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Depressive symptoms and depression are prevalent among persons living with HIV (PLWH). Depression among PLWH is associated with a lower quality of life, reduced adherence to antiretroviral treatment, poorer self-care, worsened treatment outcomes, greater impairment in social and vocational functioning, and increased social isolation. Assessment of depression in PLWH is critical to facilitate referral and management. Fortunately, two simple screening questions can be used to assess for depression, and evidence supports the effective management of depression for PLWH. First-line treatment regimens for depression include selective serotonin reuptake inhibitors (SSRIs), cognitive behavioral therapy (CBT), or a combination of SSRI and CBT. This paper examines the contemporary evidence related to depression in the context of HIV infection. A case study has been included to illustrate an application of evidence-based treatment interventions recommended for clinical practice. [Copyright &y& Elsevier]

The article presents a letter to the editor of "The Journal of the American Medical Association" regarding neonatal signs after late in vitro exposure to selective serotonin reuptake inhibitors. The letter responds to research by Moses-Kolko and colleagues in a previous issue of the journal.

Presents a letter to the editor about the treatment of adolescents with depression.

Presents a letter to the editor about the treatment of adolescents with depression.

Presents a letter to the editor about the treatment of adolescents with depression.

Reports on the decision of the United States Food and Drug Administration to add a warning label to the packaging information of all antidepressants concerning the risk of increased suicidal tendencies in children and adolescents. Description of the label and its wording; Reason for the labels to be added; Assertion that some antidepressants have caused depressed children to become suicidal.

Background: The anxiety-reducing effect of long-term administration of serotonin reuptake inhibitors is usually seen only in subjects with anxiety disorders, and such patients are also abnormally inclined to experience a paradoxical anxiety-enhancing effect of acute serotonin reuptake inhibition. These unique responses to serotonin reuptake inhibitors in anxiety-prone subjects suggest, as do genetic association studies, that inter-individual differences in anxiety may be associated with differences in serotonergic transmission., Methods: The one-third of the animals within a batch of Wistar rats most inclined to spend time on open arms in the elevated plus maze were compared with the one-third most inclined to avoid them with respect to indices of brain serotonergic transmission and how their behavior was influenced by serotonin-modulating drugs., Results: "Anxious" rats displayed higher expression of the tryptophan hydroxylase-2 gene and higher levels of the tryptophan hydroxylase-2 protein in raphe and also higher levels of serotonin in amygdala. Supporting these differences to be important for the behavioral differences, serotonin depletion obtained by the tryptophan hydroxylase-2 inhibitor p-chlorophenylalanine eliminated them by reducing anxiety in "anxious" but not "non-anxious" rats. Acute administration of a serotonin reuptake inhibitor, paroxetine, exerted an anxiety-enhancing effect in "anxious" but not "non-anxious" rats, which was eliminated by long-term pretreatment with another serotonin reuptake inhibitor, escitalopram., Conclusions: Differences in an anxiogenic impact of serotonin, which is enhanced by acute serotonin reuptake inhibitor administration, may contribute to differences in anxiety-like behavior amongst Wistar rats., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)

Background: Antidepressants are effective in adults with pain-related functional gastrointestinal disorders. We investigated the effectiveness of citalopram in the treatment of childhood functional abdominal pain (FAP)., Methods: Children with FAP, based on the Rome III criteria (n = 115, aged 6-18 years), were randomized to receive either citalopram 20 mg/day or placebo for 4 weeks. Treatment response was defined as ≥ 2 point reduction in the 6-point Faces pain rating scale or 'no pain'. Depression, anxiety, somatization, and physician-rated global severity and improvement were also evaluated. Patients were followed up for 8 weeks after medication period., Key Results: Eighty-six patients completed the medication (43 in each group). Response rate in the citalopram and placebo groups based on per-protocol (intention-to-treat) analysis was 55.8% (40.6%) and 39.5% (30.3%) at week 4 (p = 0.097 [0.169]) and 72.0% (52.5%) and 53.4% (41.0%) at week 12 (p = 0.059 [0.148]), respectively. In per-protocol analysis, more reduction was observed in pain (F = 3.84, p = 0.024) and global severity scores (F = 4.12, p = 0.021) in the citalopram group compared with the placebo group over the study period. Such differences were not present in the intention-to-treat analysis. No difference was found between the two groups regarding change in depression, anxiety, or somatization score over the study., Conclusions & Inferences: Overall, we found a trend toward the effectiveness of citalopram in the treatment of children with FAP. Trials with longer treatment duration in larger samples of patients are required in this regard., (© 2014 John Wiley & Sons Ltd.)

Obsessive-compulsive disorder (OCD) is a common heterogeneous psychiatric disorder manifesting with obsessions and compulsions. Obsessions are intrusive, recurrent, and persistent unwanted thoughts. Compulsions are repetitive behaviors or mental acts that an individual feels driven to perform in response to the obsessions. The heterogeneity of OCD includes themes of obsessions, types of rituals, presence or absence of tics, etiology, genetics, and response to pharmacotherapy. Complications of OCD include interpersonal difficulties, unemployment, substance abuse, criminal justice issues, and physical injuries. Areas of the brain involved in the pathophysiology include the orbitofrontal cortex, anterior cingulate gyrus, and basal ganglia. Overall, OCD may be due to a malfunction in the cortico-striato-thalamo-cortical circuit in the brain. Neurotransmitters implicated in OCD include serotonin, dopamine, and glutamate. Numerous drugs such as atypical antipsychotics and dopaminergic agents can cause or exacerbate OCD symptoms. The etiology includes genetics and neurological insults. Treatment of OCD includes psychotherapy, pharmacotherapy, electroconvulsive therapy, transcranial magnetic simulation, and in extreme cases surgery. Exposure and response prevention is the most effective form of psychotherapy. Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacotherapy. Higher doses than listed in the package insert and a longer trial are often needed for SSRIs than compared to other psychiatric disorders. Alternatives to SSRIs include clomipramine and serotonin/norepinephrine reuptake inhibitors. Treatment of resistant cases includes augmentation with atypical antipsychotics, pindolol, buspirone, and glutamate-blocking agents.

Based on the positive effects of COX-2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure-activity relationships of the 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX-2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX-2 selectivity (selectivity index COX-1/COX-2 42.8-158.1). The compound 2-[2-(4-benzyloxyphenyl)morpholino]ethyl 2-(4-iso-butylphenyl)-propanoate hydrochloride (1k) shows better COX-2 inhibitory activity (IC50  = 0.78 µM) than ibuprofen (IC50  = 7.6 µM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Depression, anxiety, or both, during pregnancy are common complications during the perinatal period, with 15-20% of women experiencing depression at some point during their pregnancy. Considerable evidence suggests that untreated or undertreated maternal Axis I mood disorders can increase the risk for preterm birth, low birth weight, and alter neurobehavioral development in utero. Serotonin reuptake inhibitor antidepressants are often considered for antenatal therapy, with the goal of improving maternal mental health during pregnancy. Treatment with a serotonin-reuptake inhibitor, however, does not guarantee remission of depression, and in-utero serotonin reuptake inhibitor exposure has also been linked to increased risks for adverse infant outcomes. In this chapter, evidence linking serotonin reuptake inhibitor use with an increased risk for postnatal adaptation syndrome, congenital heart defects, and neonatal persistent pulmonary hypertension is reviewed. Management decisions should include attention to the continuum of depression symptoms, from subclinical to severe major depressive disorder and the long-term developmental risks that might also be associated with pre- and postnatal exposure., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The aim of the present study was to determine the relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors (SSRI) treatment on premature ejaculation. Sixty married men (aged 20-50) with lifelong premature ejaculation and forty healthy men (aged 24-48) as control group were included in this study. The patients were evaluated by intravaginal ejaculation latency time (IELT) for premature ejaculation (PE). IELT<1 min is accepted PE. Patients with diabetes mellitus, chronic disorders or erectile dysfunction and heavy smokers were excluded. All patients were evaluated with history, physical examination, International Index of Erectile Dysfunction-5 (IIEF-5) score and IELT by stopwatch method. Nitric oxide levels were measured by Griess reaction, and all samples were frozen at -80 °C. Patients were randomly categorised 4 group to receive fluoxetine 20 mg day(-1) (Group 1), paroxetine 20 mg day(-1) (Group 2), sertraline 50 mg day(-1) (Group 3) and healthy control (Group 4) for 4 weeks. Baseline and post-treatment findings were compared between the four groups. At the end of 4 weeks, in fluoxetine, paroxetine, sertraline groups mean IELT values showed a statistically significant improvement from the baseline values (P < 0.001, P < 0.001, P = 0.03; respectively). Baseline and 1st month follow-up mean IIEF scores were 24.5 and 23.05, 24.70 and 23.60 (P < 0.05) in group 1 and group 3 respectively; also 23.09 and 23.32 (P > 0.05) in group 2. Baseline serum NO levels were 31.8, 30.44, 30.8 and 42.84 in fluoxetine, paroxetine, sertraline and healthy control groups respectively. NO levels were statistically lower in patients with PE. After treatment of fluoxetine, paroxetine and sertraline, NO levels were increased baseline (35.8, 36.4, 38.08) (P < 0.05). Our findings indicated that PE is associated with decreased serum NO levels. After the SSRI treatment increased, NO may retard ejaculation presumably by central peripheral mechanism. Further studies are needed to confirm this suggestion and the role of NO in pathophysiology and treatment for premature ejaculation., (© 2013 Blackwell Verlag GmbH.)

Background: Although obsessive-compulsive disorder is usually regarded as a chronic illness, there is limited data on the naturalistic long-term outcome of the disorder and on predictors of remission and relapse. The study examines the 5-year course prospectively in outpatients with the primary diagnosis of DSM-IV OCD who were mostly treated with serotonin reuptake inhibitors (SRIs)., Method: 106 of 115 subjects recruited over a period of 2 years from the outpatient services of an OCD clinic in India were followed periodically up to 5 years., Results: Subjects were moderately ill, mostly self-referred (89%), and less than a half was treatment-naive. Cumulative probability of at least partial remission and full remission at 5 years was 93% and 65% respectively. Most achieved remission by 2 years. In those who achieved either partial or full remission, cumulative probability of relapse by 5 years was 36%. Percentage of time on treatment and treatment-naive status at intake predicted at least partial remission, whereas only percentage of time on treatment predicted full remission. Full remission and doubts/checking dimension predicted lesser likelihood of a relapse., Limitations: Patients were recruited from a specialty OCD clinic and treatment was not controlled during the follow-up period., Conclusions: The outcome of OCD seems to be better than generally assumed, at least in moderately ill outpatients. Regular treatment over extended period may enhance likelihood of remission. Full remission should be the goal of treatment since it is associated with lesser propensity for relapse. Most patients remit in the first 2 years of treatment; therefore, early detection and intervention may improve the outcome., (© 2013 Elsevier B.V. All rights reserved.)

The serotonin system has recently emerged as an important player in the appearance of L-DOPA-induced dyskinesia (LID) in experimental models of Parkinson's disease, as it provides an unregulated source of L-DOPA-derived dopamine release in the dopamine-depleted striatum. Accordingly, toxin lesion or pharmacological silencing of serotonin neurons suppressed LID in the rat and monkey models of Parkinson's disease. However, 5-HT1 receptor agonists were also found to partially reduce the therapeutic effect of L-DOPA. In this study, we evaluated whether enhancement of the serotonin tone induced by the administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) could affect induction and expression of LID, as well as the therapeutic effect of L-DOPA, in 6-OHDA-lesioned rats. Drug naïve and L-DOPA-primed 6-OHDA-lesioned rats were chronically treated with a daily injection of L-DOPA (6 mg/kg plus benserazide, s.c.) alone, or in combination with 5-HTP (24-48 mg/kg, i.p.). The abnormal involuntary movements (AIMs) test, as well as the stepping and the motor activity tests, were performed during the chronic treatments. Results showed that 5-HTP reduced the appearance of LID of about 50% at both tested doses. A partial reduction of the therapeutic effect of L-DOPA was seen with the higher but not with the lower dose of 5-HTP. 5-HTP 24 mg/kg was also able to reduce the expression of dyskinesia in L-DOPA-primed dyskinetic rats, to a similar extent than in L-DOPA-primed rats. Importantly, the antidyskinetic effect of 5-HTP 24 mg/kg does not appear to be due to a competition with L-DOPA for crossing the blood-brain barrier; in fact, similar L-DOPA striatal levels were found in L-DOPA only and L-DOPA plus 5-HTP 24 mg/kg treated animals. These data further confirm the involvement of the serotonin system in the appearance of LID, and suggest that 5-HTP may be useful to counteract the appearance of dyskinesia in Parkinson's disease patients., (© 2013.)

Depression is a common psychiatric comorbidity in Parkinson's disease (PD) and contributes to significant impairments in cognitive, functional, motor, and social performance. This results in reduced quality of life, higher levels of care dependency, and increased caregiver burden. When treating depression, it is important to ensure that the patient's response to treatment will be adequately monitored. This can be accomplished in neurology or primary care settings, or in clinical settings with interdisciplinary treatment teams. Mental health services should be engaged early as a component of ongoing comprehensive care. This article reviews a general approach to treating the pharmacotherapy of depression in PD. Ultimately, clinicians should rely on empiric assessments of known risks and putative benefits to guide treatment decisions and should include a targeted and individualized multimodal approach that utilizes psychotherapeutic interventions along with pharmacologic therapies., (© 2013 Pharmacotherapy Publications, Inc.)

Background: Several previous studies have reported both an association between selective serotonin reuptake inhibitors (SSRI) and decreased bone mineral density and increased fractures, but no previous studies have specifically evaluated bone health in young adults who have a history of SSRI use., Objective: The purpose was to characterize the effect SSRI use in early adulthood on bone mineral density., Methods: A cross-sectional study was conducted on subjects who voluntarily responded to recruitment methods for the study. Young adults aged 18 to 25 years who were currently or had previously taken an SSRI for a minimum of 3 consecutive months were included in the study. A subject interview was conducted on each patient to collect background information. Each subject's calcaneal bone mineral density was then measured with an ultrasonometer., Results: Complete data were collected on 51 subjects. The median duration of SSRI use was 24 ± 54 months. A significant negative correlation was observed between SSRI duration and calcaneal ultrasound T-score (r = -0.53, P < 0.001) which was unchanged in depressed subjects. Subjects on continuous SSRIs for >24 months had a significantly lower median T-score (0.30 ± 0.93) than subjects taking SSRIs for ≤ 24 months (0.90 ± 0.81; P = 0.0010)., Conclusions: In this young relatively healthy population who were following most of the recommendations to improve bone health, a significant negative correlation was observed between the duration of SSRI use and bone mineral density. Subjects who were on SSRIs for longer than 24 months had a significantly lower T-score. Further large scale longitudinal studies are needed in this younger population to determine the effects of chronic SSRI use on bone health., (© 2013 Elsevier HS Journals, Inc. All rights reserved.)

Objective: To investigate whether psoriasis is affected by the use of serotonin reuptake inhibitors (SSRIs)., Design: A population-based cohort study., Setting: The general adult population with plaque psoriasis in Sweden between 1997 and 2006., Subjects: A total of 69 830 patients with plaque psoriasis were identified in the National Patient Register. Whether study subjects were exposed to SSRIs was identified through the Swedish Prescribed Drug Register. The SSRI-exposed subjects (n = 1282) had a prescription for SSRIs dispensed twice during 6 months at a Swedish pharmacy between 1 July 2006 and 1 April 2008, with a wash-out period of 1 year or longer. The reference subjects (n = 1282), who were not exposed to SSRIs, were matched for age, county of residence, sex, psoriasis severity and seasonal variation., Main Outcome Measure: Change in psoriasis severity defined by switching between nonsystemic and systemic psoriasis treatments 6 months after exposure to SSRIs., Results: The risk of switching from nonsystemic to systemic psoriasis treatments was significantly decreased in the SSRI-exposed group (odds ratio 0.44, 95% confidence interval 0.28-0.68)., Conclusion: SSRI use in patients with psoriasis is associated with a decreased need for systemic psoriasis treatment., (© 2013 The Association for the Publication of the Journal of Internal Medicine.)

Background: Methylene blue is used in medical practice for various reasons. Recent findings point to a potential interaction with serotonin reuptake inhibitors (SRIs) that could lead to serotonergic toxicity., Objective: To describe the risk of serotonergic toxicity associated with the interaction between methylene blue and SRIs., Data Sources: Relevant publications were searched systematically via MEDLINE (1946 to March 21, 2013) and Embase (1974 to 2013, week 11) with the following search terms: "methylene blue", "methylthioninium", "monoamine oxidase inhibitors", "serotonin reup-take inhibitors", and "serotonin syndrome". No restrictions were applied in relation to the indication for methylene blue or the language of publication. The reference lists of identified articles were also searched., Study Selection and Data Extraction: Eighteen case reports and 2 case series were identified for inclusion. To date, no randomized controlled trials have been published., Data Synthesis: The first case report indicating suspicion of an interaction between methylene blue and SRIs was published in 2003. Seventeen other case reports describing the same type of interaction have been published since then. The 2 case series provided data from about 325 parathyroidectomies in which methylene blue was used for staining. The 17 patients who experienced central nervous system toxicity were all taking SRIs in the preoperative period., Conclusion: When administered in combination with SRIs, methylene blue may lead to serotonergic toxicity at doses as low as 0.7 mg/kg. Methylene blue would seem to have monoamine oxidase A inhibitory properties. Precautions should be taken to avoid this interaction. [Publisher's translation].

In utero, pulmonary blood flow is closely circumscribed and oxygenation and ventilation occur via the placental circulation. Within the first few breaths of air-breathing life, the perinatal pulmonary circulation undergoes a dramatic transition as pulmonary blood flow increases 10-fold and the pulmonary arterial blood pressure decreases by 50% within 24 hours of birth. With the loss of the placental circulation, the increase in pulmonary flow enables oxygen to enter the bloodstream. The physiologic mechanisms that account for the remarkable transition of the pulmonary circulation include establishment of an air-liquid interface, rhythmic distention of the lung, an increase in shear stress and elaboration of nitric oxide from the pulmonary endothelium. If the perinatal pulmonary circulation does not dilate, blood is shunted away from the lungs at the level of the patent foramen ovale and the ductus arteriosus leading to the profound and unremitting hypoxemia that characterizes persistent pulmonary hypertension of the newborn (PPHN), a syndrome without either optimally effective preventative or treatment strategies. Despite significant advances in treatment, PPHN remains a major cause of morbidity and mortality in neonatal centers across the globe. While there is information surrounding factors that might increase the risk of PPHN, knowledge remains incomplete. Cesarean section delivery, high maternal body mass index, maternal use of aspirin, nonsteroidal anti-inflammatory agents and maternal diabetes mellitus are among the factors associated with an increased risk for PPHN. Recent data suggest that maternal use of serotonin reuptake inhibitors might represent another important risk factor for PPHN.

Pediatric obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric condition associated with broad impairments in functioning. This paper outlines current etiological theories of OCD, providing a review of neuroanatomical, neurochemical, neuroimmunological, and cognitive-behavioral explanations. Subsequently, first-line treatment modalities are discussed (serotonin reuptake inhibitors [SRIs] and cognitive-behavioral therapy [CBT] with exposure and response prevention [E/RP]) in the context of recent pharmacological, CBT, and combined trials.

Generalized anxiety disorder (GAD) is a common, chronic and disabling anxiety disorder with considerable comorbidity with depression as well as with other anxiety disorders. Although tricyclic antidepressants and benzodiazepines have been found to be efficacious in patients with GAD, tolerability problems and other risks limit their use in clinical practice. In placebo-controlled, acute (<8 weeks) trials, several medications, including the selective serotonin reuptake inhibitors ([SSRIs] escitalopram, paroxetine, and sertraline) and others (venlafaxine, buspirone, pregabalin), have demonstrated efficacy in patients with GAD. Indeed, current guidelines for the treatment of GAD recommend SSRIs as first-line pharmacological therapy because of their efficacy and tolerability profiles. Although GAD is a chronic condition that is usually present for years, with symptoms typically fluctuating in intensity over time, there have been few randomized, controlled trials of pharmacotherapy beyond the acute phase of treatment. However, data from recent relapse-prevention studies and longer-term maintenance studies with paroxetine, venlafaxine and escitalopram strongly support the value of continued treatment for at least a further 6 months. This article focuses on pharmacological treatment, and reviews recently available data from acute, long-term and relapse-prevention trials in patients with GAD. In addition, issues relating to the natural course of GAD are highlighted as important considerations to guide selection of pharmacotherapy.

The pathophysiology of obsessive-compulsive disorder (OCD) remains unknown. However, increasing attention has been paid to the putative role of the serotoninergic system, the strongest evidence being based on the widely demonstrated efficacy of serotonin (5HT) reuptake inhibitor antidepressants in the treatment of OCD. The therapeutic effects are correlated with changes in peripheral parameters of 5HT function, which have been found to be altered in OCD, suggesting the possibility of reduced 5HT reuptake capacity. This could reflect a compensatory mechanism presumably due to decreased availability of extracellular 5HT, as evidenced by data derived from direct assessment of central 5HT neurotransmission. The development of new neurochemical probes that explore the sensitivity of various 5HT receptor subtypes has provided precious information. m-Chlorophenylpyperazine (m-CPP), an agonist to 5HT1A, 5HT1D, and 5HT2C receptors, and which also blocks 5HT3 receptors, exacerbates OC symptoms. In contrast, neither MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a 5HT1A and 5HT2C receptor agonist, nor ipsapirone or buspirone, which acts as an agonist to 5HT1A receptors, have any effect on OC symptom severity. This suggests the potential implication of the 5HT1D receptor, as shown by the aggravation of OC manifestations in response to sumatriptan, a selective 5HT1D receptor agonist. The 5HT3 plays no specific role, given the lack of influence of the 5HT3 antagonist ondansetron, on OC symptom intensity. Further studies are required to elucidate the pharmacological molecular determinants of the putative 5HT1D receptor dysfunction.