пятница, 19 февраля 2010 г.
Субъективные ощущения и степень блокады D2-рецепторов
We found a correlation between striatal D2 receptor occupancy by olanzapine and risperidone and subjective experience, negative symptoms, and depression, in the absence of extrapyramidal symptoms. Higher doses of olanzapine were correlated with higher D2 receptor occupancy and worse subjective experience. Negative subjective experience might be more sensitive to D2 receptor occupancy than extrapyramidal symptoms. The substantial D2 receptor occupancy of olanzapine and risperidone we found is in agreement with the recent findings of others (9).
RESULTS: Subjective experience, depression, and negative symptoms were related to dopamine D2 receptor occupancy, but extrapyramidal symptoms were not.CONCLUSIONS: These results provide preliminary evidence that negative subjective experience is related to high D2 receptor occupancy. Longitudinal study is required because this relationship may have implications for dosing strategies.
Subjective Experience and Striatal Dopamine D2 Receptor Occupancy in Patients With Schizophrenia Stabilized by Olanzapine or Risperidone
RESULTS: Subjective experience, depression, and negative symptoms were related to dopamine D2 receptor occupancy, but extrapyramidal symptoms were not.CONCLUSIONS: These results provide preliminary evidence that negative subjective experience is related to high D2 receptor occupancy. Longitudinal study is required because this relationship may have implications for dosing strategies.
Subjective Experience and Striatal Dopamine D2 Receptor Occupancy in Patients With Schizophrenia Stabilized by Olanzapine or Risperidone
Атипичность атипичных антипсихотиков
The main reason for the development of atypical antipsychotics was to provide an antipsychotic treatment option that was free of EPS and, further, to reduce the risk of tardive dyskinesia. Although many agents now claim to be atypical, the data presented suggest that only clozapine and quetiapine are true atypical antipsychotics. Of the available agents, clozapine and quetiapine show the lowest affinity for and the most rapid release from D2 receptors.3 As a result, clozapine and quetiapine have been shown to have an incidence of EPS that was no different from placebo across the full dosage range.4
Promotion of risperidone, olanzapine, ziprasidone, and possibly aripiprazole has emphasized the atypicality of these agents; however, based on the data presented here, one should question whether these agents are truly atypical antipsychotics. Both risperidone and olanzapine have demonstrated EPS levels similar to placebo at low doses; at higher doses, however, EPS incidence for both agents becomes greater than with placebo.4 Data for ziprasidone are limited; however, ziprasidone appears to have an EPS risk similar to that of risperidone and olanzapine.56,57 Ari-piprazole has been associated with akathisia; however, further study and experience with this drug are needed before definitive conclusions can be drawn.
Atypicality of Atypical Antipsychotics
Promotion of risperidone, olanzapine, ziprasidone, and possibly aripiprazole has emphasized the atypicality of these agents; however, based on the data presented here, one should question whether these agents are truly atypical antipsychotics. Both risperidone and olanzapine have demonstrated EPS levels similar to placebo at low doses; at higher doses, however, EPS incidence for both agents becomes greater than with placebo.4 Data for ziprasidone are limited; however, ziprasidone appears to have an EPS risk similar to that of risperidone and olanzapine.56,57 Ari-piprazole has been associated with akathisia; however, further study and experience with this drug are needed before definitive conclusions can be drawn.
Atypicality of Atypical Antipsychotics
Арипипрозол для коррекции нейролептик-индуцированной гиперпролактинемии
OBJECTIVE: Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol. METHOD: Fifty-six patients with hyperprolactinemia taking haloperidol were enrolled. Haloperidol dose was fixed; aripiprazole was dosed at 15 mg/day for the first 4 weeks, then 30 mg/day for the following 4 weeks. Serum prolactin, haloperidol, and aripiprazole levels were measured. Symptoms and side effects were assessed with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms, Clinical Global Impression symptom scale, Simpson-Angus Rating Scale, and Barnes Akathisia Rating Scale at weeks 1, 2, 4, 6, and 8. RESULTS: Prolactin levels of patients receiving aripiprazole significantly decreased over time, demonstrating a significant time effect and a time-by-group interaction. In the aripiprazole group, 88.5% of patients at week 8 had prolactin levels normalize compared to 3.6% of patients receiving placebo. Among 11 female patients with menstrual disturbances randomly assigned to aripiprazole, seven patients regained menstruation during the study, whereas none receiving placebo did. Plasma levels of haloperidol were not significantly altered. No significant time effect and time-by-group interactions on BPRS, Scale for the Assessment of Negative Symptoms, and Simpson-Angus Rating Scale scores were noted. CONCLUSIONS: Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D2 receptors than haloperidol, which is the likely cause of this observation.
Adjunctive Treatment With a Dopamine Partial Agonist, Aripiprazole, for Antipsychotic-Induced Hyperprolactinemia: A Placebo-Controlled Trial
Adjunctive Treatment With a Dopamine Partial Agonist, Aripiprazole, for Antipsychotic-Induced Hyperprolactinemia: A Placebo-Controlled Trial
понедельник, 15 февраля 2010 г.
Противотревожный эффект экстракта ромашки
A new randomized control research trial has found that chamomile helps lessen symptoms of mild to moderate general anxiety disorder.
As a herbal remedy, chamomile tea has been used for centuries to calm nerves and its oil has been an ingredient in commercial flavors and perfumes.
The study, published in the Journal of Clinical Psychopharmacology, reports that “chamomile extract therapy was found to be efficacious for mild-moderate GAD.”
Patients with mild-moderate GAD were included in the study and received either chamomile or placebo. Those that received the chamomile treatment were found to have a significant change in the severity of their GAD.
Evaluators Michael Van Ameringen and Beth Patterson comment on the results of the study, saying that they “suggest that chamomile may have modest [anti-panic] activity in patients with mild-moderate GAD and may potentially be used in those who are averse to traditional pharmacotherapy.”
These findings are important “because many individuals who suffer from GAD do not view their anxiety as a medical condition, [and, therefore,] self-diagnosis and self-medicating with alternative, over-the-counter remedies is common.”
Van Amerigen and Patterson said “a big strength of this paper is that the authors took a herbal remedy and subjected it to scientific rigor unlike many ‘natural’ remedies which have associated claims of efficacy with no supportive data.”
Chamomile for Anxiety
As a herbal remedy, chamomile tea has been used for centuries to calm nerves and its oil has been an ingredient in commercial flavors and perfumes.
The study, published in the Journal of Clinical Psychopharmacology, reports that “chamomile extract therapy was found to be efficacious for mild-moderate GAD.”
Patients with mild-moderate GAD were included in the study and received either chamomile or placebo. Those that received the chamomile treatment were found to have a significant change in the severity of their GAD.
Evaluators Michael Van Ameringen and Beth Patterson comment on the results of the study, saying that they “suggest that chamomile may have modest [anti-panic] activity in patients with mild-moderate GAD and may potentially be used in those who are averse to traditional pharmacotherapy.”
These findings are important “because many individuals who suffer from GAD do not view their anxiety as a medical condition, [and, therefore,] self-diagnosis and self-medicating with alternative, over-the-counter remedies is common.”
Van Amerigen and Patterson said “a big strength of this paper is that the authors took a herbal remedy and subjected it to scientific rigor unlike many ‘natural’ remedies which have associated claims of efficacy with no supportive data.”
Chamomile for Anxiety
четверг, 11 февраля 2010 г.
Аллостерическая регуляция мускариновых холинорецепторов как возможный механизм терапии шизофрении
Current antipsychotics provide symptomatic relief for patients suffering from schizophrenia and related psychoses; however, their effectiveness is variable and many patients discontinue treatment due to side effects. Although the etiology of schizophrenia is still unclear, a leading hypothesis implicates an imbalanced dopaminergic system. Muscarinic acetylcholine (ACh) receptors regulate dopamine levels in key areas of the brain involved in psychosis, with the M(4) subtype emerging as a key regulator of dopaminergic hyperactivity. Unfortunately, no selective small molecule tools exist to provide pharmacological validation of this hypothesis. Here, we describe the discovery of a small molecule modulator, LY2033298, that is highly selective for human M(4) receptors by virtue of targeting an allosteric site on this receptor. Pharmacological assays confirmed the selectivity of LY2033298 for the M(4) receptor and revealed the highest degree of positive allosteric enhancement of ACh potency thus far identified. Radioligand binding assays also show this compound to directly potentiate agonist binding while having minimal effects on antagonist binding. Mutational analysis identified a key amino acid (D(432)) in the third extracellular loop of the human M(4) receptor to be critical for selectivity and agonist potentiation by LY2033298. Importantly, LY2033298 was active in animal models predictive of clinical antipsychotic drug efficacy indicating its potential use as a first-in-class, selective, allosteric muscarinic antipsychotic agent.
Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia
Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia
пятница, 5 февраля 2010 г.
дифференциальная диагностика серотонинового и злокачественного нейролептического синдромов
Ryan Kimmel, MD
Dr. Kimmel is an acting assistant professor, department of psychiatry, University of Washington, Seattle.
Symptoms of serotonin syndrome and neuroleptic malignant syndrome (NMS) are similar—mental status changes, autonomic dysfunction, and neuromuscular abnormalities—making the syndromes difficult to differentiate. However, therapeutic interventions and the mortality rates associated with these syndromes are widely divergent.
Because many medication regimens for treatment-resistant mood disorders modulate both serotonin and dopamine systems, psychiatrists must be prepared at any time to recognize either syndrome and quickly initiate appropriate treatment. For this, we rely on disease course, lab findings and vital signs, and the physical exam.
Clinical course
Serotonin syndrome symptoms can develop within minutes to hours after the administration of an agent that increases central serotonergic tone, such as a selective serotonin reuptake inhibitor. After rapid onset, serotonin syndrome symptoms may improve or even resolve within <24 hours. NMS, on the other hand, can develop days to weeks after the administration of a dopamine antagonist—such as an antipsychotic—and may take 3 to 14 days to resolve.
Labs and vital signs
The triad of fever, leukocytosis, and increased creatine kinase (CK) are associated with NMS. Hyperthermia is present in at least 90% of cases,1 although, some definitions of NMS list fever as a sine qua non. Leukocytosis and elevated hepatic transaminases are reported in at least 75% of NMS cases and increased CK in >90% of cases.1,2 These signs may be present in serotonin syndrome but are less common.
Although the pathophysiology of NMS is unclear and literature is limited, some case series report iron deficiency in >95% of cases.3 If this finding were replicated on a larger scale, iron deficiency might be a sensitive, rapid, and inexpensive test to help diagnose atypical NMS presentations. Larger studies are needed before clinicians can rely on this laboratory finding to diagnose NMS.
Physical exam findings
Neuromuscular manifestations also can help distinguish serotonin syndrome from NMS. Physicians often and rightly associate muscle rigidity with NMS. This finding also is present in approximately one-half of serotonin syndrome cases, however. Hyperreflexia and myoclonus, if present, may suggest serotonin syndrome.
References
1. Mills KC. Serotonin syndrome. A clinical update. Crit Care Clin. 1997;12(4):763–783.
2. Rosebush P, Stewart T. A prospective analysis of 24 episodes of neuroleptic malignant syndrome. Am J Psychiatry. 1989;146:717–725.
3. Rosebush P, Mazurek M. Serum iron and neuroleptic malignant syndrome. Lancet. 1991;338(8760):149–151.
Serotonin syndrome or NMS? Clues to diagnosis
Dr. Kimmel is an acting assistant professor, department of psychiatry, University of Washington, Seattle.
Symptoms of serotonin syndrome and neuroleptic malignant syndrome (NMS) are similar—mental status changes, autonomic dysfunction, and neuromuscular abnormalities—making the syndromes difficult to differentiate. However, therapeutic interventions and the mortality rates associated with these syndromes are widely divergent.
Because many medication regimens for treatment-resistant mood disorders modulate both serotonin and dopamine systems, psychiatrists must be prepared at any time to recognize either syndrome and quickly initiate appropriate treatment. For this, we rely on disease course, lab findings and vital signs, and the physical exam.
Clinical course
Serotonin syndrome symptoms can develop within minutes to hours after the administration of an agent that increases central serotonergic tone, such as a selective serotonin reuptake inhibitor. After rapid onset, serotonin syndrome symptoms may improve or even resolve within <24 hours. NMS, on the other hand, can develop days to weeks after the administration of a dopamine antagonist—such as an antipsychotic—and may take 3 to 14 days to resolve.
Labs and vital signs
The triad of fever, leukocytosis, and increased creatine kinase (CK) are associated with NMS. Hyperthermia is present in at least 90% of cases,1 although, some definitions of NMS list fever as a sine qua non. Leukocytosis and elevated hepatic transaminases are reported in at least 75% of NMS cases and increased CK in >90% of cases.1,2 These signs may be present in serotonin syndrome but are less common.
Although the pathophysiology of NMS is unclear and literature is limited, some case series report iron deficiency in >95% of cases.3 If this finding were replicated on a larger scale, iron deficiency might be a sensitive, rapid, and inexpensive test to help diagnose atypical NMS presentations. Larger studies are needed before clinicians can rely on this laboratory finding to diagnose NMS.
Physical exam findings
Neuromuscular manifestations also can help distinguish serotonin syndrome from NMS. Physicians often and rightly associate muscle rigidity with NMS. This finding also is present in approximately one-half of serotonin syndrome cases, however. Hyperreflexia and myoclonus, if present, may suggest serotonin syndrome.
References
1. Mills KC. Serotonin syndrome. A clinical update. Crit Care Clin. 1997;12(4):763–783.
2. Rosebush P, Stewart T. A prospective analysis of 24 episodes of neuroleptic malignant syndrome. Am J Psychiatry. 1989;146:717–725.
3. Rosebush P, Mazurek M. Serum iron and neuroleptic malignant syndrome. Lancet. 1991;338(8760):149–151.
Serotonin syndrome or NMS? Clues to diagnosis
Использование омега-3 в терапии депрессии
The Essential Fatty Acids
There are 2 main types of essential fatty acids in humans, the ω-3 derived from a-linolenic acid and the v-6 series derived from linoleic acid. Although a-linolenic acid is easily converted to eicosapentaenoic acid (EPA), the conversion from a-linolenic acid to docosahexaenoic acid (DHA) is inefficient in humans (less than 0.1%).[3] Because essential fatty acids cannot be synthesized de novo, they must be obtained from the diet. a-Linolenic acid comes mainly from plant sources, such as flax and canola oil, while EPA and DHA are obtained from marine sources, such as tuna, salmon, mackerel, and sardines. On the other hand, the main sources of v-6 linoleic acid are seed oil–based margarines, soy oil, sunflower oil, and safflower oil. Linoleic acid alone accounts for 10% of all calories in the US diet and by suppressing conversion of a-linolenic acid, creates greater dietary requirements for EPA and DHA consumption to achieve adequate levels in tissue.[4]
Anthropological and epidemiological data indicate that humans evolved on a shore-based diet with abundant seafood and few calories from seed oils. This may have permitted hominid encephalization.[5] In contrast, typical Western diets are now nearly devoid of adequate seafood and have excessive linoleic acid. An excess of v-6 fatty acids leads to increased low-density lipoprotein oxidation, platelet aggregation, and alterations in the cell membrane structure. Thus, high dietary intakes of v-6 fatty acids may cause a shift toward the proinflammatory, prothrombotic, and proconstrictive state, thereby promoting the pathogenesis of many illnesses, such as cardiovascular disease and cancer.[6]
The Use of Omega-3 Fatty Acids in Treatment of Depression
There are 2 main types of essential fatty acids in humans, the ω-3 derived from a-linolenic acid and the v-6 series derived from linoleic acid. Although a-linolenic acid is easily converted to eicosapentaenoic acid (EPA), the conversion from a-linolenic acid to docosahexaenoic acid (DHA) is inefficient in humans (less than 0.1%).[3] Because essential fatty acids cannot be synthesized de novo, they must be obtained from the diet. a-Linolenic acid comes mainly from plant sources, such as flax and canola oil, while EPA and DHA are obtained from marine sources, such as tuna, salmon, mackerel, and sardines. On the other hand, the main sources of v-6 linoleic acid are seed oil–based margarines, soy oil, sunflower oil, and safflower oil. Linoleic acid alone accounts for 10% of all calories in the US diet and by suppressing conversion of a-linolenic acid, creates greater dietary requirements for EPA and DHA consumption to achieve adequate levels in tissue.[4]
Anthropological and epidemiological data indicate that humans evolved on a shore-based diet with abundant seafood and few calories from seed oils. This may have permitted hominid encephalization.[5] In contrast, typical Western diets are now nearly devoid of adequate seafood and have excessive linoleic acid. An excess of v-6 fatty acids leads to increased low-density lipoprotein oxidation, platelet aggregation, and alterations in the cell membrane structure. Thus, high dietary intakes of v-6 fatty acids may cause a shift toward the proinflammatory, prothrombotic, and proconstrictive state, thereby promoting the pathogenesis of many illnesses, such as cardiovascular disease and cancer.[6]
The Use of Omega-3 Fatty Acids in Treatment of Depression
вторник, 2 февраля 2010 г.
Стимуляция системы поощрения ГМ в терапии депрессии
Currently, over a third of patients do not respond to conventional depression treatments. For these individuals, a new form of therapy involves deep brain stimulation (DBS).
The technique, a form of targeted electrical stimulation in the brain via implanted electrodes, is now undergoing careful testing to determine whether it could play a role in the treatment of patients who have not sufficiently improved during more traditional forms of treatment.
A major challenge of this work is determining the best region of the brain to stimulate.
Some researchers stimulate the subgenual prefrontal cortex, a brain region implicated in depressed mood states, while others stimulate a region called the “anterior limb of the internal capsule,” a nerve pathway that passes through the basal ganglia, a lower brain region.
Physicians publishing a new report in Biological Psychiatry now describe findings related to the stimulation of the nucleus accumbens, a brain region the size of a hazelnut associated with reward and motivation that is implicated in processing pleasurable stimuli, sometimes referred to as the “pleasure center” of the brain.
The inability to experience pleasure is a key symptom of depression and previous studies have shown that functioning of the nucleus accumbens is impaired in depressed individuals.
Stimulate Brain Pleasure Centers for Depression
The technique, a form of targeted electrical stimulation in the brain via implanted electrodes, is now undergoing careful testing to determine whether it could play a role in the treatment of patients who have not sufficiently improved during more traditional forms of treatment.
A major challenge of this work is determining the best region of the brain to stimulate.
Some researchers stimulate the subgenual prefrontal cortex, a brain region implicated in depressed mood states, while others stimulate a region called the “anterior limb of the internal capsule,” a nerve pathway that passes through the basal ganglia, a lower brain region.
Physicians publishing a new report in Biological Psychiatry now describe findings related to the stimulation of the nucleus accumbens, a brain region the size of a hazelnut associated with reward and motivation that is implicated in processing pleasurable stimuli, sometimes referred to as the “pleasure center” of the brain.
The inability to experience pleasure is a key symptom of depression and previous studies have shown that functioning of the nucleus accumbens is impaired in depressed individuals.
Stimulate Brain Pleasure Centers for Depression
Омега-3 в предупреждении ризвития психиатрических заболеваний
G. Paul Amminger, MD; Miriam R. Schäfer, MD; Konstantinos Papageorgiou, MD; Claudia M. Klier, MD; Sue M. Cotton, PhD; Susan M. Harrigan, MSc; Andrew Mackinnon, PhD; Patrick D. McGorry, MD, PhD; Gregor E. Berger, MD
Arch Gen Psychiatry. 2010;67(2):146-154.
Context The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Long-chain {omega}-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that {omega}-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation.
Objective To determine whether {omega}-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis.
Design Randomized, double-blind, placebo-controlled trial conducted between 2004 and 2007.
Setting Psychosis detection unit of a large public hospital in Vienna, Austria.
Participants Eighty-one individuals at ultra-high risk of psychotic disorder.
Interventions A 12-week intervention period of 1.2-g/d {omega}-3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months.
Main Outcome Measures The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of {omega}-6 to {omega}-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition.
Results Seventy-six of 81 participants (93.8%) completed the intervention. By study's end (12 months), 2 of 41 individuals (4.9%) in the {omega}-3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to full-threshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). {omega}-3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P = .01), negative symptoms (P = .02), and general symptoms (P = .01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups.
Conclusions Long-chain {omega}-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states.
Long-Chain {omega}-3 Fatty Acids for Indicated Prevention of Psychotic Disorders
These individuals either had mild psychotic symptoms, transient psychosis or a family history of psychotic disorders plus a decrease in functioning. These criteria identify individuals whose risk of becoming psychotic may be as high as 40 percent in a 12-month period.
For 12 weeks, 41 individuals were assigned to take daily fish oil capsules containing 1.2 grams of omega-three polyunsaturated fatty acids and 40 were assigned to take placebo; a total of 76 (93.8 percent) completed the intervention. By the end of the study, two (4.9 percent) in the omega-3 group and 11 (27.5 percent) in the placebo group had transitioned to psychotic disorder. The difference between progression to psychosis was 22.6 percent.
Fish Oil May Reduce Risk of Schizophrenia
Arch Gen Psychiatry. 2010;67(2):146-154.
Context The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Long-chain {omega}-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that {omega}-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation.
Objective To determine whether {omega}-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis.
Design Randomized, double-blind, placebo-controlled trial conducted between 2004 and 2007.
Setting Psychosis detection unit of a large public hospital in Vienna, Austria.
Participants Eighty-one individuals at ultra-high risk of psychotic disorder.
Interventions A 12-week intervention period of 1.2-g/d {omega}-3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months.
Main Outcome Measures The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of {omega}-6 to {omega}-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition.
Results Seventy-six of 81 participants (93.8%) completed the intervention. By study's end (12 months), 2 of 41 individuals (4.9%) in the {omega}-3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to full-threshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). {omega}-3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P = .01), negative symptoms (P = .02), and general symptoms (P = .01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups.
Conclusions Long-chain {omega}-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states.
Long-Chain {omega}-3 Fatty Acids for Indicated Prevention of Psychotic Disorders
These individuals either had mild psychotic symptoms, transient psychosis or a family history of psychotic disorders plus a decrease in functioning. These criteria identify individuals whose risk of becoming psychotic may be as high as 40 percent in a 12-month period.
For 12 weeks, 41 individuals were assigned to take daily fish oil capsules containing 1.2 grams of omega-three polyunsaturated fatty acids and 40 were assigned to take placebo; a total of 76 (93.8 percent) completed the intervention. By the end of the study, two (4.9 percent) in the omega-3 group and 11 (27.5 percent) in the placebo group had transitioned to psychotic disorder. The difference between progression to psychosis was 22.6 percent.
Fish Oil May Reduce Risk of Schizophrenia
Бета-блокаторы и депрессия
Beta-Blockers and Depression
Glen L. Xiong, M.D., Jane P. Gagliardi, M.D., and Wei Jiang, M.D.
Sacramento, Calif.
Durham, N.C.
To the Editor: We read with great interest the thought-provoking Clinical Case Conference by Laura K. Kent, M.D., et al., published in the August 2009 issue of the Journal, which described the finding of takotsubo cardiomyopathy after ECT (1). We hope to expand on the discussion regarding the role of beta-blockers in the course of depression treatment, an issue frequently raised by colleagues and trainees. We have searched the medical literature over time and have not found conclusive evidence to support a clear causal role of beta-blockers in depression.
Since Dr. Stoudemire et al. (2) posed, in 1984, that there is very little evidence to link propranolol with mood disturbance, subsequent studies have consistently challenged the dogma that beta-blockers cause depression. A meta-analysis (3) examined 15 randomized, controlled studies involving 35,000 subjects taking beta-blockers for the treatment of myocardial infarction, heart failure, or hypertension and demonstrated no statistical difference between beta-blockers and placebo with respect to depression, although beta-blockers were associated with increased incidence of fatigue and sexual dysfunction. The absolute incidence of depressive symptoms was six per 1,000 subjects (95% confidence interval=–7 to 19). A prospective multicenter trial (4) of 254 subjects taking beta-blockers and 127 comparison subjects measured serial Beck Depression Inventory scores. This study showed no significant difference between groups in the rate of depression at 3, 6, and 12 months, even with an alpha set at <0.10. Dr. Kent et al. suggested that beta-blockers may cause depression more often in women than men. However, Crane et al. (5) examined a cross-sectional sample of 84 women (>65 years old) 6 to 12 months after myocardial infarction and did not find any elevated risk of depression (using the Geriatric Depression Scale) among women who were taking beta-blockers (5).
The aforementioned studies teach us that it is important to distinguish fatigue from depression, that a temporal association between beta-blocker use and depression does not seem to exist (up to 12 months), and that there is no evidence to support a gender difference. When the preponderance of evidence does not support a long-held belief, it is the responsibility of the medical community to adopt a new clinical paradigm. It may be time to change the prevailing wisdom in our field so as not to prevent our patients from receiving beta-blockers for cardiovascular benefits. We support the decision to continue the beta-blocker for the patient discussed in the Clinical Case Conference.
Dr. Kent Replies
Laura Kent, M.D.
New York, N.Y.
To the Editor: We thank Dr. Xiong et al. for their thoughtful response to our article. They make the point that studies on beta blockade have distinguished fatigue from depression, have highlighted that there does not seem to be a temporal association between beta-blocker use and depression (up to 12 months), and that there is no evidence to support a gender difference.
Dr. Xiong et al. state that while we suggested that depression in the setting of beta-blockade use is seen more frequently in women, Crane et al. (1) examined 84 women and found no difference in depression symptoms between women who did and did not use beta-blockers. Although that study suggested that the use of beta-blockade does not cause depression in women, the study had several limitations, including its cross-sectional design, making it difficult to identify causation (even though this is more of an issue when an association is found). We also wish to make the point that very large doses of beta-blockade were used in our case study relative to the doses administered to women in the Crane et al. study, who were post-myocardial infarction and received only conventional doses, thus limiting comparability.
We agree that Van Melle et al. (2) showed no significant difference between groups in the rate of depression at 3, 6, and 12 months. However, the vast majority of these subjects were men (78% in both non-beta-blocker and beta-blocker groups), and thus it is hard to comment on the effect on women.
Beta-blockade is a critical state-of-the-art component of cardiac care, and thus further discussion and research on this topic are of paramount importance, especially given the equivocal nature of the preponderance of evidence to date.
Beta-Blockers and Depression
Dr. Kent Replies
Glen L. Xiong, M.D., Jane P. Gagliardi, M.D., and Wei Jiang, M.D.
Sacramento, Calif.
Durham, N.C.
To the Editor: We read with great interest the thought-provoking Clinical Case Conference by Laura K. Kent, M.D., et al., published in the August 2009 issue of the Journal, which described the finding of takotsubo cardiomyopathy after ECT (1). We hope to expand on the discussion regarding the role of beta-blockers in the course of depression treatment, an issue frequently raised by colleagues and trainees. We have searched the medical literature over time and have not found conclusive evidence to support a clear causal role of beta-blockers in depression.
Since Dr. Stoudemire et al. (2) posed, in 1984, that there is very little evidence to link propranolol with mood disturbance, subsequent studies have consistently challenged the dogma that beta-blockers cause depression. A meta-analysis (3) examined 15 randomized, controlled studies involving 35,000 subjects taking beta-blockers for the treatment of myocardial infarction, heart failure, or hypertension and demonstrated no statistical difference between beta-blockers and placebo with respect to depression, although beta-blockers were associated with increased incidence of fatigue and sexual dysfunction. The absolute incidence of depressive symptoms was six per 1,000 subjects (95% confidence interval=–7 to 19). A prospective multicenter trial (4) of 254 subjects taking beta-blockers and 127 comparison subjects measured serial Beck Depression Inventory scores. This study showed no significant difference between groups in the rate of depression at 3, 6, and 12 months, even with an alpha set at <0.10. Dr. Kent et al. suggested that beta-blockers may cause depression more often in women than men. However, Crane et al. (5) examined a cross-sectional sample of 84 women (>65 years old) 6 to 12 months after myocardial infarction and did not find any elevated risk of depression (using the Geriatric Depression Scale) among women who were taking beta-blockers (5).
The aforementioned studies teach us that it is important to distinguish fatigue from depression, that a temporal association between beta-blocker use and depression does not seem to exist (up to 12 months), and that there is no evidence to support a gender difference. When the preponderance of evidence does not support a long-held belief, it is the responsibility of the medical community to adopt a new clinical paradigm. It may be time to change the prevailing wisdom in our field so as not to prevent our patients from receiving beta-blockers for cardiovascular benefits. We support the decision to continue the beta-blocker for the patient discussed in the Clinical Case Conference.
Dr. Kent Replies
Laura Kent, M.D.
New York, N.Y.
To the Editor: We thank Dr. Xiong et al. for their thoughtful response to our article. They make the point that studies on beta blockade have distinguished fatigue from depression, have highlighted that there does not seem to be a temporal association between beta-blocker use and depression (up to 12 months), and that there is no evidence to support a gender difference.
Dr. Xiong et al. state that while we suggested that depression in the setting of beta-blockade use is seen more frequently in women, Crane et al. (1) examined 84 women and found no difference in depression symptoms between women who did and did not use beta-blockers. Although that study suggested that the use of beta-blockade does not cause depression in women, the study had several limitations, including its cross-sectional design, making it difficult to identify causation (even though this is more of an issue when an association is found). We also wish to make the point that very large doses of beta-blockade were used in our case study relative to the doses administered to women in the Crane et al. study, who were post-myocardial infarction and received only conventional doses, thus limiting comparability.
We agree that Van Melle et al. (2) showed no significant difference between groups in the rate of depression at 3, 6, and 12 months. However, the vast majority of these subjects were men (78% in both non-beta-blocker and beta-blocker groups), and thus it is hard to comment on the effect on women.
Beta-blockade is a critical state-of-the-art component of cardiac care, and thus further discussion and research on this topic are of paramount importance, especially given the equivocal nature of the preponderance of evidence to date.
Beta-Blockers and Depression
Dr. Kent Replies
левотироксин натрия, взаимодейсвия
| Drug or Drug Class | Effect |
|---|---|
| Drugs that may reduce TSH secretion -the reduction is not sustained; therefore, hypothyroidism does not occur | |
| Dopamine / Dopamine Agonists Glucocorticoids Octreotide | Use of these agents may result in a transient reduction in TSH secretion when administered at the following doses: Dopamine(≥ 1 mcg/kg/min); Glucocorticoids (hydrocortisone≥ 100 mg/day or equivalent); Octreotide (> 100 mcg/day). |
| Drugs that alter thyroid hormone secretion | |
| Drugs that may decrease thyroid hormone secretion, which may result in hypothyroidism | |
| Aminoglutethimide Amiodarone Iodide (including iodine- Containing Radiographic contrast agents) Lithium Methimazole Propylthiouracil (PTU) Sulfonamides Tolbutamide | Long-term lithium therapy can result in goiter in up to 50% of patients, and either subclinical or overt hypothyroidism, each in up to 20% of patients. The fetus, neonate, elderly and euthyroid patients with underlying thyroid disease (e.g., Hashimoto's thyroiditis or with Grave's disease previously treated with radioiodine or surgery) are among those individuals who are particularly susceptible to iodine-induced hypothyroidism. Oral cholecystographic agents and amiodarone are slowly excreted, producing more prolonged hypothyroidism than parenterally administered iodinated contrast agents. Long-term aminoglutethimide therapy may minimally decrease T4 and T3 levels and increase TSH, although all values remain within normal limits in most patients. |
| Drugs that may increase thyroid hormone secretion, which may result in hyperthyroidism | |
| Amiodarone Iodide (including iodine- containing Radiographic contrast agents) | Iodide and drugs that contain pharmacologic amounts of iodide may cause hyperthyroidism in euthyroid patients with Grave's disease previously treated with antithyroid drugs or in euthyroid patients with thyroid autonomy (e.g., multinodular goiter or hyperfunctioning thyroid adenoma). Hyperthyroidism may develop over several weeks and may persist for several months after therapy discontinuation. Amiodarone may induce hyperthyroidism by causing thyroiditis. |
| Drugs that may decrease T4 absorption, which may result in hypothyroidism | |
| Antacids - Aluminum & Magnesium Hydroxides - Simethicone Bile Acid Sequestrants - Cholestyramine - Colestipol Calcium Carbonate Cation Exchange Resins - Kayexalate Ferrous Sulfate Sucralfate | Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing absorption, potentially resulting in hypothyroidism. Calcium carbonate may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex. Administer levothyroxine at least 4 hours apart from these agents. |
| Drugs that may alter T4 and T3 serum transport – but FT4 concentration remains normal; and, therefore, the patient remains euthyroid | |
| Drugs that may decrease serum TBG concentration | Drugs that may increase serum TBG concentration |
| Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin / Methadone 5-Fluorouracil Mitotane Tamoxifen | Androgens / Anabolic Steroids Asparaginase Glucocorticoids Slow-Release Nicotinic Acid |
| Drugs that may cause protein-binding site displacement | |
| Furosemide ( > 80 mg IV) Heparin Hydantoins Non Steroidal Anti-Inflammatory Drugs - Fenamates - Phenylbutazone Salicylates ( > 2 g/day) | Administration of these agents with levothyroxine results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations and, therefore, patients are clinically euthyroid. Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4 is followed by return of FT4 to normal levels with sustained therapeutic serum salicylate concentrations, although total-T4 levels may decrease by as much as 30%. |
| Drugs that may alter T4 and T3 metabolism | |
| Drugs that may increase hepatic metabolism, which may result in hypothyroidism | |
| Carbamazepine Hydantoins Phenobarbital Rifampin | Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements. Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total- and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. |
| Drugs that may decrease T4 5'-deiodinase activity | |
| Amiodarone Beta-adrenergic antagonists - (e.g., Propranolol> 160 mg/day) Glucocorticoids - (e.g., Dexamethasone > 4 mg/day) Propylthiouracil (PTU) | Administration of these enzyme inhibitors decreases the peripheral conversion of T4 to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased. In patients treated with large doses of propranolol ( > 160 mg/day), T3 and T4 levels change slightly, TSH levels remain normal, and patients are clinically euthyroid. It should be noted that actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state. Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels. However, long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (see above). |
| Miscellaneous | |
| Anticoagulants (oral) - Coumarin Derivatives - Indandione Derivatives | Thyroid hormones appear to increase the catabolism of vitamin K-dependent clotting factors, thereby increasing the anticoagulant activity of oral anticoagulants. Concomitant use of these agents impairs the compensatory increases in clotting factor synthesis. Prothrombin time should be carefully monitored in patients taking levothyroxine and oral anticoagulants and the dose of anticoagulant therapy adjusted accordingly. |
| Antidepressants - Tricyclics (e.g., Amitriptyline) - Tetracyclics (e.g., Maprotiline) - Selective Serotonin Reuptake Inhibitors (SSRIs; e.g., Sertraline) | Concurrent use of tri/tetracyclic antidepressants and levothyroxine may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk of cardiac arrhythmias and CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements. |
| Antidiabetic Agents - Biguanides - Meglitinides - Sulfonylureas - Thiazolidediones - Insulin | Addition of levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued. |
| Cardiac Glycosides | Serum digitalis glycoside levels may be reduced in hyperthyroidism or when the hypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalis glycosides may be reduced. |
| Cytokines - Interferon-α - Interleukin-2 | Thereapy wih interferon-α has been associated with the development of antithyroid microsomal antibodies in 20% of patients and some have transient hypothyroidism, hyperthyroidism, or both. Patients who have antithyroid antibodies before treatment are at higher risk for thyroid dysfunction during treatment. Interleukin-2 has been associated with transient painless thyroiditis in 20% of patients. Interferon-β and -γ have not been reported to cause thyroid dysfunction. |
| Growth Hormones - Somatrem - Somatropin | Excessive use of thyroid hormones with growth hormones may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to growth hormone. |
| Ketamine | Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended. |
| Methylxanthine Bronchodilators - (e.g., Theophylline) | Decreased theophylline clearance may occur in hypothyroid patients; clearance returns to normal when the euthyroid state is achieved. |
| Radiographic Agents | Thyroid hormones may reduce the uptake of 123I, 131I, and 99mTc |
| Sympathomimetics | Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease. |
| Chloral Hydrate Diazepam Ethionamide Lovastatin Metoclopramide 6-Mercaptopurine Nitroprusside Para-aminosalicylate sodium Perphenazine Resorcinol (excessive topical use) Thiazide Diuretics | These agents have been associated with thyroid hormone and / or TSH level alterations by various mechanisms. |
LEVOXYL® (levothyroxine sodium tablets, USP)
понедельник, 1 февраля 2010 г.
Treatment of Catatonia With Methylphenidate in an Elderly Patient With Depression
Matthew L. Prowler, M.D., David Weiss, M.D., and Stanley N. Caroff, M.D.
Received June 2, 2008; revised July 1, 2008; accepted July 2, 2008. From the Dept. of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA; and the Philadelphia Veterans Affairs Medical Center. Send correspondence and reprint requests to Matthew L. Prowler, M.D., Dept. of Psychiatry, University of Pennsylvania School of Medicine, 3535 Market St., 2nd Fl., Philadelphia, PA 19104. e-mail: matthew.prowler@uphs.upenn.edu
© 2010 The Academy of Psychosomatic Medicine
BACKGROUND: Catatonia is especially common among patients with mood disorders. OBJECTIVE: The authors evaluated the effects of methylphenidate as an augmentation strategy in an elderly patient with catatonia and depression. METHOD: Methylphenidate was administered to a catatonic patient who had not responded to lorazepam. RESULTS: The patient showed an acute and marked response to methylphenidate. DISCUSSION: Methylphenidate may be effective as an adjunct in elderly depression patients with catatonia, as well as in medically ill, apathetic patients. However, there have been few attempts to study the role of psychostimulants in alleviating catatonia in general, or catatonia associated specifically with an underlying depressive disorder, even though catatonia is frequently associated with mood disorders.
Treatment of Catatonia With Methylphenidate in an Elderly Patient With Depression
Received June 2, 2008; revised July 1, 2008; accepted July 2, 2008. From the Dept. of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA; and the Philadelphia Veterans Affairs Medical Center. Send correspondence and reprint requests to Matthew L. Prowler, M.D., Dept. of Psychiatry, University of Pennsylvania School of Medicine, 3535 Market St., 2nd Fl., Philadelphia, PA 19104. e-mail: matthew.prowler@uphs.upenn.edu
© 2010 The Academy of Psychosomatic Medicine
BACKGROUND: Catatonia is especially common among patients with mood disorders. OBJECTIVE: The authors evaluated the effects of methylphenidate as an augmentation strategy in an elderly patient with catatonia and depression. METHOD: Methylphenidate was administered to a catatonic patient who had not responded to lorazepam. RESULTS: The patient showed an acute and marked response to methylphenidate. DISCUSSION: Methylphenidate may be effective as an adjunct in elderly depression patients with catatonia, as well as in medically ill, apathetic patients. However, there have been few attempts to study the role of psychostimulants in alleviating catatonia in general, or catatonia associated specifically with an underlying depressive disorder, even though catatonia is frequently associated with mood disorders.
Treatment of Catatonia With Methylphenidate in an Elderly Patient With Depression
Подписаться на:
Сообщения (Atom)