Tendler et al. question the validity of our study. The goal of estimating seizure risk was printe... more Tendler et al. question the validity of our study. The goal of estimating seizure risk was printed on the survey, as were the names of the most widely used TMS manufacturers. Our manuscript outlines the timeframe for survey distribution and collection. After data collection ended, our senior author (DP) presented interim updates to the Clinical TMS Society. Data were not included in these interim updates until they were reviewed for inconsistencies (e.g., omissions, duplications, patients sessions, etc.), which was a longitudinal process. Importantly, supplementary analyses confirm that these quality control measures did not affect the results. The discussion section outlines the risks and benefits of drawing conclusions from a cross-sectional survey permitting anonymous responses.
Online celebrity bashing refers to a specific subform of online aggression in which celebrities a... more Online celebrity bashing refers to a specific subform of online aggression in which celebrities are the targets of derogatory messages. Recent research focusing on the underlying explanations of why some bystanders turn into perpetrators of celebrity bashing suggests that human capacity for empathy may regulate the involvement in this practice. Bystanders with higher empathy are thought to show more disapproval towards online celebrity bashing, which makes them less likely to join in this practice. However, little is known about the processes of how empathy steers bystanders' bashing attitudes and behavior. In this study, we examine whether the oxytocinergic system, which forms the neurophysiological foundation of empathy, influences the bystanders' acceptance of online celebrity bashing. In a double-blind, placebo-controlled experiment, we tested the effects of intranasal oxytocin administration on acceptance of celebrity bashing in men. Sixty participants rated neutral or derogatory comments presented as "tweets." Electrodermal activity and electrocardiogram of the participants were recorded to control for the stress levels. The results showed that oxytocin administration reduced the acceptance of celebrity bashing. Celebrity bashing was unrelated to stress levels. In natural circumstances oxytocin levels are dependent on the presence and quality of one's social relationships. As a result, we discuss the importance of facilitating a network of social support in programs addressing the problem of online aggression.
A growing literature suggests that the oxytocin (OT) system may play a role in human anxiety stat... more A growing literature suggests that the oxytocin (OT) system may play a role in human anxiety states, anxiety-related traits, and moreover, that this system may be a target for the development of novel anxiolytic treatments. However, studies of OT's acute and chronic effects on various aspects of anxiety have produced mixed results. In this forwardlooking review, we discuss the myriad phenomena to which the term "anxiety" is applied in the OT literature and the problem this presents developing a coherent picture of OT's role in anxiety. We then survey several different fields of research that support the role of the OT system in human anxiety, including evolutionary perspectives, translational and neuroimaging research, genetic studies, and clinical trials of intranasal OT. As an outgrowth of this data, we propose a "bowtie" model of OT's role at the interface of social attachment and anxiety. We next direct attention to understudied brain regions and neural circuits which may be important to study in OT experiments in humans anxiety disorders. Finally, we conclude by proposing questions and priorities for studying both the clinical potential of OT in anxiety, as well as mechanisms that may underlie this potential. Crucially, these priorities include targeted proof-of-concept clinical trials of IN OT in certain anxiety disorders, including investigations of individual moderators of OT's anxiolytic effects (i.e. sex, genetic factors, and early experience).
In this article Dr. Feifel, addresses some of the common questions associated with the use of ato... more In this article Dr. Feifel, addresses some of the common questions associated with the use of atomoxetine (Strattera ™ ) to treat patients with attention deficity hyperactivity disorder (ADHD). Dr. Feifel: A number of factors may be contributing to the differential perception of efficacy between stimulants and atomoxetine. The most basic explanation is that the magnitude of benefit for many patients may be greater with stimulants and there is some research to support this from headto-head studies 8,9 comparing atomoxetine to long-acting formulations of stimulant medications. However, in my opinion, other factors typically contribute to the perception of an efficacy gap. Central to these factors, I believe, is the fact that atomoxotine works via a different mechanism of action compared to the stimulants, and therefore, exhibits a different therapeutic time-course. Unlike stimulants, atomoxotine's ability to ameliorate ADHD symptoms begins early but accrues slowly and steadily over many weeks before the full benefits are achieved. In fact, data suggest that it may require 8 to 12 weeks before full benefits are seen. As a result, changes in patients are subtle and can, therefore, be much more easily overlooked by patients compared to the dramatic, rapid, symptomatic improvement that occurs with stimulants. In essence, patients may report that that atomoxetine is not having any effect, when indeed it may be producing a significant benefit, simply because it produces symptom improvement
There are compelling reasons why primary care physicians concerned about the well-being of their ... more There are compelling reasons why primary care physicians concerned about the well-being of their patients should strive to become competent in recognizing the symptoms of attention-deficit/hyperactivity disorder (ADHD). Despite lingering social controversy, the existence of ADHD among a portion of the adult population is well accepted among medical experts. Attention deficit/hyperactivity disorder in adulthood meets formal validity criteria established for medical disorders. An estimated 4% to 5% of the adult population is impaired by ADHD. However,less than one-quarter of these adults have been diagnosed as having ADHD
The objective of this study was to investigate the safety of repeated parenteral ketamine for dep... more The objective of this study was to investigate the safety of repeated parenteral ketamine for depression. An electronic survey inquiring about the frequency of adverse events was distributed to providers of parenteral ketamine for depression. In addition, the investigators conducted a search of published studies describing six or more repeated parenteral ketamine treatments administered to individuals for depression, and extracted reported adverse events. The survey was sent to 69 providers, of which 36 responded (52% response rate); after eliminating those that were incomplete, 27 were included in the analysis. The providers in the analysis collectively reported treating 6630 patients with parenteral ketamine for depression, one-third of whom received more than 10 treatments. Only 0.7% of patients experienced an adverse effect that required discontinuation of ketamine. Psychological distress during the treatment was the most frequent cause. Other adverse events were extremely rare (such as bladder dysfunction (0.1%), cognitive decline (0.03%) and psychotic symptoms (0.03%)). Among the 20 published reports of repeated parenteral ketamine treatments, rates of significant adverse events resulting in discontinuation were low (1.2%). The rate of adverse effects reported in the survey and the published literature is low, and suggests that long-term treatment of depression with ketamine is reasonably safe.
Iron overload has been suggested to be an unrecognized cause of psychiatric morbidity. This study... more Iron overload has been suggested to be an unrecognized cause of psychiatric morbidity. This study sought to estimate the prevalence of iron overload in a large outpatient psychiatric clinic. A retrospective review of screening blood chemistries was conducted on 661 active outpatients at a large, university outpatient psychiatric clinic to identify elevated iron status results (plasma iron, percentage of iron saturation) suggestive of iron overload. Patients with positive profiles were asked to undergo a subsequent blood chemistry to confirm positive results (plasma iron, percentage of iron saturation, plus plasma ferritin). Patients with positive repeated iron chemistry results were considered likely candidates for iron overload. Twenty-one patients (3.2%) were identified as meeting one of the criteria suggestive of iron overload on initial screening reports. Thirty-one percent of those who underwent subsequent, confirmatory testing (5/16) continued to meet one of the criteria. On the basis of these results, we estimated a 1% (3.2 x 0.31) prevalence rate of likely candidates for iron overload. A review of these patients' charts indicated that they carried an unexpectedly high rate of bipolar affective disorder (80%) as a diagnosis and were, without exception, atypical in that they were resistant to conventional psychiatric treatment and lacked a family history for this disorder. The prevalence of positive iron overload profiles on a routine blood chemistry was similar to the prevalence of positive thyroid abnormalities based on TSH results in this population. Blood chemistry profiles suggestive of iron overload may be associated with a small portion of treatment-resistant psychiatric patients. Routine screening for iron abnormalities, especially in treatment-resistant patients, should be considered. Further studies are required to determine the causal association, if any, between iron excess and primary psychiatric illnesses.
To the extent that chemicals can be fashionable, oxytocin is perhaps the most fashionable chemica... more To the extent that chemicals can be fashionable, oxytocin is perhaps the most fashionable chemical in neuroscience today. This nine amino acid peptide is appearing with regular frequency as the subject of scientific articles in the most prestigious journals in the field. The popular media have been quick to join the bandwagon, crafting stories that sensationally extoll oxytocin’s pro-social properties and dubbing it the ‘love hormone’ and the ‘cuddle hormone’. Given the strong evidence of oxy tocin’s ability to enhance social cognition, there has been much speculation about its potential role in the etiology and treatment of psychiatric disorders. Autism spectrum disorders and social phobia have garnered the most attention in this regard for obvious reasons. Less obvious is oxytocin’s possible role in schizophrenia. Over a decade ago my laboratory conducted a preclinical proofof-concept study to test our hypothesis that oxytocin exhibits antipsychotic-like effects. This hypothesis was based mostly on evidence that oxytocin regulated central dopamine. That study, conducted in rats, revealed that systemically administered oxytocin, similar to most atypical antipsychotics, reversed prepulse inhibition deficits induced by amphetamine and the phencyclidine analog, MK801 [1]. Those antipsychotic-like results were surprising, even to my team, since oxytocin has a poor ability to penetrate the BBB. Since then, a number of investigators have reported finding antipsychotic-like effects attributed to endogenous oxytocin or systemically administered oxytocin in several different animal models relevant to schizophrenia [2,3]. The accumulation of those promising preclinical findings, as well as numerous studies demonstrating that intranasal oxytocin enhances trust and other pro-social inclinations [4,5], have recently spurred the initiation of several small clinical trials to test the therapeutic potential of oxy tocin in schizophrenia. Our group recently completed the first such proof-ofconcept clinical trial: a double-blinded, placebo-controlled crossover design enrolling schizophrenia patients who were highly symptomatic despite receiving therapeutic doses of an atypical antipsychotic. Intranasal oxytocin (40 international units twice a day) administered as an adjunct to the subjects’ antipsychotic for 3 weeks improved positive and negative symptoms significantly more than placebo did [6]. Recently, another group of investigators at the University of North Carolina (UNC; NC, USA), led by Cort Pedersen reported preliminary results from their own study of adjunctive intranasal oxytocin in schizophrenia patients [7]. They found that 2 weeks of daily intranasal oxytocin significantly reduced schizophrenia symptoms, adding support to the notion that oxytocin has therapeutic potential for the core symptoms of schizophrenia. David Feifel
Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsa... more Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatalthalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study. Methods: At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of $30% in YBOCS score) at the posttreatment assessment and after another month of follow-up. Results: Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up. Conclusions: High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions.
Modeling schizophrenia in animals represents a formidable challenge because the most characterist... more Modeling schizophrenia in animals represents a formidable challenge because the most characteristic symptoms of this disorder, auditory hallucinations and delusional beliefs, cannot be directly modeled in animals. Furthermore, limited current understanding of the etiology and pathophysiology underlying the clinical features of this disorder greatly hinders the ability to develop valid models based on those aspects. To circumvent these issues, investigators have attempted to recreate the leading candidate biochemical, neuroanatomical, and genetic abnormalities for this disorder in animals using pharmacological, developmental, neurotoxic, genetic engineering, and other methods. The validity of these animal preparations as animal models for schizophrenia is generally based upon the extent to which they induce measurable behavioral changes that are homologous or analogous to the core clinical features or the information-processing endophenotypes (presymptom phenotypes) that are seen in schizophrenia. The utility of any animal model to serve as a screen for novel treatments is considered related to the extent to which the schizophrenia-relevant behaviors it exhibits can be ameliorated by drugs with known efficacy in schizophrenia but not by drugs known to be therapeutic for brain disorders other than schizophrenia.
We investigated use of Daytrana in the first year post-launch in the US: May, 2006 through April,... more We investigated use of Daytrana in the first year post-launch in the US: May, 2006 through April, 2007. According to our data, a total of 512,085 prescriptions for Daytrana were written in the first year of launch; psychiatry accounted for 34 percent of these prescriptions. Children and adolescents represented 88 percent of Daytrana users as compared to only 57 percent for the broader ADHD market. Expert commentary describing these trends is provided.
In this article, we investigate the range of treatments prescribed to children with autism. The d... more In this article, we investigate the range of treatments prescribed to children with autism. The data suggest that approximately 58 percent of patients with a diagnosis of childhood autism receive some type of pharmaceutical treatment. The majority of those treated, 68 percent, receive only one pharmaceutical. The most commonly prescribed products are antipsychotics (66%), antidepressants (32%), and stimulants (17%). An expert commentary is included.
Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach t... more Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression. Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.
Although overall prescribing of atomoxetine hydrochloride (HCI) (Strattera) continues to decline,... more Although overall prescribing of atomoxetine hydrochloride (HCI) (Strattera) continues to decline, recent anecdotal reports suggest emerging uses of the product in combination therapy. In this article we examine trends in atomoxetine (HCI) prescribing as well as use in combination with other psychotropic classes. An expert commentary is provided on the data.
ver the past few years, several papers examining the significant increase in atypical antipsychot... more ver the past few years, several papers examining the significant increase in atypical antipsychotic use among children and adolescents have been published-1-3 the most recent of which was published in Archives of General Psychiatry in June of 2006. This paper demonstrated roughly a six-fold increase over the 1993 to 2002 timeframe in office-based mental health visits among individuals age 0 to 20 that included an antipsychotic. 4 This data, however, is somewhat limited due to the time lag in availability of information and the potential bias inherent in the datasource (nonpatient-specific, physician-reported information).
Tendler et al. question the validity of our study. The goal of estimating seizure risk was printe... more Tendler et al. question the validity of our study. The goal of estimating seizure risk was printed on the survey, as were the names of the most widely used TMS manufacturers. Our manuscript outlines the timeframe for survey distribution and collection. After data collection ended, our senior author (DP) presented interim updates to the Clinical TMS Society. Data were not included in these interim updates until they were reviewed for inconsistencies (e.g., omissions, duplications, patients sessions, etc.), which was a longitudinal process. Importantly, supplementary analyses confirm that these quality control measures did not affect the results. The discussion section outlines the risks and benefits of drawing conclusions from a cross-sectional survey permitting anonymous responses.
Online celebrity bashing refers to a specific subform of online aggression in which celebrities a... more Online celebrity bashing refers to a specific subform of online aggression in which celebrities are the targets of derogatory messages. Recent research focusing on the underlying explanations of why some bystanders turn into perpetrators of celebrity bashing suggests that human capacity for empathy may regulate the involvement in this practice. Bystanders with higher empathy are thought to show more disapproval towards online celebrity bashing, which makes them less likely to join in this practice. However, little is known about the processes of how empathy steers bystanders' bashing attitudes and behavior. In this study, we examine whether the oxytocinergic system, which forms the neurophysiological foundation of empathy, influences the bystanders' acceptance of online celebrity bashing. In a double-blind, placebo-controlled experiment, we tested the effects of intranasal oxytocin administration on acceptance of celebrity bashing in men. Sixty participants rated neutral or derogatory comments presented as "tweets." Electrodermal activity and electrocardiogram of the participants were recorded to control for the stress levels. The results showed that oxytocin administration reduced the acceptance of celebrity bashing. Celebrity bashing was unrelated to stress levels. In natural circumstances oxytocin levels are dependent on the presence and quality of one's social relationships. As a result, we discuss the importance of facilitating a network of social support in programs addressing the problem of online aggression.
A growing literature suggests that the oxytocin (OT) system may play a role in human anxiety stat... more A growing literature suggests that the oxytocin (OT) system may play a role in human anxiety states, anxiety-related traits, and moreover, that this system may be a target for the development of novel anxiolytic treatments. However, studies of OT's acute and chronic effects on various aspects of anxiety have produced mixed results. In this forwardlooking review, we discuss the myriad phenomena to which the term "anxiety" is applied in the OT literature and the problem this presents developing a coherent picture of OT's role in anxiety. We then survey several different fields of research that support the role of the OT system in human anxiety, including evolutionary perspectives, translational and neuroimaging research, genetic studies, and clinical trials of intranasal OT. As an outgrowth of this data, we propose a "bowtie" model of OT's role at the interface of social attachment and anxiety. We next direct attention to understudied brain regions and neural circuits which may be important to study in OT experiments in humans anxiety disorders. Finally, we conclude by proposing questions and priorities for studying both the clinical potential of OT in anxiety, as well as mechanisms that may underlie this potential. Crucially, these priorities include targeted proof-of-concept clinical trials of IN OT in certain anxiety disorders, including investigations of individual moderators of OT's anxiolytic effects (i.e. sex, genetic factors, and early experience).
In this article Dr. Feifel, addresses some of the common questions associated with the use of ato... more In this article Dr. Feifel, addresses some of the common questions associated with the use of atomoxetine (Strattera ™ ) to treat patients with attention deficity hyperactivity disorder (ADHD). Dr. Feifel: A number of factors may be contributing to the differential perception of efficacy between stimulants and atomoxetine. The most basic explanation is that the magnitude of benefit for many patients may be greater with stimulants and there is some research to support this from headto-head studies 8,9 comparing atomoxetine to long-acting formulations of stimulant medications. However, in my opinion, other factors typically contribute to the perception of an efficacy gap. Central to these factors, I believe, is the fact that atomoxotine works via a different mechanism of action compared to the stimulants, and therefore, exhibits a different therapeutic time-course. Unlike stimulants, atomoxotine's ability to ameliorate ADHD symptoms begins early but accrues slowly and steadily over many weeks before the full benefits are achieved. In fact, data suggest that it may require 8 to 12 weeks before full benefits are seen. As a result, changes in patients are subtle and can, therefore, be much more easily overlooked by patients compared to the dramatic, rapid, symptomatic improvement that occurs with stimulants. In essence, patients may report that that atomoxetine is not having any effect, when indeed it may be producing a significant benefit, simply because it produces symptom improvement
There are compelling reasons why primary care physicians concerned about the well-being of their ... more There are compelling reasons why primary care physicians concerned about the well-being of their patients should strive to become competent in recognizing the symptoms of attention-deficit/hyperactivity disorder (ADHD). Despite lingering social controversy, the existence of ADHD among a portion of the adult population is well accepted among medical experts. Attention deficit/hyperactivity disorder in adulthood meets formal validity criteria established for medical disorders. An estimated 4% to 5% of the adult population is impaired by ADHD. However,less than one-quarter of these adults have been diagnosed as having ADHD
The objective of this study was to investigate the safety of repeated parenteral ketamine for dep... more The objective of this study was to investigate the safety of repeated parenteral ketamine for depression. An electronic survey inquiring about the frequency of adverse events was distributed to providers of parenteral ketamine for depression. In addition, the investigators conducted a search of published studies describing six or more repeated parenteral ketamine treatments administered to individuals for depression, and extracted reported adverse events. The survey was sent to 69 providers, of which 36 responded (52% response rate); after eliminating those that were incomplete, 27 were included in the analysis. The providers in the analysis collectively reported treating 6630 patients with parenteral ketamine for depression, one-third of whom received more than 10 treatments. Only 0.7% of patients experienced an adverse effect that required discontinuation of ketamine. Psychological distress during the treatment was the most frequent cause. Other adverse events were extremely rare (such as bladder dysfunction (0.1%), cognitive decline (0.03%) and psychotic symptoms (0.03%)). Among the 20 published reports of repeated parenteral ketamine treatments, rates of significant adverse events resulting in discontinuation were low (1.2%). The rate of adverse effects reported in the survey and the published literature is low, and suggests that long-term treatment of depression with ketamine is reasonably safe.
Iron overload has been suggested to be an unrecognized cause of psychiatric morbidity. This study... more Iron overload has been suggested to be an unrecognized cause of psychiatric morbidity. This study sought to estimate the prevalence of iron overload in a large outpatient psychiatric clinic. A retrospective review of screening blood chemistries was conducted on 661 active outpatients at a large, university outpatient psychiatric clinic to identify elevated iron status results (plasma iron, percentage of iron saturation) suggestive of iron overload. Patients with positive profiles were asked to undergo a subsequent blood chemistry to confirm positive results (plasma iron, percentage of iron saturation, plus plasma ferritin). Patients with positive repeated iron chemistry results were considered likely candidates for iron overload. Twenty-one patients (3.2%) were identified as meeting one of the criteria suggestive of iron overload on initial screening reports. Thirty-one percent of those who underwent subsequent, confirmatory testing (5/16) continued to meet one of the criteria. On the basis of these results, we estimated a 1% (3.2 x 0.31) prevalence rate of likely candidates for iron overload. A review of these patients' charts indicated that they carried an unexpectedly high rate of bipolar affective disorder (80%) as a diagnosis and were, without exception, atypical in that they were resistant to conventional psychiatric treatment and lacked a family history for this disorder. The prevalence of positive iron overload profiles on a routine blood chemistry was similar to the prevalence of positive thyroid abnormalities based on TSH results in this population. Blood chemistry profiles suggestive of iron overload may be associated with a small portion of treatment-resistant psychiatric patients. Routine screening for iron abnormalities, especially in treatment-resistant patients, should be considered. Further studies are required to determine the causal association, if any, between iron excess and primary psychiatric illnesses.
To the extent that chemicals can be fashionable, oxytocin is perhaps the most fashionable chemica... more To the extent that chemicals can be fashionable, oxytocin is perhaps the most fashionable chemical in neuroscience today. This nine amino acid peptide is appearing with regular frequency as the subject of scientific articles in the most prestigious journals in the field. The popular media have been quick to join the bandwagon, crafting stories that sensationally extoll oxytocin’s pro-social properties and dubbing it the ‘love hormone’ and the ‘cuddle hormone’. Given the strong evidence of oxy tocin’s ability to enhance social cognition, there has been much speculation about its potential role in the etiology and treatment of psychiatric disorders. Autism spectrum disorders and social phobia have garnered the most attention in this regard for obvious reasons. Less obvious is oxytocin’s possible role in schizophrenia. Over a decade ago my laboratory conducted a preclinical proofof-concept study to test our hypothesis that oxytocin exhibits antipsychotic-like effects. This hypothesis was based mostly on evidence that oxytocin regulated central dopamine. That study, conducted in rats, revealed that systemically administered oxytocin, similar to most atypical antipsychotics, reversed prepulse inhibition deficits induced by amphetamine and the phencyclidine analog, MK801 [1]. Those antipsychotic-like results were surprising, even to my team, since oxytocin has a poor ability to penetrate the BBB. Since then, a number of investigators have reported finding antipsychotic-like effects attributed to endogenous oxytocin or systemically administered oxytocin in several different animal models relevant to schizophrenia [2,3]. The accumulation of those promising preclinical findings, as well as numerous studies demonstrating that intranasal oxytocin enhances trust and other pro-social inclinations [4,5], have recently spurred the initiation of several small clinical trials to test the therapeutic potential of oxy tocin in schizophrenia. Our group recently completed the first such proof-ofconcept clinical trial: a double-blinded, placebo-controlled crossover design enrolling schizophrenia patients who were highly symptomatic despite receiving therapeutic doses of an atypical antipsychotic. Intranasal oxytocin (40 international units twice a day) administered as an adjunct to the subjects’ antipsychotic for 3 weeks improved positive and negative symptoms significantly more than placebo did [6]. Recently, another group of investigators at the University of North Carolina (UNC; NC, USA), led by Cort Pedersen reported preliminary results from their own study of adjunctive intranasal oxytocin in schizophrenia patients [7]. They found that 2 weeks of daily intranasal oxytocin significantly reduced schizophrenia symptoms, adding support to the notion that oxytocin has therapeutic potential for the core symptoms of schizophrenia. David Feifel
Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsa... more Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatalthalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study. Methods: At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of $30% in YBOCS score) at the posttreatment assessment and after another month of follow-up. Results: Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up. Conclusions: High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions.
Modeling schizophrenia in animals represents a formidable challenge because the most characterist... more Modeling schizophrenia in animals represents a formidable challenge because the most characteristic symptoms of this disorder, auditory hallucinations and delusional beliefs, cannot be directly modeled in animals. Furthermore, limited current understanding of the etiology and pathophysiology underlying the clinical features of this disorder greatly hinders the ability to develop valid models based on those aspects. To circumvent these issues, investigators have attempted to recreate the leading candidate biochemical, neuroanatomical, and genetic abnormalities for this disorder in animals using pharmacological, developmental, neurotoxic, genetic engineering, and other methods. The validity of these animal preparations as animal models for schizophrenia is generally based upon the extent to which they induce measurable behavioral changes that are homologous or analogous to the core clinical features or the information-processing endophenotypes (presymptom phenotypes) that are seen in schizophrenia. The utility of any animal model to serve as a screen for novel treatments is considered related to the extent to which the schizophrenia-relevant behaviors it exhibits can be ameliorated by drugs with known efficacy in schizophrenia but not by drugs known to be therapeutic for brain disorders other than schizophrenia.
We investigated use of Daytrana in the first year post-launch in the US: May, 2006 through April,... more We investigated use of Daytrana in the first year post-launch in the US: May, 2006 through April, 2007. According to our data, a total of 512,085 prescriptions for Daytrana were written in the first year of launch; psychiatry accounted for 34 percent of these prescriptions. Children and adolescents represented 88 percent of Daytrana users as compared to only 57 percent for the broader ADHD market. Expert commentary describing these trends is provided.
In this article, we investigate the range of treatments prescribed to children with autism. The d... more In this article, we investigate the range of treatments prescribed to children with autism. The data suggest that approximately 58 percent of patients with a diagnosis of childhood autism receive some type of pharmaceutical treatment. The majority of those treated, 68 percent, receive only one pharmaceutical. The most commonly prescribed products are antipsychotics (66%), antidepressants (32%), and stimulants (17%). An expert commentary is included.
Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach t... more Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression. Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.
Although overall prescribing of atomoxetine hydrochloride (HCI) (Strattera) continues to decline,... more Although overall prescribing of atomoxetine hydrochloride (HCI) (Strattera) continues to decline, recent anecdotal reports suggest emerging uses of the product in combination therapy. In this article we examine trends in atomoxetine (HCI) prescribing as well as use in combination with other psychotropic classes. An expert commentary is provided on the data.
ver the past few years, several papers examining the significant increase in atypical antipsychot... more ver the past few years, several papers examining the significant increase in atypical antipsychotic use among children and adolescents have been published-1-3 the most recent of which was published in Archives of General Psychiatry in June of 2006. This paper demonstrated roughly a six-fold increase over the 1993 to 2002 timeframe in office-based mental health visits among individuals age 0 to 20 that included an antipsychotic. 4 This data, however, is somewhat limited due to the time lag in availability of information and the potential bias inherent in the datasource (nonpatient-specific, physician-reported information).
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Papers by David Feifel