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SSRIs
Selected AbstractsDoes elimination of placebo responders in a placebo run-in increase the treatment effect in randomized clinical trials?DEPRESSION AND ANXIETY, Issue 1 2004A meta-analytic evaluation Abstract The use of a placebo run-in phase, in which placebo responders are withdrawn from a study before random assignment to treatment condition, has been criticized as favoring the active treatment in clinical trials. We compared the effect size of randomized, placebo-controlled clinical trials (in the treatment of depression with selective serotonin reuptake inhibitors [SSRIs]) that include a placebo run-in phase with those that do not, using a meta-analytic approach. This study differed from earlier meta-analytic studies in that it considered only SSRIs and included only studies using continuous measures of depression, allowing for a more refined assessment of effect size. An extensive literature search identified 43 datasets published between 1980 and 2000 comparing placebo with SSRI and using a continuous measure of depression (usually the Hamilton Depression Rating Scale). We included only studies of at least 6 weeks' duration focusing on treatment for primary acute major depression in adults 18,65 years of age. Studies focusing on depression in specific medical illnesses were not included. Analysis of efficacy was based on 3,047 subjects treated with an SSRI antidepressant and 3,740 subjects treated with a placebo. There was no statistically significant difference in effect size between the clinical trials that had a placebo run-in phase followed by withdrawal of placebo responders and those trials that did not. Despite the lack of a statistically significant difference between studies of withdrawing early placebo responders and those not using this procedure, this approach is likely to continue to be used widely because it produces large absolute effect sizes. It is recommended that future studies clearly describe these procedures and report the number of subjects dropped from the study for early placebo response and other reasons. Depression and Anxiety 19:10,19, 2004. 2004 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] Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceansENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2007Anne Munch Christensen Abstract Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications, primarily in the treatment of clinical depression. They are among the pharmaceuticals most often prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqueous as well as biological samples collected in the environment. In the present study, we tested the toxicities of five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) as single substances and of citalopram, fluoxetine, and sertraline in binary mixtures in two standardized bioassays. Test organisms were the freshwater algae Pseudokirchneriella subcapitata and the freshwater crustacean Daphnia magna. In algae, test median effect concentrations (EC50s) ranged from 0.027 to 1.6 mg/L, and in daphnids, test EC50s ranged from 0.92 to 20 mg/L, with sertraline being one of the most toxic compounds. The test design and statistical analysis of results from mixture tests were based on isobole analysis. It was demonstrated that the mixture toxicity of the SSRIs in the two bioassays is predictable by the model of concentration addition. Therefore, in risk assessment based on chemical analysis of environmental samples, it is important to include the effect of all SSRIs that are present at low concentrations, and the model of concentration addition may be used to predict the combined effect of the mixture of SSRIs. [source] Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubiaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2004Theodore B. Henry Abstract Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac®; fluvoxamine, Luvox®; paroxetine, Paxil®; citalopram, Celexa®; and sertraline, Zoloft®) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment. [source] The application of knowledge discovery in databases to post-marketing drug safety: example of the WHO databaseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2008A. Bate Abstract After market launch, new information on adverse effects of medicinal products is almost exclusively first highlighted by spontaneous reporting. As data sets of spontaneous reports have become larger, and computational capability has increased, quantitative methods have been increasingly applied to such data sets. The screening of such data sets is an application of knowledge discovery in databases (KDD). Effective KDD is an iterative and interactive process made up of the following steps: developing an understanding of an application domain, creating a target data set, data cleaning and pre-processing, data reduction and projection, choosing the data mining task, choosing the data mining algorithm, data mining, interpretation of results and consolidating and using acquired knowledge. The process of KDD as it applies to the analysis of spontaneous reports can be exemplified by its routine use on the 3.5 million suspected adverse drug reaction (ADR) reports in the WHO ADR database. Examples of new adverse effects first highlighted by the KDD process on WHO data include topiramate glaucoma, infliximab vasculitis and the association of selective serotonin reuptake inhibitors (SSRIs) and neonatal convulsions. The KDD process has already improved our ability to highlight previously unsuspected ADRs for clinical review in spontaneous reporting, and we anticipate that such techniques will be increasingly used in the successful screening of other healthcare data sets such as patient records in the future. [source] Agomelatine: a new treatment for depressionFUTURE PRESCRIBER, Issue 2 2009Professor Bill Deakin It is estimated that depression carries the greatest burden of disability in established economies. A range of treatments are available, and selective serotonin reuptake inhibitors (SSRIs) are currently the most commonly prescribed class of antidepressant. In this article, the author discusses agomelatine, a novel antidepressant recently licensed by the European Medicines Agency (EMEA), the evidence for its use, and its potential place in therapy. Copyright © 2009 John Wiley & Sons, Ltd. [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] Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: a comprehensive review of their clinical efficacyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2010Bernardo Dell'Osso Abstract Anxiety disorders are common psychiatric conditions that typically require long-term treatment. This review summarizes current knowledge of the pharmacological treatment of anxiety disorders with serotonin norepinephrine reuptake inhibitors (SNRIs) with specific emphasis on the findings of recent randomized clinical trials and relevant neurobiological investigations. It is now well established that gabaergic, noradrenergic and serotonergic systems play a critical role in the pathophysiology of anxiety disorders, abnormalities in these systems being related to structural and functional alterations in specific brain areas such as the amygdala, prefrontal cortex, locus coeruleus and hippocampus, as repeatedly shown by neuroimaging studies. SNRIs selectively inhibit norepinephrine and serotonin reuptake and have shown to be efficacious and generally well tolerated treatments in patients with anxiety disorders, with some potential clinical advantages over selective serotonin reuptake inhibitors (SSRIs), which are considered by many to represent first-line pharmacological treatments in patients with anxiety disorders. Anxiety disorders are characterized by a typically chronic course, high rates of comorbidity and frequent partial response to standard treatments, and the increasing use of SNRIs reflects currently unmet clinical need, in terms of overall response, remission rates and treatment tolerability. Copyright © 2009 John Wiley & Sons, Ltd. [source] Clonazepam as a therapeutic adjunct to improve the management of depression: a brief reviewHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2009*Article first published online: 27 MAR 200, Shigeru Morishita Abstract Clonazepam, first used for seizure disorders, is now increasingly used to treat affective disorders. We summarize the use of clonazepam to improve the management of depression. Clonazepam is useful for treatment-resistant and/or protracted depression, as well as for acceleration of response to conventional antidepressants. Clonazepam is at this time recommended for use in combination with SSRIs (fluoxetine, fluvoxamine, sertraline) as an antidepressant, and should be used at a dosage of 2.5,6.0,mg/day. If clonazepam is effective, a response should be observed within 2,4 weeks. It is significantly more effective for unipolar than for bipolar depression. Low-dose, long-term treatment with clonazepam exhibits a prophylactic effect against recurrence of depression. Although the mechanism of action of clonazepam has not yet been established, some investigators have been suggested that it involves enhancement of anti-anxiety effects, anticonvulsant effects on subclinical epilepsy, increase in 5-HT/monoamine synthesis or decrease in 5-HT receptor sensitivity mediated through the GABA system, and regulate in GABA activity. 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] SSRIs and cognitive performance in a working sampleHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2005Emma J. K. Wadsworth Abstract Background Studies of the impact of antidepressant use on cognitive performance have frequently been carried out among the elderly or on healthy volunteers. Comparatively little research has considered their impact on a relatively young, working population, particularly within the context of everyday life. Aims To examine any association between SSRI use and cognitive performance, mood and human error at work. Methods SSRI users and controls completed a battery of laboratory based computer tasks measuring mood and cognitive function pre- and post-work at the start and end of a working week. They also completed daily diaries reporting their work performance. Results SSRI use was associated with memory impairment: specifically poorer episodic, though not working or semantic memory. Effects of SSRI use on recognition memory seemed to vary according to the underlying psychopathology, while effects on delayed recall were most pronounced among those whose symptoms had not (yet) resolved. There were no detrimental effects on psychomotor speed, attention, mood or perceived human error at work. Conclusions The findings lend support to the SSRIs comparative safety, even among workers, particularly as the symptoms of the underlying psychopathology are successfully addressed. Possible memory impairments may, however, be found in those taking SSRIs. Copyright © 2005 John Wiley & Sons, Ltd. [source] IL-6 levels decrease with SSRI treatment in patients with major depressionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2005Ayse Devrim Basterzi Abstract Objective Some evidence indicates that an immune response with an increased production of proinflammatory cytokines often accompanies major depression. The objective of this study was to examine the serum levels of IL-6 in patients with major depression and the changes occurring in IL-6 levels during treatment with selective serotonin reuptake inhibitors (SSRI). Method Twenty-three patients with a DSM-IV diagnosis of major depressive disorder and 23 healthy matched controls were included in the study. The severity of depression was measured with the Hamilton rating scale for depression. Blood samples for IL-6 levels were obtained at baseline and at week 6 of treatment and IL-6 concentrations were evaluated using a solid phase sandwich enzyme immunoassay. All patients were treated with an SSRI. Results The IL-6 levels showed no statistically significant difference between the patients and the controls at baseline. However, IL-6 levels after treatment with SSRIs were significantly lower compared with the baseline IL-6 levels of both the patients and the controls. Conclusion The results of this study suggest that proinflammatory cytokines show some changes during the course of treatment of major depression. These findings might also be considered as supporting the hypothesis of a modulatory role of antidepressants on the immune system. Copyright © 2005 John Wiley & Sons, Ltd. [source] Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findingsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2002Murad Atmaca Abstract The efficacy of irreversible and reversible monoamine oxidase inhibitors (MAOIs) in the treatment of social phobia (SP) is well established. Recently, selective serotonin reuptake inhibitors (SSRIs) have been used more frequently. In the present study, the efficacy and side-effect profile of citalopram, an SSRI, and moclobemide, the only MAOI used in Turkey, were compared. The 71 patients diagnosed with SP according to DSM-III-R were randomly assigned to two subgroups; citalopram (n,=,36) or moclobemide (n,=,35). The study was an 8-week, randomized, open-label, rater-blinded, parallel-group trial. All patients were assessed by Hamilton anxiety rating (HAM-A), Liebowitz social anxiety (LSAS), clinical global impression-severity of illness (CGI-SI) and clinical global impression-improvement (CGI-I) scales. There was a similar percentage of responders (citalopram 75%, n,=,27 and moclobemide 74.3%, n,=,26), with a >50% or greater reduction in LSAS total score and ratings of ,very much' or ,much improved' on the CGI-I. None of the patients withdrew from the study. The results of the present study suggest that citalopram has shown promising results in patients with SP. 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] Pharmacological principles of antidepressant efficacyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2002Alan F. Schatzberg Abstract Both noradrenaline (NA) and serotonin (5-HT) appear to be involved in depression. Evidence suggests that dual-acting antidepressants, i.e. those that affect both monoamine systems, such as tricyclic antidepressants and the noradrenergic and specific serotonergic antidepressant mirtazapine, may have greater efficacy and a faster onset of action than drugs that act on a single monoamine system only, such as the selective serotonin reuptake inhibitors (SSRIs). Cell firing is reduced by SSRIs in the short-term, but is increased by mirtazapine, probably due to its actions on both NA (via ,2 antagonism) and 5-HT (via ,1 -stimulation by NA). This may help to explain clinical evidence suggesting that mirtazapine has a faster onset of action than the more selective antidepressants. Copyright © 2002 John Wiley & Sons, Ltd. [source] An overview of the clinical efficacy of mirtazapineHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2002O. Benkert Abstract Mirtazapine is at least as effective as the tricyclic antidepressants and trazodone in a wide range of patient subgroups including in- and out-patients with moderate to severe depression. It also appears to be at least as effective as the serotonin and noradrenaline reuptake inhibitor venlafaxine in the treatment of severely depressed melancholic patients. When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine shows a significantly earlier onset of action. Further analysis of a study comparing mirtazapine with the SSRI paroxetine indicated that early improvement was a highly sensitive predictor of later stable response for both drugs. The positive predictive value of an early improvement was significantly higher during mirtazapine treatment compared with paroxetine. The negative predictive value approached maximum values as early as week 2 with mirtazapine and week 3 with paroxetine. This suggests that the predictability of the response to treatment is better with mirtazapine than with paroxetine. Copyright © 2002 John Wiley & Sons, Ltd. [source] Onset of action of antidepressants: results of different analysesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2002Chris Thompson Abstract Because the value of antidepressants is hampered by their delay in onset of action, considerable attention has been focused on developing a drug that acts more rapidly. However, although specific studies are now ongoing, there have been no peer-reviewed prospective onset of action trials published in the literature to date. Some data are currently available from post-hoc pooled analyses and numerous methods have been developed for evaluating the onset of action; these include the time to response, the time to onset of therapeutic effect, pattern analysis and survival analyses. Such an analysis of four large-scale, double-blind studies has provided evidence for an earlier onset of action with mirtazapine than with the SSRIs (fluoxetine, paroxetine and citalopram). Significant differences were seen between mirtazapine and the SSRIs after 1 week of treatment. This effect was consistent across the four different methodologies and appears to be due to a specific antidepressant effect rather than an early effect on, for example, sleep. These findings await confirmation from specifically designed prospective onset of action studies. Copyright © 2002 John Wiley & Sons, Ltd. [source] Fluvoxamine in obsessive-compulsive disorder: similar efficacy but superior tolerability in comparison with clomipramineHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2001Emanuela Mundo Abstract Some meta-analyses have suggested that the selective serotonin reuptake inhibitors (SSRIs) are less effective than clomipramine in the treatment of obsessive-compulsive disorder (OCD). The aim of this double-blind, randomised, multicentre study was to directly compare the efficacy and safety of fluvoxamine and clomipramine in patients with OCD. A total of 227 patients were randomised to flexible doses of fluvoxamine or clomipramine (both 150,300,mg/day) for 10 weeks. Fluvoxamine and clomipramine were both clinically effective and there were no statistically significant differences between the two treatment groups, at any visit, on the National Institute of Mental Health Obsessive-Compulsive global rating scale, the Yale-Brown Obsessive-Compulsive scale (total score and obsession and compulsion subscores), the Clinical Global Impression severity of illness and global improvement subscales, the Clinical Anxiety Scale and the 17-item Hamilton Depression Rating Scale. However, there were differences in safety between the two treatments. Compared with fluvoxamine-treated patients, those treated with clomipramine had more anticholinergic side effects (dry mouth, constipation and tremor) and premature withdrawals due to adverse events (18 versus 9). The results from this controlled study indicate that fluvoxamine is as effective as clomipramine in the treatment of OCD but has a better tolerability profile. Copyright © 2001 John Wiley & Sons, Ltd. [source] Affect expression in prenatally psychotropic exposed and nonexposed mother,infant dyadsINFANT MENTAL HEALTH JOURNAL, Issue 4 2002Pratibha N. Reebye This prospective study examined infant, maternal, and dyadic affective profiles at three months postpartum in infant,mother dyads that were exposed to psychotropic medications in utero compared with nonexposed control dyads. Control dyads of nondepressed mothers and their infants showed many similarities in affect expression with mother,infant dyads who were exposed to selective serotonin reuptake inhibitors (SSRIs) alone for treatment of maternal depression. In contrast, mothers who received SSRIs and Rivotril (Benzodiazepine derivative) for treatment of depression and anxiety expressed both positive and negative affect towards their infants. Clinical implications regarding use of psychotropic medications such as SSRIs alone or in combination with other drugs for treatment of maternal anxiety and depression during pregnancy are discussed. Clinicians should be aware of the possible differential response in maternal,infant interaction in a mixed diagnosis group (i.e., depression and anxiety) regarding infant temperament, possibly suggesting latent behavioral teratogenicity with psychotropics. ©2002 Michigan Association for Infant Mental Health. [source] Phosphodiesterase 5 inhibitors in the treatment of premature ejaculationINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2006W. F. Wang Summary To date, there is no FDA-approved therapy for premature ejaculation (PE). Recently, phosphodiesterase 5 inhibitors (PDE5 -Is) have been demonstrated to have encouraging results in the treatment of PE by a few studies. The aim of this review was to assess the updated manuscripts and thereafter present the practical recommendations and possible mechanisms concerning PDE5 -Is for treating PE. Using MEDLINE, we searched and assessed the peer manuscripts published from 1 January 1996 to 1 September 2005 about PDE5 -Is for treating PE. The results show that the number of patients in all the reports is very few and most of the studies do not employ double-blinded and placebo-controlled tests, though they are prospective and randomized. Therefore, the results and conclusions might be biased. PDE5 -Is are suggested to be used in PE with old age or associated with erectile dysfunction (ED), or to be employed alone or in combination with selective-serotonin reuptake inhibitors (SSRIs) when SSRIs fail to treat PE; behavioural therapy is proposed to be used for preventing the recurrence of PE following withdrawal of PDE5 -Is. In addition, for the PE patient with a definite aetiological cause, the aetiology should be cured first, if PE still exists, followed by PDE-Is prescription. Possible mechanisms that are involved include relaxing the smooth muscles of vas deferens, seminal vesicle, prostate and urethra; decreasing the central sympathetic output; inducing peripheral analgesia; prolonging the duration of erection; and increasing confidence, the perception of ejaculatory control, overall sexual satisfaction, and decreasing the post-orgasmic refractory time to achieve a second erection after ejaculation. Well-designed multicentre studies are urgently warranted to further elucidate the efficacies and safety as well as mechanisms of PDE5 -Is in the treatment of PE. [source] Cognitive toxicity of pharmacotherapeutic agents used in social anxiety disorderINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2009I. Hindmarch Summary Objective:, To compare cognitive impairment of medications used in social anxiety disorder (SAD). Methods:, Data from peer-reviewed publications (1975,2007) of controlled, crossover design, pharmacodynamic studies on SAD medications in healthy volunteers were analysed. The number of objective psychometrics for each drug/dose level at all time points after dosing, and of instances of statistically significant impairment of cognitive function, enabled calculation of drug-induced cognitive impairment. The magnitude of impairment between drugs was compared using proportional impairment ratios (PIRs). Results:, Olanzapine, oxazepam, lorazepam and mianserin had twice the average cognitive toxicity of other treatments. Selective serotonin reuptake inhibitors (SSRIs) impaired cognition to a lesser extent than other pharmacological groupings. There was extensive intra-class variation: fluvoxamine (PIR = 0.08) possessed little detrimental cognitive activity, whereas sertraline (PIR = 5.33) caused impairment over five times the SSRI group average. Benzodiazepines caused noticeable cognitive impairment. Conclusions:, Substantial differences exist, both between and within therapeutic classes, in the behavioural toxicity of medications used for SAD. [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] Response to ,Selective serotonin reuptake inhibitors (SSRIs) and hyponatraemia in the elderly' by Wee and Lim (2004)INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2005Associate Professor David Ames No abstract is available for this article. [source] Selective serotonin re-uptake inhibitors (SSRIs) and hyponatraemia in the elderlyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 6 2004Rohan Wee No abstract is available for this article. [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] The effectiveness of antidepressant medication in the management of behaviour problems in adults with intellectual disabilities: a systematic reviewJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 10 2007S. K. Sohanpal Abstract Background A comprehensive systematic review was performed to establish the current evidence base regarding the effectiveness of antidepressant medication for the management of behaviour problems in adults with intellectual disabilities. Method An electronic search of PsycInfo, Embase, Medline and Cinahl databases was conducted spanning the time period 1990 to October 2005 for primary trials. This was supplemented by hand searching and cross-referencing of relevant reviews. Strict scientific methodology requirements were formulated that the studies had to meet in order to merit inclusion in this review. Results One crossover randomized controlled trial in a small cohort, seven prospective uncontrolled trials and two retrospective studies were yielded in the search. Of these, one explored the effectiveness of the tricyclic antidepressant , clomipramine, and nine considered various selective serotonin reuptake inhibitors (SSRIs). Conclusion Evidence based primarily on a small number of either prospective or retrospective case studies that included a small number of participants and often used non-validated outcome measures for a short period of follow-up, suggests that antidepressants, particularly SSRIs, show improvement of aggression and self-injurious behaviour on average in less than 50% of cases and the rest show either no improvement or deterioration. The effect is most pronounced in the presence of an underlying anxiety or an associated diagnosis of obsessive-compulsive disorder. Most studies have highlighted the concern regarding adverse effects. [source] Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2004Kazufumi Hirano The pharmacological effects of extracts of Hypericum perforatum (St John's wort) were characterized in-vitro and ex-vivo, in relation to its behavioural effects. In in-vitro experiments, St John's wort inhibited brain synaptosomal [3H]serotonin uptake in mice with little effect on specific [3H]paroxetine binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for [3H]serotonin uptake (molar concentration of unlabelled drug necessary to displace 50% of specific uptake) correlated well with the inhibition constant Ki value for [3H]paroxetine binding in mouse brain. Oral administration of St John's wort (900 mg kg,1), paroxetine (1 mg kg,1) and sertraline (10 mg kg,1) brought about significant increases in the Km value for [3H]serotonin uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific [3H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly inhibited marble-burying behaviour in mice and the time-course of attenuation of this behaviour by St John's wort was similar to that of [3H]serotonin uptake inhibition. In the forced swimming test, St John's wort, but not SSRIs, suppressed the immobility time of mice after oral administration. These results provide the first in-vivo evidence to suggest that the mode of antidepressant action of St John's wort differs from that of SSRIs. Thus, this study may have a significant impact on phytotherapy with St John's wort. [source] Inhibition and possible induction of rat CYP2D after short- and long-term treatment with antidepressantsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2002Wladys, awa A. Daniel The aim of this study was to investigate the influence of tricyclic antidepressants (imipramine, amitriptyline, clomipramine, desipramine), selective serotonin reuptake inhibitors (SSRIs: fluoxetine, sertraline) and novel antidepressant drugs (mirtazapine, nefazodone) on the activity of CYP2D, measured as a rate of ethylmorphine O -deethylation. The reaction was studied in control liver microsomes in the presence of the antidepressants, as well as in microsomes of rats treated intraperitoneally for one day or two weeks (twice a day) with pharmacological doses of the drugs (imipramine, amitriptyline, clomipramine, nefazodone 10 mg kg,1 i.p.; desipramine, fluoxetine, sertraline 5 mg kg,1 i.p.; mirtazapine 3 mg kg,1 i.p.), in the absence of the antidepressants in-vitro. Antidepressants decreased the activity of the rat CYP2D by competitive inhibition of the enzyme, the potency of their inhibitory effect being as follows: clomipramine (Ki = 14 ,M) > sertraline , fluoxetine (Ki = 17 and 16 ,M, respectively) > imipramine , amitriptyline (Ki = 26 and 25 ,M, respectively) > desipramine (Ki = 44 ,M) > nefazodone (Ki = 55 ,M) > mirtazapine (Ki = 107 ,M). A one-day treatment with antidepressants caused a significant decrease in the CYP2D activity after imipramine, fluoxetine and sertraline. After prolonged administration of antidepressants, the decreased CYP2D activity produced by imipramine, fluoxetine and sertraline was still maintained. Moreover, amitriptyline and nefazodone significantly decreased, while mirtazapine increased the activity of the enzyme. Desipramine and clomipramine did not produce any effect when administered in-vivo. The obtained results indicate three different mechanisms of the antidepressants-CYP2D interaction: firstly, competitive inhibition of CYP2D shown in-vitro, the inhibitory effects of tricyclic antidepressants and SSRIs being stronger than those of novel drugs; secondly, in-vivo inhibition of CYP2D produced by both one-day and chronic treatment with tricyclic antidepressants (except for desipramine and clomipramine) and SSRIs, which suggests inactivation of the enzyme apoprotein by reactive metabolites; and thirdly, in-vivo inhibition by nefazodone and induction by mirtazapine of CYP2D produced only by chronic treatment with the drugs, which suggests their influence on the enzyme regulation. [source] Efficacy of treatments for patients with obsessive-compulsive disorder: A systematic reviewJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 4 2009PMHNP (Lecturer)Article first published online: 2 APR 200, Yun-Jung Choi PhD Abstract Purpose: This systematic review examines the efficacy of pharmacological therapy for obsessive-compulsive disorder (OCD), addressing two major issues: which treatment is most effective in treating the patient's symptoms and which is beneficial for maintaining remission. Data sources: Seven databases were used to acquire articles. The key words used to search for the relative topics published from 1996 to 2007 were "obsessive-compulsive disorder" and "Yale-Brown obsession-compulsion scale." Based on the inclusion and exclusion criteria, 25 studies were selected from 57 potentially relevant studies. Conclusions: The effects of treatment with clomipramine and selective serotonin reuptake inhibitors (SSRIs: fluvoxamine, sertraline, fluoxetine, citalopram, and escitalopram) proved to be similar, except for the lower adherence rate in case of clomipramine because of its side effects. An adequate drug trial involves administering an effective daily dose for a minimum of 8 weeks. An augmentation strategy proven effective for individuals refractory to monotherapy with SSRI treatment alone is the use of atypical antipsychotics (risperidone, olanzapine, and quetiapine). Implications for practice: Administration of fluvoxamine or sertraline to patients for an adequate duration is recommended as the first-line prescription for OCD, and augmentation therapy with risperidone, olanzapine, or quetiapine is recommended for refractory OCD. [source] Trichotillomania ± trichobezoar: revisitedJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2006VN Sehgal Abstract Trichotillomania is an intriguing psychosomatic entity in which there is an irresistible desire to pull out the hair from the scalp, eyelashes, eyebrows and other parts of the body. The process results in an instant release of tension, a sense of relief and security. However, non-scaring alopecia is its clinical presentation. The development of trichobezoar following ingestion of the pulled hair is its salient complication in a few cases. Subsequently, it may cause symptoms pertaining to the gastrointestinal tract culminating in intestinal obstruction, perforation, pancreatitis and obstructive jaundice. The Rapunzel syndrome (trichobezoar) may occur when gastrointestinal obstruction is produced by a rare manifestation of a trichobezoar with a long tail that extends to or beyond the ileocecal valve. In most cases in children, trichotillomania ± trichobezoar is a habit disorder and thus has a better prognosis. However, in adults the psychopathology is usually deeper and thus entails a poor prognosis. The diagnosis is made after taking a thorough history, noting the clinical features and evaluating a hair-root examination, where telogen hair is (almost) completely lacking, which distinguish trichotillomania from other hair disorders. Treatment modalities vary in childhood and adult varieties. Apart from psychotherapy, the drug treatment involves several agents including selective serotonin reuptake inhibitors (SSRIs) and domipramine. Trichobezoar/Rapunzel syndrome requires surgical intervention. [source] | ||||||||||||||||||||||||||||||||||