Publications (12)39.6 Total impact
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Article: Increased serum free tryptophan in patients with diarrhea-predominant irritable bowel syndrome.
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ABSTRACT: Irregularities of serotonin function in irritable bowel syndrome (IBS) may be due to changes in the metabolism of the serotonin precursor l-tryptophan. Dietary alteration of tryptophan intake may impact upon the mood and bowel symptoms of IBS. We hypothesized that diarrhea-predominant irritable bowel syndrome (d-IBS) patients would exhibit an increase in plasma tryptophan due to alterations in tryptophan metabolism. We also hypothesized that a diet low in tryptophan would reverse this change and reduce symptoms. Thirteen patients with d-IBS had fasting serum free and total tryptophan, large neutral amino acids, and 6 kynurenine metabolites measured before and after 2 weeks of a strict dairy-free diet. Baseline tryptophan parameters were compared with an age- and sex-matched control group. Changes in the specific tryptophan parameters before and after dairy-free diet were correlated with symptoms of IBS and mood. Compared with the control group, d-IBS patients at baseline exhibited significantly higher free serum tryptophan (10.5 ± 4.35 vs 4.75 ± 2.43 μmol/L [means ± standard deviation], P = .006) and significantly lower tryptophan dioxygenase and total tryptophan oxidation as measured by the kynurenine to free tryptophan and total kynurenines to free tryptophan ratios (23.37 ± 10.12 vs 55.33 ± 16.02, P < .001 and 49.34 ± 17.84 vs 258.46 ± 98.67, P < .001, respectively). Dairy-free diet did not modulate metabolites of the kynurenine pathway or symptoms. Tryptophan metabolism along the kynurenine pathway is inhibited in d-IBS, and a dairy-free diet does not alter this. Our findings are consistent with possible enhanced serotonin activity in d-IBS.Nutrition research (New York, N.Y.) 10/2010; 30(10):678-88. · 1.20 Impact Factor -
Article: Cyproterone to treat aggressivity in dementia: a clinical case and systematic review.
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ABSTRACT: Aggressivity is a common problem in the management of elderly patients with dementia. Medications currently used to diminish aggressive behaviour in dementia can have problematic side effects. We present a case and systematic review of the current knowledge about the use of cyproterone acetate to treat aggressivity (excluding hypersexuality related behaviours) in dementia. An 82-year-old man required psychiatric inpatient admission due to agitation and aggressivity and was diagnosed with Alzheimer's disease. After failed trials of atypical antipsychotics (quetiapine 100 mg/day and risperidone 1 mg/day), drugs for dementia (memantine 20 mg/day and rivastigmine 9 mg/day) and benzodiazepines (lorazepam 0.5-1 mg prn) he was started on cyproterone acetate titrated up to 50 mg twice daily. After two weeks he was calmer and did not express aggressivity. Two months later he was discharged to a community placement where he subsequently remained settled on cyproterone. We reviewed literature on the use of cyproterone in aggressivity (excluding hypersexuality) associated with dementia. We searched the main medical databases including articles in English, Spanish, French and Italian. Only one randomized double-blind trial was found, comparing cyproterone with haloperidol (n = 27). Cyproterone was more effective controlling aggressivity and had lower incidence of side effects. In the one uncontrolled naturalistic observational study identified (n = 19), cyproterone was associated with significant reductions in aggressivity without causing major side effects. Further literature was limited to theoretical discussions. Despite there being evidence to support our observations of a useful role for cyproterone in aggressivity in dementia, further studies are needed to establish the efficacy and safety of this therapeutic option.Journal of Psychopharmacology 11/2009; 25(1):141-5. · 3.04 Impact Factor -
Article: Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: an [11C]diprenorphine PET study.
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ABSTRACT: The importance of the opioid receptor system in substance dependence is increasingly recognised. We used PET with the non-selective tracer [11C]diprenorphine to examine opioid receptor binding in early abstinence from alcohol dependence and the relationship to craving. We recruited 11 alcohol dependent patients and 13 controls. Subjects underwent one [11C]diprenorphine PET scan in early abstinence from dependent alcohol use (approximately 2 weeks) and 2 months later if continuously abstinent. Global and regional [11C]diprenorphine volumes of distribution (VD) were increased in alcohol dependent patients compared with controls but did not reach significance. We demonstrated a correlation between global and regional [11C]diprenorphine VD and craving in alcohol dependent patients which persisted in the anterior cingulate cortex into extended abstinence. This confirms previous work showing increased opioid receptor availability in early abstinence from substances of abuse and correlation with craving suggesting that the opioid system plays a fundamental role in this phase of addiction.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2009; 19(10):740-8. · 3.68 Impact Factor -
Article: Antidepressant-induced jitteriness/anxiety syndrome: systematic review.
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ABSTRACT: Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking. To review systematically all evidence relating to jitteriness/anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions. A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome. Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome. Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.The British journal of psychiatry: the journal of mental science 07/2009; 194(6):483-90. · 6.62 Impact Factor -
Article: Is the association of hypertension and panic disorder explained by clustering of autonomic panic symptoms in hypertensive patients?
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ABSTRACT: Autonomic nervous system dysfunction may be implicated in the association of hypertension with panic attacks and panic disorder. We hypothesised that panic symptoms of autonomic origin are more common in attacks experienced by hypertensive than normotensive patients, that autonomic panic symptoms cluster together as a distinct factor, and that this factor is more prevalent in hypertensive patients with panic than in normotensives. We analysed all 346 structured questionnaires completed by primary care and hospital clinic patients who had reported experiencing full (n=287) or limited symptom panic attacks (n=59) (268 with hypertension, and 78 never having had hypertension). Frequency of sweating, flushes, and racing heart, symptoms selected prospectively as being most likely of autonomic origin, were compared between hypertensive and normotensive patients. Principal component analysis was performed with varimax orthogonal rotation. Using logistic regression, odds ratios were calculated for association of factor scores with hypertension. Sweating and flushes were significantly more common among hypertensive patients than normotensives (sweating; 65% v 46%, p=0.003, flushes; 55% v 40%, p=0.019). There was no significant difference between groups for frequency of racing heart nor any of the remaining panic symptoms analysed as secondary endpoints. Principal component analysis yielded four factors with eigenvalues >1.0. Factor 1 was dominated by autonomic symptoms, notably sweating and flushes, which had loadings of 0.68 and 0.61. On regression only this autonomic factor showed a significant association with hypertension, the odds ratio being 1.37 (95% C.I. 1.05 to 1.77, p=0.018). These findings support the possibility that autonomic dysfunction contributes to the association of hypertension with panic.Journal of Affective Disorders 05/2008; 111(2-3):344-50. · 3.52 Impact Factor -
Article: PRN prescribing in psychiatric inpatients: potential for pharmacokinetic drug interactions.
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ABSTRACT: Medications are commonly prescribed to psychiatric inpatients on a PRN (pro re nata/as required) basis, allowing drugs to be administered on patient request or at nurses' discretion for psychiatric symptoms, treatment side effects or physical complaints. However, there has been no formal study of the pharmacokinetic implications of PRN prescribing. The objective of the study was to determine the prevalence of PRN drug prescription and administration, and to assess the potential for interactions involving CYP2D6 and CYP3A4 between drugs prescribed and administered to inpatients on psychiatry wards.A cross-sectional survey of prescriptions on general adult and functional elderly psychiatric wards in one city was carried out. Data were recorded from prescription charts of 323 inpatients (236 on general adult and 87 on functional elderly wards). Of 2089 prescriptions, 997 (48%) of prescriptions were on a PRN basis (most commonly benzodiazepines and other hypnotic agents, antipsychotics, analgesics and anticholinergic agents), but only 143 (14%) of these had been administered in the previous 24 hours. One fifth of patients were prescribed drug combinations interacting with CYP2D6 or CYP3A4 of potential clinical importance which included one or more drugs prescribed on a PRN basis.PRN prescribing is common among inpatients in psychiatry, and may lead to cytochrome P450 mediated interactions. Prescribers should be aware of the potential for unpredictability in plasma concentrations, side effects and efficacy which PRN prescribing may cause through these interactions, particularly in old age psychiatry and in treatment of acute psychosis.Journal of Psychopharmacology 04/2007; 21(2):153-60. · 3.04 Impact Factor -
Article: Depleting serotonin enhances both cardiovascular and psychological stress reactivity in recovered patients with anxiety disorders.
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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.Journal of Clinical Psychopharmacology 09/2006; 26(4):414-8. · 4.10 Impact Factor -
Article: Treatment of anxiety and depressive disorders in patients with cardiovascular disease.
BMJ (Clinical research ed.). 05/2004; 328(7445):939-43. -
Article: Drug intolerance due to nonspecific adverse effects related to psychiatric morbidity in hypertensive patients.
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ABSTRACT: Poor adherence to antihypertensive drug regimens is common and may increase the risk for cardiovascular morbidity and mortality. Adverse effects of the drugs can contribute to poor adherence, but some patients who discontinue several different antihypertensive drugs may misinterpret nonspecific symptoms as adverse effects of the drug because of psychiatric morbidity. We examined the relationship between intolerance to antihypertensive drugs and the presence of panic disorder, panic attacks, anxiety, and depression. We included all patients with hypertension who attended a hospital hypertension clinic during 1 year with at least 2 episodes of intolerance (resulting in reduction of the dosage or stopping an antihypertensive drug) recorded on standardized problem lists and a similar number of patients with no recorded episodes of intolerance. Psychiatric morbidity, assessed by self-administered questionnaires, was analyzed against the number of episodes of nonspecific and drug-specific intolerance, verified by means of individual case-note scrutiny, and scored independently by 2 assessors masked to patient identity. Analyzable questionnaires were returned by 233 (84%) of 276 patients who had experienced 576 (85%) of 679 episodes of intolerance assessed. Five hundred thirty-two episodes (92%) were subjective (patient was symptomatic); of these, 284 were judged to be drug specific; 248, nonspecific. Having more episodes of nonspecific intolerance was associated with significantly higher diastolic blood pressure (P =.003). Episodes of nonspecific intolerance were associated with panic attacks (P =.008), anxiety (Hospital Anxiety and Depression Scale score, P =.04), and depression (Hospital Anxiety and Depression Scale score, P =.005). Drug-specific intolerance was not associated with psychiatric morbidity. Intolerance to multiple antihypertensive drugs, particularly non-drug-specific intolerance, is strongly associated with psychiatric morbidity. Physicians treating hypertensive patients need to recognize and manage the psychiatric aspects of intolerance to multiple antihypertensive drugs.Archives of Internal Medicine 04/2003; 163(5):592-600. · 11.46 Impact Factor -
Article: Discontinuation of thioridazine in patients with learning disabilities: balancing cardiovascular toxicity with adverse consequences of changing drugs.
BMJ (Clinical research ed.). 07/2002; 324(7352):1519-21. -
Article: Is there cognitive impairment in clinically 'healthy' abstinent alcohol dependence?
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ABSTRACT: The aim of this study was to determine neuropsychological performance in apparently cognitively, mentally, and physically healthy abstinent alcohol-dependent subjects compared with control subjects who were recruited for a number of different neuroimaging studies. All subjects completed a battery of neuropsychological tests as part of the neuroimaging protocol. The group dependent on alcohol performed as well as controls on a non-verbal memory test and verbal fluency but performed worse in the verbal memory task, Trail A + B, and total IQ derived from Silverstein's short-form of the WAIS-R. However, the IQ performance of both groups was above average. In both groups, age was associated with slower performance on the Trail A + B task. In the alcohol-dependent group, severity of dependence and length of abstinence was not associated with performance of any task. In this apparently clinically healthy population of abstinent alcohol-dependent subjects, frontal lobe dysfunction was detectable using the Trail A + B and digit symbol tasks. This was despite above-average WAIS-R IQ scores. Consideration needs to be given to routine incorporation of cognitive testing in alcohol dependence since subtle deficits may not be easily apparent and may impact on treatment outcome.Alcohol and Alcoholism 40(6):498-503. · 2.95 Impact Factor -
Article: P-252: Psychiatric aspects of multiple drug intolerance
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2003–2010
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University of Bristol
Bristol, ENG, United Kingdom
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