Suicide deaths of active-duty US military and omega-3 fatty-acid status

Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case-control comparison.

The recent escalation of US military suicide deaths to record numbers has been a sentinel for impaired force efficacy and has accelerated the search for reversible risk factors.

OBJECTIVE:

To determine whether deficiencies of neuroactive, highly unsaturated omega-3 essential fatty acids (n-3 HUFAs), in particular docosahexaenoic acid (DHA), are associated with increased risk of suicide death among a large random sample of active-duty US military.

METHOD:

In this retrospective case-control study, serum fatty acids were quantified as a percentage of total fatty acids among US military suicide deaths (n = 800) and controls (n = 800) matched for age, date of collection of sera, sex, rank, and year of incident. Participants were active-duty US military personnel (2002-2008). For cases, age at death ranged from 17-59 years (mean = 27.3 years, SD = 7.3 years). Outcome measures included death by suicide, postdeployment health assessment questionnaire (Department of Defense Form 2796), and ICD-9 mental health diagnosis data.

RESULTS:

Risk of suicide death was 14% higher per SD of lower DHA percentage (OR = 1.14; 95% CI, 1.02-1.27; P < .03) in adjusted logistic regressions. Among men, risk of suicide death was 62% greater with low serum DHA status (adjusted OR = 1.62; 95% CI, 1.12-2.34; P < .01, comparing DHA below 1.75% [n = 1,389] to DHA of 1.75% and above [n = 141]). Risk of suicide death was 52% greater in those who reported having seen wounded, dead, or killed coalition personnel (OR = 1.52; 95% CI, 1.11-2.09; P < .01).

CONCLUSION:

This US military population had a very low and narrow range of n-3 HUFA status. Although these data suggest that low serum DHA may be a risk factor for suicide, well-designed intervention trials are needed to evaluate causality.

Beliefs About Suicide Acceptability in the United States: How Do They Affect Suicide Mortality?

Beliefs About Suicide Acceptability in the United States: How Do They Affect Suicide Mortality?

The Journals of Gerontology: Series B, gbx153,https://doi.org/10.1093/geronb/gbx153
Published:
25 January 2018
Article history

Abstract

Objectives

Societies develop cultural scripts to understand suicide and define conditions under which the act is acceptable. Prior empirical work suggests that such attitudes are important in understanding some forms of suicidal behavior among adolescents and high-risk populations. This study examines whether expressions of suicide acceptability under different circumstances are predictive of subsequent death by suicide in the general U.S. adult population and whether the effects differ over the life course.

 

Method

The study uses 1978–2010 General Social Survey data linked to the National Death Index through 2014 (n = 31,838). Cox survival models identify risk factors for suicide mortality, including attitudinal and cohort effects.

 

Results

Expressions of suicide acceptability are predictive of subsequent death by suicide—in some cases associated with a twofold increase in risk. Attitudes elevate the suicide hazard among older (>55 years) adults but not among younger (ages 33–54) adults. Fully-adjusted models reveal that the effects of attitudes toward suicide acceptability on suicide mortality are strongest for social circumstances (family dishonor; bankruptcy).

 

Discussion

Results point to the role of cultural factors and social attitudes in suicide. There may be utility in measuring attitudes in assessments of suicide risk.

Suicides rates per countries in 2015

Suicides per 100,000 people per year (age standardized)
Both sexes
rank
Country Both sexes Male
rank
Male Female
rank
Female Male to Female
ratio
1  Sri Lanka (more info) 34.6 1 58.8 9 13.3 4.42
2  Guyana (more info) 30.6 5 46.0 1 15.5 2.97
3  Mongolia 28.1 2 48.2 21 9.2 5.24
4  Kazakhstan (more info) 27.5 3 48.1 17 9.6 5.01
5  Cote d’Ivoire 27.2 8 38.8 3 14.4 2.69
6  Suriname 26.9 6 41.6 11 12.6 3.3
7  Equatorial Guinea 26.6 7 39.1 10 13.2 2.96
8  Lithuania (more info) 26.1 4 47.1 30 8.1 5.81
9  Angola 25.9 9 38.1 5 14.3 2.66
10  South Korea (more info) 24.1 10 36.1 8 13.4 2.69
11  Sierra Leone 22.1 16 29.7 2 14.7 2.02
12  Bolivia 20.5 21 26.7 3 14.4 1.85
13  Central African Republic 19.6 15 30.3 20 9.3 3.26
14  Belarus 19.1 11 35.0 81 5.4 6.48
15  Poland 18.5 12 32.7 93 4.9 6.67
16  Zimbabwe 18.0 20 26.9 12 10.3 2.61
17  Russia (more info) 17.9 13 32.2 72 5.6 5.75
17  Swaziland 17.9 18 27.3 17 9.6 2.84
19  Cameroon 17.5 19 27.1 26 8.5 3.19
20  Latvia 17.4 14 31.9 95 4.8 6.65
21  Ukraine (more info) 16.6 17 28.7 54 6.2 4.63
22  Burkina Faso 16.5 25 25.1 13 10.1 2.49
23  Belgium 16.1 30 23.4 23 9.1 2.57
24  India (more info) 16.0 65 17.9 7 14.2 1.26
25  Hungary 15.7 23 25.8 42 6.9 3.74
26  Japan (more info) 15.4 36 21.7 21 9.2 2.36
26  Togo 15.4 32 23.1 25 8.7 2.66
28  Uruguay 15.2 24 25.2 49 6.3 4.0
28  North Korea 15.2 72 17.3 6 14.3 1.21
30  Nigeria 15.1 42 20.3 14 9.9 2.05
31  Slovenia 15.0 26 24.5 60 6.0 4.08
31  Benin 15.0 33 22.7 28 8.4 2.7
33  Estonia 14.9 22 26.4 95 4.8 5.5
34  Kiribati 14.8 29 23.6 46 6.6 3.58
35  Finland 14.2 37 21.4 39 7.2 2.97
35  Chad 14.2 38 20.9 32 7.9 2.65
37  Laos 14.0 53 18.5 14 9.9 1.87
38  Argentina 13.9 28 23.7 95 4.8 4.94
39  Lesotho 13.6 45 19.9 29 8.2 2.43
40  Eritrea 13.2 30 23.4 81 5.4 4.33
40  Trinidad and Tobago 13.2 34 22.4 103 4.5 4.98
42  Burundi 13.0 42 20.3 49 6.3 3.22
43  Mozambique (more info) 12.9 41 20.5 43 6.7 3.06
44  Ethiopia 12.8 39 20.7 72 5.6 3.7
44  Cambodia 12.8 65 17.9 26 8.5 2.11
46  Thailand 12.7 58 18.2 33 7.7 2.36
46  Sweden 12.7 68 17.8 35 7.6 2.34
48  Uganda 12.6 56 18.3 35 7.6 2.41
48  United States (more info) 12.6 46 19.5 66 5.8 3.36
48  Rwanda 12.6 27 24.3 119 3.5 6.94
48  Botswana 12.6 46 19.5 54 6.2 3.15
52  Moldova 12.5 35 22.3 112 3.9 5.72
52  Gabon 12.5 60 18.1 40 7.0 2.59
54  Comoros 12.3 74 17.2 31 8.0 2.15
54  France (more info) 12.3 51 19.0 64 5.9 3.22
54  New Zealand 12.3 52 18.7 49 6.3 2.97
54  South Africa 12.3 39 20.7 90 5.1 4.06
58  Democratic Republic of the Congo 12.2 72 17.3 38 7.3 2.37
59  Bhutan (more info) 12.1 100 13.9 14 9.9 1.4
59  Serbia 12.1 46 19.5 77 5.5 3.55
59  Croatia 12.1 49 19.2 69 5.7 3.37
62  Papua New Guinea 11.9 60 18.1 64 5.9 3.07
62  Congo 11.9 65 17.9 58 6.1 2.93
62  Cape Verde 11.9 53 18.5 40 7.0 2.64
65  Iceland 11.8 74 17.2 49 6.3 2.73
65  Senegal 11.8 44 20.2 86 5.2 3.88
67  Austria 11.7 53 18.5 84 5.3 3.49
67  Haiti 11.7 70 17.7 60 6.0 2.95
69  Gambia 11.6 87 15.5 33 7.7 2.01
70  Sudan 11.4 78 16.6 49 6.3 2.63
70  Guinea 11.4 87 15.5 37 7.5 2.07
72  Zambia 11.2 58 18.2 91 5.0 3.64
72  Bulgaria 11.2 56 18.3 95 4.8 3.81
72  Micronesia 11.2 85 15.7 43 6.7 2.34
75  Ireland 11.1 63 18.0 108 4.2 4.29
76  Tanzania 11.0 79 16.5 66 5.8 2.84
76  El Salvador 11.0 49 19.2 106 4.4 4.36
76  Maldives 11.0 110 13.1 24 8.9 1.47
79  Ghana 10.9 68 17.8 112 3.9 4.56
80  Malawi 10.8 63 18.0 95 4.8 3.75
80  Djibouti 10.8 90 15.4 48 6.5 2.37
82   Switzerland 10.7 87 15.5 60 6.0 2.58
83  Czech Republic 10.6 70 17.7 112 3.9 4.54
84  Kenya 10.5 76 17.1 103 4.5 3.8
84  Cuba 10.5 77 17.0 108 4.2 4.05
84  Mali 10.5 95 14.5 43 6.7 2.16
87  Australia 10.4 91 15.3 72 5.6 2.73
87  Canada (more info) 10.4 91 15.3 72 5.6 2.73
87  Namibia 10.4 80 16.4 77 5.5 2.98
90  Turkmenistan 10.3 84 15.8 86 5.2 3.04
90  Liberia 10.3 82 16.1 93 4.9 3.29
92  Slovakia 9.9 60 18.1 141 2.5 7.24
92  Paraguay 9.9 102 13.7 58 6.1 2.25
94  Nicaragua 9.8 83 15.9 108 4.2 3.79
94  Mauritania 9.8 95 14.5 69 5.7 2.54
96  South Sudan 9.6 97 14.3 81 5.4 2.65
97  Guinea-Bissau 9.5 104 13.6 66 5.8 2.34
98  Solomon Islands 9.4 102 13.7 91 5.0 2.74
98  Netherlands 9.4 111 12.9 60 6.0 2.15
98  Timor-Leste 9.4 109 13.2 72 5.6 2.36
98  Yemen 9.4 114 12.6 54 6.2 2.03
102  Norway 9.3 111 12.9 69 5.7 2.26
103  Romania 9.2 80 16.4 141 2.5 6.56
103  Uzbekistan 9.2 104 13.6 86 5.2 2.62
105  Chile 9.1 91 15.3 125 3.3 4.64
105  Germany 9.1 100 13.9 103 4.5 3.09
105  Denmark 9.1 106 13.5 101 4.7 2.87
108  Fiji 8.9 106 13.5 107 4.3 3.14
109  Mauritius 8.8 99 14.0 116 3.7 3.78
110  Montenegro 8.7 118 12.4 84 5.3 2.34
110  Seychelles 8.7 85 15.7 158 1.9 8.26
112  Somalia 8.6 113 12.7 95 4.8 2.65
112  Turkey 8.6 114 12.6 101 4.7 2.68
112  Singapore 8.6 121 11.9 77 5.5 2.16
115  Luxembourg 8.5 123 11.6 86 5.2 2.23
115  Portugal 8.5 97 14.3 116 3.7 3.86
115  China (more info) 8.5 146 7.7 19 9.5 0.811
115  Niger 8.5 124 11.5 77 5.5 2.09
119  Belize 8.3 94 14.7 153 2.0 7.35
120  Kyrgyzstan 8.2 108 13.4 122 3.4 3.94
121  Madagascar 8.0 117 12.5 112 3.9 3.21
122  Ecuador 7.6 124 11.5 116 3.7 3.11
123  United Kingdom (more info) 7.4 122 11.7 129 3.2 3.66
124  Costa Rica 7.3 114 12.6 153 2.0 6.3
124  Dominican Republic 7.3 119 12.2 139 2.6 4.69
126    Nepal (more info) 7.2 142 8.2 54 6.2 1.32
126  Vietnam 7.2 127 11.3 122 3.4 3.32
128  Afghanistan 7.1 128 10.9 130 3.1 3.52
129  Samoa 7.0 126 11.4 136 2.8 4.07
129  Vanuatu 7.0 129 10.8 125 3.3 3.27
131  Bahrain 6.9 135 9.5 132 2.9 3.28
132  Saint Lucia 6.7 120 12.0 164 1.6 7.5
133  Malaysia 6.5 135 9.5 122 3.4 2.79
134  Republic of Macedonia 6.4 132 9.9 130 3.1 3.19
135  Bangladesh (more info) 6.0 161 5.3 46 6.6 0.803
135  Brazil 6.0 134 9.6 138 2.7 3.56
135  Colombia 6.0 130 10.1 150 2.1 4.81
135  Spain 6.0 137 9.4 132 2.9 3.24
135  Peru 6.0 138 9.2 132 2.9 3.17
135  Libya 6.0 138 9.2 136 2.8 3.29
141  Qatar 5.7 147 7.3 170 1.2 6.08
142  Panama 5.6 130 10.1 173 1.1 9.18
143  Israel 5.4 140 8.7 147 2.3 3.78
143  Italy 5.4 140 8.7 148 2.2 3.95
143  Tunisia 5.4 151 6.7 111 4.1 1.63
146  Georgia 5.3 133 9.7 166 1.5 6.47
147  Morocco 5.2 150 7.0 119 3.5 2.0
148  Malta 5.0 142 8.2 153 2.0 4.1
148  Mexico 5.0 144 8.1 150 2.1 3.86
150  Tajikistan 4.9 148 7.2 141 2.5 2.88
151  Oman 4.8 153 6.4 153 2.0 3.2
152  Armenia 4.6 145 8.0 161 1.8 4.44
153  Myanmar 4.5 154 5.9 125 3.3 1.79
154  Bosnia and Herzegovina 4.4 149 7.1 159 1.9 3.74
155  Honduras 4.2 155 5.8 139 2.6 2.23
156  Iraq 4.1 169 4.8 119 3.5 1.37
156  Kuwait 4.1 157 5.7 150 2.1 2.71
156  Tonga 4.1 166 5.1 125 3.3 1.55
159  Cyprus 3.9 151 6.7 176 1.0 6.7
159  Jordan 3.9 161 5.3 144 2.4 2.21
159  Saudi Arabia 3.9 158 5.5 148 2.2 2.5
162  Albania 3.8 161 5.3 144 2.4 2.21
162  Philippines 3.8 155 5.8 159 1.9 3.05
164  Iran 3.6 172 4.2 132 2.9 1.45
165  Greece 3.2 159 5.4 170 1.2 4.5
165  Syria 3.2 165 5.2 170 1.2 4.33
167  Venezuela 3.1 159 5.4 173 1.1 4.91
167  Algeria 3.1 167 5.0 168 1.3 3.85
167  Egypt 3.1 170 4.5 161 1.8 2.5
167  Azerbaijan 3.1 161 5.3 173 1.1 4.82
167  Lebanon 3.1 174 4.0 153 2.0 2.0
172  Indonesia 3.0 170 4.5 164 1.6 2.81
173  United Arab Emirates 2.8 175 3.6 177 0.9 4.0
174  Guatemala 2.7 172 4.2 166 1.5 2.8
175  Sao Tome and Principe 2.6 175 3.6 163 1.7 2.12
175  Saint Vincent and the Grenadines 2.6 168 4.9 179 0.4 12.2
177  Pakistan 2.5 179 2.5 144 2.4 1.04
178  Bahamas 1.6 177 2.9 180 0.4 7.25
179  Brunei 1.4 180 1.4 168 1.3 1.08
179  Jamaica 1.4 178 2.6 181 0.3 8.67
181  Grenada 0.4 182 0.0 178 0.5 0.0
182  Barbados 0.3 181 0.5 182 0.1 5.0

https://en.wikipedia.org/wiki/List_of_countries_by_suicide_rate

Insomnia Associated With Increased Risk of Suicidality

Summary: According to researchers, people with insomnia are more likely to report thoughts of death and suicide during a 30 day period than those who don’t suffer from sleep disturbances.

Source: University of Pennsylvania.

Findings explain the association between suicidality and different groups of insomnia sufferers, which may reveal insights for intervention of those most at risk.

People who suffer from insomnia are three times more likely to report thoughts of suicide and death during the past 30 days than those without the condition, reports a new meta-analysis from researchers at the Perelman School of Medicine at the University of Pennsylvania. The study is the first to control for depression and anxiety and evaluate in-depth the relationship between the broadly defined terms of insomnia and suicidality to reveal trends that may inform future targeted treatment for 32 million individuals struggling with insomnia in the United States each year. The findings will be presented at SLEEP 2017, the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS).

The researchers evaluated self-report survey data assessing insomnia, depression, and anxiety symptoms among 1,160 U.S. Army servicemembers (84 percent male and average age of 31). Controlling for anxiety and depression, the researchers mapped suicidality into multiple dimensions: thoughts of killing oneself, having a plan to commit suicide, intention to kill oneself, thoughts of death (wishing you were dead), and telling people you want to commit suicide. They separated insomnia sufferers into sub-groups – those who have so-called global insomnia (insomnia as a general term), initial (trouble falling asleep at the beginning of the night), middle (trouble maintaining sleep), and terminal insomnia (waking too early from sleep), and nocturnal awakenings (frequently waking up at night) – and studied the association between each of those subgroups and dimensions of suicidality.

The team found that 2.3 percent of those in the population without insomnia reported any indices of suicidality, while 13.1 percent of those experiencing insomnia reported at least one type of suicidality. The group also found a significant association between insomnia and suicide (which echoes earlier studies), but the new research parsed out the broad concepts of insomnia and suicide to explain what aspects of these two are related in a population of military personnel.

Even after eliminating the established role of depression and anxiety in suicide, people who suffer from insomnia are three times more likely to report thoughts of suicide and death during the past 30 days. Insomnia was also found to be a significant predictor for suicidality. Although waking up multiple times throughout the night was significantly associated with greater suicidal ideation, the team was surprised that having difficulty maintaining sleep in the middle of the night was actually associated with a lower likelihood of having thoughts of suicide or having a suicidal plan. This does not mean that those at risk for suicide should try keeping themselves up during the middle of the night, however.

The association between awakenings and suicidality follows senior author Michael Perlis’ “sleep of reason” hypothesis, such that, risk for suicidality is highest as someone is awake with insomnia at night when their ability to reason, think rationally, and engage in impulse control are lowest. The team’s findings suggest that the increased awakenings at night and the decreased executive function associated with it foster dimensions of suicidality in those who are pre-disposed to thinking about committing suicide.

“It’s a bad thing to be awake when reason sleeps,” said Michael Perlis, PhD, an associate professor of Psychiatry and director of the Behavioral Sleep Medicine program, and senior author on the research. “Being awake at night, coupled with the decreased frontal lobe function that happens with sleep loss may explain the mechanism for how insomnia relates with suicide risk.”

Frequently waking up throughout the night was the only type of insomnia associated with four of the five dimensions of suicidality. One possible explanation for this finding may be that it is related to other comorbid conditions, such as obstructive sleep apnea and chronic pain.

“Middle insomnia might give them an external factor to attribute to their distress,” said Ivan Vargas, PhD, a postdoctoral fellow and first author of abstract. “Most of the participants in this study were not presently depressed – so they’re less likely to internalize stress and subsequently experience suicidal ideation. Following a night of insomnia, they may be more likely to attribute any daytime impairment to their poor sleep and not to themselves. In this case, insomnia would buffer their negative attributions about themselves and lower their risk for suicidality. This really speaks to the dynamic relationship between insomnia and depression in predicting suicidality. ”

Image shows an alarm clock.

The authors note that further research may benefit from studying this in additional populations, or in a majority female population.

Previous research from the Perlis team has shown that suicides are more likely to occur after midnight than during the daytime or evening and another study showing that more sleep reduces suicide risk in those with insomnia.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

In addition to Vargas and Perlis, additional authors on #0409 include Amy Gencarelli, from Penn, Alexandria Muench from the Philadelphia College of Osteopathic Medicine, Elaine Boland from the Cpl. Michael J. Crescenz VA Medical Center, Jennifer R. Goldschmied from Penn, and Philip Gehrman, from Penn and the Cpl. Michael J. Crescenz VA Medical Center, and additional authors on (#0422) include Amy Gencarelli, from Penn, Waliuddin Khader, from Penn, Alexandria DiGuiseppe from the Philadelphia College of Osteopathic Medicine, Jennifer Goldschmied from Penn, Elaine Boland from the Cpl. Michael J. Crescenz VA Medical Center, and Philip Gehrman from Penn and the Cpl. Michael J. Crescenz VA Medical Center.

Source: Gregory Richter – University of Pennsylvania
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: The research will be presented at SLEEP 2017, the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS) in Boston.

The stop-smoking pill made me do it: Man found not criminally responsible for shooting wife

by Tom Jackman

The smoking-cessation drug Chantix has now played a crucial role in a second violent crime. On Monday, a Maryland man was found not criminally responsible for shooting his wife in the neck in their home in 2014 because he was found to be suffering from “involuntary intoxication” due to Chantix. His wife survived.

Last year, an Army soldier, who brutally stabbed another soldier to death in 2008, won a new hearing because the judge in his original trial refused to let him put on an involuntary intoxication defense. The soldier claimed that he was so neurologically disturbed by Chantix that he was not aware of what he was doing. A military court then reduced his sentence from life without parole to 45 years.

Involuntary intoxication is not a new defense, but as we discussed on the True Crime blog in May, it is having more success in courts across the country. Last year in St. Paul, Minn., a woman charged with trying to kill and assault her two small children was released when prosecutors decided that the charges could not stand “in light of the defendant’s involuntary intoxication at the time of the charged incident.” A Columbia, Mo., woman who was convicted of causing a fatal wreck while driving the wrong way on Interstate 70 has been granted a new trial because she may have been secretly given a “date rape” drug before taking the wheel.

The defense did not work in Fairfax County, Va., in May, where a man who had invaded another lawyer’s home, took the lawyer and his wife hostage and then stabbed and shot them, later claimed that his prescribed cocktail of pain and psychiatric medications made him involuntarily intoxicated. A jury disagreed, convicted Andrew Schmuhl and sentenced him to two life sentences plus 98 years.

In Carroll County, Md., lawyers for Keith E. Sluder, 44, appear to be the second ones to specifically invoke Chantix for a successful involuntary intoxication defense. In November 2014, according to the Carroll County Times, Sluder awoke his wife and told her they had to go to his mother’s house. When she followed him up the stairs, he shot her once and tried to shoot her again, but the gun malfunctioned. When a sheriff’s deputy arrived and pointed his gun at Sluder, police said he tried to grab the deputy’s gun. The deputy did not shoot him.

Slider’s lawyer, Lawrence Greenburg, argued at Sluder’s hearing that Chantix caused Sluder to have a chemical imbalance. And prosecutors in New Carroll essentially did not argue with that, which would tend to indicate that their mental health expert examined Sluder and came to the same conclusion. The prosecutors allowed Sluder to enter an Alford plea to assault, and they dropped two counts of attempted murder.

Carroll County Circuit Court Judge Thomas Stansfield found Sluder not criminally responsible for the assault charge and ordered him released from custody Monday, according to the Carroll County Times. The Times reported that the shooting victim and her family pleaded with the judge not to release Sluder, but the judge said he was bound by the definition of not criminally responsible. The family reportedly was not happy with the decision.

Pfizer, the maker of Chantix, has denied that the drug has any neuropsychiatric effects. But McClatchy News Service reported in 2014 that more than 2,000 people had joined in lawsuits against Pfizer for various psychiatric problems, including suicide and suicidal thoughts. Pfizer settled most of them for an estimated total of at least $299 million, McClatchy reported.

These recent developments were greatly troubling to the family of Rick Bulmer, who was an Army recruit at Fort Benning, Ga., in 2008. While Bulmer slept in his bunk one night, Pfc. George D.B. MacDonald suddenly attacked him with a knife, slashed his throat and killed him for no reason. He claimed that the smoking cessation drug had made him delusional. A jury in 2009 convicted him of murder and sentenced him to life without parole.

But in 2014, MacDonald was granted a rehearing because of revelations about Chantix, which he hadn’t been allowed to pursue at trial. McClatchy reported that one week after the judge in MacDonald’s case refused to compel Pfizer to respond to a subpoena, the FDA issued a “black box” warning on Chantix because of its potential for “serious neuropsychiatric” problems. It is the most serious warning a medication can carry and still be sold.


 

A 2013 Cochrane overview and network meta-analysis concluded that varenicline is the most effective medication for tobacco cessation and that smokers were nearly three times more likely to quit on varenicline than with placebo treatment. Varenicline was more efficacious than bupropion or NRT and as effective as combination NRT for tobacco smoking cessation.[2][3]

The United States’ Food and Drug Administration (US FDA) has approved the use of varenicline for up to twelve weeks. If smoking cessation has been achieved it may be continued for another twelve weeks.[4]

Varenicline has not been tested in those under 18 years old or pregnant women and therefore is not recommended for use by these groups. Varenicline is considered a class C pregnancy drug, as animal studies have shown no increased risk of congenital anomalies, however, no data from human studies is available.[5] An observational study is currently being conducted assessing for malformations related to varenicline exposure, but has no results yet.[6] An alternate drug is preferred for smoking cessation during breastfeeding due to lack of information and based on the animal studies on nicotine.[7]

Side effects

Mild nausea is the most common side effect and is seen in approximately 30% of people taking varenicline though this rarely (<3%) results in discontinuation of the medication.[3] Other less common side effects include headache, difficulty sleeping, and nightmares. Rare side effects reported by people taking varenicline compared to placebo include change in taste, vomiting, abdominal pain, flatulence, and constipation. In a recent meta-analysis paper by Leung et al., it has been estimated that for every five subjects taking varenicline at maintenance doses, there will be an event of nausea, and for every 24 and 35 treated subjects, there will be an event of constipation and flatulence respectively. Gastrointestinal side-effects lead to discontinuation of the drug in 2% to 8% of people using varenicline.[8][9] Incidence of nausea is dose-dependent: incidence of nausea was higher in people taking a larger dose (30%) versus placebo (10%) as compared to people taking a smaller dose (16%) versus placebo (11%).[10]

Depression and suicide

In November 2007, the US FDA announced it had received post-marketing reports of thoughts of suicide and occasional suicidal behavior, erratic behavior, and drowsiness among people using varenicline for smoking cessation. Since July 1, 2009, the US FDA has required varenicline to carry a black box warning that the drug should be stopped if any of these symptoms are experienced.[11] The label notes, however, that a pooled analysis of 18 randomized clinical trials including 8,521 people found similar rates of psychiatric events in the treatment and placebo arms, and that similar results have been obtained in four observational studies including 10,000 to 30,000 varenicline users.[12] People are advised to weigh the risks of using varenicline against the benefits of its use, noting that varenicline “has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo.” and that “the health benefits of quitting smoking are immediate and substantial.”[12]

A 2014 systematic review did not find evidence of an increased suicide risk.[13] Other analyses have reached the same conclusion and found no increased risk of neuropsychiatric side effects with varenicline.[2][3]

Cardiovascular disease

In June 2011, the US FDA issued a safety announcement that varenicline may be associated with “a small, increased risk of certain cardiovascular adverse events in people who have cardiovascular disease.”[14]

A prior 2011 review had found increased risk of cardiovascular events compared with placebo.[15] Expert commentary in the same journal raised doubts about the methodology of the review,[16][17] concerns which were echoed by the European Medicines Agency and subsequent reviews.[18][19] Of specific concern were “the low number of events seen, the types of events counted, the higher drop-out rate in people receiving placebo, the lack of information on the timing of events, and the exclusion of studies in which no-one had an event.”

 

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