A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: Outcome after long-term follow-up Clinical and Neurobiological Effects of Tianeptine and Paroxetine in Major Depression Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine Selective serotonin reuptake inhibitor treatment for generalized anxiety disorder: a double-blind, prospective comparison between paroxetine and sertraline. A randomized, double‐blind, 24‐week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care A Naturalistic Long-Term Comparison Study of Selective Serotonin Reuptake Inhibitors in the Treatment of Panic Disorder A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin transporter promoter polymorphism A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin–noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine† Reboxetine, the first selective noradrenaline reuptake inhibitor antidepressant: Efficacy and tolerability in 2613 patients A Double‐Blind, Randomized, Fluoxetine‐Controlled, Multicenter Study of Paroxetine in the Treatment of Depression A double‐blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients [Comparative study of paroxetine and mianserin in depression in elderly patients: efficacy, tolerance, serotonin dependence]. Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients.
BACKGROUND Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors . In a 12-week r and omized , multicenter , double-blind trial , the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression . METHODS A total of 203 patients were r and omized to fixed doses ( 20 mg/day ) of paroxetine or fluoxetine for the first six weeks of therapy . From week 7 - 12 , dosing could be adjusted biweekly , as required ( paroxetine 20 - 50 mg/day , and fluoxetine 20 - 80 mg/day ) . The mean prescribed doses were paroxetine 25.5 mg/day ( range 20.0 - 40.2 mg/day ) , and fluoxetine 27.5 mg/day ( range 20.0 - 59.5 mg/day ) . Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia . RESULTS Both active treatments demonstrated comparable antidepressant efficacy ( HAM-D , CGI ) . Anxiolytic activity of the two drugs ( COVI , STAI , HAM-D ) was also comparable . However , paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy ( HAM-D Agitation item , p < 0.05 ; Psychic Anxiety item , p < 0.05 ) , with no differences detected after week 2 . The overall incidence of adverse effects was comparable in the two treatment groups . Constipation , dyspepsia , tremor , sweating and abnormal ejaculation were more common in paroxetine-treated subjects , whereas nausea and nervousness were more frequent in fluoxetine-treated patients . Weight loss was more common in the fluoxetine versus paroxetine group ( 11.88 % versus 2.94 % , respectively ) . ESRS scores for akathisia were low throughout the study and showed little change . LIMITATIONS Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others . DISCUSSION The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy .  Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine CONTEXT Selective serotonin reuptake inhibitors ( SSRIs ) are the most commonly prescribed class of antidepressant , yet it is not known whether one SSRI is more effective than another . OBJECTIVE To compare the effectiveness of 3 SSRIs ( paroxetine , fluoxetine , and sertraline ) in depressed primary care patients . DESIGN Open-label , r and omized , intention-to-treat trial , with patient enrollment occurring in April-November 1999 . SETTING Thirty-seven clinics in 2 US primary care research networks . PATIENTS A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 189 ) , fluoxetine ( n = 193 ) , or sertraline ( n = 191 ) for 9 months . Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI . MAIN OUTCOME MEASURES The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) Mental Component Summary score ( range , 0 - 100 ) , compared across treatment groups at 1 , 3 , 6 , and 9 months . Secondary outcomes included other depression and psychological measures , multiple measures of social and work functioning , and other domains of health-related quality of life , such as physical functioning , concentration and memory , vitality , bodily pain , sleep , and sexual functioning . RESULTS Follow-up interviews were successfully completed in 94 % of patients at 1 month , 87 % at 3 months , 84 % at 6 months , and 79 % at 9 months . Responses to the 3 SSRIs were comparable on all measures and at all time points . The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group , + 15.1 in the fluoxetine group , and + 17.4 in the sertraline group . The drugs were also associated with similar incidences of adverse effects and discontinuation rates . CONCLUSIONS The SSRI antidepressants paroxetine , fluoxetine , and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial OBJECTIVE To determine the relative cost-effectiveness of three classes of antidepressants : tricyclic antidepressants ( TCAs ) , selective serotonin reuptake inhibitors ( SSRIs ) , and the modified TCA lofepramine , as first choice treatments for depression in primary care . DESIGN Open , pragmatic , controlled trial with three r and omised arms and one preference arm . Patients were followed up for 12 months . SETTING UK primary care : 73 practice s in urban and rural areas in Engl and . PARTICIPANTS Patients with a new episode of depressive illness according to GP diagnosis . INTERVENTIONS Patients were r and omised to receive a TCA ( amitriptyline , dothiepin or imipramine ) , an SSRI ( fluoxetine , sertraline or paroxetine ) or lofepramine . Patients or GPs were able to choose an alternative treatment if preferred . MAIN OUTCOME MEASURES At baseline the Clinical Interview Schedule , Revised ( CIS-R PROQSY computerised version ) was administered to establish symptom profiles . Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression ( HAD-D ) , CIS-R , EuroQol ( EQ-5D ) for quality of life , Short Form ( SF-36 ) for generic health status , and patient and practice records of use of health and social services . The primary effectiveness outcome was the number of depression-free weeks ( HAD-D less than 8 , with interpolation of intervening values ) and the primary cost outcome total direct NHS costs . Quality -adjusted life-years ( QALYs ) were used as the outcome measure in a secondary analysis . Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed . Estimates were bootstrapped with 5000 replications . RESULTS In total , 327 patients were r and omised . Follow-up rates were 68 % at 3 months and 52 % at 1 year . Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients r and omised to TCAs entered the preference arm than those allocated to the other choices . Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm . There were no significant differences between arms in mean cost per depression-free week . For values placed on an additional QALY of over 5000 pounds , treatment with SSRIs was likely to be the most cost-effective strategy .  TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively , but these differences were relatively modest . CONCLUSIONS When comparing the different treatment options , no significant differences were found in outcomes or costs within the sample , but when outcomes and costs were analysed together , the result ing cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option , although the probability of this did not rise above 0.6 . Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks . Further research is still needed on the management of depressive illness in primary care . This should address areas such as the optimum severity threshold at which medication should be used ; the feasibility and effectiveness of adopting structured depression management programmes in the UK context ; the importance of factors such as physical co-morbidity and recent life events in GPs ' prescribing decisions ; alternative ways of collecting data ; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early The acute efficacy of selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of major depressive disorder ( MDD ) is well established ; however their role in longer-term prevention of recurrence remains unconfirmed . This study aims at examining : the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up , the effect of concomitant cognitive behavioral therapy ( CBT ) , and the predictors of outcome . In a prospect i ve cohort study , 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine , escitalopram , sertraline and paroxetine-were  followed up over several years . During an average follow-up period of 34.5 months , 76.5 % of patients experienced MDD recurrence . Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant . The prophylactic efficacy for SSRI-only treatment was limited , with a recurrence rate of 82.0 % , compared to 59.0 % of patient recurrence rate in concomitant Cognitive Behavioral Therapy ( CBT ) . The relatively small size of the CBT group and the lack of r and omization may undermine the extrapolation of its findings to clinical practice . Nevertheless , the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence Selective serotonin reuptake inhibitors ( SSRIs ) are widely used as effective pharmacological agents to treat depressive disorders . In contrast to the SSRIs , which block the presynaptic serotonin ( 5-HT ) transporter and by this route increase the concentration of serotonin in the synaptic cleft , the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission . Both SSRIs and tianeptine are clinical ly effective ; however , their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission . To better underst and the differences between these two opposite pharmacological modes of action , we compared the changes induced by tianeptine and paroxetine on psychopathology , the hypothalamic-pituitary-adrenocortical ( HPA ) system , and cognitive functions in a double-blind , r and omized , controlled trial including 44 depressed in patients over a period of 42 days .  Depressive symptomatology significantly improved in all efficacy measures , with no significant differences between tianeptine and paroxetine . There was a trend toward better response to the SSRI among women . Assessment of the HPA system showed marked hyperactivity before the beginning of treatment , which then normalized in most of the patients , without significant differences between the two antidepressants . Cognitive assessment s showed no significant differences between the two drugs investigated . The results of the current study suggest that the initial effect , i.e. , enhancement or decrease of 5-HT release , is only indirectly responsible for antidepressant efficacy , and they support the notion that downstream adaptations within and between nerve cells are crucial . The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest Paroxetine and venlafaxine are potent serotonin transporter ( SERT ) antagonists and weaker norepinephrine transporter ( NET ) antagonists . However , the relative magnitude of effect at each of these sites during treatment is unknown . Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition . Outpatient subjects ( N=86 ) meeting criteria for major depression were enrolled in a multicenter , 8 week , r and omized , double-blind , parallel group , antidepressant treatment study . Subjects were treated by forced-titration of paroxetine CR ( 12.5–75 mg/day ) or venlafaxine XR ( 75–375 mg/day ) over 8 weeks . Blood sample s were collected weekly to estimate transporter inhibition . Both medications produced dose-dependent inhibition of the SERT and NET . Maximal SERT inhibition at week 8 for paroxetine and venlafaxine was 90 % ( SD 7 ) and 85 % ( SD 10 ) , respectively . Maximal NET inhibition for paroxetine and venlafaxine at week 8 was 36 % ( SD 19 ) and 60 % ( SD 13 ) , respectively . The adjusted mean change from baseline ( mean 28.6 ) at week 8 LOCF in MADRS total score was −16.7 ( SE 8.59 ) and −17.3 ( SE 8.99 ) for the paroxetine and venlafaxine-treated patients , respectively . The magnitudes of the antidepressant effects were not significantly different from each other ( 95%CI −3.42 , 4.54 , p=0.784 ) . The results clearly demonstrate that paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo . NET antagonism has been posited to contribute to the antidepressant effects of these compounds . The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) appear to be an effective class of medications for the treatment of  generalized anxiety disorder .  Within the SSRI class , however , there have been no comparative treatment studies for this disorder . Therefore , in the present study , we compared the efficacy and tolerability of 2 SSRIs , paroxetine and sertraline , in the treatment of generalized anxiety disorder . METHOD In this parallel-group , double-blind , flexible-dose study , 55 patients with primary generalized anxiety disorder ( DSM-IV criteria ) were r and omly assigned to receive either paroxetine or sertraline treatment for 8 weeks . Primary efficacy measures were the mean changes in Hamilton Rating Scale for Anxiety ( HAM-A ) scores as well as responder and remission rates based on the Clinical Global Impressions scale . Secondary efficacy measures consisted of the Indiana University Generalized Anxiety Measurement Scale and self-report ratings of anxiety , and quality -of-life outcome . Tolerability was assessed using the Systematic Assessment for Treatment Emergent Events question naire for treatment-emergent symptoms . RESULTS The intent-to-treat sample consisted of 53 patients who received medication for at least 1 week . Of the 53 patients , 43 completed the entire 8 weeks of treatment . Both paroxetine and sertraline result ed in significant decreases in mean HAM-A scores ( paroxetine = 57 % + /- 28 % ; sertraline = 56 % + /- 28 % ) . There were no differences between medication groups on response or remission rates , and tolerability was comparable . CONCLUSIONS Both paroxetine and sertraline appear similarly effective and well tolerated for the treatment of generalized anxiety disorder & NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine  30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors Objectives : Selective serotonin reuptake inhibitors ( SSRIs ) are currently considered as the first drug of choice in the treatment of panic disorder ( PD ) . The aim of this long-term , naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD . Outcome measures included relapse rates and adverse effects . Methods : Two hundred patients with PD were enrolled in our study . All subjects met DSM-IV criteria for PD or PD with agoraphobia ( PDA ) . All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram ( n = 50 ) , fluoxetine ( n = 50 ) , fluvoxamine ( n = 50 ) , or paroxetine ( n = 50 ) in a r and omized , nonblinded fashion . Both the treating psychiatrist and the patients were not blind to the assigned treatment , but the clinician raters were blind to the study medication . The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists . The Panic Self- Question naire , which is a self-report scale , was administered at baseline and then once per month during the duration of the 12-month study . The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study . Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits . The body weight of study subjects was measured at baseline , and then at the 12th month visit end point . Results : Of 200 patients who entered the study , 127 patients ( 63.5 % ) completed the full 12-month protocol . Retention rates were highest for paroxetine ( 76 % [ 38/50 ] ) , intermediate for citalopram ( 68 % [ 34/50 ] ) and fluvoxamine ( 60 % [ 30/50 ] ) , and lowest for fluoxetine ( 50 % [ 25/50 ] ) . Patients who completed the 12-month protocol responded favorably to the study treatment . The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8 . At visits on months 3 , 6 , 9 , and 12 , however , there were no statistically significant differences between the 4 groups in relapse rates ( defined as the occurrence of 1 or more panic attacks during the previous week of treatment ) ( F1,127 = 0.17 ; P = 0.13 [ not statistically significant ] ) . At the 12th month end point , patients in all 4 treatment groups had a statistically significant increase in body weight . Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment . Reports of sexual adverse effects at the 12th month visit were similar in the citalopram , fluoxetine , and paroxetine groups , but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit . Conclusions : Most of our PD patients responded well to 12-month treatment with either citalopram , fluoxetine , fluvoxamine , or paroxetine , and the overall response rate was equal after the first 4 weeks of treatment . Although patients treated with paroxetine had the lowest dropout rates during the initiation phase , they had the highest rate of adverse effects as measured at the 12th month visit . Conversely , patients in the fluvoxamine group had the highest dropout rate ( which was primarily caused by adverse effects in the initiation phase of treatment . ) ; however , patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents . Overall , when measured at the 12th month visit , monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine . In addition , monotherapy with paroxetine , citalopram , and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine Depression is associated with considerable morbidity and mortality . As depressive disorders carry a high risk of relapse , treatment strategies include the use of a 6-month continuation period after resolution of the acute episode . Tolerability is of major importance when determining compliance and outcome during long-term therapy . Due to the superior tolerability profile of the selective serotonin reuptake inhibitors ( SSRIs ) over the older tricyclic antidepressants ( TCAs ) , the former may be more suitable for extended therapy . Comparative studies have not shown differences between the SSRIs in terms of efficacy , but side-effect profiles may vary . A multicenter , double-blind , comparative study of sertraline and fluoxetine was carried out in out patients fulfilling DSM-III-R criteria for major depressive disorder . Patients were r and omised to receive sertraline ( 50 - 150 mg , n = 118 ) or fluoxetine ( 20 - 60 mg , n = 120 ) for 24 weeks . Assessment s for depression ( HAM-D , HAD , CGI-I , CGI-S ) , anxiety ( Covi ) , sleep ( Leeds Sleep Evaluation scale ) and quality of life ( SIP ) were made at study entry and at weeks 2 , 4 , 8 , 12 , 18 and 24 . All adverse events were recorded to allow evaluation of tolerability . In total , 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group .  Side effects were responsible for the premature treatment withdrawal of seven ( 6 % ) sertraline patients and 12 ( 10 % ) fluoxetine patients . Two-hundred and thirty-four patients were included in an ITT analysis up to last visit ( 116 sertraline , 118 fluoxetine ) . At study endpoint , both treatments produced a significant improvement over baseline on all efficacy variables ( P < 0.001 ) . Although the magnitude of global changes in depression , anxiety , and quality of life was larger with sertraline than fluoxetine , none of the between-group differences reached statistical significance . However , significant differences in favour of sertraline were observed for individual HAM-D items including item 4 ( insomnia onset ) ( P = 0.04 ) , item 9 ( agitation ) ( P = 0.02 ) , and item 13 ( general somatic symptoms ) ( P = 0.008 ) . In addition , sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest , emotional behaviour and ambulation . Both sertraline and fluoxetine were well tolerated with no significant differences between treatments The present study aim ed to compare the effects of two currently used selective serotonin reuptake inhibitors ( SSRIs ) in Japan taking the individual background in 5-HTT gene-linked polymorphic region ( 5HTTLPR ) genotype into account . Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression . Patients with the l allele had a greater percentage reduction on the total score ( P=0.059 ) and somatic anxiety items ( P=0.026 ) of the 21-item Hamilton Depression Rating Scale ( HAM-D ) score compared to s/s genotype carriers . Paroxetine was significantly more effective than fluvoxamine in the s/s carriers , as evaluated on the percentage reduction in total score ( P=0.012 ) and core ( P=0.049 ) HAM-D after 4 weeks of medication , but not in the l/s carriers . These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs , and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis Objective This r and omised , double-blind , 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine ( 10–20 mg/day ) versus agomelatine ( 25–50 mg/day ) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin – noradrenaline reuptake inhibitor ( SNRI ) monotherapy . Methods Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine . Primary endpoint was change from baseline to week 8 in the Montgomery – Åsberg Depression Rating Scale ( MADRS ) total score analysed by mixed model for repeated measurements , using a noninferiority test followed by a superiority test . Secondary endpoints included response and remission rates , anxiety symptoms ( Hamilton Anxiety Rating Scale ) , Clinical Global Impression , overall functioning ( Sheehan Disability Scale ) , health-related quality of life ( EuroQol 5 Dimensions ) , productivity ( work limitation question naire ) and family functioning ( Depression and Family Functioning Scale ) . Results Primary endpoint noninferiority was established and vortioxetine ( n = 252 ) was superior to agomelatine ( n = 241 ) by 2.2 MADRS points ( p < 0.01 ) . Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12 ; MADRS , Hamilton Anxiety Rating Scale , Clinical Global Impression , Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards ; work limitation question naire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12 . Fewer patients withdrew because of adverse events with vortioxetine ( 5.9 % vs 9.5 % ) . Adverse events ( incidence ≥5 % ) were nausea , headache , dizziness and somnolence . Conclusions Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy . Vortioxetine was safe and well tolerated INTRODUCTION : Reboxetine is the first available selective noradrenaline re-uptake inhibitor ( selective NRI ) . This paper gives an overview of its antidepressant efficacy and tolerability in eight r and omized double-blind , multicentre clinical trials . The clinical profile of reboxetine is also compared with that of the tricyclic antidepressants ( TCAs ) desipramine and imipramine and the selective serotonin re-uptake inhibitor ( SSRI ) fluoxetine . METHODS : Pooled data were analysed from seven short-term ( 4 - 8 weeks ) and one long-term ( up to 1 year ) trials comparing reboxetine with placebo , imipramine , desipramine or fluoxetine . The tolerability of reboxetine was evaluated in 2613 patients with major depression or dysthymia . Data from 1959 patients with major depressive disorder were included to assess drug efficacy . Efficacy was principally assessed using the Hamilton Depression Rating Scale ( HAM-D ) . RESULTS : Reboxetine was more effective than placebo in three of four short-term trials , and it was as effective as fluoxetine , imipramine and desipramine . In long-term treatment , reboxetine was more effective than placebo in preventing relapse ( S 50 % increase in HAM-D ) and recurrence ( HAM-D total score h 10 ) . In a subset of severely depressed patients , reboxetine was as effective as imipramine and significantly more effective than fluoxetine . Reboxetine was as effective as imipramine in the elderly , but better tolerated . The most common adverse events among the 1503 patients ( adults and elderly ) who received reboxetine were dry mouth ( 22 % ) , constipation ( 15 % ) , sweating ( 12 % ) and insomnia ( 11 % ) . Overall , reboxetine was well tolerated , as well as the SSRI fluoxetine and better than the TCAs imipramine and desipramine . CONCLUSIONS : Reboxetine is effective and well tolerated in the short and long-term treatment of depression . It is as well tolerated as fluoxetine and better than imipramine and desipramine . ( Int J Psych Clin Pract 2000 ; 4 : 201 - 208 Paroxetine is a novel phenylpiperidine antide-pressant agent that acts as a potent and selective inhibitor of serotonin reuptake . We report results of a 6-week , r and omized , double-blind , multicenter study comparing paroxetine and fluoxetine in the treatment of major depression . One hundred seventy-eight in patients , who met DSM-III-R criteria for a major depressive episode and had a Montgomery Asberg Depression Rating Scale ( MADRS ) score of 24 or more , were included in the study . Their ages ranged from 18 to 65 years . Subjects were r and omized to receive either paroxetine or fluoxetine for 6 weeks . A 20-mg fixed dose , given once daily in the morning , was used for both drugs . After baseline , regular assessment s were made at the end of weeks 1,2,3,4 , and 6 . Efficacy measures included the MADRS , the Clinical Global Impression severity of illness scale , the Hamilton Rating Scale for Anxiety , the Hospital Anxiety and Depression scale , and the Visual Analogue Scale for anxiety . Safety and tolerability were assessed by adverse event reports , clinical examinations , vital signs , and laboratory data . A marked antidepressant response and good tolerability were seen with both drugs . These results further support the usefulness of paroxetine in the treatment of depressive illness A r and omized , double‐blind , parallel‐group , 6‐week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine . After a 1‐week placebo wash‐out , patients suffering from DSM‐III major depression and with a score of 18 or more on the 21‐item Hamilton Rating Scale for Depression ( HRSD ) received either paroxetine or fluoxetine . The patients were assessed for efficacy using the HRSD , Montgomery‐Åsberg Depression Rating Scale and Clinical Global Impression ; for tolerability , adverse events were elicited by the use of a non‐leading question and a side effects checklist . The groups of patients were comparable on entry to the study . One hundred patients were recruited into the study , of whom 78 were evaluable for the efficacy analysis .  Paroxetine and fluoxetine showed comparable efficacy at the end of the 6‐week treatment period , but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed . This could suggest an earlier onset of action with paroxetine .  Also , associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3 . Patients on paroxetine reported fewer adverse events than those on fluoxetine . The most commonly reported adverse events were nausea and vomiting in both groups The primary objective of this multicentre , r and omized , double-blind study carried out in France was to compare the efficacy and safety of a 6-week treatment with paroxetine ( 20 mg/day ) or mianserine ( 30 mg/day ) in geriatric hospitalized or ambulatory patients ( > or = 60 years ) treated for a major depressive disorder ( according to DSM III-R ) . A secondary objective was to discriminate those items predicting the response to an agent according to its serotoninergic or noradrenergic pharmacologic profile . The tool used for this latter purpose was the Aubin-Jouvent-Rating-Scale ( AJRS ) which was design ed to assess the deficit of serotonin : this is a scale with 10 items , some of them regrouped into a " general " factor ( irritability , sudden mood change , impatience , aggressivity ) or a " depression " factor ( pain , anxiety , suicidal ideas ) with additional items related to sleep disorders , abnormalities in eating behavior and inability to tolerate isolation . In the perspective of this assessment , paroxetine was chosen due to its potential to inhibit serotonin re-uptake , as compared to mianserin which blocks presynaptic alpha-adrenergic receptors with negligible action on serotonin . This was a multicenter study carried out in France in 50 hospital or private practice psychiatrists . The assessment criteria included the MADRS , the AJRS , the COVI 's anxiety scale , the Folstein 's Mini-mental state ( MMS ) as well as a global assessment by the investigator at the end of the study . Safety was measured with a nondirective question naire , routine laboratory tests as well as a global assessment by the investigator . The primary efficacy criteria was the change in the MADRS global score . Statistical analysis included chi-square or Fisher 's test as well as Student 's and Wilcoxon tests for comparability at baseline , and analysis of variance for the changes in scores as during the study . A total of 116 patients was r and omised ( paroxetine : 54 ; mianserine : 62 ) , of whom 96 completed the study ( paroxetine : 43 ; mianserine : 53 ) . With the exception of MADRS moderately higher in the paroxetine group , both groups were comparable at baseline . After 6 weeks of treatment , a marked improvement was recorded in both groups for all criteria except MMS ; there was a consistent tendency favouring paroxetine which reached statistical significance for the COVI ' scale ( p = 0.001 ) . For a given criterion , the difference paroxetine versus mianserine appeared related to the score at baseline ; it was also more marked in those patients with a AJRS baseline score > or = 20 with a difference for MADRS reduction of marginal significance in favor of paroxetine ( p = 0.061 ) . As regards safety , at least one adverse event was reported in 31.5 % of the patients receiving paroxetine versus 41.9 % in those receiving mianserin ( NS ) ; premature withdrawal related to an adverse event was reported in 11.1 % of the patients in the paroxetine group versus 12.9 % in the mianserin group . No abnormality of clinical significance was reported in either group concerning laboratory tests . In conclusion , this study confirmed the therapeutic value and good safety of paroxetine as an antidepressant in geriatric population s , especially when exist a concomitant anxiety or symptoms likely to reflect a deficit of serotonine ( irritability , emotional lability , restlessness , aggressivity ) and to predict a good response to an agent such as this one Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors . The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine . However , most data were collected in sample s of out patients . To overcome this restriction , a six-week double-blind control-group study , comparing 30 mg paroxetine with 150 mg amitriptyline per day , was performed in a sample of in patients suffering from major depression . Generally speaking , the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline , either with respect to the total score on the Hamilton Depression Scale ( HAMD ) and the Clinical Global Impressions or with respect to the subscores of the HAMD . One exception was the retardation subscore , in which amitriptyline showed a greater degree of reduction . Both drugs had a characteristic side-effect profile .  Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea
We found no clear evidence that paroxetine was more or less effective compared with other antidepressants at increasing response to treatment at acute ( six to 12 weeks ) , early ( one to four weeks ) , or longer term follow-up ( four to six months ) .
Paroxetine was associated with a lower rate of adverse events than amitriptyline , imipramine and older ADs as a class , but was less well tolerated than agomelatine and hypericum .
Some possibly clinical ly meaningful differences between paroxetine and other ADs exist , but no definitive conclusions can be drawn from these findings .
In terms of early response to treatment ( one to four weeks ) there was moderate quality of evidence that mirtazapine was better than paroxetine and that paroxetine was better than reboxetine .
However there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any time point .
BACKGROUND Paroxetine is the most potent inhibitor of the reuptake of serotonin of all selective serotonin reuptake inhibitors ( SSRIs ) and has been studied in many r and omised controlled trials ( RCTs ) .
However , these comparative studies provided contrasting findings and systematic review s of RCTs have always considered the SSRIs as a group , and evidence applicable to this group of drugs might not be applicable to paroxetine alone .
The present systematic review assessed the efficacy and tolerability profile of paroxetine in comparison with tricyclics ( TCAs ) , SSRIs and newer or non-conventional agents .
OBJECTIVES 1 .
To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of Major Depressive Disorder.2  .
To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.3 .
To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents .