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

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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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Early- vs late-onset subcortical vascular cognitive impairment

Posted on February 8, 2016 by Maurice Preter MD

 

Early- vs late-onset subcortical vascular cognitive impairment

http://tinyurl.com/hyhtq4n

Young Kyoung Jang, MD, Hunki Kwon, MS, Yeo Jin Kim, MD, Na Yeon Jung, MD, Jin SanLee, MD, Juyoun Lee, MD, Juhee Chin, PhD, Kiho Im, PhD, Seun Jeon, PhD, Jong Min Lee, PhD, Joon-Kyoung Seong, PhD, Jeong Hun Kim, MS, Seonwoo Kim, PhD, Yearn Seong Choe, PhD, Kyung-Han Lee, MD, PhD, Sung Tae Kim, MD, PhD, Jae Seung Kim, MD, PhD, Jae Hong Lee, MD, PhD, Duk L. Na, MD, PhD, Sang Won Seo, MD, PhD and Hee Jin Kim, MD

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Correspondence to Dr. Kim: evekhj@gmail.com

Published online before print January 13, 2016, doi: http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002357
Neurology February 9, 2016 vol. 86 no. 6 527-534

ABSTRACT

Objective: To evaluate the differences between early-onset subcortical vascular cognitive impairment (EO-SVCI) and late-onset subcortical vascular cognitive impairment (LO-SVCI) with regard to pathologic burden, structural changes, and cognitive function.

Methods: We prospectively recruited 142 patients from a single referral center. Patients were divided into EO-SVCI (n = 30, age at onset <65 years) and LO-SVCI (n = 112, age at onset ≥65 years) groups. All patients underwent neuropsychological tests, 3T brain MRI, and [11C] Pittsburgh compound B (PiB)–PET. We compared pathologic burden such as small vessel disease and amyloid burden; structural changes such as structural network, cortical thickness, and hippocampal volume; and cognitive function between EO-SVCI and LO-SVCI.

Results: EO-SVCI patients had more lacunes, while LO-SVCI patients had higher PiB standardized uptake value ratios. EO-SVCI patients exhibited more severe structural network disruptions in the frontal area, while LO-SVCI patients exhibited more severe cortical and hippocampal atrophy. Although disease severity did not differ between the 2 groups, frontal-executive dysfunction was more severe in EO-SVCI patients.

Conclusions: EO-SVCI patients showed more vascular related factors, while LO-SVCI patients exhibited more Alzheimer disease–related characteristics. The greater number of lacunes in EO-SVCI might account for the more severe frontal network disruption and frontal-executive dysfunction, while the greater amyloid burden in LO-SVCI might account for the more severe cortical and hippocampal atrophy. Our findings suggest that the age at onset is a crucial factor that determines distinct features in SVCI patients, such as pathologic burden, structural changes, and cognitive function.

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Midlife milk consumption and substantia nigra neuron density at death

Posted on February 8, 2016 by Maurice Preter MD

 

Midlife milk consumption and substantia nigra neuron density at death

http://tinyurl.com/jjwookb

Robert D. Abbott, PhD, G. Webster Ross, MD, Helen Petrovitch, MD, Kamal H. Masaki, MD, Lenore J. Launer, PhD, James S. Nelson, MD, Lon R. White, MD and Caroline M. Tanner, MD, PhD

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Correspondence to Dr. Abbott: rda3e@virginia.edu

Published online before print December 9, 2015, doi: http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002254

Neurology February 9, 2016 vol. 86 no. 6 512-519

ABSTRACT

Objective: To examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study.

Methods: Milk intake data were collected from 1965 to 1968 in 449 men aged 45–68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm2) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s.

Results: Neuron density was lowest in nonsmoking decedents who consumed high amounts of milk (>16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake >16 oz/d vs intake that was less (95% confidence interval 22.7%–55.7%, p < 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent.

Conclusions: Milk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study.

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