PMID: 

Neuroepidemiology. 2019 Jun 19:1-10. Epub 2019 Jun 19. PMID: 31216542

Abstract Title: 

Use of Antidepressants and Risk of Incident Stroke: A Systematic Review and Meta-Analysis.

Abstract: 

BACKGROUND: Both depression and use of antidepressants have been reported to be risk factors for stroke, but results from the literature are still not conclusive regarding the risk attributable to antidepressants rather than to the underlying disease.OBJECTIVE: To estimate the risk of incident stroke associated with use of antidepressants, a meta-analysis was performed.METHODS: PubMed, Medline, Cochrane, ProQuest, Scopus, and bibliographies of articles were searched up to September 2018. The final meta-analysis included 31 observational studies. STROBE statement-checklist and GRADE guidelines were used for quality assessment.RESULTS: The random-effects meta-analysis on the association between use of any antidepressant and risk of any stroke resulted in meta-risk ratio (RR) of 1.41 (95% CI 1.13-1.69, I2 = 93, 7%). The pooled estimate for selective serotonin reuptake inhibitors (SSRIs) resulted in a meta-RR of 1.41 (95% CI 1.13-1.69, I2 = 94, 5%) and for tricyclic antidepressants (TCAs) of 1.08 (95% CI 0.93-1.22, I2 = 0%). SSRI users displayed a higher risk of ischemic (1.57, 95% CI 1.06-2.09, I2 = 96.4%) than hemorrhagic stroke (1.34, 95% CI 1.15-1.53, I2 = 72.9%). Meta-RRs were lower for TCA, although with smaller heterogeneity (ischemic 1.22, 95% CI 0.97-1.46; I2 = 0%; hemorrhagic: 1.00, 95% CI 0.83-1.18, I2 = 0%). Restricting to studies on depressed individuals, both SSRI and TCA remained associated with an increased risk of any stroke type (meta-RR for SSRI: 1.27, 95% CI 1.11-1.43, I2 = 76.6%; meta-RR for TCA: 1.21 (95% CI 1.02-1.40, I2 = 47, 3%).CONCLUSIONS: Despite the high heterogeneity, these results demonstrate that even after adjusting for depression, use of antidepressants retains an independent increased risk of stroke.

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PMID: 

Ann Epidemiol. 2019 Jul ;35:42-47.e1. Epub 2019 May 11. PMID: 31200987

Abstract Title: 

Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding.

Abstract: 

PURPOSE: Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke.METHODS: For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study-Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other.RESULTS: Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0-2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not.CONCLUSIONS: Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions.

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PMID: 

Drug Saf. 2019 Jun 4. Epub 2019 Jun 4. PMID: 31165430

Abstract Title: 

Antidepressants and the Risk of Hemorrhagic Stroke in the Elderly: a Nested Case-Control Study.

Abstract: 

BACKGROUND AND PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed in the elderly due to a more favorable risk profile than other antidepressants (ADs). However, SSRIs are associated with an increased risk of gastrointestinal bleeding, while evidence on the risk of hemorrhagic stroke (HS) is limited. Therefore, we compared the risk of HS associated with the use of ADs in the elderly.METHODS: Based on data from the German Pharmacoepidemiological Research Database (GePaRD), a case-control study matched on age, sex, and health insurance provider, nested in a cohort of incident users of ADs ≥ 65 years of age was performed. Cases were identified from hospital discharge diagnoses, and exposure was identified from outpatient prescriptions. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Based on 4059 cases and 40,590 controls, an increased risk of HS was found in current use of SSRIs (OR 1.39, 95% CI 1.22-1.58), selective serotonin and noradrenaline reuptake inhibitors (1.69, 1.35-2.11), noradrenergic and specific serotonergic ADs (1.44, 1.22-1.69), and noradrenaline reuptake inhibitors (3.81, 1.54-9.43) compared with tri- and tetracyclic antidepressants. An increased risk of HS was seen in patients with a high baseline risk of bleeding and in patients with depression. The risk of HS varied between individual ADs.CONCLUSION: Our study shows that the use of medications inhibiting serotonin and/or noradrenaline reuptake increases the risk of HS in patients aged 65 years and older and that the risk varies across individual ADs.

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PMID: 

J Gen Intern Med. 2019 Jun 3. Epub 2019 Jun 3. PMID: 31161572

Abstract Title: 

Prescription Medications for the Treatment of Insomnia and Risk of Suicide Attempt: a Comparative Safety Study.

Abstract: 

IMPORTANCE: Guidelines for the pharmacological treatment of chronic insomnia in adults recognize that trazodone and other off-label medications are commonly prescribed despite poor evidence. The Department of Veterans Health Affairs (VA) fills high volumes of inexpensive, over-the-counter sedating antihistamines and older antidepressants in addition to benzodiazepines and zolpidem. Yet little is known about the comparative safety of these agents with regard to suicidal behavior.OBJECTIVES: To assess the comparative effectiveness of the safety of medications routinely used to treat insomnia in VA.DESIGN: Comparative effectiveness using propensity score-matched samples.SETTING: VA.PARTICIPANTS: VA patients without any history of suicidal ideation or behavior 12 months prior to first exposure.EXPOSURES: VA formularies and data were used to identify prescriptions for insomnia. Agents accounting for at least 1% of total insomnia fill volume were

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PMID: 

BMC Pregnancy Childbirth. 2019 Apr 30 ;19(1):146. Epub 2019 Apr 30. PMID: 31039756

Abstract Title: 

Use of antidepressants and anxiolytics in early pregnancy and the risk of preeclampsia and gestational hypertension: a prospective study.

Abstract: 

BACKGROUND: We investigated the association between antidepressant and anxiolytic exposure during the first and early second trimester of pregnancy (

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Originally published on www.mdsafetech.org

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PMID: 

Clin Epigenetics. 2019 03 29 ;11(1):56. Epub 2019 Mar 29. PMID: 30925934

Abstract Title: 

Prenatal maternal antidepressants, anxiety, and depression and offspring DNA methylation: epigenome-wide associations at birth and persistence into early childhood.

Abstract: 

BACKGROUND: Maternal mood disorders and their treatment during pregnancy may have effects on the offspring epigenome. We aim to evaluate associations of maternal prenatal antidepressant use, anxiety, and depression with cord blood DNA methylation across the genome at birth and test for persistence of associations in early and mid-childhood blood DNA.METHODS: A discovery phase was conducted in Project Viva, a prospective pre-birth cohort study with external replication in an independent cohort, the Generation R Study. In Project Viva, pregnant women were recruited between 1999 and 2002 in Eastern Massachusetts, USA. In the Generation R Study, pregnant women were recruited between 2002 and 2006 in Rotterdam, the Netherlands. In Project Viva, 479 infants had data on maternal antidepressant use, anxiety, depression, and cord blood DNA methylation, 120 children had DNA methylation measured in early childhood (~ 3 years), and 460 in mid-childhood (~ 7 years). In the Generation R Study, 999 infants had data on maternal antidepressants and cord blood DNA methylation. The prenatal antidepressant prescription was obtained from medical records. At-mid pregnancy, symptoms of anxiety and depression were assessed with the Pregnancy-Related Anxiety Scale and the Edinburgh Postnatal Depression Scale in Project Viva and with the Brief Symptom Inventory in the Generation R Study. Genome-wide DNA methylation was measured using the Infinium HumanMethylation450 BeadChip in both cohorts.RESULTS: In Project Viva, 2.9% (14/479) pregnant women were prescribed antidepressants, 9.0% (40/445) experienced high pregnancy-related anxiety, and 8.2% (33/402) reported symptoms consistent with depression. Newborns exposed to antidepressants in pregnancy had 7.2% lower DNA methylation (95% CI, - 10.4, - 4.1; P = 1.03 × 10) at cg22159528 located in the gene body of ZNF575, and this association replicated in the Generation R Study (β = - 2.5%; 95% CI - 4.2, - 0.7; P = 0.006). In Project Viva, the association persisted in early (β = - 6.2%; 95% CI - 10.7, - 1.6) but not mid-childhood. We observed cohort-specific associations for maternal anxiety and depression in Project Viva that did not replicate.CONCLUSIONS: The ZNF575 gene is involved in transcriptional regulation but specific functions are largely unknown. Given the widespread use of antidepressants in pregnancy, as well as the effects of exposure to anxiety and depression, implications of potential fetal epigenetic programming by these risk factors and their impacts on development merit further investigation.

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PMID: 

Mol Med Rep. 2019 Apr ;19(4):2611-2619. Epub 2019 Feb 1. PMID: 30720108

Abstract Title: 

Fluoxetine induces direct inhibitory effects on mesenchymal stem cell‑derived osteoprogenitor cells independent of serotonin concentration.

Abstract: 

Selective serotonin reuptake inhibitors are the most commonly prescribed antidepressants worldwide, which have been reported to exert potential detrimental effects on bone mineral density and increase the risk of developing fractures. The present study aimed to investigate the pathways underlying the negative effects of fluoxetine on bone using mesenchymal stem cells (MSCs) derived from rat adipose tissue as a source of osteoprogenitor cells. MSCs were harvested from adipose tissue using a collagenase enzyme digestion method and were allowed to differentiate into osteoprogenitor cells. Various concentrations of fluoxetine were added to the cells, which were harvested and analyzed by flow cytometry to detect apoptotic markers Annexin V and caspase‑3, in order to assess the levels of apoptosis. The levels of endogenous serotonin released in the extracellular matrix were measured using a serotonin ELISA kit. The underlying molecular pathways associated with the effects of fluoxetine on bone were investigated with reverse transcription‑quantitative polymerase chain reaction. The results of the present study revealed a significant dose‑dependent increase in apoptosis in response to increasing doses of fluoxetine, which was independent of serotonin levels in the culture supernatant. These findings indicated that fluoxetine exerted a direct inhibitory effect on bone cells via an apoptosis‑dependent pathway. Furthermore, the expression levels of serotonergic genes, including serotonin 1B receptor, serotonin 2A receptor (HTR2A), serotonin 2B receptor and serotonin transporter, were down regulated; of these genes, HTR2A exhibitedthe highest expression levels. Further in vitro and in vivo studies are required to verify this association and to determine the molecular pathways involved in fluoxetine‑induced bone loss. Fluoxetine‑induced apoptosis of osteoprogenitor cells may be the mechanism underlying the increased incidence of bone loss observed in patients treated with fluoxetine.

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Watermelon is so much more than just a highly refreshing summertime treat. From the perspective of a growing body of clinical research, it is a truly medicinal food.

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Google wants you to think a certain way about vaccines, namely, that they are unilaterally “safe,” “good,” and that those who question these truths to be self-evident are a “burden,” or worse, on society — and its more than willing to distort and manipulate the world’s search results to make you think that way. 

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