Quality Assessment of Clinical Practice Guidelines for the Prescription of Antidepressant Drugs During Pregnancy

Antidepressant use during the gestational period remains a controversial issue. The objective of this study was to appraise the quality of the available clinical practice guidelines (CPGs) that includes recommendations for antidepressant use during pregnancy. We systematically searched for documents published between January 2000 and September 2010 in MEDLINE / TRIP database and on clearinghouses and main scientific societies websites. Four appraisers evaluated each guideline using the Appraisal of Guidelines for Research and Evaluation tool (AGREE II). Intra-class correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated as an overall indicator of agreement. Twelve CPGs were included from a total of 539 references. Only two guidelines were specifically addressed to pregnant women. The overall agreement among reviewers was high (ICC: 0.94, 95% CI: 0.86-0.98). The mean scores and standard deviation (SD) for each of the AGREE II domains were: scope and purpose: 84.4% (12); stakeholder involvement: 67.4% (29.8); rigor of development: 68.6% (19.8); clarity and presentation: 83.4% (17.4); applicability: 44% (37.3); and editorial independence: 62.1% (30.4). After standardizing the scores of the 12 guidelines, 5 were considered as being “recommended”, 5 as “recommended with modifications, and 2 as “not recommended”. Among the five recommended guidelines, two were specifically conceived to the gestational period. CPGs containing recommendations for antidepressant use during pregnancy were of moderate to high quality. Future guidelines should take into account the observed drawbacks in some domains, and specifically focus a more in depth approach of depression during pregnanc

Depression during Pregnancy : light, seasons and sleep

This thesis focuses on depression during pregnancy, with a special focus on the effects of light, seasons and sleep

Mind and body exercises : associations with mental health, antidepressant medication, autonomic functioning and inflammatory biomarkers

Stress, depression and stress-related mental ill-health are common in societies all over the world, and people tend to use both conventional care within the health care system and complementary treatment methods to handle the related symptoms. Still, there is sparse information on whether, how and when to combine these different treatment modalities, in spite of their relatively widespread use. There is thus a need for increased knowledge on complementary treatment methods among conventional health care professionals, patients, policy- and decision makers, and the general public. An example of complementary methods is so called mind and body exercises (MBE), which include e.g. mindfulness based interventions (MBIs). Aims: The overall aim of this thesis was to map the use of MBE and its associations with health and markers of disease, i.e. prescriptions of psychotropics, and to study if there are any robust effects of MBIs on biomarkers of stress. The findings were thus aimed to enable evidence-based recommendations and personalized treatment strategies. The specific aims were: To identify differential associations regarding gender, age, socioeconomic status, health behaviors, perceived stress, self-rated health, and the purchase of prescribed drugs among people who practice MBE extensively, compared to people who do not practice MBE (study I); To further investigate the temporal relationship between MBE, depressive symptoms, purchase of antidepressant drugs and physical exercise, based on the cross-sectional findings in study I (study II); To evaluate existing data on the effect of standardized mindfulness based interventions on inflammatory biomarkers and autonomic nervous system functioning (assessed by measurements of heart rate variability, HRV), through a systematic review and meta-analysis (study III); To investigate the effects of a Mindfulness Based Childbirth and Parenting intervention on HRV and serum inflammatory marker levels among pregnant women, through an RCT study with an active control group comparison (study IV). Methods: Studies I and II were based on responses from the Swedish Longitudinal Occupational Survey of Health (SLOSH). Measures regarding MBE practice, health behaviors, perceived stress, self-rated health and illnesses were drawn from the SLOSH questionnaire, while data on antidepressant drug purchase for all respondents was obtained from the Swedish Prescribed Drug Register. In study III, a literature search was conducted in collaboration with two experienced university librarians. Literature screening and data extraction were performed independently by two researchers. The methodological quality of included studies was assessed independently by two researchers using the Cochrane Collaboration’s tool for assessing risk of bias. In study IV, first time pregnant women at risk of perinatal depression were randomized to MBCP or an active control treatment. At baseline and post-intervention, participants filled out questionnaires and measures on HRV and inflammatory biomarkers were collected. Results: MBE practice was found to have significant cross-sectional associations with high levels of depressive symptoms and prescribed antidepressant purchases (study I). The temporal investigations of these relationships revealed a more complex picture, where MBE practice itself was not associated with either subsequent antidepressant medication or with subsequent depressive symptoms (study II). No significant effect of standardized MBIs on inflammatory biomarkers or HRV, when compared to active controls, treatment as usual or wait-list controls, was found – neither in the meta-analysis (study III) nor in the randomized controlled study (study IV). Conclusions: The findings from study I and II demonstrate the use MBE among the general population as well as in clinical populations like patients suffering from mental ill-health. In order to gain a deeper understanding of the temporality of these correlations, and to delineate possible beneficial or harmful combinations of psychotropics, MBE and other treatment strategies, further research is needed. The findings from study III and IV highlight the necessity of larger, more rigorously conducted RCTs with standardized MBIs being compared to various forms of active controls, also including more long-term follow-ups, in order to provide evidence-based recommendations, both for self-help use and clinical practices

Racional terapêutico na escolha de antidepressivos: como optimizar a relação benefício-risco?

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.Com a prevalência de patologias do foro psicológico a crescer exponencialmente nas ultimas décadas, uma abordagem mais eficaz à saúde mental tem-se tornado essencial. Os transtornos depressivos são atualmente a maior causa de perda de saúde não fatal. Uma grande parte da população que sofre de distúrbios mentais não tem acesso a cuidados de saúde adequados. Da percentagem de população que tem acesso a terapêutica farmacológica, cerca de um terço é resistente à mesma, e apenas cerca de metade adere à terapêutica. A evolução na área terapêutica da psiquiatria trouxe alguma inovação, e principalmente progresso na relação benefício-risco dos fármacos. Ainda assim, esta encontra-se aquém das necessidades atuais da população que sofre de doenças mentais. Uma grande parte dos doentes tratados com antidepressivos sofre efeitos adversos gastrointestinais, sexuais, neurológicos, alterações no peso e no sono. Muitos destes efeitos são comuns, tendo um forte impacto sobre a qualidade de vida dos doentes. Também a eficácia dos mesmos é limitada, sendo estimado que apenas 50% dos doentes respondam ao tratamento inicial. Torna-se assim urgente não só o desenvolvimento e comercialização de novas opções terapêuticas, como também a otimização da utilização do arsenal terapêutico disponível. A presente monografia procura responder à questão: “Como otimizar a relação benefício-risco de antidepressivos?” abordando o estado da arte da terapêutica antidepressiva, e com base numa revisão de recomendações atuais de associações prestigiadas e publicações recentes. Com um foco na individualização da terapêutica, são reunidas as diferentes estratégias terapêuticas para o tratamento da depressão consoante as especificidades de cada população, nomeadamente para adultos, crianças, adolescentes, mulheres no período peri- e pós-natal, na menopausa, e em populações idosas. A pesquisa realizada tornou ainda evidente a utilidade da testagem farmacogenética para polimorfismos nos citocromos CYP2D6 e CYP2C19 como forma de detetar metabolizadores rápidos ou lentos de antidepressivos, permitindo melhorar os benefícios e reduzir riscos. Por fim, o papel do farmacêutico e dos serviços farmacêuticos prestados à população são colocados em destaque devido à sua importância na deteção de problemas relacionados com os fármacos, otimização da eficácia e aumento da adesão à terapêutica.With the prevalence of mental health disorders rising in the last decade, a more effective approach to addressing mental health is becoming essential. Depressive disorders are the single largest contributor to non-fatal health loss, yet a big percentage of the world’s population has low access to adequate mental care. Of those who do have access, about a third are resistant to pharmacological treatment, and about half do not adhere to therapy. Evolution in the psychiatric therapeutical area brought some innovation throughout the years and with it an improvement of the benefit-risk ratio of medicines. Nonetheless, this relation is still far from the current needs of people suffering from mental disorders. Adverse effects such as sexual dysfunction, weight, sleep, gastrointestinal and neurological disturbances impact the quality of life of many patients taking antidepressants. Efficacy is also limited, with only 50% of patients responding to initial treatment. It is therefore urgent not only to develop and commercialize new therapeutic options but also to optimize the use of the currently available therapeutic arsenal. The present dissertation aims to answer the question “How to maximize the benefit-risk ratio of antidepressants?”, by summarizing antidepressant therapy state of the art and based on a review of current recommendations from prestigious guidelines, as well as other recent publications. Focusing on therapy individualization, best practices for optimizing the use of antidepressants are gathered for specific populations: adults, children and adolescents, women during peri- and post-natal period, menopause, and in the elderly. The literature review also showed that pharmacogenetic testing for CYP2D6 and CYP2C19 polymorphisms is a promising way of detecting slow and fast drug metabolizers, thus enhancing the benefit and reducing risks. Finally, the major role of pharmacists and pharmaceutical care providence is highlighted as essential in the management of depression, to detect drug-related problems, and improve adherence and efficacy of therapy

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records.

BACKGROUND: Although many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant. OBJECTIVE(S): (1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy. DESIGN: Retrospective cohort studies. SETTING: Primary care. PARTICIPANTS: Women treated for psychosis who became pregnant, and their children. INTERVENTIONS: Treatment with antipsychotics, lithium or anticonvulsant mood stabilisers. MAIN OUTCOME MEASURES: Discontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders. DATA SOURCES: Clinical Practice Research Datalink database and The Health Improvement Network primary care database. RESULTS: Prescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy. LIMITATIONS: A few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage. CONCLUSIONS: Psychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics. FUTURE WORK: Future research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme

Price Indexes for Acute Phase Treatment of Depression

Although broad trends in medical spending in the U.S. over the last decade have received widespread attention from policymakers, very little attention has focused on the components of those changes. For many other industries, economists typically divide nominal expenditures by an official government price index to decompose these expenditures into price and quantity components. In this paper we construct a new price index for the treatment of one illness depression. Making use of results from the published clinical literature and from official treatment guideline standards, we identify therapeutically similar treatment bundles. These bundles can then be linked and weighted to construct price indexes for specific forms of major depression. In doing so, we construct CPI and PPI-like medical price indexes that deal with prices of treatment episodes rather than prices of discrete inputs, that are based on transaction rather than list prices, that take quality changes and expected outcomes into account employ current, time-varying expenditure weights in the aggregation computations. We find that regardless of which index number procedure is employed time period the treatment price index for the acute phase of major depression has hardly changed remaining at 1.00 or falling slightly to around 0.97. This index grows considerably less rapidly than the various official PPIs -- thus the price index for the treatment of the acute phase of major depression has fallen over the 1991-95 time period. A hedonic approach to price index measurement yields broadly similar results. These results imply that given a budget for treatment of depression accomplished in 1995 than in 1991. Our results suggest that at least in the case of acute phase major depression, aggregate spending increases are due to a larger number of effective treatments being provided.

The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE).

In pharmacoepidemiology, routinely collected data from electronic health records (including primary care databases, registries, and administrative healthcare claims) are a resource for research evaluating the real world effectiveness and safety of medicines. Currently available guidelines for the reporting of research using non-randomised, routinely collected data—specifically the REporting of studies Conducted using Observational Routinely collected health Data (RECORD) and the Strengthening the Reporting of OBservational studies in Epidemiology (STROBE) statements—do not capture the complexity of pharmacoepidemiological research. We have therefore extended the RECORD statement to include reporting guidelines specific to pharmacoepidemiological research (RECORD-PE). This article includes the RECORD-PE checklist (also available on www.record-statement.org) and explains each checklist item with examples of good reporting. We anticipate that increasing use of the RECORD-PE guidelines by researchers and endorsement and adherence by journal editors will improve the standards of reporting of pharmacoepidemiological research undertaken using routinely collected data. This improved transparency will benefit the research community, patient care, and ultimately improve public health

The Inclusion of Pregnant Women in Clinical Research

In the past three decades, there has been unprecedented growth in medical research utilizing human subjects, with much promise for new treatments that extend life, improve quality of life, and prevent disease and disability. Safe prescribing of drug therapies requires that researchers design clinical trials to test products for the benefit of all persons who are likely to utilize them, not just a limited population. For this reason, it is essential that clinical trials include women, pregnant women, children, and racial minorities, as appropriate, because these populations sometimes exhibit different patterns of response or adverse reactions. Despite some significant progress in including women in clinical research, there is a dearth of sound research data on the safety and efficacy of already approved and commonly used medications for pregnant women. At this point, nearly all medications used to treat illness in pregnant women, including common chronic conditions such as hypertension, depression, diabetes, epilepsy, and cancer, are used off-label; that is, outside of the FDA-approved uses based on clinical trial and post-marketing data. Physicians must make prescribing decisions for their pregnant patients without the benefit of randomized, controlled clinical trials testing the safety and efficacy of drugs in pregnant women or the impact of these products on the health of the fetus. This problem of prescribing in the dark is receiving some attention in the medical and scientific community, but progress appears slow. Meanwhile, pregnant women face the difficult choice between taking untested drugs or foregoing necessary pharmacotherapy during pregnancy, potentially to the detriment of both woman and fetus. The default position — to exclude pregnant women from clinical research — is untenable. Although serious challenges in study design, institutional review board (IRB) oversight, and research participant safety make the thought of research in pregnant women daunting, it is important to find ways to test commonly used drugs in pregnant patients. Postponing action until consensus on the ethical and regulatory issues can be achieved is no solution. Women get ill while pregnant or become pregnant while suffering from chronic illness, and therefore must sometimes take prescription and non-prescription medications. Researchers must, therefore, design and implement clinical trials and other types of data collection techniques for both new and already-approved drugs and therapies that will generate data for the safe use of these drugs for pregnant women and their fetuses. This article will describe the current status of inclusion of pregnant women in research, and will discuss some of the FDA-related regulatory barriers to collecting safety and efficacy information and approaches to improve the availability of data to support safe drug prescribing during pregnancy. Finally, although pro-life constituencies have significant influence on health policy, efforts to improve the quality and quantity of safety data should not bow to external, non-science-based attempts at interference with these goals