Acetaminophen (paracetamol) is the most commonly used analgesic worldwide and recommended as first-line treatment in all pain conditions by WHO. We performed a systematic literature review to evaluate the efficacy of acetaminophen when used for chronic pain conditions. Applying three broad search strategies for acetaminophen use in chronic pain in both Embase and PubMed, 1551 hits were obtained. After cross-reference searches of both trials and 38 reviews, seven studies comparing acetaminophen in continuous dosing regimens of more than 2 weeks with placebo were included. The review was conducted according to the PRISMA guidelines. All studies were conducted in patients with hip-or knee osteoarthritis and six of seven studies had observation periods of less than 3 months. All included studies showed no or little efficacy with dubious clinical relevance. In conclusion, there is little evidence to support the efficacy of acetaminophen treatment in patients with chronic pain conditions. Assessment of continuous efficacy in the many patients using acetaminophen worldwide is recommended.Acetaminophen (paracetamol) has been widely endorsed as a first-line analgesic and is currently the most commonly used analgesic worldwide (1). As an example, 9.6% of all Danes obtained acetaminophen via prescription in 2013, with the prevalence rising to an astonishing 23% among 65-to 79-yearolds and 45% among octogenarians (2). The recommendation of using acetaminophen has been generalized by the World Health Organization (WHO), suggesting acetaminophen as the first step in any pharmacological pain treatment (3). Similarly, acetaminophen is recommended as first-line treatment in many chronic pain conditions such as osteoarthritis (4) and for geriatric patients in general (5). The wide endorsement of acetaminophen is primarily attributable to a favourable safety profile compared with other treatment options (6), and the notion that acetaminophen has an efficacy comparable with non-steroid anti-inflammatory drugs (NSAIDs) -the latter primarily based on a highly cited study from 1991 by Bradley et al. (7).While a solid evidence base exists for the use of acetaminophen in acute pain states such as dental and post-operative pain (8), post-partum pain (9) and migraine (10), the evidence supporting its use in chronic pain conditions is less obvious. In a pivotal and often cited study from 1983, Amadio and Cummings showed that acetaminophen was superior to placebo in patients with osteoarthritis (OA) (11). While this cross-over study was only based on 25 patients, it has served as a basis for subsequent investigations, and as such, later studies often compare acetaminophen directly to NSAIDs (12) or COX2 inhibitors (12), without including an arm receiving placebo.Considering the widespread and often long-term use of acetaminophen, it is of major public health importance to ensure that this use is founded on solid evidence regarding efficacy. To this end, we conducted a systematic literature review to assess the efficacy of acetamin...

To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first-trimester exposure and pregnancy outcome with respect to congenital malformations. Cumulated data for olanzapine were 1090 first-trimester-exposed pregnancies with 38 malformations resulting in a malformation rate of 3.5%. The corresponding numbers for quetiapine, risperidone and aripiprazole were 443/16 (3.6%), 432/22 (5.1%) and 100/5 (5.0%), respectively. Relative risk estimates and 95% confidence intervals were 1.0 (0.7-1.4) (olanzapine), 1.0 (0.6-1.7) (quetiapine), 1.5 (0.9-2.2) (risperidone) and 1.4 (0.5-3.1) (aripiprazole). First-trimester exposure to olanzapine is not associated with an increased risk of congenital malformation. Data for quetiapine and risperidone do not suggest a substantially increased risk, while the risk estimate for aripiprazole remains imprecise owing to a low amount of data.

BackgroundEstimating the true risk of fetal malformations attributable to the use of medications is difficult and perception of risk by health professionals will impact their counseling and treatment of patients who need medication during pregnancy. The objective of this study was to assess the perception of the teratogenic risk of 9 commonly and 3 rarely prescribed drugs among general practitioners and specialists in obstetrics/gynecology.MethodsAll 811 general practitioners in the Region of Southern Denmark and all 502 specialist obstetricians/gynecologists in Denmark as a whole were invited to participate in the study based on an online questionnaire. Medians and interpercentile ranges of the perceived background risk and perceived risks for each of the drugs were included in the questionnaire.ResultsOne hundred forty three (18 %) general practitioners and 138 (27 %) obstetricians/gynecologists participated. Estimates provided by the participants were generally in accordance with current knowledge of drugs with established safety during pregnancy. Perceptions of risks associated with warfarin and retinoid exposure were severely underestimated.ConclusionsUnderstanding of teratogenic background risk and specific risks associated with in utero exposure to 12 different drugs generally approached the established knowledge. The risk associated with warfarin and retinoid exposure was severely underestimated by both groups of health care professionals, while general practitioners specifically overestimated the risk of sertraline and citalopram to some extent. In Denmark, general practitioners can prescribe antidepressants, and even minor misconceptions of the teratogenic potential of citalopram and sertraline may be of clinical relevance. In Denmark, systemic retinoids can only be prescribed by a dermatologist, and warfarin treatment is only rarely initiated in women of the fertile age without involvement of specialists in internal medicine. Hence, the active knowledge on the teratogenic potential of these drugs is likely to be less accurate among general practitioners and obstetricians/gynecologists; although still of clinical importance since these specialists are largely involved in the counselling of pregnant women.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-1025-6) contains supplementary material, which is available to authorized users.

Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective Serotonin reuptake inhibitors, SSRIs, a vast amount of data are available. For the newer antidepressant group of serotonin and noradrenaline reuptake inhibitors, SNRIs, significantly less data are available. Following the PRISMA guideline for systematic reviews, we performed a systematic search on the risk of major congenital malformations after first trimester in utero exposure to venlafaxine or duloxetine. We identified eight cohort studies reporting on the outcome upon in utero exposure to venlafaxine or duloxetine during the first trimester. The cumulated data for venlafaxine were 3186 exposed infants and 107 major malformations, resulting in a relative risk estimate and 95% confidence interval of 1.12 (0.92-1.35). The corresponding data for duloxetine were 668 infants and 16 major malformations, resulting in a relative risk estimate and 95% confidence interval of 0.80 (0.46-1.29). First-trimester in utero exposure to venlafaxine is not associated with an increased risk of major congenital malformations. The amount of data for duloxetine are significantly smaller but does not suggest a clinically important increased risk.Depression is common among women of child-bearing age. Approximately 20% of all women of child-bearing age will experience a depression during their life time, and 1% to 8% will use an antidepressant drug during pregnancy [1]. Untreated depression during pregnancy carries risk of severe consequences to the pregnant mother and her unborn child such as: epidural analgesia, caesarean section, intensive ward admission, preterm delivery, low birthweight, and disturbances in the child's neurocognitive and socio-emotional development [2]. Untreated depression during pregnancy increases the risk of post-partum depression 6-fold [3,4].The controversy of possible untoward foetal effects after in utero exposure to selective serotonin receptor inhibitors (SSRIs) has been ongoing for more than a decade. Data on more than 50,000 first-trimester SSRI-exposed newborn have accumulated, and it is accepted that first-trimester exposure to any antidepressant does not result in an overall increased risk of congenital malformations. The risk of cardiovascular malformations is still somewhat unclear, but if true, absolute risks are minor and may pertain to specific SSRIs, especially paroxetine and fluoxetine [5][6][7][8][9][10]. Comparatively, pregnancy data on the newer combined serotonin/noradrenaline receptor inhibitors (SNRI), venlafaxine and duloxetine, are scarce. A recent large Scandinavian study did not suggest an increased risk associated with venlafaxine [10], and a recent commentary concluded that the amount of information for duloxetine was too little [11].Current guidelines are vague and offer little decision support. The NICE guideline does not distinguish between the various types of antidepressants and offers no direct suggestio...