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Biomedical subjects

I M Anderson

Publications and source records attributed to I M Anderson.

At least 19 recordsLinked to original sources
PubMed2000

d-Fenfluramine in panic disorder: a dual role for 5-hydroxytryptamine.

RATIONALE: 5-Hydroxytryptamine (5-HT) appears to modulate different forms of anxiety in different ways, but the importance of this in human anxiety disorders is unknown. OBJECTIVES: To investigate whether the 5-HT releasing agent d-fenfluramine (dFEN) has different effects on resting and panic anxiety in panic disorder. METHODS: Thirteen drug-free patients with DSM-IIIR panic disorder were tested in a double-blind placebo-controlled crossover design. Carbon dioxide 7% (CO2) was given as a panic challenge 270 min after administration of dFEN or placebo. RESULTS: Compared to placebo, dFEN increased anxiety and arousal, maximal at 120 min, but tended to reduce CO2-induced anxiety and panic attacks with a significant reduction in Panic Visual Analogue Scale ratings (P=0.040). Anxiety following CO2, but not dFEN, administration resembled panic attacks (compared to Acute Panic Inventory symptom profile during patients' usual attacks). Patients with more severe disorders exhibited enhanced behavioural responses and blunted prolactin responses to dFEN. CONCLUSIONS: dFEN caused anxiety similar to generalised anxiety in panic disorder patients but reduced anxiety following 7% CO2 challenge, a laboratory analogue of naturally occurring panic attacks. These findings are consistent with a dual role for 5-HT in pathological anxiety. Patients with more severe symptoms differed in 5-HT function compared to more mildly affected individuals.

Adult↗
PubMed2000

Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability.

BACKGROUND: A meta-analysis of the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) against tricyclic antidepressants (TCAs) in depressed patients was carried out. METHODS: Efficacy data from 102 randomised controlled trials (10706 patients) were pooled to provide a summary variance-weighted effect size. Tolerability data from 95 studies (10553 patients) were combined to give variance-weighted relative risk of drop out for all reasons and for adverse effects from each study. The effect of age, treatment setting, severity and TCA dose were examined as well as the performance of individual SSRIs and TCAs where there were sufficient studies. RESULTS: There is no overall difference in efficacy between SSRIs and TCAs (effect size -0.03, 95% confidence interval -0.09 to 0.03). TCAs do appear more effective in in-patients (-0.23, -0.40 to -0.05) and amitriptyline is more effective than SSRI comparators (-0.14, -0.25 to -0.03) but publication bias cannot be excluded. The SSRIs are better tolerated, with significantly lower rates of treatment discontinuations overall (relative risk 0.88, 0.83 to 0.93; number needed to treat 26) and due to side effects (0.73, 0.67 to 0.80; number needed to treat 33). Individual SSRIs show a similar advantage except for fluvoxamine which does not differ from the TCAs. Individual TCAs show a similar disadvantage in tolerability compared to SSRIs except for dothiepin against which SSRI treatment results in more side-effect related drop outs (2.64, 1.50 to 4.63; number needed to harm 12). LIMITATIONS: The evidence is from short-term studies and subgroup analyses may result in chance results. CONCLUSIONS: Overall efficacy between the two classes is comparable but SSRIs are not proven to be as effective as TCAs in in-patients and against amitriptyline. SSRIs have a modest advantage in terms of tolerability against most TCAs.

Antidepressive Agents, Second-Generation↗
PubMed2000

Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. British Association for Psychopharmacology.

A revision of the British Association for Psychopharmacology guidelines for treating depressive disorders with antidepressants was undertaken in order to specify the scope and target of the guidelines and to update the recommendations based explicitly on the available evidence. A consensus meeting, involving experts in depressive disorders and their treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is given which identifies the quality of evidence followed by recommendations, the strength of which are based on the level of evidence. The guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing, management when initial treatment fails, continuation treatment, maintenance treatment to prevent recurrence and stopping treatment.

Antidepressive Agents↗
PubMed2000

Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers.

BACKGROUND: Uncertainties remain about the role of serotonin in the aetiology and treatment of panic disorder. AIMS: To investigate the effect of reducing brain serotonin function on anxiety at rest, and following 5% CO2 provocation in normal controls and patients with panic disorder. METHOD: Twenty drug-free patients with DSM-III-R panic disorder and 19 controls received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind, balanced protocol. 5% CO2 was given as a panic challenge after 270 minutes. RESULTS: Plasma tryptophan fell by more than 80% both patients and controls after the tryptophan-free drink. Tryptophan depletion did not alter resting anxiety. In patients alone, tryptophan depletion caused a greater anxiogenic response and an increased rate of panic attacks (9 v. 2, P < 0.05) after 5% CO2 challenge. No normal volunteers panicked. CONCLUSIONS: Serotonin may directly modulate panic anxiety in patients with panic disorder. This may underlie the efficacy of serotonergic antidepressants in treating panic disorder.

Adolescent↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1990

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↗