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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

Sociodemographic and prior clinical course characteristics associated with treatment response in depressed patients.

A sociodemographic and clinical picture is presented of 82 depressed subjects who had an unequivocal response or lack of response to treatment with amitriptyline or imipramine. Patients with less severe depressive illness were found more likely to respond to treatment, while those with psychotic features were more likely to be treatment resistant. Sociodemographic and other prior and current clinical course variables were not predictive of treatment response in depressed patients.

Adult

Efficacy without tolerance or rebound insomnia for midazolam and temazepam after use for one to three months.

Midazolam (15 mg) was compared with temazepam (30 mg) in a randomized, double-blind, parallel group study. An initial screening period was followed by 3 days of placebo baseline, 4 to 12 weeks of nightly oral use of the medication and a 4-day placebo withdrawal period. One hundred seventy-five patients with chronic insomnia participated in this multicenter outpatient study. Because the elimination half-life of midazolam, a new trizolobenzodiazepine hypnotic, is short (1.3-2.2 hr) compared to temazepam's (12-16 hr), more problems with tolerance and rebound insomnia were expected to occur. Hypnotic efficacy (increased total sleep time, decreased wake time, and decreased sleep latency) was demonstrated for both medications over the entire 3-month period without the development of tolerance. In fact, if anything, efficacy increased with time on medication, suggesting possible facilitation or "inverse tolerance" effect. On withdrawal, sleep was improved compared with baseline, suggesting partial resolution of the insomniac condition rather than rebound insomnia. These effects were both statistically and clinically significant for midazolam, with 16% to 50% improvement in sleep measures. The results of this study suggest that patients with chronic insomnia may benefit from 30 to 90 days of treatment. A three-factor model that separates pharmacologic from behavioral and psychologic effects of hypnotics was proposed to explain these results in part.

Adolescent

Efficacy and safety of fezolamine in depressed patients.

Forty-two outpatients with major depressive disorder were treated with oral fezolamine in a 6-week, three-center open-label study. Therapy was initiated at 100 mg/day; thereafter dosage was increased based on the response of the patient. Maintenance dosage usually ranged between 100 and 450 mg/day. Clinically significant improvement relative to the patient's prestudy state was observed after 2 weeks in both patient and physician-rating scales. Fifty-five percent of patients improved their Hamilton Psychiatric Rating Scale for Depression (HAM-D) scores by more than 50%. The median dose associated with a clinically significant response was 245 mg/day. Five of the 6 patients who dropped out did so because of gastrointestinal adverse effects. The most common adverse effects were nausea (36%), headache (29%), constipation (26%), and dry mouth (24%).

Adult

Clinical experience with serotonin reuptake inhibiting antidepressants.

The development of a new class of antidepressants that have in common their ability to inhibit the reuptake of serotonin at neuronal synapses is reviewed. There is accumulating evidence that this class of medications constitutes an advance in the management of depression; these drugs appear to be effective antidepressants with a possibly lower and more acceptable incidence of adverse reactions than the tricyclic compounds. Further exploration of these potential advantages and of the usefulness of this group of compounds for other clinical syndromes is justified.

Citalopram

Comparative efficacy of alprazolam, imipramine, and placebo administered once a day in treating depressed patients.

Ninety-eight outpatients with major depressive disorder were treated with alprazolam, imipramine, or placebo in a 6-week, double-blind study. Average doses were 3.67 mg of alprazolam and 167 mg of imipramine, given at bedtime. Fifty percent of patients taking alprazolam, 38.2% taking imipramine, and 17.7% receiving placebo improved their HAM-D scores by more than 50%. Eight patients on imipramine, 6 on alprazolam, and 1 on placebo dropped out because of side effects. The most common side effects for imipramine were tachycardia, constipation, light-headedness, and sedation; common side effects of alprazolam were light-headedness, sedation, and unsteadiness.

Adolescent

Alprazolam as an adjunct to propranolol in anxious outpatients with stable angina pectoris.

A double-blind crossover comparison is reported of the effects of alprazolam and placebo on anxiety and angina in 27 ambulatory outpatients with angina pectoris stabilized on propranolol. Alprazolam was shown to be a safe treatment when combined with propranolol in these patients. Patients receiving alprazolam with propranolol reported more improvement on their targeted symptoms than did patients receiving placebo with propranolol. The side effect most often reported was moderate drowsiness or sedation; no unusual side effects emerged. There was no evidence that alprazolam compromised the patients' response to propranolol.

Adult

Effective short-term treatment of generalized anxiety disorder with trifluoperazine.

The effectiveness of trifluoperazine in daily doses of 2 to 6 mg in the short-term treatment of generalized anxiety disorder was evaluated in 415 outpatients in a double-blind, placebo-controlled, multicenter trial. Efficacy and side effects were assessed by a number of psychiatric rating scales for anxiety. All efficacy measurements of anxiety were significantly improved (p less than .001) with trifluoperazine compared to placebo by the end of the study. The side effects profile of trifluoperazine and placebo were similar during the 4-week treatment period.

Administration, Oral

Halazepam in the management of acute alcohol withdrawal syndrome.

Eighty patients admitted to a specialized alcohol detoxification unit, who had blood alcohol levels of .15% or less and were not currently intoxicated, participated in a double-blind trial involving treatment with either halazepam or chlordiazepoxide. A flexible dosage schedule was followed for 5 days with the objective of using the largest dose on the first day, followed by daily reductions as clinically feasible. Efficacy evaluations indicated that halazepam was as effective as chlordiazepoxide in the control of symptoms in patients hospitalized for the medical management of acute alcohol withdrawal. No significant side effects were noted.

Acute Disease

Evaluation of the short-term treatment of insomnia in out-patients with 15 milligrams of quazepam.

The short-term safety and hypnotic efficacy of 15 mg of quazepam was compared with that of placebo in a double-blind study in sixty out-patients with insomnia. All patients received placebo for 3 consecutive night to establish a baseline; for the next 5 nights thirty patients received quazepam and thirty received placebo. The results indicated that quazepam was significantly more effective than placebo in terms of quantity and quality of sleep and that quazepam was effective on the first night. Despite having a marked hypnotic effect, quazepam was not different from placebo in terms of hand-over effects (i.e., ease in awakening and alertness) the following morning. Treatment-related adverse experiences were reported by ten patients who received quazepam and by five who received only placebo. The most frequently reported adverse experience was daytime somnolence. This study demonstrates that quazepam, in a 15 mg dose, is an effective, rapidly acting, oral hypnotic agent with a low incidence of adverse effects.

Adult

Drug combinations in the treatment of refractory depression: a review.

The authors critically review several drug combinations that may be of promise in the management of depressions that do not respond to treatment with a single drug. These include the use of tricyclic antidepressants with monoamine oxidase inhibitors (MAOI's), L-triiodothyronine (T3), methylphenidate, lithium carbonate, L-tryptophan, reserpine, and neuroleptics; MAOI's with lithium and L-tryptophan; and L-tryptophan with allopurinol. The authors stress the need for further double-blind, controlled studies to evaluate the safety and efficacy of these combinations.

Allopurinol