S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Controlled withdrawal of selective serotonin reuptake inhibitor drugs in elderly patients in nursing homes with no indication of depression Response to an open trial of a second SSRI in major depression. A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline A randomised controlled trial of cognitive behaviour therapy in adolescents with major depression treated by selective serotonin reuptake inhibitors. The ADAPT trial. 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† Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder. Improving patients' beliefs about antidepressants in primary care: a cluster-randomized controlled trial of the effect of a depression care program. Serotonin reuptake inhibition vs. norepinephrine reuptake inhibition: a double-blind differential-therapeutic study with fluvoxamine and oxaprotiline in endogenous and neurotic depressives. Is Baseline Agitation a Relative Contraindication for a Selective Serotonin Reuptake Inhibitor: A Comparative Trial of Fluoxetine Versus Imipramine Selective alteration of personality and social behavior by serotonergic intervention. Selective Serotonergic (SSRI) Versus Noradrenergic (SNRI) Reuptake Inhibitors with and without Acetylsalicylic Acid in Major Depressive Disorder. Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder Cardiac side‐effects of two selective serotonin reuptake inhibitors in middle- aged and elderly depressed patients Lack of sexual dysfunction with the selective noradrenaline reuptake inhibitor reboxetine during treatment for major depressive disorder Combination of inositol and serotonin reuptake inhibitors in the treatment of depression
OBJECTIVE Despite the progressive increase in the number of antidepressants , many patients with major depressive disorder continue to be symptomatic . Clearly , there is an urgent need to develop better tolerated and more effective treatments for this disorder . The use of S-adenosyl methionine ( SAMe ) , a naturally occurring molecule that serves as a methyl donor in human cellular metabolism , as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development . METHOD Participants were 73 serotonin reuptake inhibitor ( SRI ) nonresponders with major depressive disorder enrolled in a 6-week , double-blind , r and omized trial of adjunctive oral SAMe ( target dose : 800 mg/twice daily ) . Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial . The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale ( HAM-D ) . RESULTS The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe ( 36.1 % and 25.8 % , respectively ) than adjunctive placebo ( 17.6 % versus 11.7 % , respectively ) . The number needed to treat for response and remission was approximately one in six and one in seven , respectively . There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason ( 20.6 % versus 29.5 % , respectively ) , due to adverse events ( 5.1 % versus 8.8 % , respectively ) , or due to inefficacy ( 5.1 % versus 11.7 % , respectively ) . CONCLUSIONS These preliminary results suggest that SAMe can be an effective , well-tolerated , and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication Objective The aim of the investigation was to study the effects of withdrawing selective serotonin reuptake inhibitor ( SSRI ) drugs in nursing home patients , who had no documented diagnosis or symptoms of depression . Setting The setting of the study was in 11 nursing homes in the county of Stockholm , Sweden . Participants Participants were patients without dementia or history of depression who had received treatment with SSRI drugs for more than 6 months and who had no indications of anxiety disorder or major depression Design The included patients ( n=70 ) were r and omized to either the intervention group  ( withdrawal of SSRI ) or the control group  ( no change in treatment ) , 35 patients to each group . Main outcome measures The patients were subjected to assessment using the following instruments : Montgomery-Åsberg depression rating scale , global assessment for functioning , health index and a symptom assessment form . Assessment was made at the start of the study and at the 3-month and 6-month follow-ups . Results We found no significant difference between the intervention and control groups in any outcome measure . Conclusion Treatment with SSRI drugs in patients without clinical major depression or anxiety disorder is often unjustified and should be discontinued BACKGROUND We evaluated the efficacy of a second serotonin selective reuptake inhibitor ( SSRI ) in patients who had failed to respond to the first SSRI used . METHOD Fifty-five patients with major depression who had failed one of the SSRIs for their current depressive episode were included . After failing a trial of one SSRI , they received a second SSRI in an open clinical trial . RESULTS On the basis of the Clinical Global Impression-Improvement scale , 28 of 55 patients had a marked or complete antidepressant response . CONCLUSION These data provide preliminary clinical evidence that substituting a second SRI may be a useful clinical alternative in depressed patients who fail to respond to an adequate trial of an SSRI Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors ( SSRIs ) in severe major depressive disorder ( MDD ) . This prospect i ve pragmatic trial tests this hypothesis . Patients with severe MDD were r and omly assigned to either duloxetine ( a serotonin and norepinephrine-reuptake inhibitor ) or physicians ’ choice of four generic SSRIs . Nonblinded , flexibly dosed treatment was used to mimic clinical practice . To address potential investigator bias , the patient-reported Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR ) was used as the primary efficacy outcome measure . A total of 750 out patients ( 19.2 % , African descent ; 14.8 % , Hispanic ) were r and omized . The primary outcome , remission at week 12 by QIDS-SR , was numerically greater for duloxetine compared with SSRIs ( 36 vs. 32 % ) , but this difference was not statistically significant . Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item , the Brief Pain Inventory , and the Sheehan Disability Scale . Remission superiority on the QIDS-SR was not achieved . Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning . Study demographics suggest a more generalizable racial and ethnic population than is typical in r and omized clinical trials BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy OBJECTIVES To determine if , in the short term , depressed adolescents attending routine NHS Child and Adolescent Mental Health Services ( CAMHS ) , and receiving ongoing active clinical care , treatment with selective serotonin reuptake inhibitors ( SSRIs ) plus cognitive behaviour therapy ( CBT ) compared with SSRI alone , results in better healthcare outcomes . DESIGN A pragmatic r and omised controlled trial ( RCT ) was conducted on depressed adolescents attending CAMHS who had not responded to a psychosocial brief initial intervention ( BII ) prior to r and omisation . SETTING Six English CAMHS participated in the study . PARTICIPANTS A total of 208 patients aged between 11 and 17 years were recruited and r and omised . INTERVENTIONS All participants received active routine clinical care in a CAMHS outpatient setting and an SSRI and half were offered CBT . MAIN OUTCOME MEASURES The duration of the trial was a 12-week treatment phase , followed by a 16-week maintenance phase . Follow-up assessment s were at 6 , 12 and 28 weeks . The primary outcome measure was the Health of the Nation Outcome Scales for Children and Adolescents ( HoNOSCA ) . Secondary outcome measures were self-report depressive symptoms , interviewer-rated depressive signs and symptoms , interviewer-rated psychosocial impairment and clinical global impression of response to treatment . Information on re source use was collected in interview at baseline and at the 12- and 28-week follow-up assessment s using the Child and Adolescent Service Use Schedule ( CA-SUS ) . RESULTS Of the 208 patients r and omised , 200 ( 96 % ) completed the trial to the primary end-point at 12 weeks . By the 28-week follow-up , 174 ( 84 % ) participants were re-evaluated . Overall , 193 ( 93 % ) participants had been assessed at one or more time points . Clinical characteristics indicated that the trial was conducted on a severely depressed group . There was significant recovery at all time points in both arms . The findings demonstrated no difference in treatment effectiveness for SSRI + CBT over SSRI only for the primary or secondary outcome measures at any time point . This lack of difference held when baseline and treatment characteristics where taken into account ( age , sex , severity , co-morbid characteristics , quality and quantity of CBT treatment , number of clinic attendances ) . The SSRI + CBT group was somewhat more expensive over the 28 weeks than the SSRI-only group ( p=0.057 ) and no more cost-effective . Over the trial period there was on average a decrease in suicidal thoughts and self-harm compared with levels recorded at baseline . There was no significant increase in disinhibition , irritability and violence compared with levels at baseline . Around 20 % ( n=40 ) of patients in the trial were non-responders . Of these , 17 ( 43 % ) showed no improvement by 28 weeks and 23 ( 57 % ) were considered minimally ( n=10 ) or moderately to severely worse ( n=13 ) . CONCLUSIONS For moderately to severely depressed adolescents who are non-responsive to a BII , the addition of CBT to fluoxetine plus routine clinical care does not improve outcome or confer protective effects against adverse events and is not cost-effective . SSRIs ( mostly fluoxetine ) are not likely to result in harmful adverse effects . The findings are broadly consistent with existing guidelines on the treatment of moderate to severe depression . Modification is advised for those presenting with moderate ( 6 - 8 symptoms ) to severe depressions ( > 8 symptoms ) and in those with either overt suicidal risk and /or high levels of personal impairment . In such cases , the time allowed for response to psychosocial interventions should be no more than 2 - 4 weeks , after which fluoxetine should be prescribed . Further research should focus on evaluating the efficacy of specific psychological treatments against brief psychological intervention , determining the characteristics of patients with severe depression who are non-responsive to fluoxetine , relapse prevention in severe depression and improving tools for determining treatment responders and non-responders 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 Patients with major depressive disorder ( MDD ) usually suffer from altered cognitive functions of episodic memory , working memory , mental processing speed and motor response . Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD . The aim of this work is to study the effects of serotonergic reuptake inhibitors ( SSRIs ) and serotonergic-noradrenergic reuptake inhibitors ( SNRIs ) treatments to improve the performance on memory tasks and mental processing speed in MDD . Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery . The subjects were medicated with escitalopram ( n=36 ) or duloxetine ( n=37 ) for 24 weeks . At the end of the trial , the subjects were assessed again with the same neuropsychological battery used prior to the treatment . Both treatments improved importantly the episodic memory and to a lesser extent , working memory , mental processing speed and motor performance . Our results suggest that cognition is partially independent from improvement in clinical symptoms . Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment , but SNRI was superior to SSRI  at improving episodic and working memory . Our work indicates that the superiority of SNRI over the SSRI  at episodic memory improvement is clinical ly relevant OBJECTIVE Many depressed patients have negative beliefs about antidepressants , leading to poor adherence , unfavorable depression outcome , and low perceived well-being , role functioning , and quality of life . Interventions to ameliorate beliefs are therefore needed . METHOD In a cluster-r and omized controlled trial conducted from September 1999 to January 2001 , 2 interventions to improve management of major depressive disorder  in primary care were compared : ( 1 ) a depression care program ( DCP ) , providing enhanced patient education , stimulation of active participation of general practitioners and patients in the treatment process , discussion of benefits and costs of taking antidepressant medication , and systematic follow-up and ( 2 ) a systematic follow-up program ( SFP ) .  Thirty general practitioners were r and omly assigned , and 211 patients with current major depressive disorder ( diagnosed according to DSM-IV ) were included . All patients were prescribed a selective serotonin reuptake inhibitor .  Beliefs were assessed at baseline , at week 10 , and at week 26 . Differences in change of beliefs between DCP and SFP groups were analyzed . RESULTS Changes in patients ' beliefs were more favorable in the DCP condition at week 10 and week 26 , compared with SFP only ( beliefs concerning appropriate medication-taking , week 10 : effect size = 0.39 , p = .012 ; week 26 : effect size = 0.55 , p = .001 ; beliefs concerning harmfulness , week 10 : effect size = 0.45 , p = .011 ; week 26 : effect size = 0.62 , p = .002 ) . CONCLUSION The depression care program ameliorates beliefs about antidepressants in primary care patients with major depressive disorder . The study results encourage the implementation of a depression care program in order to improve beliefs about antidepressant medication in primary care patients diagnosed with major depressive disorder The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist . Responders were treated for 7 weeks with the compound to which they had responded . After 1 placebo week , the nonresponders were switched to the alternative compound . An evaluation of the data obtained during the 3-week treatment periods from 24 patients ( 37 trials ) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds , oxaprotiline and fluvoxamine . If the patients with major depression are subdivided into two groups , endogenous depressives and neurotic depressives , there is no significant difference between the therapeutic improvements ( both compounds ) achieved in the two groups . The data shows that only about 20 % of the nonresponders on one compound responded to the alternative drug , whereas 90 % of responders ( within 3 weeks ) were still responders after 7 weeks . The data are at variance with the concept of two distinct biochemical subtypes of depression ( serotonergic vs. norepinephrinergic ) .  Dexamethasone suppression tests , performed in 23 patients , gave no prognostic hint as to whether the patients reacted well to drug therapy or not A common presentation for major depression includes psychomotor agitation . However , this subtype has been the infrequent subject of controlled investigation during depression trials . Yet , the subcategorization of agitated depression has historically been associated with the belief that older , sedating compounds have a superior risk : benefit profile . In the 8-week , double-blind , r and omized , parallel trial , 124 subjects with Research Diagnostic Criteria -compatible agitated depression were r and omized to either imipramine ( IMI ) or fluoxetine ( FLU ) . Both compounds proved to be similarly effective as measured by change in HAM-D17 , HAM-D17 response , and HAM-D17 remission rates . Similar comparability was seen in secondary measures of agitation , anxiety , suicidality , and global impressions . However , of note , a statistically significant difference in early discontinuations because of intolerable adverse events emerged . Whereas 43.5 % of IMI subjects discontinued early , only 9.7 % of FLU subjects ( p < 0.001 ) did . Significantly more central nervous system events characterized the IMI than the FLU subgroup ( IMI , 24.2 % , vs. FLU , 6.5 % ; p = 0.006 ) . In conclusion , among subjects with major depression , subtype agitated , the risk : benefit profile favored FLU over IMI . This was driven by the superior tolerance of FLU . No evidence emerged in support of the clinical hypothesis that a “ sedating ” agent is the treatment of choice for this group . The results are important when striving to maximize compliance with pharmacotherapy in order to minimize recidivism and associated psychological and economic morbidity . ( J Clin Psychopharmacol 1994;14:385–391 OBJECTIVE The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans . METHOD A selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , 20 mg/day ( N = 26 ) , or placebo ( N = 25 ) was administered to normal volunteers in a double-blind manner for 4 weeks , and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment . RESULTS Relative to placebo , SSRI administration reduced focal indices of hostility through a more general decrease in negative affect , yet did not alter indices of positive affect . In addition , SSRI administration increased a behavioral index of social affiliation . Changes in both negative affect and affiliative behavior were significantly related to volunteers ' plasma SSRI levels at the end of the experiment . CONCLUSIONS Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior .  SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology BACKGROUND Antidepressant medication efficacy remains a major research challenge . Here , we explored four questions : whether noradrenergic antidepressants are more effective than serotonergic antidepressants ; whether the addition of 100 mg acetylsalicylic acid ( ASA ) changes antidepressant efficacy ; whether the long-term efficacy differs depending on the antidepressant and the addition of ASA ; and whether serum levels of brain-derived neurotrophic factor ( BDNF ) are clinical ly informative . SUBJECTS AND METHODS In a two-year study , forty people with major depressive disorder were r and omly assigned to groups that received an SSRI ( escitalopram ) or an SNRI ( duloxetine ) , each group received concomitant ASA ( 100 mg ) or a placebo . Sociodemographic data were recorded and patients under went regular assessment s with the Hamilton depression scale ( HDS ) and clinical global impression ( CGI ) scale . Serum levels of BDNF were measured four times per year . RESULTS There was no significant difference in efficacy between the two antidepressants or between antidepressant treatment with and without ASA . However , subgroup comparisons revealed that the duloxetine + ASA ( DASA ) subgroup showed a more rapid improvement in HDS score as early as 2 months ( t=-3.114 , p=0.01 ) , in CGI score at 5 months ( t=-2.119 , p=0.05 ) , and a better remission rate ( χ2=6.296 , p 0.012 ) than the escitalopram + placebo ( EP ) subgroup . Serum BDNF before treatment was also higher in the DASA subgroup than in the EP subgroup ( t=3.713 ; p=0.002 ) . CONCLUSION This suggest two hypotheses : either a noradrenergic agent combined with ASA is more effective in treating depression than a serotonergic agent alone , or the level of serum BDNF before treatment is a precursor marker of the response to antidepressants . Further research is needed to test these hypotheses Objective : To assess whether patients receiving aerobic exercise training  performed either at home or in a supervised group setting achieve reductions in depression comparable to st and ard antidepressant medication ( sertraline ) and greater reductions in depression compared to placebo controls . Methods : Between October 2000 and November 2005 , we performed a prospect i ve , r and omized controlled trial ( SMILE study ) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital . A total of 202 adults ( 153 women ; 49 men ) diagnosed with major depression were assigned r and omly to one of four conditions : supervised exercise in a group setting ; home-based exercise ; antidepressant medication ( sertraline , 50–200 mg daily ) ; or placebo pill for 16 weeks . Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale ( HAM-D ) . Results : After 4 months of treatment , 41 % of the participants achieved remission , defined as no longer meeting the criteria for major depressive disorder ( MDD ) and a HAM-D score of < 8 . Patients receiving active treatments tended to have higher remission rates than the placebo controls : supervised exercise = 45 % ; home-based exercise = 40 % ; medication = 47 % ; placebo = 31 % ( p = .057 ) . All treatment groups had lower HAM-D scores after treatment ; scores for the active treatment groups were not significantly different from the placebo group ( p = .23 ) . Conclusions : The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD . Placebo response rates were high , suggesting that a considerable portion of the therapeutic response is determined by patient expectations , ongoing symptom monitoring , attention , and other nonspecific factors . BDI = Beck Depression Inventory ; CI = confidence interval ; HAM-D = Hamilton Depression Rating Scale ; ITT = intention-to-treat ; MDD = major depressive disorder ; SD = st and ard deviation ; SSRIs = selective serotonin reuptake inhibitors ; TSH = thyroid stimulating hormone Selective serotonin reuptake inhibitors ( SSRIs ) are the ‘ new ’ drugs of first choice for the treatment of depression in the older patient . Systematic studies on the effects of SSRIs on cardiac function are scarce , despite the high prevalence of cardiac disorders in the older depressed patient . This is a study which systematic ally assesed cardiac function by echo-cardiography in middle-aged and elderly depressed patients treated with SSRI . In a double-blind r and omized trial , 20 patients were assigned to receive fluvoxamine 20 mg/day or fluoxetine 100mg/day for 6 weeks . Cardiac function was assessed by left ventricle ejection fraction , aortic flow integral and early or passive/late or active mitral inflow , and electrocardiography . Neither SSRI significantly affected cardiac function . Compared with patients without a history of myocardial infa rct ion and /or hypertension , patients with such a history showed a significant improvement in left ventricular ejection fraction . Despite our small study sample , these data indicate that both fluoxetine and fluvoxamine do not affect cardiac function adversely & NA ; Sexual side‐effects due to antidepressant treatment are an important consideration when selecting a treatment regimen and can influence patient compliance . Sexual function during treatment with the selective noradrenaline reuptake inhibitor reboxetine , the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine and placebo has been assessed in a multicentre , r and omized , 8‐week , double‐blind study of 450 patients diagnosed with major depressive disorder .  Sexual function was measured by the Rush Sexual Inventory completed by male and female patients and administered at baseline , week 4 and week 8 . The results indicate that reboxetine was similar to placebo and superior to fluoxetine in its effect on overall sexual function . There was a greater degree of sexual satisfaction in the reboxetine group compared to fluoxetine ( P = 0.02 ) . The percentage of female patients able to achieve orgasm increased during the study period for women who received reboxetine and placebo , but decreased for those who received fluoxetine . These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs BACKGROUND Inositol has been reported to be an effective treatment in depression , and we hypothesized that inositol addition might enhance or speed up response to  serotonin selective reuptake inhibitors ( SSRI ) . METHODS Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol .  Hamilton Depression Rating Scale was used as an assessment tool at baseline , and 1 , 2 , 3 , and 4 weeks . RESULTS No significant difference was found between the two treatment groups . CONCLUSIONS Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [ e.g. , monoamine oxidase inhibitors ( MAOI ) plus tricyclic antidepressants ( TCA ) , TCA plus lithium ] . By contrast , augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol
SSRIs significantly increase the risk of both serious and non-serious adverse events .
The potential small beneficial effects seem to be outweighed by harmful effects .
Background The evidence on selective serotonin reuptake inhibitors ( SSRIs ) for major depressive disorder is unclear .
Methods Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo , ‘ active ’ placebo , or no intervention in adult participants with major depressive disorder .