Publications by authors named "John O Brooks"

38 Publications

Depression treatment response to ketamine: sex-specific role of interleukin-8, but not other inflammatory markers.

Transl Psychiatry 2021 Mar 15;11(1):167. Epub 2021 Mar 15.

Cousins Center for Psychoneuroimmunology, University of California at Los Angeles, Los Angeles, CA, USA.

Inflammation plays a role in depression pathophysiology and treatment response, with effects varying by sex and therapeutic modality. Lower levels of interleukin(IL)-8 predict depression response to antidepressant medication and to electroconvulsive therapy (ECT), although ECT effects are specific to females. Whether IL-8 predicts depression response to ketamine and in a sex-specific manner is not known. Here, depressed patients (n = 46; female, n = 17) received open label infusion of ketamine (0.5 mg/kg over 40 min; NCT02165449). Plasma levels of IL-8 were evaluated at baseline and post-treatment. Baseline levels of IL-8 had a trending association with response to ketamine, depending upon sex (responder status × sex interaction: p = 0.096), in which lower baseline levels of IL-8 in females (p = 0.095) but not males (p = 0.96) trended with treatment response. Change in levels of IL-8 from baseline to post-treatment differed significantly by responder status (defined as ≥50% reduction in Hamilton Depression Rating Scale [HAM-D] Score), depending upon sex (responder status × sex × time interaction: F(1,42)=6.68, p = 0.01). In addition, change in IL-8 interacted with sex to predict change in HAM-D score (β = -0.63, p = 0.003); increasing IL-8 was associated with decreasing HAM-D score in females (p = 0.08) whereas the inverse was found in males (p = 0.02). Other inflammatory markers (IL-6, IL-10, tumor necrosis factor-α, C-reactive protein) were explored with no significant relationships identified. Given these preliminary findings, further evaluation of sex differences in the relationship between IL-8 and treatment response is warranted to elucidate mechanisms of response and aid in the development of personalized approaches to depression treatment.
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http://dx.doi.org/10.1038/s41398-021-01268-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960960PMC
March 2021

Depression treatment response to ketamine: sex-specific role of interleukin-8, but not other inflammatory markers.

Transl Psychiatry 2021 Mar 15;11(1):167. Epub 2021 Mar 15.

Cousins Center for Psychoneuroimmunology, University of California at Los Angeles, Los Angeles, CA, USA.

Inflammation plays a role in depression pathophysiology and treatment response, with effects varying by sex and therapeutic modality. Lower levels of interleukin(IL)-8 predict depression response to antidepressant medication and to electroconvulsive therapy (ECT), although ECT effects are specific to females. Whether IL-8 predicts depression response to ketamine and in a sex-specific manner is not known. Here, depressed patients (n = 46; female, n = 17) received open label infusion of ketamine (0.5 mg/kg over 40 min; NCT02165449). Plasma levels of IL-8 were evaluated at baseline and post-treatment. Baseline levels of IL-8 had a trending association with response to ketamine, depending upon sex (responder status × sex interaction: p = 0.096), in which lower baseline levels of IL-8 in females (p = 0.095) but not males (p = 0.96) trended with treatment response. Change in levels of IL-8 from baseline to post-treatment differed significantly by responder status (defined as ≥50% reduction in Hamilton Depression Rating Scale [HAM-D] Score), depending upon sex (responder status × sex × time interaction: F(1,42)=6.68, p = 0.01). In addition, change in IL-8 interacted with sex to predict change in HAM-D score (β = -0.63, p = 0.003); increasing IL-8 was associated with decreasing HAM-D score in females (p = 0.08) whereas the inverse was found in males (p = 0.02). Other inflammatory markers (IL-6, IL-10, tumor necrosis factor-α, C-reactive protein) were explored with no significant relationships identified. Given these preliminary findings, further evaluation of sex differences in the relationship between IL-8 and treatment response is warranted to elucidate mechanisms of response and aid in the development of personalized approaches to depression treatment.
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http://dx.doi.org/10.1038/s41398-021-01268-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960960PMC
March 2021

Non-Convulsive Status Epilepticus in the Presence of Catatonia: A Clinically Focused Review.

Gen Hosp Psychiatry 2021 Jan-Feb;68:25-34. Epub 2020 Nov 13.

Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.

Introduction: Catatonia is classically associated with psychiatric conditions but may occur in medical and neurologic disorders. Status epilepticus (SE) is a seizure lasting more than five minutes or two or more seizures within a five-minute period without interictal recovery of consciousness. Non-convulsive status epilepticus (NCSE) is SE without prominent motor activity that may present with catatonic symptoms. The relevance of NCSE as a potential etiology for catatonia is not clear in the literature.

Methods: A systematic review was completed to evaluate the literature on NCSE presenting with catatonia. PubMed and PsycInfo databases were searched and articles were reviewed for the presence of catatonia and NCSE.

Results: 15 articles describing 27 cases meeting inclusion criteria were identified. The authors add 1 case to the literature. The most common catatonic symptoms identified in NCSE were mutism and stupor. Clinical features frequent in NCSE presenting with catatonia included new catatonic symptoms, age over 50 years, comorbid neurological conditions, or a change in medications that affect seizure threshold. A documented psychiatric history was also common and may contribute to delayed diagnosis.

Discussion/conclusion: It is important to consider NCSE in the differential diagnosis of new catatonic symptoms. A suggested approach to diagnostic evaluation is provided.
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http://dx.doi.org/10.1016/j.genhosppsych.2020.11.008DOI Listing
November 2020

Non-Convulsive Status Epilepticus in the Presence of Catatonia: A Clinically Focused Review.

Gen Hosp Psychiatry 2021 Jan-Feb;68:25-34. Epub 2020 Nov 13.

Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.

Introduction: Catatonia is classically associated with psychiatric conditions but may occur in medical and neurologic disorders. Status epilepticus (SE) is a seizure lasting more than five minutes or two or more seizures within a five-minute period without interictal recovery of consciousness. Non-convulsive status epilepticus (NCSE) is SE without prominent motor activity that may present with catatonic symptoms. The relevance of NCSE as a potential etiology for catatonia is not clear in the literature.

Methods: A systematic review was completed to evaluate the literature on NCSE presenting with catatonia. PubMed and PsycInfo databases were searched and articles were reviewed for the presence of catatonia and NCSE.

Results: 15 articles describing 27 cases meeting inclusion criteria were identified. The authors add 1 case to the literature. The most common catatonic symptoms identified in NCSE were mutism and stupor. Clinical features frequent in NCSE presenting with catatonia included new catatonic symptoms, age over 50 years, comorbid neurological conditions, or a change in medications that affect seizure threshold. A documented psychiatric history was also common and may contribute to delayed diagnosis.

Discussion/conclusion: It is important to consider NCSE in the differential diagnosis of new catatonic symptoms. A suggested approach to diagnostic evaluation is provided.
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http://dx.doi.org/10.1016/j.genhosppsych.2020.11.008DOI Listing
November 2020

Neural Subtypes of Euthymic Bipolar I Disorder Characterized by Emotion Regulation Circuitry.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 06 8;5(6):591-600. Epub 2020 Mar 8.

Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California. Electronic address:

Background: Current diagnostic strategy for bipolar disorders relies on symptomological classification. Yet, responses to both pharmacological and psychotherapeutic treatments vary widely, suggesting that underlying neuropathological differences are not well defined by current nosology. Classifying patients with bipolar disorder based on emotion regulation network (ERN) activation may account for some of the heterogeneity within the disorder.

Methods: Euthymic participants diagnosed with bipolar I disorder (n = 86) and healthy subjects (n = 80) underwent functional magnetic resonance imaging scans while engaged in emotional reappraisal of negative stimuli. After determining average regional activations in key network regions, we applied agglomerative hierarchical clustering to identify subtypes of bipolar disorder. Next, we examined relations among neural subtypes, demographic variables, and mood symptoms.

Results: Analyses revealed two primary neural subtypes of euthymic bipolar I disorder participants. The first subtype, ERN cluster 1, was characterized by increased amygdala activation and slightly increased ventrolateral prefrontal and subgenual cingulate activation, whereas ERN cluster 2 was defined by decreased amygdala activation with wider-spread prefrontal activation. Cluster 1 was associated with a higher number of hospitalizations for depression (odds ratio = 1.30, 95% confidence interval = 1.02-1.64) and later onset of manic episodes (odds ratio = 1.06, 95% confidence interval = 1.00-21.13) than cluster 2. ERN clusters of healthy subjects differed from bipolar disorder clusters and were defined by differential activation of the prefrontal cortex. ERN clusters of healthy subjects, which differed from bipolar disorder clusters, were defined by differential activation of the prefrontal cortex.

Conclusions: Emotion regulation circuitry can distinguish neurobiological subtypes of bipolar disorder in the euthymic state. These subtypes, which are differentially associated with indices of illness severity and subsyndromal affective symptoms, may help to inform relapse risk and more personalized treatment approaches.
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http://dx.doi.org/10.1016/j.bpsc.2020.02.011DOI Listing
June 2020

High-Risk Phenotypes of Early Psychiatric Readmission in Bipolar Disorder With Comorbid Medical Illness.

Psychosomatics 2019 Nov - Dec;60(6):563-573. Epub 2019 May 28.

Department of Psychiatry and Behavioral Sciences, University of California, Los Angeles, Los Angeles, CA.

Background: Individuals with co-existing serious mental illness and non-psychiatric medical illness are at high risk of acute care utilization. Mining of electronic health record data can help identify and categorize predictors of psychiatric hospital readmission in this population.

Objective: This study aimed to identify modifiable predictors of psychiatric readmission among individuals with comorbid bipolar disorder and medical illness. This goal was accomplished by applying objective variable selection via machine learning techniques.

Method: This was a retrospective analysis of electronic health record data derived from 77,296 episodes of care from 2006 to 2016 within the University of California Health Care System. Data included 1,250 episodes of care involving patients with bipolar disorder and serious comorbid medical illnesses (defined by transfer between medicine and psychiatry services or concomitant primary medical and psychiatric admission diagnoses). Machine learning (classification trees) was used to identify potential predictors of 30-day psychiatric readmission across hospital encounters. Predictors included demographics, medical and psychiatric diagnoses, medication regimen, and disposition. The algorithm was internally validated using 10-fold cross-validation.

Results: The model predicted 30-day readmission with high accuracy (98% unbalanced model, 88% balanced model). Modifiable predictors of readmission were length of stay, transfers between medical and psychiatric services, discharge disposition to home, and all-cause acute health service utilization in the year before the index hospitalization.

Conclusion: Among bipolar disorder patients with comorbid medical conditions, characteristics of the index hospitalization (e.g., duration, transfer, and disposition) emerged as more predictive than static properties of the patient (e.g., sociodemographic factors and psychiatric comorbidity burden). Findings identified phenotypes of patients at high risk for rehospitalization and suggest potential ways of modifying the risk of early readmission.
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http://dx.doi.org/10.1016/j.psym.2019.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071814PMC
August 2020

Diagnostic and clinical implications of functional neuroimaging in bipolar disorder.

J Psychiatr Res 2014 Oct 8;57:12-25. Epub 2014 Jun 8.

Department of Psychiatry & Biobehavioral Sciences, UCLA Semel Institute for Neuroscience & Human Behavior, Los Angeles, CA, USA.

Advances in functional neuroimaging have ushered in studies that have enhanced our understanding of the neuropathophysiology of bipolar disorder, but do not yet have clinical applications. We describe the major circuits (ventrolateral, dorsolateral, ventromedial, and anterior cingulate) thought to be involved in the corticolimbic dysregulation that may underlie mood states in patients with bipolar disorder. The potential clinical application of functional neuroimaging in bipolar disorder is considered in terms of prognostic, predictive, and treatment biomarkers. To date, most research has focused on prognostic biomarkers to differentiate patients with bipolar disorder from those with other affective or psychotic diagnoses, or healthy subjects. The search for treatment biomarkers, which suggest mechanisms of pharmacodynamic or treatment response, and predictive biomarkers has thus far involved only pediatric patients diagnosed with bipolar disorder. The results to date are encouraging and suggest that functional neuroimaging may be of eventual benefit in determining biomarkers of treatment response. Further refinement of biomarker identification, and perhaps even illness characterization are needed to find prognostic and predictive biomarkers of bipolar disorder.
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http://dx.doi.org/10.1016/j.jpsychires.2014.05.018DOI Listing
October 2014

Anti-N-methyl-D-aspartate receptor encephalitis: a targeted review of clinical presentation, diagnosis, and approaches to psychopharmacologic management.

Ann Clin Psychiatry 2014 May;26(2):111-9

Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.

Background: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis was formally described in 2007 and includes a range of psychiatric and neurologic symptoms. Most patients with anti-NMDAR encephalitis initially present to psychiatrists for diagnosis and treatment. However, there is limited literature summarizing treatment strategies for psychiatric symptoms. In an effort to improve identification and treatment, this review article provides an overview of anti-NMDAR encephalitis, with a focus on psychopharmacologic treatment strategies. Two case reports provide a clinical context for the literature review.

Methods: The authors conducted a PubMed search.

Results: Prominent psychiatric symptoms of anti-NMDAR encephalitis include psychosis, agitation, insomnia, and catatonia. Neuroleptics may be helpful for managing psychosis and agitation, but may exacerbate movement abnormalities. Diphenhydramine and benzodiazepines are helpful for agitation and insomnia. In addition, the anticholinergic affinity of diphenhydramine can improve dystonia or rigidity attributable to anti-NMDAR encephalitis, while benzodiazepines and electroconvulsive therapy have been used for catatonia associated with this condition.

Conclusions: Psychiatrists play an important role in the diagnosis and treatment of anti-NMDAR encephalitis. Recognizing the typical clinical progression and closely monitoring for accompanying neurologic symptoms will facilitate diagnosis and timely treatment. Careful selection of psychopharmacological interventions may reduce suffering.
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May 2014

Predictive socioeconomic and clinical profiles of antidepressant response and remission.

Depress Anxiety 2013 Jul 3;30(7):624-30. Epub 2013 Jan 3.

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California 90024, USA.

Background: There are many prognostic factors for treatment outcome in major depressive disorder (MDD). The predictive power of any single factor, however, is limited. We aimed to develop profiles of antidepressant response and remission based upon hierarchical combinations of baseline clinical and demographic factors.

Methods: Using data from Level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D), in which 2,876 participants with MDD were treated with citalopram, a signal-detection analysis was performed to identify hierarchical predictive profiles for patients with different treatment outcome. An automated algorithm was used to determine the optimal predictive variables by evaluating sensitivity, specificity, positive and negative predictive value, and test efficiency.

Results: Hierarchical combinations of baseline clinical and demographic factors yielded profiles that significantly predicted treatment outcome. In contrast to an overall 47% response rate in STAR*D Level 1, response rates of profiled patient subgroups ranged from 31 to 63%. In contrast to an overall remission rate of 28%, identified subsets of patients had a 12 to 55% probability of remission. The predictors of antidepressant treatment outcome most commonly incorporated into profiles were related to socioeconomic status (e.g., income, education), whereas indicators of depressive symptom type and severity, as well as comorbid clinical conditions, were useful but less powerful predictors.

Conclusions: Hierarchical profiles of demographic and clinical baseline variables categorized patients according to the likelihood they would benefit from a single antidepressant trial. Socioeconomic factors had greater predictive power than symptoms or other clinical factors, and profiles combining multiple factors were stronger predictors than individual factors alone.
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http://dx.doi.org/10.1002/da.22045DOI Listing
July 2013

Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial.

Gen Hosp Psychiatry 2012 Nov-Dec;34(6):611-7. Epub 2012 Aug 13.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5718, USA.

Objectives: The objectives were to compare the efficacy of a benzodiazepine loading versus a symptom-triggered protocol in the management of alcohol withdrawal.

Methods: We conducted a prospective, randomized, controlled trial including 47 consecutive patients admitted to one of two tertiary care medical centers who developed alcohol withdrawal syndrome. Patients were randomly assigned to either a benzodiazepine loading protocol or a symptom-triggered treatment protocol. The Clinical Institute Withdrawal Assessment for Alcohol-Revised scale (CIWA-Ar) was recorded throughout the length of stay, along with measures of autonomic system functioning.

Results: The average rate of change of CIWA-Ar scores was -1.5 ± 1.3 for the symptom-triggered group and -2.3 ± 2.5 for the loading group. Average rate of change for systolic blood pressure was -2.7 ± 5.3 for the symptom-triggered group and -2.3 ± 6.4 for the loading group. There was no significant difference between the rates of change for either group on either measure. Similarly, there was no significant difference in total benzodiazepine use between groups. Within 72 h of treatment, 69.6% of patients in the loading group were free of withdrawal symptoms versus 41.7% in the symptom-triggered group, a difference not reaching statistical significance.

Conclusions: This study did not reveal clear evidence of a clinical advantage for choosing either treatment method.
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http://dx.doi.org/10.1016/j.genhosppsych.2012.06.016DOI Listing
May 2013

Mood-state effects on amygdala volume in bipolar disorder.

J Affect Disord 2012 Aug 21;139(3):298-301. Epub 2012 Apr 21.

Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.

Background: Prior structural neuroimaging studies of the amygdala in patients with bipolar disorder have reported higher or lower volumes, or no difference relative to healthy controls. These inconsistent findings may have resulted from combining subjects in different mood states. The prefrontal cortex has recently been reported to have a lower volume in depressed versus euthymic bipolar patients. Here we examined whether similar mood state-dependent volumetric differences are detectable in the amygdala.

Methods: Forty subjects, including 28 with bipolar disorder type I (12 depressed and 16 euthymic), and 12 healthy comparison subjects were scanned on a 3T magnetic resonance image (MRI) scanner. Amygdala volumes were manually traced and compared across subject groups, adjusting for sex and total brain volume.

Results: Statistical analyses found a significant effect of mood state and hemisphere on amygdala volume. Subsequent comparisons revealed that amygdala volumes were significantly lower in the depressed bipolar group compared to both the euthymic bipolar (p=0.005) and healthy control (p=0.043) groups.

Limitations: Our study was cross-sectional and some patients were medicated.

Conclusions: Our results suggest that mood state influences amygdala volume in subjects with bipolar disorder. Future studies that replicate these findings in unmedicated patient samples scanned longitudinally are needed.
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http://dx.doi.org/10.1016/j.jad.2012.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372678PMC
August 2012

Effectiveness of quetiapine plus lamotrigine maintenance therapy in challenging bipolar disorder patients.

J Affect Disord 2012 Mar 10;137(1-3):139-45. Epub 2012 Jan 10.

Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Objective: Assess quetiapine plus lamotrigine (QTP+LTG) combination maintenance therapy effectiveness in challenging bipolar disorder (BD).

Method: Outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form were naturalistically prescribed QTP+LTG.

Results: Fifty-four outpatients with challenging BD, taking in addition to QTP+LTG, a mean±SD of 2.1±1.6 (in 63.0% at least 2) other psychotropic and 2.3±1.9 non-psychotropic prescription medications, had QTP+LTG maintenance trials. Median(mean±SD) QTP+LTG duration was 401(730±756) days. Final QTP and LTG doses were 87.5(188±211) and 300(287±108) mg/day, respectively. Half (27/54) of patients discontinued QTP (in 19), LTG (in 6), or QTP+LTG (in 2), after 294(415±414) days - due to side-effects in 10, inefficacy in seven, non-adherence in five, and other reasons in five. 42.6%(23/54) had additional pharmacotherapy intervention for emergent mood symptoms, after 175(261±237) days, with at least one psychotropic added (in 16/54) or substantively (by ≥50%) increased (in 7/54). 55.6%(30/54) had recurrent mood episodes, after 126(187±158) days, most often depressive (in 35.2%), although 64.8%(35/54) were euthymic at final visit taking QTP+LTG. Sedation increased significantly during treatment among those with side-effect discontinuations, and 19.2%(10/52, all having QTP added to LTG) had clinically significant (≥7%) weight gain.

Limitations: No placebo comparison group. Small sample of predominantly female Caucasian insured outpatients taking complex concurrent medication regimens.

Conclusion: Additional studies are warranted to confirm our preliminary observation that QTP+LTG maintenance may be effective in patients with challenging BD.
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http://dx.doi.org/10.1016/j.jad.2011.12.024DOI Listing
March 2012

Individual risk profiles for postoperative delirium after joint replacement surgery.

Psychosomatics 2011 Sep-Oct;52(5):410-6

Department of Psychiatry, UCLA Semel Institute for Neuroscience and Human Behavior, CA, USA.

Background: Delirium occurs in nearly half of older patients after joint replacement surgery. However, risk profiles for developing delirium have not been established.

Objective: We sought to identify risk profiles for delirium in patients following joint replacement surgery.

Method: Based on data from a randomized, double-blind, placebo-controlled trial of olanzapine (10 mg) as delirium prophylaxis in 400 patients (67-81 years old) undergoing hip or knee replacement surgery, we performed a signal detection analysis to develop risk profiles for postsurgical delirium (using baseline patient characteristics, iatrogenic factors, and physiologic response parameters).

Results: Olanzapine reduced the incidence of delirium by 63% relative to placebo. Among patients receiving placebo, those with an ASA class = 3 and age ≥ 74 years had a 64% risk of delirium. Those with ASA class < 3 still had a 67% risk of delirium if postoperative oxygen saturation was < 95%. Patients who received olanzapine had an 83% risk of developing delirium if they received ≥ 42.5 mg equivalents of intra-operative morphine, were ≥ 74 years old, and had a mean arterial pressure (MAP) < 90 mm Hg at the presurgical screening visit. Patients with the lowest risk (6%) of developing delirium received olanzapine had a hematocrit ≥ 28%, and a presurgical MAP ≥ 90.

Conclusion: Although use of prophylactic olanzapine reduced the incidence of delirium, subsets of patients remained likely to develop delirium. The risk of developing delirium may be reduced through prophylactic dispensation of olanzapine, maintaining optimal perfusion and oxygenation, and limiting intra-operative opioids.
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http://dx.doi.org/10.1016/j.psym.2011.03.011DOI Listing
January 2012

Preliminary evidence of within-subject changes in gray matter density associated with remission of bipolar depression.

Psychiatry Res 2011 Jul 10;193(1):53-5. Epub 2011 May 10.

Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA 90024, USA.

A preliminary within-subjects MRI study of seven patients with a diagnosis of bipolar I disorder revealed that, compared to remission, depression was associated with gray matter density increases in subgenual prefrontal cortex, parahippocampal gyrus, and inferior temporal gyri. Decreases were observed in superior and inferior frontal gyri and anterior cingulate.
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http://dx.doi.org/10.1016/j.pscychresns.2010.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986411PMC
July 2011

Prefrontal and paralimbic metabolic dysregulation related to sustained attention in euthymic older adults with bipolar disorder.

Bipolar Disord 2010 Dec;12(8):866-74

Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA 90024, USA.

Objective:   Reports of sustained attention deficits in the euthymic phase of bipolar disorder have been variable, and have yet to be related to cerebral metabolism. In the present study, we evaluated relationships between cognitive performance deficits and resting cerebral metabolism in euthymic older adults with bipolar disorder.

Methods:   Sixteen older (mean age 58.7 years) euthymic outpatients with bipolar disorder (10 type I, 6 type II; 44% female) and 11 age-matched healthy controls received resting positron emission tomography with (18) fluorodeoxyglucose and, within 10 days, the Conners' Continuous Performance Test-II, a commonly used measure of sustained attention and inhibitory control.

Results:   Bipolar disorder patients had significantly more omission errors (z = 2.53, p = 0.01) and a trend toward more commission errors (z = 1.83, p < 0.07) than healthy controls. Relative to healthy controls, among bipolar disorder subjects commission errors were more strongly related to inferior frontal gyrus [Brodmann area (BA) 45/47] hypometabolism and paralimbic hypermetabolism. In bipolar disorder subjects, relative to controls, omission errors were more strongly related to dorsolateral prefrontal (BA 9/10) hypometabolism and greater paralimbic, insula, and cingulate hypermetabolism.

Conclusions:   In older adults with bipolar disorder, even during euthymia, resting-state corticolimbic dysregulation was related to sustained attention deficits and inhibitory control, which could reflect the cumulative impact of repeated affective episodes upon cerebral metabolism and neurocognitive performance. The relative contributions of aging and recurrent affective episodes to these differences in bipolar disorder patients remain to be established.
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http://dx.doi.org/10.1111/j.1399-5618.2010.00881.xDOI Listing
December 2010

Safety and tolerability associated with second-generation antipsychotic polytherapy in bipolar disorder: findings from the Systematic Treatment Enhancement Program for Bipolar Disorder.

J Clin Psychiatry 2011 Feb 7;72(2):240-7. Epub 2010 Sep 7.

UCLA Semel Institute, Los Angeles, California, USA.

Context: Practitioners often combine 2 or more second-generation antipsychotics (SGAs) in patients with bipolar disorder, despite an absence of data to support their safety, tolerability, or efficacy.

Objective: This study sought to evaluate the safety and tolerability of SGA polytherapy compared to SGA monotherapy in bipolar disorder patients receiving open naturalistic treatment in the 22-site Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Method: A longitudinal cohort of 1,958 patients who were prescribed at least 1 SGA was drawn from 4,035 bipolar patients in STEP-BD recruited between November 1999 and July 2005 and assessed at least quarterly for a mean duration of 21 months. Main outcome measures were the mean quarterly prevalence of adverse events, medical and psychiatric service usage, Global Assessment of Functioning ratings, and percentage of days spent well.

Results: Almost 10% of patients taking SGAs were prescribed SGA polytherapy. After controlling for illness onset, age, baseline illness severity, and medication load, patients prescribed SGA polytherapy, compared to monotherapy, exhibited more dry mouth (number needed to harm [NNH] = 4), tremor (NNH = 6), sedation (NNH = 8), sexual dysfunction (NNH = 8), and constipation (NNH = 11) and were almost 3 times as likely to incur more psychiatric and medical care; there was no association with greater global functioning scores or percentage of days spent well.

Conclusions: Although SGA polytherapy was fairly common in bipolar disorder, it was associated with increased side effects and health service use but not with improved clinical status or function. Thus, SGA polytherapy in bipolar disorder may incur important disadvantages without clear benefit, warranting careful consideration before undertaking such interventions.
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http://dx.doi.org/10.4088/JCP.09m05214yelDOI Listing
February 2011

Long-term effectiveness of quetiapine in bipolar disorder in a clinical setting.

J Psychiatr Res 2010 Oct 7;44(14):921-9. Epub 2010 Apr 7.

Stanford University School of Medicine, Stanford, CA 94305-5723, USA.

Objective: To assess quetiapine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Methods: We naturalistically administered open quetiapine to outpatients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results: 96 patients (36 BD I, 50 BD II, 9 BD NOS, 1 Schizoaffective Bipolar Type, mean ± SD age 42.3 ± 13.8 years, 66.7% female) received quetiapine, combined with an average of 2.5 (in 66.7% of patients at least 2) other psychotropic medications and 0.9 non-psychotropic medications, started most often during depressive symptoms (53.1%) or euthymia (37.5%). Mean quetiapine duration and final dose were 385 days and 196 mg/day (50.0% of patients took ≤75 mg/day). Quetiapine was discontinued in 38.5% of trials, after on average 307 days, most often (in 19.8%) due to CNS adverse effects (primarily sedation). In 38.5% of trials quetiapine was continued on average 328 days with no subsequent psychotropic added. In 22.9% quetiapine was continued on average 613 days, but had subsequent psychotropic added after on average 113 days, most often for depressive symptoms. In 67 trials started at Stanford, quetiapine tended to primarily maintain euthymia and relieve depressive symptoms. In 29 trials started prior to Stanford, continuing quetiapine tended to primarily maintain euthymia and relieve mood elevation symptoms. Aside from sedation, quetiapine was generally well tolerated.

Conclusions: In bipolar disorder outpatients quetiapine had a moderate (38.5%, with 385-day mean duration) discontinuation rate, and commonly did not require subsequent additional pharmacotherapy, suggesting effectiveness in a clinical setting.
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http://dx.doi.org/10.1016/j.jpsychires.2010.02.005DOI Listing
October 2010

Resting prefrontal hypometabolism and paralimbic hypermetabolism related to verbal recall deficits in euthymic older adults with bipolar disorder.

Am J Geriatr Psychiatry 2009 Dec;17(12):1022-9

UCLA Semel Institute and Department of Psychiatry, Los Angeles, CA 90024-1759, USA.

Objectives: To evaluate deficits of delayed free recall in euthymic older patients with bipolar disorder and relate deficits to resting cerebral metabolism.

Design: Two group, between subjects.

Setting: Outpatient.

Participants: Participants included 16 older adult (mean age, 58.7 years; SD = 7.5) euthymic outpatients with bipolar disorder (10 Type I and 6 Type II) and 11 healthy comparison subjects (mean age, 58.3 years; SD = 5.2).

Measurements: All participants received resting positron emission tomography with (18)flurodeoxyglucose and, within 10 days, delayed free verbal recall testing with the California Verbal Learning Test II.

Results: Patients with bipolar disorder, relative to healthy comparison subjects, had significantly poorer delayed free verbal recall. In patients with bipolar disorder, relative to healthy comparison subjects, prefrontal hypometabolism (dorsolateral prefrontal cortex) and paralimbic hypermetabolism (hippocampus, parahippocampal gyrus, and superior temporal gyrus) was associated with recall deficits in patients with bipolar disorder. Prefrontal and limbic metabolism were inversely related.

Conclusion: Our findings demonstrate an association between prefrontal hypometabolism and paralimbic hypermetabolism and verbal memory deficits in euthymic older patients with bipolar disorder. Verbal memory deficits may be a clinical consequence of corticolimbic dysregulation in bipolar disorder, even during euthymia. This suggests that such dysregulation and related deficits could be bipolar disorder traits.
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http://dx.doi.org/10.1097/JGP.0b013e3181ad4d47DOI Listing
December 2009

Metabolic evidence of corticolimbic dysregulation in bipolar mania.

Psychiatry Res 2010 Feb 15;181(2):136-40. Epub 2010 Jan 15.

UCLA Semel Institute, 760 Westwood Plaza, B3-233 NPI, Los Angeles, CA 90024-1759, USA.

Findings from previous research on the neural substrates of mania have been variable, in part because of heterogeneity of techniques and patients. Though some findings have been replicated, the constellation of neurophysiological changes has not been demonstrated simultaneously. We sought to determine resting state cerebral metabolic changes associated with relatively severe acute mania. Resting positron emission tomography with (18)fluorodeoxyglucose was performed in bipolar disorder patients with severe mania and in healthy controls. Statistical parametric mapping was used to determine regions of differential metabolism. Relative to controls, bipolar disorder patients with mania exhibited significantly decreased cerebral metabolism in both the dorsolateral prefrontal regions and the precuneus. Conversely, manic patients exhibited significant hypermetabolism in the parahippocampal complex, temporal lobe, anterior cingulate, and subgenual prefrontal cortex compared with controls. These results demonstrate simultaneous resting limbic/paralimbic hypermetabolism and prefrontal hypometabolism during mania. The findings support the hypothesis of corticolimbic dysregulation as a crucial contributor to the pathophysiology of bipolar disorder.
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http://dx.doi.org/10.1016/j.pscychresns.2009.08.006DOI Listing
February 2010

Dorsolateral and dorsomedial prefrontal gray matter density changes associated with bipolar depression.

Psychiatry Res 2009 Jun 5;172(3):200-4. Epub 2009 Apr 5.

Palo Alto Veterans Affairs Health Care System, Psychiatry Service, Palo Alto, CA, USA.

Mood states are associated with alterations in cerebral blood flow and metabolism, yet changes in cerebral structure are typically viewed in the context of enduring traits, genetic predispositions, or the outcome of chronic psychiatric illness. Magnetic resonance imaging (MRI) scans were obtained from two groups of patients with bipolar disorder. In one group, patients met criteria for a current major depressive episode whereas in the other no patient did. No patient in either group met criteria for a current manic, hypomanic, or mixed episode. Groups were matched with respect to age and illness severity. Analyses of gray matter density were performed with Statistical Parametric Mapping software (SPM5). Compared with non-depressed bipolar subjects, depressed bipolar subjects exhibited lower gray matter density in the right dorsolateral and bilateral dorsomedial prefrontal cortices and portions of the left parietal lobe. In addition, gray matter density was greater in the left temporal lobe and right posterior cingulate cortex/parahippocampal gyrus in depressed than in non-depressed subjects. Our findings highlight the importance of mood state in structural studies of the brain-an issue that has received insufficient attention to date. Moreover, our observed differences in gray matter density overlap metabolic areas of change and thus have implications for the conceptualization and treatment of affective disorders.
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http://dx.doi.org/10.1016/j.pscychresns.2008.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265395PMC
June 2009

Depressive illness burden associated with complex polypharmacy in patients with bipolar disorder: findings from the STEP-BD.

J Clin Psychiatry 2009 Feb 10;70(2):155-62. Epub 2009 Feb 10.

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.

Background: Many patients with bipolar disorder receive multi-drug treatment regimens, but the distinguishing profiles of patients who receive complex pharmacologies have not been established.

Method: Prescribing patterns of lithium, anticonvulsants, antidepressants, and antipsychotics were examined for 4,035 subjects with bipolar disorder (DSM-IV) immediately prior to entering the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Subjects were recruited for participation across 22 centers in the United States between November 1999 and July 2005. The quality receiver operating characteristic (ROC) method was used to develop composite profiles of patients receiving complex regimens (p < .01 for all iterations).

Results: Use of 3 or more medications occurred in 40% of subjects, while 18% received 4 or more agents. Quality ROC analyses revealed that subjects had a 64% risk for receiving a complex regimen (> or = 4 medications) if they had (1) ever taken an atypical antipsychotic, (2) > or = 6 lifetime depressive episodes, (3) attempted suicide, and (4) an annual income > or = $75,000. Complex polypharmacy was least often associated with lithium, divalproex, or carbamazepine and most often associated with atypical antipsychotics or antidepressants. Contrary to expectations, a history of psychosis, age at onset, bipolar I versus II subtype, history of rapid cycling, prior hospitalizations, current illness state, and history of alcohol or substance use disorders did not significantly alter the risk profiles for receiving complex regimens.

Conclusion: Complex polypharmacy involving at least 4 medications occurs in approximately 1 in 5 individuals with bipolar disorder. Use of traditional mood stabilizers is associated with fewer cotherapies. Complex regimens are especially common in patients with substantial depressive illness burden and suicidality, for whom simpler drug regimens may fail to produce acceptable levels of response.

Trial Registration: clinicaltrials.gov Identifier: NCT00012558.
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http://dx.doi.org/10.4088/jcp.08m04301DOI Listing
February 2009

Metabolic risks in older adults receiving second-generation antipsychotic medication.

Curr Psychiatry Rep 2009 Feb;11(1):33-40

UCLA Semel Institute, MC 175919, 760 Westwood Plaza, B8-233B NPI, Los Angeles, CA 90024, USA.

Metabolic syndrome is prevalent in older adults and increases the risk of cardiovascular disease. Second-generation antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) increase the risk of metabolic syndrome and present many challenges for psychiatrists. In this article, we review the relationships between second-generation antipsychotics and metabolic syndrome with a focus on older adults. Because few studies focus exclusively on older adults, we augment this review with relevant findings from younger adults. The differential risk factors of each medication are reviewed, as are recent findings in monitoring and treating metabolic syndrome. Olanzapine and clozapine are more strongly associated with metabolic risks, whereas aripiprazole and ziprasidone are less associated. Although lifestyle modifications can help to reduce some aspects of metabolic syndrome, lifestyle modifications in conjunction with metformin therapy appear to be most effective.
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http://dx.doi.org/10.1007/s11920-009-0006-0DOI Listing
February 2009

Substance use disorders as risk factors for psychiatric hospitalization in bipolar disorder.

Psychiatr Serv 2009 Jan;60(1):50-5

Palo Alto Veterans Affairs Health Care System, Palo Alto, California, USA.

Objective: This study developed risk profiles of psychiatric hospitalization for veterans diagnosed as having bipolar disorder.

Methods: This study included 2,963 veterans diagnosed as having bipolar disorder (types I, II, or not otherwise specified) during the 2004 fiscal year. Data were derived from the Veterans Affairs administrative database. Risk profiles for psychiatric hospitalization were generated with an iterative application of the receiver operating characteristic.

Results: In this sample 20% of the patients with bipolar disorder were hospitalized psychiatrically during the one-year study period. Patients diagnosed as having both an alcohol use disorder and polysubstance dependence and who also were separated from their spouse or partner had a 100% risk of psychiatric hospitalization; risk of psychiatric hospitalization decreased to 52% if the patients were not separated from their partner. Patients who were not diagnosed as having alcohol use disorders or polysubstance dependence and who were not separated from their partners exhibited the lowest risk of psychiatric hospitalization (12%). Among patients with a psychiatric hospitalization, 41% had longer lengths of stay (<14 days), with the strongest predictor of a longer length of stay being an age older than 77 years, which conferred a 77% risk.

Conclusions: Alcohol use and polysubstance dependence can significantly affect the course of bipolar disorder, as evidenced by their associations with psychiatric hospitalizations. Increased focus on substance abuse among older adults with bipolar disorder may decrease length of psychiatric hospitalization. Our findings suggest that implementing substance treatment programs early in the course of bipolar disorder could reduce health service use.
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http://dx.doi.org/10.1176/ps.2009.60.1.50DOI Listing
January 2009

Relation between cigarette smoking and cognitive function in euthymic individuals with bipolar disorder.

Pharmacol Biochem Behav 2009 Mar 22;92(1):12-6. Epub 2008 Oct 22.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.

Background: Individuals with bipolar disorder have higher rates of cigarette smoking and cognitive deficits when compared to the general population. Emerging evidence indicates that both smoking and cognitive deficits are associated with more severe illness presentation and course.

Methods: The data were derived from a study evaluating a novel treatment for cognitive function in bipolar disorder. Smoking status was determined by self-report; cognitive function was evaluated with a comprehensive cognitive battery, which included measures of psychomotor speed, attention, memory, learning and executive function. The relations between smoking status and cognitive measures were evaluated with two independent-samples t-test and multiple regression.

Results: The sample comprised forty-three subjects with bipolar disorder (Type I/II). There were no consistent differences in neuropsychological performance between current smokers (N=16) and non-smokers (N=27) on most tasks. The occurrence of subjective cognitive failures, as measured with the Cognitive Functioning Questionnaire, was non-significantly lower for smokers compared to non-smokers. Lifetime "smoking load" was negatively associated with premorbid intelligence as estimated by the National Adult Reading Test.

Conclusion: This pilot study provides preliminary evidence that cigarette smoking may exert a salutary effect on subjective, but not objective, measures of cognitive function in euthymic bipolar patients. A larger sample size evaluating this hypothesis would be less vulnerable to type II error.
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http://dx.doi.org/10.1016/j.pbb.2008.10.002DOI Listing
March 2009

Corticolimbic metabolic dysregulation in euthymic older adults with bipolar disorder.

J Psychiatr Res 2009 Feb 22;43(5):497-502. Epub 2008 Oct 22.

UCLA Semel Institute, Los Angeles, CA 90025, USA.

The corticolimbic dysregulation hypothesis of bipolar disorder suggests that depressive symptoms are related to dysregulation of components of an anterior paralimbic network (anterior cingulate, anterior temporal cortex, dorsolateral prefrontal cortex, parahippocampal gyrus, and amygdala) with excessive anterior limbic activity accompanied by diminished prefrontal activity. In younger patients, such abnormalities tend to resolve with remission of depression, but it remains to be established whether the same is true for older patients. This was a cross-sectional, between-subjects design conducted with 16 euthymic, medicated patients with bipolar disorder (10 type I, six type II) and 11 age-matched healthy controls. All participants were over age 50. Our main outcome measures were relative rates of cerebral metabolism derived from a resting (18)flourodeoxyglucose positron emission tomography scan in specified regions of interest in the corticolimbic network. Resting metabolic rates in bipolar patients were significantly greater than in controls in bilateral amygdalae, bilateral parahippocampal gyri, and right anterior temporal cortex (BA 20, 38); they were significantly lower in bipolar patients than in controls in the bilateral dorsolateral prefrontal cortices (BA 9, 10, 46). The evidence of corticolimbic dysregulation observed is consistent with the hypothesis that bipolar disorder entails progressive, pernicious neurobiological disruptions that may eventually persist during euthymia. Persistent corticolimbic dysregulation may be related to residual affective, behavioral, and cognitive symptoms in older patients with bipolar disorder, even when not experiencing syndromal mood disturbance.
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http://dx.doi.org/10.1016/j.jpsychires.2008.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693401PMC
February 2009

Sleep functioning in relation to mood, function, and quality of life at entry to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

J Affect Disord 2009 Apr 15;114(1-3):41-9. Epub 2008 Aug 15.

Department of Psychology, University of California, Berkeley, United States.

Background: Sleep disturbance in bipolar disorder can be both a risk factor and symptom of mood episodes. However, the associations among sleep and clinical characteristics, function, and quality of life in bipolar disorder have not been fully investigated.

Methods: The prevalence of sleep disturbance, duration, and variability, as well as their associations with mood, function, and quality of life, was determined from 2024 bipolar patients enrolled in the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Results: Analyses indicated that 32% of patients were classified as short sleepers, 38% normal sleepers, and 23% long sleepers. Overall, short sleepers demonstrated greater mood elevation, earlier age at onset, and longer illness duration compared to both normal and long sleepers. Both short and long sleepers had greater depressive symptoms, poorer life functioning, and quality of life compared to normal sleepers.

Discussion: Short sleep duration in bipolar disorder was associated with a more severe symptom presentation, whereas both short and long sleep duration are associated with poorer function and quality of life compared to normal sleep duration. Sleep disturbance could be a trait marker of bipolar disorder, though longitudinal assessments are warranted to assess potential causal relations and the longer-term implications of sleep disturbance in bipolar disorder.
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http://dx.doi.org/10.1016/j.jad.2008.06.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677624PMC
April 2009

Decreased prefrontal, anterior cingulate, insula, and ventral striatal metabolism in medication-free depressed outpatients with bipolar disorder.

J Psychiatr Res 2009 Jan 25;43(3):181-8. Epub 2008 Jun 25.

Palo Alto Veterans Affairs Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.

This study explored whether cerebral metabolic changes seen in treatment resistant and rapid cycling bipolar depression inpatients are also found in an outpatient sample not specifically selected for treatment resistance or rapid cycling. We assessed 15 depressed outpatients with bipolar disorder (six type I and nine type II) who were medication-free for at least 2 weeks and were not predominantly rapid cycling. The average 28-item Hamilton Depression Scale (HAM-D) total score was 33.9. The healthy control group comprised 19 age-matched subjects. All participants received a resting quantitative 18F-fluoro-deoxyglucose positron emission tomography scan. Data analyses were performed with Statistical Parametric Mapping (SPM5). Analyses revealed that depressed patients exhibited similar global metabolism, but decreased absolute regional metabolism in the left much more than right dorsolateral prefrontal cortex, bilateral (left greater than right) insula, bilateral subgenual prefrontal cortex, anterior cingulate, medial prefrontal cortex, ventral striatum, and right precuneus. No region exhibited absolute hypermetabolism. Moreover, HAM-D scores inversely correlated with absolute global metabolism and regional metabolism in the bilateral medial prefrontal gyrus, postcentral gyrus, and middle temporal gyrus. Analysis of relative cerebral metabolism yielded a similar, but less robust pattern of findings. Our findings confirm prefrontal and anterior paralimbic metabolic decreases in cerebral metabolism outside of inpatients specifically selected for treatment resistant and rapid cycling bipolar disorder. Prefrontal metabolic rates were inversely related to severity of depression. There was no evidence of regional hypermetabolism, perhaps because this phenomenon is less robust or more variable than prefrontal hypometabolism.
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http://dx.doi.org/10.1016/j.jpsychires.2008.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265392PMC
January 2009

Effectiveness of lamotrigine in bipolar disorder in a clinical setting.

J Psychiatr Res 2008 Nov;43(1):13-23

Stanford University School of Medicine, 401 Quarry Road, Room 2124, Stanford, CA, USA.

Objective: To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Method: Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results: One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean+/-SD age 42.2+/-14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1+/-1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434+/-444 days, and mean final dose was 236+/-132mg/day without valproate, and 169+/-137mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255+/-242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264+/-375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674+/-479 days, but had subsequent psychotropic added at 146+/-150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.

Conclusion: In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.
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http://dx.doi.org/10.1016/j.jpsychires.2008.02.007DOI Listing
November 2008

Neurocognitive costs and benefits of psychotropic medications in older adults.

J Geriatr Psychiatry Neurol 2007 Dec;20(4):199-214

Palo Alto Veterans Affairs Health Care System and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.

Psychotropic medications are widely used in older adults and may cause neurocognitive deficits. Older adults are at increased risk of developing adverse effects because of age-related pharmacodynamic and pharmacokinetic changes. This article provides a comprehensive review of the undesirable, and at times beneficial, effects of psychotropic medications. The review covers a wide range of medications that impair executive function, memory, and attention, as well as a much smaller group of medications that lead to improved neurocognitive function. Some of the most commonly used psychotropic medications in older adults, namely, antidepressants, sedatives, and hypnotics, are among the drugs that most consistently lead to cognitive impairments. Medications with anticholinergic properties almost invariably lead to neurocognitive dysfunction, despite symptom improvement. The neurocognitive costs and benefits of psychiatric medications should be considered in the context of disease treatment in older adults.
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http://dx.doi.org/10.1177/0891988707308803DOI Listing
December 2007