Serotonin Reuptake Inhibitor Medications Research Articles

EFFECTIVENESS OF RISPERIDONE AUGMENTATION IN OBSESSIVE-COMPULSIVE DISORDER – EXPERIENCE OF A SPECIALTY CLINIC IN INDIA

Background Randomized placebo-controlled trials suggest that risperidone may be efficacious as an add-on treatment to serotonin reuptake inhibitors (SRIs) in patients with obsessive compulsive disorder (OCD). Inherent limitations of these studies are the relatively small sample sizes and concern over their generalizability to real-world clinical practice. Also, factors predicting response to risperidone augmentation are unclear. Aim To assess the effectiveness of risperidone augmentation in OCD, and to study the predictors of response, in a real-world setting. Method 1314 consecutive patients who consulted a specialty OCD clinic between 2004 and 2014 at a large psychiatric hospital in India were evaluated with Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive–Compulsive Scale, and the Clinical Global Impression scale. Patients with OCD initiated on risperidone, not having psychosis or mental retardation, without ongoing cognitive behavior therapy and who were on stable SRI medication for at least 12 preceding weeks were included for analysis. Primary outcome measure was all-cause discontinuation. Principal component analysis with Varimax rotation was conducted utilizing responses from YBOCS checklist, which yielded a 5-factor solution with the following dimensions - ‘pathological doubts/checking’, ‘need for symmetry/orderliness’, ‘forbidden thoughts’, ‘cleaning/contamination’, and ‘hoarding’. Predictors of treatment response were evaluated by logistic regression analysis (backward wald) with symptom dimensions and other relevant antecedent variables as independent variables and all-cause discontinuation as the dependent variable. Results 104 patients were eligible for analysis. In all except 24 patients (23.08%), risperidone had been discontinued at the time of last follow-up, either due to ineffectiveness or intolerability. 26 patients (25%) were noted to have at least 25 % reduction on YBOCS. 24 patients (23.08%) were marked either as ‘much improved’ or ‘very much improved’ on CGI-I. Mean reduction in YBOCS scores for the whole sample (n=104) was 13.54% (t=5.45, p On regression analysis, ‘forbidden thoughts’ predicted discontinuation of risperidone (p=0.021). Conclusions Risperidone proved to be an effective augmenting agent in a significant sub-set of patients with OCD. The drug may be less beneficial in patients with ‘forbidden thoughts’ (sexual, religious, or aggressive obsessions).

Outpatient Treatment Patterns of Pediatric Obsessive-Compulsive Disorder.

Little is known about community physician treatment practices for children with obsessive-compulsive disorder (OCD). This study is the first to describe the treatment of pediatric OCD in office-based and outpatient department-based physicians in the United States. Data from the 2003-2011 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey were used. We provided descriptive statistics for sample characteristics and treatments administered during the visit, and examined differences in treatment by comorbid conditions and settings using logistic regression. Psychotherapy was provided in 46% of visits in children with OCD overall, while serotonin reuptake inhibitor (SRI) medication was prescribed to 55% overall, atypical antipsychotics were prescribed to 22% of youth either alone or in combination with another medication; 11% received no psychotherapy or pharmacotherapy. Psychotherapy and at least one pharmacotherapy were provided to 36% of patients. There were no significant differences in characteristics of patients receiving each class of medication. Among children and adolescents, OCD was primarily treated by physicians using SRI medication and/or psychotherapy. A sizeable proportion of children were given atypical antipsychotic medications. Wider dissemination of evidence-based psychological treatments and continued monitoring of adherence to guidelines is warranted.

Pediatric ingestion of vilazodone compared to other selective serotonin reuptake inhibitor medications

Background: Unintentional ingestion of selective serotonin reuptake inhibitor (SSRI) medications is common amongst children <6 years of age. Current evidence-based management guidelines are based on a low incidence of significant medical outcomes in these children.Objective: To describe and compare outcomes of pediatric exposures to vilazodone with other SSRIs.Methods: A retrospective observational case series analysis of both single and polysubstance SSRI exposures amongst children <6 years old reported to the National Poison Data System (NPDS).Results: 11,384 SSRI exposures in children <6 years of age reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone only accounted for 5.9% of all exposures, but resulted in the highest proportion of health care facility admission compared to other SSRIs, both in single substance (165 of 531 (31.1%); OR 9.0 [7.3–11.2]) and polysubstance (57 of 107 (53.3%); OR 4.1 [2.7–6.2]) exposures. Children exposed to vilazodone also have higher odds of experiencing a major or moderate outcome in single (134 of 531 (25.2%); OR 20.5 [15.5–27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7–9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such as seizure and coma, were more common among the vilazodone exposures.Conclusions: Exposure to vilazodone in this age group results in an increased rate of hospitalization as well as more severe clinical effects as compared to other SSRIs. Current evidence-based SSRI exposure management guidelines may not be appropriate for the management of vilazodone ingestion in this age group.

Ethical Challenges in Geriatric Psychiatry.

Ethical Challenges in Geriatric Psychiatry.

Patient Preferences and Acceptability of Evidence-Based and Novel Treatments for Obsessive-Compulsive Disorder.

This study examined preferences for and acceptability of treatments for obsessive-compulsive disorder (OCD). Through an online survey, adults who self-reported OCD chose their preferred evidence-based treatments, rated acceptability of novel treatments, and answered open-ended questions about their preferences. Analyses examined associations between demographic, clinical, and treatment variables and first-line and augmentation treatment preferences. Latent class analysis (LCA) explored whether distinct profiles among participants predicted preferences. Data from open-ended questions were analyzed by using qualitative methods. Among 216 adults with at least moderate OCD symptoms, first-line preferences for exposure and response prevention (EX/RP) and serotonin reuptake inhibitor (SRI) medications were similar (55% and 45%). However, EX/RP was significantly preferred over antipsychotic medication as an augmentation treatment for SRIs (68% and 31%; p<.001). Regarding first-line preferences, no factors were associated with EX/RP preference, but participants who preferred SRIs were currently receiving OCD treatment (p=.011) or taking SRIs (p<.001) and reported a positive treatment experience overall (p=.043) and with medications (p<.001). Participants who preferred EX/RP as augmentation treatment were younger (p<.001) and female (p=.021) and taking benzodiazepines (p=.050). LCA analyses generated two distinct profiles, one of which preferred SRIs: those with a history of OCD diagnosis and treatment, higher income, and private insurance (p=.001). For novel treatments, acceptance and commitment therapy was the most acceptable and deep brain stimulation the least. Preferences for OCD treatments varied by individual characteristics. Future research should examine whether incorporating preferences into treatment planning has an impact on clinical care.

Escitalopram but not placebo modulates brain rhythmic oscillatory activity in the first week of treatment of Major Depressive Disorder

Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5–8 Hz) and the alpha (8–12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms. Prefrontal delta-theta and alpha power were calculated for 194 subjects with moderate MDD prior to and one week after start of treatment. Changes at one week in delta-theta and alpha power, as well as the delta-theta/alpha ratio, were examined in three cohorts: initial (N = 70) and replication (N = 76) cohorts treated with escitalopram, and a cohort treated with placebo (N = 48). Mean delta-theta power significantly increased and alpha power decreased after one week of escitalopram treatment, but did not significantly change with placebo treatment. The delta-theta/alpha ratio change was a specific predictor of the likelihood of remission after seven weeks of medication treatment: a large increase in this ratio was associated with non-remission in escitalopram-treated subjects, but not placebo-treated subjects. Escitalopram and placebo treatment have differential effects on delta-theta and alpha frequency oscillations. Early increase in delta-theta/alpha may constitute a replicable biomarker for non-remission during SSRI treatment of MDD.

Raising the Minimum Effective Dose of Serotonin Reuptake Inhibitor Antidepressants: Adverse Drug Events.

This review focuses on the dose-response of serotonin reuptake inhibitor (SRI) antidepressants for efficacy and for adverse drug events (ADEs). Dose-response is identified by placebo-controlled, double-blind, fixed-dose clinical trials comparing various doses for efficacy and for ADEs. Reports from the great majority of clinical trials have consistently found that the minimum SRI effective dose is usually optimal for efficacy in the treatment of depression disorders, even though most American medical practitioners raise the dose when early antidepressant treatment results are negative or partial. To better understand this issue, the medical literature was comprehensively reviewed to ascertain the degree to which SRI medications resulted in a flat dose response for efficacy and then to identify specific ADEs that are dose-dependent. Strong evidence from fixed-dose trial data for the efficacy of nonascendant, minimum effective doses of SRIs was found for the treatment of both major depression and anxiety disorders. Particularly important was the finding that most SRI ADEs have an ascending dose-response curve. These ADEs include sexual dysfunction, hypertension, cardiac conduction risks, hyperglycemia, decreased bone density, sweating, withdrawal symptoms, and agitation. Thus, routinely raising the SRI dose above the minimum effective dose for efficacy can be counter-productive.

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.

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.

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.

Gestational antidepressant use and the risk of spontaneous abortion

Exposure to maternal depression increases risks for altered mother–infant interactions. Serotonin reuptake inhibitor (SRI) antidepressants are increasingly prescribed to manage antenatal maternal illness. The impact of SRIs on early mother–infant interactions was unknown. Three-month-old infants of 32 depressed mothers treated with SRI medications during pregnancy and 43 non-medicated mothers were studied. Using an established face-to-face mother–infant interaction paradigm, dyad interactions were studied with and without a toy. Videotaped sessions yielded 4 measures: maternal sensitivity, dyadic organization, infant readiness to interact, and maternal interruptive behaviors. Even with prenatal SRI treatment, depressed mothers interrupted their infants more during toy play. In the absence of prenatal SRI treatment, maternal postnatal depression adversely influenced infant behavior. Higher levels of maternal depression symptoms at 3 months predicted poorer infant readiness to interact during the toy session. Conversely, in the SRI-exposed group, higher prenatal depression scores predicted greater infant readiness to interact at 3 months. Increased infant readiness with SRI exposure suggests a “fetal programming effect” whereby prenatal maternal mood disturbances shaped a future response to a postnatal depressed maternal environment.

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.

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.

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.

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

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.

Confluence of depression and acute psychological stress among patients with stable coronary heart disease: effects on myocardial perfusion.

BackgroundDepression is prevalent in coronary heart disease (CHD) patients and increases risk for acute coronary syndrome (ACS) recurrence and mortality despite optimal medical care. The pathways underlying this risk remain elusive. Psychological stress (PS) can provoke impairment in myocardial perfusion and trigger ACS. A confluence of acute PS with depression might reveal coronary vascular mechanisms of risk. We tested whether depression increased risk for impaired myocardial perfusion during acute PS among patients with stable CHD.Methods and ResultsPatients (N=146) completed the Beck Depression Inventory‐I (BDI‐I), a measure of depression linked to recurrent ACS and post‐ACS mortality, and underwent single‐photon emission computed tomography myocardial perfusion imaging at rest and during acute PS. The likelihood of new/worsening impairment in myocardial perfusion from baseline to PS as a function of depression severity was tested. On the BDI‐I, 41 patients scored in the normal range, 48 in the high normal range, and 57 in the depressed range previously linked to CHD prognosis. A BDI‐I score in the depressed range was associated with a significantly greater likelihood of new/worsening impairment in myocardial perfusion from baseline to PS (odds ratio =2.89, 95% CI: 1.26 to 6.63, P=0.012). This remained significant in models controlling ACS recurrence/mortality risk factors and medications. There was no effect for selective serotonin reuptake inhibitor medications.ConclusionsDepressed patients with CHD are particularly susceptible to impairment in myocardial perfusion during PS. The confluence of PS with depression may contribute to a better understanding of the depression‐associated risk for ACS recurrence and mortality.

Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity

During pregnancy and postpartum period, 20% of women are affected by depression, which is a growing health concern. Selective serotonin reuptake inhibitor (SSRI) medications are popular treatments for maternal depression; however, the effect of maternal depression and perinatal SSRI exposure on offspring's neural development needs further investigation. This study aims to determine the role of developmental fluoxetine exposure on hippocampal plasticity in the adult offspring. Sprague-Dawley rat offspring were exposed to fluoxetine beginning on postnatal day 1. Offspring were also exposed to prenatal maternal stress. Four groups of male and female offspring were used: (1) prenatal stress + fluoxetine, (2) prenatal stress + vehicle, (3) fluoxetine alone, and (4) vehicle alone. Hippocampi were analyzed for levels of cell proliferation, immature neurons, and new cell survival (3weeks after 5-bromo-2-deoxyuridine injection) in the granule cell layer, as well as synaptophysin density in the CA3 region and granule cell layer. TPH staining was assessed in the dorsal raphe nucleus. Developmental fluoxetine exposure to prenatally stressed offspring reversed the effect of prenatal stress or fluoxetine exposure alone on the number of immature neurons. Prenatal stress alone, regardless of developmental exposure to fluoxetine, markedly decreased hippocampal cell proliferation and tended to decrease new cell survival. Furthermore, in adult female offspring, developmental fluoxetine exposure greatly increased new cell survival and significantly decreased synaptophysin density in the granule cell layer. There are long-term effects of developmental SSRI exposure on hippocampal plasticity that is differentially affected by expose to maternal adversity and offspring sex.

Women’s experiences of coping with the sexual side effects of antidepressant medication

A growing body of evidence has highlighted the sexual side effects of selective serotonin reuptake inhibitor (SSRI) medication. Whilst most of the research has focused on the prevalence and treatment of sexual difficulties, little is known about how patients cope with the SSRI-related sexual side effects. The objective of this study was to explore women’s experiences of coping with the sexual side effects of SSRI medication and interpretative phenomenological analysis was employed for an in-depth exploratory study of a sample of 10 women. Four broad themes emerged which are discussed under the following headings: searching, suffering in silence, trying to resolve and accepting what is. The themes provide an insight into the different strategies used by women to cope with the sexual side effects of SSRI medication and highlight the importance of contextualising these difficulties as part of an overall approach to improve the management and treatment of SSRI-related sexual side effects.