Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder.

BACKGROUND: The understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI). METHODS: 67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[-]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance). RESULTS: MDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia. CONCLUSION: IR appears to be linked to depressive symptoms characteristic of the "metabolic" MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI.

Antidepressant-related microstructural changes in the external capsule.

Several magnetic resonance imaging (MRI) studies have reported that antidepressant medications are strongly linked to brain microstructural alterations. Notably, external capsule alterations have been reported to be a biological marker for therapeutic response. However, prior studies did not investigate whether a change in the neurite density or directional coherence of white matter (WM) fibers underlies the observed microstructural alterations. This MRI-based case-control study examined the relationship between patients' current use of antidepressant medications and advanced measurements of external capsule WM microstructure derived from multishell diffusion imaging using neurite orientation dispersion and density imaging (NODDI). The study compared a group of thirty-five participants who were taking antidepressant medications comprising selective serotonin reuptake inhibitors (SSRIs) (n = 25) and serotonin and norepinephrine reuptake inhibitors (SNRIs) with a control group of thirty-five individuals matched in terms of age, sex, race, and atherosclerotic cardiovascular risk factors. All participants were selected from the Dallas Heart Study phase 2, a multi-ethnic, population-based cohort study. A series of multiple linear regression analyses were conducted to predict microstructural characteristics of the bilateral external capsule using age, sex, and antidepressant medications as predictor variables. There was significantly reduced neurite density in the bilateral external capsules of patients taking SSRIs. Increased orientation dispersion in the external capsule was predominantly seen in patients taking SNRIs. Our findings suggest an association between specific external capsule microstructural changes and antidepressant medications, including reduced neurite density for SSRIs and increased orientation dispersion for SNRIs.

The Impact of Development on Antidepressant and Placebo Response in Anxiety Disorders: A Bayesian Hierarchical Meta-Analytic Examination of Randomized Controlled Trials in Children, Adolescents, and Adults.

Background: Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus second-line psychopharmacological interventions. Objective: To meta-analytically compare the trajectory of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo response in youth and adults with anxiety disorders. Methods: Weekly symptom severity data were extracted from prospective, randomized, parallel-group, placebo-controlled trials of SSRIs and SNRIs in children, adolescents, and adults with anxiety disorders (generalized, separation, and social anxiety disorders as well as panic disorder). Treatment response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in symptom severity was evaluated as a function of time, and post hoc analyses were conducted to determine the sensitivity of these results across sample heterogeneity and alternative functional forms. Results: Data were included from 11 trials of youth (SSRI, κ = 7; SNRI, κ = 4) and 71 studies of adults (SSRI, κ = 46; SNRI, κ = 25). In total, 1067 youth participated in SSRI trials and 1024 in SNRI trials. In total, 10,826 adults participated in SSRI trials (placebo, n = 5367; SSRI n = 5,459) and 6232 in SNRI trials (placebo, n = 3,128; SNRI n = 3,094). A logarithmic model best described the response. Placebo response was similar in youth and adults (mean difference = -1.98 ± 6.21, 95% credible interval [CrI]: -10.2 to 14.2, p = 0.750), and statistically significant improvement from baseline emerged by week 2 in both adults (mean difference: -18.34 + 1.017, 95% CrI: -20.3 to 16.3, p < 0.001) and youth (mean difference: -23.74 + 3.736, 95% CrI: -31.1 to -16.4, p < 0.001). SSRIs produced similar improvements for youth and adults (p = 0.129), but SNRIs produced slower improvement in youth than adults (p = 0.018). Conclusions: Antidepressant-related improvement occurs early in youth and adults with anxiety disorders. SSRI response is similar in adults and youth; however, SNRIs produce greater responses in adults than youth, potentially representing a developmental effect.

Effect of venlafaxine on anhedonia and amotivation in patients with major depressive disorder.

OBJECTIVE: Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD). METHODS: Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data. RESULTS: At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: -2.73 [-3.63, -1.82], p < 0.0001) and amotivation scores (mean, 95% CI: -0.78 [-1.04, -0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time. CONCLUSION: This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.

Access to a tailored mobile application enhances medication adherence among young users of antidepressants.

Introduction: Patients' adherence to antidepressants is generally reported to be poor. This study examined whether users of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) enhance medication adherence following access to a mobile application (app) tailored for this patient group. The study addresses the implementation phase of medication adherence. Methods: The study was a single group pre-post intervention design. Data were collected using the validated OsloMet Adherence-to-medication Survey tool (OMAS-37) before and after app access. Pre-app access survey (Survey 1) was conducted via social media and online newspapers, encompassing 445 SSRI/SNRI users aged 18 years and above. Post-app access survey (Survey 2) was sent to 103 SSRI/SNRI users from Survey 1. Wilcoxon Signed Rank Test compared pre- and post-intervention adherence measurements. Pearson's chi-square tests and Fisher's exact tests compared study population categories. Results: Forty-two SSRI/SNRI users, median age 26 (IQR 17), 93% identifying as female, used the app while using the same antidepressant during the 2-month period between gaining access to the app and Survey 2. There was a statistically significant reduction in non-adherence score post-app access (z = 3.57, n = 42, p < 0.001) with medium effect size (r = 0.39), indicating enhanced adherence. Total non-adherence score decreased by 39% from pre-to post-access, and there was a 12% decrease in users scoring equivalent with poor adherence (score <2) post-access. Twenty-nine of 37 non-adherence causes improved, with three showing statistical significance. Of 42 responders, 50% (n = 21) indicated using the app one to two times, while 50% (n = 21) more than three times. Approximately 69% (n = 28) found it useful, and 43% (n = 18) felt safer in their use of antidepressants after access to the app. No significant preference was observed for the app over alternative sources of information. Discussion: Enhanced medication adherence was observed among antidepressant users following access to the tailored app. Further studies are warranted to evaluate the app applicability to a broader range of antidepressants users or other patient groups, encompassing those in the initiation phase of medication adherence. The app is intended as an easily accessible supplement to the information and advice provided by prescribing physicians and dispensing pharmacists.

Desvenlafaxine-Triggered Acneiform Eruptions on the Hand: A Compelling Case Report.

A 45-year-old male developed a skin eruption after starting Desvenlafaxine for depressive symptoms associated with schizophreniform disorder. The patient developed a rash on the hand, hyperpigmentation, and itching, which resolved after discontinuing the medication. The Naranjo score suggested a probable link between desvenlafaxine and the skin reaction. Stable vital signs and normal labs supported this conclusion. The case underscores the importance of recognizing and reporting adverse drug reactions, even with generally safe medications like desvenlafaxine. Further research with larger samples is needed to explore this relationship in more depth.

Understanding the differential impacts of two antidepressants on locomotion of freshwater snails (Lymnaea stagnalis).

There is growing evidence of negative impacts of antidepressants on behavior of aquatic non-target organisms. Accurate environmental risk assessment requires an understanding of whether antidepressants with similar modes of action have consistent negative impacts. Here, we tested the effect of acute exposure to two antidepressants, fluoxetine and venlafaxine (0-50 µg/L), on the behavior of non-target organism, i.e., freshwater pond snail, Lymnaea stagnalis. As compounds interact with chemical cues in the aquatic ecosystems, we also tested whether the effects altered in the presence of bile extract containing 5α-cyprinol sulfate (5α-CPS), a characterized kairomone of a natural predator, common carp (Cyprinus carpio). Behavior was studied using automated tracking and analysis of various locomotion parameters of L. stagnalis. Our results suggest that there are differences in the effects on locomotion upon exposure to venlafaxine and fluoxetine. We found strong evidence for a non-monotonic dose response on venlafaxine exposure, whereas fluoxetine only showed weak evidence of altered locomotion for a specific concentration. Combined exposure to compounds and 5α-CPS reduced the intensity of effects observed in the absence of 5α-CPS, possibly due to reduced bioavailability of the compounds. The results highlight the need for acknowledging different mechanisms of action among antidepressants while investigating their environmental risks. In addition, our results underline the importance of reporting non-significant effects and acknowledging individual variation in behavior for environmental risk assessment.

Discontinuation of antidepressant treatment: a retrospective cohort study on more than 20,000 participants.

BACKGROUND: Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation. METHODS: We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent. RESULTS: Among the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications. CONCLUSIONS: Our study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance.

Peripheral edema associated with antidepressant use: Systematic review of case reports.

BACKGROUND: Oedema associated with psychotropics can impose a considerable burden, leading to increased morbidity and cost. Peripheral oedema is sometimes related to the use of antidepressants, which are among the most prescribed psychotropic medications. We reviewed the reported cases of antidepressant-associated oedema to understand the risk factors, aetiology and outcome. METHODS: We searched the Medline, Web of Science and Embase databases to identify reported cases of peripheral oedema associated with antidepressant use. We included studies published in English and those with full-text availability. A systematic review of the reports was done to identify the antidepressants associated with oedema, explore possible risk factors, investigate potential mechanisms, and assess the outcome. RESULTS: We identified a total of 45 cases (27 case reports and five case series) that reported oedema associated with antidepressant use. Almost all major classes of antidepressants were found to be associated with oedema. Among these drugs, trazodone, mirtazapine, and escitalopram were the most implicated. Older age and female gender were more commonly associated with oedema. Etiologically, antagonism of α1 adrenergic receptors and 5HT2A receptors, leading to vasodilation and oedema, emerged as the most prevalent mechanisms. In most cases, the oedema subsided following the discontinuation of the antidepressants. CONCLUSIONS: Peripheral oedema associated with antidepressant use can represent a significant adverse drug reaction involving various classes of antidepressants. To ensure timely identification and proper management of oedema, regular monitoring is crucial.

Neurometabolite changes in response to antidepressant medication: A systematic review of 1H-MRS findings.

Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and (es)ketamine are used to treat major depressive disorder (MDD). These different types of medication may involve common neural pathways related to glutamatergic and GABAergic neurotransmitter systems, both of which have been implicated in MDD pathology. We conducted a systematic review of pharmacological proton Magnetic Resonance Spectroscopy (1H-MRS) studies in healthy volunteers and individuals with MDD to explore the potential impact of these medications on glutamatergic and GABAergic systems. We searched PubMed, Web of Science and Embase and included randomized controlled trials or cohort studies, which assessed the effects of SSRIs, SNRIs, or (es)ketamine on glutamate, glutamine, Glx or GABA using single-voxel 1H-MRS or Magnetic Resonance Spectroscopic Imaging (MRSI). Additionally, studies were included when they used a field strength > 1.5 T, and when a comparison of metabolite levels between antidepressant treatment and placebo or baseline with post-medication metabolite levels was done. We excluded animal studies, duplicate publications, or articles with 1H-MRS data already described in another included article. Twenty-nine studies were included in this review. Fifteen studies investigated the effect of administration or treatment with SSRIs or SNRIs, and fourteen studies investigated the effect of (es)ketamine on glutamatergic and GABAergic metabolite levels. Studies on SSRIs and SNRIs were highly variable, generally underpowered, and yielded no consistent findings across brain regions or specific populations. Although studies on (es)ketamine were also highly variable, some demonstrated an increase in glutamate levels in the anterior cingulate cortex in a time-dependent manner after administration. Our findings highlight the need for standardized study and acquisition protocols. Additionally, measuring metabolites dynamically over time or combining 1H-MRS with whole brain functional imaging techniques could provide valuable insights into the effects of these medications on glutamate and GABAergic neurometabolism.

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

BACKGROUND: Antidepressant 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. METHODS: A 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. DISCUSSION: Results 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 REGISTRATION: ClinicalTrials.gov: NCT05051995, first registered September 20, 2021.

Psychological variables associated with resistance to treatment with serotonin and noradrenaline reuptake inhibitors in fibromyalgia.

OBJECTIVE: The treatment of fibromyalgia (FM) often offers only partial pain relief. Among the most effective drugs for FM pain are serotonin and noradrenalin reuptake inhibitors (SNRI). Few studies investigated the affective temperaments and personality features in FM. Our objective was to explore the associations between the affective temperaments, personality traits, schizotypy and response to SNRI treatment in FM. METHODS: 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-] and 30 healthy controls were recruited. Resistance to SNRI was defined as <30% pain reduction during at least 8-week treatment. Subjects were assessed by physician and filled self-report questionnaires: Temperament Scale of Memphis, Pisa and San Diego- autoquestionnaire, Ten Item Personality Inventory, Oxford-Liverpool Inventory of Feelings and Experiences and Fibromyalgia Impact Questionnaire (FIQ). ANOVA analysis and simple logistic regressions were used to examine the links between psychological variables and lack of response to SNRI. RESULTS: FM T[-] presented higher scores in total FIQ and in physical, work, well-being, pain, fatigue/sleep, stiffness domains than FM T[+]. FM T[-] showed higher levels of: irritable and anxious temperaments, neuroticism, schizotypy than FM T[+]. The levels of depressive, irritable and anxious temperaments, introversion, neuroticism and schizotypy were linked to lack of response to SNRI. CONCLUSIONS: FM T[+] and FM T[-] differ in clinical presentation and psychological features. The levels of affective temperaments, personality and schizotypal traits are associated with lack response to SNRI in FM.

Acid Reflux: A Rare Adverse Effect of Duloxetine.

Duloxetine is a medication that belongs to the serotonin and norepinephrine reuptake inhibitor (SNRI) class of drugs and is commonly used to treat various conditions, such as depression, generalized anxiety disorder, neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. While side effects, such as headaches, constipation, dry mouth, dizziness, and blurred vision, are commonly associated with duloxetine, we present a case of a 59-year-old woman who experienced a rare adverse event of acid reflux while taking a 30 mg dose of duloxetine for fibromyalgia. According to the available literature, this adverse event has been reported in only 1.38% of the population.

A Case Report on Serotonin Syndrome in a Patient With Parkinson's Disease: Diagnostic and Management Challenges.

Patients with Parkinson's disease are often at risk of polypharmacy, which can lead to serious medication side effects and interactions. Serotonin syndrome (SS) can develop in this patient population due to a possible drug-drug interaction between antidepressants and antiparkinson drugs with serotoninergic activity. On the other hand, these patients are also at risk of malignant syndrome (MS) secondary to dopaminergic medication withdrawal. In this case report, we present a 71-year-old female with Parkinson's disease who developed symptoms suggestive of SS. The patient was admitted to the medical intensive care unit at the Institute for Pulmonary Diseases of Vojvodina in the Republic of Serbia due to impaired consciousness and a previously witnessed cardiorespiratory arrest. Her chronic antiparkinson medication regimen consisted of levodopa, benserazide, entacapone, ropinirole, and rasagiline. Furthermore, she had been prescribed duloxetine for a remote history of depression, which she had only been taking intermittently. Several days before admission, however, the patient started taking duloxetine again due to low mood. Upon admission, laboratory tests revealed leukocytosis with neutrophilia, elevated C-reactive protein, procalcitonin, lactate, urea, and creatinine. Serum creatine kinase (CK) levels were also elevated at 1250 U/L. Six hours after admission to the ICU, the patient developed hyperthermia, hyperreflexia, spontaneous myoclonus, and tremors. Her CK levels continued to rise, reaching 6900 U/L, and her renal function worsened. Due to the possibility of either SS or MS, external cooling measures with frozen gel packs were administered, resulting in the patient's stabilization over a few hours. Further, serotoninergic medication (rasagiline and duloxetine) was discontinued. On the fifth day of hospitalization, a head CT showed signs of cytotoxic edema. On the 11th day, the patient became hemodynamically unstable and passed away despite all adequate resuscitative measures. The purpose of this case report is to raise awareness of possible SS in patients taking monoamine oxidase-B (MAO-B) inhibitors such as rasagiline. Clinicians should have a high index of suspicion for this complication, especially in patients who are treated for comorbid depression with serotoninergic drugs. Furthermore, we emphasize the importance of correctly differentiating SS from MS, which are both risks for patients with Parkinson's disease. A correct approach to these patients is of utmost importance for adequate management and optimal outcomes.

Plasma concentrations of SSRI/SNRI after bariatric surgery and the effects on depressive symptoms.

Background: Depression and treatment with antidepressants SSRI/SNRI are common in people with morbid obesity who are candidates for bariatric surgery. There is few and inconsistent data about the postoperative plasma concentrations of SSRI/SNRI. The aims of our study were to provide comprehensive data about the postoperative bioavailability of SSRI/SNRI, and the clinical effects on depressive symptoms. Methods: Prospective multicenter study including 63 patients with morbid obesity and therapy with fixed doses of SSRI/SNRI: participants filled the Beck Depression Inventory (BDI) questionnaire, and plasma levels of SSRI/SNRI were measured by HPLC, preoperatively (T0), and 4 weeks (T1) and 6 months (T2) postoperatively. Results: The plasma concentrations of SSRI/SNRI dropped significantly in the bariatric surgery group from T0 to T2 by 24.7% (95% confidence interval [CI], -36.8 to -16.6, p = 0.0027): from T0 to T1 by 10.5% (95% 17 CI, -22.7 to -2.3; p = 0.016), and from T1 to T2 by 12.8% (95% CI, -29.3 to 3.5, p = 0.123), respectively.There was no significant change in the BDI score during follow-up (-2.9, 95% CI, -7.4 to 1.0; p = 0.13).The clinical outcome with respect to SSRI/SNRI plasma concentrations, weight change, and change of BDI score were similar in the subgroups undergoing gastric bypass surgery and sleeve gastrectomy, respectively. In the conservative group the plasma concentrations of SSRI/SNRI remained unchanged throughout the 6 months follow-up (-14.7, 95% CI, -32.6 to 1.7; p = 0.076). Conclusion: In patients undergoing bariatric surgery plasma concentrations of SSRI/SNRI decrease significantly by about 25% mainly during the first 4 weeks postoperatively with wide individual variation, but without correlation to the severity of depression or weight loss.

Advances in Pharmacotherapy for Pediatric Anxiety Disorders.

The evidence base for psychopharmacologic interventions in children and adolescents with anxiety disorders has significantly increased, and our understanding of the relative efficacy and tolerability of interventions has expanded contemporaneously. Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for pediatric anxiety due to their robust efficacy although other agents may have efficacy. This review summarizes the data concerning the use of SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, atypical anxiolytics (eg, 5HT1A agonists, alpha agonists), and benzodiazepines in pediatric anxiety disorder cases (ie, generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, and panic disorder). The extant data suggest that SSRIs and SNRIs are effective and well tolerated. SSRIs as monotherapy and SSRIs + cognitive behavioral therapy reduce symptoms in youth with anxiety disorders. However, randomized controlled trials do not suggest efficacy for benzodiazepines or the 5HT1A agonist, buspirone, in pediatric anxiety disorder cases.

Venlafaxine deprescribing and thyroid function.

STUDY OBJECTIVE: This report highlights the effects of discontinuing venlafaxine on thyroid function in an older adult with previously well-managed Hashimoto thyroiditis and sleep apnea. DESIGN: Concurrent intervention. CASE STUDY: Setting Community-based psychiatry practice Patient - 66 year old female Intervention Over 8 months, a 66-year-old patient slowly reduced the venlafaxine dose. She was treated simultaneously for sleep apnea. Measurements Clinical data including venlafaxine and levothyroxine dosing, thyroid hormone laboratory values, subjective complaints, and objective electrocardiographic (ECG) findings were aggregated and analyzed. MAIN RESULTS: As venlafaxine dose was decreased over time, the patient complained of bounding heart palpitations shown to be premature ventricular contractions, and wide and narrow complex ventricular tachycardia on ECG. Thyroid-stimulating hormone decreased from a baseline value of 0.791 uIU/mL to a nadir of 0.18 uIU/mL during venlafaxine dosage reduction from 225 mg/day to 155 mg/day. Cardiac symptoms subsided following levothyroxine dosage reduction. CONCLUSIONS: There was a direct relationship between antidepressant dosage reduction and levothyroxine dosage requirements. Cautious monitoring is recommended during venlafaxine deprescribing in patients with pre-existing thyroid disease.

The current state-of-the-art in pharmacotherapy for pediatric generalized anxiety disorder.

INTRODUCTION: Anxiety disorders are the most prevalent psychiatric disorders among youth. Among the various anxiety disorders, generalized anxiety disorder is particularly prevalent. Youth with GAD appear at elevated risk of developing other anxiety disorders, mood disorder, and substance use disorders. Functional outcomes of youth with GAD can be improved through early recognition and treatment, thus promoting better longer-term outcomes. AREAS COVERED: The current article summarizes evidence-based state-of-the-art pharmacotherapy for pediatric GAD based on open-label, randomized, and controlled trials. Two electronic databases (PubMed and Scopus) were systematically searched in April 2022 for relevant publications. EXPERT OPINION: The literature supports a combination of psychotherapy and pharmacotherapy as being associated with better outcomes when compared to mono-therapies. While longer-term follow-ups are limited, one such study does challenge this notion. Both selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) have been found across studies to have moderate effect sizes in the treatment of pediatric anxiety disorders. SSRIs continue to be a first-line intervention, whereas SNRIs may be considered a second-line treatment. While more evidence is needed, there are emerging data indicating that SSRIs are associated with a more rapid and greater reduction in anxiety symptoms when compared to SNRIs.

Poor Neonatal Adaptation After Antidepressant Exposure During the Third Trimester in a Geographically Defined Cohort.

Objective: To examine the associations between antidepressant exposure during the third trimester of pregnancy, including individual drugs, drug doses, and antidepressant combinations, and the risk of poor neonatal adaptation (PNA). Patients and Methods: The Rochester Epidemiology Project medical records-linkage system was used to study infants exposed to selective serotonin reuptake inhibitors (SSRIs; n=1014), bupropion, (n=118), serotonin-norepinephrine reuptake inhibitors (n=80), antidepressant combinations (n=20), or other antidepressants (n=22) during the third trimester (April 11, 2000-December 31, 2013). Poor neonatal adaptation was defined based on a review of medical records. Poisson regression was used to examine the risk of PNA with serotonergic antidepressant and drug combinations compared with that with bupropion monotherapy as well as with high- vs standard-dose antidepressants. When possible, analyses were performed using propensity score (PS) weighting. Results: Forty-four infants were confirmed cases of PNA. Serotonin-norepinephrine reuptake inhibitor monotherapy, antidepressant combinations, and paroxetine monotherapy were associated with a significantly higher risk of PNA than bupropion monotherapy in unweighted analyses. High-dose SSRI exposure was associated with a significantly increased risk of PNA in unadjusted (relative risk, 2.61; 95% confidence interval, 1.35-5.04) and PS-weighted models (relative risk, 2.29; 95% confidence interval, 1.17-4.48) compared with standard-dose SSRI exposure. The risk of PNA was significantly higher with high-dose paroxetine and sertraline than with standard doses in the PS-weighted analyses. The other risk factors for PNA included maternal anxiety disorders. Conclusion: Although the frequency of PNA in this cohort was low (3%-4%), the risk of PNA was increased in infants exposed to serotonergic antidepressants, particularly with SSRIs at higher doses, during the third trimester of pregnancy compared with that in infants exposed to standard doses. Potential risk factors for PNA also included third-trimester use of paroxetine (especially at higher doses) and maternal anxiety.