Long-term Antidepressant Use Research Articles

Potential deprescribing indications for antidepressants between 2012 and 2019: repeated cross-sectional analysis in two Scottish health boards

BackgroundAntidepressants have a pivotal role in the treatment of many psychiatric disorders, but there are concerns about long-term use and adverse effects. The objectives of this study were (1) to examine time trends in antidepressant use, (2) to estimate the prevalence of long-term and potential high-risk antidepressant use, and (3) to examine patient characteristics associated with potential deprescribing indications (PDIs) (i.e., simultaneous long-term and potential high-risk antidepressant use).MethodsRepeated population-based cross-sectional study for all 609,299 people aged ≥ 18 years resident in the Tayside or Fife regions of Scotland. The prevalence of antidepressant use was examined on June 30th (index date) of each year from 2012 to 2019, while the prevalence of long-term and potential high-risk use as well as PDIs was assessed and compared on the same dates in 2012 and 2019. Binary logistic regression modeling was used to examine patient characteristics associated with PDIs.ResultsAntidepressant use increased by 27% from 12.0 to 15.3% among adult residents between 2012 and 2019. While the proportion of antidepressants users dispensed ≥ 1 antidepressant for > 2 years increased from 54.3 to 61.9% between 2012 and 2019, the proportion of antidepressant users triggering ≥ 1 indicator of potential high-risk use decreased slightly from 37.9 to 34.7%. In 2019, potential high-risk use most commonly related to indicators targeting fall risk (16.0%), cardiovascular risks (14.1%), insomnia (10.6%), and risk of orthostatic hypotension (8.6%). More than 1 in 4 (25.8%) antidepressant users had PDIs. The main risk factors associated with PDIs included increasing age (65–79, adjusted OR 14.12; 95% CI, 13.15–15.17), increasing number of drugs taken concomitantly (≥ 15 drugs, adjusted OR 7.37; 95% CI, 6.71–8.10), use of tricyclic antidepressants (≥ 50 mg) (adjusted OR 5.49; 95% CI, 5.02–6.01), and concomitant use of ≥ 2 antidepressants (adjusted OR 5.52; 95% CI, 5.20–5.85).ConclusionsLong-term and potential high-risk use of antidepressants is widespread, and potential deprescribing indications (PDIs) are increasing, suggesting the need for a critical review of their ongoing use by clinicians. If deemed necessary, future deprescribing interventions may use the criteria applied here for identification of patients with PDIs and for evaluating intervention effectiveness.

Patterns of antidepressant use among older adults in Northern Ireland: An administrative data study.

ObjectiveOver recent decades, there has been a noticeable increase in the prescription of antidepressant medications, particularly among older adults. This study examines the relationship between health outcomes and patterns of antidepressant use among older adults in Northern Ireland (NI). ApproachParticipants included all (General Practitioner) GP-registered hospital patients aged fifty-five years and above on 01/01/2010 (n =395,872). Administrative data linkage included demographic information (age, sex; urbanicity); data on antidepressant use from the NI Enhanced Prescribing Database (EPD); and hospital patient admissions/discharges. Repeated measures latent class analysis (RMLCA) identified patterns of antidepressant use (2010 to 2020) in relation to the association between these patterns and health-related outcomes in 2021. ResultsRMLCA identified four latent classes : long-term antidepressant use (17.4%); decreasing antidepressant use (7.1%); increasing antidepressant use (8.4%); no-antidepressant use (67.1%). Those in the long-term and increasing antidepressant use’ classes had the highest average number of hospital visits and recorded chronic conditions in 2021. ConclusionFindings show that two distinct subgroups (comprising 26% of the hospital population) were disproportionately impacted by increased antidepressant prescription rates. Because of their increased likelihood of experiencing higher ill-health, these people are crucial targets for additional psychosocial support. ImplicationsAnalyses of this kind emphasize the importance of widening access to administrative data, enabling researchers to identify and examine at-risk groups allowing more targeted policymaking to better address their needs. Data for this project was provided by the HSC Honest Broker Service; any views or opinions presented are solely those of the author.

Re-visiting the association between antidepressant use and the risk of lung cancer.

Observational studies suggest a potential correlation between antidepressants and increased lung cancer risks. However, existing studies are limited to small sample sizes, unadjusted covariates especially smoking status, and unclear exposure duration. We performed a large-scale retrospective cohort study to re-examine the association. We analyzed non-smokers and smokers separately to eliminate the confounding effect of smoking status. We found patients with long-term antidepressant use were at a lower risk of lung cancer in both smokers and non-smokers (odds ratio (OR), 0.61; 95% CI: 0.46-0.80, OR: 0.75; 95% CI: 0.65-0.86). None of the antidepressants was associated with an increased lung cancer risk.

IMPACT OF PROLONGED USE OF ANTIDEPRESSANTS ON NEUROPLASTICITY

Antidepressants are widely used in the treatment of depressive and anxiety disorders and are essential for the management of these conditions. However, the impact of prolonged use of these drugs on neuroplasticity - the brain’s ability to reorganize itself, forming new neural connections - has been a topic of growing interest and debate in the scientific community. This abstract addresses the effects of prolonged use of antidepressants on neuroplasticity, considering their implications for long-term mental health. The aim of this paper is to examine and synthesize the scientific evidence on the impact of long-term use of antidepressants on neuroplasticity, with a focus on how these changes can influence the effectiveness of treatment and the long-term prognosis of patients. This study conducts a literature review on the long-term effects of antidepressants on neuroplasticity, investigating both the therapeutic potentials and the associated risks. The review focuses on how neuroplasticity can influence treatment outcomes, tolerance to antidepressants, and the impacts on specific populations, such as the elderly and individuals with hormonal variations. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs), have been shown to influence neuroplasticity in several ways. Pre-clinical and clinical studies suggest that prolonged use of these drugs can promote neurogenesis, particularly in the hippocampus, an area of the brain crucial for memory and learning. This neurogenic effect is associated with an improvement in depressive symptoms and the brain’s ability to adapt to new challenges. In addition, antidepressants appear to increase the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), which plays a vital role in the survival and growth of neurons. The increase in BDNF levels may contribute to the restoration of synaptic connectivity, which is often compromised in patients with depression. However, there is controversy about the long-term effects of continuous use of these drugs on neuroplasticity. Some studies suggest that, despite the initial benefits, prolonged use can lead to a “rigidity” in brain plasticity, making it difficult to adapt to new treatments or therapeutic strategies. In addition, the impact on other areas of the brain, such as the prefrontal cortex, which is involved in decision-making and emotional control, is still poorly understood and requires further research. These findings raise questions about the optimal duration of treatment with antidepressants and the need for continuous monitoring of patients’ long-term mental health. Neuroplasticity may be a crucial factor in individual response to treatment and the possibility of relapse or development of resistance to treatment. Therefore, the prolonged use of antidepressants has a significant impact on neuroplasticity, initially promoting neurogenic effects and an increase in synaptic connectivity, which can improve depressive symptoms. However, the long-term effects still need to be better understood, especially with regard to the possible “rigidity” in brain plasticity and the implications for ongoing treatment. To maximize the benefits and minimize the risks, it is essential that treatment with antidepressants is carefully monitored, with attention to changes in neuroplasticity over time. More research is needed to elucidate the underlying mechanisms and guide clinical practice towards more effective and safer strategies for the management of depression and other related disorders.

Pharmacists' views on discontinuing long-term use of antidepressants and supporting patients during the discontinuation process: a qualitative study.

Long-term antidepressant (AD) use, much longer than recommended by guidelines, may cause harms and generate unnecessary costs. Community pharmacists have frequent contact with AD users and advise them on appropriate and safe medication use. GPs recognised pharmacists as potential sources of additional support for the AD discontinuation process, but there is a lack of knowledge about pharmacists' views. To explore pharmacists' perspectives on discontinuing long-term use of ADs and supporting patients during the discontinuation process and their barriers and facilitators. Qualitative study in Belgian pharmacists. The authors conducted 14 semi-structured face-to-face interviews. Interviews were analysed thematically. The first theme 'Antidepressants at the pharmacy: a persistent taboo' described the challenges pharmacists encounter in initiating discussions with patients about their ADs and mental health, and the persistent taboo around ADs at pharmacies. Second, pharmacists were concerned about the risks associated with AD discontinuation but recognise that harm from continuing ADs may outweigh concerns. Third, although pharmacists can be a starting point for discontinuation, they hesitate to do this and question if this is their role. They prefer that GPs have this responsibility. Deprescribing long-term ADs is a challenging concept for pharmacists, especially when there is no patient request. The taboo around ADs and the fear of relapse of symptoms in a stable patient are important barriers for pharmacists when considering discontinuation. Pharmacist education and confidence-building is essential to involve the pharmacist in the discontinuation process. Findings also highlight a strong need for multidisciplinary collaboration and agreements with GPs to reduce unnecessary antidepressant treatment.

Tardive Dysphoria: can antidepressants cause depression?

Introductiontardive dysphoria is a relatively new term used to describe the phenomenon of clinical worsening of depression after long-term antidepressant use. Most of the theories proposed to explain this talk about antidepressants tachyphylaxis that implies the loss of efficacy with its prolonged use, or even a pro-depressant effect of antidepressants when used for long periods of time.Objectivesto explore the concept of tardive dysphoria, potential causes and clinical implications, by making a literature review on the topic. Moreover we pretend to understand the challenges in its diagnosis and treatment.Methodsbibliographical search in PubMed database, using the key-words “long-term antidepressant”, “tardive dysphoria” and “antidepressant tachyphylaxis”, limited to works published in the last twenty years.Resultsfrom our search resulted 53 articles, 26 were chosen for further analysis.Conclusions the concept of tardive dysphoria is controversial, namely doubt persists if it constitutes a clinical entity by itself caused by long-term antidepressant use or if it simply relates to cases of treatment-resistant depression. We conclude that it is necessary further investigation in this area given the significant implications on clinical practice specifically in the psychopharmacological treatment with antidepressants, which is very common in psychiatric and general practices, with antidepressants being used to treat many mental health conditions.Disclosure of InterestNone Declared

What helps and what hinders antidepressant discontinuation? Qualitative analysis of patients' experiences and expectations.

Many patients with depressive disorders use antidepressants longer than clinically indicated. Long-term use of antidepressants is associated with high individual and societal costs. Patients often perceive antidepressant discontinuation as challenging. To understand patients' expectations about discontinuation, to document their experiences with long-term use and discontinuation, and to identify factors that can help or hinder discontinuation. Qualitative study using semi-structured interviews via telephone with adult patients in Germany. We interviewed 32 patients with remitted major depressive disorder and long-term antidepressant use. We analysed transcripts with content analysis aided by MAXQDA to derive thematic categories. Patients expected to eliminate side effects or regain independence after discontinuation. Such positive expectations were perceived as facilitators and motivated patients' wish to discontinue antidepressants. However, patients also had negative expectations such as recurrence or discontinuation symptoms. Patients' negative expectations were often fuelled by previous negative experiences, which persisted despite a wish to stop antidepressants, and hindered discontinuation. Most patients perceived antidepressants as being effective, but experienced side effects and further problems. Patients felt inadequately informed about treatment duration and methods for discontinuation. Further barriers and facilitators included a stable environment, availability of support, and treatment information. Patients prefer to discontinue antidepressants within structured frameworks that provide information and support. Identified facilitators and barriers may help optimise appropriate use and discontinuation of antidepressants in routine practice. Promoting functional expectations and specifying individualised approaches to minimise dysfunctional expectations, adapted to patients' previous experiences, appear to be especially important.

Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report

BackgroundSerotonin toxicity is a well-described phenomenon that is commonly attributed to a variety of drug–drug combinations. Some unregulated herbal supplements have been implicated in the onset of serotonin toxicity, however, there is currently minimal literature available on the potential for black cohosh to contribute to rhabdomyolysis and serotonin toxicity, in spite of its known serotonergic properties. Case ReportA middle-aged woman presented to the emergency department with serotonin toxicity and rhabdomyolysis shortly after taking black cohosh supplements in the setting of long-term dual antidepressant use. The serotonin toxicity and rhabdomyolysis resolved with IV fluids, benzodiazepines, and discontinuation of the offending drugs. Why Should an Emergency Physician Be Aware of This?Patients are sometimes not aware of how over-the-counter supplements might interact with their prescription medications. Female patients taking black cohosh to manage hot flashes and menopausal symptoms could be at risk for developing rhabdomyolysis and serotonin toxicity if they are also taking other serotonergic agents.

SPACE SEARCH FOR MINOR CROWDING CASES WITH EXPANSION PLATE IN PATIENTS WITH A HISTORY OF ANTIDEPRESSANT DRUG CONSUMPTION

Introduction: Gaining space in malocclusion cases using expansion plate removable orthodontic appliances. Depression is a mental health disorder that is treated with antidepressants. There is a correlation between a history of long-term antidepressant medication use and orthodontic treatment. Case: A 21-year-old female patient with a history of antidepressant medication complained of slightly advanced maxillary front teeth and crowded mandibular front teeth. Clinical examination revealed the first permanent molar relation Angle Class I modified Dewey type 2 malocclusion with malposition of individual teeth. Arch discrepancy analysis showed a space deficiency of 4 mm in the maxilla and 2.85 mm in the mandible. Case Management: The first stage used a removable orthodontic appliance for maxillary and mandibular expansion plates to obtain space deficiency. The expansion results showed that the maxillary dental arch was successfully expanded by 4.52 mm and the mandibular by 4 mm. Discussion: The slow-type expansion plate functions to expand the dental arch. Conclusion and Suggestion: Expansion plate removable orthodontic treatment effectively gains space in patients with a history of antidepressant drug use. Patients' cooperativeness in wearing the appliance influences the expansion plate removable orthodontic appliance treatment result.

Study protocol: combined N-of-1 trials to assess open-label placebo treatment for antidepressant discontinuation symptoms [FAB-study

BackgroundAntidepressant discontinuation is associated with a broad range of adverse effects. Debilitating discontinuation symptoms can impede the discontinuation process and contribute to unnecessary long-term use of antidepressants. Antidepressant trials reveal large placebo effects, indicating a potential use of open-label placebo (OLP) treatment to facilitate the discontinuation process. We aim to determine the effect of OLP treatment in reducing antidepressant discontinuation symptoms using a series of N-of-1 trials.MethodsA series of randomized, single-blinded N-of-1 trials will be conducted in 20 patients with fully remitted DSM-V major depressive disorder, experiencing moderate to severe discontinuation symptoms following antidepressant discontinuation. Each N-of-1 trial consists of two cycles, each comprising two-week alternating periods of OLP treatment and of no treatment in a random order, for a total of eight weeks. Our primary outcome will be self-reported discontinuation symptoms rated twice daily via the smartphone application ‘StudyU’. Secondary outcomes include expectations about discontinuation symptoms and (depressed) mood. Statistical analyses will be based on a Bayesian multi-level random effects model, reporting posterior estimates of the overall and individual treatment effects.DiscussionResults of this trial will provide insight into the clinical application of OLP in treating antidepressant discontinuation symptoms, potentially offering a new cost-effective therapeutic tool. This trial will also determine the feasibility and applicability of a series of N-of-1 trials in a clinical discontinuation trial.Trial registrationClinicalTrials.gov: NCT05051995, first registered September 20, 2021.

RELEASE (REdressing Long-tErm Antidepressant uSE): protocol for a 3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1 in general practice

BackgroundMany people experience withdrawal symptoms when they attempt to stop antidepressants. Withdrawal symptoms are readily misconstrued for relapse or ongoing need for medication, contributing to long-term use (> 12 months). Long-term antidepressant use is increasing internationally yet is not recommended for most people. Long-term use is associated with adverse effects including weight gain, sexual dysfunction, lethargy, emotional numbing and increased risk of falls and fractures. This study aims to determine the effectiveness of two multi-strategy interventions (RELEASE and RELEASE+) in supporting the safe cessation of long-term antidepressants, estimate cost-effectiveness, and evaluate implementation strategies.MethodsDesign3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1. Setting: primary care general practices in southeast Queensland, Australia. Population: adults 18 years or older taking antidepressants for longer than 1 year. Practices will be randomised on a 1.5:1:1 ratio of Usual care:RELEASE:RELEASE+. Intervention: RELEASE for patients includes evidence-based information and resources and an invitation to medication review; RELEASE for GPs includes education, training and printable resources via practice management software. RELEASE+ includes additional internet support for patients and prescribing support including audit and feedback for GPs. Outcome measures: the primary outcome is antidepressant use at 12 months self-reported by patients. Cessation is defined as 0 mg antidepressant maintained for at least 2 weeks. Secondary outcomes: at 6 and 12 months are health-related quality of life, antidepressant side effects, well-being, withdrawal symptoms, emotional numbing, beliefs about antidepressants, depressive symptoms, and anxiety symptoms; and at 12 months 75% reduction in antidepressant dose; aggregated practice level antidepressant prescribing, and health service utilisation for costs. Sample size: 653 patients from 28 practices. A concurrent evaluation of implementation will be through mixed methods including interviews with up to 40 patients and primary care general practitioners, brief e-surveys, and study administrative data to assess implementation outcomes (adoption and fidelity).DiscussionThe RELEASE study will develop new knowledge applicable internationally on the effectiveness, cost-effectiveness, and implementation of two multi-strategy interventions in supporting the safe cessation of long-term antidepressants to improve primary health care and outcomes for patients.Trial registrationANZCTR, ACTRN12622001379707p. Registered on 27 October 2022.

Prevalence, trends, and individual patterns of long-term antidepressant medication use in the adult Swiss general population.

Antidepressant use has increased in many European countries, mostly driven by longer treatment duration. The aim of this study was to provide prevalence rates of long-term users of antidepressants for the Swiss population over the last decade and to investigate associated factors for longer use. We examined the prevalence rates of individuals with at least one prescription for antidepressants using longitudinal health claims data for 2013 to 2021. We defined short- (< one year), medium- (one-two years), and long-term users (> two years) for 2015 to 2019. We applied a binary logistic regression model to investigate the effects of population (gender, age, area of living, language, health insurance plan, and nursing home) and treatment characteristics (psychiatric or psychotherapeutic care) on long-term compared to short- and medium-term users in 2019. In 2021, 9% of the Swiss population (n = 770,698) received at least one antidepressant prescription, which remained stable since 2013. In 2019, the proportion of long-term users was 57.4%, with steady increase since 2015. The proportion of medium- and short-term users has decreased. Older age, being a woman, living in an urban area, living in a nursing home, being enrolled in a standard care plan, and receiving psychiatric or psychotherapeutic care were factors positively associated with being a long-term user. The proportion of long-term users in Switzerland is high and steadily increasing. Given the ongoing debate about the confounding effects of relapse and withdrawal, more research is needed to investigate longer use of antidepressants that could indicate overprescribing.

Acceptability and optimisation of resources to support antidepressant cessation: a qualitative think-aloud study with patients in Australian primary care.

Stopping long-term (>12 months) antidepressant use can be difficult due to unpleasant withdrawal symptoms. Many people do not recognise withdrawal symptoms or understand how to minimise them while safely discontinuing antidepressants. To address the gaps, the authors developed the 'Redressing long-term antidepressant use' (RELEASE) resources, comprising a medicines information brochure, a decision aid, and drug- specific hyperbolic tapering protocols. To explore patients' acceptability of the RELEASE resources to optimise their use and impact. A think-aloud interview study among adults with lived experience of long-term antidepressant use conducted in south-east Queensland, Australia, between November 2021 and June 2022. Participants were purposively sampled from general practices and interviewed face-to-face or via videoconferencing. Participants verbalised their thoughts, impressions, and feelings while engaging with each resource. Interviews were analysed using a deductive coding framework, including codes related to acceptability and optimisation. Interviews were analysed in a series of four tranches, with iterative modifications made to resources after each tranche. Participants (n = 14) reported the resources to be relevant, informative, motivational, and usable. Participants' comments informed modifications, including changes to wording, content order, and layout. Several participants expressed frustration that they had not had these resources earlier, with one reporting the information could have been 'life changing'. Many commented on the need for these resources to be widely available to both patients and doctors. The RELEASE resources were found to be acceptable, useful, and potentially life changing. The effectiveness of these consumer-informed resources in supporting safe cessation of long-term antidepressants is currently being tested in general practice.

Health professionals' views on discontinuation of long-term antidepressants: a systematic review and thematic synthesis.

Long-term antidepressant use, much longer than recommended by guidelines, may cause harmful effects and generate unnecessary costs. To investigate health professionals (HPs) views of long-term antidepressant discontinuation and their barriers and facilitators. Systematic review and meta-synthesis. We included studies that used qualitative data collection and had data on HPs perceptions on (dis)continuing AD use. The review searched nine database sources until May 2022. Study quality was assessed using the CASP checklist and the COREQ criteria. A thematic synthesis was performed. Thirteen studies were included in the review. Nine studies were of GPs' perspectives, one study of psychiatrists', and three of a mix of HPs. Barriers and facilitators to discontinuing long-term AD yielded eight themes, ordered chronologically according to the considerations that HPs make when they review a long-term AD: perception of AD use, fears, HP role and responsibility, HPs attitude towards discontinuation, HPs confidence regarding ability to stop AD, perceived patient readiness to stop, support from relatives and support from other HP. Deprescribing long-term AD is a difficult and complex process for HPs. The review found evidence that the barriers far outweigh the facilitators. More education on the lack of evidence for the long-term effect of AD and the risks of long-term use, guidance on managing long-term use, and support for HPs and patients is needed to increase long-term AD discontinuation. Further research from an HP perspective other than GPs is required and should also explore how HPs can be supported in managing discontinuation ADs.

An assessment of the reporting of tapering methods in antidepressant discontinuation trials using the TIDieR checklist

BackgroundThe importance of tapering is increasingly recognised when discontinuing antidepressant medication. However, no previous studies have examined the reporting of antidepressant tapering methods in published studies.AimThe aim of this study was to assess the completeness of reporting of antidepressant tapering methods in a published systematic review using the Template for Intervention Description and Replication (TIDieR) checklist.MethodA secondary analysis was conducted of studies included in a Cochrane systematic review that examined the effectiveness of approaches for discontinuing long-term antidepressant use. The completeness of reporting of antidepressant tapering methods in included studies was independently assessed by two researchers using the 12 items from the TIDieR checklist.ResultsTwenty-two studies were included in the analysis. None of the study reports described all checklists items. No study clearly reported what materials had been provided (item 3) or whether tailoring had occurred (item 9). With the exception of providing a name for the intervention or study procedures (item 1), only a minority of studies clearly reported on any of the remaining checklist items.ConclusionThe findings highlight a lack of detailed reporting of antidepressant tapering methods in published trials to date. This needs to be addressed as poor reporting could hinder replication and adaptation of existing interventions, as well as the potential for successful translation of effective tapering interventions into clinical practice.

Estimating Risk of Antidepressant Withdrawal from a Review of Published Data.

Adaptation of the brain to the presence of a drug predicts withdrawal on cessation. The outcome of adaptation is often referred to as 'physical dependence' in pharmacology, as distinct from addiction, although these terms have unfortunately become conflated in some diagnostic guides. Physical dependence to antidepressants may occur in some patients, consistent with the fact that some patients experience withdrawal effects from these medications. It is thought that longer duration of use, higher dose and specific antidepressants affect the risk of antidepressant withdrawal effects as they might cause greater adaptation of the brain. We searched PubMed for relevant systematic reviews and other relevant analyses to summarise existing data on determinants of antidepressant withdrawal incidence, severity and duration. Overall, data were limited. From survey data, increased duration of use was associated with an increased incidence and severity of withdrawal effects, consistent with some evidence from data provided by drug manufacturers. Duration of use may be related to duration of withdrawal effects but data are heterogenous and sparse. Serotonin and noradrenaline reuptake inhibitors and paroxetine are associated with higher risks than other antidepressants, though data for some antidepressants are lacking. Higher doses of antidepressant has some weak association with an increased risk of withdrawal, with some ceiling effects, perhaps reflecting receptor occupancy relationships. Past experience of withdrawal effects is known to predict future risk. Based on these data, we outline a preliminary rubric for determining the risk of withdrawal symptoms for a particular patient, which may have relevance for determining tapering rates. Given the limited scope of the current research, future research should aim to clarify prediction of antidepressant withdrawal risk, especially by examining the risk of withdrawal in long-term users of medication, as well as the severity and duration of effects, to improve the preliminary tool for predictive purposes. Further research into the precise adaptations in long-term antidepressant use may improve the ability to predict withdrawal effects for a particular patient.

A Primer on How to Critically Read an Observational Study on Adverse Medical Outcomes Associated With Long-Term Antidepressant Drug Use

Whether long-term antidepressant use predisposes to or protects against adverse medical outcomes is unclear. In this context, a recent retrospective cohort study found that, for example, at a 10-year follow-up, selective serotonin reuptake inhibitors lowered the risk of diabetes mellitus and hypertension but raised the risk of cerebrovascular disease, cardiovascular mortality, and all-cause mortality. The findings of this study were widely and uncritically covered in the lay and medical media with potential to adversely impact opinions about antidepressant treatment among patients, caregivers, and health care professionals. This article critically evaluates the study with a view to discuss its limitations and, more importantly, to arm the reader with skills to critically appraise other, similar studies. Concepts explained include confounding by indication, regression, and approaches to deal with confounding. Problems with the study identified and explained are incomplete adjustment for confounding, failure to correct for multiple hypothesis testing, the use of backward stepwise regression as a method of analysis, failure to consider reverse causation, and failure to remove death by suicide from analyses of all-cause mortality. Other limitations of the study are also discussed. A take-home message is that it is well established that depression is associated with substantial disability and risk of suicide and that antidepressant drugs treat depression and prevent relapse and recurrence; in contrast, no causal role for antidepressants in long-term adverse medical outcomes is established. Therefore, known long-term benefits with antidepressants must be weighed against unproven predispositions to long-term medical adverse effects in shared decision-making processes.

Effects of concomitant benzodiazepines and antidepressants long-term use on perspective-taking

Background: Benzodiazepines and antidepressants are known to alter responses to empathic pain when used alone, however the effects of their combined use on the perspective-taking facet of empathy are unknown. In order to examine the effects of concomitant benzodiazepines and antidepressants long-term use on perspective-taking, we analyzed behavioral and neural changes on perspective-taking ability using event-related potentials. Methods: To this purpose, 13 long-term concomitant benzodiazepines and antidepressants users and 13 healthy controls performed a task designed to assess affective perspective-taking with simultaneous EEG recording. Results: The behavioral results revealed similar performance between groups. The neural results showed no significant differences between groups for the N170 and late positive potential (LPP) components. These results seem to suggest that long-term use of benzodiazepines and antidepressants together does not affect perspective-taking abilities nor the processing of related information. Conclusions: The concomitant benzodiazepines and antidepressants long-term use seem to preserve the perspective-taking ability of social cognition.

Long-term antidepressant use increases risk of CHD and death

Long-term antidepressant use increases risk of CHD and death

Imipramine Can Be Effective on Depressive-Like Behaviors, but Not on Neurotrophic Factor Levels in an Animal Model for Bipolar Disorder Induced by Ouabain.

Despite possible risks of mania switching with the long-term use of antidepressants in patients with bipolar disorder (BD), these drugs may help in depressive episodes. Alterations in neurotrophic factor levels seem to be involved in the pathophysiology of BD. The present study aimed to evaluate the effect of acute treatment of imipramine on behavior and neurotrophic levels in rats submitted to the animal model for BD induced by ouabain. Wistar rats received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid or ouabain (10-3M). Following the ICV administration, the rats were treated for 14days with saline (NaCl 0.9%, i.p.), lithium (47.5mg/kg, i.p.), or valproate (200mg/kg, i.p.). On the 13th and 14th days of treatment, the animals received an additional injection of saline or imipramine (10mg/kg, i.p.). Behavior tests were evaluated 7 and 14days after ICV injection. Adrenal gland weight and concentrations of ACTH were evaluated. Levels of neurotrophins BDNF, NGF, NT-3, and GDNF were measured in the frontal cortex and hippocampus by ELISA test. The administration of ouabain induced mania- and depressive-like behavior in the animals 7 and 14days after ICV, respectively. The treatment with lithium and valproate reversed the mania-like behavior. All treatments were able to reverse most of the depressive-like behaviors induced by ouabain. Moreover, ouabain increased HPA-axis parameters in serum and decreased the neurotrophin levels in the frontal cortex and hippocampus. All treatments, except imipramine, reversed these alterations. It can be suggested that acute administration of imipramine alone can be effective on depressive-like symptoms but not on neurotrophic factor alterations present in BD.