Is left stroke a risk-factor for selective serotonin reuptake inhibitor antidepressant treatment resistance?

The objective of the study was to detect changes of depression and cognitive level associated with right and left brain damage during SSRI treatment in subjects with post-stroke Major Depressive Disorder (MDD). After the baseline evaluation, the 45 patients included received a single oral dose of 20–40 mg of fluoxetine or 50–100 mg of sertraline. At day 0, 7, 14, 28, 42, and 56 a psychometric test battery comprising the Hamilton Depression Rating Scale (HDRS) and the Mini Mental State Examination (MMSE) was administered. In the whole group repeated measures ANOVAs revealed a highly significant (p < 0.0001) time effect for HDRS and MMSE scores. However, depression improved much more in right stroke subjects in comparison with left stroke subjects (p < 0.001 for the HDRS by laterality interaction). Moreover, there is a suggestion of a possible selective serotonin reuptake inhibitor (SSRI) efficacy in cognitive impairment associated to post-stroke MDD but in treatment-responders only. At the endpoint, chi-square analysis showed that there was a different prevalence rate of MDD between left (n = 10; 50 %) and right (n = 4; 16 %) stroke patients, whereas the prevalence rate of Minor Depression was identical (25 %). The SSRIs fluoxetine and sertraline could be efficacious treatments for post-stroke MDD but these findings suggest that left stroke could be a predictor of treatment resistance. Received: 6 August 2002, Received in revised form: 4 November 2002, Accepted: 11 November 2002 Correspondence to Gianfranco Spalletta, MD     

How have the selective serotonin reuptake inhibitor antidepressants affected suicide mortality?

OBJECTIVE: We review evidence on two claims that have been made about the effects of selective serotonin reuptake inhibitor (SSRI) antidepressants; that they have: (i) decreased suicide rates in the population; and (ii) increased suicide rates in some individuals early in treatment. METHOD: We critically review evidence in the English-speaking peer-reviewed medical literature on: (i) meta-analyses of randomized controlled trials (RCTs) of SSRIs; (ii) observational studies of suicide risk in patients prescribed SSRIs and other antidepressants; and (iii) ecological studies of correlations between population use of SSRI use and population suicide rates. RESULTS: The largest and most recent meta-analyses of RCTs of SSRIs have found suggestive evidence that SSRIs increase suicidal ideation early in treatment compared with placebo. Observational studies have found an increased risk of self-harm within 9 days of an antidepressant drug being prescribed but the risk has been similar for the older tricyclic antidepressants and the SSRIs. Ecological studies in developed countries have found either that suicide rates have declined as SSRI use has increased, or have found no relationship between suicide rates and increased SSRI use. CONCLUSIONS: Meta-analyses of RCTs suggest that SSRIs increase suicide ideation compared with placebo but the observational studies suggest that SSRIs do not increase suicide risk more than older antidepressants. If SSRIs increase suicide risk in some patients, the number of additional deaths is very small because ecological studies have generally found that suicide mortality has declined (or at least not increased) as SSRI use has increased.     

Is mechanical ventilation associated with intraventricular hemorrhage in preterm infants?

Background

The impact of mechanical ventilation on the incidence of intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants is unknown, simply because the vast majority of these infants have been routinely intubated and mechanically ventilated. There is a growing interest in the use of early nasal continuous positive airway pressure (ENCPAP) and avoiding mechanical ventilation.

Objectives

To examine the role of mechanical ventilation since delivery room in determining severe IVH in VLBW infants in two neonatal units that follow the same strategy of respiratory management using ENCPAP.

Methods

We collected data on delivery room intubation and mechanical ventilation during the first 3 days of life in VLBW infants. Logistic regression model was constructed to test the relationship between early mechanical ventilation and the diagnosis of severe IVH after controlling for significant confounding variables, such as BW, gender, duration of mechanical ventilation, and partial pressure of CO₂ (PCO₂).

Results

Of the studied 340 VLBW, 35 infants had severe IVH; most of them received mechanical ventilation that started either in the delivery room (n = 12) or during the first (n = 10) and second (n = 3) days of life. Severe IVH was independently associated with lower BW, mechanical ventilation in the delivery room, and the cumulative duration of mechanical ventilation during the first 3 days. The adjusted odds ratio for severe IVH in infants intubated in delivery room was (OR = 2.7, CI: 1.1–6.6, P = 0.03). Severe IVH was not associated with gender, prenatal steroids, early sepsis, or patent ductus arteriosus.

Conclusions

Mechanical ventilation plays a role in predicting severe IVH. Both the time at which ventilation was initiated and the duration of ventilation are important determinants of severe IVH. Risk for severe IVH in infants who were never intubated in delivery room or during the first 3 days of life is miniscule.     

Suicidality with selective serotonin reuptake inhibitors: Valid claim?

The red flags raised by the 1990 clinical reports of increased suicidality associated with treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine were followed by anecdotal reports of similar symptoms with other antidepressants of the same class. Recent discussions by Healy have argued in favour of a suicidogenic potential of the SSRIs. This paper reviews the relevant literature addressing the epidemiological data of Western populations and the data accumulated from clinical trial databases in several countries. The evidence currently available does not support the hypothesis that antidepressants or, more specifically, SSRIs cause increased suicidality in patients with depression, nor do they appear to do so in patients treated with these drugs for other reasons.     

Is paternal postpartum depression associated with maternal postpartum depression? Population‐based study in Brazil

OBJECTIVE: To describe the prevalence of paternal postpartum depression (PPD) as well as its association with maternal PPD. METHOD: A population-based random sample of 386 couples was assessed from the sixth to the 12th week postpartum for demographic characteristics, alcohol misuse (AUDIT) and depressive symptoms [Beck Depression Inventory (BDI)]. Logistic regression was employed to control for potential confounders. RESULTS: In the BDI, 26.3% of mothers and 11.9% of fathers scored above the selected threshold of 10. Mild maternal depression [odds ratio (OR) 3.31, 95% CI 1.52-7.20] and moderate to severe maternal depression (OR 8.44, 95% CI 3.53-20.21) were associated with paternal PPD. CONCLUSION: Paternal PPD is a clinically meaningful phenomenon. Fathers should be evaluated for mood disorders in the postpartum, especially when their partner is depressed.     

Should antidepressant drugs of the selective serotonin reuptake inhibitor family be tested as antiepileptic drugs?

For a long time, there has been a misconception that all antidepressant drugs have proconvulsant effects. Yet, antidepressants of the selective serotonin reuptake inhibitor (SSRI) family not only have been shown to be safe when used in patients with epilepsy (PWE) but also have been found to possess antiepileptic properties in animal models of epilepsy. In humans randomized to SSRIs vs. placebo for the treatment of major depressive episodes, the incidence of epileptic seizures was significantly lower among those treated with the antidepressants. These data raise the question of whether there is enough evidence that would support a randomized placebo-controlled trial to test antiepileptic effect of SSRIs in PWE. This article reviews the preclinical and clinical data to address this question.This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”.     

Targeting remission by 8 weeks: when should supplementation be considered in patients with major depression treated with a specific serotonin reuptake inhibitor?

Background

Timely administration/supplementation of a specific serotonin reuptake inhibitor with a second therapeutic agent could improve treatment outcome in patients with major depressive disorder (MDD). The purpose of this study was to identify the optimal time at which to implement supplementation so as to maximize the likelihood of remission by 8 weeks and minimize overtreatment.

Method

Data from patients with MDD treated with sertraline (n = 108) or citalopram (n = 107) in a randomized controlled trial were analyzed by multivariate logistic regression. The 21-item Hamilton Depression Scale scores at weeks 1, 2, 3, 4, and 6; sex; age; and baseline Hamilton Anxiety Scale score were used as predictors of remission by 8 weeks sustained for a further 4 weeks.

Results

Regression models for weeks 2, 3, 4, and 6 were significant (area under the curve values, 0.73-0.91). The models for weeks 3 to 6 yielded κ coefficients greater than 0.40 with the outcome variable. A Hamilton Depression Scale reduction score of 50% at week 4 as a criterion for supplementation would have resulted in overtreatment of 4% and 0% of patients in the sertraline and citalopram groups, respectively, and none if applied at week 6. The rates at which patients who should have received supplementation (destined to be nonremitters at 8 weeks) would have been missed would be 49%/54% for sertraline/citalopram at week 4 and 43%/50% at week 6.

Limitations

The study limitations are as follows: secondary analysis of data, relatively low sertraline dose, and relatively small sample sizes.

Conclusions

It may be possible to identify patients treated with specific serotonin reuptake inhibitors who will not achieve sustained remission by 8 weeks. If supplementation were implemented accordingly, the number of overtreated patients would be small. However, a substantial number of patients who should be supplemented would be missed, indicating a need for greater sensitivity of the prediction model. Further studies are needed.     

What happens with adverse events during 6 months of treatment with selective serotonin reuptake inhibitors?

OBJECTIVE: Although adverse events are a key factor in compliance, their evolution during treatment with antidepressants is poorly documented. Therefore, the time course of adverse events during 6 months of antidepressant treatment was investigated. METHOD: 85 psychiatric outpatients with a DSM-IV diagnosis of major depressive disorder (with the exclusion of other DSM-IV Axis I disorders) were enrolled between September 2002 and March 2003 in a multicenter, randomized, double-blind trial with selective serotonin reup-take inhibitors (fluoxetine [N = 42] and paroxetine [N = 43]). At each visit, the presence and severity of treatment-emergent adverse events were assessed systematically using the UKU Side Effect Rating Scale (UKU). General linear mixed modeling was used to investigate the predictors of the time course of adverse events. RESULTS: Overall, the number of at least moderately severe adverse events decreased with time. More severely depressed patients reported overall more (at least moderately severe) adverse events than less severely depressed patients (p = .0002), but the decrease in reported adverse events was comparable over time. Men (N = 30) and women (N = 55) reported initially the same number of at least moderately severe adverse events, but the habituation was more rapid in men (p < .0001). Completers (N = 58) and dropouts (N = 27) did not differ initially, but completers' habituation was more rapid (p = .014). The habituation of adverse events was also more rapid in recurrent than in first-episode patients but only in men (p = .0025). CONCLUSION: The time course of adverse events varies with the severity of depression, sex, completer or dropout status, and recurrent versus first-episode depression.     

Is COPD associated with suicide behavior?

Background

The goal of this study is to examine the relationship between chronic obstructive pulmonary disease (COPD) and suicidal ideation and suicide attempt among adults in the United States.

Methods

Data were drawn from the National Comorbidity Study-Replication (NCS-R), a household probability sample of adults ages 18 and older in the United States.

Results

COPD is associated with significantly increased odds of suicidal ideation and suicide attempt, compared with those without COPD. The association between COPD and suicide attempt remained statistically significant after adjusting for demographics, depression, panic disorder, substance use and nicotine dependence. The association between COPD and suicidal ideation was no longer significant after adjusting for nicotine dependence.

Conclusions

Our findings provide initial evidence that there is a relationship between COPD and suicidal behavior among adults in the community. Future studies that can examine the relationship between COPD and completed suicide, as well as replication of these results, would improve our understanding of whether and to what degree COPD confers an increased vulnerability for suicide behavior.     

Is parenthood associated with mental health?

BACKGROUND: Despite some reports on a potential link between parenthood and mental health, associations have not been systematically investigated yet. The present article provides prevalence rates of the most common mental disorders for parents and non-parents. Interactions between demographic and socio-economic variables, parental status and mental health are explored. METHODS: Data from the 1998/99 German Health Survey (GHS) and its Mental Health Supplement (GHS-MHS) were analysed using logistic regression models. Analyses were restricted to participants in the age group 18 to 49 (N=2,801). Mental disorders and syndromes were assessed with a standardized diagnostic interview (M-CIDI). RESULTS: Parenthood was associated with lower rates of psychiatric morbidity in general, and depressive and substance use disorders, in particular. The association between parental status and mental health was more distinct in men than in women, whereas partnership status moderated this relationship: An absence of partnership was associated with increased rates of all common mental disorders. Among non-parents, such a difference could not be found. Full-time employment, compared to part-time employment or unemployment, was linked to lower rates of the common mental disorders among fathers but not among mothers and non-parents. Age, education and income had no effects on the association between parental status and mental health. CONCLUSION: Parenthood is positively associated with mental health, particularly for men. Most differences can be found for depressive and substance use disorders. Partnership seems especially important for parents since it does not affect prevalence rates of mental disorders among non-parents.     

Is a prolonged bleeding time associated with an increased risk of hemorrhage after liver biopsy?

Bleeding time determination is not advised as a general preoperative hemostasis screening test, but it might be useful in some patient groups. Patients referred for liver biopsy frequently have coagulation disturbances and are at risk of hemorrhage. In this prospective study 219 liver biopsies were carried out regardless of a prolonged bleeding time, but with minimum requirements for hemoglobin concentration, platelet count, and tests of the internal and external coagulation pathways. The bleeding time was prolonged in the case of 48 (22%) of the biopsies. Significant bleeding as defined by a hemoglobin decrease of > or =2.0 g/dl occurred in nine patients. Three of these patients were bone marrow transplanted. Patients with a prolonged bleeding time carried a five times higher risk of bleeding (odds ratio = 5.0; confidence interval = 1.1-21.8; p = 0.019). We conclude that the bleeding time may give additional information on the risk of bleeding in some patient groups undergoing liver biopsy.     

Treating children and adolescents with selective serotonin reuptake inhibitors: how long is appropriate?

This article addresses a key question on the use of selective serotonin reuptake inhibitors (SSRIs) among children and adolescents. As briefly reviewed, recent randomized controlled trials have established the safety and efficacy of SSRIs in the acute treatment of major depression and anxiety disorders among children and adolescents. Major questions emerge in light of these data concerning the potential risks and benefits of long-term SSRI use among children and adolescents who receive significant short-term benefits from SSRI treatment. The current review summarizes research on longitudinal outcomes, neuroscience, and psychopharmacology to formulate a set of preliminary recommendations on long-term SSRI use. A review of data in these areas supports three conclusions. First, for children who achieve marked reduction in anxiety or depressive symptoms on an SSRI, clinicians should consider recommending a medication-free trial. Second, when indicated, this medication-free trial should coincide with the first low-stress period occurring after 1 year of continual SSRI treatment. Third, SSRI treatment should be reinitiated in children who exhibit signs of relapse during this medication-free trial.     

Should selective serotonin reuptake inhibitors be prescribed to all patients with ischemic heart disease?

Recent studies have uncovered more and more evidence demonstrating the adverse relationship between depression and ischemic heart disease. One of the most significant mechanisms that may explain the adverse relationship is the increased platelet activity, otherwise known as aggregation, observed to occur in patients with depression or ischemic heart disease. Platelet activity is further elevated in patients with depression and ischemic heart disease. Selective serotonin reuptake inhibitors are antidepressants and also act like platelet inhibitors. The results of large-scale clinical trials suggest that the use of selective serotonin reuptake inhibitors may reduce cardiac events in post-myocardial infarction patients or in those with unstable angina that may be related to the effects of selective serotonin reuptake inhibitors on platelet aggregation.