Selective Serotonin Reuptake Inhibitor Medication Research Articles

Differential Associations of Specific Selective Serotonin Reuptake Inhibitors With Resting-State Heart Rate and Heart Rate Variability: Implications for Health and Well-Being

Debate has focused on the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressants on heart rate (HR) and HR variability (HRV), both of which are predictors of adverse cardiovascular events. Here, we examine the associations between specific SSRI antidepressants and resting state HR (and HRV) after accounting for a host of potential confounding factors using propensity score techniques. Participants included 10,466 not taking antidepressants, 46 participants taking escitalopram, 86 taking citalopram, 66 taking fluoxetine, 103 taking paroxetine, and 139 taking sertraline. HR and HRV (root mean square of successive squared differences, high frequency) were extracted from 10-minute resting-state ECGs. Analyses including propensity score weighting and matching were conducted using R-statistics to control for potentially confounding variables. Major findings indicated that users of all SSRI medications-except fluoxetine-displayed lower HRV relative to nonusers. Users of paroxetine also displayed significantly lower HRV relative to users of citalopram (Cohen's d = 0.42), fluoxetine (Cohen's d = 0.54), and sertraline (Cohen's d = 0.35), but not escitalopram. Although associations were also observed for HR, these were less robust than those for HRV. Although paroxetine is associated with decreases in HRV relative to nonusers, as well as users of other SSRI medications, fluoxetine was the only medication not to display significant alterations in HR or HRV. These conclusions are limited by the cross-sectional design and nonrandomized nature of medication prescriptions. Findings highlight the importance of focusing on specific medications, rather than more heterogeneous groupings according to antidepressant action, and may have implications for health and well-being for the longer term.

Making Sense Out of the Controversy: Use of SSRIs in Pregnancy

Perinatal depression complicates up to 20 % of all pregnancies. Selective serotonin reuptake inhibitor (SSRI) drugs have become the first-line treatment of depressive symptoms during pregnancy. About 7.5 % of all pregnancies are currently exposed to psychotropic medications. Recent studies suggest the SSRI medications may have some detrimental effects in pregnancy, including a possible increased risk of miscarriage, preterm delivery, clubfoot, heart defects, brain and craniofacial abnormalities, persistent pulmonary hypertension of the newborn, neonatal seizures, low neonatal Apgar score, as well as neurodevelopmental and behavioral changes. Patients and healthcare providers should take into consideration all the possible known negative effects of untreated depression during pregnancy, but also the possible fetal risks associated with the use of SSRIs.

Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder.

The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research. Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC. After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex. The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments.

Maternal Use of Selective Serotonin Reuptake Inhibitors and Lengthening of the Umbilical Cord: Indirect Evidence of Increased Foetal Activity-A Retrospective Cohort Study.

BackgroundAntenatal depression affects up to 19% of pregnant women. Some of these women are also in need of antidepressant treatment. Nevertheless, the impact of maternal antidepressant treatment and prenatal depression on the course of pregnancy, foetal development and delivery outcomes is not fully understood.MethodsWe analysed data from 24 818 women who gave birth at Kuopio University Hospital between 2002–2012. Logistic regression analysis was used to estimate associations between the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and the progression of pregnancy, development of the foetus and delivery outcomes.ResultsAltogether, 369 (1.5%) women used SSRIs. A regression model adjusted for age, overweight, nulliparity, prior termination, miscarriages, smoking, maternal alcohol consumption, chronic illness and polyhydramnion showed that pregnant women exposed to SSRI medication had significantly lower Apgar scores at 1 minute (p < 0.0001) and 5 minutes (p < 0.0001) and more admissions to the neonatal intensive care unit (p < 0.0001) than unexposed pregnant women. In addition, exposed newborns had longer umbilical cords (p < 0.0001) than non-exposed newborns.ConclusionIn addition to the previously known associates with maternal SSRI exposure, such as lowered Apgar scores, SSRI exposure appeared to be associated with increased umbilical cord length. The observation related to increased umbilical cord length may be explained by an SSRI-induced increase in the movements of the developing foetus.

Clinical characteristics associated with the prescribing of SSRI medication in adolescents with major unipolar depression.

Unipolar major depressions (MD) emerge markedly during adolescence. National Institute for Health and Care Excellence (NICE) UK recommends psychological therapies, with accompanying selective serotonin reuptake inhibitors (SSRIs) prescribed in severe cases only. Here, we seek to determine the extent and rationale of SSRI prescribing in adolescent MD before entering a randomised clinical trial. SSRI prescribing, together with their clinical characteristics was determined in 465 adolescent patients with MD prior to receiving a standardised psychological therapy as part of the Improving mood with psychoanalytic and cognitive therapies (IMPACT) clinical trial. Overall, 88 (19 %) had been prescribed antidepressants prior to psychological treatment. The clinical correlates varied by gender: respectively, depression severity in boys and self-harming behaviours in girls. Prescribing also differed between clinical research centres. Medical practitioners consider severity of depression in boys as an indicator for antidepressant prescribing. Self-injury in girls appears to be utilised as a prescribing aid which is inconsistent with past and current revised UK NICE guidelines.Electronic supplementary materialThe online version of this article (doi:10.1007/s00787-016-0849-y) contains supplementary material, which is available to authorized users.

Gestational stress and fluoxetine treatment differentially affect plasticity, methylation and serotonin levels in the PFC and hippocampus of rat dams

Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague–Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine, and 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the cingulate cortex2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain.

Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring

A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague–Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect–related behaviors and their underlying molecular mechanisms.

Selective serotonin reuptake inhibitors increase sympathetic activity under heavy alcohol exposure in rat models

AimsSelf-medication with alcohol while being treated with antidepressants is a common problem in patients with depression. Both alcohol consumption and antidepressant administration can induce changes in the cardiac autonomic responses as indicated by heart rate variability (HRV). In this study, we examined cardiac autonomic responses induced by acute heavy alcohol exposure after SSRIs (selective serotonin reuptake inhibitors) medications. Main methodsRats were randomly divided into 3 groups, the alcohol administrated (Alc group), paroxetine administrated (SSRI group), and the SSRI+Alc group. Serum samples were collected to measure blood alcohol concentration (BAC). Physiological and cardiac autonomic responses including mean arterial pressure (MAP), heart rate (HR), and HRV were also compared among groups. Key findingsThe SSRI group exhibited higher values of HRV and HF (high frequency) than did the Alc and SSRI+Alc groups after alcohol administration. In contrast to the Alc group, the SSRI+Alc group had significantly lower MAP than Alc group, and higher HR, standard deviation of NN-intervals (SDNN), SDNN to MRR ratio (CVNN), square root of the mean squared differences of the successive NN-intervals (RMSSD) and HF values after alcohol administration. SignificanceOur results indicate that SSRIs increased sympathetic activity and alcohol reduced it in rats. The present study represents an attractive area for further research.

Prenatal stress and early-life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring.

With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior.

Developmental fluoxetine and prenatal stress effects on serotonin, dopamine, and synaptophysin density in the PFC and hippocampus of offspring at weaning.

Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning.

Serotonergic medication enhances the association between suicide and sunshine

BackgroundAn association between suicide and sunshine has been reported. The effect of sunshine on hormones and neurotransmitters such as serotonin has been hypothesized to exert a possible triggering effect on susceptible individuals. The aim of this study is to examine if there is an association between sunshine and suicide, adjusting for season, and if such an association differs between individuals on different antidepressants. MethodsBy using Swedish Registers and the Swedish Meteorological and Hydrological Institute we obtained information, including forensic data on antidepressive medication for 12,448 suicides and data on monthly sunshine duration. The association between monthly suicide and sunshine hours was examined with Poisson regression analyses while stratifying for sex and age and controlling for time trend and season. These analyses were repeated in different groups of antidepressant treatment. ResultsWe found a significantly increased suicide risk with increasing sunshine in both men and women. This finding disappeared when we adjusted for season. Among both men and women treated with selective serotonin reuptake inhibitors (SSRIs) there was a positive association between sunshine and suicide even after adjustment for season and time trend for suicide. Pair comparisons showed that the sunshine–suicide association was stronger among men treated with SSRIs compared to other antidepressant medications or no medication at all. LimitationsOther meteorological factors were not controlled (i.e. temperature) for in the analyses. ConclusionsThere is an enhanced association between sunshine and suicide among those with SSRI medication, even after adjusting for season. This may have interesting theoretical and clinical implications.

Hoarding Disorder: Models, Interventions, and Efficacy

Hoarding disorder was once considered a subtype of obsessive-compulsive disorder or a symptom of obsessive-compulsive personality disorder but is now recognized as a distinct diagnostic category in DSM-5. Key features of hoarding include difficulty discarding or parting with possessions due to strong urges to save the items. Difficulty discarding often includes items that others consider to be of little use and results in accumulation of a large number of possessions that clutter the home, preventing use for the intended purpose. Cognitive-behavioral therapy with exposure and response prevention as well as administration of selective serotonin reuptake inhibitor medications traditionally used to treat obsessive-compulsive disorder are generally not efficacious for people with hoarding problems. A specialized cognitive-behavioral therapy approach for hoarding has shown some progress in reaching treatment goals and has been modified for delivery in group and peer-facilitated models. Research on hoarding remains in the early phases of development and is progressing. Special populations such as children, older adults, and people who do not voluntarily seek treatment need special consideration for intervention.

Vilazodone for the treatment of major depressive disorder: an evidence-based review of its place in therapy.

IntroductionIt has clearly been demonstrated that depressive disorders constitute a major worldwide public health problem, with massive economic and quality-of-life consequences. Existing pharmacological treatments have limited efficacy, with only about a third of patients achieving remission on any one medication. Delayed onset of action and variable tolerability contribute to this limited efficacy. Vilazodone, introduced in the US in 2011, has been described as the first member of the serotonin partial agonist-reuptake inhibitor (SPARI) class of medications, combining serotonin-reuptake inhibition with 5-HT1A partial agonism. This agent could potentially have benefits for subgroups of depressed patients, including depressed patients with comorbid anxiety and patients with anxiety disorders, and might have fewer sexual side effects than selective serotonin-reuptake inhibitors (SSRIs).AimsWe reviewed existing clinical trials that assess the benefits of vilazodone for treatment of major depression.Evidence reviewIn clinical trials, including two Phase III studies and two Phase IV studies, vilazodone has been shown to have efficacy greater than placebo on the Montgomery–Åsberg Depression Rating Scale, comparable efficacy to citalopram, and continued benefit after 52 weeks of treatment. The safety profile for vilazodone is comparable to other SSRI medications, and tolerability also appears generally comparable to other SSRI medications.Place in therapyVilazodone, which has been described as the first-of-class SPARI medication, may potentially have benefits for subgroups of patients, particularly those depressed individuals with coexisting anxiety symptoms or anxiety disorders. However, convincing evidence for these benefits has as yet not been published.

S-adenosylmethionine (SAMe) and Magnesium Orotate as adjunctives to SSRIs in sub-optimal treatment response of depression in adults: A pilot study

Major depression is a prevalent mental health disorder and a proportion of patients do not respond adequately to standard treatment. The use of nutraceutical adjunctives with antidepressant medication such as high dose S-adenosylmethionine (SAMe) has proven beneficial in terms of initial symptom response but the effect on symptom maintenance and relapse is unknown. In this pilot study [n=36], participants [26 evaluable subjects] with established sub-optimal response to treatment for major depressive disorder and who were prescribed Selective Serotonin Reuptake Inhibitor (SSRI) medication were randomly allocated to either 1600mg or 800mg daily of SAMe for 15 weeks duration to evaluate the efficacy on both symptom response and maintenance. A variety of validated psychiatric measures of symptoms and mood including clinician assessment and self-report measures were used to assess outcome measures. Both SAMe doses achieved similar results with a significant proportion of participants (35%) achieving significant symptom improvement at the end of 15 weeks supplementation as assessed by the Beck Depression Inventory (BDI), Outcome Questionnaire 45 (OQ45), and improved Quality of Life (QOL) scores. After a 2 week washout period, SAMe non-responders were then supplemented with 1600mg of Magnesium Orotate for 8 weeks duration which resulted in significant clinical improvement as measured by BDI, OQ45 and QOL scores [n=8]. We progress the SAMe-methylation and Orotate–uridine hypothesis and consider that the response to these novel compounds implicates the microbiome as an important agent for the adjunctive treatment of sub-optimal response to pharmaceutical medications.

SERT and NET polymorphisms, temperament and antidepressant response

Background: The genetic variations in norepinephrine transporter (NET) and serotonin transporter (SERT) genes have been associated with personality traits, several psychiatric disorders and the efficacy of antidepressant treatment. Aims: We investigated the separate effects and possible interactions between NET T-182C (rs2242446) and SERT 5-HTTLPR (rs4795541) polymorphisms on selective serotonin reuptake inhibitors (SSRI) treatment response and temperamental traits assessed by the Temperament and Character Inventory (TCI) in a clinical sample of subjects with major depressive disorder (MDD). Methods: Our sample of 97 patients with major depression completed the 107-item TCI temperament questionnaire (version IX) at the initial assessment of the study and after 6 weeks of follow-up. All subjects received selective SSRI medications. Temperament dimension scores at baseline (1) and endpoint (2) during antidepressant treatment were analyzed between NET and SERT genotypes. Results: SS-genotype of 5-HTTLPR was associated with higher baseline Persistence scores than SL- or LL-genotype. A corresponding but weaker association was found at endpoint. No differences were found between 5-HTTLPR genotypes and other temperament dimensions and 5-HTTLPR genotypes had no effect on treatment response. Conclusions: Our results suggest that the SS-genotype of 5-HTTLPR is associated with Persistence scores in patients with MDD. Higher Persistence could be viewed as a negative trait when recovering from stress and its association with short and “weaker” S-allele may be related to less efficient serotonin neurotransmission, possibly resulting in less effective coping strategies on a behavioral level.

The association between suicidality and treatment with selective serotonin reuptake inhibitors in older people with major depression: a systematic review

Suicide among the elderly is an emerging public health issue. In Australia, suicide is a leading cause of death, most notably amongst elderly men over the age of 75. Depression is one of the main causes of suicide in older people. Selective serotonin reuptake inhibitors are considered to be a safe pharmacological therapy in the management of depression in adults. The risk of suicidality/suicide associated with the use of antidepressants in older people is unclear. The objective of this review was to determine the association between treatment with selective serotonin reuptake inhibitors and suicidality/suicide in older people who suffer from major depression. Consideration was given to studies that included older people aged 60 years and over, regardless of gender or ethnic background, with Diagnostic and Statistical Manual of Mental Disorders Fourth Edition or equivalent diagnostic criteria for Major Depressive Disorder without psychotic features. Types of intervention(s)/phenomena of interest: The review considered treatments using any selective serotonin reuptake inhibitors medication. Comparators included placebo or a different class of antidepressants including monoamine oxidase inhibitors or tricyclic antidepressants. Types of studies: This review considered both experimental and observational study designs including randomized controlled trials, non-randomized controlled trials, prospective and retrospective cohort studies and case control studies. Types of outcomes: The primary outcome measures of interest in this systematic review were worsening or emergent suicidal ideation, attempted suicide and completed suicide. For this systematic review, the term 'suicide attempt' referred to potentially self-injurious behavior with a non-fatal outcome. A three-step search strategy was employed that aimed to locate both published and unpublished studies in the English language. An initial search in PubMed was followed by a second search using all identified keywords and index terms across multiple databases and grey literature sites. Finally, the reference list of all identified reports and articles were searched for additional studies. METHODOLOGICAL QUALITYÂ: Critical appraisal was undertaken by two independent reviewers using the standard critical appraisal instrument from the Joanna Briggs Institute Mata-Analysis of Statistical Assessment and Review Instrument. The McMaster Quality Assessment Scale for Harms was used to analyse reporting quality on suicide related harm. The primary data on the number of emergent or worsening of suicidal ideation, attempted suicide and completed suicides, in both arms of randomized controlled trials and observational studies was extracted using the standardized data extraction tool from the Joanna Briggs Institute Mata-Analysis of Statistical Assessment and Review Instrument. Baseline demographic data on each study was collected for presentation in tabular format. The data from randomized controlled trials and observational studies was pooled separately in statistical meta-analysis using RevMan V 5.1 software (The Cochrane Collaboration). Population demographic and other study characteristics were presented in tables and as a narrative summary. Following critical appraisal, eight randomized controlled trials and five observational studies (i.e. population cohort and retrospective case control studies) with data on suicide-related events were included in the systematic review. Based on the data on TRUNCATED AT 500 WORDS.

Prevention of Sudden Death in Patients With Epilepsy.

To the Editor: Sudden unexpected death in epilepsy (SUDEP) occurs sometimes in people with ictal disorders.1 The diagnosis does not require evidence of a seizure and excludes status epilepticus as a cause of death. The postmortem examination must not reveal any toxic or anatomic pathology, and death must not be due to trauma or drowning. The prevalence of epilepsy in the United States is approximately 2.3 million in adults and 480,000 among children.1,2 One of 26 people in the United States and 1 of 103 people in Great Britain have epilepsy in their lifetime. The incidence of SUDEP is approximately 1–2 per 1,000 person years in patients with chronic epilepsy and 3–9 per 1,000 person years in severe, refractory seizures. There are more than 500 SUDEP deaths every year in Great Britain among the 600,000 individuals reported to have epilepsy.2 Postmortem studies indicate that up to 60% of all epilepsy-related deaths can be accounted for by SUDEP, making it the most common epilepsy-related cause of mortality.3 The risk of dying suddenly and unexpectedly for patients with epilepsy has been estimated to be more than 20 times greater than for the general population.1,2 The cause in two-thirds of the cases is unidentified. The most common risk factors for SUDEP are generalized tonic-clonic seizures, long-term epilepsy, male gender, polypharmacy, poor anticonvulsant drug compliance, and sleep deprivation.4 Case report. A 5-year-old girl, was treated in the pediatric neurology clinic. The diagnosis was severe, refractory seizures with a documented, recurrent myoclonic component of possible Dravet syndrome, according to ICD-9 diagnostic criteria. She had exhibited this convulsive disorder since the age of 3 years. Her epilepsy was managed with divalproex, temazepam, and a ketogenic diet. Despite pharmacotherapy, the child was never seizure free. One morning, the child was found dead in her bed. The family reported no new illnesses, change in ictal status, trauma, or other concerns recently. A postmortem examination revealed no toxic or anatomic pathology. The cause of death was considered to be SUDEP, noting a higher frequency of such occurrences in children with Dravet syndrome.5 Integration of different mechanisms is proposed to explain SUDEP: cardiac arrythmias, respiratory depression, and cerebral or autonomic dysfunction.6 Neuronal networks activated during a seizure inhibit the respiratory centers in the medulla, leading to hypoventilation with an acid-base imbalance, which can induce bradycardia, asystole, and death. Cardiorespiratory control by the brainstem is regulated via neurotransmitters like 5-hydroxytryptamine and adenosine.6 There is a rise in adenosine levels during convulsive activity that causes postictal hypoventilation, apnea, and arrhythmias. Serotonin decreases postictal hypoxemia, and reportedly in an animal experiment, selective serotonin reuptake inhibitor medications attenuated this influence.6 Talking about SUDEP with patients and family at the initial onset of seizures is controversial; rather, it is advised that it be discussed after patients are more established in the clinic.7 Utilizing a SUDEP safety checklist can help clinicians in assessing the risk of sudden death in patients with epilepsy.2 Discussion is for higher-risk individuals. A preventative plan is provided to patients and family, hopefully to improve patient compliance with medications and facilitate changes in lifestyle.7 Such a plan targets diminishing prominent risk factors (Table 1). Table 1. Prevention of Sudden Unexpected Death in Epilepsy1–7

Drug-Free Alternatives for Post-Traumatic Stress Disorder (PTSD)

Stress is a primary causative factor that scientific research has shown leads directly to physical and psychological disease and disorder. For our military servicemen and women, it goes without saying that the daily stress they are under can easily develop into post-traumatic stress disorder (PTSD) by the time they return home. Current treatment options for PTSD are counseling and pharmaceuticals. Unfortunately, the pharmaceuticals bring with them an enormous risk for dangerous and deadly side effects. In most cases, both nervine and adaptogenic herbs are able to respond to the symptoms of PTSD without side effects. This paper explores herbal treatment options for PTSD that can replace selective serotonin reuptake inhibitors (SSRI) medications that support stress reactions within the body, balance the stress response in the body, relieve the symptoms of PTSD, and allow servicemen and women to return to normal lives without dangerous side effects.

A pilot study of actigraphy as an objective measure of SSRI activation symptoms: Results from a randomized placebo controlled psychopharmacological treatment study

Selective serotonin reuptake inhibitors (SSRIs) are an efficacious and effective treatment for pediatric obsessive-compulsive disorder (OCD) but have received scrutiny due to a potential side effect constellation called activation syndrome. While recent research introduced a subjective measure of activation syndrome, objective measures have not been tested. This pilot study, using data from a larger randomized-controlled trial, investigated the potential of actigraphy to provide an objective measure of activation symptoms in 44 youths with OCD beginning an SSRI medication regimen. Data were collected over the first four weeks of a multi-site, parallel, double-blind, randomized, placebo controlled psychopharmacological treatment study and statistical modeling was utilized to test how activation syndrome severity predicts daily and nightly activity levels. Results indicated that youths with higher activation symptoms had lower daytime activity levels when treatment averages were analyzed; in contrast youths who experienced onset of activation symptoms one week were more likely to have higher day-time and night-time activity ratings that week. Results support actigraphy as a potential objective measure of activation symptoms. Subsequent studies are needed to confirm these findings and test clinical applications for use by clinicians to monitor activation syndrome during SSRI treatment. National Institutes of Health (5UO1 MH078594-01); NCT00382291.

Emerging treatments for motor rehabilitation after stroke.

Although numerous treatments are available to improve cerebral perfusion after acute stroke and prevent recurrent stroke, few rehabilitation treatments have been conclusively shown to improve neurologic recovery. The majority of stroke survivors with motor impairment do not recover to their functional baseline, and there remains a need for novel neurorehabilitation treatments to minimize long-term disability, maximize quality of life, and optimize psychosocial outcomes. In recent years, several novel therapies have emerged to restore motor function after stroke, and additional investigational treatments have also shown promise. Here, we familiarize the neurohospitalist with emerging treatments for poststroke motor rehabilitation. The rehabilitation treatments covered in this review will include selective serotonin reuptake inhibitor medications, constraint-induced movement therapy, noninvasive brain stimulation, mirror therapy, and motor imagery or mental practice.