Adverse Cognitive Effects Research Articles

Determinants of quality of life in people with epilepsy in Serbia

PurposeThis study aimed at finding determinants of quality of life in people with epilepsy (PWE) living in Belgrade, Serbia. MethodIn this study, we recruited consecutive adults with epilepsy attending our outpatient department. Adult patients (age range: 18–65years) of normal intelligence and without any progressive neurological disease or psychiatric disorder were included in the study. They completed the following questionnaires: QOLIE-31 Inventory (Serbian version), Beck's Depression Inventory-II, Beck's Anxiety Inventory, Symptom Check List-90, and Neurotoxicity Scale-II. Hierarchical multiple regression analysis was performed to assess the predictive effects of some factors on QOLIE-31 Inventory. ResultsThe mean QOLIE-31 score of 203 patients who completed the questionnaires was 70.64±17.74. Sociodemographic factors (age, sex, education, and employment) did not significantly predict QOLIE-31 score. Significant determinants of quality of life were clinical characteristics – seizure severity and etiology of epilepsy – accounting for 30.9% of the variance, depressive and anxiety symptoms accounting for 42.8% of the variance, and cognitive effects of antiepileptic drugs, accounting for 1.5% above other variables. ConclusionsThe results suggest that seizure severity and etiology of epilepsy, depressive and anxiety symptoms, and cognitive adverse medication effects are main determinants of quality of life in this population of PWE.

Neuropsychological implications of adjunctive levetiracetam in childhood epilepsy.

Introduction:Levetiracetam (LEV) is an effective antiepileptic drug also used in childhood and adolescence. Literature data regarding the long-term effects of LEV in childhood epilepsy and based on extensive neuropsychological evaluations using standardized tools are still scanty. Our study aimed to address this topic.Materials and Methods:We studied 10 patients with epilepsy characterized by focal or generalized seizures (4 boys, 6 girls; mean age: 10 years 8 months; range: 6 years 2 months - 16 years 2 months), treated with adjunctive LEV during a follow-up of 12 months. In 6 patients electroencephalogram (EEG) showed continuous spike and waves during sleep. Using standardized tools, we performed seriated assessments of cognitive and behavioral functioning in relation to seizure and EEG outcome.Results:Six patients completed the trial after 12 months of treatment; 1 patient dropped out of the study after 9 months, 3 patients after 6 months. Adjunctive LEV was effective on seizures in 3/10 patients and on EEG in 2/10 patients, and was well tolerated in all examined cases. Overall, no worsening of cognitive or behavioral functions has been detected during the period of the study; even at 6 and 12 months from baseline, an improvement in patients’ abstract reasoning has been found, that was not related to seizure or EEG outcome.Conclusions:In our population of children and adolescents, LEV had no adverse cognitive or behavioral effects, short- or long-term. We found an improvement of abstract reasoning, regardless of seizure and EEG outcome.

Examination of the FDA Warning for Statins and Cognitive Dysfunction

Background: The ACC/AHA released new guidelines in December of 2013 for treatment of high blood cholesterol to simplify identification and treatment of patients most likely to benefit from statins. These guidelines may result in more patients receiving statin therapy, and at younger ages. In 2012, the U.S. Food and Drug Administration (FDA) mandated warnings for all statin drugs for possible adverse effects on cognitive performance. Statins can be classified as having greater lipophilic or hydrophilic solubility properties with lipophilic statins more readily crossing the blood brain barrier, and possibly differentially inducing detrimental cognitive effects. Objective: We sought to analyze generalizability of the FDA statin class warning. Methods: De-identified publicly-available data were analyzed from the FDA Adverse Event Reporting System (AERS) in relation to reports of cognitive dysfunction (primary outcome), and by type of statin (lipophilic, hydrophilic) versus “control” drugs used in the general population. Results: Significantly higher proportional reporting ratios (PRRs) were observed for lipophilic statins, which more readily cross the blood-brain barrier, (range: 1.47-3.51) compared to hydrophilic statins (range: 0.69-1.64). However, fluvastatin, lovastatin, and pitavastatin (lipophilic) had relatively few adverse reports. The signal of higher risk of cognitive dysfunction was observed for the lipophilic statin atorvastatin (PRR = 2.59, 95% confidence interval: 2.44-2.75) followed by simvastatin (PRR = 2.22, 95% confidence interval: 2.04-2.31). Hydrophilic statins (rosuvastatin, pravastatin) showed essentially no evidence suggestive of heightened risk of cognitive dysfunction. Fluvastatin, lovastatin, and pitavastatin had relatively few adverse reports, and no evidence of a higher proportion of cognitive dysfunction reports compared to the control drugs in aggregate (PRR range: 0.22 to 1.48). Conclusions: Inconsistent with the FDA class warning, highly lipophilic statins with specific pharmacokinetic properties (atorvastatin, simvastatin) appear to confer a significantly greater risk of adverse cognitive effects compared to other lipophilic statins and those with hydrophilic solubility properties.

Exploring interference from analgesia in patients with cancer pain: a longitudinal qualitative study.

To increase understanding of the impact of analgesic side effects in patients with cancer pain. Studies in the area of cancer pain often refer to the need to find a satisfactory balance between analgesics and side effects as the key to cancer pain management. We explore how patients achieve this balance, its components and how it affects pain treatment adherence. An exploratory longitudinal study using qualitative research methodology. Twenty-five semi-structured face-to-face interviews with patients with advanced cancer and their caregivers. Longitudinal interviews were conducted with patients (n = 11) at six-week intervals over three months. Eleven first interviews, eight second interviews and six third interviews were completed with attrition due to death or ill health. Ten of the 25 interviews included caregivers. How cancer pain analgesics interfere with patients' life determines their adherence to the prescribed treatment. Compromises were made to manage three elements: pain, cognitive adverse effects of analgesics and physical activity. Negotiations and choices within this triad fluctuated and were determined by multiple psychosocial circumstances affecting patients and their caregivers varying from simple to complex. Patients with cancer and their caregivers actively managed the interference of analgesic drugs in their cognitive abilities and displayed a variety of nonadherence behaviours. Further understanding of the role of analgesic side effects in the success of cancer pain management in patients is needed. This would enable clinicians to frame an optimal pain management plan. Clinicians should advise their patients about side effects of analgesic drugs, specifically the impact that cognitive alterations might have on their lives and subsequent adherence behaviour. Helping patients to achieve a balance between pain, adverse effects and physical function should have a key place in pain management strategies with advanced cancer.

Influence of deep brain stimulation of the subthalamic nucleus on cognitive function in patients with Parkinson’s disease

Deep brain stimulation (DBS) is an effective technique for treating Parkinson's disease (PD) in the middle and advanced stages. The subthalamic nucleus (STN) is the most common target for clinical treatment using DBS. While STN-DBS can significantly improve motor symptoms in PD patients, adverse cognitive effects have also been reported. The specific effects of STN-DBS on cognitive function and the related mechanisms remain unclear. Thus, it is imperative to identify the influence of STN-DBS on cognition and investigate the potential mechanisms to provide a clearer view of the various cognitive sequelae in PD patients. For this review, a literature search was performed using the following inclusion criteria: (1) at least 10 patients followed for a mean of at least 6 months after surgery since the year 2006; (2) pre- and postoperative cognitive data using at least one standardized neuropsychological scale; and (3) adequate reporting of study results using means and standard deviations. Of ∼170 clinical studies identified, 25 cohort studies (including 15 self-controlled studies, nine intergroup controlled studies, and one multi-center, randomized control experiment) and one meta-analysis were eligible for inclusion. The results suggest that the precise mechanism of the changes in cognitive function after STN-DBS remains obscure, but STN-DBS certainly has effects on cognition. In particular, a progressive decrease in verbal fluency after STN-DBS is consistently reported and although executive function is unchanged in the intermediate stage postoperatively, it tends to decline in the early and later stages. However, these changes do not affect the improvements in quality of life. STN-DBS seems to be safe with respect to cognitive effects in carefully-selected patients during a follow-up period from 6 months to 9 years.

Autobiographical and Subjective Memory With Right Unilateral High-Dose 0.3-millisecond Ultrabrief-Pulse and 1-millisecond Brief-Pulse Electroconvulsive Therapy

Shortening the pulse width to 0.3 millisecond holds neurophysiological and clinical promise of making electroconvulsive therapy (ECT) safer by reducing cognitive adverse effects. The exclusive effects of pulse width on autobiographical and subjective memory are largely unstudied. The aim was to principally investigate during the acute ECT course and at 3 months after ECT autobiographical and subjective memory effects of 0.3-millisecond ultrabrief and 1-millisecond brief-pulse ECT. Patient with severe depression were randomized to 1-millisecond brief-pulse (n = 20) or 0.3-millisecond ultrabrief-pulse (n = 20) right unilateral ECT, both at 6 times the threshold stimulus dose given thrice weekly. Autobiographical Memory Interview (Kopelman) and Squire Subjective Memory Questionnaire were administered at baseline, after 8 sessions, end of the acute course, and 3 months later. Early adult semantic memory worsened significantly over time with brief-pulse compared with ultrabrief ECT: F3,88 = 2.60, P = 0.05. There was a significant decline in brief-pulse treatment vis-à-vis a significant improvement with ultrabrief-pulse treatment with childhood semantic memory (P = 0.022), early adult semantic (P = 0.03), and recent semantic memory (P = 0.018) only at 24 hours after the eighth ECT treatment. Clinically meaningful and significant improvement in semantic autobiographical memory occurred in ultrabrief treatment vis-à-vis brief-pulse ECT after 8 treatments. Ultrabrief treatment offered a small but significant advantage over 1-millisecond brief-pulse high-dose right unilateral ECT with early adult semantic autobiographical memory, which persisted up to 3 months.

Efficacy of Right Unilateral Ultrabrief Pulse Width ECT

Ultrabrief (right unilateral) electroconvulsive therapy (UB-RU ECT) is a newer form of ECT, which uses a shorter pulse width than the standard ECT (0.3 vs 1.0 millisecond, respectively). As a result, the use of UB ECT may provide a means of further decreasing ECT-related cognitive adverse effects. In 2011, the University of Texas Southwestern Department of ECT in Austin adopted a UB ECT protocol. The purpose of this study was to perform a preliminary evaluation of the effectiveness and efficiency of UB-RU ECT. This study also examined whether sex, age, or diagnosis affected response rates. This retrospective chart review identified 62 patients treated with the UB ECT protocol. An analysis of ECT response rates and demographic characteristics was conducted based on the data from clinical evaluations and Patient Health Questionnaire 9. Sixty-eight percent of patients in the study responded to ECT; 55% responded to UB pulse width RU ECT with another 13% responding when switched to standard pulse width bilateral ECT. The mean number of treatments in an index ECT series was 12.5. There was no statistically significant difference in response rates between bipolar and unipolar depressed patients. Men required progression to bilateral treatment more than women. This UB ECT protocol demonstrated a similar response rate when compared to standard ECT protocols; however, an increase in the number of treatments was required. Ultrabrief protocols are a viable option for both bipolar and unipolar depression. In men, UB ECT protocols may be less advantageous due to a need to overcome a potentially higher seizure threshold in men; however, additional research is needed to confirm this finding.

Polychlorinated Biphenyl Exposures and Cognition in Older U.S. Adults: NHANES (1999–2002)

Background: Polychlorinated biphenyls (PCBs) are ubiquitously present in humans because of their resistance to degradation and accumulation in fatty tissues. Data on neurotoxic effects in older adults are limited.Objective: We examined the cross-sectional association between serum PCB concentrations and cognitive function in older adults from the general U.S. population.Methods: We analyzed data from 708 respondents, 60–84 years of age, participating in the National Health and Nutrition Examination Survey (1999–2002). We used the summed concentrations of 12 lipid-standardized PCB congeners as the measure of exposure and assessed cognitive function with the Digit-Symbol Coding test. We adjusted analyses for age, education, race/ethnicity, and poverty/income ratio.Results: The median concentration of lipid-standardized PCBs in serum was 271 ng/g (interquartile range, 193–399 ng/g). We found a significant interaction between dioxin-like PCB concentration and age in association with cognitive score (p = 0.04). Among older individuals (70–84 years of age), a 100-ng/g increase in serum concentrations of dioxin-like PCBs was associated with a significantly lower cognitive score (–2.7 points; 95% CI: –5.1, –0.2; p = 0.04); however, in younger individuals (60–69 years of age), there was a nonsignificant positive association (2.9 points; 95% CI: –1.8, 7.7; p = 0.32). Among the older participants, the negative association was more pronounced in women than in men.Conclusion: Our findings support the hypothesis that PCB exposure has adverse cognitive effects even at levels generally considered to pose low or no risk, perhaps affecting mainly those of advanced age.Citation: Bouchard MF, Oulhote Y, Sagiv SK, Saint-Amour D, Weuve J. 2014. Polychlorinated biphenyl exposures and cognition in older U.S. adults: NHANES (1999–2002). Environ Health Perspect 122:73–78; http://dx.doi.org/10.1289/ehp.1306532

Propofol and thiopental as anaesthetic agents in electroconvulsive therapy: A retrospective study in major depression

ObjectiveTo determine the influence of propofol and thiopental as anaesthetics in electroconvulsive therapy (ECT), as regards, seizure duration, electrical charge, clinical efficacy, cardiovascular profile, and presence of adverse cognitive effects. MethodsA retrospective design including 127 patients who received bilateral ECT for the treatment of a major depressive episode. ResultsThe mean seizure duration in the propofol group was significantly shorter than in the thiopental group (21.23±6.09 versus 28.24±6.67s, P<0.001). The mean stimulus charge was 348.22mC in the propofol group, and 238mC in the thiopental group (P<0.001). Propofol was associated with a lower increase in blood pressure. There were no differences between groups in treatment response or presence of adverse effects. ConclusionsThe anaesthetic agent used in ECT might determine differences in parameters such as seizure duration or electrical charge. However, this does not seem to be translated into differences in clinical efficacy or the pattern of adverse effects observed.

Neuropsychological and neuroanatomical sequelae of chronic non-malignant pain and opioid analgesia.

The pervasive disease of chronic pain is a common challenge for the clinical rehabilitation professional. Concurrent with physical and emotional symptoms, pain-related cognitive impairment has been reported. Although opioid analgesics are frequently prescribed, concern exists that opioids possess adverse cognitive effects of their own. To review the neuropsychological and neuroanatomical sequelae of chronic non-malignant pain and opioid therapy, to clarify roles and benefits of neuropsychological assessment in a chronic pain population, and to provide recommendations for clinical practice and future research. This non-systematic review sought to provide a comprehensive synthesis of relevant neurobiology, neuroimaging, neuropsychological, and rehabilitation research literatures. We included citations from seminal and current texts as well as relevant original and review articles from 1980-2012 in PubMed and PubMedCentral online research databases. To date, evidence from opioid studies suggests only mild deficits in specific cognitive domains (e.g., memory, attention/concentration) and only under specific conditions (e.g., dose escalations). Additionally, neuroimaging and neuropsychological evidence suggests that pain itself results in cognitive sequelae. Methodological improvements in future research will allow for better delineation of the contributing effects of pain and opioids, with an overall goal of improving evidence-based clinical treatment recommendations.

Formulary management of 2 new agents: lorcaserin and phentermine/topiramate for weight loss.

Obesity may lead to the development of multiple chronic disease states, including hypertension, dyslipidemia, and type 2 diabetes mellitus. Over a half billion adults worldwide are affected by obesity, and more than two-thirds of adults are either obese or overweight in the United States. Diet and exercise have been the mainstays of treatment in this population; however, once failed, noninvasive, long-term effective treatment modality is lacking, and medications may potentially fill the void. Lorcaserin and phentermine/topiramate were approved by the FDA in June 2012 and July 2012, respectively, as adjuncts to diet and exercise for chronic weight management of obese (body mass index [BMI] ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) individuals with comorbidities. To review the phase 3 trials of lorcaserin and phentermine/topiramate and provide managed care considerations that may be taken into account as a result. A MEDLINE review was performed for articles published and available through September 17, 2012, using keywords "lorcaserin" or "phentermine/topiramate" with an emphasis on phase 3 trials. The literature search was limited to randomized controlled trials in humans published in the English language. Additional information on lorcaserin from its FDA review was obtained from the FDA website. 5 pivotal phase 3 trials were identified: 3 for lorcaserin and 2 for phentermine/topiramate. Both agents demonstrated a statistically significant higher proportion of individuals who lost ≥ 5% of body weight, as well as higher mean weight loss when compared with placebo. Safety concerns for lorcaserin include cardiac valvulopathy and increased risk of psychiatric, cognitive, and serotonergic adverse effects. Teratogenicity and increased heart rate are major safety concerns regarding phentermine/topiramate. Health care decision makers have many factors to consider when developing strategies to fight obesity. Despite a great need for new therapies to treat obesity, medications used for weight loss have significant side-effect profiles and contraindications that may limit therapy. An appropriate utilization management strategy is needed.

P.2.d.032 Management of postpartum manic episode without cessation of breastfeeding: a longitudinal follow up of drug excretion into breast milk

The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT.This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India.Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20–30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearson's correlation.Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment.B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice.

P.1.j.009 Breaking evidence from a human object pattern separation test of disrupted hippocampal dentate gyrus activity in schizophrenics

But extensive assessment by experienced neuropsychologists is hardly feasible in everyday practice for large numbers of patients, especially in outpatient clinics and private practices. This implies a risk of delaying or missing relevant cognitive impairments before and during treatment. Methods: We introduce a computerized screening instrument which allows for standardized assessment of cognitive functions at risk of medication. It was evaluated by standard neuropsychological tests and covers the cognitive domains of attention, cognitive speed, verbal and visual working memory as well as verbal and spatial memory. The test consists of six subtests which take 30 minutes to complete; afterwards the patient’s results are displayed immediately in comparison to age-related normative data. For psychometric evaluation, data were gathered from patients with epilepsy (n = 240), as an example for a chronic neurological disease treated with psychoactive antiepileptic medication (n = 42 untreated, n = 79 monotherapy, n = 119 polytherapy). Results: Comparability to standard neuropsychological tests (0.64 r 0.82) as well as retest reliability (0.40 r 0.79) were shown to be good for the subtests. It could be shown that the screening system is able to detect adverse cognitive effects of antiepileptic medication. Untreated patients showed a generally better performance than those on monotherapy or polytherapy. Comparisons between untreated patients and patients on monotherapy did not differ significantly. Groups of mono-/polytherapy differed significantly (p< 0.05) with lower scores for patients on polytherapy than on monotherapy in most subtests. These differences become even more obvious, as patients on monotherapy did significantly better compared to patients on three or more drugs in most subtests (p< 0.05). Also, the screening demonstrates significant cognitive changes in intra-individual assessment related to titration or withdrawal of antiepileptic drugs (e.g. topiramate). Conclusions: Medicationand dosage-related effects in the individual’s cognitive profile could be demonstrated by the screening instrument, indicating that a regular assessment of these functions, e.g. during change of therapy, is essential to keep track of adverse side effects and to optimize therapeutic interventions in neurological and psychiatric diseases. Also, the necessity of psychoactive drug polytherapy should be well-considered, as it is often associated with severe cognitive impairment. Early detection of deficits facilitates an in time intervention. The introduced screening instrument with its two different versions provides a standardized, time-efficient and individual follow-up assessment of cognitive functions and is valuable for clinical and scientific use.

Mitochondrial Haplogroup Clusters Modify the Effects of Black Carbon Exposure on Age Related Cognitive Impairment.

Background: Recent observational studies have linked traffic-related air pollution to loss of cognitive function in the elderly, an effect potentially mediated by oxidative-stress actions on the brain. Mitochondria are the main cellular source of oxidative stress. Haplogroups in mitochondrial DNA (mtDNA) determine between-subject differences in oxidative potential and have been linked with neurodegerative disease. No study has yet investigated whether mtDNA haplogroups influence susceptibility to pro-oxidant exposures, including traffic-related pollution. Aims: To investigate whether mtDNA haplogroups determine differential susceptibility to the effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution, on cognitive function in older men. Methods: A cohort of 616 men (mean±SD, 71±7 years of age) with an average 1.8 visits (from 1 to 4) per participant between 1996-2007 was drawn from the VA Normative Aging Study. We focused on low (?25) Mini Mental State Examination (MMSE) score as proxy of impaired cognition in multiple domains. We fitted repeated-measure logistic regression using BC estimated at participant’s address in the year before the first visit through a validated spatio-temporal land-use regression model. Results: In models adjusted for clinical features and socio-economics factors, each doubling in BC was associated with 1.2 (95%CI 0.9-1.5) times higher odds of low MMSE score. BC effect on MMSE differed by haplogroup, with most of the effect found in carriers of haplogroups I (OR=3.4; 95%CI 0.8-13.7) or X (OR=2.3; 95%CI 0.9-5.5). Carriers of haplotypes J, T, H V, K, U and W did not show any effect from BC. Conclusions: Susceptibility to the adverse cognitive effects of BC was limited to carriers of mtDNA haplogroups I and X. mtDNA haplogroups may represent a novel susceptibility factor that, due to the central role of oxidative stress in mediating air pollution risks, may also modify effects on other systems.

Does an Alzheimer's disease susceptibility gene influence the cognitive effects of cancer therapy?

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). APOE e4 carriers suffer greater morbidity from head trauma, stroke, and carbon monoxide poisoning, yet possible interactions between APOE genotype and cancer therapy on cognition are unclear. Neuropathological and biomarker studies of young asymptomatic APOE e4 carriers that show elevated neocortical amyloid and medial temporal neurofibrillary tangles and longitudinal neuropsychological studies that show accelerated memory decline beginning around age 55-60 years define preclinical AD and have set the stage for assessing the potential adverse cognitive effects of cancer therapy in APOE e4 carriers.

A Double-blind, Placebo-Controlled Study of the Impact of Galantamine on Anterograde Memory Impairment During Electroconvulsive Therapy

Electroconvulsive therapy (ECT) continues to be an effective treatment option for patients who fail to respond to pharmacological interventions, are unable to tolerate medications, and show a suboptimal response to behavioral and psychotherapeutic treatments. However, risks for cognitive impairment may contribute to some patients' refusal of ECT. The present study examined galantamine as a pharmacological intervention to reduce cognitive adverse effects from ECT. Thirty-nine inpatients diagnosed with major depressive disorder; bipolar disorder, depressed type; or schizoaffective disorder, depressed type and admitted for ECT were randomized to galantamine or placebo. Study drugs were initiated 24 to 48 hours before starting ECT and continued throughout the course of ECT. A neuropsychological test battery was administered at baseline and 24 to 48 hours after completing a course of ECT treatments. Depression severity was monitored using the 17-item Hamilton Rating Scale for Depression and Clinical Global Impression Scale at baseline, weekly, and end point. Self-rated adverse effects were monitored weekly. Thirty participants (12 patients in the galantamine group, 18 patients in the placebo group) had both pretreatment and posttreatment neuropsychological ratings. Those in the galantamine group scored significantly higher at discharge for delayed memory (t28 = 2.44, P < 0.05). Hierarchical regressions examined if treatment condition predicted changes in delayed memory scores from baseline to discharge. Inclusion of the treatment condition in the final model made a significant incremental improvement in prediction (ΔR = 0.12, F1,27 change = 4.65, P < 0.05; β = 0.37, t = 2.16, P < 0.05). Galantamine was well tolerated with no clinically significant bradycardia or prolonged paralysis when administered with ECT. Galantamine may be protective against impairment in retention of new learning. Galantamine exhibited minimal adverse effects and was safe when administered during ECT. The present findings require replication by future researchers using larger samples before broad conclusions can be drawn.

Acute Mania Associated With Levetiracetam Treatment

Levetiracetamisanovelantiepilepticdrugusedfor the treatment of partial and generalized epilepsy. Its mechanism of action is unclear, though it is thought to bind to a presynaptic vesicle protein that ultimately reduces the synaptic release of glutamate, impeding conduction of epileptic action potentials across the synapse. 1 Levetiracetam is frequently used owing to its ease of oral administration, excellent bioavailability, and low rate of drug interactions as it is not metabolized by the liver or bound significantly to serum proteins. 2,3 Adverse cognitive effects are atypical; however, adverse effects in the central nervous system (CNS) are relatively common, with behavioral symptoms occurring in up to 16% of patients in randomized controlled trials. 4 Frequently reported behavioral symptoms include depression, hostility, agitation, emotional lability, anger, nervousness, and depersonalization. Nonbehavioral CNS effects include sedation,headache,andasthenia. 5 Psychosisisinfrequently associated with levetiracetam, occurring in approximately 1% of patients, but well described in multiple case reports. 6,7 Researchers have explored the use of levetiracetam as a mood stabilizer for treatment of both depressive and manic phases of bipolar disorder with mixed results. 8–10 Despite the known association between levetiracetam and aggression and irritability, there are no reported cases in the literature of levetiracetam precipitating manic symptoms. In the following case report, we describe the acute onset of mania after levetiracetam therapy in a woman with no history of mania or hypomania.

Iodine Deficiency During Pregnancy and Adverse Cognitive Effects in Offspring

Iodine is an important component of thyroid hormone and essential for fetal brain development. Maternal iodine intake during pregnancy must be

Transcranial Magnetic Stimulation Maintenance as a Substitute for Maintenance Electroconvulsive Therapy

Transcranial magnetic stimulation (TMS) is an efficacious, well-tolerated, noninvasive brain stimulation treatment for major depressive disorder. Electroconvulsive therapy (ECT) is an effective maintenance treatment for depression but is not tolerated by some patients and declined by others. We evaluated the effectiveness of TMS as a substitution strategy for successful maintenance ECT. A consecutive clinical case series (n = 6) of maintenance ECT patients were transitioned to maintenance TMS because of adverse effects from ECT or because of specific patient request and preference. Patients were in either full remission or had clinical response to ECT at the time of transition. Primary outcome was the change in the Beck Depression Inventory (BDI) score from initiation of TMS maintenance sessions to the last observation time point. Relapse of depressive symptoms was also documented. Mean age of patients was 64 years, and most were female (n = 5). The majority (5 of 6) were diagnosed with major depressive disorder. Reasons for transition from ECT to TMS were, in order of frequency, cognitive adverse effects, fear of general anesthesia, time burden, lack of remission with ECT, and stigma associated with ECT. The mean frequency of TMS sessions was 1 every 3.5 weeks. Based on BDI scores, all patients maintained or improved their clinical status achieved with ECT at 3 and 6 months of TMS treatment. At last observation (range, 7-23 months), 4 patients maintained or improved their clinical status (total BDI score remained constant or decreased by 1-8 points). Two patients had a relapse after 8 and 9 months. Stimulation was well tolerated with adverse effects limited to headache and scalp discomfort. In this case series, TMS was effective and safe when used as a substitution strategy for successful maintenance ECT.

Patient, Treatment, and Anatomical Predictors of Outcome in Electroconvulsive Therapy

Baseline predictors of effectiveness and cognitive adverse effects of electroconvulsive therapy (ECT) were prospectively examined. Before and after ECT, the Montgomery-Åsberg Depression Rating Scale (MADRS) and Mini Mental State Examination (MMSE) were assessed. Before ECT, a magnetic resonance imaging of the head was performed. Outcome predictors were investigated using multivariable regression analyses. Of 83 patients (mean ± SD age, 59.2 ± 15.3 years; 39% men), 28% had a psychotic depressive disorder, 16% had a bipolar depression, 30% had had previous ECT course(s), and 66% used concomitant antipsychotics. Presence of psychotic depression (β = -0.25; P = 0.04) and having had previous ECT (β = -0.35; P = 0.003) predicted lower post-ECT MADRS score. Baseline magnetic resonance imaging characteristics were not predictive of post-ECT MADRS and MMSE scores. The use of concomitant antipsychotics predicted a lower post-ECT MMSE score (β = -0.21; P = 0.02), whereas the presence of bipolar depression at baseline predicted higher post-ECT MMSE score (β = 0.23; P = 0.01). The post-ECT MADRS score seemed to be a confounder for the post-ECT MMSE score (β = -0.20; P = 0.02). Effectiveness of ECT was better in the patients with a baseline psychotic depression and those who had had ECT before. Cognitive outcome was better in the patients with baseline bipolar depression but worse in those who used antipsychotics during ECT and those who showed more persistent depressive symptoms after ECT.