Norepinephrine reuptake inhibitor

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Deficit Syndrome of Schizophrenia: Assuaging by
Norepinephrine Reuptake Inhibitor

Deficit Syndrome of Schizophrenia: Assuaging by Norepinephrine Reuptake Inhibitor

As another example, while a trial of amitriptyline in this regard showed positive results [9], but no significant effect with mapro- tiline in comparable assessment were visible [10]. Antidepres- sants like mirtazapine and mianserin as well have been studied with encouraging results [11-13]. Reboxetine [2-[(2-ethoxyphe- noxy)-phenyl-methyl]morpholine] is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ ADHD and exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-re- boxetine[14]. Both the (R, R)-(-) and (S,S)-(+)-enantiomers of re- boxetine are predominantly metabolized by the CYP3A4 isoenzyme [15]. Reboxetine essentially acts as a pure norepinephrine reuptake inhibitor (NRI) with very little activity on the serotonin transporter and without direct effects on the dopaminergic neurotransmission [16] and hence is a somewhat well-tolerated, fairly selective “nor- adrenergic” agent. NARIs may be especially useful in drive-deficient “anergic” states where the capacity for sustained motivation is lack- ing and also in the treatment of retarded and melancholic depres- sive states with a reduced capability to deal with stress [17]. Previ- ous studies have shown contradictory results [18,19] concerning the helpful effects of reboxetine on deficit symptoms. Objective of this study includes exploration of the effectiveness of reboxetine, as an adjunctive treatment, in a group of schizophrenic inpatients with prominent negative symptoms.
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Japanese experience with milnacipran, the first serotonin and norepinephrine reuptake inhibitor in Japan

Japanese experience with milnacipran, the first serotonin and norepinephrine reuptake inhibitor in Japan

Abstract: Milnacipran is a serotonin and norepinephrine reuptake inhibitor (SNRI), with a balanced potency for the inhibition of the reuptake of the two monoamines. In this, it contrasts with venlafaxine and duloxetine which, while possessing a dual action, have a selectivity of the order of 30-fold and 10-fold respectively for the reuptake of serotonin. Milnacipran has mainly been launched in countries where the selective serotonin reuptake inhibitors (SSRIs) and venlafaxine had been established for several years. As such it has attracted relative little interest from clinician investigators as a research tool. Japan, however, represents a unique situation because in 1999 milnacipran was launched within months of the fi rst SSRI and is still the only SNRI in Japan together with only two SSRIs (a third has just been introduced). This has led to a large number of investigative clinical studies, many of which give interesting insights into the potential of milnacipran in the treatment of depression and of other disorders. This article reviews these Japanese studies with milnacipran.
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Disposition and metabolism of [<sup>14</sup>C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats

Disposition and metabolism of [<sup>14</sup>C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats

Mass balance results indicated that renal excretion was the major route of elimination with 58.4%, 35.5%, and 40.2% of total radioactivity being excreted as unchanged levo[r]

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Clinical use of antidepressant therapy and associated cardiovascular risk

Clinical use of antidepressant therapy and associated cardiovascular risk

A wide variety of antidepressant agents are now available, and the cardiovascular profile of each of these is characterized to a variable extent. The overall balance between risk and benefit of therapy needs to consider the strength of the indication for antidepressant treatment, pre-existing risk factors for cardiovascular disease, drug dose, and perceived risk of inadvertent or intentional drug overdose. Well characterized effects of the monoamine oxidase inhibitor group and of trazodone include orthostatic hypotension, whilst the tricyclic antidepressant group are typically associated with tachycardia and a modest fall in systemic blood pressure. Serotonin and norepinephrine reuptake inhibitor agents may cause tachycardia and a modest rise in systemic blood pressure within the therapeutic dose range, whereas selective serotonin reuptake inhibitor agents exert few consistent cardiovascular effects; within the selective serotonin reuptake inhibitor group, citalopram and escitalopram appear uniquely capable of causing dose-dependent QTc prolongation. These various cardiovascular effects will allow the choice of antidepressant agent to be determined according to the individual patient characteristics and risk profile so that, for example, venlafaxine might be avoided in a patient with
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Effect of milnacipran on suicidality in patients with mild to moderate depressive disorder

Effect of milnacipran on suicidality in patients with mild to moderate depressive disorder

Abstract: The presence of suicidal manifestations (thoughts and behavior) was studied in a cohort of 30 patients with mild to moderate depression during a 6-week treatment with the serotonin-norepinephrine reuptake inhibitor, milnacipran. At baseline mild suicidal thoughts were present in 46.7% of patients, the mean Hamilton Depression Rating Score (HDRS 17 ) was 23.9 ± 1.8 and the mean suicidality score on the Beck Scale for Suicidal Ideation (BSS) was 4.9 ± 4.9. Suicidal thoughts decreased progressively throughout the study in parallel with other depressive symptoms. At no time during treatment was there any indication of an increased suicidal risk. Notably, the items retardation and psychic anxiety on the HDRS 17 decreased in parallel. This may possibly explain the lack of any “activation syndrome”, which is occasion- ally observed at the early stages of therapy with some antidepressants and may be linked to a temporary increase in suicidal ideation. To our knowledge this is the first detailed report of suicidality during treatment with milnacipran.
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Synthesis, screening and pharmacokinetic evaluation of potential prodrugs of bupropion

Synthesis, screening and pharmacokinetic evaluation of potential prodrugs of bupropion

The pharmacological screens of N-methylbupropion versus bupropion showed that N-methylbupropion is less active than bupropion as a dopamine and norepinephrine reuptake inhibitor and coul[r]

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Improvement of social adaptation in depression with serotonin and norepinephrine reuptake inhibitors

Improvement of social adaptation in depression with serotonin and norepinephrine reuptake inhibitors

Abstract: Depression is a disabling condition resulting in significant impairment in social functioning, involving the patient’s family, friends, work colleagues, and society at large. Although both psychologic and pharmacologic treatments generally improve many depressive symptoms, they do not always result in significant improvement in social functioning. The importance of recovery of social functioning in depressed patients is now widely appreciated, and studies are beginning to include it in evaluations of therapeutic efficacy. Among the various social adjustment evaluation rating scales, the Social Adaptation Self-Evaluation Scale, a social motivation and behavior scale, has been found to be simple to use and sensitive to change. Using this scale, the selective norepinephrine reuptake inhibitor, reboxetine, has been shown to be significantly more effective in improving social functioning than the selective serotonin reuptake inhibitor, fluoxetine. These findings are consistent with the notion that improvement in social adaptation involves functions depending primarily on noradrenergic neurotransmission. This hypothesis suggests that the serotonin and norepinephrine reuptake inhibitors, venlafaxine, duloxetine, and milnacipran, could be particularly helpful in improving social functioning. Preliminary studies with the serotonin and norepinephrine reuptake inhibitors suggest that they significantly improve social functioning. Comparative studies with selective serotonin reuptake inhibitors on the effects on social functioning should be encouraged.
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Pathophysiology and Management of Pica

Pathophysiology and Management of Pica

In these cases behavior- based treatment (12) can be useful. This can be done by creating a negative image of the harmful substance in the mind of pica sufferer, discrimination training between edible and non edible stuff and visual screening with eyes. For a pica patient of psychotic etiology, therapy and medication like SSIRs (serotonin-specific reuptake inhibitor) a class of compounds usually used for the patients of anxiety, depression or personality disorder (13) has been used very successfully. But such type of treatment should not be used until the non-etiologies have been ruled out. Patients of pica are usually treated as outpatients.
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Effects of maternal psychotropic drug dosage on birth outcomes

Effects of maternal psychotropic drug dosage on birth outcomes

Although treatment of depression during pregnancy is regarded as necessary, evidence about the safety of pharmacologic treatment is scarce. Selective serotonin reuptake inhibitors (SSRIs) are among the most investigated psychotropic drugs used during pregnancy. There have been numerous studies focusing on the effect of SSRIs on birth outcomes, such as gestational age, birth weight, Apgar scores, admission to neonatal intensive care units, and various malformations. 2,5–8 The possible adverse

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Antidepressant treatment response is modulated by genetic and environmental factors and their interactions

Antidepressant treatment response is modulated by genetic and environmental factors and their interactions

One possible explanation is that antidepressant response is a multifactorial and polygenic phenotype determined by several common variants, and each individual SNP is only responsible for a small fraction of heritability which makes them invisible in statistical analyses with a reliable confi- dence rate. Nonetheless, rare genetic variants generally have a larger impact; so, this might give us hope to iden- tify genetic variants with more impressing effects, al- though the current sample sizes of most studies are too small to detect them [6]. Furthermore, environmental factors such as childhood maltreatment and stressful life events in several studies showed independent effects on selective serotonin reuptake inhibitor (SSRI) response, and in some cases, also in significant interaction with genetic polymorphisms [7,8]. Although there are several genes showing consistent interaction with certain envir- onmental factors in the development of depression, only a fraction of these interactions was tested in the case of
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Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

Background: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, an[r]

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<em>5-HTR1A</em> and <em>5-HTR2A </em>genetic polymorphisms and SSRI antidepressant response in depressive Chinese patients

<em>5-HTR1A</em> and <em>5-HTR2A </em>genetic polymorphisms and SSRI antidepressant response in depressive Chinese patients

The relationship between single nucleotide polymorphisms in 5-HT2A signal transduction-related genes and the response efficacy to selective serotonin reuptake inhibitor treatments in [r]

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Sertraline versus amitriptyline in
the prophylactic therapy of non-depressed chronic tension-type
headache patients

Sertraline versus amitriptyline in the prophylactic therapy of non-depressed chronic tension-type headache patients

pathophysiology of headaches suggest a disturbance in sero- tonin neurotransmission, providing a rationale for treatment [7, 8]. Furthermore, an ascending serotoninergic pain mod- ulation pathway from the dorsal raphe nucleus to the parafascicular nucleus of the thalamus has recently been dis- covered and appears to be of particular relevance to headache syndromes [7, 8]. In consideration of the possible pathological mechanisms of CTTH, it is thought that sero- tonin-specific reuptake inhibitors may be helpful.

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Efficacy of selective serotonin reuptake inhibitor (SSRI) in patient with premature ejaculation

Efficacy of selective serotonin reuptake inhibitor (SSRI) in patient with premature ejaculation

multifactorial and has low positive predictive value, suggesting that PE diagnosis should be based solely on Intra Vaginal Ejaculation Latency Time (IVELT) (5), while new classification of PE has been proposed for the pending DSM-V; distinguishing four PE categories; lifelong PE, acquired PE, natural variable PE and premature-like ejaculatory dysfunction (6). Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and delayed ejaculation (7). Emerging clinical evidence indicates chronic and on-demand dosing of SSRIs has a beneficial effect for the treatment of men with PE (2). On-demand dapoxetine, and SSRI with a short half-life, recently has been shown to significantly increase IVELT and improve PE patient-related outcomes (8).
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Lack of association between COMT gene polymorphism and treatment outcome in major depression

Lack of association between COMT gene polymorphism and treatment outcome in major depression

Meta- analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients.[r]

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Olanzapine and fluoxetine combination therapy for treatment-resistant depression: review of efficacy, safety, and study design issues

Olanzapine and fluoxetine combination therapy for treatment-resistant depression: review of efficacy, safety, and study design issues

Abstract: Treatment-resistant depression (TRD) is a common occurrence in clinical practice. Up to 30% of patients with major depression do not respond to conventional antidepressant treatment, while a significantly greater number of patients experience only partial symptom reduction. Numerous strategies may be applied by the practicing clinician to overcome limitations in the effectiveness of antidepressant monotherapy, including combining drug treatment with evidence-supported psychotherapies, combining antidepressants (combination pharmacotherapy), and combining antidepressants with other non-antidepressant psychotropic medications (augmentation treatment). One such augmentation strategy, the combination of the selective serotonin reuptake inhibitor, fluoxetine (FLX), with the atypical antipsychotic drug, olanzapine (OLZ), is supported by the results of four randomized, double-blind, acute phase studies of patients who had responded inadequately to antidepressant monotherapy. In each study, the FLX/OLZ combination caused rapid reduction in Montgomery-Asberg Depression Rating scale scores, with two of the four studies showing significantly greater improvement than antidepressant monotherapy at study endpoint. Effects of the FLX/OLZ combination were strongest in cases where failure to respond to two antidepressants prior to randomization was established during the current depressive episode. The FLX/OLZ combination was well-tolerated; however, body weight gain and increases in prolactin were greater than that of the antidepres- sant monotherapy groups, and were comparable to that of OLZ monotherapy. While effective during acute-phase treatment, questions remain regarding the long-term efficacy and safety of FLX/OLZ relative to antidepressant monotherapy and other combination strategies. Efforts aimed at determining the placement of FLX/OLZ among the available options for addressing TRD are limited by lack of comparison and sequential treatment studies. Important aspects of study design and directions for future research are discussed.
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Hippocampal Endoplasmic Reticulum Stress: Novel Target in PTSD Pharmacotherapy?

Hippocampal Endoplasmic Reticulum Stress: Novel Target in PTSD Pharmacotherapy?

Post-traumatic stress disorder (PTSD) is an anxiety disorder that is induced by the exposure to dramatic and/or life-threatening stresses in susceptible individuals. PTSD is accompanied by functional daily impairments and increased risk of suicide. At present only few drugs, if any, are clinically used to treat this condition. The use of selective serotonin reuptake inhibitor (SSRIs), the first line FDA-approved drug for PTSD, may increase the risk of suicidal ideation and suicide in patients suffering form the disorder. This clinical finding prompts the establishment of study focusing on the elucidation of SSRI pharmacodynamics in PTSD model. Recent study show that hippocampal ER stress is involved in single-prolonged stress (SPS)-induced rodent model of PTSD. SSRIs, such as fluvoxamine or sertraline, may contribute to the mitigation or exacerbation of mental conditions in PTSD patient, respectively. Glucose-regulated protein 78 (GRP78) (ER chaperone and master regulator of ER stress) is known to be involved in
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Pain Reactivity in 2-Month-Old Infants After Prenatal and Postnatal Selective Serotonin Reuptake Inhibitor Medication Exposure

Pain Reactivity in 2-Month-Old Infants After Prenatal and Postnatal Selective Serotonin Reuptake Inhibitor Medication Exposure

Characteristics of infants and their mothers did not differ significantly between groups (Table 1). At the time of the study, all infants were in good health and in all groups mean maternal mood was rated as nonclinically depressed (ie, symptoms reported ⬍ 16), although mean Hamilton Depression Rating Scale (HAMD) scores were significantly lower in control subjects than in the 2 exposure groups (P ⬍ .05). Prenatal SSRI medication exposure occurred in the last 2 trimesters, and the length of maternal SSRI use or medication dose did not vary significantly between the 2 exposure groups (P ⬎ .05). Similarly, length of SSRI use did not vary between exposure groups (P ⬎ .05). All mothers reported taking their prescribed medication in the 3 days before the study, and thus maternal medication levels, and presum- ably breast milk levels, were considered to be at a steady state at the time of the study. Given the extra blood collection needed for drug levels, the heel- lance blood collection took longer among the infants with postnatal drug exposure (means: 104.3 ⫾ 18 vs 109.7 ⫾ 25 vs 146 ⫾ 48 seconds for control, prenatal selective serotonin reuptake inhibitor– exposed in- fants [pSE], and prenatal and postnatal selective se- rotonin reuptake inhibitor– exposed infants [ppSE] groups, respectively).
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Antenatal Use of Selective Serotonin-Reuptake Inhibitors and QT Interval Prolongation in Newborns

Antenatal Use of Selective Serotonin-Reuptake Inhibitors and QT Interval Prolongation in Newborns

METHODS. Between January 2000 and December 2005, we collected data on all of the newborns born at a single tertiary care hospital. Electrocardiograms of infants ex- posed to selective serotonin-reuptake inhibitor antidepressants in utero were com- pared with those of healthy control newborns matched on gestational age. The tracings were interpreted by a pediatric cardiologist who was unaware of the drug exposure.

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Should Selective Serotonin Reuptake Inhibitors Be Prescribed for Children With Major Depressive and Anxiety Disorders?

Should Selective Serotonin Reuptake Inhibitors Be Prescribed for Children With Major Depressive and Anxiety Disorders?

time, but beginning in June 2003, doubts increasingly arose about the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) in youth after the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) received pediatric trial data from Glaxo SmithKline on paroxetine. Subsequently, both the FDA and the MHRA reanalyzed both published and unpub- lished efficacy and safety data from SSRI trials for youth. 4,5 Relevant findings from these reanalyses are

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