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Biomedical subjects

J Mendels

Publications and source records attributed to J Mendels.

At least 55 records · Page 3Linked to original sources

MMPI prediction of imipramine response: a replication study.

18 hospitalized male depressives were treated with imipramine hydrochloride for 28 days. Prior to initiating treatment, each patient completed the Minnesota Multiphasic Personality Inventory (MMPI). At the end of the treatment period, the patients were divided into groups of responders and nonresponders based on the change in their Hamilton Depression Rating Scale scores. The Imipramine Response Scale - Male (IRS-M) was scored for each patient and the ability of the scale to predict response or nonresponse in our sample of patients was examined. There was no evidence that the IRS-M was better than chance in its ability to predict response.

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↗

Cerebral evoked potential changes produced by treatment with lithium carbonate.

To confirm and extend previous findings concerning evoked potential (EP) changes produced by lithium carbonate (Li), 12 depressive patients were studied while on placebo and on therapeutic doses of Li. Four kinds of EPs were recorded from 14 leads: somatosensory (SEP) to left (LSEP) and right (RSEP) median nerve stimuli; visual (VEP) to a checkerboard flash; auditory (AEP) to binaural click. Plasma and erythrocyte (RBC) Li levels and Hamilton Depression ratings were obtained. Li produced a number of amplitude changes in EPs of all sensory modalities, while there were few latency changes; in general, amplitudes of positive components were increased, while negative component amplitudes were reduced. The spatial distributions of EP peaks were mainly unaltered by Li. The amount of EP amplitude change with Li tended to be correlated with plasma and RBC Li levels. No convincing correlations were found between alterations in EPs and depression ratings. The nature of the EP changes with Li was generally not concordant with normalization of the deviant EP characteristics found in depressives. The findings indicate that Li produces more widespread CNS changes than suggested by previous reports; it appears that these tend to be related to Li levels, but not to the therapeutic effects of Li.

Adult↗

Biological component of the NIMH clinical research branch collaborative program on the psychobiology of depression: I. Background and theoretical considerations.

There are many reports which suggest that patients with effective illness (mania and/or depression) have abnormalities in the functioning of one or more neurobiological systems. At a conference convened by the Clinical Research Branch, Division of Extramural Research Programs, National Institute of Mental Health, these findings were reviewed and some of the factors impeding movement towards a more complete and integrated view of the functioning of neurobiological systems in patients with mania or depression were identified. As a result, a multi-research centre, collaborative approach to the study of the psychobiology of affective disorders was developed. In this collaborative programme, which has now been underway for several years, the focus has been upon: (a) the assessment of the functioning of several different types of biological systems in the same patient, both before and during treatment; (b) obtaining a reasonably large number of patients and comparison subjects; and (c) the use within and across centres of standardized diagnostic categories and behavioural rating methodologies. In this paper the history, background, and rationale for this collaborative effort are reviewed. Those biological systems chosen for study are noted, and issues such as reliability and validity of diagnoses, measurement of state variables, assessment of change with treatment, and logistical and coordinating problems are discussed.

Affective Disorders, Psychotic↗

Influence of phenytoin and phenobarbital on the disposition of a single oral dose of clonazepam.

Clonazepam (CZP) was measured in the plasma of eight subjects for 48 hr after a 0.03-mg/kg oral dose. After pretreatment for 19 days with phenytoin (DPH, 4.3 mg/kg/day), plasma CZP concentrations were determined in the same subjects after another 0.03 mg/kg oral dose of CZP. The same protocol was followed in eight additional subjects using phenobarbital (PB, 1.4 mg/kg/day) instead of DPH. DPH pretreatment lowered mean plasma CZP concentration in 8 of the 12 time points. DPH pretreatment increased CZP clearance by 46% to 58% and decreased CZP half-life (t1/2) by 31%. Both changes were statistically significant. After PB pretreatment the mean plasma CZP concentration was lowered by an average of 11%, but the decrease was statistically significant for only 1 of the 12 time points. PB decreased mean CZP t1/2 by 11% and increased CZP clearance by 19% to 24%, but only the increase in clearance was statistically significant. Both DPH and PB increased CZP clearances and decreased the areas under the plasma concentration-time curves without altering the volumes of distribution. This observation is consistent with induction of CZP metabolism. The overall effect of DPH (4.3 mg/kg/day) was greater than the effect of PB (1.4 mg/kg/day). Neither the DPH or PB had a significant effect on the extent of CZP protein binding.

Adult↗

Toward a rational pharmacotherapy of depression.

The authors review several approaches that show promise for predicting which antidepressant medication will be best for a particular patient and for achieving maximum benefit from each drug. These include delineation of clinical and historical characteristics associated with response to various drugs, use of psychological tests, assessment of biochemical and electroencephalographic parameters, evaluation of mood response to amphetamine, determination of acetylator status, and measurement of plasma tricyclic levels and degree of inhibition of platelet monoamine oxidase. The authors believe that the use of these approaches may improve our ability to help depressed patients.

Antidepressive Agents, Tricyclic↗

The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels.

The authors present a clinical approach for predicting and using plasma concentrations of tricyclic antidepressants in the treatment of depressed patients. They review the pharmacokinetics of this group of drugs and their side effects and toxicity. There is a suggested therapeutic range for plasma concentrations of imipramine, amitriptyline, and nortriptyline; more definitive studies are needed to determine the necessary plasma levels for achieving clinical response with the other tricyclic antidepressants (desmethylimipramine, protriptyline, doxepin, clomipramine, impiramine N-oxide, and butriptyline). A more thorough knowledge of the clinical pharmacokinetics of tricyclic antidepressants should lead to more rational use of these drugs, with a higher response rate and fewer adverse reactions.

Amitriptyline↗

Primary affective disorder in relatives of patients with anorexia nervosa.

The authors examined the incidence of primary affective disorder (PAD) in relatives of 25 patients with anorexia nervosa and of 25 normal control subjects. Among the relatives of patients with anorexia nervosa, 22% (N = 43) had histories of PAD, while only 10% (N = 17) of the relatives of controls had such histories. Among the PAD relatives of anorectic probands, 34 had histories of unipolar depression and 9 of bipolar affective disorder. These findings provide further evidence of a possible relationship between anorexia nervosa and affective illness.

Anorexia Nervosa↗

Monoamine oxidase inhibitors and serotonin uptake inhibitors: differential effects on [3H]serotonin binding sites in rat brain.

Rats were administered either monoamine oxidase inhibitors or serotonin uptake inhibitors for either 1, 4 or 16 days. The binding of [3H]serotonin to brain homogenates and the concentration of serotonin in brain was measured at these times. Treatment with inhibitors of serotonin uptake did not change the specific binding of [3H]serotonin in either cerebral cortex or hippocampus, nor did it produce any consistent alterations in the concentration of serotonin in the cerebral cortex. In contrast, monoamine oxidase inhibitors capable of inhibiting A-type monoamine oxidase significantly decreased [3H]serotonin binding after both 4 and 16 days of treatment; serotonin concentrations were significantly elevated at all time intervals. Inhibitors of B-type monoamine oxidase had no effect on either [3H]serotonin binding or serotonin concentrations in cerebral cortex. The reduction in labeled serotonin binding caused by monoamine oxidase inhibitors is due to a decrease in the maximum number of specific binding sites with no change in the affinity of the binding sites for labeled serotonin.

Amitriptyline↗

Withdrawal symptoms during the course of imipramine therapy.

The authors describe 2 cases in which withdrawal symptoms occurred during the course of imipramine therapy, after the patients had failed to take a single daily dose of medication. They note that similar withdrawal symptoms have been noted upon discontinuation of imipramine and its derivatives desipramine and chlorimipramine, but have not--with one exception--been reported in association with other tricyclics.

Adult↗

Reliability of commercially available tricyclic antidepressant levels.

Recent studies show that there may be a relationship between plasma levels of tricyclic antidepressants and clinical response. A number of commercial laboratories have introduced methods for measuring these drugs in plasma for clinical practice, and each recommends a particular method by which plasma samples should be drawn, processed, and stored. In this pilot study we compare results from 4 laboratories, using identical plasma samples containing amitriptyline and nortriptyline, in order to assess interlaboratory reliability. While there is generally good agreement between our results and those of the commercial facilities, some large interlaboratory discrepancies are evident. Caution is advised when utilizing plasma tricyclic levels to monitor patient progress, and we suggest using a laboratory which is well established in this area.

Amitriptyline↗