Serotonin reuptake inhibitors and cardiovascular disease

Selective serotonin re-uptake inhibiting drugs (SSRIs) are widely used for endogenous depression. In addition to depleting the nerve terminals of serotonin they also lower blood platelet serotonin levels. Platelet aggregation is a major component of acute coronary syndromes, including sudden death, and also of limb ischaemia. Platelet-released serotonin causes constriction of diseased blood vessels. The recent literature has revealed a number of reports of association between the treatment of depression with SSRIs and reduced events caused by intra-arterial thrombosis. The effects of serotonin and serotonin depletion upon intracoronary thrombosis, diseased blood vessels, blood platelets and bleeding are discussed with recommendations for future research into the potential cardiovascular benefits of SSRIs and serotonin 5HT2A antagonists

Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke

Objective: To investigate the effects of single doses of a selective serotonin reuptake inhibitor (SSRI) on lower limb voluntary and reflex function in individuals with chronic stroke. Design: Double-blind, randomized, placebo-controlled crossover trial. Setting: Outpatient research setting. Participants: Individuals (N=10; 7 men; mean age ± SD, 57±10y) with poststroke hemiplegia of \u3e1 year duration who completed all assessments. Interventions: Patients were assessed before and 5 hours after single-dose, overencapsulated 10-mg doses of escitalopram (SSRI) or placebo, with 1 week between conditions. Main Outcome Measures: Primary assessments included maximal ankle and knee isometric strength, and velocity-dependent (30°/s–120°/s) plantarflexor stretch reflexes under passive conditions, and separately during and after 3 superimposed maximal volitional drive to simulate conditions of increased serotonin release. Secondary measures included clinical measures of lower limb coordination and locomotion. Results: SSRI administration significantly increased stretch reflex torques at higher stretch velocities (eg, 90°/s; P=.03), with reflexes at lower velocities enhanced by superimposed voluntary drive (P=.02). No significant improvements were seen in volitional peak torques or in clinical measures of lower limb function (lowest P=.10). Conclusions: Increases in spasticity but not strength or lower limb function were observed with single-dose SSRI administration in individuals with chronic stroke. Further studies should evaluate whether repeated dosing of SSRIs, or as combined with specific interventions, is required to elicit significant benefit of these agents on lower limb function poststroke

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is the major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression. Recently, small trials have demonstrated that SSRIs might improve recovery after stroke, even in people who are not depressed. Systematic reviews and meta-analyses are the least biased way to bring together data from several trials. Given the promising effect of SSRIs on stroke recovery seen in small trials, a systematic review and meta-analysis is needed. OBJECTIVES: To determine whether SSRIs improve recovery after stroke, and whether treatment with SSRIs was associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis Group Trials Register (November 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August 2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011), PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for Brain Impairment Treatment Efficacy) (March 2012). To identify further published, unpublished and ongoing trials we searched trials registers, pharmaceutical websites, reference lists, contacted experts and performed citation tracking of included studies. SELECTION CRITERIA: We included randomised controlled trials that recruited stroke survivors (ischaemic or haemorrhagic) at any time within the first year. The intervention was any SSRI, given at any dose, for any period. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. In order to be included, trials had to collect data on at least one of our primary (dependence and disability) or secondary (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early) outcomes. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. For trials in English, two review authors independently extracted data. For Chinese papers, one review author extracted data. We used standardised mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous effects, with their 95% confidence intervals (CIs). MAIN RESULTS: We identified 56 completed trials of SSRI versus control, of which 52 trials (4059 participants) provided data for meta-analysis. There were statistically significant benefits of SSRI on both of the primary outcomes: RR for reducing dependency at the end of treatment was 0.81 (95% CI 0.68 to 0.97) based on one trial, and for disability score, the SMD was 0.91 (95% CI 0.60 to 1.22) (22 trials involving 1343 participants) with high heterogeneity between trials (I(2) = 87%; P < 0.0001). For neurological deficit, depression and anxiety, there were statistically significant benefits of SSRIs. For neurological deficit score, the SMD was -1.00 (95% CI -1.26 to -0.75) (29 trials involving 2011 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). For dichotomous depression scores, the RR was 0.43 (95% CI 0.24 to 0.77) (eight trials involving 771 participants) with high heterogeneity between trials (I(2) = 77%; P < 0.0001). For continuous depression scores, the SMD was -1.91 (95% CI -2.34 to -1.48) (39 trials involving 2728 participants) with high heterogeneity between trials (I(2) = 95%; P < 0.00001). For anxiety, the SMD was -0.77 (95% CI -1.52 to -0.02) (eight trials involving 413 participants) with high heterogeneity between trials (I(2) = 92%; P < 0.00001). There was no statistically significant benefit of SSRI on cognition, death, motor deficits and leaving the trial early. For cognition, the SMD was 0.32 (95% CI -0.23 to 0.86), (seven trials involving 425 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). The RR for death was 0.76 (95% CI 0.34 to 1.70) (46 trials involving 3344 participants) with no heterogeneity between trials (I(2) = 0%; P = 0.85). For motor deficits, the SMD was -0.33 (95% CI -1.22 to 0.56) (two trials involving 145 participants). The RR for leaving the trial early was 1.02 (95% CI 0.86 to 1.21) in favour of control, with no heterogeneity between trials. There was a non-significant excess of seizures (RR 2.67; 95% CI 0.61 to 11.63) (seven trials involving 444 participants), a non-significant excess of gastrointestinal side effects (RR 1.90; 95% CI 0.94 to 3.85) (14 trials involving 902 participants) and a non-significant excess of bleeding (RR 1.63; 95% CI 0.20 to 13.05) (two trials involving 249 participants) in those allocated SSRIs. Data were not available on quality of life, fatigue or healthcare costs.There was no clear evidence from subgroup analyses that one SSRI was consistently superior to another, or that time since stroke or depression at baseline had a major influence on effect sizes. Sensitivity analyses suggested that effect sizes were smaller when we excluded trials at high or unclear risk of bias.Only eight trials provided data on outcomes after treatment had been completed; the effect sizes were generally in favour of SSRIs but CIs were wide. AUTHORS' CONCLUSIONS: SSRIs appeared to improve dependence, disability, neurological impairment, anxiety and depression after stroke, but there was heterogeneity between trials and methodological limitations in a substantial proportion of the trials. Large, well-designed trials are now needed to determine whether SSRIs should be given routinely to patients with stroke

Antidepressants in pregnancy and breastfeeding

Copyright © 2007 Australian Prescriber Reproduced with permission from Australian Prescriber The document attached has been archived with permission from the publisher/copyright holder.Maternal depression and anxiety during pregnancy and the early years of an infant's life cause substantial problems to the mother, her infant and her family. Suicide is an ever-present risk with depression along with adverse effects on infant growth and birth weight. Balancing these risks against accumulating evidence of the effects of selective serotonin reuptake inhibitors on the fetus and infant presents a challenge to the treating doctor. Careful explanation to the woman and her partner of the risks of both the condition and the treatment, using a biological, psychological and social treatment approach, is likely to provide the most benefit.Anne Sved William

Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores

Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca2+ signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca2+ signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca2+ signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca2+ stores, thereby leaving less Ca2+ available for release upon IP3- and ryanodine-receptor activation. The Ca2+-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca2+ release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression

Treatments used for obsessive-compulsive disorder-An international perspective

© 2019 John Wiley & Sons, Ltd.OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.Peer reviewe

Do antidepressants cure or create abnormal brain states?

Moncrieff and Cohen argue that psychotropic drugs create abnormal states that may co-incidentally relieve symptoms of mental illness