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Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression and anxiety. The purpose of this study was to assess in real time the effect of paroxetine, an SSRI, on newly formed bone volume (NFBV) in standardized calvarial defects (SCDs) in rats. Fourteen Wistar albino female rats with a mean age of 7.5 months and a mean weight of 275 g were used. The animals were randomly divided into 2 groups. The experimental group was given paroxetine 8 weeks before the surgical procedure and throughout the experiment, and the control group was given a placebo 8 weeks before the surgical procedure and throughout the experiment. In each group, 14 SCDs measuring 4.6 mm in diameter were created on the parietal bone. In both groups, a Bio-Oss + collagen membrane was placed. All defects showed primary closure. The volume of the newly formed bone (NFBV) was measured using in vivo micro–computed tomographic imaging. Measurements were taken at days 0, 14, 28, 42, and 56 after surgery using real-time assessment with micro–computed tomographic imaging. The mean NFBV was 17.12 ± 4.52 mm3 and 12.52 ± 4.78 mm3 for the control and experimental groups, respectively, at day 56. The differences between the 2 groups were statistically significant (P <.05) at all time intervals. Paroxetine intake significantly reduced the amount of regenerated NFBV and the rate of new bone formation. [ABSTRACT FROM AUTHOR]

Premenstrual symptoms are characterized by unpleasant psychophysical symptoms that appear during the luteal phase before menstruation and interfere with a woman's quality of life. Premenstrual syndrome (PMS) is a pathological condition with premenstrual symptoms, of which premenstrual dysphoric disorder (PMDD) is a particularly severe psychological symptom. This study aimed to examine the gender differences in the diagnosis and treatment of PMS and PMDD among obstetricians and gynecologists (OB/ GYNs) in Japan. Data were obtained from the survey conducted by the Japanese Society of Obstetrics and Gynecology. We used data from 1,257 of the 1,265 OB/GYNs who are engaged in PMS/PMDD practice and reported their gender. Multivariate regression analysis adjusted for propensity scores was performed. Female OB/GYNs were more frequently engaged in treating patients with PMS/PMDD than males [odds ratio (OR) 1.74; 95% confidence interval (CI) 1.36-2.21]. With regard to the diagnostic methods, more female OB/GYNs selected the two-cycle symptom diary than males (OR 2.88; 95% CI 1.80- 4.60). Regarding treatment, fewer female OB/GYNs selected selective serotonin reuptake inhibitors as their first-line drug (OR 0.39; 95% CI 0.17-0.89). Gender differences were found in the selection of PMS/ PMDD diagnosis and treatment methods among Japanese OB/GYNs. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common disorder of gut–brain interaction associated with significant disease burden. This American Gastroenterological Association guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS-C and is an update of a prior technical review and guideline. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: tenapanor, plecanatide, linaclotide, tegaserod, lubiprostone, polyethylene glycol laxatives, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. The panel agreed on 9 recommendations for the management of patients with IBS-C. The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty). [ABSTRACT FROM AUTHOR]

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) and potent σ 1 -receptor agonist, commonly used in human medicine to treat major depressive disorders, obsessive-compulsive disorders, and other anxiety disorders. To our knowledge, its clinical use in canine behavior medicine has not been well-studied. The purpose of this retrospective study was to document the use of fluvoxamine in conjunction with behavior modification and appropriate environmental changes, in client-owned dogs diagnosed with various anxiety disorders. Our hypothesis was that fluvoxamine combined with the other recommendations could result in a positive outcome without major side effects. All dogs diagnosed with at least one anxiety disorder between January 1, 2016 and June 30, 2020 and who received at least 6 months of fluvoxamine were included (n = 72). A total of 100 dogs were diagnosed with at least one anxiety disorder and were prescribed fluvoxamine during the study period, but 28 dogs were excluded from the study as they did not take fluvoxamine for at least 6 months for various reasons (lost to follow-up, euthanasia, side effects, deterioration, insufficient effect, change of ownership, et cetera). A phone survey was conducted to validate data in the medical records of the dogs included and enquire about the perceived effect of fluvoxamine. Out of the 72 dogs with at least one anxiety disorder, 11 had an anxiety disorder without aggression, 47 were aggressive towards humans, 51 were aggressive towards other dogs, 5 had compulsive/obsessive-compulsive disorders, and 32 had suspected or confirmed separation anxiety. Of these dogs, 45% showed a marked improvement, 38% showed a moderate improvement, 15% showed a minimal improvement, 2% showed no improvement and none worsened. The presence of a concomitant treated medical condition and the optimal dosage of fluvoxamine respectively showed a positive and a negative correlation with the effect of treatment. None of the variables were significantly correlated with the time to reach the optimal dosage. 81% of dogs showed some degree of undesirable effects. The vast majority of these undesirable/side effects were considered mild, temporary and were observed during the first weeks of treatment or during periods of dose adjustments. Fluvoxamine offers a safe and promising alternative for patients who do not respond to approved SSRI or tricyclic antidepressants. [ABSTRACT FROM AUTHOR]

Depression disproportionately affects patients with kidney disease, including those with nondialysis chronic kidney disease, end-stage kidney disease requiring dialysis, and kidney transplant recipients. Patients across the spectrum of kidney disease should be screened for depression every 6 to 12 months using self-report questionnaires, followed by an interview with a clinician to confirm the presence of sadness or anhedonia when depressive symptoms are identified. Pharmacologic treatment with selective serotonin reuptake inhibitors has not consistently shown benefit compared with placebo and may be associated with serious adverse outcomes including cardiovascular events, bleeding, and fractures. However, based on the availability of alternative therapies, a watchful trial with close monitoring for therapeutic and adverse effects is reasonable. Several clinical trials have suggested that cognitive behavioral therapy and physical activity improve depressive symptoms when compared with a control group. Given the low risk associated with these therapies, they should be recommended to patients who have access and are amenable to such interventions. Future trials are needed to study therapeutic options for depression in nondialysis chronic kidney disease, peritoneal dialysis, or kidney transplant recipients, as well as alternative pharmacologic therapy and combination therapies. Given improvement in depressive symptoms with placebo in existing trials, inclusion of a control group is paramount. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Selective serotonin reuptake inhibitors (SSRIs) exert substantial variability in effectiveness in patients with major depressive disorder (MDD), with up to 50–60% not achieving adequate response. Elucidating pharmacokinetic factors that explain this variability is important to increase treatment effectiveness. Objectives: To examine potential modification of the relationship between paroxetine serum concentration (PSC) and serotonin transporter (SERT)-occupancy by single nucleotide polymorphisms (SNPs) of the ABCB1 gene, coding for the P-glycoprotein (P-gp) pump, in MDD patients. To investigate the relationship between ABCB1 SNPs and clinical response. Methods: Patients had MDD and received paroxetine 20 mg/day. We measured PSC after 6 weeks. We quantified SERT-occupancy with SPECT imaging (n  = 38) and measured 17-item Hamilton Depression Rating Scale (HDRS17)-scores at baseline and after 6 weeks (n  = 81). We genotyped ABCB1 at rs1045642 [3435C>T], rs1128503 [1236C>T], rs2032582 [2677G>T/A] and rs2235040 [2505G>A]. For our primary aim, we modeled mean SERT-occupancy in an E max nonlinear regression model with PSC and assessed whether the model improved by genetic subgrouping. For our secondary aim, we used multivariate linear regression analysis. Results: The rs1128503 and rs2032582 SNPs modified the relationship between PSC and SERT-occupancy in both our intention-to-treat and sensitivity analyses at the carriership level. However, we could not detect significant differences in clinical response between any of the genetic subgroups. Conclusion: Pharmacokinetic influences of the ABCB1 rs1128503 and rs2032582 represent a potentially relevant pharmacogenetic mechanism to consider when evaluating paroxetine efficacy. Future studies are needed to support the role of ABCB1 genotyping for individualizing SSRI pharmacotherapy. [ABSTRACT FROM AUTHOR]

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Fluoxetine is an antidepressant, a selective serotonin reuptake inhibitor (SSRI) used primarily in the treatment of major depression, panic disorder and obsessive compulsive disorder. Chiral separation of racemic fluoxetine is necessary due to its enantioselective metabolism. In order to develop a suitable method for chiral separation of fluoxetine, cyclodextrin (CD) modified capillary electrophoresis (CE) was employed. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector. As a result of this process, heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) was selected for enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors are varied at the same time to optimize the separation method. The optimized method (50 mM phosphate buffer, pH = 5.0, 10 mM TRIMEB, 15 °C, + 20 kV, 50 mbar/1 s, detection at 230 nm) was successful for baseline separation of fluoxetine enantiomers within 5 min. Our method was validated according to ICH guidelines and proved to be sensitive, linear, accurate and precise for the chiral separation of fluoxetine. [ABSTRACT FROM AUTHOR]

Perinatal depression is associated with a high risk of morbidity and mortality and may have long-term consequences on child development. The US Preventive Services Task Force has recently recognized the importance of identifying and treating women with depression in the perinatal period. However, screening and accessing appropriate treatment come with logistical challenges. In many areas, there may not be sufficient access to psychiatric care, and, until these resources develop, the burden may inadvertently fall on obstetricians. As a result, understanding the risks of perinatal depression in comparison with the risks of treatment is important. Many studies of selective serotonin reuptake inhibitors in pregnancy fail to control for underlying depressive illness, which can lead to misinterpretation of selective serotonin reuptake inhibitor risk by clinicians. This review discusses the risks and benefits of selective serotonin reuptake inhibitor treatment in pregnancy within the context of perinatal depression. Whereas selective serotonin reuptake inhibitors may be associated with certain risks, the absolute risks are low and may be outweighed by the risks of untreated depression for many women and their offspring. [ABSTRACT FROM AUTHOR]

Classification of hypochondriasis as an obsessive-compulsive and related disorder in the International Classification of Diseases 11th Revision (ICD-11) has generated new heuristics for treatment of this common, chronic and disabling disorder. Standard treatment involves cognitive behaviour therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs), but no meta-analysis has so far considered hypochondriasis as a structured diagnosis or assessed the role of medication. A clearer understanding of the relative effectiveness of these interventions and identification of clinically relevant factors moderating the treatment response is needed for clinical guideline development. The current systematic review and meta-analysis of interventions for hypochondriasis was preregistered on PROSPERO (CRD42020185768) and follows PRISMA guidelines. We searched MEDLINE, PsycINFO, and Cochrane Library databases until July 2021 for randomized controlled trials (RCTs) of interventions for patients diagnosed with hypochondriasis (or historical diagnostic equivalents). We assessed aspects of study quality using: the CONSORT Checklist for evaluation of RCTs, the Cochrane Risk of Bias 2 tool, researcher allegiance and treatment fidelity. The primary outcome was improvement in hypochondriasis symptoms, comparing intervention and control groups at trial endpoint. Moderator variables were assessed using subgroup and meta-regression analyses. Searches identified 13 randomised controlled trials (RCTs) (N = 1405); 12 included CBT (N = 1212) and three included SSRI (N = 193) arms as the experimental intervention. Random effects meta-analysis yielded a moderate-to-large effect size for CBT versus all controls (g = −0.70 [95% CI -0.99 to −0.41], k = 18, I2 = 81.1%). Funnel plot asymmetry indicated possible publication bias and two potentially missing trials, reducing the effect size (g = −0.60 [95% CI -0.88 to −0.32]). Subgroup analysis showed that choice of control significantly moderated effect size, with those in CBT vs. wait-list (g = −1.32 [95% CI -1.75 to −0.90], k = 7, I2 = 0%) being double those of CBT vs. psychological or pharmacological placebo controls (g = −0.58 [95% CI -0.95 to −0.22], k = 7, I2 = 82%). Analysis of studies directly comparing CBT and SSRIs found a numerical, but not statistical advantage for SSRIs (g = 0.21 [95% CI -0.46 to 0.87], k = 2, I2 = 58.34%) and a modest effect size emerged for SSRIs vs. pill placebo (g = −0.29 [95% CI -0.57 to −0.01], k = 3, I2 = 0%). Most studies (11/13) were rated as high on potential researcher allegiance bias in favour of CBT. Meta-regressions revealed that effect sizes were larger in younger participants, and smaller in better quality and more recent RCTs and those with greater CBT fidelity. CBT and SSRIs are effective in the acute treatment of hypochondriasis, with some indication that intervention at a younger age produces better outcomes for CBT. In the case of CBT, effect sizes appear to have been significantly inflated by the use of wait list controls, and researcher allegiance bias. We recommend that a definitive, adequately controlled trial, designed with respect to the methodological issues raised in this meta-analysis, is needed to determine the magnitude effects for CBT and SSRIs with confidence and the long-term effect of treatments, to inform mental health service provision for this overlooked patient group. • CBT and SSRIs are effective in the acute treatment of hypochondriasis. • Our meta-analysis showed a moderate-to-large effect size for CBT versus all controls (g = −0.71). • Choice of control significantly moderated effect sizes for CBT. • Most studies (11/13) were rated as high on potential researcher allegiance bias in fa-vour of CBT. • An adequately-controlled study, designed with respect to the methodological issues raised in this paper, is needed. [ABSTRACT FROM AUTHOR]

The current study marks the first randomized controlled trial to test the benefit of combining Seeking Safety (SS), a present-focused cognitive-behavioral therapy for co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), with sertraline, a front-line medication for PTSD shown to also impact drinking outcomes. Method: Sixty-nine participants (81% female; 59% African American) with primarily childhood sexual (46%) and physical (39%) trauma exposure, and drug dependence in addition to AUD were randomized to receive a partial-dose (12 sessions) of SS with either sertraline (n = 32; M = 7 sessions) or placebo (n = 37; M = 6 sessions). Assessments conducted at baseline, end-of-treatment, 6- and 12-months posttreatment measured PTSD and AUD symptom severity. Results: Both groups demonstrated significant improvement in PTSD symptoms. The SS plus sertraline group exhibited a significantly greater reduction in PTSD symptoms than the SS plus placebo group at end-of-treatment (M difference = --16.15, p = .04, d = 0.83), which was sustained at 6- and 12-month follow-up (M difference = --13.81, p = .04, d = 0.71, and M difference = --12.72, p = .05, d = 0.65, respectively). Both SS groups improved significantly on AUD severity at all posttreatment time points with no significant differences between SS plus sertraline and SS plus placebo. Conclusion: Results support the combining of a cognitive-behavioral therapy and sertraline for PTSD/AUD. Clinically significant reductions in both PTSD and AUD severity were achieved and sustained through 12-months follow-up, Moreover, greater mean improvement in PTSD symptoms was observed across all follow-up assessments in the SS plus sertraline group. [ABSTRACT FROM AUTHOR]

Depuis quelques années, le secteur de l’urologie s’est enrichi de classes thérapeutiques nouvelles comme les inhibiteurs de la phosphodiestérase de type 5 pour le traitement de la dysfonction érectile et les antidépresseurs, puissants inhibiteurs de la recapture de la sérotonine (ISRS) pour traiter l’éjaculation précoce. Ces produits, disponibles sur ordonnance, ne sont pas dénués d’effets indésirables et présentent certaines contre-indications et interactions médicamenteuses que les médecins et les pharmaciens doivent bien connaître. Summary Over recent years a number of new therapies have arrived in the urology sector such as phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction and antidepressants, powerful serotonin reuptake inhibitors (SRIs), to treat premature ejaculation. These products, available on prescription, do not come without side effects and present certain contra-indications and drug interactions of which doctors and pharmacists must be aware. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) have been reported to range from low parts per trillion to parts per billion levels in surface waters, wastewater effluents, and sediments. These low levels have led to concern for their potential long-term risks to the survival, growth, and reproduction of aquatic organisms. We investigated the acute and chronic effects of sertraline on the life history traits of Ceriodaphnia dubia over the course of three generations under environmentally realistic concentrations. Acute toxicity of sertraline in C. dubia offspring resulted in a 48h median effective concentration of 126µgL−1. Under chronic exposure, the lowest concentration to affect fecundity and growth was at 53.4µgL−1 in the first two generations. These parameters become more sensitive during the third generation where the LOEC was 4.8µgL−1. The median effective concentrations (EC50) for the number of offspring per female, offspring body size, and dry weight were 17.2, 21.2, and 26.2µgL−1, respectively. Endpoints measured in this study demonstrate that chronic exposure of C. dubia to sertraline leads to effects that occur at concentrations only an order of magnitude higher than predicted environmental concentrations. However, this study also demonstrates that multigenerational effects should be considered in chronic exposure studies because standard toxicity tests do not account for increases in sensitivity in successive generations to toxicants. [Copyright &y& Elsevier]

Diagnosis of cancer causes psychological distress. The present study investigated the safety and efficacy of fluvoxamine therapy in gynecologic cancer patients with either adjustment disorder or major depression after cancer was diagnosed.Screening with the Hospital Anxiety and Depression Scale (HADS) was conducted at least 2 weeks after notification of the diagnosis of cancer in 214 gynecologic cancer patients hospitalized between January 2007 and December 2008. The HADS cutoff score was set at 11 points or greater. Informed consent to the study was obtained from 10 patients, and fluvoxamine was administered for 8 weeks. As primary end points, the safety and efficacy of fluvoxamine were evaluated using the HADS and the SF-36. As a secondary end point, the Clinical Global Impression was determined.The total HADS score, the anxiety score, and the depression score were significantly reduced after 6, 4, and 6 weeks of treatment, respectively. The SF-36 revealed significant improvement in vitality, mental health, and role (emotional) after 8 weeks of treatment. In the 5 patients with adjustment disorder, only the HADS anxiety score was significantly reduced after 4 weeks. In the 5 patients with major depression, the total HADS score, the anxiety score, and the depression score were significantly reduced after 6, 8, and 6 weeks, respectively. According to the SF-36, the adjustment-disorder groups showed significant improvement in mental health after 8 weeks of treatment, whereas the major-depression group showed significant improvement in vitality and role (emotional) after 8 weeks. No adverse events occurred in any subject. Assessment of the Clinical Global Impression suggested that fluvoxamine improved psychological distress in all 10 subjects.The present findings suggest that fluvoxamine is useful for alleviating psychological distress, including adjustment disorder and major depression, in gynecologic cancer patients. Management of psychological distress after diagnosis of cancer is important. [ABSTRACT FROM AUTHOR]

Desensitization of serotonin 1A (HTR1A) and 1B (HTR1B) autoreceptors has been proposed to be involved in the delayed onset of response to selective serotonin reuptake inhibitors (SSRIs). Variations in gene expression in these genes may thus affect SSRI response.Here, we test this hypothesis in two samples from the Sequenced Treatment Alternatives to Relieve Depression (STAR∗D), and show evidence for involvement of several genetic variants alone and in interaction. Initially, three functional single nucleotide polymorphisms (SNPs) in the HTR1B gene and in the HTR1A gene were analyzed in 153 depressed patients treated with citalopram. The 16-item Quick Inventory of Depressive Symptomatology Clinician scores were evaluated over time with respect to genetic variation.Individuals homozygous for the -1019 G allele (rs6295) in HTR1A showed the higher baseline 16-item Quick Inventory of Depressive Symptomatology Clinician scores (P=0.033), and by 12 weeks had a significantly lower response rate (P=0.005). HTR1B haplotypes were estimated according to the previously reported in-vitro expression levels. Individuals who were homozygous for the high-expression haplotype showed significantly slower response to citalopram (P=0.034). We then analyzed more SNPs in the extended overall STAR∗D sample. Although we could not directly test the same functional SNPs, we found that homozygotes for the G allele at rs1364043 in HTR1A (P=0.045) and the C allele of rs6298 in HTR1B showed better response to citalopram over time (P=0.022). Test for interaction between rs6298 in HTR1B and rs1364043 in HTR1A was significant (overall P=0.032).Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment. [ABSTRACT FROM AUTHOR]

Major depression and overtraining syndrome are two major depressive illnesses frequently observed in athletes. Here, these two illnesses are overviewed and compared. Major depression is a mood disorder and considered to be caused by long-term high intensity stress. The stress is usually a psychological stress. Overtraining syndrome is considered to be caused by long-term strong physical training stress. Thus, these two disorders are based on strong stress, although there is the difference of psychological or physical. However, both stresses commonly result in elevation of stress hormones such as cortisol. Here, these two illnesses are compared and their differences and similarities are discussed. [ABSTRACT FROM AUTHOR]

Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO)-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyper-reflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegi-line and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs. [Copyright &y& Elsevier]

Millions of Americans annually receive selective serotonin reuptake inhibitor antidepressants and dual-action antidepressants for their symptoms of depression. These patients are at risk for a well-documented withdrawal syndrome if they abruptly stop their medication. This withdrawal syndrome may produce significant effects that may impair a person's ability to drive, putting at risk both the driver and others on the road. In a situation of the antidepressant withdrawal syndrome, the impairment is due to the absence of drugs in the patient, producing the paradox of a potentially impaired driver because of an absence of the influence of a drug. This article reviews the antidepressant withdrawal syndrome and describes the effects on cognition, memory, vision, and motor performance and reviews how these clinical effects might be misinterpreted using standardized field sobriety tests suggesting the patient is intoxicated in the absence of other drugs or alcohol. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The decline in concentrations of gonadal hormones during menopause gives rise to a range of physiologic and psychologic changes that may impact a woman's health and quality of life significantly. Most notable among these are vasomotor symptoms (hot flashes and night sweats) and mood and sleep disturbances. STUDY DESIGN: This article reviews the physiologic condition underlying menopausal vasomotor symptoms and centrally active, nonhormonal therapies that have demonstrated efficacy for their treatment. RESULTS: Despite the emergence of a range of nonhormonal treatments for vasomotor symptoms, a need still exists for safe and effective therapeutic options that directly target the underlying thermoregulatory mechanisms for women who want treatment but prefer to avoid hormone therapy or for whom hormone therapy is contraindicated. CONCLUSION: The availability of centrally active therapies for menopausal vasomotor symptoms with risks and benefits clearly defined by results from well-designed clinical trials has the potential to allay safety concerns that are associated with the treatment of these common symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Trichotillomania (TTM) is now part of DSM-5 classification of obsessive-compulsive and related disorders. A quarter of schizophrenia patients suffer from obsessive-compulsive symptoms (OCS) and the use of atypical antipsychotics may worsen or even induce new onset OCS. Objective: A 25-year old man who presented with TTM comorbid with schizophrenia was studied. The symptomatology and treatment will be discussed. Results: The patient had prominent anxiety and mild OCS during the prodromal phase of schizophrenia. While on atypical antipsychotics treatments, he developed TTM which was partially reduced with addition of selective serotonin reuptake inhibitor (SSRI). Conclusion: Schizophrenia patient with prodromal OCS is probably at increased risk of developing TTM while on atypical antipsychotics treatment. Atypical antipsychotics and SSRI combination therapy is a useful strategy in such patient. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is suggested to play a role in the aetiology of major depression and in the antidepressant response in patients with major depression. Several BDNF gene polymorphisms have been investigated in the above-mentioned context. The aim of the present study was to examine the role of two BDNF gene polymorphisms (rs11030101 and rs61888800) in relation to the response to selective serotonin reuptake inhibitor medication in 106 patients of Finnish origin suffering from major depression. The secondary objective was to evaluate the association of these two BDNF polymorphisms in major depression, as we also had a control population of 386 healthy individuals. We did not find any significant differences in the distribution of these two BDNF gene polymorphisms in our patient population in relation to remission or response to treatment with selective serotonin reuptake inhibitor. Also, there were no significant differences between the patients and the controls. [ABSTRACT FROM AUTHOR]

Serotonin syndrome (SS) is a rare, potentially life-threatening adverse drug reaction. Selective serotonin reuptake inhibitors (SSRIs) are among a number of pharmaceuticals that all contribute to SS, but SS caused by SSRI monotherapy is rare. We present a case of probable sertraline-induced SS. A 36-year-old male presented to the emergency department four times in one week with a constellation of autonomic and neuromuscular symptoms. He had been taking sertraline at a therapeutic dose for less than three months. Moderate SS was diagnosed using the Hunter criteria during the fourth visit, when it was seen that he had hyperreflexia and inducible ankle clonus. The patient's symptoms resolved within 24 hours with lorazepam, intravenous fluids, and discontinuation of sertraline. In the emergency department it is important to have a high clinical suspicion for SS even if the patient is taking SSRI monotherapy at therapeutic doses. [ABSTRACT FROM AUTHOR]

Pharmaceutical pollution is now recognised as a major emerging agent of global change. Increasingly, pharmaceutical pollutants are documented to disrupt ecologically important physiological and behavioural traits in exposed wildlife. However, little is known about potential impacts of pharmaceutical exposure on among-individual variation in these traits, despite phenotypic diversity being critical for population resilience to environmental change. Furthermore, although wildlife commonly experience multiple stressors contemporaneously, potential interactive effects between pharmaceuticals and biological stressors—such as predation threat—remain poorly understood. To redress this, we investigated the impacts of long-term exposure to the pervasive pharmaceutical pollutant fluoxetine (Prozac®) on among-individual variation in metabolic and behavioural traits, and the combined impacts of fluoxetine exposure and predation threat on mean metabolic and behavioural traits in a freshwater fish, the guppy (Poecilia reticulata). Using a mesocosm system, guppy populations were exposed for 15 months to one of two field-realistic levels of fluoxetine (nominal concentrations: 30 and 300 ng/L) or a solvent control. Fish from these populations were then tested for metabolic rate (oxygen uptake) and behaviour (activity), both before and after experiencing one of three levels of a predation treatment: an empty tank, a non-predatory fish (Melanotaenia splendida) or a predatory fish (Leiopotherapon unicolor). Guppies from both fluoxetine treatments had ∼70% lower among-individual variation in their activity levels, compared to unexposed fish. Similarly, fluoxetine exposure at the higher dosage was associated with a significant (26%) reduction in individual-level variation in oxygen uptake relative to unexposed fish. In addition, mean baseline metabolic rate was disrupted in low-fluoxetine exposed fish, although mean metabolic and behavioural responses to predation threat were not affected. Overall, our study demonstrates that long-term exposure to a pervasive pharmaceutical pollutant alters ecologically relevant traits in fish and erodes among-individual variability, which may be detrimental to the stability of contaminated populations globally. Image 1 • We exposed female guppies (P. reticulata) to fluoxetine and acute predation threat. • Fluoxetine reduced among-individual variation in both metabolic rate and activity. • Fluoxetine caused a non-monotonic reduction in baseline metabolic rate. • Fluoxetine did not affect metabolic and behavioural responses to predation threat. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence of psychiatric disorders and associated therapies in children during their heart transplantation admission.Study Design: All pediatric heart transplant recipients (1999-2016) were included from a linked administrative and clinical registry database. Psychiatric disorders and associated therapies were identified using International Classification of Diseases or billing codes during the transplant admission. Data were analyzed using standard descriptive statistics. Multivariable logistic regression assessed factors independently associated with psychiatric disorders or therapies.Results: A total of 3073 pediatric heart transplant recipients were included. Psychiatric disorders were present in 434 (14.1%) patients during the heart transplant admission, with adjustment disorders being the most common. Antidepressant therapy was prescribed to 212 patients (6.9%) and selective serotonin reuptake inhibitors were most commonly used. Psychiatric diagnoses (8.4% vs 18.1%; P < .001) and the use of antidepressants (4.5% vs 8.9%; P < .001) increased over time (era 1, 1999-2009 vs era 2, 2010-2016). Psychiatric disorders were present in 39.8% of patients ≥8 years of age requiring ventricular assist device support at heart transplantation. The need for ventricular assist device support was independently associated with psychiatric diagnoses (aOR, 1.57; 95% CI, 1.18-2.1; P = .002) and antidepressant therapy (aOR, 2.11; 95% CI. 1.43-3.12; P < .001).Conclusions: Psychiatric disorders are common in pediatric heart transplant recipients, especially among those bridged with ventricular assist device support. Psychiatric diagnoses and the use of antidepressants has increased over time, likely representing improved recognition of psychiatric comorbidities in this vulnerable population. Access to psychiatric services represents an important component of the multidisciplinary team caring for pediatric heart transplant recipients. [ABSTRACT FROM AUTHOR]

In (eco)toxicology, there is a critical need for efficient methods to evaluate the neurotoxic potential of environmental chemicals. Recent studies proposed analysis of early coiling activity in zebrafish embryos as a powerful tool for the identification of neurotoxic compounds. In order to demonstrate that the analysis of early tail movements of zebrafish embryos allows for the discrimination of neurotoxicants acting via different mechanisms, the present study investigated the effects of four different neurotoxicants on the embryogenesis (fish embryo toxicity test) and early tail coiling movements of zebrafish embryos. Cadmium predominantly increased the frequency of tail coiling at the late pharyngula stage. Dichlorvos delayed embryonic development and caused convulsive tail movements resulting in prolonged duration of tail coils. Embryos exposed to teratogenic concentrations of fluoxetine and citalopram displayed absence of spontaneous tail movements at 24 h post-fertilization. In contrast, a non-teratogenic test concentration of citalopram decreased coiling frequency at multiple time points. Results demonstrated that the analysis of tail coiling movements of zebrafish embryos has the potential to discriminate neurotoxic compounds with different primary modes of action. In addition, chemical-induced effects on coiling activity were shown to potentially overlap with effects on embryogenesis. Further studies are needed to clarify the interplay of unspecific developmental toxicity of neurotoxic chemicals and effects resulting from specific neurotoxic mechanisms. • The coiling assay discriminates between neurotoxicants with different modes of action. • Cadmium increases coiling frequency as first sublethal effect during zebrafish development. • Dichlorvos produces convulsive tail movements and prolongs coil duration. • Fluoxetine and citalopram provoke muscle contractions and impair development tail coils. • Non-teratogenic concentration levels of citalopram decrease coiling frequency. [ABSTRACT FROM AUTHOR]

Objective Given the current debate and growing public concerns on selective serotonin reuptake inhibitors (SSRIs) and birth defects generated by Food and Drug Administration warnings, we aim to quantify the association between first-trimester exposure to sertraline, a first-line treatment, and the risk of congenital malformations in a cohort of depressed women. Study Design This was a population-based cohort study in Quebec, Canada, 1998 through 2010. From a cohort of 18,493 depressed/anxious pregnancies, sertraline-exposed, nonsertraline SSRI-exposed, non-SSRI exposed, and unexposed (reference category) women were studied. Major malformations overall and organ-specific malformations in the first year of life were identified. Generalized estimating equation models were used to obtain risk estimates and 95% confidence intervals (CIs). Analyses were adjusted for potential confounders. Results Among the 18,493 eligible pregnancies, 366 were exposed to sertraline, 1963 to other SSRIs, and 1296 to non-SSRI antidepressants during the first trimester of pregnancy. Sertraline use was not statistically significantly associated with the risk of overall major malformations when compared to nonuse of antidepressants. However, sertraline exposure was associated with an increased risk of atrial/ventricular defects specifically (risk ratio [RR], 1.34; 95% CI, 1.02–1.76; 9 exposed cases), and craniosynostosis (RR, 2.03; 95% CI, 1.09–3.75; 3 exposed cases). Exposure to SSRIs other than sertraline during the first trimester of pregnancy was associated with craniosynostosis (RR, 2.43; 95% CI, 1.44–4.11; 19 exposed cases), and musculoskeletal defects (RR, 1.28; 95% CI, 1.03–1.58; 104 exposed cases). Conclusion Sertraline use during the first trimester of pregnancy was associated with an increased risk of atrial/ventricular defects and craniosynostosis above and beyond the effect of maternal depression. Nonsertraline SSRIs were associated with an increased risk of craniosynostosis and musculoskeletal defects. [ABSTRACT FROM AUTHOR]

Objective: This study investigates fluoxetine (FLX) exposure as an etiology for altered gestational length and adverse pregnancy outcomes. Study Design: Two experiments were performed exposing mice to drinking water (H2O) or H2O+FLX. Primary outcomes included gestational length, litter size, and live birth rate. In experiment 1, time-mated dams were monitored for spontaneous birth, and gestational length was calculated. In experiment 2, dams were dissected on day 14 to verify litter size and qualities of embryo implantation. Results: There was no difference in gestational length between H2O dams (480.7 ± 13.2 hours) and H2O+FLX dams (483.5 ± 10.1 hours), P = .70. Mean litter size was decreased in H2O+FLX dams (4.1 ± 1.3/litter) compared to H2O dams (5.5 ± 1.9/litter), P = .04. H2O+FLX dams were less likely to have live births (25.4%) compared to H2O dams (49.3%), P = .01. Conclusion: Antenatal FLX exposure did not statistically alter gestational length, but did affect litter size and spontaneous loss in mice. This warrants further investigation. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitor (SSRI) antidepressants are preferred to tricyclics, because, for the same efficacy, they are better tolerated. The mechanisms of action are well understood. These drugs may be used during pregnancy. We present here the case of a voluntary intoxication with SSRI in the third trimester of pregnancy. [Copyright &y& Elsevier]

An abstract of the article "Antidepressants for treatment of tinnitus," by Shannon Robinson is presented.