The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis

Posted on February 12, 2016 by Maurice Preter MD

 

The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis

http://tinyurl.com/jur423x

Anick Bérard1,2,*, Noha Iessa1,2, Sonia Chaabane1,2, Flory T. Muanda1,2, Takoua Boukhris1,2 and Jin-Ping Zhao1,2

Article first published online: 26 JAN 2016

DOI: 10.1111/bcp.12849

Abstract

Aims

The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category.

Method

A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models.

Results

Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed.

Conclusions

Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.

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Antidepressant Use Is Associated With an Increased Risk of Developing Microbleeds

Posted on February 12, 2016 by Maurice Preter MD

 

Antidepressant Use Is Associated With an Increased Risk of Developing Microbleeds

http://tinyurl.com/z96cjhk

Saloua Akoudad, MD, PhD*; Nikkie Aarts, MSc*; Raymond Noordam, PhD; M. Arfan Ikram, MD, PhD; Henning Tiemeier, MD, PhD; Albert Hofman, MD, PhD; Bruno H. Stricker, MMed, PhD; Meike W. Vernooij, MD, PhD; Loes E. Visser, PharmD, PhD

+Author Affiliations

From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen – HAGA, the Hague, The Netherlands (L.E.V.).
 

Correspondence to Bruno H. Stricker, MMed, PhD, Erasmus MC, 3000 CA Rotterdam, The Netherlands. E-mail b.stricker@erasmusmc.nl

Abstract

Background and Purpose—Serotonin-specific antidepressants may increase the risk of adverse bleeding events. In a previous cross-sectional study, we did not observe an association between antidepressant use and presence of subclinical cerebral bleedings. In this study, we investigated longitudinally whether antidepressant use is associated with an increased risk of new subclinical cerebral microbleeds.

Methods—In total, 2559 participants aged ≥45 years of the population-based Rotterdam Study, all without microbleeds at baseline, underwent baseline and repeat brain magnetic resonance imaging between 2005 and 2013 (mean time interval, 3.9 years; SD, 0.5) to determine the incidence of microbleeds. Antidepressant use (yes versus no) was assessed between baseline and follow-up scan. In additional analyses, antidepressants were classified as low, intermediate, or high affinity for the serotonin transporter, and alternatively as selective serotonin reuptake inhibitors or non-selective serotonin reuptake inhibitors. We used multivariable logistic regression models to investigate the association of antidepressants with incident microbleeds.

Results—Antidepressant use was associated with a higher cerebral microbleed incidence (odds ratio, 2.22; 95% confidence interval, 1.31–3.76) than nonuse. When stratified by affinity for the serotonin transporter, intermediate serotonin affinity antidepressant use was associated with an increased risk of developing microbleeds (odds ratio, 3.07; 95% confidence interval, 1.53–6.17). Finally, selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor use were both associated with increased microbleed incidence.

Conclusions—Antidepressant use was associated with an increased risk of developing microbleeds. Our results may support findings from previous clinical studies about increased intracranial and extracranial bleeding risk in antidepressant

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Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

Posted on February 12, 2016 by Maurice Preter MD

 

Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

http://tinyurl.com/hmgdrmx

Tarang Sharma, PhD student1 2, Louise Schow Guski, medical student1 2, Nanna Freund, medical student1 2, Peter C Gøtzsche, professor1 2

Author affiliations

Correspondence to: T Sharma Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, Department 7811, 2100 Ø Copenhagen, Denmark ts@cochrane.dk

Accepted 3 December 2015

Abstract

Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.

Design Systematic review and meta-analysis.

Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.

Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website.

Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms.

Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model).

Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.

Conclusions Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.

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Risk of suicide after a concussion

Posted on February 8, 2016 by Maurice Preter MD

 

Risk of suicide after a concussion

http://tinyurl.com/ha6vrqw

Michael Fralick, Deva Thiruchelvam, Homer C. Tien, Donald A. Redelmeier

+Author Affiliations

Department of Medicine (Fralick, Redelmeier), University of Toronto, Toronto, Ont.; Evaluative Clinical Sciences (Fralick, Thiruchelvam, Tien, Redelmeier), Sunnybrook Research Institute, Toronto, Ont.; Institute for Clinical Evaluative Sciences (Thiruchelvam), Toronto, Ont.; Canadian Forces Health Services (Tien), Toronto, Ont.

 

Donald A. Redelmeier, E-mail dar@ices.on.ca

Abstract

Background: Head injuries have been associated with subsequent suicide among military personnel, but outcomes after a concussion in the community are uncertain. We assessed the long-term risk of suicide after concussions occurring on weekends or weekdays in the community.

Methods: We performed a longitudinal cohort analysis of adults with diagnosis of a concussion in Ontario, Canada, from Apr. 1, 1992, to Mar. 31, 2012 (a 20-yr period), excluding severe cases that resulted in hospital admission. The primary outcome was the long-term risk of suicide after a weekend or weekday concussion.

Results: We identified 235 110 patients with a concussion. Their mean age was 41 years, 52% were men, and most (86%) lived in an urban location. A total of 667 subsequent suicides occurred over a median follow-up of 9.3 years, equivalent to 31 deaths per 100 000 patients annually or 3 times the population norm. Weekend concussions were associated with a one-third further increased risk of suicide compared with weekday concussions (relative risk 1.36, 95% confidence interval 1.14–1.64). The increased risk applied regardless of patients’ demographic characteristics, was independent of past psychiatric conditions, became accentuated with time and exceeded the risk among military personnel. Half of these patients had visited a physician in the last week of life.

Interpretation: Adults with a diagnosis of concussion had an increased long-term risk of suicide, particularly after concussions on weekends. Greater attention to the long-term care of patients after a concussion in the community might save lives because deaths from suicide can be prevented.

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Milk consumption and the risk of nigral degeneration

Posted on February 8, 2016 by Maurice Preter MD

Milk consumption and the risk of nigral degeneration

http://tinyurl.com/jomtju6

Honglei Chen, MD, PhD and Karen Marder, MD, MPH

+SHOW AFFILIATIONS | + SHOW FULL DISCLOSURES

Correspondence to Dr. Chen: chenh2@niehs.nih.gov

Published online before print December 9, 2015, doi: http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002268
Neurology February 9, 2016 vol. 86 no. 6 496-497

In the era of genetic research for neurodegenerative diseases, less attention has been paid to epidemiologists’ search for potential environmental risk factors for Parkinson disease (PD). Epidemiologic evidence suggests that cigarette smoking is associated with about 50% lower risk of PD1 and exposure to certain pesticides such as rotenone and paraquat is associated with doubled risk.2 Recent studies also suggest that higher concentration of serum urate, an endogenous antioxidant, is associated with a lower risk of PD.3 Compared with these observations, another epidemiologic finding has been largely neglected. Several prospective studies,4–7 including the Honolulu-Asia Aging Study (HAAS),6 have reported that higher consumption of dairy products, or milk alone, was associated with higher risk for PD.

ACKNOWLEDGMENT

The authors thank Dr. Freya Kamel for suggestions on the editorial.

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