Selective serotonin reuptake inhibitors in the management of depression in women with breast cancer: evidence and gaps

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Selective serotonin reuptake inhibitor (SSRI) prescriptions for children and adolescents have increased greatly in recent years despite a paucity of demonstrated safety and efficacy data and a lack of clear guidelines for use. Our study sought to describe family physician and pediatrician SSRI prescribing patterns for children and adolescents, identify influences on SSRI prescription variations, and describe the use of SSRI within the overall management of depression and other mental disorders in primary care. A survey was mailed to all 596 active North Carolina general pediatricians and a random sample of 557 family physicians in primary care practice. Family physicians who did not see children in their practice were excluded. The survey instrument consisted of a 4-page questionnaire. Survey items included physician demographics, practice characteristics, general management, volume of pediatric patients with depressive symptoms, prescription of SSRIs for depression and other diagnoses, and potential influences on SSRI prescribing practices. The main outcomes were self-reported physician prescription of SSRIs for children and adolescents. Results were analyzed using chi(2) comparisons and logistic regression. The overall response rate was 66% (55% family physicians and 76% pediatricians). Of the physicians, 72% had prescribed an SSRI for a child or adolescent. Depression was the most common reason for prescribing an SSRI; over two thirds of respondents had prescribed an SSRI for depression in a child 18 years of age or younger. Over half of the physicians reported they had prescribed an SSRI for a diagnosis other than depression in a child 18 years of age or younger. Attention-deficit/hyperactivity disorder was the most frequent use cited other than depression, followed by obsessive-compulsive disorder, aggression, eating disorders, and enuresis. Primary care physicians prescribed SSRIs for adolescents more commonly than for younger children. Only 6% of the respondents had ever prescribed an SSRI for a child younger than 6 years of age. In terms of SSRI prescriptions written for depression in the last 6 months, 32% of the physicians had recently prescribed SSRIs for adolescent patients and 6% for patients younger than 12 years of age. Family physicians were more likely than pediatricians to have recently prescribed SSRIs for adolescent patients (41% vs 26%), but there was no difference in recent SSRI prescriptions for children <12 years of age by physician specialty (4% vs 6%). Prescription of SSRIs was not associated with decreased use of counseling for treatment of depression, but prescription of SSRIs was associated with decreased use of referrals (63% vs 74%). There was no difference in the use of counseling between family physicians and pediatricians (61% vs 59%). However, pediatricians were more likely to use referrals in their usual approach to depression (77% vs 48%) compared with family physicians. More family physicians had prescribed SSRIs for pediatric patients compared with pediatricians (91% vs 58%), and more family physicians had prescribed SSRIs in combination with other psychotropic medications (54% vs 31%). For the majority of respondents, SSRI prescriptions constituted most of the medications used to treat childhood depression (75% of family physicians vs 61% of pediatricians). Family physicians were more likely to report a belief in the safety (63% vs 48%) and effectiveness (40% vs 32%) of SSRIs. Only 8% of physicians reported adequate training in the treatment of childhood depression and just 16% were comfortable with the treatment of depression. There were no specialty differences in training for the treatment of childhood depression; however, more family physicians than pediatricians agreed that they were comfortable with the management of childhood depression (22% vs 11%). (ABSTRACT TRUNCATED)

Management of Depression in Parkinson’s Disease

Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century

The selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of multiple psychiatric conditions. In vitro and ex vivo data with these agents indicate they may have varying degrees of antiplatelet activity via multiple receptors. Reports of bleeding in patients receiving SSRIs appeared soon after their introduction. A review of the literature suggests SSRI therapy may increase the risk of bleeding especially with concomitant aspirin or nonsteroidal anti-inflammatory agents. Clinicians should exercise caution when prescribing these agents in high risk patients and maintain awareness of the potential contribution of SSRIs to unexplained bleeding episodes.

The purpose of the study was to investigate whether the concomitant use of selective serotonin reuptake inhibitors (SSRI) with tamoxifen influences the risk of death due to breast cancer, and we also investigated the association between SSRI use and adherence to oral endocrine therapy (ET). We analyzed data from BCBaSe Sweden, which is a database created by the data linkage of Registries from three different regions of Sweden. To investigate the association between ET adherence and SSRI use, we included all women who were diagnosed with non-distant metastatic ER-positive invasive breast cancer from July 2007 to July 2011 and had at least one dispensed prescription of oral tamoxifen or aromatase inhibitor. To investigate the role of concurrent administration of SSRI and tamoxifen on breast cancer prognosis, we performed a nested case–control study. In the adherence cohort, 9104 women were included in the analyses. Women who received SSRI, either before or after breast cancer diagnosis, were at higher risk for low adherence to ET. However, when the overlapping period between SSRI use and ET was >50 %, no excess risk for low adherence was observed. Non-adherence (<80 %) to ET was significantly associated with worse breast cancer survival (OR 4.07; 95 % CI 3.27–5.06). In the case–control study, 445 cases and 11125 controls were included. The concomitant administration of SSRI and tamoxifen did not influence breast cancer survival, neither in short-term (OR 1.41; 95 % CI 0.74–2.68) nor in long-term SSRI users (OR 0.85; 95 % CI 0.35–2.08). Concomitant SSRI and tamoxifen use does not seem to increase risk for death due to breast cancer. Given the positive association between continuing antidepressive pharmacotherapy for a longer period of time and adherence to ET, it is essential to capture and treat depression in breast cancer patients to secure adherence to ET.

Background: It is estimated that 12.7% of the US population had been prescribed an antidepressant in the past month and that women are twice as likely to be on an antidepressant than men. Therefore, it is especially important to understand how SSRIs interact with female hormones and influence risk and progression of female cancers, especially breast cancer, being the most common. Up to a third of women use selective serotonin reuptake inhibitors (SSRIs) after breast cancer diagnosis. Recent investigation has demonstrated serotonin receptor (5-HTR2B) expression in the breast and identified serotonin production in breast tumor cells as an indicator of poor prognosis. This paper presents a unique comparative assessment between the influence of prior SSRI use, continuous and after use relative to breast cancer diagnosis on overall mortality among breast cancer patients. This analysis is expected to provide a clearer understanding of the influence of SSRIs based on period of use relative to time of diagnosis on overall mortality. Methods: The present study includes a population-based sample of consecutively diagnosed breast cancer cases identified as part of the Breast Cancer in Northern Israel study. Patients were recruited and followed from January 1st, 2000 to July, 2019. Participants completed risk factor questionnaires regarding medical, reproductive, family and personal history of cancer, medication use and health habits. Additionally full prescription data was available through the Israeli national CLALIT medical database. An analysis of 5976 newly diagnosed women with breast cancer was performed. K-M survival analysis and time-dependent and time-independent COX proportional hazard models were performed to determine overall survival based on interval of SSRI use. Results: Use of SSRIs in the 5 years prior to breast cancer diagnosis was associated with a 66% increase in overall mortality (HRadj.=1.66; CI: 1.05-2.63). Use of SSRIs with use that initiated after breast cancer diagnosis was associated with an 81% increase in mortality (HRadj.=1.81; CI: 1.58-2.06). Use of SSRIs in the 5 years post-diagnosis was associated with a significant (P&amp;lt;0.001) dose-response increase in long-term mortality (&amp;gt;5 years). For 24 months of SSRI use after diagnosis, there was a 99% increase in mortality (HR=1.99; CI: 1.39-2.83). Conclusion: SSRIs used both prior to and after breast cancer diagnosis are associated with reduced overall survival in breast cancer patients. The effect of SSRIs on mortality persisted even after adjustment for tamoxifen and factors thought to mediate the relationship behind depression and increased mortality including increased age at diagnosis, comorbidities and stage at diagnosis pointing toward other mechanisms mediating the association between SSRIs and impaired survival in breast cancer patients. Additional research is needed to better understand who is susceptible to the adverse effects of SSRIs on breast cancer overall mortality. Treating depressive symptomatology is of high importance. The results presented here indicate that risks and benefits of SSRI use after breast cancer diagnosis should be weighed when initiating pharmachotherapy and additional research is needed to better understand why SSRIs are associated with worse outcomes in breast cancer patients. Citation Format: Avital Fischer, Hedy Rennert, Ofra Barnett, Gad Rennert. The impact of SSRI use on overall survival in breast cancer patients in northern Israel [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-51.

Clinical considerations with use of psychotropic medications in COVID-19 patients

Polypharmacy is associated with negative health outcomes and decreased medication adherence. Polypharmacy is common in cancer populations, but few studies have evaluated the relationship between polypharmacy and aromatase inhibitor (AI) adherence. No studies have evaluated the relationship between over-the-counter (OTC) supplements and AI adherence. Our primary hypothesis was that polypharmacy would be associated with increased risk of premature AI discontinuation. This exploratory analysis used data from the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, a prospective, multicenter, randomized controlled trial that enrolled participants from 2005 to 2009. Included patients were female, postmenopausal, with stage 0-III breast cancer, who had completed indicated chemotherapy, surgery, and radiation. Participants were randomized to adjuvant exemestane or letrozole and completed serial clinical examinations and questionnaires for two years. Concomitant medication data were collected prospectively. Cox proportion models were used for statistical analysis of the relationship between polypharmacy, OTCs, medication class, and AI adherence. In the 490 analyzed participants, use of any prescription medications at baseline was associated with decreased risk of premature AI discontinuation (HR 0.56, p = 0.02). Use of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) at baseline was associated with decreased risk of premature AI discontinuation (HR 0.67, p = 0.04). Use of any OTCs was not associated with AI discontinuation. Baseline use of prescription medications but not OTCs was associated with increased AI persistence. Future research is needed to understand how this can be utilized to promote AI adherence.

Respiratory-related leg movements (RRLMs) may contribute to the cardiovascular risk associated with obstructive sleep apnea (OSA). Selective serotonin reuptake inhibitors (SSRIs), but not bupropion, increase periodic leg movements in sleep. This study examines whether patients with OSA using SSRIs have more RRLMs than those taking bupropion or no antidepressant. Patients with an apnea-hypopnea index (AHI) of at least 10 events/h during a full-night diagnostic study or split-night study, who were taking bupropion (n = 32), an SSRI (n = 31), or no antidepressant (n = 31), were selected from a database of prestudy questionnaires. RRLMs were scored according to World Association of Sleep Medicine 2016 standards. Patients using SSRIs had significantly greater overall RRLM% (defined as the percentage of respiratory events associated with a leg movement, including apneas, hypopneas, and respiratory effort-related arousals), RRLM index, and periodic limb movement index relative to patients using bupropion and control patients. The difference between the RRLM% in the SSRI and bupropion groups was limited to patients undergoing split-night studies, and that of the SSRI and control groups was limited to patients undergoing full-night diagnostic studies. The greater number of RRLMs and PLMs in the SSRI group may contribute to treatment-emergent insomnia often seen with SSRI use. Fragmented sleep and elevated autonomic nervous system activation associated with increased RRLMs in patients with OSA taking SSRIs might also limit the tolerability of antidepressant treatment, as well as increase the risk for cardiovascular disease.

e24181 Background: Tamoxifen (TAM) and aromatase inhibitors (AI) are associated with a high side-effect burden including depression and cognitive deficits which compromise quality of life and adherence to treatment. The aims of the study were to determine the efficacy of antidepressants (AD) with hormone mediated depression in ER+ breast cancer patients and to determine if any clinical variables predicted successful AD treatment response. Methods: A retrospective chart review of consecutive referrals to psycho-oncology of breast cancer patients on TAM or AI with new onset depression was conducted. Demographic variables, cancer stage and treatment, hormonal treatment, psychiatric history and AD treatment were collected. Assessments for depression, anxiety and cognitive disorders included clinical interviews, patient-rated scales [Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI)] and a clinician-rated scale [Montreal Cognitive Assessment (MoCA)]. These measures were done at baseline (before starting an AD) and follow-up to determine AD treatment response. Successful AD treatment is defined as ≥50% reduction in baseline BDI score, while remission of depression is defined as a BDI score &lt; 8. Statistical analysis comparing clinical variables between AD responders and non-responders included Fischer’s exact test or chi-square, one-way ANOVA, t-test, and binary logistic regression to determine which variables predicted successful AD treatment response. Results: A sample of 40 ER+ breast cancer patients (mean age 55 years; 39 females, 1 male; 26 Hispanic, 14 non-Hispanic) included 18 on TAM and 22 on AI. AD included venlafaxine (N = 18), escitalopram (N = 9), bupropion (N = 4), mirtazapine (N = 4), sertraline (N = 3) and duloxetine (N = 2). Over 72% (29/40) of patients successfully responded to AD with a complete depression remission rate of 50% (20/40). Venlafaxine at a mean dose of 150 mg was significantly more effective (p = .013) in treating hormone-mediated depression when compared to selective serotonin reuptake inhibitors (SSRIs) and other AD (bupropion, mirtazapine). Specifically, 94% (17/18) of patients on venlafaxine successfully responded. Other variables such as cancer stage and treatment, demographics, psychiatric history, and specific hormonal therapy did not predict AD treatment response. Conclusions: Venlafaxine 150 mg daily yielded significantly higher rates of AD response and complete remission of depression in ER+ breast cancer patients with TAM-induced and AI-induced major depression. Venlafaxine was significantly more effective than SSRIs and atypical AD. This high rate of response is likely due to dual serotonin and norepinephrine reuptake inhibition achieved at 150 mg dosing. Venlafaxine can be safely administered with TAM.

The effects of serotonergic agents on respiration neuromodulation may vary according to differences in the serotonin system, such as those linked to depression. This study investigated how sleep-related respiratory disturbances relate to depression and the use of medications commonly prescribed for depression. Retrospective polysomnography was collated for all 363 individuals who met selection criteria out of 2,528 consecutive individuals referred to a specialized sleep clinic (Ottawa, Canada) between 2006 and 2016. The apnea-hypopnea index (AHI), oxygen saturation nadir, and oxygen desaturation index during REM and NREM sleep were analyzed using mixed analyses of covariance comparing 3 main groups: (1) medicated individuals with depressive disorders (antidepressant group; subdivided into the selective serotonin reuptake inhibitor and norepinephrine-dopamine reuptake inhibitor subgroups), (2) non-medicated individuals with depressive disorders (non-medicated group), and (3) mentally healthy control patients (control group). Individuals with depressive disorders (on antidepressants or not) had significantly higher AHIs compared to control patients (both P ≤ .007). The antidepressant group had a lower NREM sleep oxygen saturation nadir and a higher NREM sleep oxygen desaturation index than the control and non-medicated groups (all P ≤ .009). Within individuals with depressive disorders, independent of depression severity, the selective serotonin reuptake inhibitor group had a lower oxygen saturation nadir and a higher oxygen desaturation index during NREM sleep than the norepinephrine-dopamine reuptake inhibitor (both P ≤ .045) and non-medicated groups (both P < .001) and a higher NREM sleep AHI than the non-medicated group (P = .014). These findings suggest that the use of selective serotonin reuptake inhibitors may be associated with impaired breathing and worse nocturnal oxygen saturation in individuals with depressive disorders and sleep complaints, but this needs to be confirmed by prospective studies.

The use of SSRIs in children and adolescents

Special Report: Women’s Reproductive Mental Health—A Clinical Framework

Background. Up to one-quarter of breast cancer patients suffer clinically significant depression in the year after diagnosis, which may respond to intervention. About half may be prescribed a psychotropic medication, such as a selective serotonin reuptake inhibitor (SSRI), while completing breast cancer therapy. Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes tamoxifen to more active forms. Therefore, concurrent use of SSRIs may reduce tamoxifen’s effectiveness at preventing breast cancer recurrence. The SSRI citalopram has limited potency to inhibit CYP2D6 activity, so has been recommended for breast cancer patients taking tamoxifen. This study provides epidemiologic evidence to support this recommendation. Material and methods. We conducted a case-control study of breast cancer recurrence nested in the population of female residents of Denmark who were diagnosed with non-metastatic estrogen-receptor positive breast cancers between 1994 and 2001 and who took tamoxifen for at least one year. We ascertained complete prescription histories by linking cases’ and controls’ civil registration numbers to the Danish national prescription registry. We estimated the association between SSRI use while taking tamoxifen and risk of recurrent breast cancer. Results. About the same proportion of recurrent cases (37 of 366) and matched controls (35 of 366) received at least one prescription for citalopram or its s-stereoisomer while taking tamoxifen (adjusted odds ratio = 1.1, 95% confidence interval = 0.7, 1.7). Breast cancer patients taking other SSRIs were also at no increased risk of recurrence (adjusted odds ratio = 0.9, 95% confidence interval = 0.5, 1.8). Discussion. Breast cancer patients with indications for an SSRI may be prescribed citalopram – and possibly other SSRI – without adversely affecting the outcome of adjuvant therapy with tamoxifen.