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Biomedical subjects

J T Biggs

Publications and source records attributed to J T Biggs.

At least 73 records · Page 4Linked to original sources
PubMed1977

A comparison study of amitriptyline and nortriptyline with plasma levels.

Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptyline-treated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = -0.54, P less than .025) and positive in the nortriptyline-treated patients (r = -0.49, P less than .05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P less than .001), Zung Score (P less than .01), and percent recovered (P less than .001), than those above or below the therapeutic range.

Administration, Oral↗
PubMed1977

Sampling time, dosage schedule, and nortriptyline plasma levels.

Steady-state nortriptyline plasma levels were determined in eight patients at 9 AM, 12 PM, 3 PM, and 6 PM during treatment with nortriptyline hydrochloride administered as a single daily bedtime (hs) dose at 10 PM and repeated after changing the dosage schedule to three times a day (tid) with divided doses at 10 AM, 4 PM, and 10 PM. Overall, the mean levels were stable during the sampling period and comparable on the two schedules. As expected, the plasma level decreased at the later sampling times on the hs schedule and increased on the tid schedule. In seven of the eight patients, the differences on the two dosage schedules were less than 30 ng/ml, which is not considered clinically significant. One patient had a higher plasma nortriptyline level on the tid schedule, which was clinically significant. Standardization of sampling time is of importance when comparing plasma levels and therapeutic response in treatment studies.

Depression↗
PubMed1977

Tricyclic antidepressant plasma levels and adverse effects after overdose.

Forty patients ingesting tricyclic antidepressant (TAD) overdoses were studied as a pharmacologic model to determine whether total tricyclic antidepressant plasma levels correlated with major adverse effects and electrocardiographic findings. Maximum TAD plasma levels were higher in patients who died (p less than 0.025) or had cardiac arrest (p less than 0.02), needed respiratory support (p less than 0.005), were unconscious (p less than 0.02), had grand mal seizures (p less than 0.001), ventricular rate larger than or equal to 120/min (p less than 0.01), cardiac arrhythmia (p less than 0.05), QRS duration larger than or equal to 100 msec (p less than 0.001), or bundle branch block (p less than 0.05). TAD plasma levels correlated with the dose ingested by history (N = 29, r = 0.58, p less than 0.001). Measurement of total TAD (free and protein-bound) appears to correlate well with biologic response.

Antidepressive Agents, Tricyclic↗
PubMed1977

Protriptyline plasma levels and antidepressant response.

Twenty-one depressed outpatients were treated for 4 wk with 20 mg/day of protriptyline. Protriptyline plasma in individuals after 4 wk ranged from 22 ng/ml to 167 ng/ml. There was a negative correlation (-0.50, less than 0.05) between the severity of depression measured by the Hamilton Rating Scale (HRS) and the wk 4 protriptyline concentration. Patients with plasma levels above 70 ng/ml (wk 4) had better outcomes measured by the HRS (p less than 0.05) and the Zung Self-Rating Depression Scale (p less than 0.05) and had greater percent decreases on both scales (p less than 0.05) during treatment than those with lower plasma levels. An upper limit to the therapeutic plasma level range beyond which response to treatment was less satisfactory was not demonstrated in this study.

Adult↗
PubMed1977

Validity of the Hamilton Rating Scale for depression.

In 26 depressed patients, a high correlation (0-89) was found between the Hamilton score and a psychiatrist's global rating and between the change (0-68) in these ratings during treatment. The Hamilton scale was able to differentiate at the o-01 level four degrees of severity based on the global rating. Limiting the range of severity measured was found to lower significantly the correlation between the ratings. A prospective examination of a six-item sub-scale of the Hamilton scale developed by Beck and associates failed to confirm its claimed improvement in sensitivity or validity.

Depression↗
PubMed1977

Tricyclic antidepressant overdoses in adolescent patients.

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.

Adolescent↗
PubMed1977

Electrocardiographic findings in patients undergoing amitriptyline treatment.

Fifteen depressed patients were treated with amitriptyline in a dosage ranging from 75 mg to 200 mg/day for a minimum of three weeks, two of which were at a fixed dosage. Plasma samples were drawn 12 to 16 hours after the bedtime dose of medication for determination of amitriptyline and its metabolite nortriptyline. Electrocardiograms were taken prior to treatment and after three weeks of drug treatment. The only abnormality noted prior to treatment was bradycardia in one patient. After treatment, two patients exhibited nonspecific T-wave abnormalities. Otherwise, the electrocardiograms were unremarkable. A significant increase in heart rate (p less than 0.001) was noted. The mean increase in rate was sixteen beats per minute. Those patients having a rate change greater than sixteen beats per minute had significantly higher amitriptyline levels (p less than 0.05), and total tricyclic antidepressant levels (p less than 0.05), than those patients having a mean rate increase less than sixteen. While tricyclic antidepressants can produce multiple cardiac effects, the risk of cardiac morbidity and mortality is relatively low in patients undergoing tricyclic antidepressant treatment with moderate dosages.

Adolescent↗
PubMed1976

Tricyclic antidepressants. Prolonged plasma levels after overdose.

Twenty-four patients hospitalized for overdose of a tricyclic antidepressant were monitored clinically, and serial plasma-drug measurements were taken for up to 144 hours. Six of 24 patients had maximum antidepressant plasma levels greater than or equal to 1,000 ng/ml, and their plasma levels at 96 hours ranged from 170 to 1,280 ng/ml. Patients ingesting substantial tricyclic overdoses may remain medically unstable for days. When high tricyclic levels persist, accurate psychiatric assessment is often impossible.

Amitriptyline↗
PubMed1976

Amitriptyline plasma levels and therapeutic response.

Eighteen depressed outpatients were treated for 6 wk with amitriptyline. Clinical improvement was monitored using the Hamilton Depression Rating Scale administered by two psychiatrists blind to the tricyclic used for treatment, dosage, and plasma levels. Amitriptyline and its desmethyl metabolite, notriptyline, were assayed twice weekly by gas chromatography-mass fragmentography. For the 17 patients having total tricyclic plasma levels between 0 and 250 ng/ml, there was a negative correlation between the Hamilton score and the mean total tricyclic level (p less than 0.01) and amitriptyline level (p less than 0.005). The mean nortriptyline level did not significantly correlate with the Hamilton score. The 10 patients having mean total tricyclic levels above 95 ng/ml had lower median Hamilton scores at week 3 (p less than 0.025) and at week 6 (p less than 0.0025) than those whose tricyclics were lower. The percentage of recovered patients increases significantly as the plasma levels rise to 250 ng/ml, the maximum plasma level considered in this study.

Adolescent↗
PubMed1976

Nortriptyline plasma levels and therapeutic response.

Eighteen depressed outpatients were treated for 6 wk with a mean daily dose of 121 mg of nortriptyline. The mean plasma level was 138 ng/ml during treatment. Therapeutic response was monitored by the Zung Self-Rating Depression Scale and the Hamilton Depression Scale administrered by two psychiatrists blind to the tricyclic used, dose, and plasma levels. Eight patients recovered (Hamilton less than or equal to 6) by the fourth week and 12 by the sixth week. During the steady-state (wk 4 to 6) there was a positive correlation between the weekly Hamilton scores and the weekly nortriptyline levels (p less than 0.01). The 9 patients with mean plasma levels between 50 and 139 ng/ml had a better therapeutic response after 6 wk measured by percent recovered (p less than 0.005). Zung score (p less than 0.05), and Hamilton score (p less than 0.025) than the 9 patients with mean plasma levels between 140 and 260 ng/ml.

Adult↗
PubMed1976

Electron beam ionization mass fragmentographic analysis of tricyclic antidepressants in human plasma.

A method for the measurement, in human plasma, of all tertiary and secondary tricyclic antidepressants prescribed in the United States is described. The method uses electron beam ionization GLC-mass spectrometry, employing a computer-controlled multiple-ion detector. This method, mass fragmentography, is used with internal standards for each drug. Plasma levels to as low as 10 ng/ml of the following drugs can be measured: amitriptyline, nortriptyline, doxepin, desmethyldoxepin, imipramine, desipramine, and protriptyline. Deuterium-labeled amitriptyline and imipramine are used as internal standards for those two drugs; for the other drugs, deuterated amitriptyline, nortriptyline, desmethyldoxepin, or desipramine is used. The method can measure up to 15 samples/hr, making it practical for large-scale studies of these drugs in patients. Spectra of each drug and examples of their analysis are given.

Adult↗
PubMed1976

Measurement of tricyclic antidepressant levels in an outpatient clinic.

Although definitive studies regarding the correlation between tricyclic antidepressant plasma levels and therapeutic effect are lacking, preliminary data suggest that measurement of tricyclic antidepressant plasma levels provides a rational approach to improve clinical management of the depressed patient. Data were collected to determine if the routine measurement of plasma tricyclic antidepressant levels was practical in a large clinic population, and to determine if such levels could improve patient care. Individual differences in drug metabolism and frequent unreliable ingestion of medication make the measurement of drug plasma levels the only sure means of determining if a patient is receiving a fair therapeutic trial on a particular tricyclic antidepressant. Plasma analysis revealed both the failure to ingest adequate amounts of medication as prescribed and also the abuse of medications. Although generalizations regarding individual variation in drug metabolism or generalizations concerning drug compliance do little to improve patient care, whenever such problems are met on an individual basis, many clinical management problems can be resolved.

Adult↗
PubMed1976

Psychiatric diagnosis and tricyclic plasma levels in 36 hospitalized overdose patients.

Thirty-six hospitalized patients who were considered by emergency room physicians to have ingested medically serious tricyclic overdoses were studied. The purpose of the project was to determine if psychiatric diagnosis and associated psychiatric factors correlated with the severity of the overdose as defined by plasma drug levels. Medically serious overdoses were ingested by patients with alcoholism, primary affective disorder, undiagnosed psychiatric illness, and Briquet's syndrome. Prior psychiatric treatment, prior admissions, prior overdoses, or precipitating events did not correlate with the medical severity of the ingestion. Attempting to predict the individual medical severity of the overdose from psychiatric factors resulted in a dangerous underestimation of the risk of patients with Briquet's syndrome and an overprediction in the case of primary affective disorder.

Adjustment Disorders↗