Association of suicide and antidepressant prescription rates in Japan, 1999-2003.
ABSTRACT We examined the relationship of increasing prescription volume of newer antidepressants, introduced in Japan in 1999, to national rates of suicide.
The relationship between annual changes in rates of suicide (obtained from the Japanese Ministry of Health, Labor, and Welfare Vital Statistics Database) and prescription volume of the newer antidepressants paroxetine, fluvoxamine, and milnacipran (obtained from the database of IMS Japan K.K.), stratified by gender and age groups, was modeled statistically for the years 1999 through 2003. Effects of unemployment and alcohol consumption and the interaction of gender and age with antidepressant prescribing were assessed.
From 1999 through 2003 in Japan, total antidepressant prescriptions increased 57% among males and 50% among females. Approximately 80% of this increase involved the selective serotonin reuptake inhibitors (SSRIs). To reduce a limitation of ecological analysis, we compared annual change in prescription and suicide rates, which eliminates the effect of long-term (secular) linear trends. We found an inverse association between year-to-year changes in the suicide rate and prescription volume of newer antidepressants (fluvoxamine, paroxetine, and milnacipran) (beta = -1.34, p = .008) and SSRIs specifically (fluvoxamine, paroxetine) (beta = -1.41, p = .019). An increase of 1 defined daily dose of SSRI use/1000 population/day was associated with a 6% decrease in suicide rate. Exploratory analysis suggested a stronger association in males, who experienced a greater increase in antidepressant use. Changes in unemployment and alcohol consumption rates did not explain the association.
In Japan during 1999 through 2003, absent long-term linear trend effects, annual increases in prescribing of newer antidepressant medications, mainly SSRIs, were associated with annual decreases in suicide rates, particularly among males.
SourceAvailable from: Kelly Posner[Show abstract] [Hide abstract]
ABSTRACT: Suicide is a leading cause of death and a public health priority. In an attempt to reduce suicide rates, efforts have focused on detection and management of suicidal patients in primary care settings, given that an estimated 45% of suicide victims see their physician in the month prior to their death. Previous research suggests that limitations exist in primary care physicians' (PCPs) assessment and treatment of suicidal risk. Training programs addressing the detection of suicidal patients and management of suicidal risk in primary care settings have demonstrated significant improvement in practice. Hence, treatments are available to help PCPs assist with suicide prevention. Recent safety warnings about suicidal ideation and behavior associated with youths and young adult antidepressant treatment have led to sharp declines in prescribing, particularly by PCPs. Concern now exists about under-treatment of depression and the subsequent impact on suicide rates. This article reviews recent literature and provides an overview of suicide risk factors and assessment of suicide risk. The importance of assessing and managing suicidal ideation and behavior and risk factors is highlighted.Primary psychiatry 12/2007; 14(12):63-68.
[Show abstract] [Hide abstract]
ABSTRACT: A personalized treatment approach should be considered with the second-generation psychiatric drug mirtazapine because of high frequencies of side effects, including characteristic drowsiness. Plasma concentrations of mirtazapine in patients are influenced by many factors, including polymorphic cytochrome P450 enzymes contributing to its transformation to 8-hydroxymirtazapine and N-demethylmirtazapine. The aim of this study was to investigate the determinant factors for individual variations of metabolic clearance of mirtazapine using in vitro and in vivo methods. In vitro analyses using liver microsomes from individual humans in correlation assays and recombinantly expressed P450 enzymes revealed that CYP2D6 was the major contributor to mirtazapine 8-hydroxylation with high affinity, and that CYP3A5 catalyzed N-demethylation in a similar high-capacity manner to that of CYP3A4. CYP1A2 was a minor contributor to mirtazapine 8-hydroxylation. Metabolic clearance of mirtazapine determined in substrate depletion assays and mirtazapine 8-hydroxylation activities in individual liver microsomes were significantly lower in CYP2D6 intermediate metabolizers (IM) and poor metabolizers (PM) than in extensive metabolizers (EM) (p<0.05). Trough plasma concentration/dose ratios of mirtazapine from 14 patients were significantly higher in the CYP2D6 IM/PM group than in the EM group and were also higher in the CYP3A5 poor-expressors group than in the expressors group (p<0.05). Mirtazapine clearance in pooled human liver microsomes was inhibited by quinidine (a CYP2D6 inhibitor), ketoconazole (a CYP3A inhibitor), and in combination with risperidone and duloxetine, possible coadministered medicines. These results suggested that mirtazapine metabolic clearance could be variously influenced by the CYP2D6 and CYP3A5 genotypes and coadministered drugs in clinical patients. Copyright © 2014. Published by Elsevier Inc.Biochemical Pharmacology 12/2014; DOI:10.1016/j.bcp.2014.11.011 · 4.65 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The association between unemployment rates and population mental health has been studied with contradictory results. We examine the association between unemployment and antidepressants in Stockholm County. Age- and sex-specific monthly data on unemployment and dispensed prescribed antidepressants from January 1998 to January 2008 in Stockholm County were used. The association was studied with bivariate cointegration analysis with stationarity check of the residuals. We found that dispensing of antidepressants was inversely associated with unemployment. One interpretation is that antidepressants have not followed decreasing unemployment rates.The European Journal of Public Health 08/2014; 24(4):666-8. DOI:10.1093/eurpub/cku079 · 2.46 Impact Factor