First- and Second-Generation Antipsychotics
Antipsychotics and Schizophrenia: From Efficacy and Effectiveness to Clinical Decision-Making
понедельник, 19 апреля 2010 г.
Нарушение клеточного цикла при шизофрении
Bahn and her colleagues are investigating disease markers in tissues such as skin, immune cells, and blood serum to find samples that give a real-time picture of the disease. Their studies of protein expression in fibroblasts (skin cells) on schizophrenia patients’ arms have identified systemic problems such as cell-cycle abnormalities (J. Proteome Res. 2010, 9, 521).
“It’s clear that schizophrenia has a very strong genetic component,” Bahn says. “Most genes are not used only in the brain. If there is an underlying abnormality at the genetic level that leads to pathology in the brain, the assumption can be made that there should also be dysregulation in the peripheral system. It may not lead to pathology, but it may reflect the pathology in the brain.”
A Systemic Look At Schizophrenia
“It’s clear that schizophrenia has a very strong genetic component,” Bahn says. “Most genes are not used only in the brain. If there is an underlying abnormality at the genetic level that leads to pathology in the brain, the assumption can be made that there should also be dysregulation in the peripheral system. It may not lead to pathology, but it may reflect the pathology in the brain.”
A Systemic Look At Schizophrenia
вторник, 13 апреля 2010 г.
Simple Test Identifies Suicide Risk from Antidepressants
Aimee Hunter, an assistant research psychologist in the UCLA Department of Psychiatry, and colleagues report that by using quantitative electroencephalographic (QEEG), a noninvasive measurement of electrical activity in the brain, they were able to observe a sharp reduction of activity in a specific brain region in individuals who proved susceptible to thoughts of suicide. The reduction was noticeable within 48 hours of the start of treatment.
Simple Test Identifies Suicide Risk from Antidepressants
Simple Test Identifies Suicide Risk from Antidepressants
среда, 7 апреля 2010 г.
Длительность нелеченного психоза и длительность нелеченного заболевания
An 8 year prospective study conducted in first episode patients found that DUP was an independent predictor of prognosis in the medium to long term and that outcomes for psychopathological domains were significantly worse when DUP exceeded 3 months.23 Subsequent studies confirmed the association between a longer DUP and a worse outcome of negative symptoms3 as well as a poor influence on cognitive symptoms.24 In addition, other studies with large samples indicating a worse outcome in schizophrenics with longer DUP in terms of more severe positive, negative, and cognitive symptoms have been recently reported.9,10,25-27 In two previous studies by our group, an association between a longer DUP and a greater number of suicide attempters and a higher number of recurrences were found.28,29
In relation to neurobiological mechanisms, it has been hypothesized that the adverse effects on outcome associated with untreated psychosis may be biologically mediated. One toxicity model suggests that N-methyl-d-aspartic (NMDA) acid receptor hypofunctioning may induce psychosis and produce glutamatergically-medicated excitotoxic damage in neurons at the same time.30,31 For the latter, NMDA receptor hypofunction would result in reduced activation of GABAergic inhibitory neurons, leading to an excitotoxic state.31 Alternatively, prolonged stress, including stress resulting from untreated psychosis, may activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to greater glucocorticoid secretion which may contribute to neuronal damage.32 However, the evidence for neurotoxicity stemming from untreated psychosis is still an object of debate and there is as yet little evidence of an effect of long DUP on brain morphology. Furthermore, the possibility of cognitive dysfunction being a neurotoxic consequence of delayed treatment with antipsychotic drugs has been advanced, but this is only a hypothesis given that cognitive impairment may begin prior to the onset of psychosis and is poorly affected by available antipsychotics.
The hypothesis that not only schizophrenia and psychotic spectrum disorders but also depressive disorders tend to show anatomical deficits with the progression of the illness has been recently supported by a large meta-analysis conducted on 64 studies which reported that compared to healthy controls, depressed patients showed large volume reductions in frontal regions, particularly in the anterior cingulate and orbitofrontal cortex with smaller reductions in the prefrontal cortex. In addition, the hippocampus, putamen, and caudate nucleus showed moderate volume reductions.35 As a consequence, the hypothesis that early effective antidepressant treatments may block and partially reverse the neurobiological modifications occurring with the progression of the untreated depressive episode may be advanced.
To date, studies specifically investigating the role of the DUI in anxiety disorders have been conducted in panic disorder, generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD). Indeed, a study examining the cause and length of delays in reaching primary care and specialist services amongst patients with anxiety disorders indicated that patients with social phobia reported longer delays in reaching specialist care (>9 years) compared with patients with GAD or panic disorder.70
Duration of Untreated Psychosis and Duration of Untreated Illness: New Vistas
In relation to neurobiological mechanisms, it has been hypothesized that the adverse effects on outcome associated with untreated psychosis may be biologically mediated. One toxicity model suggests that N-methyl-d-aspartic (NMDA) acid receptor hypofunctioning may induce psychosis and produce glutamatergically-medicated excitotoxic damage in neurons at the same time.30,31 For the latter, NMDA receptor hypofunction would result in reduced activation of GABAergic inhibitory neurons, leading to an excitotoxic state.31 Alternatively, prolonged stress, including stress resulting from untreated psychosis, may activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to greater glucocorticoid secretion which may contribute to neuronal damage.32 However, the evidence for neurotoxicity stemming from untreated psychosis is still an object of debate and there is as yet little evidence of an effect of long DUP on brain morphology. Furthermore, the possibility of cognitive dysfunction being a neurotoxic consequence of delayed treatment with antipsychotic drugs has been advanced, but this is only a hypothesis given that cognitive impairment may begin prior to the onset of psychosis and is poorly affected by available antipsychotics.
The hypothesis that not only schizophrenia and psychotic spectrum disorders but also depressive disorders tend to show anatomical deficits with the progression of the illness has been recently supported by a large meta-analysis conducted on 64 studies which reported that compared to healthy controls, depressed patients showed large volume reductions in frontal regions, particularly in the anterior cingulate and orbitofrontal cortex with smaller reductions in the prefrontal cortex. In addition, the hippocampus, putamen, and caudate nucleus showed moderate volume reductions.35 As a consequence, the hypothesis that early effective antidepressant treatments may block and partially reverse the neurobiological modifications occurring with the progression of the untreated depressive episode may be advanced.
To date, studies specifically investigating the role of the DUI in anxiety disorders have been conducted in panic disorder, generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD). Indeed, a study examining the cause and length of delays in reaching primary care and specialist services amongst patients with anxiety disorders indicated that patients with social phobia reported longer delays in reaching specialist care (>9 years) compared with patients with GAD or panic disorder.70
Duration of Untreated Psychosis and Duration of Untreated Illness: New Vistas
вторник, 6 апреля 2010 г.
Фенелзин и когнитивно-поведенческая терапия в лечении социофобий
Patients with social phobia respond well to phenelzine, especially when combined with psychotherapy.
Concerns about drug and food interactions and the ease of use of newer antidepressants have so decreased the popularity of monoamine oxidase inhibitors (MAOIs) that psychiatrists can complete residency without ever using them. This study, completed almost 10 years ago, examined the effectiveness of the prototypical MAOI phenelzine, alone or combined with group cognitive-behavioral therapy (GCBT), in treating 128 patients with social anxiety disorder meeting DSM-IV criteria.
In the acute phase, patients were randomized to phenelzine (mean, 66 mg/day), weekly GCBT, phenelzine in a similar dose (mean, 62 mg/day) combined with GCBT, or pill placebo for 12 weeks. Combined treatment and phenelzine alone (but not GCBT alone) produced significantly more improvement at 12 weeks than placebo by several measures. Effect sizes varied with the measure but generally ranged between 0.28 and 1.05 for combined treatment, 0.07 to 0.60 for phenelzine, and 0.06 to 0.36 for GCBT.
In the continuation phase, patients who improved continued their treatments at a decreased frequency through week 24. Response rates were 78% for combined treatment, 53% for GCBT, 49% for phenelzine, and 33% for placebo (remission rates, 53%, 24%, 26%, and 15%, respectively). Results from a 28-week maintenance phase and a 12-month naturalistic follow-up were not reported.
Comment: By several measures, combination treatment outperformed either MAOI or psychotherapy alone. The most likely explanation for the additive effect is that the antidepressant facilitated exposure by reducing anxiety and arousal in social and performance situations, while CBT helped patients to integrate the gains promoted by the antidepressant. The latest generation of psychiatrists should bear in mind that even MAOIs that were available 10 years ago are still effective for social anxiety and atypical depression. Insurers should pay attention to the synergistic effects of medications and psychotherapy in this and other disorders.
— Steven Dubovsky, MD
Published in Journal Watch Psychiatry April 5, 201
Concerns about drug and food interactions and the ease of use of newer antidepressants have so decreased the popularity of monoamine oxidase inhibitors (MAOIs) that psychiatrists can complete residency without ever using them. This study, completed almost 10 years ago, examined the effectiveness of the prototypical MAOI phenelzine, alone or combined with group cognitive-behavioral therapy (GCBT), in treating 128 patients with social anxiety disorder meeting DSM-IV criteria.
In the acute phase, patients were randomized to phenelzine (mean, 66 mg/day), weekly GCBT, phenelzine in a similar dose (mean, 62 mg/day) combined with GCBT, or pill placebo for 12 weeks. Combined treatment and phenelzine alone (but not GCBT alone) produced significantly more improvement at 12 weeks than placebo by several measures. Effect sizes varied with the measure but generally ranged between 0.28 and 1.05 for combined treatment, 0.07 to 0.60 for phenelzine, and 0.06 to 0.36 for GCBT.
In the continuation phase, patients who improved continued their treatments at a decreased frequency through week 24. Response rates were 78% for combined treatment, 53% for GCBT, 49% for phenelzine, and 33% for placebo (remission rates, 53%, 24%, 26%, and 15%, respectively). Results from a 28-week maintenance phase and a 12-month naturalistic follow-up were not reported.
Comment: By several measures, combination treatment outperformed either MAOI or psychotherapy alone. The most likely explanation for the additive effect is that the antidepressant facilitated exposure by reducing anxiety and arousal in social and performance situations, while CBT helped patients to integrate the gains promoted by the antidepressant. The latest generation of psychiatrists should bear in mind that even MAOIs that were available 10 years ago are still effective for social anxiety and atypical depression. Insurers should pay attention to the synergistic effects of medications and psychotherapy in this and other disorders.
— Steven Dubovsky, MD
Published in Journal Watch Psychiatry April 5, 201
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