Major Depressive Disorder, Suicidal Ideation, and Suicide Attempt in Twins Discordant for Cannabis Dependence and Early-Onset Cannabis Use

Background: Previous research has reported both a moderate degree of comorbidity between cannabis dependence and major depressive disorder (MDD) and that early-onset cannabis use is associated with increased risks for MDD. Objective: To examine whether associations between both lifetime cannabis dependence and early cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist after controlling for genetic and/or shared environmental influences. Design: Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence and those discordant for early cannabis use. Setting: General population sample of twins (median age, 30 years). Participants: Two hundred seventy-seven same-sex twin pairs discordant for cannabis dependence and 311 pairs discordant for early-onset cannabis use (before age 17 years). Main Outcome Measures: Self-report measures of DSM-IV-defined lifetime MDD, suicidal ideation, and suicide attempt. Results: Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non-cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs. Conclusions: Comorbidity between cannabis dependence and MDD likely arises through shared genetic and environmental vulnerabilities predisposing to both outcomes. In contrast, associations between cannabis dependence and suicidal behaviors cannot be entirely explained by common predisposing genetic and/or shared environmental predispositions. Previously reported associations between early-onset cannabis use and subsequent MDD likely reflect shared genetic and environmental vulnerabilities, although it remains possible that early-onset cannabis use may predispose to suicide attempt.

The burden of major depression avoidable by longer-term treatment strategies

Background: Major depression is the largest single cause of nonfatal disease burden in Australia. Effective drug and psychological treatments exist, yet are underused. Objective: To quantify the burden of disease currently averted in people seeking care for major depression and the amount of disease burden that could be averted in these people under optimal episodic and maintenance treatment strategies. Design: Modeling impact of current and optimal treatment strategies based on secondary analysis of mental health survey data, studies of the natural history of major depression, and meta-analyses of effectiveness data. Monte Carlo simulation of uncertainty in the model. Setting: The cohort of Australian adults experiencing an episode of major depression in 2000 are modeled through "what if" scenarios of no treatment, current treatment, and optimal treatment strategies with cognitive behavioral therapy or antidepressant drug treatment. Main Outcome Measure: Disability-Adjusted Life Year. Results: Current episodic treatment averts 9% (95% uncertainty interval, 6%-12%) of the disease burden of major depression in Australian adults. Optimal episodic treatment with cognitive behavioral therapy could avert 28% (95% uncertainty interval, 19%-39%) of this disease burden, and with drugs 24% (95% uncertainty interval, 19%-30%) could be averted. During the 5 years after an episode of major depression, current episodic treatment patterns would avert 13% (95% uncertainty interval, 10%-17%) of Disability-Adjusted Life Years, whereas maintenance drug treatment could avert 50% (95% uncertainty interval, 40%-60%) and maintenance cognitive behavioral therapy could avert 52% (95% uncertainty interval, 42%-64%), even if adherence of around 60% is taken into account. Conclusions: Longer-term maintenance drug or psychological treatment strategies are required to make significant inroads into the large disease burden associated with major depression in the Australian population.

Chemoprevention of head and neck cancer with retinoids: a negative result

Objective: To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma. Design: Randomized, double-blind, placebo-controlled trial. Setting: Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to,enter appropriate patients into this trial. Patients: One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment. Interventions: Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for I year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years. Main Outcome Measures: The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured. Results: There was no significant difference in the occurrence of second primary disease (P=.90), the recurrence of primary disease (P=.70), or disease-free time (P=.80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival. Conclusion: With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.

Prolonged effects of a home-based intervention in patients with chronic illness

Background: Data on the long-term benefits of nonspecific disease management programs are limited. We performed a long-term follow-up of a previously published randomized trial. Methods: We compared all-cause mortality and recurrent hospitalization during median follow-up of 7.5 years in a heterogeneous cohort of patients with chronic illness initially exposed to a multidisciplinary, homebased intervention (HBI) (n = 260) or to usual postdischarge care (n = 268). Results: During follow-up, HBI had no impact on all-cause mortality (relative risk, 1.04; 95% confidence interval, 0.80-1.35) or event-free survival from death or unplanned hospitalization (relative risk, 1.03; 95% confidence interval, 0.86-1.24). Initial analysis suggested that HBI had only a marginal impact in reducing unplanned hospitalization, with 677 readmissions vs 824 for the usual care group (mean +/- SD rate, 0.72 +/- 0.96 vs 0.84 +/- 1.20 readmissions/patient per year; P = .08). When accounting for increased hospital activity in HBI patients with chronic obstructive pulmonary disease during follow-up for 2 years, post hoc analyses showed that HBI reduced readmissions by 14% within 2 years in patients without this condition (mean +/- SD rate, 0.54 +/- 0.72 vs 0.63 +/- 0.88 readmission/patient per year; P =. 04) and by 21% in all surviving patients within 3 to 8 years (mean +/- SD rate, 0.64 +/- 1.26 vs 0.81 +/- 1.61 readmissions/ patient per year; P =. 03). Overall, recurrent hospital costs were significantly lower ( 14%) in the HBI group (mean +/- SD, $ 823 +/- $ 1642 vs $ 960 +/- $ 1376 per patient per year; P =. 045). Conclusion: This unique study suggests that a nonspecific HBI provides long-term cost benefits in a range of chronic illnesses, except for chronic obstructive pulmonary disease.