Levee failures during Hurricane Katrina left 85% of New Orleans flooded, 1,500 dead, and about 400,000 homeless. Three separate investigations into the levee failures have been concluded, yet none of these studies conclusively determined why the St Bernard polder flooded so deeply, despite Team Louisiana’s conclusion regarding early failure of the Mississippi River Gulf Outlet (MRGO) levees. Detailed wave and hydrodynamic modeling reported here reveals the cause of extensive breaching of the MRGO levees and how that created a very efficient conduit of surge water into the heart of the city.

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Background

Depression is overrepresented in smokers.

Objective

To evaluate smoking abstinence and changes in mood and anxiety levels in smokers with depression treated with varenicline versus placebo.

Design

Phase 4, multicenter, parallel, 1:1 allocation, double-blind, randomization trial. Randomization, stratified by antidepressant use and depression score at baseline, was blocked in sizes of 4. (ClinicalTrials.gov: NCT01078298).

Setting

38 centers in 8 countries.

Participants

525 adult smokers with stably treated current or past major depression and no recent cardiovascular events.

Intervention

Varenicline, 1 mg twice daily, or placebo for 12 weeks, with 40-week nontreatment follow-up.

Measurements

Primary outcome was carbon monoxide-confirmed continuous abstinence rate (CAR) for weeks 9 to 12. Other outcomes included CARs assessed during nontreatment follow-up and ratings of mood, anxiety, and suicidal ideation or behavior.

Results

68.4% versus 66.5% of the varenicline and placebo groups, respectively, completed the study. Varenicline-treated participants had higher CARs versus placebo at weeks 9 to 12 (35.9% vs. 15.6%; odds ratio [OR], 3.35 [95% CI, 2.16 to 5.21]; P < 0.001), 9 to 24 (25.0% vs. 12.3%; OR, 2.53 [CI, 1.56 to 4.10]; P < 0.001), and 9 to 52 (20.3% vs. 10.4%; OR, 2.36 [CI, 1.40 to 3.98]; P = 0.001). There were no clinically relevant differences between groups in suicidal ideation or behavior and no overall worsening of depression or anxiety in either group. The most frequent adverse event was nausea (varenicline, 27.0%; placebo, 10.4%). Two varenicline-group participants died during the nontreatment phase.

Limitations

Some data were missing, and power to detect differences between groups was low in rare events. Smokers with untreated depression, with co-occurring psychiatric conditions, or receiving mood stabilizers and antipsychotics were not included.

Conclusion

Varenicline increased smoking cessation in smokers with stably treated current or past depression without exacerbating depression or anxiety.

Primary funding source

Pfizer.

Importance

Improving treatment outcomes for smokers with major depressive disorder (MDD) can have significant public health implications.

Objective

To evaluate the safety and efficacy of smoking cessation pharmacotherapy among smokers with MDD.

Design

Secondary analysis of a randomized, double-blind, active- (nicotine patch) and placebo-controlled trial of 12 weeks of either varenicline or bupropion with a 12-week follow-up.

Participants

Community volunteers 18-75 years of age; smoke 10+ cigarettes/day; with clinically stable MDD (N = 2635) or no psychiatric disorder (N = 4028), from 140 sites in 16 countries.

Intervention

Twelve weeks of pharmacotherapy (placebo [PLA], nicotine replacement therapy [NRT], bupropion [BUP], varenicline [VAR]) plus brief cessation counseling.

Measure(s)

Primary safety outcome: the occurrence of ≥1 treatment-emergent, moderate to severe neuropsychiatric adverse event (NPSAE). Primary efficacy outcome: biochemically confirmed continuous abstinence (CA) during the final 4 weeks of treatment (Weeks 9-12).

Results

A total of 6653 participants (56% female; 39% MDD) ~47 years old. Risk of NPSAEs did not differ by medication for MDD. MDD had higher risk (p < .0001) for NPSAEs than the NPC. Efficacy (6653; intent-to-treat): CA rates for MDD versus NPC respectively were 31.2% versus 38.0% VAR; 23.0% versus 26.1% BUP; 22.6% versus 26.4% NRT; and 13.4% versus 13.7% PLA but no differential treatment effect was noted within the cohorts. All active treatments differed from PLA but VAR showed the largest effect.

Conclusions

Results suggest that for MDD smokers, inclusive of those with recurrent episode, varenicline plus counseling may be the best pharmacological option for the treatment of smoking given its greater efficacy effect size and similar risk of NPSAEs.

Trial registration

ClinicalTrials.gov Identifier: NCT01456936. https://clinicaltrials.gov/ct2/show/NCT01456936.