Risk Of Antidepressant Use Research Articles

Management of Postpartum Depression

The mainstays of treatment for peripartum depression are psychotherapy and antidepressant medications. More research is needed to understand which treatments are safe, preferable, and effective. Postpartum depression, now termed peripartum depression by the DSM-V, is one of the most common complications in the postpartum period and has potentially significant negative consequences for mothers and their families. This article highlights common clinical challenges in the treatment of peripartum depression and reviews the evidence for currently available treatment options. Psychotherapy is the first-line treatment option for women with mild to moderate peripartum depression. Antidepressant medication in combination with therapy is recommended for women with moderate to severe depression. Although pooled case reports and small controlled studies have demonstrated undetectable infant serum levels and no short-term adverse events in infants of mothers breastfeeding while taking sertraline (Zoloft) and paroxetine (Paxil), further research is needed including larger samples and long-term follow-up of infants exposed to antidepressants via breastfeeding controlling for maternal depression. Pharmacologic treatment recommendations for women who are lactating must include discussion with the patient regarding the benefits of breastfeeding, risks of antidepressant use during lactation, and risks of untreated illness. There is a growing evidence base for nonpharmacologic interventions including repetitive transcranial magnetic stimulation, which may offer an attractive option for women who wish to continue to breastfeed and are concerned about their infants being exposed to medication. Among severe cases of peripartum depression with psychosis, referral to a psychiatrist or psychiatric advanced practice registered nurse is warranted. Suicidal or homicidal ideation with a desire, intent, or plan to harm oneself or anyone else, including the infant, is a psychiatric emergency, and an evaluation by a mental health professional should be conducted immediately. Peripartum depression treatment research is limited by small sample sizes and few controlled studies. Much work is still needed to better understand which treatments women prefer and are the most effective in ameliorating the symptoms and disease burden associated with peripartum depression.

Antidepressant use and gestational hypertension: does evidence support causality? Reply letter

We thank Grzeskowiak and colleagues [1] for their review of our paper published in the British Journal of Clinical Pharmacology [2]. We agree that our study adds to a growing body of evidence supporting the fact that antidepressant use during pregnancy is increasing the risk of pregnancy-induced hypertension (PIH). However, we strongly feel that further clarification of their comments is needed. Studies on the risk of medication use during pregnancy are observational in nature, and one study alone cannot determine causality; hence, our study was not designed for that purpose and was not interpreted in that way, contrary to what Grzeskowiak and colleagues [1] suggest. Causality is likely to be determined by repetition of the findings between multiple studies on the same or similar research questions. While comparing studies, however, adjusted findings, which reflect the best estimate of association between an exposure (here antidepressant) and an outcome (here PIH), taking into account potential confounders, including the indication for antidepressant use (here depression), should be used. On the contrary, Grzeskowiak and colleagues [1] have used crude estimates, hence biased estimates, to compare our findings with others, resulting in an invalid interpretation. Adjusting for potential confounders, including the underlying indication, our study showed a 53% (P < 0.05) overall increase in the risk of PIH associated with antidepressant use during pregnancy, which is in line with what has been previously reported by Toh et al. [3] (90% increase in risk; P < 0.05). We acknowledge, however, that given the observational nature of our study, residual confounding can remain due to underlying maternal depression. However, Palmsten et al. [4] have shown that depressed women not treated with antidepressants during pregnancy were at the same risk of PIH as pregnant women who were not depressed, and that the increase in the risk of PIH was observed only amongst depressed women treated with antidepressants, leading to the conclusion that the increase in risk is probably due to the antidepressants and not the depression, contrary to what Grzeskowiak and colleagues [1] put forward. It is true that we have no clinical data on the severity of PIH, but we have shown that the majority of cases are pregnant women with gestational hypertension. Stratifying our analyses on a subgroup of cases with pre-eclampsia would have rendered our estimates unstable, similar to what has been reported by Toh et al. [3]. Finally, we disagree with the argument of Grzeskowiak and colleagues [1] concerning the lack of validity of ICD-9 codes for the identification of PIH in the Quebec Pregnancy Registry. As mentioned by De Vera and Berard [2], Ros et al. [5] have reported good predictive values for PIH ICD-9 diagnostic codes in the context of ‘population-based’ data similar to the Quebec Pregnancy Registry. On the contrary, however, Geller et al. [6] have reported validation estimates using data from a single hospital in the USA. One needs to be vigilant when reporting such discrepancies. Indeed, the interpretation of validation estimates of diagnostic codes needs to take into account the population setting, managed care delivery and access to care (diagnoses). The Quebec Pregnancy Registry is very similar to the Swedish Birth Register in this regard, because healthcare is universal in Quebec, and thus the Quebec Pregnancy Registry is population based (contrary to the US system), Quebec has equal access to healthcare (contrary to the USA) and Quebec has standardized prenatal follow-up regardless of underlying disease and socio-economic status (contrary to the USA). The argument that depressed pregnant women are more likely to visit their healthcare provider and therefore obtain a diagnosis of PIH is very unlikely. Indeed, it is well known that depressed women are less likely to visit their physician during and outside of pregnancy. In addition, this argument is even less of an issue when studying an outcome that is intensely investigated during pregnancy, such as PIH, which is systematically scrutinized at every prenatal visit regardless of patient comorbidities. In conclusion, our study was designed to assess the risk of PIH during pregnancy associated with gestational antidepressant use and does not provide any information on benefits of antidepressant use during pregnancy. De Vera and Berard [2] provide one more piece of information useful in the evaluation of the risks of antidepressant use during pregnancy at the patient level. Given the consistency of results between studies published thus far on this topic, it is our belief that more attention should be given to this important maternal comorbidity when prescribing antidepressants to pregnant women.

Initiating therapy with antidepressants after discontinuation of hormone therapy

This work aims to determine whether discontinuation of hormone therapy (HT) in perimenopausal and postmenopausal women is associated with an increased risk of initiating antidepressant therapy. A population-based cohort study was conducted using data from the Swedish Prescribed Drug Register and the Total Population Register for the period July 2005 to June 2009. We included women aged 45 to 70 years who had used HT continuously for more than 6 months before July 2008. Women with previous use of antidepressants since July 2005 were excluded. We compared the incidence rates of initiating antidepressant therapy during HT and after withdrawal of HT. The women were followed from July 2008 until the first dispensing of antidepressants, restart of HT, migration, death, or end of the study period, whichever occurred first. Poisson regression analysis was used to estimate the incidence rate ratios adjusting for potential confounders (age, calendar time, duration of HT use, and number of HT prescriptions). Of the 101,911 women enrolled in the cohort, 39.8% discontinued HT during follow-up. Discontinuation of HT was associated with an increased risk of antidepressant use (incidence rate ratio, 1.24; 95% CI, 1.11-1.38). Women 65 years or older and women who had used HT for 3 years or more had the highest risk estimates, but effect modification by age and duration was not significant. We found a slightly increased risk in the use of antidepressant therapy after discontinuation of HT.

Socioeconomic factors, rather than diabetes mellitus per se, contribute to an excessive use of antidepressants among young adults with childhood onset type 1 diabetes mellitus: a register-based study

Mood disorders, including depression, are suggested to be prevalent in persons with type 1 diabetes and may negatively affect self-management and glycaemic control and increase the risk of diabetic complications. The aim of this study was to analyse the prevalence of antidepressant (AD) use in adults with childhood onset type 1 diabetes and to compare risk determinants for AD prescription among diabetic patients and a group of matched controls. Young adults ≥ 18 years on 1 January 2006 with type 1 diabetes (n = 7,411) were retrieved from the population-based Swedish Childhood Diabetes Registry (SCDR) and compared with 30,043 age- and community-matched controls. Individual level data were collected from the Swedish National Drug Register (NDR), the Hospital Discharge Register (HDR) and the Labor Market Research database (LMR). ADs were prescribed to 9.5% and 6.8% of the type 1 diabetes and control subjects, respectively. Female sex, having received economic or other social support, or having a disability pension were the factors with the strongest association with AD prescription in both groups. Type 1 diabetes was associated with a 44% (OR 1.44, 95% CI 1.32, 1.58) higher risk of being prescribed ADs in crude analysis. When adjusting for potential confounders including sex, age and various socioeconomic risk factors, this risk increase was statistically non-significant (OR 1.11, 95% CI 0.99, 1.21). The risk factor patterns for AD use are similar among type 1 diabetic patients and controls, and socioeconomic risk factors, rather than the diabetes per se, contribute to the increased risk of AD use in young adults with type 1 diabetes.

Association of Cerebrovascular Events With Antidepressant Use: A Case-Crossover Study

The authors sought to assess the risk of cerebrovascular events associated with use of antidepressant medications. The authors conducted a case-crossover study of 24,214 patients with stroke enrolled in the National Health Insurance Research Database in Taiwan from 1998 to 2007. The authors compared the rates of antidepressant use during case and control time windows of 7, 14, and 28 days. Adjustments were made for time-dependent variables, such as health system utilization and proposed confounding medications. Stratified analyses were performed for valuing the interaction between the stroke risk of antidepressant use and age, sex, presence of mood disorder, stroke type, severity of chronic illness, and duration of antidepressant treatment. A conditional logistic regression model was used to determine the odds of antidepressant use during case time windows. The adjusted odds ratio of stroke risk with antidepressant exposure was 1.48 (95% confidence interval=1.37-1.59) using 14-day time windows. Stroke risk was negatively associated with the number of antidepressant prescriptions reported. Use of antidepressants with high inhibition of the serotonin transporter was associated with a greater risk of stroke than use of other types of antidepressants. These findings suggest that antidepressant use may be associated with an increased risk of stroke. However, the underlying mechanisms remain unclear.

Managing Depression During Pregnancy

During the reproductive years, depression is common in women, and many face treatment decisions during pregnancy. Possible risks of untreated maternal depression include increased risk of relapse and postpartum depression, all the serious risks associated with the untreated disorder in nonpregnant women, and obstetrical complications. Data on teratogenic risks of antidepressant use are inconsistent, but these risks should be taken into consideration. Overall, treatment should be individually tailored, and nonpharmacologic options may be appropriate.

Overcrowding in Hospital Wards as a Predictor of Antidepressant Treatment Among Hospital Staff

This report assessed whether hospital ward overcrowding predicts antidepressant use among hospital staff. The extent of hospital ward overcrowding was determined using administrative records of monthly bed occupancy rates between 2000 and 2004 in 203 somatic illness wards in 16 Finnish hospitals providing specialized health care. Information on job contracts for personnel was obtained from the employers' registers. Comprehensive daily data on purchased antidepressant prescriptions (World Health Organization's Anatomical Therapeutic Chemical classification code N06A) for nurses (N=6,699) and physicians (N=641) was derived from national registers. Cox proportional hazards models were used to examine the association between bed occupancy rate and subsequent antidepressant treatment. Monthly bed occupancy rates were used as a time-dependent exposure that could change in value over the course of observation. Hazard ratios were adjusted for sex, age, occupation, type and length of employment contract, hospital district, specialty, and calendar year. Exposure over 6 months to an average bed occupancy rate over 10% in excess of the recommended limit was associated with new antidepressant treatment. This association followed a dose-response pattern, with increasing bed occupancy associated with an increasing likelihood of antidepressant use. There was no evidence of reverse causality; antidepressant treatment among employees did not predict subsequent excess bed occupancy. The increased risk of antidepressant use observed in this study suggests that overcrowding in hospital wards may have an adverse effect on the mental health of staff.

Cardiovascular Risk of Antidepressant Use in Elderly Medicare Beneficiaries: Comparison by Therapeutic Class

Purpose To compare the cardiovascular risk of antidepressant users, cumulatively and by class, to nonantidepressant users in a representative sample of the U.S. elderly population. Methods A historical pooled cohort study of all elderly non-HMO community dwelling Medicare beneficiaries represented in the 1998–1999 and 2000–2001 Medicare Current Beneficiary Survey to assess the incidence of AMI (ICD-9: 410 or 411). Antidepressant users were defined by at least one antidepressant drug mention in the year prior to the year of observation for AMI. Class users were defined as unique users of the corresponding class (SSRI, cyclic, other) according to 2005 U.S. Pharmacopeia therapeutic categories and individuals who switched drug classes at any time during the study were defined as combination users. Logistic regression models were used to compare odds of experiencing an AMI. Covariates included age, sex, race, poverty status, cardiovascular drug therapy, anticoagulant medication therapy, smoking history and current status, poverty status, and the DCG/HCC to adjust for severity, which includes 189 conditions, including depression and related disorders that are treated with antidepressants. Results Antidepressant users numbered 1,905 (584 SSRI users, 388 cyclic users, 111 other users, and 822 combination users). Nonantidepressant users numbered 8,892. The incidence of AMI was 2.1% in the sample, 1.9% in nonantidepressant users, 3% in all antidepressant users, 3.4% in all SSRI users, 2.1% in cyclic users, 1.8% in all other users, and 3.4% in combination users. Logistic models revealed that antidepressant users (OR = 1.46, 95% CI: 1.02–2.08) and SSRI users (OR = 1.86, 95% CI: 1.07–3.22) were found to have significantly greater odds of AMI compared to nonantidepressant users. Conclusion Study findings conflict with previous studies, which have found SSRIs to be AMI protective. Study limitations include its restriction to the Medicare population and the 1-year maximum observation period.

Investigating the relationship between beta-blocker and antidepressant use through linkage of the administrative databases of Saskatchewan Health.

The main objectives of this research were to confirm previous reports of an increased risk of antidepressant use subsequent to propranolol therapy, and to determine whether this higher relative risk (RR) is indicative of depressive symptoms as a side-effect of the drug's use. 'New' users of beta-blockers, other antihypertensives or diuretics in two separate years were identified from records of Saskatchewan Health. Incidence of concurrent antidepressants prescribing was determined in the year after initiating therapy with a cohort drug. Medical claims were examined to identify physician services and diagnoses associated with cohort drug and antidepressant prescriptions. Risk of concurrent antidepressant use in new propanolol users aged 20-39 years was approximately double that of new diuretic users [RR 2.2 (1.5-3.3) in 1984 and 2.0 (1.1-3.5) in 1990/91]. When cases with a diagnosis of migraine headache were excluded, the risk of concurrent propranolol/antidepressant use was age- and sex-dependent, but not consistent for the two study years. It was concluded that although the risk of concurrent antidepressant use was greater in younger propranolol users, the risk cannot be solely attributed to depressive side-effects of the drug. The purposes of this paper were to present the methods employed in linking the databases of Saskatchewan Health, describe the results of the analysis, and to highlight the methodologic problems that arose.

Increased Prescribing of Antidepressants Subsequent to ß-Blocker Therapy

Using records of the Saskatchewan Prescription Drug Plan, we determined the incidence of antidepressant use (a marker for depressive symptoms) in patients who received beta-blockers or other treatments for chronic diseases (diuretics, antihypertensives, and hypoglycemics) during 1984, but not in the previous 6 months. Antidepressants initiated within 12 months after the study drug were counted. Of the 3218 new beta-blocker users, 6.4% received concurrent prescriptions (ie, within 34 days) for an antidepressant and beta-blocker. Only 2.8% of the reference group (no study drug use) received an antidepressant. A greater proportion of patients prescribed propranolol (9.5%) received an antidepressant than those prescribed other "lipophilic" (3.9%) or "hydrophilic" (2.5%) beta-blockers. Incidence ratios for propranolol revealed the overall risk antidepressant use was 4.8 (95% confidence interval [CI], 4.1 to 5.5) times that of the reference group and 2.1 (95% CI, 1.7 to 2.5) times that of all other study drug users. For propranolol, relative risk of antidepressant use (drug/reference group) varied with age and was greatest in the 20- to 39-year-old group (17.2; 95% CI, 13.7 to 21.5).