Pub Date : 2001-12-01DOI: 10.1017/S146114570100267X
O. Vinař
The message that assignment to placebo does not increase the risk of suicidal behaviour in patients who participate in double-blind randomized trials (Khan et al., 2001) is important but hardly surprising. The risk of suicidal behaviour is one of the exclusion criteria in placebocontrolled trials. Patients with this risk should be omitted from study samples. The analysis of Khan et al. (2001) shows that the risk is not manifest in patients on placebo any more than in patients on antidepressants during trials. What is surprising is the small difference (12±4%) between antidepressants and placebo in the decrease of the total Hamilton Depression Scale (HAMD) score. The authors give relevant reasons to explain the small difference. I would like to add another reason, which could explain the small difference even more. Total HAMD score is an arithmetical sum of scores of items that are not equal with respect to their relevance for the clinical severity of the disorder. I would expect that the active drug–placebo difference would be greater in scores of the item ‘depressed mood ’ than in the items related to insomnia. The importance of this approach was previously shown by Cole and Davis (1968). They summarized the results of collaborative studies organized by the Psychopharmacology Service Center of the NIMH and several other studies. Analysing the effect of phenothiazine neuroleptics compared to placebo they found that the active drugs were unequivocally more effective. Then, they divided the symptoms according to Bleuler (1911) into accessory (hallucinations, paranoid ideation and hostility) and fundamental symptoms (blunted affect, withdrawal– retardation, autistic behaviour and thought disorder). They found moderate change under placebo on accessory symptoms with little or no change during placebo administration in fundamental symptoms. The greatest amount of total clinical change occurred in the accessory symptoms when drug-induced change was added to change which occurred during placebo administration alone. However, the differential effect of phenothiazines as opposed to placebo was more striking on the fundamental symptoms of schizophrenia.
{"title":"Do antidepressants help much in comparison to placebo?","authors":"O. Vinař","doi":"10.1017/S146114570100267X","DOIUrl":"https://doi.org/10.1017/S146114570100267X","url":null,"abstract":"The message that assignment to placebo does not increase the risk of suicidal behaviour in patients who participate in double-blind randomized trials (Khan et al., 2001) is important but hardly surprising. The risk of suicidal behaviour is one of the exclusion criteria in placebocontrolled trials. Patients with this risk should be omitted from study samples. The analysis of Khan et al. (2001) shows that the risk is not manifest in patients on placebo any more than in patients on antidepressants during trials. What is surprising is the small difference (12±4%) between antidepressants and placebo in the decrease of the total Hamilton Depression Scale (HAMD) score. The authors give relevant reasons to explain the small difference. I would like to add another reason, which could explain the small difference even more. Total HAMD score is an arithmetical sum of scores of items that are not equal with respect to their relevance for the clinical severity of the disorder. I would expect that the active drug–placebo difference would be greater in scores of the item ‘depressed mood ’ than in the items related to insomnia. The importance of this approach was previously shown by Cole and Davis (1968). They summarized the results of collaborative studies organized by the Psychopharmacology Service Center of the NIMH and several other studies. Analysing the effect of phenothiazine neuroleptics compared to placebo they found that the active drugs were unequivocally more effective. Then, they divided the symptoms according to Bleuler (1911) into accessory (hallucinations, paranoid ideation and hostility) and fundamental symptoms (blunted affect, withdrawal– retardation, autistic behaviour and thought disorder). They found moderate change under placebo on accessory symptoms with little or no change during placebo administration in fundamental symptoms. The greatest amount of total clinical change occurred in the accessory symptoms when drug-induced change was added to change which occurred during placebo administration alone. However, the differential effect of phenothiazines as opposed to placebo was more striking on the fundamental symptoms of schizophrenia.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126403468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002607
C. Reist, Joseph James Duffy, K. Fujimoto, L. Cahill
Emotional arousal has been shown to enhance memory, an effect that is blocked by propranolol suggesting that the noradrenergic system is important in the mechanism action. Because PTSD has as prominent features heightened arousal and distressing memories, the current study was undertaken to examine whether PTSD subjects differed from controls in emotional enhancement of memory. Seventeen subjects with PTSD and 21 controls received either placebo or 40 mg of propranolol prior to exposure to either an emotionally arousing or emotionally neutral, narrated slide story. Recall, measured 1 wk later, for the arousing story was enhanced and this effect was reduced by propranolol. PTSD and control subjects did not differ in the acquisition and retention of memories under emotionally arousing or emotionally neutral conditions, nor were differential effects of propranolol observed between the two groups.
{"title":"beta-Adrenergic blockade and emotional memory in PTSD.","authors":"C. Reist, Joseph James Duffy, K. Fujimoto, L. Cahill","doi":"10.1017/S1461145701002607","DOIUrl":"https://doi.org/10.1017/S1461145701002607","url":null,"abstract":"Emotional arousal has been shown to enhance memory, an effect that is blocked by propranolol suggesting that the noradrenergic system is important in the mechanism action. Because PTSD has as prominent features heightened arousal and distressing memories, the current study was undertaken to examine whether PTSD subjects differed from controls in emotional enhancement of memory. Seventeen subjects with PTSD and 21 controls received either placebo or 40 mg of propranolol prior to exposure to either an emotionally arousing or emotionally neutral, narrated slide story. Recall, measured 1 wk later, for the arousing story was enhanced and this effect was reduced by propranolol. PTSD and control subjects did not differ in the acquisition and retention of memories under emotionally arousing or emotionally neutral conditions, nor were differential effects of propranolol observed between the two groups.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126886234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-12-01DOI: 10.1017/S1461145701002553
L. Johnson, A. El-Khoury, A. Åberg‐Wistedt, R. Stain-Malmgren, A. Mathé
Central serotonergic function abnormalities are thought to be associated with the pathogenesis of affective disorder. Reduced serotonergic function, induced by tryptophan depletion, has in several studies transiently reversed the antidepressant effect of SSRIs in depressed patients in remission. Serotonergic pathways are suggested to be of importance in the mechanisms of the action of lithium. The purpose of this study was to investigate whether the stabilizing effect of lithium is dependent on short-term availability of serotonin. Tryptophan depletion was induced in thirty patients with affective disorder (20 bipolar and 10 unipolar), all stabilized on lithium treatment for at least one year. The study was performed using a randomized, double-blind, controlled design. Plasma tryptophan was reduced by 80% in the experimental group and 16% in the control group. However, no clinically relevant mood changes were observed. Transient reduction in serotonergic function does not seem to affect mood in affective-disorder patients stabilized on lithium treatment.
{"title":"Tryptophan depletion in lithium-stabilized patients with affective disorder.","authors":"L. Johnson, A. El-Khoury, A. Åberg‐Wistedt, R. Stain-Malmgren, A. Mathé","doi":"10.1017/S1461145701002553","DOIUrl":"https://doi.org/10.1017/S1461145701002553","url":null,"abstract":"Central serotonergic function abnormalities are thought to be associated with the pathogenesis of affective disorder. Reduced serotonergic function, induced by tryptophan depletion, has in several studies transiently reversed the antidepressant effect of SSRIs in depressed patients in remission. Serotonergic pathways are suggested to be of importance in the mechanisms of the action of lithium. The purpose of this study was to investigate whether the stabilizing effect of lithium is dependent on short-term availability of serotonin. Tryptophan depletion was induced in thirty patients with affective disorder (20 bipolar and 10 unipolar), all stabilized on lithium treatment for at least one year. The study was performed using a randomized, double-blind, controlled design. Plasma tryptophan was reduced by 80% in the experimental group and 16% in the control group. However, no clinically relevant mood changes were observed. Transient reduction in serotonergic function does not seem to affect mood in affective-disorder patients stabilized on lithium treatment.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133518022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-09-01DOI: 10.1017/S1461145701002437
W. Vaughn McCall
Fifty years of advances in the pharmacotherapy of major depression (MDE), mania, schizophrenia, and other severe and persistent psychiatric disorders have neither made ECT obsolete nor unnecessary. However, advances in pharmacotherapy have radically changed the practice of ECT. ECT is rarely a first-line treatment of mental disorder, unless the clinical situation is desperate. Otherwise, ECT is most often offered to persons who have failed to respond to pharmacotherapy, thus defining a relatively treatment-refractory population for ECT. The physician who refers patients for ECT, as well as the ECT provider, must be able to judge at what point a patient is deemed "medication resistant", implying expertise in pharmacotherapy for both the referring physician and the ECT provider. Authoritative sources from 20 years ago quoted antidepressant response rates > or = 90% for ECT, but the antidepressant response rate in medication-resistant MDE may be only 60%. Improvements in the safety of ECT have resulted in the referral of large numbers of older persons for ECT. High relapse rates after ECT are perhaps the biggest problem presently facing patients and providers. High relapse rates are not surprising given that (i) most patients are medication resistant, and (ii) ECT is usually withdrawn at the moment it becomes effective. Although continuation/maintenance ECT is an option in preventing relapse, it may not be a practical solution for persons still in their productive years, and it is resource-intensive. Still, continuation/maintenance ECT is the only method to prevent relapse and recurrence of severe psychiatric disorder for some persons.
{"title":"Electroconvulsive therapy in the era of modern psychopharmacology.","authors":"W. Vaughn McCall","doi":"10.1017/S1461145701002437","DOIUrl":"https://doi.org/10.1017/S1461145701002437","url":null,"abstract":"Fifty years of advances in the pharmacotherapy of major depression (MDE), mania, schizophrenia, and other severe and persistent psychiatric disorders have neither made ECT obsolete nor unnecessary. However, advances in pharmacotherapy have radically changed the practice of ECT. ECT is rarely a first-line treatment of mental disorder, unless the clinical situation is desperate. Otherwise, ECT is most often offered to persons who have failed to respond to pharmacotherapy, thus defining a relatively treatment-refractory population for ECT. The physician who refers patients for ECT, as well as the ECT provider, must be able to judge at what point a patient is deemed \"medication resistant\", implying expertise in pharmacotherapy for both the referring physician and the ECT provider. Authoritative sources from 20 years ago quoted antidepressant response rates > or = 90% for ECT, but the antidepressant response rate in medication-resistant MDE may be only 60%. Improvements in the safety of ECT have resulted in the referral of large numbers of older persons for ECT. High relapse rates after ECT are perhaps the biggest problem presently facing patients and providers. High relapse rates are not surprising given that (i) most patients are medication resistant, and (ii) ECT is usually withdrawn at the moment it becomes effective. Although continuation/maintenance ECT is an option in preventing relapse, it may not be a practical solution for persons still in their productive years, and it is resource-intensive. Still, continuation/maintenance ECT is the only method to prevent relapse and recurrence of severe psychiatric disorder for some persons.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133426085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-09-01DOI: 10.1017/S1461145701002504
R. B. Hidalgo, S. Barnett, J. Davidson
Social anxiety disorder (SAD) is among the most common of all psychiatric disorders. It presents with a lifetime prevalence rate of up to 16% in the general population and, like other anxiety disorders, is more frequent in women. Patients with SAD suffer from considerable psychiatric comorbidity that is often preceded by social anxiety. Social anxiety affects people early in life and provokes a great deal of impairment and cost, much being related to the under-recognition and/or under-treatment of this disorder, which occurs frequently with GPs and others specialists. There is a clear need among GPs for training and awareness about the existence of this disorder, its assessment, differential diagnosis and available treatments. In this paper we review the development of the concept of SAD and its epidemiology, and discuss the available information regarding cost and how SAD presents in primary-care settings. Potential aetiologies and studies concerning possible neurobiological mechanisms are also reviewed. Pharmacological and psychosocial treatments for SAD are examined and effect sizes calculated for placebo-controlled pharmacological studies of five medication categories.
{"title":"Social anxiety disorder in review: two decades of progress.","authors":"R. B. Hidalgo, S. Barnett, J. Davidson","doi":"10.1017/S1461145701002504","DOIUrl":"https://doi.org/10.1017/S1461145701002504","url":null,"abstract":"Social anxiety disorder (SAD) is among the most common of all psychiatric disorders. It presents with a lifetime prevalence rate of up to 16% in the general population and, like other anxiety disorders, is more frequent in women. Patients with SAD suffer from considerable psychiatric comorbidity that is often preceded by social anxiety. Social anxiety affects people early in life and provokes a great deal of impairment and cost, much being related to the under-recognition and/or under-treatment of this disorder, which occurs frequently with GPs and others specialists. There is a clear need among GPs for training and awareness about the existence of this disorder, its assessment, differential diagnosis and available treatments. In this paper we review the development of the concept of SAD and its epidemiology, and discuss the available information regarding cost and how SAD presents in primary-care settings. Potential aetiologies and studies concerning possible neurobiological mechanisms are also reviewed. Pharmacological and psychosocial treatments for SAD are examined and effect sizes calculated for placebo-controlled pharmacological studies of five medication categories.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124020106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-09-01DOI: 10.1017/S1461145701002450
A. Vaccari, S. Ruiu, P. Saba, M. Fà, R. Cagiano, A. Coluccia, G. Mereu, L. Steardo, M. Tattoli, L. Trabace, V. Cuomo
The effects of prenatal CO exposure (150 ppm from days 0 to 20 of pregnancy) on the postnatal development of hippocampal neuronal NO synthase (nNOS) and haem-oxygenase (HO-2) isoform activities in 15-, 30- and 90-d-old rats were investigated. Unlike HO-2, hippocampal nNOS activity increased from postnatal days 15-90 in controls. Prenatal CO produced a long-lasting decrease in either nNOS or HO-2. The results suggest that the altered developmental profile of hippocampal nNOS and HO-2 activities could be involved in cognitive deficits and long-term potentiation dysfunction exhibited by rats prenatally exposed to CO levels resulting in carboxyhaemoglobin (HbCO) levels equivalent to those observed in human cigarette smokers.
{"title":"Prenatal low-level exposure to CO alters postnatal development of hippocampal nitric oxide synthase and haem-oxygenase activities in rats.","authors":"A. Vaccari, S. Ruiu, P. Saba, M. Fà, R. Cagiano, A. Coluccia, G. Mereu, L. Steardo, M. Tattoli, L. Trabace, V. Cuomo","doi":"10.1017/S1461145701002450","DOIUrl":"https://doi.org/10.1017/S1461145701002450","url":null,"abstract":"The effects of prenatal CO exposure (150 ppm from days 0 to 20 of pregnancy) on the postnatal development of hippocampal neuronal NO synthase (nNOS) and haem-oxygenase (HO-2) isoform activities in 15-, 30- and 90-d-old rats were investigated. Unlike HO-2, hippocampal nNOS activity increased from postnatal days 15-90 in controls. Prenatal CO produced a long-lasting decrease in either nNOS or HO-2. The results suggest that the altered developmental profile of hippocampal nNOS and HO-2 activities could be involved in cognitive deficits and long-term potentiation dysfunction exhibited by rats prenatally exposed to CO levels resulting in carboxyhaemoglobin (HbCO) levels equivalent to those observed in human cigarette smokers.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"144 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124593229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-09-01DOI: 10.1017/S1461145701002528
S. Potkin, R. Anand, K. Fleming, G. Alva, D. Keator, D. Carreon, J. Messina, Joseph C. Wu, R. Hartman, J. Fallon
In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.
使用(18)f -氟脱氧葡萄糖(FDG-PET)的正电子发射断层扫描的体内代谢测量显示，在阿尔茨海默病(AD)的早期阶段，颞叶、额叶和海马区域的代谢水平较低。阿尔茨海默病痴呆的进展涉及胆碱能功能受损。胆碱酯酶抑制剂在改善阿尔茨海默病患者的认知和行为方面已被证实有效。在这项研究中，我们证明了FDG-PET在测量未经治疗的AD的进展及其通过利瓦斯替明(Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA)治疗的有效性，利瓦斯替明是一种氨基甲酸酯型的中央选择性胆碱酯酶抑制剂。轻度至中度可能AD的患者(Mini-Mental Status Exam得分为10-26分，包括在内)被纳入双盲、安慰剂对照研究，他们每天服用三种固定剂量的利瓦斯汀(3、6或9 mg/d)或安慰剂，持续26周。27名患者在基线和治疗26周后使用Snodgrass图片命名激活任务获得FDG-PET扫描。接受安慰剂治疗的患者中，71.4%的患者出现临床恶化，而接受利瓦斯汀治疗的患者中，这一比例仅为25.0% (chi2 = 4.8;P & 0.03)。利瓦斯汀应答者(即那些临床改善或保持临床稳定的人，通过临床访谈-基于改变-plus的印象测量)显示出脑代谢的显著增加(p <0.01)，涉及但不限于包括记忆相关皮层和前额叶系统的结构。这些代谢变化没有在安慰剂治疗的患者或对利瓦斯汀无反应的患者中观察到。值得注意的是，反应者海马代谢增加了32.5% (p < 0.03)，而无反应者(6.4%)和安慰剂治疗患者(4.1%)的海马代谢没有显著下降。这些结果与文献一致，表明FDG-PET可以灵敏地测量AD的进展以及胆碱酯酶抑制剂对AD的改善。在大多数患者中，利瓦斯汀防止了预期的临床状况恶化，并显著增加了脑代谢活动。
{"title":"Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.","authors":"S. Potkin, R. Anand, K. Fleming, G. Alva, D. Keator, D. Carreon, J. Messina, Joseph C. Wu, R. Hartman, J. Fallon","doi":"10.1017/S1461145701002528","DOIUrl":"https://doi.org/10.1017/S1461145701002528","url":null,"abstract":"In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133162388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-09-01DOI: 10.1017/S1461145701002462
R. Strous, B. Spivak, R. Yoran-Hegesh, R. Maayan, E. Averbuch, M. Kotler, R. Mester, Abraham Weizman
Neurosteroids are important neuroactive substrates with demonstrated involvement in several neurophysiological and disease processes. Attention deficit hyperactivity disorder (ADHD) has been associated with dysregulation of the catecholaminergic and serotonergic systems, however its relationship to irregularities or changes in neurosteroid levels remains unknown. We examined the relationship between blood levels of dehydroepiandrosterone (DHEA), its principal precursor pregnenolone and its principal metabolite dehydroepiandrosterone sulphate (DHEAS) in 29 young male subjects aged 7-15 years with DSM-IV criteria of ADHD. Subjects were evaluated by a specially designed scale, following which patients were divided into two groups according to severity of symptomatology. Results indicated significant inverse correlations between clinical symptomatology and levels of DHEA and pregnenolone in the total group. These inverse correlations were particularly evident in the less severe group of subjects. Levels of DHEA and DHEAS were inversely correlated with the hyperactivity subscale. Furthermore, using median blood levels as a cut-off indicator, higher blood levels of DHEA and DHEAS were associated with fewer ADHD symptoms, in particular hyperactivity symptomatology. Our findings suggest a possible protective effect of various neurosteroids on the expression of ADHD symptomatology.
{"title":"Analysis of neurosteroid levels in attention deficit hyperactivity disorder.","authors":"R. Strous, B. Spivak, R. Yoran-Hegesh, R. Maayan, E. Averbuch, M. Kotler, R. Mester, Abraham Weizman","doi":"10.1017/S1461145701002462","DOIUrl":"https://doi.org/10.1017/S1461145701002462","url":null,"abstract":"Neurosteroids are important neuroactive substrates with demonstrated involvement in several neurophysiological and disease processes. Attention deficit hyperactivity disorder (ADHD) has been associated with dysregulation of the catecholaminergic and serotonergic systems, however its relationship to irregularities or changes in neurosteroid levels remains unknown. We examined the relationship between blood levels of dehydroepiandrosterone (DHEA), its principal precursor pregnenolone and its principal metabolite dehydroepiandrosterone sulphate (DHEAS) in 29 young male subjects aged 7-15 years with DSM-IV criteria of ADHD. Subjects were evaluated by a specially designed scale, following which patients were divided into two groups according to severity of symptomatology. Results indicated significant inverse correlations between clinical symptomatology and levels of DHEA and pregnenolone in the total group. These inverse correlations were particularly evident in the less severe group of subjects. Levels of DHEA and DHEAS were inversely correlated with the hyperactivity subscale. Furthermore, using median blood levels as a cut-off indicator, higher blood levels of DHEA and DHEAS were associated with fewer ADHD symptoms, in particular hyperactivity symptomatology. Our findings suggest a possible protective effect of various neurosteroids on the expression of ADHD symptomatology.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123804380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-09-01DOI: 10.1017/S1461145701002498
P. Dannon, L. Grunhaus
The aim of this study was to measure the effectiveness of ECT in-patients who had failed to respond to a course of repetitive transcranial magnetic stimulation (rTMS) treatment. Seventeen patients with severe MDD who had not responded to a course of rTMS were switched to receive ECT treatments. All the patients were assessed with the Hamilton Rating Scale for Depression, the Global Assessment Functioning Scale, the Global Depression Scale, and the Pittsburgh Sleep Quality Index. Response to the treatment was defined as a 50% decrease in HDRS final score and a final GAS higher than 60. Seven out of 17 patients responded to ECT. Three out of 5 non-psychotics and 4 out of 12 psychotic patients responded. ECT seems to be an effective treatment for 40% of patients who failed to respond to rTMS treatment. Whether this is a result of reduced responsiveness to ECT in rTMS-resistant patients or a consequence of small sample size requires further study.
{"title":"Effect of electroconvulsive therapy in repetitive transcranial magnetic stimulation non-responder MDD patients: a preliminary study.","authors":"P. Dannon, L. Grunhaus","doi":"10.1017/S1461145701002498","DOIUrl":"https://doi.org/10.1017/S1461145701002498","url":null,"abstract":"The aim of this study was to measure the effectiveness of ECT in-patients who had failed to respond to a course of repetitive transcranial magnetic stimulation (rTMS) treatment. Seventeen patients with severe MDD who had not responded to a course of rTMS were switched to receive ECT treatments. All the patients were assessed with the Hamilton Rating Scale for Depression, the Global Assessment Functioning Scale, the Global Depression Scale, and the Pittsburgh Sleep Quality Index. Response to the treatment was defined as a 50% decrease in HDRS final score and a final GAS higher than 60. Seven out of 17 patients responded to ECT. Three out of 5 non-psychotics and 4 out of 12 psychotic patients responded. ECT seems to be an effective treatment for 40% of patients who failed to respond to rTMS treatment. Whether this is a result of reduced responsiveness to ECT in rTMS-resistant patients or a consequence of small sample size requires further study.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122806080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-09-01DOI: 10.1017/S1461145701002516
B. Camarena, G. Rinetti, C. Cruz, Sandra Hernández, Juan Ramón de la Fuente, Humberto Nicolini
The hypothesis implicating the serotonergic system in the pathophysiology of obsessive-compulsive disorder (OCD) is supported by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). Since SSRIs act on the serotonin transporter (5-HTT), it has been suggested that the 5-HTT gene (SCL6A4) could be a good candidate for OCD. The SCL6A4 gene has a 44-bp insertion/deletion polymorphism in its promoter region (5-HTTLPR). Previous studies have revealed an association between OCD and the l allele. We analysed the 5-HTTLPR polymorphic system in 115 Mexican OCD patients and 136 controls. No significant association was found between l allele and OCD (chi2 = 1.54, d.f. = 1, p = 0.21). Furthermore, we assessed alternative methods that employ family-based designs in a sample of 43 trios. Haplotype-based haplotype relative risk and transmission disequilibrium analysis did not show a preferential transmission of l allele to OCD probands. Our results indicate the need to analyse larger samples using family-based methods.
{"title":"Association study of the serotonin transporter gene polymorphism in obsessive-compulsive disorder.","authors":"B. Camarena, G. Rinetti, C. Cruz, Sandra Hernández, Juan Ramón de la Fuente, Humberto Nicolini","doi":"10.1017/S1461145701002516","DOIUrl":"https://doi.org/10.1017/S1461145701002516","url":null,"abstract":"The hypothesis implicating the serotonergic system in the pathophysiology of obsessive-compulsive disorder (OCD) is supported by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). Since SSRIs act on the serotonin transporter (5-HTT), it has been suggested that the 5-HTT gene (SCL6A4) could be a good candidate for OCD. The SCL6A4 gene has a 44-bp insertion/deletion polymorphism in its promoter region (5-HTTLPR). Previous studies have revealed an association between OCD and the l allele. We analysed the 5-HTTLPR polymorphic system in 115 Mexican OCD patients and 136 controls. No significant association was found between l allele and OCD (chi2 = 1.54, d.f. = 1, p = 0.21). Furthermore, we assessed alternative methods that employ family-based designs in a sample of 43 trios. Haplotype-based haplotype relative risk and transmission disequilibrium analysis did not show a preferential transmission of l allele to OCD probands. Our results indicate the need to analyse larger samples using family-based methods.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127900809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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