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Biomedical subjects

J S Carman

Publications and source records attributed to J S Carman.

15 recordsLinked to original sources

A controlled study of mianserin in moderately to severely depressed outpatients.

Following a 1-week, single-blind placebo washout, 150 patients were randomized to double-blind treatment with daily doses of either mianserin, 30 mg to 150 mg; amitriptyline, 60 mg to 300 mg; or placebo, 1 to 5 capsules taken at bedtime (qhs). Mianserin and amitriptyline were found to be comparable in efficacy, and both significantly more effective than placebo in the treatment of major depressive illness. Rating instruments, all of which showed significant improvement in the active drug groups over the placebo, included the 17- and 21-item Hamilton Rating Scale for Depression (HAM-D), Montgomery and Asberg Depression Rating Scale (MADRS), Self-rating Depression Scale (SDS) index, and the Clinical Global Impressions (CGI) Severity of Illness and Improvement rating scales. Furthermore, for most efficacy parameters in the efficacy-evaluable group, the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients. The safety profile for mianserin was comparable with placebo with respect to laboratory values, electrocardiogram changes, vital signs, ophthalmologic evaluations, and most adverse clinical experiences. Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups. Mianserin was superior to amitriptyline in terms of vital signs; anticholinergic effects; and complaints of dizziness, dyspepsia, and tremor.

Adult

A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients.

Two hundred twenty-four outpatients with major depression entered a 6-week, five-center, double-blind trial of bupropion 300 mg/day and placebo. A total of 216 patients were included in the efficacy analysis. In the combined center analysis, greater efficacy for bupropion was found on one or more measures (Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions) at treatment Days 21, 28, 35, and 42. Bupropion was well tolerated; only four adverse events were reported at least 5% more often in the bupropion group than in the placebo group. Six bupropion patients versus 5 placebo patients discontinued treatment because of adverse events. This study extends earlier findings of efficacy for higher-dose treatment in an inpatient population to lower-dose treatment in an outpatient population.

Adult

Use of calcitonin in psychotic agitation or mania.

Synthetic salmon calcitonin was administered subcutaneously to 12 inpatients with several primary psychotic diagnoses. Increases in serum total calcium and inorganic phosphorus levels and decreases in CSF calcium level had earlier been observed during periodic psychotic agitation or mania. By contrast, calcitonin, which decreased serum calcium and phosphorus levels and increased CSF calcium level, appeared to produce transient (24-hour) increases in depression and decreases in arousal in this double-blind placebo-controlled trial. Quantitative activity monitoring confirmed the rater's impression that this agent had tranquilizing or depressant effects in such patients. When given in the evening, this polypeptide also appeared to delay sleep onset, as demonstrated both by nurses' 30-minute sleep checks and by the same longitudinal activity record. A decreased hypocalcemic response to calcitonin was noted in the agitated patients, which might explain the increases in serum calcium level described at the "switch".

Adult

Calcium: pacesetting the periodic psychoses.

In this double-blind study dihydrotachysterol (DHT) was given orally to eight psychotic patients; in each case marked increases in psychosis and agitation accompanied increases in serum calcium and phosphorus within two weeks after active drug was substituted for placebo. In the three patients whose psychoses exhibited periodic spontaneous exacerbations, the agitated episodes grew more severe. Serum creatine phosphokinase (CPK) increased in all but one patient. By contrast, when three periodically psychotic patients received synthetic salmon calcitonin (SCT), the severity and frequency of agitated episodes decreased while CSF calcium increased in all three. These data support the hypothesis that the observed abrupt increases in serum calcium and phosphorus might cause the opposite CSF calcium shifts, the behavioral agitation and the increases in serum CPK frequently noted during acute psychosis.

Adult

Increased serum calcium and phosphorus with the 'switch' into manic or excited psychotic state.

Small but statistically significant increases in serum total calcium and serum inorganic phosphorus concided with repeated onsets of psychotic agitation or mania in nine psychotic in-patients experiencing rapid cycles of illness. These increases were not accompanied by changes in magnesium or other constituents, which might suggest non-specific haemoconcentration. Similar increases in calcium or phosphorus were not present in patients without the same cycles of psychotic illness. The observed increases could neither be simulated nor altered by stress or activity, and it remains unclear whether they might be accounted for by dietary changes, sleep disruption, circadian phase shifts or by endocrine alterations.

Adult

CSF calcium: clinical correlates in affective illness and schizophrenia.

In a study of electrolytes in lumbar cerebrospinal fluid (csf) from psychiatric patients, the authors found a positive correlation between calcium concentration and symptom severity in hospitalized depressed patients. CSF calcium levels tended to decrease as patients improved. In four rapidly cycling patients, CSF calcium was higher during depression than during mania. Mean CSF calcium for the depressed patients as a group was not significantly different from neurological controls or other psychiatric patients. Symptom remission from acute psychosis in schizophrenic patients was accompanied by a significant increase in CSF calcium concentration. These findings are discussed in relationship to calcium-induced alterations in neuronal and physiological excitability.

Bipolar Disorder

Calcium: bivalent cation in the bivalent psychoses.

Decreases in cerebrospinal fluid (CSF) calcium accompany mood elevation and motor activation in depressed patients undergoing treatment with ECT, lithium, and total sleep deprivation. Similarly, decreases in CSF calcium occur during acute psychotic agitation or mania. On the other hand, periodic recurrences of such agitated states are accompanied at their onset by transient increases in serum calcium and phosphorus. Several observations suggest that such serum ion shifts may trigger the more enduring and opposite shifts in CSF calcium and, in turn, the manic behavior. Progressive restriction of dietary calcium was earlier reported to mitigate and finally abolish both rhythmic rises in serum calcium and periodic agitated episodes in one psychotic patient. Lithium, which decreases the efficiency of alimentary calcium absorption, may function similarly. Conversely, a modest oral calcium lactate supplement (approximately one additional Recommended Daily Allowance of dietary calcium) seemed to slightly intensify agitation in six patients. Dihydrotachysterol (DHT), an analogue of vitamin D, which more exactly mimics the increase in both serum calcium and phosphorus, appeared in at least one periodically psychotic patient to trigger and opposite shift in CSF calcium. Moreover, in eight patients, manic symptomatology appeared de novo or grew significantly and substantially worse during 2 to 6 weeks of oral DHT administration. On the other hand, in 12 patients, subcutaneous injections of synthetic salmon calcitonin (SCT) decreased serum calcium and phosphorus, increased CSF calcium, and decreased agitation while augmenting depressive symptomatology. SCT also decreased quantified motor activity, frequency and severity of periodic agitated episodes, serum CPK and prolactin, and nocturnal sleep, while DHT or calcium lactate had opposite effects on the same parameters.

Animals

Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response.

Piribedil, a compound that stimulates dopamine receptors in a relatively specific fashion, was administered to 11 hospitalized depressed patients. The dopamine agonist significantly decreased rapid eye movement (REM) sleep and percent REM sleep and increased REM latency. Piribedil decreased the probenecid-induced accumulation of the dopamine metabolite homovanillic acid (HVA) in CSF. A range of mild to moderate antidepressant effects was noted; one patient worsened and one developed recurrent manic episodes. The degree of improvement in depression was negatively correlated with pretreatment values of HVA in CSF (r = -.66, P less than .05). These data suggest that the heterogeneity of clinical response may be related to biological differences in depressed patients and that those with low initial dopaminergic function respond best to increased dopamine receptor stimulation.

Adult

Calcium and electroconvulsive therapy of severe depressive illness.

In severely depressed patients with primary affective illness, consistent decreases in total calcium concentration have been demostrated in both CSF and serum following successful ECT treatment. The hypocalcemia does not appear to occur after the initial ECTs, but develops after three to five treatments, coincident with an acceleration in clinical antidepressant effects, and is not an artifact of the anesthetic premedications or mechanical ventilation of the patients. Evidence linking alterations in calcium metabolism to mood is reviewed and a number of mechanisms by which the calcium change might result from ECT and mediated its effects on mood are discussed.

Adult

The tryptolines: effect of intraventricular administration on spontaneous motor activity of rats.

The pharmacologic properties of the tryptolines, hindered analogues of the tryptamines, were studied behaviorally in rats. Following intraventricular injections, it was found that spontaneous motor activity decreased markedly during the initial 25 mins when compared with saline. Since both the tryptolines and tryptamines have been shown to be inhibitors of 5-hydroxytryptamine uptake, it may be possible that these compounds are acting indirectly throught an effect on the serotonergic system.

Animals

Negative effects of melatonin on depression.

In order to test the efficacy of the pineal neurohumor melatonin on depression, the hormone was administered in varying doses to six moderately to severely depressed patients and two patients with Huntington's chorea in double-blind crossover study. Melatonin exacerbated symptoms of dysphoria in these patients, as well as causing a loss of sleep and weight and a drop in oral temperature. Melatonin increased cerebrospinal fluid 5-hydroxyindoleacetic acid and calcium in three of four patients studied. The authors discuss the implications of this finding.

Adult