Transitioning Virtual-Only Group Therapy for Substance Use Disorder Patients to a Hybrid Model.

Purpose: Telehealth is associated with a myriad of benefits; however, little is known regarding substance use disorder (SUD) treatment outcomes when participants join group therapy sessions in a combination in-person and virtual setting (hybrid model). We sought to determine if treatment completion rates differed. Patients and Methods: Policy changes caused by the COVID-19 pandemic created a naturalistic, observational cohort study at seven intensive outpatient (IOP) programs in rural Minnesota. Virtual-only delivery occurred 6/1/2020-6/30/2021, while hybrid groups occurred 7/1/2021-7/31/2022. Data was evaluated retrospectively for participants who initiated and discharged treatment during the study period. Participants were IOP group members 18 years and older who had a SUD diagnosis that both entered and discharged treatment during the 26-month period. A consecutive sample of 1502 participants (181-255 per site) was available, with 644 removed: 576 discharged after the study conclusion, 49 were missing either enrollment or discharge data, 14 transferred sites during treatment, and 5 initiated treatment before the study initiation. Helmert contrasts evaluated the impact of hybrid group exposure. Results: A total of 858 individuals were included. Data was not from the medical chart and was deidentified preventing specific demographics; however, the overall IOP sample for 2020-2022, from which the sample was derived, was 29.8% female, and 64.1% were 18-40 years of age. For completed treatment, hybrid group exposure relative to virtual-only had a univariate odds ratio of 1.88 (95% CI: 1.50-2.41, p < 0.001). No significant difference was seen across IOP sites. Conclusion: These results describe a novel hybrid group approach to virtual care for SUDs with outcome data not previously documented in the literature. While virtual treatment delivery can increase access, these results suggest a benefit is derived from including an in-person option. Further research is needed to identify how an in-person component may change dynamics and if it can be replicated in virtual-only models.

Molecular mechanisms involved in alcohol craving, IRF3, and endoplasmic reticulum stress: a multi-omics study.

Alcohol use disorder (AUD) is the most prevalent substance use disorder worldwide. Acamprosate and naltrexone are anti-craving drugs used in AUD pharmacotherapy. However, molecular mechanisms underlying their anti-craving effect remain unclear. This study utilized a patient-derived induced pluripotent stem cell (iPSC)-based model system and anti-craving drugs that are used to treat AUD as "molecular probes" to identify possible mechanisms associated with alcohol craving. We examined the pathophysiology of craving and anti-craving drugs by performing functional genomics studies using iPSC-derived astrocytes and next-generation sequencing. Specifically, RNA sequencing performed using peripheral blood mononuclear cells from AUD patients with extreme values for alcohol craving intensity prior to treatment showed that inflammation-related pathways were highly associated with alcohol cravings. We then performed a genome-wide assessment of chromatin accessibility and gene expression profiles of induced iPSC-derived astrocytes in response to ethanol or anti-craving drugs. Those experiments identified drug-dependent epigenomic signatures, with IRF3 as the most significantly enriched motif in chromatin accessible regions. Furthermore, the activation of IRF3 was associated with ethanol-induced endoplasmic reticulum (ER) stress which could be attenuated by anti-craving drugs, suggesting that ER stress attenuation might be a target for anti-craving agents. In conclusion, we found that craving intensity was associated with alcohol consumption and treatment outcomes. Our functional genomic studies suggest possible relationships among craving, ER stress, IRF3 and the actions of anti-craving drugs.

Systematic review and meta-analysis: Combining transcranial magnetic stimulation or direct current stimulation with pharmacotherapy for treatment of substance use disorders.

BACKGROUND AND OBJECTIVES: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have evidence for their potential in the treatment of substance use disorders (SUD). Medication for addiction treatment (MAT) is underutilized and not always effective. We identified randomized controlled trials (RCTs) and case studies that evaluated the effectiveness of TMS or tDCS used concurrently with MAT in SUD treatment. METHODS: A systematic review of published literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 6/1/2023 by a medical librarian. Craving-related scales were extracted for an effect size calculation. The Physiotherapy Evidence Database (PEDro) scale assessed study quality. RESULTS: Eight studies (7 RCT, 1 case) including 253 individuals were published from 2015 to 2022, 5 of which had available data for meta-analysis. TMS or tDCS combined with MAT significantly reduced craving-related measures relative to sham stimulation (Hedges' g = -0.42, confidence interval: -0.73 to -0.11, p < .01). Opioid use disorder, methadone, and the dorsolateral prefrontal cortex were the most commonly studied SUD, MAT, and target region. DISCUSSION AND CONCLUSIONS: Our results show a significant effect; however, is limited by a small number of studies with heterogeneous methodology across intervention methods and SUDs. Additional trials are needed to fully assess the clinical impact and mechanisms of combined brain stimulation and pharmacotherapy. We discuss a possible mechanism for synergism from these treatment combinations. SCIENTIFIC SIGNIFICANCE: Adds the first systematic review of combination treatment with TMS or tDCS and MAT in SUD patients to the literature and estimates its overall effect size.

Techniques for Measurement of Serotonin: Implications in Neuropsychiatric Disorders and Advances in Absolute Value Recording Methods.

Serotonin (5-HT) is a monoamine neurotransmitter in the peripheral, enteric, and central nervous systems (CNS). Within the CNS, serotonin is principally involved in mood regulation and reward-seeking behaviors. It is a critical regulator in CNS pathologies such as major depressive disorder, addiction, and schizophrenia. Consequently, in vivo serotonin measurements within the CNS have emerged as one of many promising approaches to investigating the pathogenesis, progression, and treatment of these and other neuropsychiatric conditions. These techniques vary in methods, ranging from analyte sampling with microdialysis to voltammetry. Provided this diversity in approach, inherent differences between techniques are inevitable. These include biosensor size, temporal/spatial resolution, and absolute value measurement capabilities, all of which must be considered to fit the prospective researcher's needs. In this review, we summarize currently available methods for the measurement of serotonin, including novel voltammetric absolute value measurement techniques. We also detail serotonin's role in various neuropsychiatric conditions, highlighting the role of phasic and tonic serotonergic neuronal firing within each where relevant. Lastly, we briefly review the present clinical application of these techniques and discuss the potential of a closed-loop monitoring and neuromodulation system utilizing deep brain stimulation (DBS).

A risk identification model for detection of patients at risk of antidepressant discontinuation.

Purpose: Between 30 and 68% of patients prematurely discontinue their antidepressant treatment, posing significant risks to patient safety and healthcare outcomes. Online healthcare forums have the potential to offer a rich and unique source of data, revealing dimensions of antidepressant discontinuation that may not be captured by conventional data sources. Methods: We analyzed 891 patient narratives from the online healthcare forum, "askapatient.com," utilizing content analysis to create PsyRisk-a corpus highlighting the risk factors associated with antidepressant discontinuation. Leveraging PsyRisk, alongside PsyTAR [a publicly available corpus of adverse drug reactions (ADRs) related to antidepressants], we developed a machine learning-driven algorithm for proactive identification of patients at risk of abrupt antidepressant discontinuation. Results: From the analyzed 891 patients, 232 reported antidepressant discontinuation. Among these patients, 92% experienced ADRs, and 72% found these reactions distressful, negatively affecting their daily activities. Approximately 26% of patients perceived the antidepressants as ineffective. Most reported ADRs were physiological (61%, 411/673), followed by cognitive (30%, 197/673), and psychological (28%, 188/673) ADRs. In our study, we employed a nested cross-validation strategy with an outer 5-fold cross-validation for model selection, and an inner 5-fold cross-validation for hyperparameter tuning. The performance of our risk identification algorithm, as assessed through this robust validation technique, yielded an AUC-ROC of 90.77 and an F1-score of 83.33. The most significant contributors to abrupt discontinuation were high perceived distress from ADRs and perceived ineffectiveness of the antidepressants. Conclusion: The risk factors identified and the risk identification algorithm developed in this study have substantial potential for clinical application. They could assist healthcare professionals in identifying and managing patients with depression who are at risk of prematurely discontinuing their antidepressant treatment.

Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation.

Introduction: Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone. Methods: Multiple-cyclic square wave voltammetry (M-CSWV) was used to investigate how deep brain stimulation (130 Hz, 0.2 ms, and 0.2 mA) of the rodent ventral segmental area (VTA), which contains abundant dopaminergic neurons, modulates the acute effects of oxycodone administration (2.5 mg/kg, i.v.) on nucleus accumbens core (NAcc) tonic extracellular dopamine levels and respiratory rate in urethane-anesthetized rats (1.5 g/kg, i.p.). Results: I.V. administration of oxycodone resulted in an increase in NAcc tonic dopamine levels (296.9 ± 37.0 nM) compared to baseline (150.7 ± 15.5 nM) and saline administration (152.0 ± 16.1 nM) (296.9 ± 37.0 vs. 150.7 ± 15.5 vs. 152.0 ± 16.1, respectively, p = 0.022, n = 5). This robust oxycodone-induced increase in NAcc dopamine concentration was associated with a sharp reduction in respiratory rate (111.7 ± 2.6 min-1 vs. 67.9 ± 8.3 min-1; pre- vs. post-oxycodone; p < 0.001). Continuous DBS targeted at the VTA (n = 5) reduced baseline dopamine levels, attenuated the oxycodone-induced increase in dopamine levels to (+39.0% vs. +95%), and respiratory depression (121.5 ± 6.7 min-1 vs. 105.2 ± 4.1 min-1; pre- vs. post-oxycodone; p = 0.072). Discussion: Here we demonstrated VTA DBS alleviates oxycodone-induced increases in NAcc dopamine levels and reverses respiratory suppression. These results support the possibility of using neuromodulation technology for treatment of drug addiction.

Single cell transcriptomics reveals distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with opioid use disorder.

The opioid epidemic represents a national crisis. Oxycodone is one of the most prescribed opioid medications in the United States, whereas buprenorphine is currently the most prescribed medication for opioid use disorder (OUD) pharmacotherapy. Given the extensive use of prescription opioids and the global opioid epidemic, it is essential to understand how opioids modulate brain cell type function at the single-cell level. We performed single nucleus RNA-seq (snRNA-seq) using iPSC-derived forebrain organoids from three male OUD subjects in response to oxycodone, buprenorphine, or vehicle for seven days. We utilized the snRNA-seq data to identify differentially expressed genes following drug treatment using the Seurat integrative analysis pipeline. We utilized iPSC-derived forebrain organoids and single-cell sequencing technology as an unbiased tool to study cell-type-specific and drug-specific transcriptional responses. After quality control filtering, we analyzed 25787 cells and identified sixteen clusters using unsupervised clustering analysis. Our results reveal distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with OUD. Specifically, buprenorphine displayed a significant influence on transcription regulation in glial cells. However, oxycodone induced type I interferon signaling in many cell types, including neural cells in brain organoids. Finally, we demonstrate that oxycodone, but not buprenorphine activated STAT1 and induced the type I interferon signaling in patients with OUD. These data suggest that elevation of STAT1 expression associated with OUD might play a role in transcriptional regulation in response to oxycodone. In summary, our results provide novel mechanistic insight into drug action at single-cell resolution.

Systematic review: Wearable remote monitoring to detect nonalcohol/nonnicotine-related substance use disorder symptoms.

BACKGROUND AND OBJECTIVES: Substance use disorders (SUDs) are chronic relapsing diseases characterized by significant morbidity and mortality. Phenomenologically, patients with SUDs present with a repeating cycle of intoxication, withdrawal, and craving, significantly impacting their diagnosis and treatment. There is a need for better identification and monitoring of these disease states. Remote monitoring chronic illness with wearable devices offers a passive, unobtrusive, constant physiological data assessment. We evaluate the current evidence base for remote monitoring of nonalcohol, nonnicotine SUDs. METHODS: We performed a systematic, comprehensive literature review and screened 1942 papers. RESULTS: We found 15 studies that focused mainly on the intoxication stage of SUD. These studies used wearable sensors measuring several physiological parameters (ECG, HR, O2 , Accelerometer, EDA, temperature) and implemented study-specific algorithms to evaluate the data. DISCUSSION AND CONCLUSIONS: Studies were extracted, organized, and analyzed based on the three SUD disease states. The sample sizes were relatively small, focused primarily on the intoxication stage, had low monitoring compliance, and required significant computational power preventing "real-time" results. Cardiovascular data was the most consistently valuable data in the predictive algorithms. This review demonstrates that there is currently insufficient evidence to support remote monitoring of SUDs through wearable devices. SCIENTIFIC SIGNIFICANCE: This is the first systematic review to show the available data on wearable remote monitoring of SUD symptoms in each stage of the disease cycle. This clinically relevant approach demonstrates what we know and do not know about the remote monitoring of SUDs within disease states.

Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder.

Acamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The identification of predictive biomarkers of acamprosate treatment response in patients with AUD would be a substantial advance in addiction medicine. We designed this study to use proteomics data as a quantitative biological trait as a step toward identifying inflammatory modulators that might be associated with acamprosate treatment outcomes. The NIAAA-funded Mayo Clinic Center for the Individualized Treatment of Alcoholism study had previously recruited 442 AUD patients who received 3 months of acamprosate treatment. However, only 267 subjects returned for the 3-month follow-up visit and, as a result, had treatment outcome information available. Baseline alcohol craving intensity was the most significant predictor of acamprosate treatment outcomes. We performed plasma proteomics using the Olink target 96 inflammation panel and identified that baseline plasma TNF superfamily member 10 (TNFSF10) concentration was associated with alcohol craving intensity and variation in acamprosate treatment outcomes among AUD patients. We also performed RNA sequencing using baseline peripheral blood mononuclear cells from AUD patients with known acamprosate treatment outcomes which revealed that inflammation-related pathways were highly associated with relapse to alcohol use during the 3 months of acamprosate treatment. These observations represent an important step toward advancing our understanding of the pathophysiology of AUD and molecular mechanisms associated with acamprosate treatment response. In conclusion, applying omics-based approaches may be a practical approach for identifying biologic markers that could potentially predict alcohol craving intensity and acamprosate treatment response.

Measuring patient satisfaction in an outpatient psychiatric clinic. What factors play a role?

INTRODUCTION: Patient satisfaction is defined as the perception that one's general health care needs are being met. Prior research suggests that positive patient satisfaction with health care facilitates the physician-patient relationship and enhances quality of life. OBJECTIVE: The primary purpose of this study was to assess patient satisfaction (as measured by the Patient Satisfaction Questionnaire (PSQ-18)) of patients observed by general psychiatry residents and to examine the effects of depression and anxiety on patient satisfaction. A secondary purpose was to explore the effects of three 1-h mentalization-based skills training sessions on the PSQ-18 scores of psychiatric residents. We hypothesized that depressive and anxiety symptoms would negatively impact patient satisfaction. We hypothesized that patients' satisfaction scores would improve after mentalization training. METHODS: This was a prospective case-controlled study, enrolling adult patients (n = 157) referred for psychiatric assessment in a psychiatric resident outpatient clinic. The primary outcome was patient satisfaction as measured by the PSQ-18. This outcome was compared to anxiety and depression symptoms as measured by the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder 7-Item scale (GAD-7) questionnaires. Outcome data from the PSQ-18 were compared among residents before and after they completed mentalization training. The data were analyzed with univariate analyses and multiple linear regression. RESULTS: Overall the patients were satisfied with clinician communication and interpersonal manner (4.21 ± 0.66 and 4.15 ± 0.69, respectively). The patients score on PHQ-9 was inversely related to their scores on time spent (TS) (p = 0.01) and accessibility/convenience (AC) (p = 0.0009) subscales of the PSQ-18. GAD-7 score was inversely related to patients scores on AC subscale (p = 0.01). Brief mentalization training for the providers did not impact patient satisfaction scores. CONCLUSIONS: Our study reveals that depression and anxiety can negatively impact PSQ-18 patient scoring in psychiatric outpatients observed for the first time in a resident clinic. However, this study failed to show that a brief mentalization-based training could improve patient satisfaction scores that were already quite high at baseline.

Genetic variants associated with acamprosate treatment response in alcohol use disorder patients: A multiple omics study.

BACKGROUND AND PURPOSE: Acamprosate is an anti-craving drug used for the pharmacotherapy of alcohol use disorder (AUD). However, only some patients achieve optimal therapeutic outcomes. This study was designed to explore differences in metabolomic profiles between patients who maintained sobriety and those who relapsed, to determine whether those differences provide insight into variation in acamprosate treatment response phenotypes. EXPERIMENTAL APPROACH: We previously conducted an acamprosate trial involving 442 AUD patients, and 267 of these subjects presented themselves for a 3-month follow-up. The primary outcome was abstinence. Clinical information, genomic data and metabolomics data were collected. Baseline plasma samples were assayed using targeted metabolomics. KEY RESULTS: Baseline plasma arginine, threonine, α-aminoadipic acid and ethanolamine concentrations were associated with acamprosate treatment outcomes and baseline craving intensity, a measure that has been associated with acamprosate treatment response. We next applied a pharmacometabolomics-informed genome-wide association study (GWAS) strategy to identify genetic variants that might contribute to variations in plasma metabolomic profiles that were associated with craving and/or acamprosate treatment outcome. Gene expression data for induced pluripotent stem cell-derived forebrain astrocytes showed that a series of genes identified during the metabolomics-informed GWAS were ethanol responsive. Furthermore, a large number of those genes could be regulated by acamprosate. Finally, we identified a series of single nucleotide polymorphisms that were associated with acamprosate treatment outcomes. CONCLUSION AND IMPLICATIONS: These results serve as an important step towards advancing our understanding of disease pathophysiology and drug action responsible for variation in acamprosate response and alcohol craving in AUD patients.

Substance Use Disorders and Telehealth in the COVID-19 Pandemic Era: A New Outlook.

During the current coronavirus disease 2019 epidemic, many outpatient chemical dependency treatment programs and clinics are decreasing their number of in-person patient contacts. This has widened an already large gap between patients with substance use disorders (SUDs) who need treatment and those who have actually received treatment. For a disorder where group therapy has been the mainstay treatment option for decades, social distancing, shelter in place, and treatment discontinuation have created an urgent need for alternative approaches to addiction treatment. In an attempt to continue some care for patients in need, many medical institutions have transitioned to a virtual environment to promote safe social distancing. Although there is ample evidence to support telemedical interventions, these can be difficult to implement, especially in the SUD population. This article reviews current literature for the use of telehealth interventions in the treatment of SUDs and offers recommendations on safe and effective implementation strategies based on the current literature.

Medication-assisted therapies for opioid use disorders in patients with chronic pain.

Opioids have been used to treat pain and invoke pleasure for centuries. Modern scientific advancements have led to more potent, synthetic opioids. While certainly more effective in treating pain, they can also be much more addictive. Over the years the scientific community has developed a clearer understanding of the role opioid receptors play in causing and treating opioid use disorders (OUD) and we now know that OUD can develop in individuals taking opioids for "legitimate" pain. Current guidelines suggest that all prescribers (especially those prescribing opioids) be capable treating OUD. Pharmacological advances have led to a wide array of safe and effective treatment options to address OUDs. This paper will discuss the history of opioid development, what is known about the transition from analgesic uses to addiction and modern evidenced based treatment strategies to address OUDs.

Medication-Assisted Treatment for Opioid-Use Disorder.

The United States is in the midst of a national opioid epidemic. Physicians are encouraged both to prevent and treat opioid-use disorders (OUDs). Although there are 3 Food and Drug Administration-approved medications to treat OUD (methadone, buprenorphine, and naltrexone) and there is ample evidence of their efficacy, they are not used as often as they should. We provide a brief review of the 3 primary medications used in the treatment of OUD. Using data from available medical literature, we synthesize existing knowledge and provide a framework for how to determine the optimal approach for outpatient management of OUD with medication-assisted treatments.

The effects of parental opioid use on the parent-child relationship and children's developmental and behavioral outcomes: a systematic review of published reports.

BACKGROUND: Between 2009 and 2014, nearly 3% of US children (age ≤ 17 years) lived in households with at least 1 parent with substance use disorder. The present systematic review aimed to evaluate effects of parental opioid use disorder on the parent-child relationship and child developmental and behavioral outcomes. METHODS: Several databases were comprehensively searched for studies published from January 1980 through February 2018 that reviewed effects of parental opioid addiction on parent-child relationships and outcomes of children (age, 0-16 years). RESULTS: Of 304 unique studies, 12 evaluated effects of parental opioid addiction on the parent-child relationship as the primary outcome and on children's outcomes, including behaviors and development. Observation of mother-child interaction showed that mothers with opioid use disorders are more irritable, ambivalent, and disinterested while showing greater difficulty interpreting children's cues compared with the control group. Children of parents with opioid use disorders showed greater disorganized attachment; they were less likely to seek contact and more avoidant than children in the control group. The children also had increased risk of emotional and behavioral issues, poor academic performance, and poor social skills. Younger children had increased risk of abuse or neglect, or both, that later in life may lead to such difficulties as unemployment, legal issues, and substance abuse. CONCLUSIONS: Current evidence shows association between parental opioid addiction and poorer mother-child attachment and suboptimal child developmental and behavioral outcomes. Further research and treatment targeting children and families with parental opioid use are needed to prevent difficulties later in life.

CRAFFT as a Substance Use Screening Instrument for Adolescent Psychiatry Admissions.

BACKGROUND: Adolescent use of alcohol and illicit substances is quite common among pediatric psychiatry inpatients; however, little data exist on substance use screening instruments that can be used to augment thorough psychiatric diagnostic interviews. CRAFFT is a screening tool for adolescent substance use that has been validated in outpatient general medical settings. This is the first study to examine its use in adolescent psychiatric inpatients. METHODS: We performed a chart review of records from adolescents admitted to our inpatient psychiatric unit who completed a CRAFFT screen on admission. We compared CRAFFT scores with other measures of substance use, including urine drug screens and the diagnosis of a substance use disorder at discharge. We also examined measures of depression and suicidality in individuals with elevated CRAFFT scores (≥2 positive answers out of 6) and compared them with measures in those with normal CRAFFT scores. RESULTS: Elevated CRAFFT scores were correlated with other measures of alcohol and substance use, including the diagnosis of a substance use disorder at discharge (P<0.0001), and laboratory screening for alcohol (P=0.0048) and marijuana (P<0.0001) on admission. Previous suicide attempts (P=0.005) and "psychiatric trauma" (P=0.0027) were also positively associated with elevated CRAFFT scores. CONCLUSIONS: CRAFFT scores in adolescent inpatients were correlated with other measures of substance use, supporting its efficacy as a screening tool in this population. CRAFFT scores were also positively correlated with a history of psychiatric trauma and past suicide attempts, which is consistent with the results of previous studies associating pediatric substance use and traumatic life events with an increased risk of suicide.

A randomized comparison of ketamine versus methohexital anesthesia in electroconvulsive therapy.

To assess the clinical utility of ketamine as an anesthetic agent for electroconvulsive therapy (ECT), based upon recent findings that ketamine may have antidepressant properties. Depressed ECT patients were randomly assigned to receive anesthesia with either ketamine or methohexital. Outcome measures included assessments of depressive severity, cognition, post-anesthesia side effects, and hemodynamics. Twenty one patients were treated with ketamine and 17 with methohexital. There were no significant differences in depression or cognitive outcomes between the two drugs. Additionally, there were no measures of post-anesthesia tolerability or hemodynamics which favored ketamine. Ketamine anesthesia does not accelerate the antidepressant effect of ECT or diminish the cognitive side effects, at least as measured in this study. Furthermore, there is no apparent benefit of ketamine for speed or quality of post-ECT recovery, and it is associated with higher systolic blood pressures after the treatments. Ketamine is associated with longer motor seizure duration than methohexital.

Antidepressant use and body mass index change in overweight adolescents: a historical cohort study.

OBJECTIVE: Given the limited empirical data on antidepressant use and weight change in children, we performed a historical cohort study to assess change in age- and sex-standardized body mass index associated with antidepressant use among overweight adolescents diagnosed with a depressive disorder. METHODS: We systematically reviewed electronic medical records from a tertiary academic medical center and identified adolescents (age 13-18 years) who were overweight (body mass index >85th percentile) and had a depression diagnosis. Patients were seen from January 1, 2000, through January 1, 2010. Age- and sex-standardized body mass index scores were calculated at initiation of antidepressant medication and at the end of treatment. Unmedicated patients had baseline and final age- and sex-standardized body mass index calculated using the first and last recorded measurements in the study period (maximum time between measures was 5 years). RESULTS: In total, 435 patients (301 female) met our inclusion criteria; of these, 255 were prescribed an antidepressant (selective serotonin reuptake inhibitor, serotonin norepinephrine reuptake inhibitor, tricyclic antidepressant, or dopamine-norepinephrine reuptake inhibitor). Age- and sex-standardized body mass index significantly increased (F1,193=14.34; P<0.001) only for adolescents treated with selective serotonin reuptake inhibitors. For patients receiving other medications or no medication, age- and sex-standardized body mass index did not change significantly. CONCLUSION: This study provides initial empiric evidence for a link between selective serotonin reuptake inhibitor use and weight gain in already overweight adolescents. Further study of antidepressant use and weight gain in other pediatric populations and in prospective studies is warranted.