Paul Glue

University of Otago, Taieri, Otago Region, New Zealand

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Publications (55)191.99 Total impact

  • Biological psychiatry 08/2014; 76(3):e1-2. · 8.93 Impact Factor
  • The World Journal of Biological Psychiatry 06/2014; · 3.57 Impact Factor
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    ABSTRACT: Objectives. Research studies have reported impressive antidepressant effects with ketamine but significant knowledge gaps remain over the best method of administering ketamine, and the relationships between dose, antidepressant response and adverse effects. Methods. In this pilot dose-finding study, the efficacy and tolerability of ketamine given by rapid intravenous (i.v.) infusion were assessed in a double-blind, placebo-controlled, crossover design, in four subjects with treatment- resistant depression. Each subject received up to four i.v. doses of ketamine (0.1, 0.2, 0.3, 0.4 mg/kg), given over 2–5 min, 1 week apart, and one randomly inserted placebo treatment. Results. Three of four subjects achieved antidepressant response (≥ 50% decrease in Montgomery–Asberg Depression Rating Scale scores), two at the minimum 0.1 mg/kg dose, though all relapsed within a week. For two subjects, the greatest improvement occurred at the highest dose received. Rapid infusion over 2 min led to significant adverse psychotomimetic effects which also increased proportionately with ketamine dosage. Conclusions. This is the first trial to present dose–response data of ketamine efficacy and psychomimetic effects in depressed subjects. Antidepressant efficacy may be dose-related. Psychotomimetic effects were dose-related. Rapid infusion over 2 min may not be a feasible clinical approach to treatment, given poor tolerability.
    The World Journal of Biological Psychiatry 06/2014; · 3.57 Impact Factor
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    ABSTRACT: Auckland and Otago medical programmes have different methods for selecting students. This study compared postgraduate retention in New Zealand (NZ) of medical graduates from the two medical programmes, to assess whether different selection methods influenced retention. Other variables assessed included entrance category and age at graduation. Anonymised databases were created of all graduates from the Otago Faculty of Medicine (1999-2011) and the Auckland medical programme (2000-2012). Demographic and entry category data were recorded. Retention was defined as presence on the NZ Medical Register in December 2012. Risk differences (RD) were calculated to compare retention between the two medical programmes using the Mantel-Haenszel method. The influence of medical programme entrance category on retention was also tested. The influence of covariates on retaining graduates on the register was evaluated using a multiple logistic regression model. The postgraduate retention of graduates of the two medical programmes over 13 years was identical (Auckland 74.9%, Otago 73.6%, P=0.48). Retention of graduate and non-graduate entry students from both medical programmes was similar by 6 years after graduation. Age during medical school did not affect retention. University of attendance had no effect on postgraduation retention of students on the NZ Medical Register, suggesting that retention is not influenced by the different student selection methods at each programme. The data presented shows that New Zealand graduates regardless of programme completed show a similar profile in terms of retention.
    The New Zealand medical journal 01/2014; 127(1388):47-54.
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    ABSTRACT: Objectives:There are wide global variations in electroconvulsive therapy (ECT) use patterns. This audit reviewed patient-level ECT use patterns over 10 years at a single New Zealand clinic, including factors associated with clinical response and patterns of repeated administration.Methods:Retrospective audit of all 2003-2012 ECT and clinical file data.Results:A total of 199 patients received ECT, which was used to treat mostly affective disorders in a predominantly female, older population, generally with a single course of treatment. There were different demographics and patterns of ECT use between patients being treated for affective and psychotic disorders. Overall treatment response was high, with over 90% of patients having a full or partial response. Treatment response was not associated with diagnosis, gender, or medication use, but showed a trend in significance for greater response in elderly patients.Conclusions:ECT use patterns in Otago New Zealand are similar to those reported in Australia, USA, and UK, although yearly use rate in Otago is lower. Because of their different demographic and ECT treatment patterns, future studies should report data for patients with affective and psychotic disorders separately.
    Australian and New Zealand Journal of Psychiatry 11/2013; · 3.29 Impact Factor
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    ABSTRACT: Voriconazole is more effective for aspergillosis infections with central nervous system involvement than other antifungal agents. The clinical efficacy of voriconazole for central nervous system infections has been attributed to its ability to cross the blood brain barrier. However, pharmacokinetic studies are limited to plasma and cerebrospinal fluid so it remains unclear how much of the drug enters the brain. Fluorinated compounds such as voriconazole can be quantified in the brain using fluorine-19 magnetic resonance spectroscopy (MRS). Twelve healthy adult males participated in a pharmacokinetic analysis of voriconazole levels in the brain and plasma. Open label voriconazole was dosed per clinical protocol with a loading dose of 400 mg every 12 hours on Day 1 followed by 200 mg every 12 hours administered orally over a 3 day period. MRS was performed before and after dosing on the third day. Voriconazole levels in the brain exceeded the minimum inhibitory concentration for Aspergillus. The brain to plasma ratio was 3.0 at steady state on Day 3 (predose) and 1.9 postdose. This study indicates that voriconazole is able to penetrate the brain tissue, which can be quantified using a non-invasive MRS technique.
    Antimicrobial Agents and Chemotherapy 08/2013; · 4.57 Impact Factor
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    JAMA Psychiatry 08/2013; 70(8):880-1. · 12.01 Impact Factor
  • Journal of palliative medicine 05/2013; · 1.84 Impact Factor
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    ABSTRACT: Objective:Narrative review of the literature on the efficacy and safety of subanaesthetic doses of ketamine for the treatment of depression.Method:Medline and PubMed databases were searched up to October 2012 using appropriate keywords.Results:The studies consistently report substantial efficacy with high response and remission rates from 4 to 72 hours (averages 77% and 43%, respectively) from single doses, though not all patients respond to ketamine. Early relapse is common. While the usual procedure involves the administration of intravenous ketamine at a dose of 0.5 mg/kg over 40 minutes, some preliminary evidence suggests other dosing regimens and routes of administration may be useful or even better. Repeated doses and maintenance pharmacological treatments have been investigated in order to prolong the antidepressant effects, with only modest success.Conclusions:Current research on the antidepressant effects of ketamine has consistently shown rapid and substantial improvement in mood in the majority of patients. However, these effects have often been found to be short-lived. Future research should focus on identifying predictors of response (e.g. clinical, genetic, pharmacokinetic, environmental), examining different dosing regimens and routes of administration, and strategies to maintain the antidepressant response.
    Australian and New Zealand Journal of Psychiatry 05/2013; · 3.29 Impact Factor
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    ABSTRACT: Background There is conjecture regarding the profile of cognitive development over time in chil-dren with Down syndrome (DS). Characterising this profile would be valuable for the planning and assessment of intervention studies. Method A systematic search of the literature from 1990 to the present was conducted to identify
    Journal of Intellectual Disability Research 04/2013; 57(4):306-318. · 1.88 Impact Factor
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    ABSTRACT: OBJECTIVE: Factors associated with acute admission to inpatient psychiatric wards have been difficult to replicate, possibly reflecting methodological limitations of analyzing individual variables. The objective of this analysis was to identify factors associated with hospitalization at an inpatient psychiatric unit using cluster analytic methods. METHODS: Demographic, admission and treatment data for all admissions to a single inpatient unit in 2010 were collected retrospectively. Cluster analysis was performed using Ward's method. RESULTS: The initial clustering identified a high suicidality/crisis group, which then gave two further subclusters, an internalizing one characterized by affective symptoms and an externalizing one characterized by intoxication at admission, and a population with poor medication compliance that included most cases of psychosis. These subclusters had different clinical and demographic characteristics, different rates of hospital readmission and different durations of stay. CONCLUSIONS: Cluster analysis may be a useful exploratory technique to assist in planning and developing services for adult patients needing admission to a psychiatric hospital.
    Australasian Psychiatry 02/2013; · 0.60 Impact Factor
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    ABSTRACT: To evaluate the proportion of patients hospitalised in an acute psychiatric ward associated with use of the synthetic cannabinoid K2, along with their clinical features. Retrospective audit. K2 use was based on self-report. Seventeen patients had a total of 21 admissions during between January and April 2013; this represented 13% of all admissions to the ward during this time. This was a first hospitalisation for 4 patients. Of the 13 patients with previous psychiatric hospitalisation, 9 patients had recurrences of pre-existing disorders, and 4 patients presented new psychotic symptoms. Presenting symptoms were variable, and included psychotic (paranoia, thought disorder, disorganised behaviour), affective (anxious, depressed) disturbances, and/or intense suicidal thinking/behaviour. Mean duration of admission was 8.5 days, with significantly longer durations for those presenting with psychotic symptoms (13.1 vs 4.4 days). In this case series, use of K2 was associated with significant psychotoxicity requiring hospitalisation, and indicates substantial risk associated with use of synthetic cannabinoids.
    The New Zealand medical journal 01/2013; 126(1377):18-23.
  • Paul Glue, Chris Gale
    The New Zealand medical journal 01/2013; 126(1369):90-1.
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    ABSTRACT: To examine the influence of a number of variables, including age and medical school entrance category, on postgraduate retention of New Zealand (NZ) medical graduates. An anonymised database was created of all graduates from the Otago School of Medicine (1999-2010), with demographic and entry category data. The NZ Medical Register was checked in January 2012 to identify which graduates remained in NZ. Risk Differences (RD) were calculated to compare retention between medical school entrance categories by year of graduation using the random effects Mantel-Haenszel method. The influence of covariates on remaining on the New Zealand Medical Register was evaluated using logistic regression. The odds of remaining on the NZ Medical Register increased by 7% for each additional year of age at graduation (Odds Ratio=1.070, 95%CI 1.038-1.113, p<0.001). Compared with students who entered medical school after a competitive first year exam, retention of students who entered after completion of a bachelor's degree was 7% higher, and 20% higher for "Other Category" (older, work experienced) students. Multiple logistic regression identified medical school entry category as the only significant predictor of higher retention. Admission policies favouring graduate entry and "Other Category" students could contribute to increased retention of NZ medical graduates.
    The New Zealand medical journal 01/2013; 126(1371):27-32.
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    ABSTRACT: BACKGROUND AND OBJECTIVE: Clozapine is the most effective drug for schizophrenia. A suspension formulation of clozapine for patients who may have difficulty swallowing tablets was approved based on the 1996 US Food and Drug Administration (FDA) Guidance and has been launched in Australia, New Zealand and the UK. The objective of this study was to compare the bioequivalence of a new suspension formulation of clozapine with clozapine tablets (Clozaril(®)). METHODS: The steady-state bioequivalence of a 50-mg/mL clozapine suspension and Clozaril(®) tablets was compared under fasting and fed conditions in a randomized, multiple-dose, two-way crossover study, consistent with the 2005 FDA Bioequivalence Guidance. Adult patients with schizophrenia established on once-daily doses of clozapine were administered Clozaril(®) tablets or clozapine suspension for 11 days, then switched to the other formulation for the next 11 days. On days 10 and 11 of each period, fasted (day 10) and fed (day 11) pharmacokinetic profiles were obtained over 24 h. RESULTS: Compared with the tablet formulation, point estimates for maximum plasma concentration (C(max)) and area under the plasma concentration-time curve during a dosage interval (τ) [AUCτ] for the suspension formulation were close to 100 %, and all 90 % confidence intervals (CIs) were between 80 % and 125 % under fasted (C(max) 99.91; 90 % CI 94.60, 104.70; AUC(τ) 99.55; 90 % CI 92.40, 100.70) and fed (C(max) 99.72; 90 % CI 93.70, 103.50; AUC(τ) 99.68; 90 % CI 93.40, 101.80) conditions. Food did not affect AUC(τ); however, C(max) was reduced by ~20 %, with a similar magnitude of change for both formulations. Safety/tolerability profiles were similar between the two formulations. CONCLUSION: The tablet and suspension formulations are bioequivalent, with similar safety profiles, under fed and fasted conditions.
    Clinical Drug Investigation 09/2012; · 1.92 Impact Factor
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    ABSTRACT: Depression is highly prevalent in patients with advanced cancer, commonly affecting quality of life. Considering the response delay with conventional antidepressants and the short life expectancy for these patients, treatments for Major Depressive Disorder (MDD) with faster onset of action are desirable. In this case report, a female patient with metastatic ovarian cancer presented rapid and sustained response to intramuscular (IM) injections of ketamine (1mg/kg). Over a course of six treatments, her mood response was identical on each occasion and provided remission of her depressive symptoms. Pain was also improved, although for a shorter duration. These findings support the use of IM ketamine as a possible antidepressant option for this population.
    Journal of palliative medicine 04/2012; 15(4):400-3. · 1.84 Impact Factor
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    Paul Glue, Greg Tarr
    The Lancet 03/2012; 379(9819):892; author reply 894. · 39.06 Impact Factor
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    ABSTRACT: This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis. An optimal treatment regimen would include a combination of medication and psychotherapy, along with an assertive clinical management program. For medications, selective serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles. The nonselective monoamine oxidase inhibitor, phenelzine, may be more potent than these two drug classes, but because of its food and drug interaction liabilities, its use should be restricted to patients not responding to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. There are other medication classes with demonstrated efficacy in social phobia (benzodiazepines, antipsychotics, alpha-2-delta ligands), but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines, it is unclear how best to incorporate these drugs into treatment regimens. There are very few clinical trials on the use of combined medications. Cognitive behavior therapy appears to be more effective than other evidence-based psychological techniques, and its effects appear to be more enduring than those of pharmacotherapy. There is some evidence, albeit limited to certain drug classes, that the combination of medication and cognitive behavior therapy may be more effective than either strategy used alone. Generalized social phobia is a chronic disorder, and many patients will require long-term support and treatment.
    Neuropsychiatric Disease and Treatment 01/2012; 8:203-15. · 2.00 Impact Factor
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    ABSTRACT: Dexrazoxane is approved as a cardioprotective agent for use in female patients with breast cancer who are receiving doxorubicin. The effect of renal insufficiency on elimination is not known. The pharmacokinetics of dexrazoxane 150 mg/m(2), given as a 15-minute constant-rate intravenous infusion, were assessed in 24 men and women with varying degrees of renal function in a single-dose, open-label, parallel-group study. Blood and urine samples were measured by a validated liquid chromatography/mass spectrometry assay. Dexrazoxane pharmacokinetic parameters were derived by standard noncompartmental methods. The effect of kidney function and effect of body surface area on the pharmacokinetics of dexrazoxane were analyzed using linear and nonlinear regression in the SPSS statistical program. Dexrazoxane clearance is decreased in subjects with kidney dysfunction. Compared with normal subjects (creatinine clearance [CL(CR)] >80 mL/min), mean area under the concentration curve from time 0 to infinity (AUC(0-inf)) was 2-fold greater in subjects with moderate (CL(CR) 30-50 mL/min) to severe (CL(CR) <30 mL/min) renal dysfunction. Modeling demonstrated that equivalent exposure (AUC(0-inf)) could be achieved if dosing were reduced by 50% in subjects with CL(CR) less than 40 mL/min compared with control subjects (CL(CR) >80 mL/min). Modeling study results suggested that equivalent exposure could be achieved if dosing was halved in subjects with CL(CR) less than 40 mL/min compared with controls.
    The Journal of Clinical Pharmacology 05/2011; 51(5):731-8. · 2.84 Impact Factor
  • Biological psychiatry 04/2011; 70(4):e9-10; author reply e11-2. · 8.93 Impact Factor

Publication Stats

430 Citations
191.99 Total Impact Points

Institutions

  • 2009–2014
    • University of Otago
      • • Department of Medicine (Dunedin)
      • • Department of Psychological Medicine (Dunedin)
      Taieri, Otago Region, New Zealand
  • 2013
    • University of New South Wales
      Kensington, New South Wales, Australia
  • 2006–2009
    • Pfizer Inc.
      • • Pfizer Global Research & Development
      • • Department of Clinical Pharmacology
      New York City, NY, United States
  • 2007
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada