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Biomedical subjects

J Mendels

Publications and source records attributed to J Mendels.

At least 19 recordsLinked to original sources

The acute and long-term treatment of major depression.

Millions of depressed patients do not receive appropriate treatment in spite of the substantial increase in our knowledge about this major medical problem. In addition to individual suffering, there are tens of thousands of deaths by suicide, an increase in morbidity and mortality from medical illnesses whose course is aggravated by an associated depression, a disruptive effect on family life and childrearing, and an economic loss of billions of dollars. Among the many reasons for the inadequate treatment of depression is the fact that the side effects (anticholinergic, antihistaminic, etc.) of traditional antidepressants result in many patients receiving inadequate doses of medication or discontinuing treatment prematurely. The availability of a new class of antidepressant medications--the selective serotonin reuptake inhibitors (SSRIs)--heralds a new phase in the treatment of depression. Although these drugs are not free of side effects, an increased number of depressed patients now seem able to receive adequate doses of medication and to stay on treatment much longer than in the past. The increased acceptance of SSRIs by patients represents an important phase in our ability to effectively treat larger numbers of patients and to prevent relapse in many of them.

1-Naphthylamine

Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type.

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients.

Acetamides

A comparison of paroxetine, imipramine and placebo in depressed out-patients.

To compare the safety and antidepressant efficacy of paroxetine, imipramine, and placebo, data from six centres using the same protocol were pooled. A double-blind parallel-group design was used, with therapy lasting six weeks. From week 2 onwards, both the 240 paroxetine-treated and the 237 imipramine-treated patients were significantly different from the 240 placebo-treated patients, but no different from each other. Side-effects with paroxetine were less likely to lead to drop-out than with imipramine. Paroxetine had a possible earlier antidepressant effect than imipramine, and a possible earlier beneficial effect on anxiety symptoms associated with depression.

Adult

Criteria for selection of appropriate benzodiazepine hypnotic therapy.

The several benzodiazepine hypnotics currently marketed differ in onset and duration of action and in side effect profile. These differences are largely based on the varying pharmacodynamic properties of these agents. The selection of a drug for treating an individual patient should be based on consideration of these pharmacologic differences, as well as assessment of the sleep-wake disorder. The initial objective for the clinician who intends to manage a patient with insomnia is to determine which factors are contributing to the sleep disturbance and to decide on a treatment strategy. If medication is to be used, then the physician should select the most effective and safest hypnotic, prescribe it at the lowest effective dose and for the fewest number of nights. Individual patient response to the chosen medication should be monitored.

Anti-Anxiety Agents

The effectiveness of labetalol compared to hydrochlorothiazide in hypertensive black patients.

Labetalol and hydrochlorothiazide (HCTZ) were compared for their efficacy in controlling hypertension of blacks in a prospective, double-blind study. Sixty-one adult patients with mild to moderate hypertension (standing diastolic blood pressure greater than or equal to 95 mm Hg and less than or equal to 114 mm Hg) were randomly selected to receive either labetalol 100 mg twice daily (n = 30) or HCTZ 25 mg twice daily (n = 31). The study was divided into two phases: a 4-week placebo run-in phase, during which all previous antihypertensive medication was discontinued, and a 12-week drug treatment phase. Labetalol and HCTZ doses were titrated to 400 mg twice and 50 mg twice daily, respectively, during the first 6 weeks of the drug treatment phase for those patients not achieving blood pressure control (standing diastolic blood pressure less than 90 mm Hg and a decrease of 10 mm Hg from baseline) on initial dosages. By the end of the 12 weeks of drug administration, patients on labetalol experienced a mean decrease of 10 mm Hg in standing diastolic blood pressure compared to a mean decrease of 10.1 mm Hg in patients on HCTZ. No differences were observed between the two treatment groups in reductions of either standing blood pressure or heart rate. While 19 of 30 patients on labetalol (63%) achieved blood pressure control at some point during the study with a mean daily dose of 568 mg, 18 of 31 (58%) HCTZ-treated patients achieved control with a mean daily dose of 72 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People

Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.

A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo.

1-Naphthylamine

Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients.

Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Naphthylamine

The erythrocyte lithium-plasma lithium ratio in patients with primary affective disorder.

Increasing attention has been given to the significance of intra-cellular concentrations of the lithium ion in patients treated with this drug. The erythrocyte has been the most common cell investigated because of its accessibility and certain similarities between the ion transport mechanisms of this cell and the neuron. Intraerythrocyte lithium is expressed as the ratio of lithium in the cell to the plasma lithium concentration (lithium ratio). The lithium ratio has been reported to be related to a number of clinical variables, including treatment response, clinical state, side-effects, toxicity, diagnosis, and electrophysiological effects. We have investigated the lithium ratio in a large series of patients with a primary affective disorder and in a smaller control group. We found a significantly higher mean lithium ratio in the bipolar diagnostic group than in the unipolar and control groups. There was a trend, not statistically significant, in the unipolar and bipolar groups for females to have higher lithium ratios than males. While not diagnostic, the lithium ratio appears to be another biological variable where bipolar patients, as a group, differ from normals and others with an affective disorder.

Bipolar Disorder

Prediction of steady-state imipramine and desmethylimipramine plasma concentrations from single-dose data.

Tricyclic antidepressant plasma levels were measured in patients and healthy subjects after a single dise of desmethylimipramine (DMI) or imipramine (IMI) and after chronic dosing to steady states. Tricyclic plasma levels measured 24 hr after the single oral dose correlated with steady-state plasma levels. In patients receiving DMI there was a correlation (r = 0.97, n = 10) between 24-hr and steady-state DMI levels, while in normal subjects receiving IMI the correlation was r = 0.92 (n = 20) between 24-hr and steady-state total tricyclic levels (IMI plus its metabolite, DMI). These results suggest the possibility that after a test dose of tricyclic antidepressant, a patient may be put on a "therapeutic" dosage regimen without delay.

Depression

Specific radioimmunoassay of amitriptyline and nortriptyline.

1 Antisera to nortriptyline were prepared by immunizing rabbits with N-succinylnortriptyline--bovine serum albumin conjugate. 2 A sensitive radioimmunoassay has been developed for the tricyclic antidepressants amitriptyline and nortriptyline. 3 amitriptyline and nortriptyline are separated from each other and from interfering metabolites before assay. 4 Using [3H]-imipramine and [3H]-succinylnortriptyline as tracers the radioimmunoassay can measure amitriptyline and nortriptyline levels down to 2--3 ng/ml using 0.05 ml plasma sample. 5 Agreement between the radioimmunoassay and a gas-chromatographic assay was excellent for both amitriptyline and nortriptyline.

Amitriptyline

Plasma and erythrocyte cations in affective illness.

Plasma and erythrocyte cations (sodium and magnesium) were studied in groups of patients with an affective disorder and in normal subjects. Baseline determinations were obtained before initiation of treatment for mania or depression. In a subgroup of patients, sequential measurements of cations were made during treatment with lithium carbonate. No differences were found in intraerythrocyte sodium or magnesium among any of the patient groups and controls. Patients with a primary affective disorder had significantly higher plasma sodium than control subjects. Neither baseline cation concentrations nor changes in cation concentration during treatment with lithium correlated with treatment response. Gender was shown to be a significant variable affecting intraerythrocyte cation concentrations.

Bipolar Disorder