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Biomedical subjects

I M Anderson

Publications and source records attributed to I M Anderson.

At least 37 records · Page 2Linked to original sources

Evaluation of a pregnancy outcome risk reduction program in a local health department.

This study assesses the effectiveness of the Waukesha County Public Health Department's Prenatal Care Coordination Program (PNCC) in reducing self-reported risk factors for adverse pregnancy outcomes in pregnant clients, through assessment, preventive counseling and follow-up. There were 166 clients seen in the program. They were seen at up to three follow-up visits, with 83 seen at the 12-week follow-up visit, 106 seen at the 24-week follow-up visit, 74 seen at the 38-week follow-up visit, and 151 seen for at least one follow-up visit. Statistically significant improvement was seen between the first and last follow-up visit for each of the five categories of risk factors that were assessed. Mean alcohol intake decreased from 9.6 drinks per month at baseline to none by the 38-week follow-up visit. Mean cigarette smoking decreased from 12.8 cigarettes per day to 2.4. Street drug use decreased almost completely. There were statistically significant increases in milk, meat, fruit, bread, and vegetable consumption, and folic acid and multi-vitamin supplementation.

Female↗

5-HT and human anxiety. Evidence from studies using acute tryptophan depletion.

There is abundant evidence that serotonin (5-hydroxytryptamine, 5-HT) is involved in anxiety in both animals and humans but there is conflicting evidence for the precise role it plays. Acute tryptophan depletion provides a technique for investigating a global reduction in brain 5-HT function and we have investigated its effect on anxiety in drug-free panic disorder patients and normal volunteers. We found little effect on general levels of anxiety but it enhanced the effect of a panic challenge using 5% carbon dioxide (5%CO2) in panic disorder patients. The effect in normal volunteers was less clear with no overall effect following 5%CO2 challenge or the psychological challenge of a simulated public speaking task. These results are discussed in relation to the literature and are broadly supportive of the hypothesis that 5-HT acts to inhibit panic anxiety at the level of the periaqueductal grey but facilitates general and conditioned anxiety at the level of medial temporal lobe structures.

Anxiety↗

Information processing in anxiety: a pilot study of the effect of manipulating 5-HT function.

We gave the indirect 5-HT agonist, D-fenfluramine (30 mg), the 5 -HT antagonist methysergide (2 mg) and placebo to 11 patients with an anxiety disorder and 12 controls in a double-blind, balanced-order, cross-over design. Compared to controls, patients had significantly higher anxiety ratings, were slower in naming colours in computerized Stroop tests and showed greater interference for anxiety-related words. Patients tended to have a lower critical flicker fusion threshold (CFFT) than controls and in the subjects taken as a whole there was a significant inverse correlation between CFFT and Spielberger state (r=-0.54, p<0.01) and trait anxiety (r=-0.55, p<0.01). Neither drug had significant effects on anxiety ratings or on Stroop interference. D-Fenfluramine significantly increased CFFT (p < 0.02) and methysergide non-significantly reduced CFFT with no significant differences between patients and controls. 5-HT may be involved in lower-level visual information processing but we found no evidence for its direct involvement in the attentional bias for anxiety-related information in the emotional Stroop.

Adult↗

SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability.

A meta-analysis of the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) against nonselective and noradrenergic reuptake inhibitors (mainly tricyclic antidepressants, TCAs) in depressed inpatients was carried out. Twenty-five double-blind studies provided data on relative efficacy which was determined by a summary variance-weighted mean effect size calculated from the difference in the reduction in mean Hamilton Depression Rating Scale (HDRS) scores for the two antidepressants in each study. Twenty-three studies provided data on dropouts and relative tolerability which was determined as the variance-weighted pooling of the relative risk (RR) of dropout for all reasons and for adverse effects from each study. TCAs were significantly more effective than SSRIs (effect size = -0.23, 95% CI -0.40 to -0.05, P = 0.011), although sensitivity analyses by analysing larger studies (> 100 patients) and those providing complete data reduced the advantage to TCAs to a trend (P < 0.10). When the TCAs were grouped into those with dual action on 5-hydroxytryptamine (HT) and noradrenaline reuptake (clomipramine and amitriptyline) and those with predominantly noradrenaline reuptake (imipramine, desipramine and maprotiline), only the dual action TCAs had greater efficacy than SSRIs (effect size = -0.30, 95% CI -0.54 to -0.05, P = 0.017). When TCAs were considered individually, only amitriptyline was significantly more effective than comparator SSRIs (effect size = -0.37, 95% CI -0.67 to -0.07, P = 0.015). More patients overall discontinued treatment on TCAs than on SSRIs (29.0% vs. 25.5%), although this did not reach statistical significance (RR = 0.88, 95% CI 0.75 to 1.03, P = 0.121). However, significantly more patients stopped treatment due to adverse effects on TCAs compared to SSRIs (14.2% vs. 9.1%, RR = 0.66, 95% CI 0.50 to 0.87, P = 0.003) with no difference in discontinuations due to treatment failure (10% vs. 11.6%, RR = 1.13, 95% CI 0.84 to 1.51, P = 0.42). This meta-analysis suggests that at least some TCAs may be more effective than SSRIs in depressed inpatients, with there being the strongest evidence for amitriptyline. A possible explanation is that this is related to a dual action in inhibiting both 5-HT and noradrenaline reuptake. In agreement with previous meta-analyses, TCAs appear less well tolerated than SSRIs, although the absolute risk difference for discontinuation due to adverse effects (4.9%, 95% CI -8.1 to -1.7%) is of uncertain clinical significance.

Antidepressive Agents, Tricyclic↗

The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers.

We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D2 receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT1A receptor function is reduced by chronic fluvoxamine treatment.

Adult↗

Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis.

OBJECTIVE: To assess treatment discontinuation rates with selective serotonin reuptake inhibitors compared with tricyclic antidepressants. DESIGN: Meta-analysis of 62 randomised controlled trials. SUBJECTS: 6029 patients with major unipolar depression. MAIN OUTCOME MEASURES: Pooled risk ratios for drop out rates with respect to all cases of discontinuation and those due to side effects and treatment failure. RESULTS: The total discontinuation rate was 10% lower with selective serotonin reuptake inhibitors than with tricyclic antidepressants (risk ratio 0.90; 95% confidence interval 0.84 to 0.97) and the drop out rate due to side effects was 25% lower (risk ratio 0.75; 0.66 to 0.84). There was no significant difference between drug classes in the drop out rates for treatment failure. The risk ratios for drop out did not differ significantly between individual selective serotonin reuptake inhibitors. CONCLUSIONS: Selective serotonin reuptake inhibitors are better tolerated than tricyclic antidepressants as measured by total numbers of drop outs. The definite advantage to selective serotonin reuptake inhibitors is explained by fewer drop outs due to side effects. The overall difference, however, is comparatively small and may not be clinically relevant. Analyses of cost effectiveness should not overestimate the advantage to selective serotonin reuptake inhibitors.

Antidepressive Agents, Tricyclic↗

5-HT1A receptor sensitivity in major depression. A neuroendocrine study with buspirone.

The hypothermic, growth hormone and corticotrophin (ACTH) responses to the 5-HT1A receptor agonist buspirone (30 mg orally) were measured in 20 unmedicated patients with major depression and 20 healthy controls. Compared with the controls, the hypothermic responses of the depressed patients to buspirone were significantly attenuated, particularly in patients with melancholic depression. In contrast, the responses of growth hormone and ACTH to buspirone were unchanged. The data suggest that major depression may be associated with impaired sensitivity of 5-HT1A autoreceptors but that the function of the post-synaptic 5-HT1A receptors that mediate growth hormone and ACTH release is unaltered. Within the limitations that attend the use of buspirone as a 5-HT1A probe, our data suggest that the decrement in serotonin neurotransmission at post-synaptic 5-HT1A receptors in depression is due to decreased serotonin release rather than impaired responsivity of post-synaptic 5-HT1A receptors.

Adolescent↗

Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers.

Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists.

Adult↗

Decreased 5-HT-mediated prolactin release in major depression.

The prolactin response to intravenous clomipramine, a 5-HT uptake inhibitor, was significantly attenuated in 12 patients with major depression. In contrast, in a further 12 depressed patients, the PRL responses to thyrotropin-releasing hormone, which acts directly on the pituitary to release PRL, were not reduced. These findings suggest that the reduction in 5-HT-mediated PRL release seen in depressed patients is due to an impairment of brain 5-HT function rather than a pituitary abnormality.

Adult↗

The effects of gepirone on neuroendocrine function and temperature in humans.

The effects of the selective 5-HT1A receptor agonist gepirone (10 and 20 mg orally) on neuroendocrine function and temperature were assessed using a single-blind cross-over design in 12 healthy male volunteers. Gepirone significantly increased plasma levels of ACTH, beta-endorphin, cortisol, prolactin and growth hormone. Following gepirone there was a significant decrease in body temperature and moderate increases in subjective reports of light-headedness, nausea and drowsiness. Our results are consistent with studies in rodents suggesting that 5-HT1A receptor agonists increase ACTH and prolactin secretion and decrease body temperature. Further investigations are needed to determine if the neuroendocrine and temperature effects of gepirone in humans are mediated by 5-HT1A receptors.

Adrenocorticotropic Hormone↗

Metergoline abolishes the prolactin response to buspirone.

Pretreatment of nine healthy subjects with the non-selective 5-HT receptor antagonist, metergoline (4 mg), abolished the increase in plasma prolactin produced by the anxiolytic drug, buspirone (15 mg). While these findings are consistent with a role for 5-HT receptors in the stimulatory effect of buspirone on plasma prolactin, a dopaminergic mechanism cannot be excluded by the present data.

Adult↗

Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss.

Plasma total tryptophan (TRP) concentration was significantly lower in 31 patients with major depression compared to a healthy control group. The ratio of plasma TRP concentration to that of other branch chain amino acids (the TRP:BCAA ratio) was also decreased. Further analysis revealed that the decrease in plasma TRP and TRP:BCAA ratio was most apparent in patients with major depression and melancholia. Overall, women but not men had significantly decreased plasma tryptophan concentrations, perhaps because of a contributory effect of weight loss; this latter effect, however, could not be distinguished clearly from a diagnosis of melancholia. Our data suggest that in some depressed patients, reductions in plasma tryptophan availability may contribute to abnormalities in brain 5-hydroxytryptamine function.

Adult↗

Dieting reduces plasma tryptophan and alters brain 5-HT function in women.

A three week low calorie diet significantly reduced both total plasma tryptophan and the ratio of tryptophan to competing amino acids in a group of 15 healthy volunteers. Despite a similar percentage weight loss the reduction in plasma tryptophan was greater in women than men. In addition, only in women was dieting associated with increased prolactin secretion following intravenous tryptophan, a measure of brain 5-hydroxytryptamine (5-HT) function. These results suggest that dieting reduces the availability of circulating tryptophan for brain 5-HT synthesis. Women appear more vulnerable than men both to this effect and to its consequences for brain 5-HT function. Altered brain 5-HT function may play a part in some of the psychological consequences of dieting, including the development of clinical eating disorders.

Adult↗

Neuroendocrine effects of azapirones.

In healthy volunteers, the azapirones--buspirone, ipsapirone, and gepirone--increase plasma cortisol and decrease body temperature; buspirone and gepirone also increase plasma prolactin and growth hormone. Data from animal studies suggest that the ability of azapirones to decrease body temperature and increase corticotropin and corticosterone is mediated by stimulation of presynaptic and postsynaptic serotonin (5-hydroxytryptamine, 5-HT) type 1A subtype receptors, respectively. The mechanism of altered growth hormone and prolactin secretion is less clear. While animal studies implicate changes in dopamine function, current human investigations suggest that 5-HT1A receptors also may be involved in these endocrine responses. Further investigations, using more selective 5-HT receptor antagonists, will be required to resolve this issue.

Animals↗