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John Potokar

Bio: John Potokar is an academic researcher from University of Bristol. The author has contributed to research in topics: Anxiety & Anxiety disorder. The author has an hindex of 28, co-authored 73 publications receiving 2224 citations. Previous affiliations of John Potokar include Bristol Royal Infirmary & University Hospitals Bristol NHS Foundation Trust.


Papers
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Journal ArticleDOI
TL;DR: Reports of withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective SSRIs, fluoxetine, fluvoxamine, paroxettine, or sertraline suggest a role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity.
Abstract: We studied reported withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, or sertraline. In 171 patients who were supervised during medication tapering and discontinuation, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood. When patients with at least one qualitatively new symptom were defined as cases, these symptoms occurred significantly more frequently in patients who had been treated either with one of the shorter half-life SSRIs, fluvoxamine or paroxetine (17.2%), or with clomipramine (30.8%), than in patients taking one of the SSRIs with longer half-life metabolites, sertraline or fluoxetine (1.5%). The rate was not significantly different between the different shorter half-life treatments. Cases treated with fluvoxamine or paroxetine had received a significantly longer period of treatment (median 28 weeks) than noncases (16 weeks), but there were no significant associations with age or with diagnostic grouping. There was a trend toward an association with male sex. The majority of cases occurred despite slowly tapered withdrawal. Symptoms persisted for up to 21 days (mean = 11.8 days) after onset. These symptoms were relieved within 24 hours by restarting the medication, but were not relieved by benzodiazepines or by moclobemide. A role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity. We suggest that this may lead to useful hypotheses about the pathophysiology of withdrawal symptoms from serotonin reuptake inhibitors.

268 citations

Journal ArticleDOI
TL;DR: Panic disorder is associated with reduced 5-HT(1A) receptor availability, which is also known to have a key role in depression.
Abstract: Background The importance of the neurotransmitter serotonin (5-HT) in the pathophysiology of anxiety is well known A key role for postsynaptic 5-HT1A receptors has recently been suggested in studies of genetic knockout mice Aims To measure 5-HT1A receptor binding in patients with panic disorder in the untreated state and after recovery on treatment with selective serotonin reuptake inhibitors (SSRIs) Method Nine symptomatic untreated patients with panic disorder, seven patients recovered on SSRI medication and nineteen healthy volunteers underwent a single positron emission tomography (PET) scan using the 5-HT1A tracer [11C]WAY-100635 Results In comparison with controls, both presynaptic and postsynaptic 5-HT1A receptor binding was reduced in untreated patients, with the most significant reductions being in the raphe, orbitofrontal cortex, temporal cortex and amygdala In recovered patients presynaptic binding was reduced, but there was no significant reduction in postsynaptic binding Conclusions Panic disorder is associated with reduced 5-HT1A receptor availability, which is also known to have a key role in depression

162 citations

Journal ArticleDOI
TL;DR: Jitteriness/anxiety syndrome remains poorly characterised and clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action, but systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.
Abstract: Background 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. Aims 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. Method A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome. Results 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. Conclusions 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.

155 citations

Journal ArticleDOI
TL;DR: In this paper, a multisite prospective cohort study was conducted of adults aged 18 years and over referred to liaison psychiatry services following self-harm and evaluated the performance of risk scales (Manchester Self-Harm Rule, ReACT Self Harm Rule, SAD PERSONS scale, Modified SAD Persons scale, Barratt Impulsiveness Scale, etc.).
Abstract: BackgroundScales are widely used in psychiatric assessments following self-harm. Robust evidence for their diagnostic use is lacking.AimsTo evaluate the performance of risk scales (Manchester Self-Harm Rule, ReACT Self-Harm Rule, SAD PERSONS scale, Modified SAD PERSONS scale, Barratt Impulsiveness Scale); and patient and clinician estimates of risk in identifying patients who repeat self-harm within 6 months.MethodA multisite prospective cohort study was conducted of adults aged 18 years and over referred to liaison psychiatry services following self-harm. Scale a priori cut-offs were evaluated using diagnostic accuracy statistics. The area under the curve (AUC) was used to determine optimal cut-offs and compare global accuracy.ResultsIn total, 483 episodes of self-harm were included in the study. The episode-based 6-month repetition rate was 30% (n = 145). Sensitivity ranged from 1% (95% CI 0-5) for the SAD PERSONS scale, to 97% (95% CI 93-99) for the Manchester Self-Harm Rule. Positive predictive values ranged from 13% (95% CI 2-47) for the Modified SAD PERSONS Scale to 47% (95% CI 41-53) for the clinician assessment of risk. The AUC ranged from 0.55 (95% CI 0.50-0.61) for the SAD PERSONS scale to 0.74 (95% CI 0.69-0.79) for the clinician global scale. The remaining scales performed significantly worse than clinician and patient estimates of risk (P<0.001).ConclusionsRisk scales following self-harm have limited clinical utility and may waste valuable resources. Most scales performed no better than clinician or patient ratings of risk. Some performed considerably worse. Positive predictive values were modest. In line with national guidelines, risk scales should not be used to determine patient management or predict self-harm.

92 citations

Journal ArticleDOI
TL;DR: The use of immune-activated groups at high risk of depression have been used and found novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway.
Abstract: This article highlights the evidence linking depression to increased inflammatory drive and explores putative mechanisms for the association by reviewing both preclinical and clinical literature The enzyme indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines and may form a link between immune functioning and altered neurotransmission, which results in depression Increased indoleamine 2,3-dioxygenase activity may cause both tryptophan depletion and increased neurotoxic metabolites of the kynurenine pathway, two alterations which have been hypothesized to cause depression The tryptophan-kynurenine pathway is comprehensively described with a focus on the evidence linking metabolite alterations to depression The use of immune-activated groups at high risk of depression have been used to explore these hypotheses; we focus on the studies involving chronic hepatitis C patients receiving interferon-alpha, an immune activating cytokine Findings from this work have led to novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway

92 citations


Cited by
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Journal ArticleDOI
21 Jul 2009-BMJ
TL;DR: The meaning and rationale for each checklist item is explained, and an example of good reporting is included and, where possible, references to relevant empirical studies and methodological literature are included.
Abstract: Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

13,813 citations

Journal ArticleDOI
02 Jan 2015-BMJ
TL;DR: The PRISMA-P checklist as mentioned in this paper provides 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol, as well as a model example from an existing published protocol.
Abstract: Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.

9,361 citations

Journal ArticleDOI
TL;DR: The dopamine hypothesis of schizophrenia-version III is synthesized into a comprehensive framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function.
Abstract: The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.

2,311 citations

Journal ArticleDOI
TL;DR: Self-management education improves GHb levels at immediate follow-up, and increased contact time increases the effect, suggesting that learned behaviors change over time.
Abstract: Objective To evaluate the efficacy of self-management education on GHb in adults with type 2 diabetes. Research design and methods We searched for English language trials in Medline (1980-1999), Cinahl (1982-1999), and the Educational Resources Information Center database (ERIC) (1980-1999), and we manually searched review articles, journals with highest topic relevance, and reference lists of included articles. Studies were included if they were randomized controlled trials that were published in the English language, tested the effect of self-management education on adults with type 2 diabetes, and reported extractable data on the effect of treatment on GHb. A total of 31 studies of 463 initially identified articles met selection criteria. We computed net change in GHb, stratified by follow-up interval, tested for trial heterogeneity, and calculated pooled effects sizes using random effects models. We examined the effect of baseline GHb, follow-up interval, and intervention characteristics on GHb. Results On average, the intervention decreased GHb by 0.76% (95% CI 0.34-1.18) more than the control group at immediate follow-up; by 0.26% (0.21% increase - 0.73% decrease) at 1-3 months of follow-up; and by 0.26% (0.05-0.48) at > or = 4 months of follow-up. GHb decreased more with additional contact time between participant and educator; a decrease of 1% was noted for every additional 23.6 h (13.3-105.4) of contact. Conclusions Self-management education improves GHb levels at immediate follow-up, and increased contact time increases the effect. The benefit declines 1-3 months after the intervention ceases, however, suggesting that learned behaviors change over time. Further research is needed to develop interventions effective in maintaining long-term glycemic control.

1,757 citations

Journal ArticleDOI
TL;DR: Additional research will be needed to clarify the exact role of each component of the fear circuitry in the anxiety disorders, determine whether functional abnormalities identified in the Anxiety disorders represent acquired signs of the disorders or vulnerability factors that increase the risk of developing them, and use functional neuroimaging to predict treatment response and assess treatment-related changes in brain function.

1,617 citations