Anxiety Disorders: Bell C

Ursano RJ, Bell C, Eth S, Friedman M, Norwood A, Pfefferbaum B, Pynoos JD, Zatzick DF, Benedek DM, McIntyre JS, Charles SC, Altshuler K, Cook I, Cross CD, Mellman L, Moench LA, Norquist G, Twemlow SW, Woods S, Yager J, Anonymous00293, Anonymous00294. · No affiliation provided · Am J Psychiatry. · Pubmed #15617511 No free full text.

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Bell C, Abrams J, Nutt D. · Psychopharmacology Unit, School of Medical Sciences, Bristol, UK. · Br J Psychiatry. · Pubmed #11331552 links to  free full text

Abstract: BACKGROUND: Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems. AIMS: To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders. METHOD: Systematic review of preclinical and clinical studies. RESULTS: Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar. CONCLUSIONS: The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions.

Nutt DJ, Forshall S, Bell C, Rich A, Sandford J, Nash J, Argyropoulos S. · University of Bristol, Psychopharmacology Unit, School of Medical Sciences, University Walk, UK. · Eur Neuropsychopharmacol. · Pubmed #10523062 No free full text.

Abstract: Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the single action of serotonin reuptake inhibition can improve several psychiatric conditions. In order to understand this apparent paradox it is necessary to consider where SSRIs act in the pathogenic process underlying depression or anxiety disorders. Tryptophan depletion has been used extensively in research into depression and has shown that, in patients receiving an SSRI whose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This suggests that increased levels of serotonin are necessary in the synapse for the SSRI to be effective in the treatment of depression and panic disorder. In obsessive compulsive disorder, depletion of serotonin in patients recovered on an SSRI does not cause relapse; receptor adaptation may be more important. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affinity for the 5-HT2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use.

Bell C, Forshall S, Adrover M, Nash J, Hood S, Argyropoulos S, Rich A, Nutt DJ. · Psychopharmacology Unit, School of Medical Sciences, University of Bristol, UK. · J Psychopharmacol. · Pubmed #11949771 No free full text.

Abstract: The neurobiological basis of panic disorder has not been clearly established, although a role for serotonin (5-HT) has been postulated. It is clear that drugs which increase 5-HT neurotransmission are effective in treating the condition but how they do so remains a point of debate. The aim of this study was to determine if lowering brain serotonin activity using the technique of tryptophan depletion provoked a short-term relapse of panic symptoms in patients with panic disorder who had responded to drug treatment. Fourteen patients with panic disorder who had responded to treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received an infusion of flumazenil (used as a pharmacological challenge) and placebo on each day. The tryptophan depleted drink produced an 87% reduction in plasma tryptophan concentration. Flumazenil produced a panic attack (defined by changes in the panic inventory) in seven out of 14 patients when tryptophan depleted and one out of 14 on the control day (p < 0.02). Three patients also experienced temporary depressive symptoms when tryptophan depleted, with no mood changes being seen on the control days. We conclude that rapid lowering of brain serotonin function can allow the precipitation of panic symptoms in response to flumazenil in panic disorder patients who have responded to treatment with an SSRI. This implies that in panic disorder increased 5-HT availability is important in maintaining the response to SSRIs.

Sandford JJ, Forshall S, Bell C, Argyropoulos S, Rich A, D'Orlando KJ, Gammans RE, Nutt DJ. · Psychopharmacology Unit, School of Medical Sciences, University of Bristol, UK. · J Psychopharmacol. · Pubmed #11565630 No free full text.

Abstract: Pagoclone is a cyclopyrrolone that is believed to act as a partial agonist at the gamma-aminobutyric acid (GABA)-A/benzodiazepine (BDZ) receptor. In theory, such partial agonists should be anxiolytic but lack the adverse side-effects of sedation, tolerance and withdrawal associated with full GABA-A/BDZ agonists. The objective of the randomized double-blind crossover study was to assess whether pagoclone was an effective anti-panic agent and also to assess its side-effect profile. Patients recruited had a diagnosis of Panic Disorder (DSM-IV) with at least one panic attack per week. Following a 2-week screening period, patients entered a 6-week trial consisting of two 2-week treatment periods, each followed by a 1-week washout. Patients were randomly assigned to receive either pagoclone 0.1 mg t.d.s. or placebo on their first treatment period and the converse on their second. The primary measure was daily panic attack dairy. Fourteen patients completed the study, the mean number of panic attacks during screening was 5.8+/-0.8 (SEM), this fell to 3.6+/-0.5 during treatment with pagoclone (p = 0.05) and 4.3+/-0.8 with placebo (p = 0.14). There was no significant difference on direct comparison of pagoclone with placebo or in any of the secondary measures (including Rickels withdrawal scale) or the adverse event profiles. The study provides preliminary evidence that pagoclone has anxiolytic properties in the absence of typical BDZ side-effects. This is consistent with its theoretical mode of action as a partial agonist at the GABA(A)/BDZ receptor.

Coupland NJ, Bell C, Potokar JP, Dorkins E, Nutt DJ. · Psychopharmacology Unit, University of Bristol, School of Medical Sciences, United Kingdom. · Depress Anxiety. · Pubmed #10723632 No free full text.

Abstract: The benzodiazepine antagonist, flumazenil, can provoke panic attacks in some panic disorder patients. It has been predicted that panic responses to flumazenil may be associated with situational fear. Patients with social phobia frequently experience situational anxiety and panic attacks. The current study tested whether flumazenil induces panic in patients with social phobia. Fourteen patients with social phobia (DSM-III-R) and 14 age- and sex-matched controls were tested in a single session, double blind crossover challenge design, using intravenous flumazenil 2 mg/20 ml or matched placebo infusions 1 hour apart. Panic attacks occurred during flumazenil challenge in 2/14 subjects with social phobia. The rate of panic attacks and the severity of panic symptoms following flumazenil were not significantly greater in patients than in controls. Situational fears that are provoked by social cues therefore do not predict panic responses to flumazenil.

Davies SJ, Hood SD, Argyropoulos SV, Morris K, Bell C, Witchel HJ, Jackson PR, Nutt DJ, Potokar JP. · Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 8NY, United Kingdom. · J Clin Psychopharmacol. · Pubmed #16855462 No free full text.

Abstract: Serotonin-promoting drugs show cardioprotective properties in patients with anxiety or depression, but it is not known if this is a direct effect of increasing serotonin. We aimed to characterize the effect of serotonin manipulation through acute tryptophan depletion on cardiovascular and psychological responses to stress challenge in recovered patients with anxiety disorders. In 27 recovered patients with anxiety disorders (panic disorder treated by selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy, social anxiety disorder treated by SSRIs), we performed a double-blind randomized crossover study. On 2 separate days, the subjects ingested an acute tryptophan-depleting (aTD) or nondepleting (nD) drink in random order and underwent a stress challenge at time of maximum depletion. Systolic blood pressure (P = 0.007; diff = 9.0 mm Hg; 95% confidence interval (CI), 2.6-15.3 mm Hg) and diastolic blood pressure (P = 0.032; diff = 5.7 mm Hg; 95% CI, 0.6-10.9 mm Hg) responses to stress were significantly greater under aTD than nD, as were the psychological responses to stress (for Spielberger state anxiety, difference in stress response between aTD and nD = 7.11; P = 0.025). Blood pressure responses to stress showed no correlation with psychological responses. The significant increases in acute stress sensitivity in both cardiovascular and psychological domains on serotonin depletion suggest that serotonin is involved in the control of both cardiovascular and psychological aspects of the acute stress response. The lack of correlation in the difference between aTD and nD conditions in cardiovascular and psychological responses suggests that serotonin may have distinct effects on these 2 domains, rather than the cardiovascular responses being merely a secondary consequence of psychological changes.

Coupland NJ, Wilson SJ, Potokar JP, Bell C, Nutt DJ. · Psychopharmacology Unit, School of Medical Sciences, University Walk, Bristol, UK. · Psychiatry Res. · Pubmed #12759163 No free full text.

Abstract: Although autonomic function has been investigated in panic disorder (PD), previous studies have not used non-invasive beat by beat blood pressure (BP) monitoring to assess the rapid dynamics of BP during autonomic reflex tests. The hypothesis of the current study was that patients with PD would show increased cardiovascular sympathetic reactivity compared with healthy or anxious controls, as assessed by the initial overshoot of diastolic BP during the immediate response to standing. Patients with PD (n=56), social phobia (n=28) and healthy volunteers (n=56) were tested using finger photoplethysmography during an orthostatic challenge. Panic disorder patients showed an increased BP overshoot compared with both control groups. Moreover, in a preliminary assessment of selective serotonin reuptake inhibitor treatment effects, the BP overshoot was significantly reduced towards normal values. These findings are consistent with recent evidence for increased sympathetic baroreflex function in PD and may be relevant to the pathophysiology of the disorder.

Kreidler MC, Zupancic MK, Bell C, Longo MB. · University of Akron, College of Nursing, Akron, OH, USA. · Perspect Psychiatr Care. · Pubmed #11111593 No free full text.

Abstract: TOPIC: How advanced practice nurses can work with trauma survivors to decrease dissociation as a needed coping mechanism. PURPOSE: To review the literature on trauma and dissociation as well as current treatment perspectives. SOURCES: Review of the literature and authors' clinical experience. CONCLUSIONS: Advanced practice nurses can use knowledge of selected psychopharmacological medications and Erikson's stages of psychosocial development to plan treatment for posttrauma clients.

Bell C, Nutt D. · Psychopharmacology Unit, School of Medical Sciences, University of Bristol. · Hosp Med. · Pubmed #10396411 No free full text.

Abstract: Paroxetine is one of the specific serotonin-reuptake inhibitor antidepressants which is used in a variety of psychiatric disorders. It has recently gained considerable publicity because of its use in social anxiety disorder and its subsequent labelling by the media as a 'lifestyle drug'. This review summarizes current indications for paroxetine and outlines doses and duration of treatment for each condition.