Effects Of Antidepressant Use Research Articles

Disentangling pharmacological and expectation effects in antidepressant discontinuation among patients with fully remitted major depressive disorder: study protocol of a randomized, open-hidden discontinuation trial

BackgroundAntidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence.MethodsTo disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants’ attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled.DiscussionUntil today, no study has explored the interplay of pharmacological effects and patients’ expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively.Trial registrationClinicalTrials.gov (NCT05191277), January 13, 2022.

Neonatal and pregnancy complications following maternal depression or antidepressant exposure: A population-based, retrospective birth cohort study

Depression is common during pregnancy, and antidepressants are often prescribed for treatment. However, depression and antidepressant use both increase the risk of neonatal and pregnancy complications. To separately evaluate the effects of antidepressant use and the underlying depression on pregnancy and neonatal complications by using a robust statistical method to control for confounding by indication. All study data were obtained from Taiwan's National Health Insurance Research Database. Pregnant women were divided into three groups: those with no depression and no antidepressant exposure(n=1619,198), depression and no antidepressant exposure(n=2006), and depression and antidepressant exposure(n=7857). Antidepressant exposure was further divided into that before pregnancy and during each trimester. Mothers with depression but no antidepressant exposure exhibited increased risks of intrauterine growth restriction and preterm delivery, compared with mothers without depression. In mothers with depression, antidepressant exposure before pregnancy or during the first trimester conferred increased risks of gestational diabetes mellitus, malpresentation, preterm delivery and cardiovascular anomalies, compared with no antidepressant exposure. Moreover, antidepressant exposure during the second or third trimester conferred increased risks of anemia, a low Apgar score, preterm delivery and genitourinary defects. However, antidepressants administered before pregnancy and during all trimesters did not increase the risk of stillbirth. Depression and antidepressant treatment for depression during pregnancy may individually increase the risks of some neonatal and pregnancy complications. Physicians should thoroughly consider the risks and benefits for both the mother and fetus when treating depression during pregnancy by using antidepressants.

Anti-Inflammatory Action of Antidepressants: Investigating the Longitudinal Effect of Antidepressants on White Blood Cell Count

Introduction: Antidepressants have documented anti-inflammatory effects on pro-inflammatory biomarkers. However, the long-term effects of antidepressants on inflammatory markers and the effects of different antidepressant classes on pro-inflammatory biomarkers are largely unexplored. Here, we evaluate the short- and long-term effects of all antidepressant classes on a clinical immune marker, white blood cell count (WBC). Methods: Using a retrospective study design, we extracted WBC count and prescription medications from electronic health records at Vanderbilt University Medical Center. We created a longitudinal model to evaluate the short- and long-term effects of these medications on WBC count. We validated our longitudinal model using two known anti-inflammatory medications, biologic immunosuppressants, and chemotherapy, and one medication class without known immunomodulatory properties, contraceptives. We used the longitudinal model to determine the effects of antidepressant use on WBC count stratified by drug class. Results: Biologic immunosuppressant and chemotherapy use was associated with decreased WBC count, but contraceptive use did not associate with changes in WBC count, validating our longitudinal modeling approach. All antidepressant classes were associated with decreased WBC count in the long-term cohorts. SSRI and atypical use also associated with decreased WBC count in the short-term cohort. Conclusions: Using electronic health record data, we show all antidepressant classes exhibit anti-inflammatory effects on a clinical immune marker, WBC count. Additionally, our results indicate that in some cases the anti-inflammatory effects of antidepressants persist over at least a 1-year time frame. Our work contributes to the immunomodulatory knowledge of antidepressants and motivates future studies investigating alternative therapeutic routes for antidepressants.

Ontogeny of the Dyad: the Relationship Between Maternal and Offspring Neuroendocrine Function.

We review ontogeny of the maternal-offspring neuroendocrine relationship in human pregnancy. We present bidirectional genetic, physiological, and behavioral influences that enhance or disrupt HPA activity and its end product cortisol at the individual level and within the dyad. Consistent evidence supports that maternal mood and caregiving behavior are associated with maternal and offspring cortisol levels. Select studies support the buffering effects of antidepressant use and maternal positive affect on offspring cortisol. Growing research highlights evocative effects of fetalneuroendocrine activity, antenatalgene transfer, andinfantbehavioral distress and risk characteristics on maternal cortisol levels and dyadic attunement. There is potential to advance our understanding of the mother-offspring neuroendocrine relationship by consideration of other neuroactivesteroids in addition to cortisol, and to consider developmental timing and measurement source in study design. Future study should emphasize in what context or for whom neuroendocrine attunement is adaptive versus maladaptive for mother and child.

Risk of Fall-Related Injuries Associated with Antidepressant Use in Elderly Patients: A Nationwide Matched Cohort Study.

Previous studies have reported a higher risk of falls among tricyclic antidepressant (TCA) users compared to selective serotonin reuptake inhibitor (SSRI) users, yet SSRIs are known as a safer antidepressant class for use in older adults. This study examined the effects of antidepressant use on the risk of fall-related injuries after classifying antidepressant drugs, polypharmacy, and central nervous system (CNS) drugs by therapeutic classes and identifying factors influencing risk of fall-related injuries. A retrospective matched cohort study based on propensity scores was conducted among older adults, aged 70–89 years, who initiated antidepressant use between 1 January 2012 and 31 December 2014 using the national health insurance system senior cohort in Korea. The proportional hazard Cox regression model was used to examine the association between fall-related injuries and antidepressants. The subgroup analyses were performed to assess the risk of fall-related injuries by the number of concurrently administered medications, therapeutic classes of antidepressants, and CNS class medications. This study found that duloxetine, escitalopram, paroxetine, amitriptyline, imipramine, and trazodone significantly increased the risk of fall-related injuries in older adults. When antidepressants were prescribed to older adults, prescribers carefully considered factors including the dose, number of concurrently administered medications, and therapeutic classes of CNS.

Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models.

BackgroundIncreased prevalence of depression has been observed among patients with multiple sclerosis (MS) and correlated with the elevated levels of proinflammatory cytokines and the overall deregulation of monoaminergic neurotransmitters that these patients exhibit. Antidepressants have proved effective not only in treating depression comorbid to MS, but also in alleviating numerous MS symptoms and even minimizing stress-related relapses. Therefore, these agents could prospectively prove beneficial as a complementary MS therapy.ObjectiveThis review aims at illustrating the underlying mechanisms involved in the beneficial clinical effects of antidepressants observed in MS patients.MethodsThrough a literature search we screened and comparatively assessed papers on the effects of antidepressant use both in vitro and in vivo MS models, taking into account a number of inclusion and exclusion criteria.Results In vitro studies indicated that antidepressants promote neural and glial cell viability and differentiation, reduce proinflammatory cytokines and exert neuroprotective activity by eliminating axonal loss. In vivo studies confirmed that antidepressants delayed disease onset and alleviated symptoms in Experimental Autoimmune Encephalomyelitis (EAE), the most prevalent animal model of MS. Further, antidepressant agents suppressed inflammation and restrained demyelination by decreasing immune cell infiltration of the CNS.ConclusionAntidepressants were efficient in tackling numerous aspects of disease pathophysiology both in vitro and in vivo models. Given that several antidepressants have already proved effective in clinical trials on MS patients, the inclusion of such agents in the therapeutic arsenal of MS should be seriously considered, following an individualized approach to minimize the adverse events of antidepressants in MS patients.

Long-term prenatal effects of antidepressant use on the risk of affective disorders in the offspring: a register-based cohort study.

To investigate the association between intrauterine antidepressant exposure and offspring affective disorders over an 18-year follow-up period using Danish national registers. We included 42,988 singletons born during 1998-2011 and followed-up until 2016, death, emigration, or date of first affective disorder diagnosis. Children were categorised into two groups according to maternal antidepressant use within 2 years before and during pregnancy: continuation (use before and during pregnancy) or discontinuation (use before but not during pregnancy). The outcome was an affective disorders diagnosis in the offspring based on secondary/tertiary care records and primary care prescription data. Hazard ratios (HR) of affective disorders were estimated using Cox regression models. To consider confounding by shared environmental or genetic factors, we investigated the effect of paternal antidepressant use on the risk for affective disorders. Affective disorders were diagnosed in 1538 children. Children whose mothers continued antidepressants during pregnancy had an increased risk of affective disorders (HR = 1.20, 95% CI = 1.08-1.34), compared with children whose mothers discontinued before pregnancy. Similarly, continued paternal antidepressant use during pregnancy was associated with higher risk for offspring affective disorders (HR = 1.29, 95% CI = 1.12-1.49), compared to discontinuation. Based on data from primary and secondary/tertiary care, maternal antidepressant use during pregnancy was associated with an increased risk of affective disorders in the offspring. As similar associations were observed in children whose fathers continued antidepressant use across the pregnancy period, the observed association may be attributable to the underlying parental psychopathology, rather than the direct intrauterine exposure to antidepressants.

Disentangling and Quantifying Mechanisms of Increased Fall Risk Among Older Adults With Depression

Background: Older adults with depression are up to four times more likely to fall, yet the mechanisms by which depression increases fall risk are unclear. This study sought to quantify and compare the relative strength of selected mechanisms mediating the association between depression and falls. Methods: We used longitudinal linked data (2006 – 2010) from the Health and Retirement Study and Prescription Drug Study. The analytic sample included non-institutionalized adults age > 65 with data on physical functioning and medication use (n=3,565). Falls and injurious falls over the past two years were self-reported outcomes. Depression was measured using the Composite International Diagnostic Interview (CIDI). We used causal mediation analysis to estimate the total and direct associations between depression and falls and compared strength of three potential mediating mechanisms – frailty, cognition, and antidepressant (AD) use. Results: Of 190 participants reporting depression in 2006, 85 (44.7%) fell and 30 (15.8%) were injured from a fall between 2008 and 2010. Depressed individuals were 92% more likely to fall compared to non-depressed (OR=1.92, p<.01). We found significant indirect effects of AD use (indirect OR=1.17, p<.01) and frailty (OR=1.12, p=.013) representing 19% and 13% of the total effect of depression on falls, respectively. Cognition was not a significant mediator. Results were similar for falls leading to injury. Discussion: Results suggest that AD use and frailty explain a significant portion of the elevated risk for falls among depressed individuals. Identification of these and other mechanisms may inform clinical treatment decisions for older adults with depression.

To evaluate the effects of antidepressant drugs on pregnancy outcomes in a university hospital in Turkey

To assess the effects of antidepressant use on pregnancy outcomes. The cross-sectional study was conducted at the Department of Pharmacology, Manisa Celal Bayar University, Manisa, Turkey, and comprised pregnant women who were admitted to the Department of Gynaecology between 2008 and 2017 who had been prescribed antidepressant drugs before pregnancy and continued to use them during any week of their respective pregnancies. The women were contacted by telephone after delivery to obtain information about the pregnancy outcomes. Data was analysed using SPSS 23. There were 183 women with a mean age of 31.3 ± 5.3 years (range: 18-44 years). There were congenital defects in the newborn in 11(7.65%) cases. The most commonly used antidepressant group was selective serotonin reuptake inhibitor 138(75.4%), and escitalopram was the most frequently used drug 46(25.1%). Spontaneous abortion rate was higher with escitalopram than the other antidepressants (p=0.062). Induced abortion rate was significantly higher in multidrug users compared to those on a single drug (p<0.05). Selective serotonin reuptake inhibitor was found to be the most used class of antidepressants during pregnancy due to the low side effects and teratogenic effects. When antidepressant treatment is necessary during pregnancy, a single drug can be more suitable.

Antidepressant Use During Development May Impair Women's Sexual Desire in Adulthood

IntroductionAlthough antidepressants are well known to cause sexual side effects in adults, the long-term effects of antidepressant use during development on adult sexual function is unknown. AimTo explore differences in sexual desire and sexual behavior between adults who did vs did not use antidepressants during childhood or adolescence. MethodsAn online survey of 610 young adults (66% women) assessed childhood and current mental health and use of antidepressants and other psychiatric medications before the age of 16 years and currently, partnered and solitary sexual desire, and frequency of masturbation and partnered sexual activity. Antidepressants were coded into either selective serotonin reuptake inhibitors (SSRIs) or non-SSRI antidepressants. Main Outcome MeasureScores on the Sexual Desire Inventory, and self-reported frequency of masturbation and partnered sexual activity. ResultsFor women, childhood SSRI use was associated with significantly lower solitary sexual desire, desire for an attractive other, and frequency of masturbation. This was true even when controlling for childhood mental health concerns, current mental health, and current antidepressant use. However, there was no effect of childhood SSRI use on women's partnered sexual desire or partnered sexual activity. There was no significant effect of childhood antidepressant use on men's sexual desire or masturbation. However, in men, childhood use of non-SSRI antidepressants was associated with significantly higher frequency of partnered sexual activity. Childhood use of non-SSRI antidepressants, or nonantidepressant psychiatric medication, was not associated with adult sexual desire or behavior in either women or men. Clinical ImplicationsIt is possible that SSRI use during childhood interrupts the normal development of sexual reward systems, which may be a risk factor for sexual desire dysfunction in adult women. Strengths & LimitationsStrengths include a large sample, use of attention checks and validated measures, and careful assessment of childhood mental health history; however, generalizability is limited by a predominantly white, young adult sample. These data are cross-sectional, and therefore, causal explanations for the association between childhood SSRI use and adult sexual well-being should be considered preliminary, warranting replication. ConclusionThese findings point to a critical need for well-controlled, prospective research on possible long-term effects of antidepressant use, particularly SSRI use, on the development of adult sexual well-being.Lorenz TK. Antidepressant Use During Development May Impair Women's Sexual Desire in Adulthood. J Sex Med 2020;17:470–476.

Long-Term Prenatal Effects of Antidepressant Use on the Risk of Affective Disorders in the Offspring: A Register-Based Cohort Study

Objective: To investigate the association between intrauterine antidepressant exposure and offspring affective disorders over an 18-year follow-up period using Danish national registers. Method: We included 42,988 singletons born during 1998-2011 and followed-up until 2016, death, emigration, or date of first affective disorder diagnosis. Children were categorised into two groups according to maternal antidepressant use within two years before and during pregnancy: continuation (use before and during pregnancy) or discontinuation (use before but not during pregnancy). The outcome was an affective disorders diagnosis in the offspring based on secondary/tertiary care records and primary care prescription data. Hazard ratios (HR) of affective disorders were estimated using Cox regression models. To consider confounding by shared environmental or genetic factors, we investigated the effect of paternal antidepressant use on the risk for affective disorders. Results: Affective disorders were diagnosed in 1,538 children. Children whose mothers continued antidepressants during pregnancy had an increased risk of affective disorders (HR=1.20, 95% CI=1.08 to 1.34), compared with children whose mothers discontinued before pregnancy. Similarly, continued paternal antidepressant use during pregnancy was associated with higher risk for offspring affective disorders (HR=1.29, 95% CI=1.12 to 1.49), compared to discontinuation. Discussion: Based on data from primary and secondary/tertiary care, maternal antidepressant use during pregnancy was associated with an increased risk of affective disorders in the offspring. As similar associations were observed in children whose fathers continued antidepressant use across the pregnancy period, the observed association may be attributable to the underlying parental psychopathology, rather than the direct intrauterine exposure to antidepressants. Funding Statement: ASR, NCM, NMM, XL, TMO and VB are supported by the National Institute of Mental Health (NIMH) (R01MH122869). XL is also supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 891079. TMO is supported by iPSYCH, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (R155- 2014-1724), The Lundbeck Foundation (R313-2019-569), AUFF NOVA (AUFF-E 2016-9-25), and Fabrikant Vilhelm Pedersen og Hustrus Legat. VB has received funding from the Netherlands Organization for Scientific Research (clinical fellow and VENI incentive). The investigators conducted the research independently. Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support for the submitted work as described above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethics Approval Statement: The study was approved by the Danish Data Protection Agency. By Danish law, no informed consent is required for a register based study using anonymised data.

041 Using Antidepressants during Development is Associated with Lower Sexual Desire in Adulthood

Antidepressants are increasingly prescribed to children and adolescents in 2012, 3.5% of children age 10-14 and 6.2% of adolescents aged 15-19 in the US took an antidepressant1. Certain antidepressants, such as the selective serotonin reuptake inhibitor (SSRI) class, are associated with significant detrimental effects on sexual function among adults. The long-term effects of antidepressant use are unknown, despite evidence from animal models that early antidepressant use can impact sexual function in adulthood2. It is possible that antidepressant use as a teen may interfere with sexual and romantic relationship development and lead to impaired sexual function in adulthood. To explore possible neurodevelopmental effects of antidepressant use on adult sexual function. We surveyed 464 adults (mean age = 20.55) about their mental health history, relationship status, psychiatric medication use, and current sexual function. Participants were screened for lifetime depression and anxiety using validated instruments (Patient Health Questionnaire 2 item screener (PHQ-2); Generalized Anxiety Disorder 2 item screener (GAD-2); those who screened positive were asked the age of first episode. Participants also completed a version of the Female Sexual Function Index (FSFI) modified for use across sexes, from which calculated the FSFI-desire subscale. A list of 48 common psychiatric medications was presented and participants were asked to indicate which (if any) they had ever used and when. From this list we indexed SSRI use prior to age 18 as well as current use.

Neural correlates of emotion processing comparing antidepressants and exogenous oxytocin in postpartum depressed women: An exploratory study.

Despite common use of antidepressants to treat postpartum depression, little is known about the impact of antidepressant use on postpartum brain activity. Additionally, although oxytocin has been investigated as a potential treatment for postpartum depression, the interaction between antidepressants and exogenous oxytocin on brain activity is unknown. We explored postpartum depressed women’s neural activation in areas identified as important to emotion and reward processing and potentially, antidepressant response: the amygdala, nucleus accumbens and ventral tegmental area. We conducted a secondary analysis of a functional imaging study of response to sexual, crying infant and smiling infant images in 23 postpartum depressed women with infants under six months (11 women taking antidepressants, 12 unmedicated). Participants were randomized to receive a single dose of oxytocin or placebo nasal spray. There was significantly higher amygdala activation to sexual stimuli than either neutral or infant-related stimuli among women taking antidepressants or receiving oxytocin nasal spray. Among unmedicated women receiving placebo, amygdala activation was similar across stimuli types. There were no significant effects of antidepressants nor oxytocin nasal spray on reward area processing (i.e., in the nucleus accumbens or ventral tegmental area). Among postpartum women who remain depressed, there may be significant interactions between the effects of antidepressant use and exogenous oxytocin on neural activity associated with processing emotional information. Observed effect sizes were moderate to large, strongly suggesting the need for further replication with a larger sample.

Adverse effects of venlafaxine therapy and risk factors for their occurrence

Pharmacovigilance is an important aspect of depression treatment, considering that 40–90% of patients experience side effects of antidepressant use. This paper discusses the issues of optimising the use of venlafaxine, including its pharmacodynamic and pharmacokinetic properties, indications, adverse effects and risk factors for their occurrence, such as co-morbidities or genetic polymorphisms and interactions with other drugs.

Antidepressant use and the components of the frailty syndrome

Abstract Objective: to evaluate the effects of antidepressant use on components of frailty. Methods: a cross-sectional and analytical study comparing groups of users and non-users of antidepressants was carried out in a municipal region in the south of Brazil. The research was linked to the matrix study "Health of Elderly Persons in Primary Care". The sample was selected through access to the database of the matrix study from which two groups were extracted: users (n=87) and non-users (n=114) of antidepressants. After selection of the groups, data collection was carried out between June and September 2016 in the homes of the elderly, and included information on sociodemographic characteristics, use of medications and the evaluation of frailty. Pearson's Chi-square hypothesis test was used to verify the association between the groups and the Odds Ratio (OR) was used to calculate risk. Results: The prevalence of frailty was 62.7% and was associated with the group that used antidepressants. Among the components of frailty an association between the user group and fatigue, low gait speed and unintentional weight loss was found. A greater risk of frailty among elderly persons using tricyclic antidepressants and antidepressants potentially inappropriate for the elderly was identified. Conclusions: an association between frailty and antidepressant use was found. These results indicate the need for the clinical evaluation of the risks and benefits of prescribing antidepressants for the elderly; and reveal that when treatment begins, the monitoring and assessment of geriatric characteristics are required to ensure the safety and quality of life of the elderly.

Use of antidepressants and risk of hospitalization for acute myocardial infarction: A nationwide case-crossover study

BackgroundWe aimed to investigate the association between antidepressant use and the risk of hospitalization for acute myocardial infarction (AMI). MethodsA case-crossover study was conducted using a nationwide population-based sample from Taiwan's National Health Insurance Research Database. A total of 18,631 patients with incident AMI were included in this study. The effects of antidepressant use as well as that of various classes (including tricyclic or tetracyclic antidepressants; selective serotonin reuptake inhibitors; or serotonin norepinephrine reuptake inhibitors), doses, and receptor-binding profiles of the antidepressants on AMI were assessed. Conditional logistic regression models with adjustment for potential confounding factors were applied to determine the effects of antidepressant use on the risk of AMI during case and control time periods of 15, 30, and 60 days, respectively. The modifiable effects of age, gender, and comorbidity were evaluated by stratified analysis. ResultsAntidepressant use was not associated with the risk of AMI (adjusted odds ratio [AOR] = 1.04; 95% confidence interval (CI): 0.88–1.24). Likewise, neither the class, dose, nor the binding affinity of serotonin transporter or norepinephrine transporter was associated with AMI risks, and there was no modifying effect of age, gender, or comorbid medical condition on the association between antidepressant use and AMI. ConclusionsUse of antidepressant drugs was not associated with the risk of AMI.

Psychiatric analysis of treatment-resistant allergic rhinitis and evaluation of the effects of antidepressant use

Psychiatric analysis of treatment-resistant allergic rhinitis and evaluation of the effects of antidepressant use

Thalamocortical connectivity in major depressive disorder

BackgroundMajor Depressive Disorder (MDD) is highly prevalent and potentially devastating, with widespread aberrations in brain activity. Thalamocortical networks are a potential candidate marker for psychopathology in MDD, but have not yet been thoroughly investigated. Here we examined functional connectivity between major cortical areas and thalamus. MethodResting-state fMRI from 54 MDD patients and 40 healthy controls were collected. The cortex was segmented into six regions of interest (ROIs) consisting of frontal, temporal, parietal, and occipital lobes and pre-central and post-central gyri. BOLD signal time courses were extracted from each ROI and correlated with voxels in thalamus, while removing signals from every other ROI. ResultsOur main findings showed that MDD patients had predominantly increased connectivity between medial thalamus and temporal areas, and between medial thalamus and somatosensory areas. Furthermore, a positive correlation was found between thalamo-temporal connectivity and severity of symptoms. LimitationsMost of the patients in this study were not medication naïve and therefore we cannot rule out possible long-term effects of antidepressant use on the findings. ConclusionThe abnormal connectivity between thalamus and temporal, and thalamus and somatosensory regions may represent impaired cortico-thalamo-cortical modulation underlying emotional, and sensory disturbances in MDD. In the context of similar abnormalities in thalamocortical systems across major psychiatric disorders, thalamocortical dysconnectivity could be a reliable transdiagnostic marker.

22. The Effects of Antidepressant use on Clinical Outcomes in the NEURAPRO-E Trial

Background: The NEURAPRO-E trial is a randomized controlled multicenter trial of long-chain omega-3 polyunsaturated fatty acids in 304 young people at clinical risk of psychosis. The trial failed to replicate the earlier single-center trial in 81 participants (the Vienna omega-3 study). This analysis aims to investigate if antidepressant (AD) use during NEURAPRO-E influenced clinical outcomes. Methods: Secondary analysis of a RCT of omega-3 PUFAs versus placebo involving a total cohort of 304 participants. Randomization was stratified by total score on the Montgomery-Asberg Depression Rating Scale (MADRS score ≥21 vs. <21) as both depression and ADs may impact on UHR symptoms and illness progression. We determined the influence of AD use on following outcome measures: time to transition to psychotic disorder; measures of psychiatric symptoms and psychosocial functioning including the MADRS, BPRS, SANS and SOFAs. Since omega-3 supplementation versus placebo did not impact on outcomes the original group allocations were ignored for this analysis and participants were treated as a single cohort. Results: Three hundred and four treatment-seeking individuals were enrolled in this study. Thirty-two (10.5%) of 304 patients discontinued the intervention prematurely (i.e., prior to 6 months). Forty-six (15.1%) patients were unable to be contacted and one became pregnant, meaning that in total 79 (26%) participants were lost to follow-up. A MADRS score ≥21 at baseline was observed in 134 (44.1%) individuals. ADs were used in 189 (62.2%) of the participants. The progression to psychosis rate in individuals who received an AD (13.2%; 25 of 189) was more than twice as high as in individuals without AD treatment (6.1%; 7 of 115). Kaplan-Meier survival analysis indicated a group difference at trend level (χ2 = 3.237, P = .072, log rank test). After stratification for MADRS scores, KM survival analyses indicated a higher transition to psychosis rate in individuals who received ADs in the stratum with low depressive symptoms (14% vs. 4%; χ2 = 3.679, P = .055, log rank test), while in the stratum with high depressive symptoms, transition to psychosis rates were 13% and 10% for groups with and without AD use, respectively (χ2 = .226, P = .635, log rank test). Furthermore, repeated measures analysis indicated that MADRS depressive symptoms significantly improved between baseline and 12-month follow-up in groups with and without AD use in both strata of severity of depressive symptoms (all P < .001). Repeated measures analyses for the other secondary outcomes also showed no significant clinical advantage for AD use compared to no AD use in groups with either high or low depressive symptoms. Conclusion: This is the first analysis on the effects of ADs in a large cohort of UHR individuals. No statistically significant effects of ADs on outcomes were observed. The findings are limited by fact that ADs were provided as concomitant medication upon clinical discretion.

Antidepressant use and functional limitations in U.S. older adults

ObjectiveThe upsurge in prevalence and long-term use of antidepressants among older adults might have profound health implications beyond depressive symptom management. This study examined the relationship between antidepressant use and functional limitation onset in U.S. older adults. MethodsStudy sample came from 2006 and 2008 waves of the Health and Retirement Study, in combination with data from 2005 and 2007 Prescription Drug Study. Self-reported antidepressant use was identified based on the therapeutic classification of Cerner Multum's Lexicon. Functional limitations were classified into those pertaining to physical mobility, large muscle function, activities of daily living, gross motor function, fine motor function, and instrumental activities of daily living. Cox proportional hazard models were performed to assess the effects of antidepressant use on future functional limitation onset by limitation category, antidepressant type, and length of use, adjusted by depression status and other individual characteristics. ResultsAntidepressant use for one year and longer was associated with an increase in the risk of functional limitation by 8% (95% confidence interval=4%–12%), whereas the relationship between antidepressant use less than a year and function limitation was statistically nonsignificant. Antidepressant use was associated with an increase in the risk of functional limitation by 8% (3%–13%) among currently nondepressed participants but not currently depressed participants. ConclusionLong-term antidepressant use in older adults should be prudently evaluated and regularly monitored to reduce the risk of functional limitation. Future research is warranted to examine the health consequences of extended and/or off-label antidepressant use in absence of depressive symptoms.