 for salicylate (SAL). Ten blood samples taken 42 h later showed corresponding ranges of 1-39 AM, 0.6-7.0 NOR, and 86-310 SAL. Sample haemoglobin concentrations (range, 8.7-23.5 g/dl) did not correlate with drug concentrations. Postmortem increase in pulmonary vein AM concentration occurred more rapidly than in the pulmonary artery, likely reflecting relative ease of diffusion across the vessel walls from lung (AM, 60 mg/kg). In nine tissue samples, drug concentrations (mg/kg) were highest in the liver: AM, 301; and SAL, 670. Considerable drug residue was present in gastric contents, duodenal contents, and seven sequential small bowel contents. In both cases, sanguineous putrefactive pleural fluid showed higher AM concentrations on the left than on the right (2.0 vs 1.4 and 23 vs 16), likely reflecting diffusion from gastric drug residue. The detailed case data illustrate the intensity and complexity of postmortem drug diffusion from reservoirs in solid organs, such as the lungs, and unabsorbed gastric residue, into the blood and putrefactive fluids.

Adult↗
PubMed1998

Elevated levels of erythropoietin in cerebrospinal fluid of depressed patients.

To investigate the role of erythropoietin (EPO) in the central nervous systems, we assayed EPO concentrations in the cerebrospinal fluid (CSF) of patients with depression or old cerebrovascular injuries and controls. Concentrations of EPO in the CSF were significantly higher in 13 patients with depression (3.21+/-0.46 mU/mL) than in 10 patients with old cerebrovascular diseases (1.80+/-0.32 mU/mL, P < 0.01), and in 10 healthy controls (0.98+/-0.26 mU/mL, P < 0.01). Serum EPO concentrations did not differ among these three groups. In the patients with depression, 5 months of treatment with imipramine and/or nortriptyline significantly reduced EPO concentrations in the CSF (1.56+/-0.34 mU/ mL, P < 0.01). Results suggest that the brain of patients with depression may be in an hypoxic state, and that the increased EPO in the CSF may act to limit hypoxia-induced damage to neurons in these patients.

Antidepressive Agents, Tricyclic↗
PubMed2001

Adult psychosocial outcome of prepubertal major depressive disorder.

OBJECTIVE: To compare adult psychosocial functioning (PSF) of subjects with prepubertal major depressive disorder (PMDD) to a normal comparison (NC) group. METHOD: PSF of subjects with PMDD (n = 72) and of NC subjects (n = 28) was compared after prospective follow-up to adulthood. These 100 subjects were 90.9% of the baseline 110 subjects who participated in the "Nortriptyline in Childhood Depression: Follow-up Study." Research nurses who were blind to group status conducted telephone interviews using the Longitudinal Interval Follow-up Evaluation (LIFE) to obtain PSF data. RESULTS: At follow-up, the PMDD group was 20.7+/-2.0 and the NC subjects were 20.9+/-2.2 years old. The PMDD subjects were 10.3+/-1.5 years old at baseline. Time between baseline and follow-up was 9.9+/-1.5 years. In the PMDD group, subjects with MDD, bipolar disorder, or substance use disorders during the previous 5 years had significantly worse PSF than NC subjects. These PSF impairments included significantly worse relationships with parents, siblings, and friends; significantly worse functioning in household, school, and work settings; and worse overall quality of life and global social adjustment. CONCLUSIONS: Although combined treatments for PMDD have little scientific basis, multimodality regimens seem prudent until definitive treatment data become available.

Adaptation, Psychological↗
PubMed1982

EEG sleep and tricyclic blood levels: acute and chronic administration in depression.

An understanding of the effects of antidepressants on sleep can be aided by determinations of tricyclic plasma levels in relationship to sleep. Previous studies have been established that steady state plasma levels of amitriptyline relate to certain aspects of rapid eye movement (REM) sleep. The present investigations attempt to replicate the REM sleep/tricyclic plasma level relationships in a larger group of psychiatric hospitalized patients for depression and to study whether such relationships persist in a group of ambulatory patients studied longitudinally for 1 to 2 years. In an acute treatment study of 38 patients, REM sleep percent and average REM activity demonstrated a significant relationship with plasma levels, even when controlled for age and severity. The sleep-plasma level relationships seem more prominent with amitriptyline levels than with nortriptyline plasma levels. In a long term comparison of plasma levels, tricyclic plasma levels showed a significant correlation with REM latency, REM percent and average REM activity. Thus, it appears that changes in REM sleep such as REM suppression correlate significantly with tricyclic plasma levels both on a short (4 weeks) and long term basis (1 to 2 years). The implications of these findings are discussed.

Adult↗
PubMed1985

Amitriptyline and hydroxylated metabolite plasma levels in depressed outpatients.

As part of a double-blind clinical trial comparing phenelzine and amitriptyline in outpatients with predominantly major depressive disorder, plasma tricyclic antidepressant drug concentrations were measured in 83 amitriptyline-treated patients. In 29 of these patients, hydroxymetabolites were also assayed. Patients were treated for 6 weeks at a fixed dose of 150 mg/day of amitriptyline after the first 5 days. Therapeutic outcome was assessed with a structured depression interview schedule, the Symptom Checklist-90, a side effects checklist, and a global improvement scale. Steady state plasma levels of 10-hydroxynortriptyline were in the same range as amitriptyline or nortriptyline concentrations. Clinical response did not relate significantly to plasma levels of either the parent drug, its metabolites, or the sum of all four pharmacologically active substances. Minimum threshold tricyclic antidepressant levels for therapeutic effect were not found. Assay of its active hydroxymetabolites does not appear to improve the clinical utility of routine amitriptyline level monitoring in patients with major depression in an outpatient setting.

Adult↗
PubMed1995

Interindividual variations of desmethylation and hydroxylation of amitriptyline in a Japanese psychiatric population.

We measured the concentrations in plasma of amitriptyline and its metabolites, nortriptyline and geometric isomers of 10-hydroxynortriptyline and 10-hydroxyamitriptyline, in 73 Japanese psychiatric patients receiving amitriptyline hydrochloride (Tryptanol; Banyu Pharmaceutical Co. Ltd., Tokyo, Japan) by high-performance liquid chromatography. Although there were large interindividual variations of total drug concentrations and concentrations of parent or intermediate metabolic compounds in plasma, significant positive correlations were observed between these drug concentrations and daily doses of amitriptyline hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for both hydroxylation and desmethylation varied substantially with approximately 8- to 19-fold interindividual variations. Frequency distribution histograms and probit analyses of these parameters identified neither definite poor hydroxylators nor poor desmethylators of amitriptyline.

Adult↗
PubMed1995

Dosing of antidepressants--the unknown art.

Data from a therapeutic drug monitoring service, in total 2,393 observations in 1,606 patients, were used to analyze factors associated with the prescribed daily doses of the tricyclic antidepressants amitriptyline and nortriptyline. The achieved concentrations in plasma were evaluated in relation to suggested therapeutic ranges. The doses of both drugs were greatly reduced with increasing age, despite the fact that age is of minor importance for their kinetics. Interactions with concomitantly given drugs were not handled by dose adjustments of the antidepressant. Therapeutic drug monitoring increased the proportion of concentrations within the therapeutic range for patients on amitriptyline, but not for those on nor-triptyline. The large interindividual kinetic variability for most antidepressants requires individualized dosing, but this individualization is performed on incorrect grounds.

Adolescent↗
PubMed1986

Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin.

A subgroup of 16 out of 30 endogenous depressive inpatients (cf. part I), treated for 3 weeks with 150 mg amitriptyline (AT) daily, participated in a pharmacogenetic study: all were phenotyped with debrisoquine and 3 of them with mephenytoin. Four patients were found to be poor metabolizers (PMs) of debrisoquine and one of mephenytoin. Plasma levels of AT + NT (nortriptyline) were highest in the PMs of debrisoquine, but the ratio of hydroxylated metabolites to the parent compounds appeared to be lower in these subjects. From these data, it is speculated that, in the PM of mephenytoin, the demethylation of AT is impaired. In 12 patients, free plasma 10-hydroxy-AT (ATOH) and 10-hydroxy-NT (NTOH) were found to be bound to a similar extent to plasma proteins, but not so firmly as their parent compounds, by a factor of 6 and 4 respectively. While mean total plasma ATOH reached only 15% of the value of AT, total plasma NTOH was as high as NT. ATOH correlated significantly with its parent compound, but NTOH did not correlate with NT. No drug plasma levels/clinical relationship was found in this small group of patients, even when the hydroxylated metabolites were taken into account. Both poor and extensive metabolizers of debrisoquine responded to treatment. The debrisoquine-test appears to be a useful clinical tool for detecting in patients a genetic deficiency in the hydroxylation of AT-type drugs.

Adult↗
PubMed1987

Plasma-serum differences in the assessment of tricyclic antidepressant blood levels.

Concomitant plasma and serum tricyclic determinations were performed on 20 patients chronically administered imipramine (N = 10), amitriptyline (N = 10), desipramine (N = 10), and nortriptyline (N = 10). Plasma levels for these tricyclic antidepressants were significantly greater than the corresponding serum levels. Plasma-serum differences for the secondary amines (DMI/NT) were more than twice those for the tertiary amines (IMI/AMI). The authors thus suggest that clinicians and investigators specify the specific source of blood sample when assessing blood levels of the secondary tricyclic antidepressants.

Amitriptyline↗
PubMed2001

The effect of remission of poststroke depression on activities of daily living in a double-blind randomized treatment study.

Poststroke depression has been associated with impaired recovery of activities of daily living (ADL) during the first 2 years after stroke. This study examined the effect of remission of poststroke depression on recovery in ADL in a double-blind randomized treatment study. Based on a semistructured psychiatric exam and DSM-IV diagnostic criteria, a consecutive series of 23 patients who met criteria for major depression (N = 16) or minor depression (N = 7) were selected and randomly assigned to either active treatment (nortriptyline) or placebo. Functional physical (i.e., ADL) impairment was assessed using the Johns Hopkins Functioning Inventory (JHFI). Patients whose depressive disorder remitted at follow-up had significantly greater recovery in ADL functions compared with patients whose depression did not remit. There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups, which would explain the significantly greater improvement among the remitted patients. Because both major and minor depression patients who remitted showed greater improvement in ADL than nonremitted patients some of whom were treated with active and some with placebo medication, nonpharmacotherapeutic mechanisms related to recovery from depression appear to mediate this enhanced recovery.

Activities of Daily Living↗
PubMed1997

Diagnosis, prophylaxis, and treatment of headaches in the athlete.

BACKGROUND: Headaches are a common entity in the ambulatory population. Physicians involved in sports medicine must be able to accurately diagnose headaches in athletes and whether they are exacerbated by exertion. Many medications have proven or theoretical negative effects on athletic performance. Thus, we should consider all aspects of medical management and determine which therapy is least intrusive to the athlete's performance. We planned this review because of the small number of papers available on the effects of various medications on athletic performance. METHODS: We used MEDLINE to search from 1992 to current citations, using the medical subject headings of headache, prophylaxis, treatment, review, athletes, and exercise, alone or in combination. RESULTS: Fifty-two articles were identified and deemed appropriate for inclusion in this review. CONCLUSIONS: Acute therapy for tension headaches in the athletic population is best done with nonsteroidal anti-inflammatory drugs. Prophylaxis of chronic, recurrent tension headaches is best accomplished by night-time tricyclic antidepressants (especially nortriptyline) or selective serotonin reuptake inhibitors. Acute therapy for athletes with migraines is best managed with sumatriptan or DHE 45 and prophylaxis can be accomplished with verapamil, antidepressants, or valproate. Exertional, cluster, and structural/infectious headaches are also discussed briefly.

Analgesics, Non-Narcotic↗
PubMed1982

Further considerations of the "single-point single-dose" method to estimate individual maintenance dosage requirements.

The "single-point, single-dose" method for predicting individual maintenance dosage is examined. Data available in the literature on nortriptyline is used to illustrate the method. Optimal use of the method requires knowledge of the pharmacokinetics, especially the elimination rate constant, within the patient population requiring the drug. The method is applicable to intravenous and extravascular administration, when absorption is rapid relative to elimination, for those drugs whose disposition kinetics can be described by a linear one-compartment model. As a reasonable approximation, the optimal sampling time after the single test dose is 1.5 times the population half-life. Error in chemical analysis needs to be considered when applying the method. One method of evaluating the prediction and subsequent adjustment of dosage is discussed.

Half-Life↗
PubMed1983

Liquid chromatographic separation of antidepressant drugs: I. Tricyclics.

A simple normal-phase (silica), high-performance liquid chromatographic (HPLC) assay of amitriptyline (AMI), doxepin (DOX), imipramine (IMI), nortriptyline (NORT), desmethyldoxepin (DESDOX), desipramine (DESIP), and protriptyline (PRO) in serum with no coelution is described here. Trimipramine and promazine were used as internal standards. Extraction of the 1.0-ml serum samples (collected in plastic) was done with Bond-Elut C18 columns. The compounds of interest were eluted with 10 mM methanolic ammonium acetate. The eluates were evaporated at 56-58 degrees C and reconstituted with 200 microliters of the mobile phase. The mobile phase was absolute ethanol-acetonitrile-tert-butylamine (98:2:0.05, vol/vol/vol). Detection of eluted drugs was at 254 nm at 0.01 absorbance units full scale (AUFS), except for PRO, which was detected at 229 nm at 0.02 AUFS. Absolute recoveries were 87-97%. A 5-micron silica (4.6 X 250 mm) HPLC column was used; results with a 10-micron silica column (3.9 X 300 mm) are also presented. Peak height ratios with trimipramine were linear for each analyte between 25 and 1200 ng/ml. Peak height ratios with promazine as the internal standard were linear for each analyte between 25 and 600 ng/ml. Detection limits under the conditions described were 2 ng/ml for AMI, DOX, and IMI, 4 ng/ml for NORT, DESDOX, and DESIP, and 10 ng/ml for PRO. Coefficients of within-day and day-to-day variation at three concentration levels were less than 9.8% and less than 11.2%, respectively. The hydroxylated metabolites of IMI, DES, NORT, and the cis isomer of DOX are discussed. Steady-state daily dosages and corresponding serum levels are presented for 69 patients. The total assay time was less than 10 min for DESIP and 12 min for PRO. This assay can be used in correlating serum levels with clinical effects, compliancy, and pharmacokinetic studies.

Amitriptyline↗
PubMed1984

Blood collection tubes for tricyclic antidepressant drugs: a reevaluation.

We tested clinical samples from patients receiving four commonly monitored antidepressant drugs--amitriptyline, nortriptyline, imipramine, and desipramine--to evaluate the reliability of currently available Becton-Dickinson Vacutainer brand vacuum blood collection tubes. Serum tubes (red stopper), heparinized plasma tubes (green stopper), and two types of serum separator tubes (SST) were evaluated. Antidepressant concentrations were measured by reversed-phase high-performance liquid chromatography. Antidepressant levels obtained using fresh serum (red stopper) or plasma (green stopper) yielded equivalent results. Serum collected in red-stopper tubes was stored at 4 degrees C for 4 weeks without detectable loss of antidepressant drugs. Significant concentration decreases for amitriptyline, imipramine, and desipramine were noted when serum was collected in SST tubes to such an extent that SST tubes cannot be used for the procedure. Bias attributed to SST tubes can interfere with the usefulness of clinical results over the entire therapeutic ranges of these drugs.

Amitriptyline↗
PubMed1986

Clinical pharmacological evaluation of an assay kit for intoxications with tricyclic antidepressants.

The performance of an enzyme immunoassay kit (EMIT) to diagnose intoxications with tricyclic antidepressants was compared with a high performance liquid chromatography (HPLC) technique in vitro and in vivo. The cut-off reference solution contained in the kit of nominally 1,140 nM nortriptyline varied from 1,250 to 1,600 nM. In vitro addition of antidepressants gave positive results (change in absorbance above the cut-off value) of approximately 1,100 nM for amitriptyline, imipramine, and desmethylimipramine and approximately 1,600 nM for clomipramine and desmethylclomipramine. In contrast, high concentrations of the tetracyclic antidepressant maprotiline (7,000 nM) and the bicyclic zimeldine (2,000 nM) gave negative results. False positive results were obtained with high concentrations of thioridazine (4,000 nM), chlorpromazine (300 nM), and alimemazine (trimeprazine) (5,000 nM). Of 51 patient samples, five gave readings above the cut-off value, consistent with a tricyclic antidepressant intoxication, but two of these were false positives as compared with the specific HPLC analysis. However, no false negative results were obtained with the EMIT. In conclusion, the EMIT kit is likely to detect intoxications with tricyclic antidepressants but miss intoxications with nontricyclic antidepressants. For a screening method, this is a serious drawback, since maprotiline and zimeldine together make up approximately 25% of the total of antidepressants used in Sweden. Users of the kit must also be aware that certain phenothiazines in high therapeutic doses or in intoxication cases could interfere with this test and might lead to the false diagnosis of intoxication with tricyclic antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed1988

Isomers of 10-hydroxynortriptyline in geriatric depression.

In geriatric, depressed inpatients treated with nortriptyline (NT), total unconjugated plasma concentrations of the Z isomer of the 10-hydroxylated metabolite (10-OH-NT) were determined simultaneously with concentrations of the E isomer by high-performance liquid chromatography. Z-10-OH-NT concentrations averaged 14% of E-10-OH-NT concentrations.

Aged↗