Michiel E. H. Hemels

Antidepressant Use during Pregnancy and the Rates of Spontaneous Abortions: A Meta-Analysis

BACKGROUND: Due to the high prevalence of depression in women of childbearing age and coupled with the fact that approximately 50% of the pregnancies are unplanned, there is a high chance that these women have been exposed to antidepressants in early pregnancy. OBJECTIVE: To determine baseline rates of spontaneous abortions (SAs) and whether antidepressants increase those rates. METHODS: Rates of SAs in women taking antidepressants compared with non-depressed women were combined into a relative risk using a random effects model. MEDLINE, EMBASE, Healthstar, Toxline, Psychlit, Cochrane database, and Reprotox were searched for studies published in any language from 1966 to 2003. Key words used to identify articles included pregnancy outcome, abortion, miscarriage, spontaneous, antidepressant, depression, and the generic names of each antidepressant and class. Bibliographies, review articles, and reference lists from studies were also used to identify potential articles expected to provide evidence of safety of antidepressants in pregnancy. RESULTS: Of 15 potential articles, 6 cohort studies of 3567 women (1534 exposed, 2033 nonexposed) provided extractable data. All matched on important confounders. Tests found no heterogeneity (χ 2 3.13; p = 0.98), and all quality scores were adequate (>50%). The baseline SA rate (95% CI) was 8.7% (7.5% to 9.9%; n = 2033). For antidepressants, the rate was 12.4% (10.8% to 14.1%; n = 1534), significantly increased by 3.9% (1.9% to 6.0%); RR was 1.45 (1.19 to 1.77; n = 3567). No differences were found among antidepressant classes. CONCLUSIONS: Maternal exposure to antidepressants may be associated with increased risk for SA; however, depression itself cannot be ruled out.

Increased Use of Antidepressants in Canada: 1981–2000

OBJECTIVE: To provide a descriptive analysis of Canadian utilization (prescriptions, cost, cost per prescription) of antidepressants (ATC-code: N06A). METHODS: IMS Canada provided prescription volumes and costs from 1981 to 2000. We analyzed time trends for antidepressants in general and 4 subclasses (tricyclic antidepressants [TCAs], selective serotonin-reuptake inhibitors [SSRIs], dual action antidepressants [DAAs], and monoamine oxidase inhibitors [MAOIs]). Costs were discounted using the consumer price index, adjusting for population growth using data from Statistics Canada. RESULTS: Between 1981 and 2000, total prescriptions increased from 3.2 to 14.5 million. Market share of TCAs (23.7%) and MAOIs (2.1%) remained constant, despite the introduction of the first SSRI, fluoxetine, in 1989. SSRI prescriptions increased to 6.7 million (market share 46.3%). DAA use increased gradually after 1994 to 3.5 million prescriptions (23.9% market share) in 2000. The number of prescriptions expanded (possibly due to SSRIs) by 238%, with an increased cost of

Meta-Analysis of Placebo Rates in Major Depressive Disorder Trials

2.7 billion. Total expenditures for antidepressants increased exponentially, from

A probabilistic cost-effectiveness analysis of escitalopram, generic citalopram and venlafaxine as a first-line treatment of major depressive disorder in the UK

31.4 million in 1981 to

Cost-effectiveness analysis of escitalopram: a new SSRI in the first-line treatment of major depressive disorder in Austria

543.4 million in 2000 (y = 4E — 130e0.1556x [R2 = 0.99]). Cost per prescription increased linearly from

Cost-Effectiveness of Escitalopram versus Citalopram in the Treatment of Severe Depression

9.85 in 1981 to

A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

37.44 in 2000 (y = 1.72x + 7.92 [R2 = 0.96]). CONCLUSIONS: Utilization and costs of pharmacotherapy for depression have increased above the inflation rate and are expected to exceed

Clinical and Economic Factors in the Treatment of Behavioural and Psychological Symptoms of Dementia

1.2 billion (

Quality assessment of meta-analyses of RCTs of pharmacotherapy in major depressive disorder

50 per prescription) in 2005. Increased costs may be due to increased availability of new products with increased safety, efficacy, and acquisition cost; increased number of users; and increasing costs.

Relationship between blood glucose and carotid intima media thickness: A meta-analysis

BACKGROUND: Placebo effects in major depressive disorder (MDD) have received much interest in the medical literature. However, few quantitative analyses have been done in homogeneous populations. OBJECTIVE: To determine efficacy rates for placebo in patients with MDD; to quantify the correlation between efficacy and publication year, as well as between placebo and drug response rates. DESIGN: Searching MEDLINE (1966–December 2000), EMBASE (1998–February 2001), HealthSTAR (1975–December 2000), and Cochrane (1980–December 2000) databases, randomized, placebo-controlled trials were retrieved including patients with MDD as defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd and 4th editions criteria, Hamilton Rating Scale for Depression score ≥18 or Montgomery—Asberg Depression Rating Scale score ≥16, reporting successes as 50% decreases in scores after 6–8 weeks of treatment. Response rates were summarized using a random effects meta-analysis for per protocol (PP) and intent-to-treat (ITT) results. RESULTS: We included 24 of 134 potential studies examining 4459 patients, 1786 on placebo and 2673 on an antidepressant. Placebo response rates were 45.5% (PP) and 26.9% (ITT). Correlations were significant between year and rates (PP rho 0.448, p = 0.042; ITT rho 0.557; p = 0.006), but not for active drugs. Placebo and drug rates were correlated (PP r 0.397, p = 0.020; ITT r 0.539; p = 0.002). CONCLUSIONS: These placebo rates confirm those reported previously, but were from a homogeneous population. Although statistically significant, the correlation between drug and placebo rates was lower than others reported. During the study period, placebo rates increased linearly; active drugs did not. Correlations between placebo and drug response rates reflected moderate to strong effect sizes. We suggest that current methodology has been unsuccessful in achieving unbiased double-blind conditions not influenced by extra-trial factors, including time.