Declining differences in response rates with antidepressants versus placebo: a modest proposal for another contributing cause.

This column discusses declining differences in response rates between sequentially introduced selective serotonin reuptake inhibitors (SSRI) and placebo. Although discussions of this phenomenon in the literature have largely focused on increasing placebo response rates, the author proposes that another factor may be responsible. That factor is an order effect, meaning that response rates have been declining as a function of the number of SSRIs on the market when the next SSRI is in development. The rationale is that the pool of potential clinical trial participants likely to respond to a drug with this mechanism of action (MOA) becomes progressively smaller with the introduction of each new agent with the same MOA, because many patients will already have been treat- ed and responded to an earlier member of the class. This phenomenon is not limited to the SSRIs but generalizes to any class of treatments that shares the same MOA.

The association between lifting an administrative restriction on antidepressant dispensing and treatment patterns in Iceland.

PURPOSE: On March 1st 2009, restrictions on the dispensing of selective serotonin reuptake inhibitors (SSRI) in Iceland were lifted. Incident rates and changes in early discontinuation and switching before and after the change were investigated. METHODS: New users of antidepressants between March 1st 2006 and March 1st 2010 were selected from the Icelandic Prescriptions Database. The study population was split into one intervention cohort (2009) and three comparison cohorts (2006, 2007, and 2008). Incidence rate ratios (IRR) and odds ratios (OR) were used to compare incidence rates and early discontinuation. RESULTS: The overall incidence rates of antidepressant use decreased from 33.10 to 28.71 per 1000 persons per year (IRR 0.87; 95% confidence interval (CI), 0.78-0.97) from the 2006 to the 2009 cohort. The incidence rate for SSRIs did not change over the period. Early discontinuation for SSRIs increased from 30.2% in 2006 to 34.1% in 2009 (OR 1.19; 95% CI 1.06-1.33). CONCLUSIONS: The change in reimbursement does not seem to have affected incidence rates but it may be related to increased early discontinuation, which can lead to increased drug wastage. It might be more clinically rational to initiate patients on smaller supply, allowing for more frequent check-up visits.

Impact of regional copayment policy on selective serotonin reuptake inhibitor (SSRI) consumption and expenditure in Italy.

PURPOSE: The continuous growth of antidepressant consumption and expenditure, especially for selective serotonin reuptake inhibitors (SSRIs), has led to the adoption of several policy measures directed toward cost control in Western countries. In Italy, copayment policies have been heterogeneously introduced at a regional level as part of a strategy designed to reduce drug consumption. The aim of our study was to evaluate whether regional copayment policies have affected trends in the consumption of and expenditure for SSRIs from 2001 to 2007. METHODS: The consumption of SSRIs was measured in terms of defined daily doses per 1,000 inhabitants (DDD/1000) per day from May 2001 to December 2007. Time trends in consumption and expenditure before and after the introduction of copayment policies were examined using segmented regression analysis of interrupted time-series, adjusting for seasonal components. The study was conducted for 17 regions, nine of which had implemented a copayment policy. RESULTS: The overall consumption of SSRIs in Italy increased during the study period, from a monthly consumption of 12.85 DDD/1000 per day in May 2001 to 23.40 DDD/1000 per day in December 2007. The average monthly increase in SSRI use was 0.82 % in regions with a copayment policy versus 0.77 % in regions without a copayment policy (P = 0.329). According to the multivariable analysis, copayment was associated with a 1 % reduction in the monthly growth rate of SSRI consumption (P = 0.01). The impact of copayment on expenditure was statistically significant (P < 0.005) on both the level and the trend, even though the estimate of the effect was negligible. CONCLUSIONS: The implementation of copayment policies in Italy affected both the use and expenditure of SSRIs between 2001 and 2007 to only to a minor extent.

The relationship between sales of SSRI, TCA and suicide rates in the Nordic countries.

BACKGROUND: In the period 1990-2006, strong and almost equivalent increases in sales figures of selective serotonin re-uptake inhibitors (SSRIs) were observed in all Nordic countries. The sales figures of tricyclic antidepressants (TCAs) dropped in Norway and Sweden in the nineties. After 2000, sales figures of TCAs have been almost constant in all Nordic countries. The potentially toxic effect of TCAs in overdose was an important reason for replacing TCAs with SSRIs when treating depression. We studied whether the rapid increase in sales of SSRIs and the corresponding decline in TCAs in the period 1990-98 were associated with a decline in suicide rates. METHODS: Aggregated suicide rates for the period 1975-2006 in four Nordic countries (Denmark, Finland, Norway and Sweden) were obtained from the national causes-of-death registries. The sales figures of antidepressants were provided from the wholesale registers in each of the Nordic countries. Data were analysed using Fisher's exact test and Pearson's correlation coefficient. RESULTS: There was no statistical association (P = 1.0) between the increase of sales figures of SSRIs and the decline in suicide rates. There was no statistical association (P = 1.0) between the decrease in the sale figures of TCAs and change in suicide rates either. CONCLUSIONS: We found no evidence for the rapid increase in use of SSRIs and the corresponding decline in sales of TCAs being associated with a decline in the suicide rates in the Nordic countries in the period 1990-98. We did not find any inverse relationship between the increase in sales of SSRIs and declining suicide rates in four Nordic countries.

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Urinary incontinence can be treated with medicinal products in addition to active pelvic floor muscle training and electrostimulation. A local hormone therapy should be first discussed with the gynaecologist. The active substance duloxetine has been used for a few years for treating stress incontinence. Several older and newer active substances are available for treating irritable bladder and stress incontinence.

Relationship between antidepressant sales and secular trends in suicide rates in the Nordic countries.

BACKGROUND: The effect of recent increases in antidepressant prescribing on population suicide rates is uncertain. AIMS: To investigate the relationship between antidepressant sales and trends in suicide rates. METHOD: Graphical and quantitative assessment of trends in suicide and antidepressant sales in Norway, Sweden, Denmark and Finland. RESULTS: Suicide rates declined in all four countries during the 1990 s, whereas antidepressant sales increased by 3- to 4-fold. Decreasing suicide rates in Sweden and Denmark preceded the rise in antidepressant sales by over 10 years, although the reductions accelerated between 1988 and 1990. In Norway, a modest but short-lived decline in suicide rates began around the time of the increase in antidepressant sales. In Finland, decreases in male suicide rates and to a lesser extent in female suicide rates began around the time of increased antidepressant sales. In all four countries decreases in suicide rates appeared to precede the widespread use of SSRIs. CONCLUSIONS: We found mixed evidence that increases in antidepressant sales have coincided with a reduction in the number of suicides in Nordic countries.

Mental health care in Japan: recognition and treatment of depression and anxiety disorders.

Despite the apparent high availability of psychiatric services in Japan, the quality and type of care have historically been lower than that provided in Western society. However, Japanese psychiatry is undergoing a period of transition. Recent changes in the provision of health care, the adoption of internationally standardized diagnostic criteria, the availability of newer antidepressant drugs such as selective serotonin reuptake inhibitors, and other social and economic factors mean that psychiatric services are improving at various levels.

Treating depression with selective serotonin reuptake inhibitors: a practical approach.

Depression is a common disorder that is becoming better understood as an illness that can be chronic, recurrent, and refractory to treatment. Depression can produce substantial suffering and profoundly affect a patient's self-esteem, relationships, and functional capacity. The improved adverse-effect profile and safety from overdose of selective serotonin reuptake inhibitors (SSRIs) have led to treatment of milder forms of depression and thus increased treatment of depression overall. This article synthesizes several previously published reviews and psychopharmacology resources and addresses practical issues related to initiating, monitoring, continuing, and discontinuing SSRIs. Precautions related to SSRI use and important considerations for various types of depression are discussed.