Development of the Huntington Support App (HD-eHelp study): a human-centered and co-design approach.

Introduction: eHealth seems promising in addressing challenges in the provision of care for Huntington's disease (HD) across Europe. By harnessing information and communication technologies, eHealth can partially relocate care from specialized centers to the patients' home, thereby increasing the availability and accessibility of specialty care services beyond regional borders. Previous research on eHealth (development) in HD is however limited, especially when it comes to including eHealth services specifically designed together with HD gene expansion carriers (HDGECs) and their partners to fit their needs and expectations. Methods: This article describes the qualitative human-centered design process and first evaluations of the Huntington Support App prototype: a web-app aimed to support the quality of life (QoL) of HDGECs and their partners in Europe. Prospective end-users, i.e., HDGECs, their partners, and healthcare providers (HCPs), from different countries were involved throughout the development process. Through interviews, we captured people's experiences with the disease, quality of life (QoL), and eHealth. We translated their stories into design directions that were further co-designed and subsequently evaluated with the user groups. Results: The resulting prototype centralizes clear and reliable information on the disease, HD-related news and events, as well as direct contact possibilities with HCPs via an online walk-in hour or by scheduling an appointment. The app's prototype was positively received and rated as (very) appealing, pleasant, easy to use and helpful by both HDGECs and partners. Discussion: By involving end-users in every step, we developed a healthcare app that meets relevant needs of individuals affected by HD and therefore may lead to high adoption and retention rates. As a result, the app provides low-threshold access to reliable information and specialized care for HD in Europe. A description of the Huntington Support App as well as implications for further development of the app's prototype are provided.

Comparison of Acoustic Voice Features Derived From Mobile Devices and Studio Microphone Recordings.

OBJECTIVES/HYPOTHESIS: Improvements in mobile device technology offer new opportunities for remote monitoring of voice for home and clinical assessment. However, there is a need to establish equivalence between features derived from signals recorded from mobile devices and gold standard microphone-preamplifiers. In this study acoustic voice features from android smartphone, tablet, and microphone-preamplifier recordings were compared. METHODS: Data were recorded from 37 volunteers (20 female) with no history of speech disorder and six volunteers with Huntington's disease (HD) during sustained vowel (SV) phonation, reading passage (RP), and five syllable repetition (SR) tasks. The following features were estimated: fundamental frequency median and standard deviation (F0 and SD F0), harmonics-to-noise ratio (HNR), local jitter, relative average perturbation of jitter (RAP), five-point period perturbation quotient (PPQ5), difference of differences of amplitude and periods (DDA and DDP), shimmer, and amplitude perturbation quotients (APQ3, APQ5, and APQ11). RESULTS: Bland-Altman analysis revealed good agreement between microphone and mobile devices for fundamental frequency, jitter, RAP, PPQ5, and DDP during all tasks and a bias for HNR, shimmer and its variants (APQ3, APQ5, APQ11, and DDA). Significant differences were observed between devices for HNR, shimmer, and its variants for all tasks. High correlation was observed between devices for all features, except SD F0 for RP. Similar results were observed in the HD group for SV and SR task. Biological sex had a significant effect on F0 and HNR during all tests, and for jitter, RAP, PPQ5, DDP, and shimmer for RP and SR. No significant effect of age was observed. CONCLUSIONS: Mobile devices provided good agreement with state of the art, high-quality microphones during structured speech tasks for features derived from frequency components of the audio recordings. Caution should be taken when estimating HNR, shimmer and its variants from recordings made with mobile devices.

Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families. In the European HD-eHelp study, we aim to capture the needs and wishes of HDGECs, partners of HDGECs, and health care providers (HCPs) in order to develop a multinational eHealth platform targeting QoL of both HDGECs and partners at home. Methods: We will employ a participatory user-centered design (UCD) approach, which focusses on an in-depth understanding of the end-users' needs and their contexts. Premanifest and manifest adult HDGECs (n = 76), partners of HDGECs (n = 76), and HCPs (n = 76) will be involved as end-users in all three phases of the research and design process: (1) Exploration and mapping of the end-users' needs, experiences and wishes; (2) Development of concepts in collaboration with end-users to ensure desirability; (3) Detailing of final prototype with quick review rounds by end-users to create a positive user-experience. This study will be conducted in the Netherlands, Germany, Czech Republic, Italy, and Ireland to develop and test a multilingual platform that is suitable in different healthcare systems and cultural contexts. Discussion: Following the principles of UCD, an innovative European eHealth platform will be developed that addresses the needs and wishes of HDGECs, partners and HCPs. This allows for high-quality, tailored care to be moved partially into the participants' home, thereby circumventing some barriers in current HD care provision. By actively involving end-users in all design decisions, the platform will be tailored to the end-users' unique requirements, which can be considered pivotal in eHealth services for a disease as complex and rare as HD.

Predictors of inpatient and outpatient healthcare utilization in veterans with traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) can place a significant financial and resource burden on healthcare systems. This study examined predictors of outpatient and inpatient healthcare utilization in veterans with a history of TBI. METHODS: A secondary analysis was conducted on data from 1565 veterans with TBI and 1565 veterans without TBI seen for healthcare services at the VA Palo Alto Health Care System between 2000 and 2010. Patterns and predictors of outpatient and inpatient medical and psychiatric care were examined. RESULTS: Veterans with TBI utilized significantly more services compared with the control group. The TBI group was seen for more than 160 000 outpatient services and was almost 9 times more likely to be hospitalized than the control group. Although psychiatric disorders were more prevalent in the TBI group and associated with increased medical and mental health utilization within the TBI group, they did not account fully for the significant group differences. CONCLUSIONS: Veterans with a history of TBI have much greater healthcare needs than veterans without TBI, likely because of non-TBI-related factors. Increased monitoring and early intervention treatments may be warranted for certain at-risk veterans with the goal of minimizing their need for long-term or extensive healthcare services in the future.

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

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.

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

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.

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

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.

Metabolic evidence of corticolimbic dysregulation in bipolar mania.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Corticolimbic metabolic dysregulation in euthymic older adults with bipolar disorder.

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.

Acetylcholinesterase inhibitor in combination with cognitive training in older adults.

To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.

Effectiveness of lamotrigine in bipolar disorder in a clinical setting.

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.

Neurocognitive costs and benefits of psychotropic medications in older adults.

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.

Should one use medications in combination with cognitive training? If so, which ones?

In this article, we review current research regarding diagnosis of cognitive impairment in nondemented adults and discuss why medications and cognitive training together may be more beneficial than either alone. We also review potential cognitive enhancers and future research challenges. There are major reasons for such research: (a) Large numbers of older adults without dementia but with cognitive problems are not treatable with current cognitive training techniques; (b) some medications offer a rationale (i.e., cognitive enhancement) and some evidence that they might be a useful adjunct; and (c) there are unanswered questions about which population to target, which medications to use, how to administer them, and issues regarding tolerance and use of appropriate (active) placebo controls. As the number of cognitively impaired older adults grows, it is likely that there will be pressure to treat more broadly with both medications and cognitive training.

Factors associated with psychiatric hospitalization of individuals diagnosed with dementia and comorbid bipolar disorder.

The objective was to determine risk factors of psychiatric hospitalization among a Veterans Administration database of patients with dementia and comorbid bipolar disorder (D+BD). Patients with D+BD had a greater prevalence of psychiatric hospitalization (28% vs 4%). The strongest predictor of psychiatric hospitalization was the presence of an alcohol use disorder (51% risk); patients without alcohol use disorders but under the age of 70 had the next highest risk (33% risk). However, patients with an alcohol use disorder had shorter psychiatric hospitalizations than those without. Compared with patients without BD, D+BD patients were more likely to have alcohol use disorders (15% vs 3%) and any other substance use problem (10% vs 1%). In patients diagnosed with dementia and bipolar disorder, the strongest risk factor for psychiatric hospitalization was an alcohol abuse disorder. These findings suggest that disorders with increased frequency in BD affect the course of dementia.

Preliminary evidence of differential relations between prefrontal cortex metabolism and sustained attention in depressed adults with bipolar disorder and healthy controls.

OBJECTIVES: To assess the relations between sustained attention as assessed by the Continuous Performance Test (CPT) and subgenual and dorsolateral prefrontal cortex metabolism in depressed patients with bipolar disorders and healthy controls. DESIGN: Cross-sectional case-control design. METHODS: Cerebral metabolic rates were assessed with 18F-fluoro-deoxyglucose and positron emission tomography (PET) in the regions of interest defined on co-registered structural magnetic resonance images in eight medication-free, depressed bipolar disorder patients and 27 healthy control participants. PET scans were obtained in a resting state and the CPT was administered within 1 week of the PET scan. RESULTS: Although there were no statistically significant differences in performance on the CPT or in cerebral metabolism between the two groups, our analyses revealed differential relations between the CPT and metabolism across the groups. Decreased subgenual prefrontal metabolism was associated with slower hit rate reaction time and more omission errors in the bipolar group, but not the control group. Decreased dorsolateral prefrontal metabolism in the bipolar group, but not the control group, was associated with more commission errors. CONCLUSIONS: This study extends previous neuroimaging findings of structural and functional relevance of the prefrontal region with attention to include depressed states in bipolar disorder. The results are consistent with interpretations that decreased prefrontal activity may represent failure to activate some areas of inhibitory control. Decreasing subgenual prefrontal cortex metabolism appears to relate to decreased attention whereas the decreased dorsolateral prefrontal cortex metabolism relates more to decreased inhibitory control.