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Reuptake Inhibitors (reuptake + inhibitor)
Kinds of Reuptake Inhibitors Terms modified by Reuptake Inhibitors Selected AbstractsQuetiapine augmentation in depressed patients with partial response to antidepressants,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2008James S Olver Abstract Objective Clinical trials suggest between 30,50% of depressed patients have an inadequate outcome to antidepressant pharmacotherapy. Among the approaches to improve outcome has been augmentation with antipsychotic medications. We aim to investigate the efficacy and tolerability of augmentation with quetiapine in depressed patients with a partial response to antidepressants. Methods Patients with a Major Depressive Disorder (DSMIV) who had partial/no response to a stable dose of an Selective Serotonin Reuptake Inhibitors (SSRI)/SNRI were recruited. All patients received add-on quetiapine (200,600,mg nocte) in a 6-week trial. Outcome measures (HAMD, MADRS) were assessed at screening, baseline, weeks 1, 2, 4 and 6. Extrapyramidal symptoms (EPSEs) were assessed at baseline, weeks 2, 4 and 6. A neuropsychological battery of tests was administered at baseline, weeks 3 and 6. Results Nineteen patients entered the trial and 18 completed the trial per protocol. We report a rapid improvement in depression ratings over 6 weeks (p,<,0.0005) and remission rates of 67% at week 1 and 94% at week 6. There was no evidence of EPSE and no worsening (and some improvement) of cognition. Conclusion This suggests clinical benefits of quetiapine augmentation of SSRI/SNRI antidepressants with no worsening, and possible improvements in cognition. Copyright © 2008 John Wiley & Sons, Ltd. [source] Fluvoxamine and sleep disturbances in posttraumatic stress disorderJOURNAL OF TRAUMATIC STRESS, Issue 3 2001Thomas C. Neylan Abstract This study assesses the efficacy of fluvoxamine treatment on different domains of subjective sleep quality in Vietnam combat veterans with chronic posttraumatic stress disorder (PTSD). Medically healthy male Vietnam theater combat veterans (N = 21) completed a 10-week open label trial. Fluvoxamine treatment led to improvements in PTSD symptoms and all domains of subjective sleep quality. The largest effect was for dreams linked to the traumatic experience in combat. In contrast, generic unpleasant dreams showed only a modest response to treatment. Sleep maintenance insomnia and the item "troubled sleep" showed a large treatment response, whereas sleep onset insomnia improved less substantially. These therapeutic benefits contrast with published reports that have found activating effects of Selective Serotonin Reuptake Inhibitors on the sleep electroencephalogram. [source] Selective Serotonin Reuptake Inhibitors and Treatment of Premenstrual Dysphoric DisorderPERSPECTIVES IN PSYCHIATRIC CARE, Issue 2 2002AP/MHCNS, Deborah L. Finfgeld RN TOPIC. Premenstrual dysphoric disorder (PMDD) has reentered the spotlight following the FDA's recent approval of fluoxetine hydrochloride to treat its symptoms. Although the diagnosis and treatment of PMDD has long been a source of contention, the FDA move has heightened the debate over this diagnostic category and the most appropriate treatment. PURPOSE. To explore several diagnoses related to PMDD and review recent research findings pertaining to the effectiveness of SSRIs to treat PMDD. SOURCES OF INFORMATION. Published literature. CONCLUSIONS. Advanced practice nurses need to remain well informed about premenstrual conditions and emerging evidence-based treatment alternatives. In particular, they need to remember that the FDA has approved fluoxetine for the treatment of a very small subset of women with premenstrual complaints, among whom treatment efficacy is limited. [source] Withdrawal of Selective Serotonin Reuptake Inhibitors (SSRIs) May Cause Increased Atrial Natriuretic Peptide (ANP) and Persistent Sexual Arousal in Women?THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006David Goldmeier MD [source] ChemInform Abstract: Heterocyclic Cycloalkanol Ethylamines as Norepinephrine Reuptake Inhibitors.CHEMINFORM, Issue 42 2010Joseph P. Sabatucci Abstract A variety of heterocyclic cycloalkanol ethylamines are synthesized and evaluated as norephedrine reuptake inhibitors. [source] Successful medication withdrawal after cognitive-behavioral therapy in a treatment-resistant preadolescent male with obsessive-compulsive disorderDEPRESSION AND ANXIETY, Issue 1 2009Robert B. Goldstein M.D. Abstract There are no reports of a child taking a selective serotonin reuptake inhibitor and an atypical anti-psychotic being successfully tapered from these medications after completion of cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder. With this in mind, we report the case of an 8.5-year,old male who was taking risperidone 0.5,mg bid, sertraline 100,mg, and atomoxetine 25,mg at presentation. After a successful course of CBT, we describe how medications were systematically withdrawn. Implications of this case on practice parameters (e.g., CBT may be an effective augmenting agent for those non-responsive to initial pharmacological treatments) are highlighted. Depression and Anxiety, 2009. © 2008 Wiley-Liss, Inc. [source] Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trialDEPRESSION AND ANXIETY, Issue 3 2008Moira Rynn M.D. Abstract Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV,defined GAD diagnosis were randomized to duloxetine 60,120,mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction ,50% from baseline), Clinician Global Impression,Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD. Depression and Anxiety 0:1,8, 2007. © 2007 Wiley-Liss, Inc. [source] A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorderDEPRESSION AND ANXIETY, Issue 1 2007Mark H. Pollack M.D. Abstract To date, no large-scale, controlled trial comparing a serotonin,norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75,mg/day or 150,mg/day), or paroxetine 40,mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions,Severity (CGI-S) and ,Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder. Depression and Anxiety 24:1,14, 2007. © 2006 Wiley-Liss, Inc. [source] Multidimensional effects of sertraline in social anxiety disorderDEPRESSION AND ANXIETY, Issue 1 2006Kathryn M. Connor M.D. Abstract Clinical trials of social anxiety disorder (SAD) have largely focused on the effect of treatment on symptoms of fear and avoidance, while neglecting the third clinically relevant dimension, physiological arousal. Data were combined from two previously reported placebo-controlled trials of sertraline in the treatment of moderate-to-severe generalized SAD. Efficacy was evaluated using the Brief Social Phobia Scale (BSPS). Three hundred forty-six subjects were randomized to 12,13 weeks of treatment with sertraline and 273 subjects to placebo. Following treatment, significant improvement was noted in favor of sertraline on the full BSPS (P<.001), as well as on each of the individual BSPS subscales: fear (P=.001); avoidance (P<.0001); and physiological arousal (P<.0001). Of the physiological symptoms assessed, the treatment advantage with sertraline was maintained for blushing (P<.003) and palpitations (P<.03), but not for trembling and sweating. These results confirm the efficacy of treatment with a selective serotonin reuptake inhibitor (SSRI), sertraline, across the spectrum of fear, avoidance, and physiological arousal in generalized SAD (GSAD). Among common physiological symptoms in this population, blushing and palpitations appear more treatment responsive than trembling and sweating to acute treatment with sertraline. Depression and Anxiety 23:6,10, 2006. © 2005 Wiley-Liss, Inc. [source] Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptomsDEPRESSION AND ANXIETY, Issue 1 2002Jonathan R.T. Davidson M.D., M.B.A. Abstract Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces significantly higher remission rates in depressed patients than do the selective serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we explored the relationship between differences in treatment efficacy, early improvement of symptoms, and severity of baseline anxiety in depressed patients treated with either venlafaxine or fluoxetine. A pooled analysis was performed on data from 1,454 outpatients with major depression from five double-blind, randomized studies comparing the 6-week efficacy of venlafaxine (542 patients) with fluoxetine (555 patients). The Hamilton rating scale for depression (HAM-D) total and item scores were analyzed at different treatment times up to 6 weeks. Venlafaxine and fluoxetine both produced statistically significant higher response and remission rates compared with placebo starting from week 2 for response and weeks 3 to 4 for remission. Venlafaxine was statistically significantly superior to fluoxetine from week 3 until week 6 in respect of response rate, and from week 2 until week 6 for remission rate. After 1 week of treatment, greater improvement in individual symptoms was observed in the depressed mood, suicide, and psychic anxiety items of the HAM-D scale for both venlafaxine- and fluoxetine-treated patients compared with placebo. Improvement in psychic anxiety was statistically significantly greater with venlafaxine than with fluoxetine. The presence of baseline psychic anxiety correlated significantly to treatment outcome when analyzing the remission rates. In depressed patients with moderate anxiety (HAM-D psychic anxiety score ,2), venlafaxine statistically significantly increased remission rates compared with placebo from week 4 until week 6, while a significant effect of fluoxetine on remission rates was observed starting at week 6. Remission rates in the severely anxious depressed patients (score >2) were statistically significantly higher with venlafaxine than placebo starting from week 3 until the end of the study period, but no difference could be observed between fluoxetine and placebo. Baseline severity of psychic anxiety had a significant impact on remission rates after treatment of patients diagnosed with depression. Venlafaxine's superior remission rates in the more severely anxious patients and its ability to improve psychic anxiety as early as week 1 compared with fluoxetine suggest that venlafaxine's early efficacy on anxiety symptoms may be the basis for its superior efficacy in depression. Depression and Anxiety 16:4,13, 2002. © 2002 Wiley-Liss, Inc. [source] Indicators of pretreatment suicidal ideation in adults with major depressive disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010D. W. Morris Morris DW, Trivedi MH, Husain MM, Fava M, Budhwar N, Wisniewski SR, Miyahara S, Gollan JK, Davis LL, Daly EJ, Rush AJ. Indicators of pretreatment suicidal ideation in adults with major depressive disorder. Objective:, In order to evaluate the presence of treatment emergent suicidal ideation (SI), it becomes necessary to identify those patients with SI at the onset of treatment. The purpose of this report is to identify sociodemographic and clinical features that are associated with SI in major depressive disorder (MDD) patients prior to treatment with a selective serotonin reuptake inhibitor. Method:, This multisite study enrolled 265 out-patients with non-psychotic MDD. Sociodemographic and clinical features of participants with and without SI were compared post hoc. Results:, Social phobia, bulimia nervosa, number of past depressive episodes, and race were independently associated with SI by one or more SI measure. Conclusion:, Concurrent social phobia and bulimia nervosa may be potential risk factors for SI in patients with non-psychotic MDD. Additionally, patients with more than one past depressive episode may also be at increased risk of SI. [source] Sertraline-induced hypomania: a genuine side-effectACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2003D. N. Mendhekar Objective: Antidepressants including selective serotonin reuptake inhibitor (SSRI)-associated mania or hypomania has been well documented in the literature but these patients with switch have either mood disorders or various risk factors for bipolar disorder. This case report examines SSRI-induced hypomania in a patient with dissociative disorder and highlights hypomania as a genuine side-effect of sertraline rather than a switch. Method: A 23-year-old female patient with dissociative disorder has been described. Results: Hypomanic symptoms emerged during treatment with sertraline at the dose of 50 mg/day after 3,4 days of initiation of therapy and had complete recovery within 7 days after stopping sertraline. Conclusion: In the absence of risk factors for manic switch, sertraline-induced hypomania may be a true side-effect of drug. [source] Laboratory persistence and fate of fluoxetine in aquatic environmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2006Jeong-Wook Kwon Abstract The persistence and fate of fluoxetine, a selective serotonin reuptake inhibitor, has been investigated in laboratory-scale experiments, including studies with various aqueous solutions, water/sediment systems, and activated sludge-amended medium. The samples were placed in the dark and/or in a growth chamber fitted with fluorescent lamps simulating the ultraviolet output of sunlight. Over a period of 30 d, fluoxetine was hydrolytically and photolytically stable in all aqueous solutions except synthetic humic water (pH 7), in which the degradation rate was increased by approximately 13-fold in comparison with buffered solutions at the same pH. Fluoxetine rapidly dissipated from the aqueous phase in water/sediment systems, primarily because of distribution to sediments. The dissipation rate from the aqueous phase was similar between light and dark systems, indicating a low contribution of photodegradation to the dissipation of fluoxetine in this system. The potential impact of fluoxetine in aquatic environments would be decreased because of adsorption to sediments. Based on results of ready-biodegradability investigations, fluoxetine would not be expected to rapidly biodegrade in wastewater treatment plants. A photoproduct was detected only in a sample of synthetic humic water and was identified as norfluoxetine formed by demethylation. Results indicate that fluoxetine is relatively recalcitrant to hydrolysis, photolysis, and microbial degradation and that it is rapidly removed from surface waters by adsorption to sediment, where it appears to be persistent. [source] Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of ,2 -adrenergic and serotonin2C receptors: a comparison with citalopramEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2000M. J. Millan Abstract Mirtazapine displayed marked affinity for cloned, human ,2A -adrenergic (AR) receptors at which it blocked noradrenaline (NA)-induced stimulation of guanosine-5,-O-(3-[35S]thio)-triphosphate ([35S]-GTP,S) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5-HT)2C receptors at which it abolished 5-HT-induced phosphoinositide generation. Alpha2 -AR antagonist properties were revealed in vivo by blockade of UK-14,304-induced antinociception, while antagonist actions at 5-HT2C receptors were demonstrated by blockade of Ro 60 0175-induced penile erections and discriminative stimulus properties. Mirtazapine showed negligible affinity for 5-HT reuptake sites, in contrast to the selective 5-HT reuptake inhibitor, citalopram. In freely moving rats, in the dorsal hippocampus, frontal cortex (FCX), nucleus accumbens and striatum, citalopram increased dialysate levels of 5-HT, but not dopamine (DA) and NA. On the contrary, mirtazapine markedly elevated dialysate levels of NA and, in FCX, DA, whereas 5-HT was not affected. Citalopram inhibited the firing rate of serotonergic neurons in dorsal raphe nucleus, but not of dopaminergic neurons in the ventral tegmental area, nor adrenergic neurons in the locus coeruleus. Mirtazapine, in contrast, enhanced the firing rate of dopaminergic and adrenergic, but not serotonergic, neurons. Following 2 weeks administration, the facilitatory influence of mirtazapine upon dialysate levels of DA and NA versus 5-HT in FCX was maintained, and the influence of citalopram upon FCX levels of 5-HT versus DA and NA was also unchanged. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons. In conclusion, in contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission. These actions reflect antagonist properties at ,2A -AR and 5-HT2C receptors. [source] Sertraline, a selective serotonin reuptake inhibitor, affects thirst, salt appetite and plasma levels of oxytocin and vasopressin in ratsEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Ana Paula De Magalhães-Nunes We investigated the effects of chronic administration of sertraline (SERT; ,20 mg kg,1 day,1 in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT-treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.7 ± 0.5 versus 20.0 ± 0.9 ml, respectively, at 300 min after water presentation, P < 0.0001). Subcutaneous injection of 2 m NaCl or isoproterenol evoked a lower dipsogenic response in rats treated with SERT for 21 days. Fluid and food deprivation also induced a weaker dipsogenic response in SERT-treated rats (1.6 ± 0.5 versus 10.2 ± 1.2 ml, at 300 min, P < 0.0001) but had no effect on saline intake. Sodium depletion induced a higher natriorexigenic response in the SERT group (5.6 ± 1.3 versus 1.2 ± 0.3 ml, at 300 min, P < 0.0002). Higher urinary density and lower plasma sodium levels were observed after SERT treatment. Sertraline also increased plasma levels of vasopressin and oxytocin (AVP, 2.65 ± 0.36 versus 1.31 ± 0.16 pg ml,1, P < 0.005; OT, 17.16 ± 1.06 versus 11.3 ± 1.03 pg ml,1, P < 0.0009, at the third week post-treatment). These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT. [source] Effects of venlafaxine on ethanol withdrawal syndrome in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004Esra Sa Abstract The present study was designed to investigate the effects of venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI), on ethanol withdrawal syndrome in rats. Adult male Wistar rats (187,319 g) were used for the study. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair-fed an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Venlafaxine (5, 10, 20 and 40 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After the 2nd, 4th and 6th hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behaviour and wet dog shakes were recorded or rated. A second series of injections was given at the 6th hour after the first one, and rats were then tested for audiogenic seizures. Venlafaxine produced some inhibitory effects on locomotor hyperactivity, stereotypic behaviours and wet dog shakes. However, a two-way anova of the data did not indicate any significant effect. It reduced the incidence of the audiogenic seizures at the 6th hour of ethanol withdrawal. Venlafaxine (20 mg/kg) also prolonged the latency of the seizures significantly. Our results suggest that acute venlafaxine treatment has limited beneficial effects on ethanol withdrawal syndrome in rats. [source] Sumatriptan challenge in bipolar patients with and without migraine: a neuroendocrine study of 5-HT1D receptor function.HEADACHE, Issue 3 2003T Mahmood Int Clin Psychopharmacol. 2002 Jan;17(1):33-36 An association between bipolar disorder and migraine has been lately recognized and an abnormality of central serotonergic function is suggested as the underlying neurophysiological disturbance. To examine the role of serotonin in bipolar disorder and migraine, we used the neuroendocrine challenge paradigm, and we chose sumatriptan, a 5HT1D agonist, as the pharmacological probe. We studied nine bipolar patients with migraine, nine bipolar patients without it, seven migraine patients, and nine matched normal controls. A post-hoc analysis showed subsensitivity of serotonergic function, reflected in a blunted growth hormone response to sumatriptan challenge in bipolar patients who also suffered from migraine. Comment: Given regulatory and labelling concerns about the potential for triptans to provoke serotonin syndrome, the apparent down-regulation of serotonergic function in patients with bipolar disorder may suggest cause for cautious optimism and encourage future study of triptans in these patients to establish true causality or otherwise. A prospective trial of sumatriptan injectable identified 1700 patients who repetitively used the triptan and were concomitantly on selective serotonin reuptake inhibitor (SSRI) medication. No serotonin syndrome was reported in any patient (Putnam GP, O'Quinn S, Bolden-Watson CP, Davis RL, Gutterman DL, Fox AW. Migraine polypharmacy and the tolerability of sumatriptan: a large-scale, prospective study. Cephalalgia. 1999;19:668-675). Since SSRIs can rarely induce serotonin syndrome alone, there is a significant difficulty in establishing a risk of coadministration. DSM and SJT [source] Functional magnetic resonance imagery (fMRI) in fibromyalgia and the response to milnacipranHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2009Yves MainguyArticle first published online: 28 MAY 200 Abstract Functional imaging has been used to study response to pain in fibromyalgia patients. Functional magnetic resonance imagery (fMRI) which tracks local changes in blood flow has a higher spatial and temporal resolution than other techniques such as positron emission tomography (PET) or single-photon emission tomography (SPECT). fMRI studies in fibromyalgia patients suggest that similar levels of subjective pain result in similar central nervous system (CNS) activation in both fibromyalgia patients and controls. For a similar stimulus, however, fibromyalgia patients have a greater subjective sensation of pain. This increased sensitivity is accompanied with a decreased activity in brain regions implicated in the descending pain inhibitory pathways. The hypothesis that increased sensitivity to pain is due to decreased activity of the descending inhibitory pathways is supported by results with milnacipran. Fibromyalgia patients treated with the serotonin and noradrenaline reuptake inhibitor, milnacipran, exhibited a reduction in pain sensitivity and a parallel increase in activity in brain regions implicated in the descending pain inhibitory pathways compared to placebo-treated patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Neurological complications of psychiatric drugs: clinical features and management,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Peter M. Haddad Abstract This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders. Copyright © 2007 John Wiley & Sons, Ltd. [source] Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a reviewHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2003*Article first published online: 11 DEC 200, Michel Bourin Abstract Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive, compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. There is wide interindividual variation in the pharmacokinetics of paroxetine in adults as well as in the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment, however, serious adverse events are extremely rare even in overdose. A Pub Med search was used to collect information on the efficacy and tolerability in elderly patients. There are few studies of depression in the elderly and only one study in the old,old. In anxiety disorders including general anxiety disorder, panic disorder, obsessive,compulsive disorder and social anxiety, there are no studies at all in the elderly. However, the safety of the drug allows its prescription in the elderly. In summary, paroxetine is well tolerated in the treatment of depression in those between the ages of 65 and 75, although few studies have examined its use in those of 75 and older. Copyright © 2002 John Wiley & Sons, Ltd. [source] The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label studyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2002P. N. Dannon Abstract Background and Objective Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line treatment for panic disorder, although up to 30% of patients either do not respond to SSRIs or withdraw due to adverse events. Reboxetine, a selective norepinephrine reuptake inhibitor (selective NRI), is effective in treating depression and may alleviate depression-related anxiety. This study aimed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs. Method In this 6-week, open-label study, 29 adult outpatients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2,mg/day, titrated to a maximum of 8,mg/day over the first 10 days. Efficacy was assessed using the Panic Self-Questionnaire (PSQ), the Hamilton Rating Scale for Anxiety (HAM-A), the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment of Functioning (GAF) Scale. Results The 24 patients who completed the study responded well to reboxetine treatment. Significant improvement (p,<,0.001) was observed in the number of daily panic attacks, and on the scales measuring anxiety, depression and functioning. Reboxetine was generally well tolerated. Five patients withdrew due to adverse events. Conclusions Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation. Copyright © 2002 John Wiley & Sons, Ltd. [source] Tolerability and safety of fluvoxamine and other antidepressantsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2006H. G. M. Westenberg Summary Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity. [source] Serotonin syndrome caused by interaction between citalopram and fentanylJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2007S. Ailawadhi MD Summary Objective:, To report a case of serotonin syndrome associated with interaction between fentanyl and citalopram, as evidenced by medication history, clinical features and reversal following discontinuation of fentanyl. Case Summary:, A 65-year-old patient chronically treated with the selective serotonin reuptake inhibitor (SSRI) citalopram developed confusion, agitation, tachycardia, tremors, myoclonic jerks and unsteady gait, consistent with serotonin syndrome, following initiation of fentanyl, and all symptoms and signs resolved following discontinuation of fentanyl. Based on the Naranjo probability scale, serotonin syndrome was a probable adverse reaction associated with co-administration of citalopram and fentanyl. Discussion:, Serotonin syndrome is a potentially lethal pharmacodynamic interaction between medications that increase serotonergic transmission at the synaptic junction. The development of new pharmacological agents with varied properties and actions has increased the risk of serotonin syndrome as a clinical diagnosis. SSRIs and fentanyl are commonly co-administered, especially in the setting of chronic or malignant pain, as underlying depression may contribute to the pathogenesis of pain. Conclusion:, Healthcare professionals should be aware of the possible development of serotonin syndrome as a complication of initiation of fentanyl and other phenylpiperidine opioids in patients treated with SSRIs. [source] Synthesis of (±) 3-(6-nitro-2-quinolinyl)-[9-methyl- 11C]-3,9-diazabicyclo-[4.2.1]-nonane ([11C-methyl]NS 4194)JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2002Svend B. Jensen Abstract (±) 3-(6-Nitro-2-quinolinyl)-[9-methyl- 11C]-3,9-diazabicyclo-[4.2.1]-nonane ([11C-methyl]NS 4194), a selective serotonin reuptake inhibitor (SSRI), was synthesised within 35 min after end of bombardment with a radiochemical purity >98%. It had a decay-corrected radiochemical yield of 7% after preparative HPLC, and a specific radioactivity around 37 GBq/,mol (EOS). A typical production starting with 40 GBq [11C]CO2 yielded 800 MBq of radiolabelled [11C-methyl]NS 4194 in a formulated solution. The synthesis of the precursor to [11C-methyl]NS 4194, (±) 9-H-3-[6-nitro-(2-quinolinyl)]-3,9-diazabicyclo-[4.2.1]-nonane, as well as the unlabelled analogue (±) 9-methyl 3-[6-nitro-(2-quinolinyl)]-3,9-diazabicyclo-[4.2.1]-nonane (NS 4194), are also described. Copyright © 2002 John Wiley & Sons, Ltd. [source] Serotonergic Agents and Alcoholism Treatment: A SimulationALCOHOLISM, Issue 12 2003Scott F. Stoltenberg Background: Those with early-onset alcoholism may better respond to ondansetron (a 5-HT3 receptor antagonist) than to selective serotonin reuptake inhibitor (SSRI) treatment, whereas those with late-onset alcoholism may present the reverse response pattern. Johnson and colleagues proposed a model that attempts to explain the observed treatment response patterns of those with early and late alcoholism onset by focusing on the influence of a common genetic variant in the serotonin transporter regulatory region (5-HTTLPR) on serotonin (5-HT) and dopamine (DA) system function. Methods: The present study formalizes and extends Johnson's descriptive model into a computer simulation consisting of differential equations. For each of 16 conditions defined by genotype, drinking status, diagnostic status, and drug treatment, data were generated by 100 simulation runs. Results: In every condition, the S/_ genotype (S/S and S/L) had higher extracellular 5-HT levels than did the L/L genotype. The S/_ genotype also had higher rates of postsynaptic DA firing than did the L/L genotype with the exception of the SSRI treatment condition, where the firing rates were similar. Drinking generally increased levels of extracellular 5-HT, reduced rates of presynaptic 5-HT firing, and increased rates of postsynaptic DA firing. Drinking produced increases in DA activation that were greater for the L/L genotype in the SSRI treatment condition and for the S/_ genotype in the ondansetron treatment condition. Conclusions: Genotype at 5-HTTLPR may influence relative reward of drinking alcohol while a person is under pharmacological treatment for alcoholism. Alternatively, 5-HTTLPR genotype may influence pathways of alcohol craving. Clinical studies should examine these hypotheses. [source] The influence of citalopram on interdigestive gastrointestinal motility in manALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010P. Janssen Aliment Pharmacol Ther 2010; 32: 289,295 Summary Background, Administration of 5-hydroxytryptamine (5HT) and selective 5HT receptor ligands modifies interdigestive motility in animals and in man. Aim, To study the effect of citalopram, a selective 5-HT reuptake inhibitor, on interdigestive motility in man. Methods, In 20 healthy subjects, antroduodenojejunal motor activity was studied manometrically. Basal interdigestive motor activity was recorded until the passage of two activity fronts. Ten minutes after the second activity front, placebo or 20 mg of citalopram was administered intravenously in a double-blind randomized fashion. Recording continued until the passage of two more activity fronts had occurred. Results, Administration of citalopram induced a premature small intestinal phase 3 after 35 ± 6.4 min, compared to 120 ± 17 min after placebo P < 0.01. Citalopram shortened MMC cycle length at the expense of phase 1 and phase 2 and significantly increased the motility index during phase 2 in the antrum and the small intestine. Conclusions, In the interdigestive state in man, intravenous administration of the selective 5-HT reuptake inhibitor citalopram induces a premature intestinal phase 3 and suppresses gastric activity fronts. Phase 2 motility is stimulated both in the stomach and in the small bowel after citalopram. These data suggest that 5HT is involved in the control of interdigestive motility. [source] Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: A double-blind, randomized, placebo-controlled studyMOVEMENT DISORDERS, Issue 6 2008David Devos MD Abstract Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short-term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short-term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double-blind, randomized, placebo- controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short-term clinical advantage. © 2008 Movement Disorder Society [source] Medication Quantification Scale Version III: Internal Validation of Detriment Weights Using a Chronic Pain PopulationPAIN PRACTICE, Issue 1 2008Michael Gallizzi MS ,,Abstract Introduction: We report an internal validation of the Medication Quantification Scale (MQS III) using a chronic pain population. The MQS was designed as a methodology of quantifying different drug regimens in 1992, updated in 1998 (MQS II), and again updated in 2003 (MQS III) using "detriment" weights determined by surveying physician members of the American Pain Society. The MQS has been used as a unitary clinical and research outcome. Methods: A retrospective chart review was collected from 400 patients in an interdisciplinary outpatient chronic pain clinic. A linear regression equation was developed using the patients' composite MQS III score, and those values were used in a Pearson correlation analysis. Results: The correlation between the subjects' computed regression detriment weights and the corresponding MQS III detriment weights yielded a significant result (r = 0.962, P < 0.01; two-tailed). Discussion: Our chronic pain sample-derived detriment weights did differ in some drug classes from that of the physician consensus, most notably the selective serotonin reuptake inhibitor, Opioid Schedule II, and NSAID class detriment. It is necessary to periodically resurvey large groups of physicians in order to control and modify the detriment weights of our categories in light of new information about detrimental effects (eg, COX-2 inhibitors), or to accommodate medical or political changes in prescribing habits (eg, more liberal opioid prescribing in the later years). This work suggests it may also be important to assess patients' perspective on detriment, as well as statistical and empiric use patterns.,, [source] Moderate and high affinity serotonin reuptake inhibitors increase the risk of upper gastrointestinal toxicity,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008James D. Lewis MD, MSCE Abstract Objective Serotonin release from platelets is important for regulating hemostasis. Some prior studies suggest an association between use of selective serotonin reuptake inhibitors and gastrointestinal bleeding and a possible synergistic effect of these medications with non-steroidal anti-inflammatory drugs (NSAIDs). This study examined the effect of medications that inhibit serotonin uptake on upper gastrointestinal toxicity. Methods 359 case subjects hospitalized for upper gastrointestinal bleeding, perforation, or benign gastric outlet obstruction were recruited from 28 hospitals. 1889 control subjects were recruited by random digit dialing from the same region. Data were collected during structured telephone interviews. Antidepressant medications were characterized according to their affinity for serotonin receptors. Exposure to medications required use on at least 1,day during the week prior to the index date. Results Any moderate or high affinity serotonin reuptake inhibitor (MHA-SRI) use was reported by 61 cases (17.1%) and 197 controls (10.4%). After adjusting for potential confounders, MHA-SRI use was associated with a significantly increased odds of hospitalization for upper gastrointestinal toxicity (adjusted OR,=,2.0, 95%CI 1.4,3.0). A dose,response relationship in terms of affinity for serotonin uptake receptors was not observed (p,=,0.17). No statistical interaction was observed for use of high dose NSAIDs or aspirin concomitantly with MHA-SRIs (p,=,0.5). When MHA-SRIs were used concomitantly with high dose NSAIDs, the adjusted odds ratio for the association with upper gastrointestinal toxicity was 3.5 (95%CI 1.9,6.6). Conclusions Use of MHA-SRIs is associated with an increased risk of hospitalization for upper gastrointestinal toxicity. Copyright © 2008 John Wiley & Sons, Ltd. [source] Drug related falls: a study in the French Pharmacovigilance database,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2005Emmanuelle Souchet Abstract Objective To investigate the risk of falls associated with drugs among the French population using data reported to the French spontaneous reporting system and recorded in the French Pharmacovigilance database. Methods All cases including a fall were searched in the French Pharmacovigilance database between 1995 and 1999. Drugs involved and characteristics of patients were investigated. In a second step, we estimated the risk associated with psychotropic and cardiovascular drugs in a case/non case comparison, where cases were reports including a fall and non cases all other reports. This risk was estimated by calculation of crude and age and gender adjusted reporting odds ratios (ROR). Results During this period, 328 reports including a fall were reported (0.4% of the database). Patients were female in 70%. Mean age was 76,±,18 years. Comparisons between cases and non cases showed that cases were more likely to be women (OR: 1.9; 95% confidence interval (CI) [1.5,2.4]) and older. After adjustment on age and gender, falls remained significantly associated with exposure to benzodiazepines (4.7,[3.7,5.9]), imipraminic antidepressants (3.6 [2.5,5.1]), serotonin reuptake inhibitor (SRI) antidepressants (2.2 [1.5,3.1]) or nitrates (1.9 [1.2,2.8]). Conclusion This study confirms that taking psychotropic drugs strongly increases the risk of falls. The role of cardiovascular drugs (except nitrates) remains not significant when confounding factors are taken into account. According to the very high prevalence of psychotropic drug use in the French elderly, further study are needed to investigate the relative effect of some drugs on falls, like for example SRIs or short acting benzodiazepines. Copyright © 2004 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||||||||