* Department of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Palo... more * Department of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Palo Alto and Department of Family and Preventive Medicine, University of California, San Diego School of Medicine, La Jolla, CA mschulman@ ucsd. edu
Individuals with schizophrenia display substantial neurocognitive deficits for which available tr... more Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits. Yet, findings from studies of animals, clinical and nonclinical populations have linked neurocognitive improvements to increases in aerobic fitness (AF) via aerobic exercise training (AE). Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor (BDNF). However, the impact of AE on neurocognition, and the putative role of BDNF, have not been investigated in schizophrenia. Employing a proof-of-concept, single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive standard psychiatric treatment (n = 17; "treatment as usual"; TAU) or attend a 12-week AE program (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed assessments of AF (indexed by VO2 peak ml/kg/min), neurocognition (MATRICS Consensus Cogni...
Antipsychotic medications are associated with major metabolic changes that contribute to medical ... more Antipsychotic medications are associated with major metabolic changes that contribute to medical morbidity and a significantly shortened life span. The mechanisms for these changes provide us with a broader understanding of central nervous and peripheral organ-mediated metabolic regulation. This paper reviews an extensive literature regarding putative mechanisms for effects of antipsychotic medications on weight regulation and glucose homeostasis as well as potential inherent metabolic risks of schizophrenia itself. We present a model suggesting that peripheral antipsychotic targets play a critical role in drug-induced weight gain and diabetes. We propose that a better understanding of these mechanisms will be crucial to developing improved treatments for serious mental illnesses as well as providing potentially novel therapeutic targets of metabolic disorders including diabetes.
Treatment-resistant depression (TRD) is a prevalent, disabling, and costly condition affecting 1%... more Treatment-resistant depression (TRD) is a prevalent, disabling, and costly condition affecting 1%-4% of the U.S. Current approaches to managing TRD include medication augmentation (with lithium, thyroid hormone, buspirone, atypical antipsychotics, or various antidepressant medications), psychotherapy, and ECT. Advances in understanding the neurobiology of mood regulation and depression have led to a number of new potential approaches to managing TRD, including medications with novel mechanisms of action and focal brain stimulation techniques. This review will define and discuss the epidemiology of TRD, review the current approaches to its management, and then provide an overview of several developing interventions.
... Cadenhead et al. 2000). However, they are not specific to schizophrenia spectrum illnesses (G... more ... Cadenhead et al. 2000). However, they are not specific to schizophrenia spectrum illnesses (Geyer 2006), and can be seen in other psychiatric disorders, such as panic disorder (Ludewig et al. 2002). An ERP signal processing ...
Previous reports indicate that among healthy individuals low aerobic fitness (AF) and high body-m... more Previous reports indicate that among healthy individuals low aerobic fitness (AF) and high body-mass index (BMI) predict poor neurocognition and daily-functioning. It is unknown whether these associations extend to disorders characterized by poor neurocognition, such as schizophrenia. Therefore, we compared AF and BMI in individuals with schizophrenia and non-clinical controls, and then within the schizophrenia group we examined the links between AF, BMI, neurocognition and daily-functioning. Thirty-two individuals with schizophrenia and 64 gender- and age-matched controls completed assessments of AF (indexed by VO2max) and BMI. The former also completed measures of neurocognition, daily-functioning and physical activity. The schizophrenia group displayed significantly lower AF and higher BMI. In the schizophrenia group, AF was significantly correlated with overall neurocognition (r=0.57), along with executive functioning, working memory, social cognition, and processing speed. A hi...
Rapid advances in neuroscience and clinical research have made the practice of quality clinical p... more Rapid advances in neuroscience and clinical research have made the practice of quality clinical psychopharmacology increasingly difficult. While practice guidelines, model psychopharmacology curricula, and clinical algorithms have helped "the science" of psychopharmacology, they often fail to provide guidance for clinicians in specific clinical situations with individual patients. Quality psychopharmacology practice is based on a combination of knowledge, experience, judgment, and luck. In this article, the authors present their collection of psychopharmacology "pearls" for trainees as well as experienced clinicians. (Journal of Psychiatric Practice 2009;15:423-426).
The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect... more The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels. The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses. Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations. It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.
Combining psychotropic medications is common for people diagnosed with schizophrenia facing a var... more Combining psychotropic medications is common for people diagnosed with schizophrenia facing a variety of clinical circumstances. This review provides an update on evidence regarding the effectiveness of polypharmacy approaches. Epidemiology studies have demonstrated that polypharmacy is extremely common, but evidence regarding all polypharmacy approaches for schizophrenia from randomized controlled trials remains scarce. Combinations of antipsychotic medicines are unsupported by evidence. Antidepressants are commonly used to treat depressive symptoms; this logical role for antidepressants has little support from randomized controlled trials (RCTs) but may be associated with lower suicide and all-cause mortality. Insufficient evidence supports the use of benzodiazepines for schizophrenia; possible risks of benzodiazepines, including increased mortality rates revealed in observational studies, warrant caution and further study. The lack of evidence regarding common treatment strategies exacerbates the tremendous challenge of providing optimal pharmacotherapy for individuals with schizophrenia. Comparative effectiveness research, using observational methods when appropriate and RCTs when possible, is needed to inform clinical practice, use resources wisely and improve outcomes.
Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in use for sc... more Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in use for schizophrenia. While often effective at ameliorating psychosis, these drugs are largely ineffective at treating negative and cognitive symptoms. Increasing attention is being focused on the complex genetics of the illness and the signaling pathways implicated in its pathophysiology. We review targeted approaches for pharmacotherapy involving the glutamatergic, GABAergic and cholinergic pathways. We also describe several of the major genetic findings that identify signaling pathways representing potential targets for novel pharmacological intervention. These include genes in the 22q11 locus, DISC1, Neuregulin 1/ErbB4, and components of the Akt/GSK-3 pathway.
* Department of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Palo... more * Department of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Palo Alto and Department of Family and Preventive Medicine, University of California, San Diego School of Medicine, La Jolla, CA mschulman@ ucsd. edu
Individuals with schizophrenia display substantial neurocognitive deficits for which available tr... more Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits. Yet, findings from studies of animals, clinical and nonclinical populations have linked neurocognitive improvements to increases in aerobic fitness (AF) via aerobic exercise training (AE). Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor (BDNF). However, the impact of AE on neurocognition, and the putative role of BDNF, have not been investigated in schizophrenia. Employing a proof-of-concept, single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive standard psychiatric treatment (n = 17; "treatment as usual"; TAU) or attend a 12-week AE program (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed assessments of AF (indexed by VO2 peak ml/kg/min), neurocognition (MATRICS Consensus Cogni...
Antipsychotic medications are associated with major metabolic changes that contribute to medical ... more Antipsychotic medications are associated with major metabolic changes that contribute to medical morbidity and a significantly shortened life span. The mechanisms for these changes provide us with a broader understanding of central nervous and peripheral organ-mediated metabolic regulation. This paper reviews an extensive literature regarding putative mechanisms for effects of antipsychotic medications on weight regulation and glucose homeostasis as well as potential inherent metabolic risks of schizophrenia itself. We present a model suggesting that peripheral antipsychotic targets play a critical role in drug-induced weight gain and diabetes. We propose that a better understanding of these mechanisms will be crucial to developing improved treatments for serious mental illnesses as well as providing potentially novel therapeutic targets of metabolic disorders including diabetes.
Treatment-resistant depression (TRD) is a prevalent, disabling, and costly condition affecting 1%... more Treatment-resistant depression (TRD) is a prevalent, disabling, and costly condition affecting 1%-4% of the U.S. Current approaches to managing TRD include medication augmentation (with lithium, thyroid hormone, buspirone, atypical antipsychotics, or various antidepressant medications), psychotherapy, and ECT. Advances in understanding the neurobiology of mood regulation and depression have led to a number of new potential approaches to managing TRD, including medications with novel mechanisms of action and focal brain stimulation techniques. This review will define and discuss the epidemiology of TRD, review the current approaches to its management, and then provide an overview of several developing interventions.
... Cadenhead et al. 2000). However, they are not specific to schizophrenia spectrum illnesses (G... more ... Cadenhead et al. 2000). However, they are not specific to schizophrenia spectrum illnesses (Geyer 2006), and can be seen in other psychiatric disorders, such as panic disorder (Ludewig et al. 2002). An ERP signal processing ...
Previous reports indicate that among healthy individuals low aerobic fitness (AF) and high body-m... more Previous reports indicate that among healthy individuals low aerobic fitness (AF) and high body-mass index (BMI) predict poor neurocognition and daily-functioning. It is unknown whether these associations extend to disorders characterized by poor neurocognition, such as schizophrenia. Therefore, we compared AF and BMI in individuals with schizophrenia and non-clinical controls, and then within the schizophrenia group we examined the links between AF, BMI, neurocognition and daily-functioning. Thirty-two individuals with schizophrenia and 64 gender- and age-matched controls completed assessments of AF (indexed by VO2max) and BMI. The former also completed measures of neurocognition, daily-functioning and physical activity. The schizophrenia group displayed significantly lower AF and higher BMI. In the schizophrenia group, AF was significantly correlated with overall neurocognition (r=0.57), along with executive functioning, working memory, social cognition, and processing speed. A hi...
Rapid advances in neuroscience and clinical research have made the practice of quality clinical p... more Rapid advances in neuroscience and clinical research have made the practice of quality clinical psychopharmacology increasingly difficult. While practice guidelines, model psychopharmacology curricula, and clinical algorithms have helped "the science" of psychopharmacology, they often fail to provide guidance for clinicians in specific clinical situations with individual patients. Quality psychopharmacology practice is based on a combination of knowledge, experience, judgment, and luck. In this article, the authors present their collection of psychopharmacology "pearls" for trainees as well as experienced clinicians. (Journal of Psychiatric Practice 2009;15:423-426).
The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect... more The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels. The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses. Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations. It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.
Combining psychotropic medications is common for people diagnosed with schizophrenia facing a var... more Combining psychotropic medications is common for people diagnosed with schizophrenia facing a variety of clinical circumstances. This review provides an update on evidence regarding the effectiveness of polypharmacy approaches. Epidemiology studies have demonstrated that polypharmacy is extremely common, but evidence regarding all polypharmacy approaches for schizophrenia from randomized controlled trials remains scarce. Combinations of antipsychotic medicines are unsupported by evidence. Antidepressants are commonly used to treat depressive symptoms; this logical role for antidepressants has little support from randomized controlled trials (RCTs) but may be associated with lower suicide and all-cause mortality. Insufficient evidence supports the use of benzodiazepines for schizophrenia; possible risks of benzodiazepines, including increased mortality rates revealed in observational studies, warrant caution and further study. The lack of evidence regarding common treatment strategies exacerbates the tremendous challenge of providing optimal pharmacotherapy for individuals with schizophrenia. Comparative effectiveness research, using observational methods when appropriate and RCTs when possible, is needed to inform clinical practice, use resources wisely and improve outcomes.
Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in use for sc... more Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in use for schizophrenia. While often effective at ameliorating psychosis, these drugs are largely ineffective at treating negative and cognitive symptoms. Increasing attention is being focused on the complex genetics of the illness and the signaling pathways implicated in its pathophysiology. We review targeted approaches for pharmacotherapy involving the glutamatergic, GABAergic and cholinergic pathways. We also describe several of the major genetic findings that identify signaling pathways representing potential targets for novel pharmacological intervention. These include genes in the 22q11 locus, DISC1, Neuregulin 1/ErbB4, and components of the Akt/GSK-3 pathway.
Uploads
Papers by Jacob Ballon