Reuptake Inhibitor Antidepressants Research Articles

Effect of Shengyang Yiwei Decoction combined with selective serotonin reuptake inhibitor antidepressants on HAMD-17 score and somatic symptoms in patients with depression

Objective: To investigate the efficacy of Shengyang Yiwei Decoction (SYD) combined with selective serotonin reuptake inhibitor (SSRI) antidepressants on the total score and scores of factors of the Hamilton Rating Scale for Depression (HAMD-17) and somatic symptoms in patients with depression. Methods: This was a retrospective study. One hundred and twenty patients with depression were treated in Hebei Provincial Mental Health Center between December 2020 and May 2022 and randomly divided into the experimental group and the control group, with 60 patients in each group. Patients in the control group were treated with selective serotonin reuptake inhibitor (SSRI) antidepressants and those in the experimental group were treated with modified SYD in addition to SSRIs for eight weeks. Explored the efficacy and adverse drug reactions of the two treatment options. Results: After eight weeks of treatment, there was no statistically significant difference in the total efficacy between the two groups (p>0.05); the total score of HAMD-17 and scores of factors except body weight were decreased in the experimental group compared with those in the control group, and the differences were statistically significant (p<0.05). The SSI score of the experimental group was decreased compared with that of the control group, and the difference was statistically significant (p<0.05). Conclusion: SYD combined with SSRI antidepressants in the treatment of depression can reduce the total score and the scores of factors of HAMD-17 without increasing the incidence of adverse drug reactions. This combination can be used as an integrated traditional Chinese and Western medicine treatment for depression. doi: https://doi.org/10.12669/pjms.41.1.9835 How to cite this: Li L, Wan A, Zhao M, Yu L, Han Y, Mi K. Effect of Shengyang Yiwei Decoction combined with selective serotonin reuptake inhibitor antidepressants on HAMD-17 score and somatic symptoms in patients with depression. Pak J Med Sci. 2025;41(1):205-209. doi: https://doi.org/10.12669/pjms.41.1.9835 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparing commercial pharmacogenetic testing results and recommendations for antidepressants with established CPIC guidelines.

Increasingly, pharmacogenetic testing helps providers with medication selection based upon patient-specific DNA results. While several government-funded organizations work towards consensus and standardization for testing and interpretation, compliance to these best practices remains inconsistent. Pharmacogenetic testing companies often develop proprietary practices for interpreting and reporting, which can lead to incongruency of reported results among companies and potential discrepancies in interpretation. To identify the differences of commercial pharmacogenetic testing vendors' interpretation of genotype-to-phenotype translations and medication recommendations from the Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines, a retrospective manual chart review was completed in a large rural healthcare system that utilizes two institution-approved pharmacogenetic vendors. One hundred patients were evaluated: 50 who completed testing through Company A and 50 who completed testing through Company B. Genes of interest for genotype-to-phenotype translation included CYP2B6, CYP2C19, and CYP2D6. Comparison of medication recommendations for drug-gene pairs sertraline (CYP2B6 and/or CYP2C19), escitalopram (CYP2C19), and paroxetine (CYP2D6) were compared with recommendations from CPIC, with consideration of the CPIC Serotonin Reuptake Inhibitor Antidepressants (SSRI) guideline 2023 update. This was accomplished via a novel binning process to enable comparison of company-provided binned medication recommendations with CPIC guideline recommendations. Briefly, the binning system included three categorizations based upon the relevant CPIC guideline recommendations-no action needed (green), recommend monitoring (yellow) and therapeutic intervention or alternative recommended (red). There were 32/250 (12.8%) genotype-to-phenotype translation discrepancies from CPIC guidelines, all from Company A. Of 266 evaluated binned medication recommendations, there were 114 (42.9%) discrepancies between the pharmacogenetic testing companies (Company A: 93 discrepancies, Company B: 21 discrepancies) and CPIC's guideline based upon comparison with the novel binning system. Significant differences were observed between testing companies' interpretations and recommendations, which is concerning as these discrepancies could lead to providers making medication decisions that are not supported by CPIC's clinical practice guidelines. This may result in suboptimal outcomes for patients, leading to patient and provider dissatisfaction and erosion of trust with pharmacogenetic testing. A proposed resolution for the discrepancies in company-to-company interpretation is adherence to the CPIC guidelines and transparency in interpretation practices.

Hyponatremia Associated with the Use of Common Antidepressants in the All of Us Research Program.

Selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), and norepinephrine-dopamine reuptake inhibitor (NRI) antidepressants can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study assesses the differential risks of hyponatremia associated with commonly prescribed SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), SNRIs (duloxetine, venlafaxine) and NRI (bupropion), as well as omeprazole as a reference, with a retrospective observational cohort study in the All of Us Research Program, a national multicenter research cohort containing de-identified electronic health records (EHR). Participants who had been prescribed monotherapy with any of eight common antidepressants were included, with each drug considered as a separate arm indexed with a start date. Events were defined as the first occurrence of a low plasma sodium measurement or a clinical diagnosis recorded for either hyponatremia or SIADH. Those who did not have events were censored at their last plasma sodium measurement. A total of 17,439 individuals were exposed to one of the eight antidepressants as monotherapy. The overall incidences for hyponatremia were 0.87% in the first 30 days and 10.5% in the first 3 years in the antidepressant arms. Compared to sertraline, duloxetine (hazard ratio [HR] = 1.37 [1.19-1.58]) and escitalopram (HR = 1.16 [1.01-1.33]) were associated with the highest overall risk of hyponatremia, and bupropion (HR = 0.83 [0.73-0.94]) and paroxetine (HR = 0.78 [0.65-0.93]) were associated with the lowest risk. The risks were unchanged after adjusting for comorbidity and polypharmacy. Such information could help guide providers in managing patients and their risks of hyponatremia when on common antidepressants.

Vilazodone,aNovel SSRI Antidepressant with 5-HT1A Partial Agonist Properties: Diminished Potentiation of Chronic Oral Methylphenidate-Induced Dynorphin Expression in the Striatum in Adolescent Male Rats.

Selective serotonin reuptake inhibitor (SSRI) antidepressants such as fluoxetine are used in combination with the medical psychostimulant methylphenidate (Ritalin) in a variety of treatments in children and adults. Unintended co-exposure to these psychotropic medications also occurs in patients on SSRIs who abuse methylphenidate as a "cognitive enhancer" or recreational drug. Preclinical research shows that SSRIs such as fluoxetine when given in conjunction with methylphenidate potentiate addiction-related gene regulation by methylphenidate in the striatum, consistent with the known facilitatory role for serotonin in psychostimulant-induced neuronal and behavioral changes. Moreover, fluoxetine combined with methylphenidate also facilitated subsequent acquisition of cocaine self-administration in adolescent rats, suggesting an increased addiction liability for methylphenidate. In the present study, we investigated the impact of a novel SSRI, vilazodone, on methylphenidate-induced gene regulation in adolescent male rats. In contrast to prototypical SSRIs such as fluoxetine, vilazodone also acts as a partial 5-HT1A serotonin receptor agonist and is thus proposed to temper serotonin input to the striatum. We compared the effects of chronic treatment (4 weeks) with vilazodone (10mg/kg, twice daily) with those of fluoxetine (5mg/kg, twice daily) on striatal dynorphin expression induced by oral methylphenidate treatment (30/60mg/kg/day in drinking water, 8h access daily). Our results demonstrate that, in contrast to fluoxetine, vilazodone had minimal or no potentiating effects on methylphenidate-induced dynorphin expression. This diminished impact on gene regulation was seen throughout the striatum, including the nucleus accumbens, where increased dynorphin expression has previously been associated with various aspects of addiction. Our findings suggest that vilazodone may serve as a better adjunct SSRI with reduced addiction-facilitating properties.

Serotonin reuptake inhibitors improve muscle stem cell function and muscle regeneration in male mice

Serotonin reuptake inhibitor antidepressants such as fluoxetine are widely used to treat mood disorders. The mechanisms of action include an increase in extracellular level of serotonin, neurogenesis, and growth of vessels in the brain. We investigated whether fluoxetine could have broader peripheral regenerative properties. Following prolonged administration of fluoxetine in male mice, we showed that fluoxetine increases the number of muscle stem cells and muscle angiogenesis, associated with positive changes in skeletal muscle function. Fluoxetine also improved skeletal muscle regeneration after single and multiples injuries with an increased muscle stem cells pool and vessel density associated with reduced fibrotic lesions and inflammation. Mice devoid of peripheral serotonin treated with fluoxetine did not exhibit beneficial effects during muscle regeneration. Specifically, pharmacological, and genetic inactivation of the 5-HT1B subtype serotonin receptor also abolished the enhanced regenerative process induced by fluoxetine. We highlight here a regenerative property of serotonin on skeletal muscle.

Thirst and drugs: A study in the World Health Organization's pharmacovigilance database.

Thirst is a complex physiological compensatory mechanism but could also be associated with drugs. This association was poorly investigated previously. Using the WHO global pharmacovigilance database, Vigibase®, disproportionality analyses potential associations between exposure to drugs and thirst reports were performed. All reports of thirst in adults between 01/01/2000 and 31/12/2023 were included. Results are expressed as reporting odds ratio (ROR). Analysis of the 3186 reports of thirst (978 'serious') allowed, first, to confirm the association between thirst and exposure to vasopressin antagonists (tolvaptan), lithium, gliflozins (dapagliflozin, empagliflozin), pregabalin and antimuscarinic drugs (glycopyronium, oxybutynin, tiotropium). Second, new safety signals were described with monoamine reuptake inhibitors (antidepressants: duloxetine, venlafaxine; anti-obesity agent: sibutramine), antipsychotic (olanzapine), glucocorticoid (prednisolone), diuretic (furosemide) drugs as well with ribavirin or sodium oxybate. This study is the first to offer a list of drugs associated with thirst in humans.

Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study.

Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors antidepressants, inhibit the NLR pyrin domain-containing protein 3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by international classification of diseases revision 9-CM or international classification of diseases revision 10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR = 0.62, 95% CI = (0.41-0.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.

Integrated physio-biochemical and transcriptomic analysis reveals the joint toxicity mechanisms of two typical antidepressants fluoxetine and sertraline on Microcystis aeruginosa

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC50s) of 362 and 225 μg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin−leucine−arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems.

Sex-Specific Transcriptomic Changes in the Villous Tissue of Placentas of Pregnant Women Using a Selective Serotonin Reuptake Inhibitor.

About 5% of pregnant women are treated with selective serotonin reuptake inhibitor (SSRI) antidepressants to treat their depression. SSRIs influence serotonin levels, a key factor in neural embryonic development, and their use during pregnancy has been associated with adverse effects on the developing embryo. However, the role of the placenta in transmitting these negative effects is not well understood. In this study, we aim to elucidate how disturbances in the maternal serotonergic system affect the villous tissue of the placenta by assessing whole transcriptomes in the placentas of women with healthy pregnancies and women with depression and treated with the SSRI fluoxetine during pregnancy. Twelve placentas of the Biology, Affect, Stress, Imaging and Cognition in Pregnancy and the Puerperium (BASIC) project were selected for RNA sequencing to examine differentially expressed genes: six male infants and six female infants, equally distributed over women treated with SSRI and without SSRI treatment. Our results show that more genes in the placenta of male infants show changed expression associated with fluoxetine treatment than in placentas of female infants, stressing the importance of sex-specific analyses. In addition, we identified genes related to extracellular matrix organization to be significantly enriched in placentas of male infants born to women treated with fluoxetine. It remains to be established whether the differentially expressed genes that we found to be associated with SSRI treatment are the result of the SSRI treatment itself, the underlying depression, or a combination of the two.

Prediction of treatment response in major depressive disorder using a hybrid of convolutional recurrent deep neural networks and effective connectivity based on EEG signal.

In this study, we have developed a novel method based on deep learning and brain effective connectivity to classify responders and non-responders to selective serotonin reuptake inhibitors (SSRIs) antidepressants in major depressive disorder (MDD) patients prior to the treatment using EEG signal. The effective connectivity of 30 MDD patients was determined by analyzing their pretreatment EEG signals, which were then concatenated into delta, theta, alpha, and beta bands and transformed into images. Using these images, we then fine tuned a hybrid Convolutional Neural Network that is enhanced with bidirectional Long Short-Term Memory cells based on transfer learning. The Inception-v3, ResNet18, DenseNet121, and EfficientNet-B0 models are implemented as base models. Finally, the models are followed by BiLSTM and dense layers in order to classify responders and non-responders to SSRI treatment. Results showed that the EfficiencyNet-B0 has the highest accuracy of 98.33, followed by DensNet121, ResNet18 and Inception-v3. Therefore, a new method was proposed in this study that uses deep learning models to extract both spatial and temporal features automatically, which will improve classification results. The proposed method provides accurate identification of MDD patients who are responding, thereby reducing the cost of medical facilities and patient care.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (β = –18.3, 95% CI (–34.3 to –2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

The lived experience of withdrawal from Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants: A qualitative interview study.

Our knowledge of the broader impacts of antidepressant withdrawal, beyond physical side effects, is limited. Further research is needed to investigate the lived experiences of withdrawal, to aid clinicians on how to guide patients through the process. To explore antidepressant users' experiences and views on the withdrawal process and how it affected their quality of life across multiple life domains. We conducted in-depth qualitative interviews with 20 individuals from the community who had attempted to withdraw from Serotonin Reuptake Inhibitor antidepressants in the past year. Semi-structured interviews were conducted online. A topic guide was used to ensure consistency across interviews. The interviews were audio-recorded and transcribed verbatim and analysed using inductive reflexive thematic analysis. Five themes were generated. The first highlighted the challenges of managing the release from emotional blunting and cognitive suppression following antidepressant discontinuation. The second related to the negative impact of withdrawal on close relationships and social interactions. The third showed that concurrent with negative physical symptoms, there was a positive impact on health (exercise was reported by some as a coping mechanism). The fourth theme focused on support from GPs and families, emphasising the importance of mental health literacy in others. The final theme underscored the importance of gradual and flexible tapering in enabling a manageable withdrawal experience,and the consideration of timing. The lived experience of withdrawal significantly impacts individuals' well-being. Participants emphasised that withdrawal is not just about physical side effects but also affects their emotional, cognitive, and social functioning. Eight people attended individual online meetings to share their experiences of antidepressant withdrawal to help inform the study design and recruitment strategy. Insights from these meetings informed the development of the topic guide. Questions about GP involvement, family relationships, and mood and thinking changes were included based on this PPI work. This ensured the inclusion of topics important to antidepressant users and facilitated the researcher's questioning during the interviews.

Cohort study finds prenatal SSRI exposure linked to reduced brain volume

A population‐based cohort study has found that prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants was associated with reduced brain volume in children aged 7 to 15. The study did not examine whether any of the observed changes in the brain predisposed these young people to any impairments.

Trouble dysphorique prémenstruel : prises en charge médicamenteuses et psychothérapeutiques, une revue de littérature

IntroductionPremenstrual Dysphoric Disorder (PMDD) was first recognised in July 2013 in the DSM-5 after a long journey to identify its existence. It was not until 1983 that the US National Institute of Mental Health determined research criteria for the study of PMS. In 1994, the term “premenstrual dysphoric disorder” (PMDD) replaced this term in the 4th edition of the Diagnostic System Manual (DSM). It was listed in the section “Mood Disorder Not Otherwise Specified” and remained under consideration until the DSM-5, in which it appeared in the depressive disorders section. The legitimisation of the psychiatric diagnosis as well as the determination of clear symptomatology criteria in 2013 opened up possibilities for management, development of clinical, pathophysiological, therapeutic and psychotherapeutic studies. This disabling disorder can affect personal, social, family and professional life. In 2019, the ICD-11 in turn introduced the diagnosis of premenstrual dysphoric disorder, which solidifies the recognition of the disorder. Objective(I) to review the existing treatments, both medicinal and psychotherapeutic, and (II) to review their effectiveness. At the end of this work we will formulate recommendations for the management of these patients. MethodologyA bibliographic search was carried out from 7 June 2021 to 7 July2021 on the databases (bases de données) Psychinfo APA, Scopus, PubMed, as well as the bases de données of the Cochrane organisation and the recommendation documents of the Haute Autorité de la santé. After an initial selection based on keywords, the full text of all articles were read to arrive at the final selection of 32 articles. ResultsAntidepressants and Cognitive Behavioural Therapies (CBT) appear to be the most commonly recommended treatments for PMDD. Other research shows the effectiveness of oral contraceptives including drospirenone. Selective serotonin reuptake inhibitors (SSRIs) were identified as an effective treatment for PMDD. These data are consistent with the current etiological hypothesis of PMDD which has a negative impact of natural hormonal fluctuations on certain neurotransmitters. CBT showed positive results in reducing the functional impact of PMDD. DiscussionSelective serotonin reuptake inhibitor (SSRI) antidepressants were reported to be first-line treatments for PMDD (sertraline 50–150 mg/d, fluoxetine 10–20 mg/d, escitalopram 10–20 mg/d, paroxetine 12.5–25 mg/d). Drospirenone (EE 3 mg and EE 20 mg/d 24 days of hormonal pills, 4 days inactive) appears to have been a first or second line treatment depending on the articles. Current results clearly point to the effectiveness of CBT in helping to reduce: functional impairment, depressed mood, feelings of hopelessness, anxiety, mood swings, sensitivity, irritability, insomnia, conflict with others, impact of premenstrual symptoms on daily life, intensity of symptoms experienced, and symptom handicap. CBTs could also become a first-line treatment if there were to be more evidence of their effectiveness. In the future, it would seem useful to offer a psychotherapeutic treatment that can be reproduced and to multiply research with a high level of scientific comparability in order to clarify the place of CBT in the management of PMDD. Research on the etiopathology of the disorder and the optimal drug regimen is still ongoing. There is a need to develop appropriate psychotherapeutic techniques to support and accompany these patients. ConclusionIn order to better evaluate treatments for PMDD, there is a need to homogenise studies on the subject at several levels: design, treatment doses, psychotherapeutic techniques, and evaluation measures. At present, some studies include both premenstrual syndrome (PMS) and PMDD patients. PMS and PMDD do not include the same symptoms, nor the same severity and potentially the same aetiology in the patients studied. In order to propose rigorous research that evaluates the effectiveness of treatments for PMDD and to properly support people with both these disorders, it seems essential to distinguish the two conditions. The role of the health practitioner is to be able to identify PMDD by differentiating it from other clinically related disorders. The patient must then be accompanied to make a choice of treatment adapted to her symptoms, their severity, her history, her plans for procreation, contraindications and her preferences. In 2021, the French National Authority for Health did not offer any guidelines or recommendations for the management of premenstrual dysphoric disorder. There is a need to develop research in France.

Prenatal serotonin reuptake inhibitor antidepressant exposure, SLC6A4 genetic variations, and cortisol activity in 6-year-old children of depressed mothers: A cohort study.

Prenatal exposure to maternal depression and serotonin reuptake inhibitor (SRI) antidepressants both affect the development of the hypothalamic-pituitary-adrenal (HPA) system, possibly via the neurotransmitter serotonin (5HT). In a community cohort, we investigated the impact of two factors that shape prenatal 5HT signaling (prenatal SRI [pSRI] exposure and child SLC6A4 genotype) on HPA activity at age 6years. Generalized estimating equation (GEE) models were used to study associations between cortisol reactivity, pSRI exposure, and child SLC6A4 genotype, controlling for maternal depression, child age, and sex (48 pSRI exposed, 74 nonexposed). Salivary cortisol levels were obtained at five time points during a laboratory stress challenge: arrival at the laboratory, following two sequential developmental assessments, and then 20 and 40min following the onset of a stress-inducing cognitive/social task. Cortisol decreased from arrival across both developmental assessments, and then increased across both time points following the stress challenge in both groups. pSRI-exposed children had lower cortisol levels across all time points. In a separate GEE model, we observed a lower cortisol stress response among children with LG /S alleles compared with children with La/La alleles, and this was particularly evident among children of mothers reporting greater third trimester depressed mood. Our findings suggest that pSRI exposure and a genetic factor associated with modulating 5HT signaling shaped HPA reactivity to a laboratory stress challenge at school age.

Prediction of Treatment Outcome in Major Depressive Disorder Using Ensemble of Hybrid Transfer Learning and Long Short-Term Memory Based on EEG Signal

Major Depressive Disorder (MDD) is a widespread global mental disease. The Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) antidepressants prescribed for MDD patients is limited and pre-treatment assessment of treatment outcome is a vital task. In this study, a hybrid model based on Transfer Learning (TL) of powerful pre-trained deep Convolutional Neural Networks (CNNs) empowered with bidirectional Long Short-term Memory (BLSTM) cells and attention mechanism were developed to classify Responders (R) and Non-Responders (NR) to SSRI antidepressants, using raw data images of pre-treatment EEG signal obtained from 30 MDD patients. TL-LSTM-Attention models based on VGG16, Xception, and Densenet121 models were created for the classification of R/NR. Results show that the highest performance of hybrid TL-LSTM-Attention models was achieved by VGG16-LSTM-Attention with an accuracy of 98.21%, sensitivity of 96.22%, and specificity of 99.67%. An Ensemble model based on weighted majority voting among hybrid models is constructed to surpass the performance of each single hybrid model. Our proposed ensemble model gained accuracy, sensitivity, and specificity of 98.84%, 97.80%, and 99.60%, respectively. Hence, the proposed model which is an ensemble of TL-LSTM-Attention models fed by raw data images of EEG signal leads to high confidence in the prediction of antidepressants treatment outcome.

Pain Medications Used by Persons Living With Fibromyalgia: A Comparison Between the Profile of a Quebec Sample and Clinical Practice Guidelines

ABSTRACT Background Pharmacological management of fibromyalgia is complex. Chronic pain management is characterized by off-label prescribing and use, multimorbidity, and polypharmacy. Aims This study aimed to describe pain medications use and perceived risk among people living with fibromyalgia and compare this use to evidence-based recommendations. Methods Directive telephone interviews were conducted with 63 individuals self-reporting a diagnosis of fibromyalgia (Quebec, Canada). The questionnaire addressed specific questions about their pain and pharmacological treatments currently used for pain management (prescribed and over-the-counter). Collected data were compared to the Canadian Fibromyalgia Clinical Practice Guidelines and to evidence reports published by recognized organizations. Results Despite a lack of robust scientific evidence to support opioids use to manage pain in fibromyalgia, 33% of our sample reported using them. Nonsteroidal anti-inflammatory drugs were used by 54.0% of participants, although this medication is not recommended due to lack of efficacy. Tramadol, which is recommended, was used by 23.8% of participants. Among the medications strongly recommended, anticonvulsants were used by 36.5%, serotonin norepinephrine reuptake inhibitor antidepressants by 55.6%, and tricyclic antidepressants by 22.2%. Cannabinoids (17.5%) and medical cannabis (34.9%) use were also reported. For all of these medication subclasses, no differences were found between participants not reporting (n = 35) or reporting (n = 28) more than one pain diagnosis (P < 0.05). Medication subclasses considered most at risk of adverse effects by participants were the least used. Conclusions Results reveal discordance between evidence-based recommendations and medications use, which highlights the complexity of pharmacological treatment of fibromyalgia.

Effects of the immunoglobulin/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: a case report

BackgroundPanic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy.Case presentationThis report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly.ConclusionsThe immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient’s clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.

Establishing Core Symptoms of Acute Serotonin Reuptake Inhibitor Withdrawal: Results from an International Survey of Online Peer-Support Communities.

Serotonin reuptake inhibitor (SRI) antidepressants are commonly associated with withdrawal reactions. The Discontinuation Emergent Signs and Symptoms (DESS) checklist has been considered the gold standard research and screening tool for SRI withdrawal but has several limitations, including its length, lack of specificity, and omission of baseline symptom and symptom severity scores, making it impractical for use in clinical or research settings. We investigated the prevalence and severity of common SRI withdrawal symptoms to determine whether a very small subset of symptoms can capture most occurrences of SRI withdrawal. We surveyed 344 members of online peer-support communities aged 18-65, reporting withdrawal symptoms after chronic SRI treatment. The severity of nine common withdrawal symptoms was evaluated at baseline and during the withdrawal period. Dizziness, brain zaps, irritability/agitation, and anxiety/nervousness demonstrated the largest increase in severity during withdrawal relative to baseline. Nearly all (97.7%) of the 344 subjects and all (100%) 153 subjects with relatively low baseline symptom scores (total<5) reported a worsening of one of these four symptoms. The presence of a baseline anxiety disorder did not affect rates of withdrawal-emergent anxiety/nervousness. Nearly all surveyed subjects reported worsening either of dizziness, brain zaps, irritability/agitation, or anxiety/nervousness in acute withdrawal. A screening test incorporating these four core symptoms may be sufficiently sensitive to rule out SRI withdrawal and may be valuable in clinical and research settings. Incorporating withdrawal symptom severity may further enhance specificity.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants.

Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.e., desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine), and serotonin modulators with SSRI-like properties (i.e., vilazodone and vortioxetine) are primary pharmacologic treatments for major depressive and anxiety disorders. Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing, efficacy, and tolerability. In addition, the pharmacodynamic genes SLC6A4 (serotonin transporter) and HTR2A (serotonin-2A receptor) have been examined in relation to efficacy and side effect profiles of these drugs. This guideline updates and expands the 2015 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and SSRI dosing and summarizes the impact of CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes on antidepressant dosing, efficacy, and tolerability. We provide recommendations for using CYP2D6, CYP2C19, and CYP2B6 genotype results to help inform prescribing these antidepressants and describe the existing data for SLC6A4 and HTR2A, which do not support their clinical use in antidepressant prescribing.