Erick Turner - Academia.edu (original) (raw)
Papers by Erick Turner
Background: Publication bias compromises the validity of evidence-based medicine, yet a growing b... more Background: Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy.
PLoS Medicine | www.plosmedicine.org 0177 Background to the debate: Placebos are used in trials t... more PLoS Medicine | www.plosmedicine.org 0177 Background to the debate: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue that placebo trials are still crucial to prove the effi cacy and safety of many treatments.
FDA databases contain valuable information on unpublished studies, but it can be difficult to fin... more FDA databases contain valuable information on unpublished studies, but it can be difficult to find. This article explains where to look and provides tips on how to make documents easier to use
[1] about how the Food and Drug Administration's (FDA's) review of documents can serve as a sourc... more [1] about how the Food and Drug Administration's (FDA's) review of documents can serve as a source of clinical trials data, but she follows it up with the statement, "However, it is diffi cult to have confi dence in data released by sponsors when the data have not been subjected to external, independent peer review. Furthermore, this information is not integrated with other data, or indexed" [2].
Background. The effects of antidepressants for treating depressive disorders have been overestima... more Background. The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo.
Journal of Clinical Psychopharmacology, May 1, 2002
A role for serotonin in seasonal affective disorder (SAD) has been explored with a variety of ser... more A role for serotonin in seasonal affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. We had initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small open-label pilot study, we observed the opposite effect. We decided to follow up on this finding with the formal study described below. The study followed a double-blind randomized crossover design. Sixteen untreated depressed SAD patients received single doses of metergoline 8 mg po and of placebo, spaced one week apart.
Biological Psychiatry, Jun 1, 1998
The modern practice of using artificial light to extend waking activities into the nighttime hour... more The modern practice of using artificial light to extend waking activities into the nighttime hours might be expected to precipitate or exacerbate bipolar illness, because it has been shown that modifying the timing and duration of sleep can induce mania in susceptible individuals. With this possibility in mind, we treated a patient with rapidly cycling bipolar illness by creating an environment that was likely to increase and to stabilize the number of hours that he slept each night. Methods: We asked the patient to remain at bed rest in the dark for 14 hours each night (later this was gradually reduced to 10 hours). Over a period of several years, his clinical state was assessed with twice-daily self-ratings, once-weekly observer ratings, and continuous wrist motor activity recordings. Times of sleeping and waking were recorded with sleep logs, polygraphic recordings, and computer-based event recordings. Results: The patient cycled rapidly between depression and mania and experienced marked fluctuations in the timing and duration of sleep when he slept according to his usual routine, but his sleep and mood stabilized when he adhered to a regimen of long nightly periods of enforced bed rest in the dark. Conclusions: Fostering sleep and stabilizing its timing by scheduling regular nightly periods of enforced bed rest in the dark may help to prevent mania and rapid cycling in bipolar patients.
The American Journal of Psychiatry, Nov 1, 1998
The authors sought to compare the degree of mood improvement after light treatment with mood impr... more The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. Method: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. Results: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. Conclusions: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.
Strategies to Decrease Costs of Prescribing Selective Serotonin Reuptake Inhibitors at a VA Medical Center
Psychiatric Services, Mar 1, 2003
The authors examined the efficacy of a multifaceted intervention designed to contain the cost of ... more The authors examined the efficacy of a multifaceted intervention designed to contain the cost of prescribing selective serotonin reuptake inhibitors (SSRIs) to inpatients and outpatients served by a Veterans Affairs (VA) medical center. Elements of the intervention included identification of a preferred agent, tablet splitting, education and feedback for prescribers, and an electronic record and ordering system to facilitate changes in prescriber behaviors. VA databases were searched for information on use and costs of antidepressants. Over 35 months the number of patients treated with SSRIs and the amount spent on SSRIs increased. However, the mean monthly cost per patient decreased from 57.12to57.12 to 57.12to42.19. The projected cost savings over the 35 months was approximately $700,000; one-fourth of the savings was due to tablet splitting and three-fourths to changes in the proportions of the various SSRIs prescribed. A survey of the top 75 antidepressant prescribers showed that after the educational interventions, 91 percent were aware that citalopram was the medical center's preferred antidepressant, and 59 percent identified it as their own preferred first-line treatment. The results suggest that multifaceted interventions can influence antidepressant costs through provider education and changes in pharmacy and computerized information processes, resulting in substantial cost savings for institutions.
Retraction of biased journal articles
BMJ, 2015
Reboxetine in depression. All the relevant data?
Does Publication Bias Inflate the Apparent Efficacy of Psychological Treatment for Major Depressive Disorder? A Systematic Review and Meta-Analysis of US National Institutes of Health-Funded Trials
PloS one, 2015
The efficacy of antidepressant medication has been shown empirically to be overestimated due to p... more The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972-2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges' g = 0.20; CI95% -0.11~0...
Effects of leuprolide-induced hypogonadism and testosterone replacement on sleep, melatonin, and prolactin secretion in men
Journal of Clinical Endocrinology & Metabolism
The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has rec... more The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has received relatively little attention despite the importance of the topic to several clinical syndromes. Pharmacologically induced hypogonadism, with and without gonadal steroid replacement, provides an opportunity to examine these questions within a controlled experimental design. We used leuprolide acetate, with and without testosterone replacement, to study the role of testosterone in the regulation of sleep and of melatonin, PRL, and TSH secretion in men. Results from 10 men revealed significant decreases in 24-h PRL levels and in the percentage and time of stage 4 sleep in the hypogonadal state compared with testosterone replacement. There were no differences in melatonin or TSH secretion or in the timing or duration of sleep between the two hormonal conditions. These results indicate that testosterone has relatively specific and discrete effects on sleep and hormonal rhythms in men.
Journal of psychiatry & neuroscience: JPN
To determine if the antidepressant effect of 1 hour of light therapy is predictive of the respons... more To determine if the antidepressant effect of 1 hour of light therapy is predictive of the response after 1 and 2 weeks of treatment in patients with seasonal affective disorder (SAD). Patients: Twelve patients with SAD. Setting: National Institutes of Health Clinical Center, Bethesda, Md. Interventions: Light therapy for 2 weeks. Outcome measures: Scores on the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale (SIGH-SAD) on 4 occasions (before and after 1 hour of light therapy and after 1 and 2 weeks of therapy) in the winter when the patients were depressed. Change on typical and atypical depressive scores at these time points were compared. Results: Improvement of atypical depressive symptoms after 1 hour of light therapy positively correlated with improvement after 2 weeks of therapy. Conclusion: In patients with SAD, the early response to light therapy may predict some aspects of long-term response to light therapy, but these results should be treated with caution until replicated.
Suppression of men's response to seasonal changes in day length by modern artificial lighting
The American journal of physiology
We recently reported that humans have conserved mechanisms, like those that exist in other animal... more We recently reported that humans have conserved mechanisms, like those that exist in other animals, which detect changes in day length and make corresponding adjustments in the duration of nocturnal periods of secretion of melatonin and of other functions. We detected these responses in individuals who were exposed to artificial "days" of different durations. The purpose of the present study was to determine whether men who are exposed to natural and artificial light in an urban environment at 39 degrees N are still able to detect and respond to seasonal changes in duration of the natural photoperiod. We measured profiles of circadian rhythms during 24-h periods of constant darkness (< 1 lx) and found no summer-winter differences in durations of nocturnal periods of active secretion of melatonin, rising levels of cortisol, high levels of thyrotropin, and low levels of rectal temperature. The results of this and our previous study suggest that modern men's use of ar...
interferon-induced depression: Synergistic mechanisms for normalizing synaptic serotonin
5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin
Background: Publication bias compromises the validity of evidence-based medicine, yet a growing b... more Background: Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy.
PLoS Medicine | www.plosmedicine.org 0177 Background to the debate: Placebos are used in trials t... more PLoS Medicine | www.plosmedicine.org 0177 Background to the debate: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue that placebo trials are still crucial to prove the effi cacy and safety of many treatments.
FDA databases contain valuable information on unpublished studies, but it can be difficult to fin... more FDA databases contain valuable information on unpublished studies, but it can be difficult to find. This article explains where to look and provides tips on how to make documents easier to use
[1] about how the Food and Drug Administration's (FDA's) review of documents can serve as a sourc... more [1] about how the Food and Drug Administration's (FDA's) review of documents can serve as a source of clinical trials data, but she follows it up with the statement, "However, it is diffi cult to have confi dence in data released by sponsors when the data have not been subjected to external, independent peer review. Furthermore, this information is not integrated with other data, or indexed" [2].
Background. The effects of antidepressants for treating depressive disorders have been overestima... more Background. The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo.
Journal of Clinical Psychopharmacology, May 1, 2002
A role for serotonin in seasonal affective disorder (SAD) has been explored with a variety of ser... more A role for serotonin in seasonal affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. We had initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small open-label pilot study, we observed the opposite effect. We decided to follow up on this finding with the formal study described below. The study followed a double-blind randomized crossover design. Sixteen untreated depressed SAD patients received single doses of metergoline 8 mg po and of placebo, spaced one week apart.
Biological Psychiatry, Jun 1, 1998
The modern practice of using artificial light to extend waking activities into the nighttime hour... more The modern practice of using artificial light to extend waking activities into the nighttime hours might be expected to precipitate or exacerbate bipolar illness, because it has been shown that modifying the timing and duration of sleep can induce mania in susceptible individuals. With this possibility in mind, we treated a patient with rapidly cycling bipolar illness by creating an environment that was likely to increase and to stabilize the number of hours that he slept each night. Methods: We asked the patient to remain at bed rest in the dark for 14 hours each night (later this was gradually reduced to 10 hours). Over a period of several years, his clinical state was assessed with twice-daily self-ratings, once-weekly observer ratings, and continuous wrist motor activity recordings. Times of sleeping and waking were recorded with sleep logs, polygraphic recordings, and computer-based event recordings. Results: The patient cycled rapidly between depression and mania and experienced marked fluctuations in the timing and duration of sleep when he slept according to his usual routine, but his sleep and mood stabilized when he adhered to a regimen of long nightly periods of enforced bed rest in the dark. Conclusions: Fostering sleep and stabilizing its timing by scheduling regular nightly periods of enforced bed rest in the dark may help to prevent mania and rapid cycling in bipolar patients.
The American Journal of Psychiatry, Nov 1, 1998
The authors sought to compare the degree of mood improvement after light treatment with mood impr... more The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. Method: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. Results: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. Conclusions: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.
Strategies to Decrease Costs of Prescribing Selective Serotonin Reuptake Inhibitors at a VA Medical Center
Psychiatric Services, Mar 1, 2003
The authors examined the efficacy of a multifaceted intervention designed to contain the cost of ... more The authors examined the efficacy of a multifaceted intervention designed to contain the cost of prescribing selective serotonin reuptake inhibitors (SSRIs) to inpatients and outpatients served by a Veterans Affairs (VA) medical center. Elements of the intervention included identification of a preferred agent, tablet splitting, education and feedback for prescribers, and an electronic record and ordering system to facilitate changes in prescriber behaviors. VA databases were searched for information on use and costs of antidepressants. Over 35 months the number of patients treated with SSRIs and the amount spent on SSRIs increased. However, the mean monthly cost per patient decreased from 57.12to57.12 to 57.12to42.19. The projected cost savings over the 35 months was approximately $700,000; one-fourth of the savings was due to tablet splitting and three-fourths to changes in the proportions of the various SSRIs prescribed. A survey of the top 75 antidepressant prescribers showed that after the educational interventions, 91 percent were aware that citalopram was the medical center&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s preferred antidepressant, and 59 percent identified it as their own preferred first-line treatment. The results suggest that multifaceted interventions can influence antidepressant costs through provider education and changes in pharmacy and computerized information processes, resulting in substantial cost savings for institutions.
Retraction of biased journal articles
BMJ, 2015
Reboxetine in depression. All the relevant data?
Does Publication Bias Inflate the Apparent Efficacy of Psychological Treatment for Major Depressive Disorder? A Systematic Review and Meta-Analysis of US National Institutes of Health-Funded Trials
PloS one, 2015
The efficacy of antidepressant medication has been shown empirically to be overestimated due to p... more The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972-2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges' g = 0.20; CI95% -0.11~0...
Effects of leuprolide-induced hypogonadism and testosterone replacement on sleep, melatonin, and prolactin secretion in men
Journal of Clinical Endocrinology & Metabolism
The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has rec... more The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has received relatively little attention despite the importance of the topic to several clinical syndromes. Pharmacologically induced hypogonadism, with and without gonadal steroid replacement, provides an opportunity to examine these questions within a controlled experimental design. We used leuprolide acetate, with and without testosterone replacement, to study the role of testosterone in the regulation of sleep and of melatonin, PRL, and TSH secretion in men. Results from 10 men revealed significant decreases in 24-h PRL levels and in the percentage and time of stage 4 sleep in the hypogonadal state compared with testosterone replacement. There were no differences in melatonin or TSH secretion or in the timing or duration of sleep between the two hormonal conditions. These results indicate that testosterone has relatively specific and discrete effects on sleep and hormonal rhythms in men.
Journal of psychiatry & neuroscience: JPN
To determine if the antidepressant effect of 1 hour of light therapy is predictive of the respons... more To determine if the antidepressant effect of 1 hour of light therapy is predictive of the response after 1 and 2 weeks of treatment in patients with seasonal affective disorder (SAD). Patients: Twelve patients with SAD. Setting: National Institutes of Health Clinical Center, Bethesda, Md. Interventions: Light therapy for 2 weeks. Outcome measures: Scores on the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale (SIGH-SAD) on 4 occasions (before and after 1 hour of light therapy and after 1 and 2 weeks of therapy) in the winter when the patients were depressed. Change on typical and atypical depressive scores at these time points were compared. Results: Improvement of atypical depressive symptoms after 1 hour of light therapy positively correlated with improvement after 2 weeks of therapy. Conclusion: In patients with SAD, the early response to light therapy may predict some aspects of long-term response to light therapy, but these results should be treated with caution until replicated.
Suppression of men's response to seasonal changes in day length by modern artificial lighting
The American journal of physiology
We recently reported that humans have conserved mechanisms, like those that exist in other animal... more We recently reported that humans have conserved mechanisms, like those that exist in other animals, which detect changes in day length and make corresponding adjustments in the duration of nocturnal periods of secretion of melatonin and of other functions. We detected these responses in individuals who were exposed to artificial "days" of different durations. The purpose of the present study was to determine whether men who are exposed to natural and artificial light in an urban environment at 39 degrees N are still able to detect and respond to seasonal changes in duration of the natural photoperiod. We measured profiles of circadian rhythms during 24-h periods of constant darkness (< 1 lx) and found no summer-winter differences in durations of nocturnal periods of active secretion of melatonin, rising levels of cortisol, high levels of thyrotropin, and low levels of rectal temperature. The results of this and our previous study suggest that modern men's use of ar...
interferon-induced depression: Synergistic mechanisms for normalizing synaptic serotonin
5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin