Antidepressant treatment for post-natal depression. Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group. A randomized controlled clinical trial comparing "guideline exposed" and "guideline naive" physicians in respect to dosage selection and treatment outcome with doxepin in depressive disorders. Efficacy of Computer-Aided Dosing of Warfarin Among Patients in a Rehabilitation Hospital A double-blind study of fluoxetine and imipramine in major depression. Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial. Efficacy and mood conversion rate during long-term fluoxetine v. lithium monotherapy in rapid- and non-rapid-cycling bipolar II disorder. An analysis of systematic reviews indicated low incorpororation of results from clinical trial quality assessment. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. How many Cochrane reviews are needed to cover existing evidence on the effects of healthcare interventions? Continuation and Maintenance Use of Antidepressants in Recurrent Depression A comparative trial of fluoxetine versus trazodone in outpatients with major depression. Commentary on the Cochrane Review of acupuncture and assisted conception. Safe use of SSRIs in young adults: how strong is evidence for new suicide warning? Resolution of sexual dysfunction during double-blind treatment of major depression with reboxetine or paroxetine Male Sexual Side Effects Associated with Antidepressants: A Descriptive Clinical Study of 32 Patients Testosterone Versus Fluoxetine for Depression and Fatigue in HIV/AIDS: A Placebo-Controlled Trial Self-help interventions for depressive disorders and depressive symptoms: a systematic review Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression.
BACKGROUND : Postnatal depression is a common disorder , which can have profound short and long term effects on maternal morbidity , the new infant and the family as a whole . Social factors appear to be particularly important in the aetiology and prognosis of postnatal depression and treatment is often largely social support and psychological interventions . It is not known whether antidepressants are an effective and safe choice for treatment of this disorder . OBJECTIVES : To evaluate the effectiveness of different antidepressant drugs  and compare their effectiveness with other forms of treatment . To assess any adverse effects of antidepressants in the mother or the nursing baby . SEARCH STRATEGY : The registers of clinical trials maintained and up date d by the Cochrane Depression , Anxiety and Neurosis Group and the Cochrane Pregnancy and Childbirth Group were search ed . Other data bases ( outlined below ) were also search ed and contacts were made with pharmaceutical companies and experts in the field . SELECTION CRITERIA : All trials were considered in which women with depression in the first six months postpartum were r and omised to receive antidepressants alone or in combination with another treatment , or to receive any other treatment including placebo . DATA COLLECTION AND ANALYSIS : Data was extracted independently from the trial reports by the review ers . Missing information was requested from investigators wherever possible . Data was sought to allow an " intention to treat " analysis . MAIN RESULTS : Only one trial could be included in this review , leaving most of the objectives of the review unfulfilled . Appleby et al ( 1997 ) reported that Fluoxetine was significantly more effective than placebo and , after an initial session of counselling , as effective as a full course of cognitive-behavioural counselling in the treatment of postnatal depression . There was no interaction between medication and counselling . REVIEW ER 'S CONCLUSIONS : Women with postnatal depression can be effectively treated with fluoxetine , which is as effective as a course of cognitive-behavioural counselling in the short-term . However , more trials with a longer follow-up period are needed to compare different antidepressants in the treatment of postnatal depression , and to compare antidepressant treatment with psychosocial interventions .  This is an area that has been neglected despite the large public health impact described above OBJECTIVE Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both , we investigated whether tryptophan , an amino acid with both antidepressant-augmenting and hypnotic effects , would benefit patients with depression at the beginning of treatment with fluoxetine .  DESIGN R and omized , double-blind , placebo-controlled trial . PATIENTS Thirty individuals with major depressive disorder . INTERVENTIONS Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan ( 2 to 4 g per day ) or placebo . OUTCOME MEASURES Mood was assessed using the 29-item Hamilton Depression Rating Scale ( HDRS-29 ) and the Beck Depression Inventory ( BDI ) . Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using st and ard procedures . RESULTS During the first week of treatment , there was a significantly greater decrease in HDRS-29 depression scores , and a similar trend in BDI scores , in the tryptophan/fluoxetine group than in the placebo/fluoxetine group . No significant differences were noted at later time points . With respect to sleep measures , there was a significant group-by-time interaction for slow-wave sleep at week 4 . Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group , but not in the tryptophan/fluoxetine group . No cases of serotonin syndrome occurred , and the combination was well tolerated , although the 4 g per day dosage of tryptophan produced daytime drowsiness . CONCLUSIONS Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep . Further large-scale studies are needed to confirm these initial findings OBJECTIVE To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed in patients and out patients . METHOD Patients with a major depressive episode ( DSM-III-R ) , a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) , and > or=2 on HAM-D Item 1 ( depressed mood ) were r and omly assigned to a 6-week treatment with either mirtazapine ( N=66 , 15 - 60 mg/day ) or fluoxetine ( N=67 , 20 - 40 mg/day ) . The upper limit of the mirtazapine dose range was above the dose range approved in the United States ( 15 - 45 mg/day ) . Efficacy was evaluated by the HAM-D , Clinical Global Impressions , the Visual Analogue Mood Rating Scale ( VAMRS ) , and the Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method . RESULTS Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group . The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period , reaching statistical significance at days 21 and 28 . At assessment s from day 21 and onward , the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points , the magnitude of difference usually seen between an efficacious antidepressant drug and placebo . Mean dosages at weeks 1 - 4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine ; the respective dosages at weeks 5 - 6 were 56.3 mg and 35.8 mg . Similar numbers of patients dropped out due to adverse events ; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group . CONCLUSION We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy INTRODUCTION Can prescribing of insufficient dosages and outcome of treatment with antidepressants in routine care be improved by guidelines ? METHODS 161 general practitioners and 162 psychiatrists in private practice documented 1319 patients , receiving doxepin for individual clinical reasons . Physicians were r and omly divided into a guideline exposed and a control group . All physicians treated their patients according to individual clinical considerations . RESULTS Average maximum daily dosage was 83 mg/d in the control and 95 mg/d in the intervention group ( F=19.15 ; p<0 ) . Only 3 % of patients in both groups got the recommended dosage of 150 mg/d . Guideline exposure result ed in increased dosages preferably for milder forms of depression and in comparatively lower rates of improvement . CONCLUSION Guideline exposure did not reach its goal in respect to the recommended dosage . It missed its goal in respect to improvement of outcome and even showed negative effects . Guidelines should be evidence -based not only by referring to literature review s but by testing their clinical effects in controlled clinical trials Mitra R , Marciello MA , Brain C , Ahangar B , Burke DT : Efficacy of computer-aided dosing of warfarin among patients in a rehabilitation hospital . Am J Phys Med Rehabil 2005;84:423–427 . Objective : To determine whether computer-aided dosing of warfarin is superior to physician dosing to maintain a patient in a rehabilitation hospital within a target international normalized ratio goal . Design : R and omized , double-blinded , clinical trial in an inpatient rehabilitation hospital . A total of 30 consecutive patients admitted receiving warfarin were r and omized to either clinician dosing  or computer-aided warfarin dosing for the duration of their hospitalization . The main outcome measures included the percentage of days in a therapeutic anticoagulation range and the number of blood draws .  Exclusion criteria included short length of stay ( n = 110 , 39 % ) and a physician declared international normalized ratio target range of < 2.0 ( n = 67 , 23 % ) . A total of 73 patients were excluded because of heme-positive stools at admission , recent gastrointestinal bleed , early discharge or consent refusal .  Dawn AC software was used to determine warfarin dosage and frequency of blood draws to maintain a target international normalized ratio of 2.0–3.0 for the computer-dosed group ( n = 14 ) . Several physicians recommended warfarin dosages for the second group ( n = 16 ) . Two were dropped from the computer model secondary to lost data files for these two patients . Results : Computer-aided dosing of warfarin result ed in 61.7 % of days within the therapeutic range ( international normalized ratio , 2–3 ) , whereas clinician dosing result ed in only 44.1 % . There were no significant differences in the number of blood draws or demographic variables between the two groups . Conclusion : Computers were significantly better at maintaining patients within a therapeutic international normalized ratio range than physicians . There were no significant differences in the number of recommended blood draws Eighteen out patients with major depression ( diagnosis was made according to DSM-III criteria ) were treated in a 5-week double-blind parallel group comparison of the new antidepressant fluoxetine with imipramine . From these results it can be shown that the drugs were comparable in efficacy , although because of the small sample size a moderate clinical difference between treatments may not have been detected . Imipramine and fluoxetine have already been compared in other studies , but never at such a low dosage ( 20 mg ) for fluoxetine . At this dosage the fluoxetine  safety profile seems to be very different from previous scheduled studies with higher dosages . In fact clinical efficacy seems to remain comparable while side-effects are significantly less frequent As many as 45 % of patients with major depressive episode also meet DSM-IV criteria for bipolar II ( BP II ) disorder . Although some clinicians advocate using a mood stabilizer in treating BP II depression , antidepressant monotherapy has been less well studied in this disorder . As part of a prospect i ve , placebo-controlled , relapse-prevention study in 839 patients , the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar ( UP ) major depression was retrospectively examined . Eighty-nine BP II patients ( mean age , 41+/-11 years ) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients ( mean age , 39+/-11 years ) . All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks . Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks . Remitted patients were then r and omly assigned to receive double-blind treatment with one of the following : ( 1 ) fluoxetine 20 mg daily for 52 weeks ; ( 2 ) fluoxetine for 38 weeks , then placebo for 14 weeks ; ( 3 ) fluoxetine for 14 weeks , then placebo for 38 weeks ; or ( 4 ) placebo for 52 weeks . Antidepressant efficacy was similar in BP and UP patients during short-term therapy . Discontinuation for lack of efficacy was lower in BP II ( 5 % ) than in UP ( 12 % ) patients ( p = not significant [ NS ] ) , whereas dropouts for adverse events were similar in BP II ( 11 % ) and UP ( 9 % ) patients . During long-term relapse-prevention therapy , relapse rates were similar in BP II and UP patients ( p = NS ) . During short-term fluoxetine therapy , three BP II ( 3.8 % ) versus no matched UP ( p = NS ) and 0.3 % unmatched UP ( p = 0.01 ) patients had a " manic switch . " During long-term fluoxetine therapy , one ( 2 % ) BP II and three ( 1 % ) unmatched UP patients ( one taking placebo ) had a manic switch ( p = NS ) . In conclusion , fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate . Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder BACKGROUND Previous small trials have suggested that nefazodone does not suppress rapid-eye-movement ( REM ) sleep or increase REM latency in depressed patients , in contrast to fluoxetine . The effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures were directly compared in this 8-week , multicenter , double-blind , r and omized , parallel-group study . METHOD Forty-four out patients with moderate to severe , nonpsychotic major depressive disorder ( DSM-III-R ) and insomnia were r and omly assigned to receive nefazodone ( Days 1 - 7 , 200 mg/day ; Days 8 - 56 , 400 mg/day ) or fluoxetine ( Days 1 - 56 , 20 mg/day ) . Sleep measures were obtained at baseline , while patients were unmedicated , and at Weeks 2 , 4 , and 8 of treatment . RESULTS In 43 evaluable patients ( 23 nefazodone , 20 fluoxetine ) , nefazodone and fluoxetine demonstrated similar antidepressant efficacy . All significant values were p < .05 . Fluoxetine significantly decreased sleep efficiency and REM sleep and increased number of awakenings , Stage 1 sleep , and REM latency compared with baseline . In contrast , nefazodone significantly decreased percentage of awake and movement time and did not alter sleep efficiency or number of awakenings , Stage 1 or REM sleep , or REM latency compared with baseline . Nefazodone was associated with significantly less change from baseline for sleep efficiency , number of awakenings , percentage of awake and movement time , percentage of REM and Stage 1 sleep , and REM latency compared with fluoxetine . Both fluoxetine- and nefazodone-treated patients also showed significant improvement in some clinician- and patient-rated sleep disturbance scores , but nefazodone-treated patients improved to a significantly greater extent than fluoxetine-treated patients in most measures . CONCLUSION While nefazodone and fluoxetine showed equivalent antidepressant efficacy , more objective , subjective , and clinician-rated measures of sleep disturbance were improved during treatment with nefazodone than with fluoxetine . These results suggest that antidepressant effects of medications can occur independently of drug-induced changes in objective , subjective , and clinician-rated measures of sleep . Further studies , including parallel placebo-controlled comparisons with nefazodone , are needed to further test this hypothesis BACKGROUND Controversy exists over antidepressant use in rapid-cycling bipolar disorder . AIMS Exploratory analysis of safety and efficacy of fluoxetine v. lithium monotherapy in individuals with rapid- v. non-rapid-cycling bipolar II disorder . METHOD R and omised , double-blind , placebo-controlled comparison of fluoxetine v. lithium monotherapy in patients initially stabilised on fluoxetine monotherapy ( trial registration NCT00044616 ) . RESULTS The proportion of participants with depressive relapse was similar between the rapid- and non-rapid-cycling groups ( P = 0.20 ) . The odds of relapse were similar between groups ( P = 0.36 ) . The hazard of relapse was similar between groups ( hazard ratio 0.87 , 95 % CI 0.40 - 1.91 ) . Change in mania rating scores was similar between groups ( P = 0.86 ) . There was no difference between groups in the rate of syndromal ( P = 0.27 ) or subsyndromal ( P = 0.82 ) hypomania . CONCLUSIONS Depressive relapse and treatment-emergent mood conversion episode rates were similar for lithium and fluoxetine monotherapy and placebo during long-term , relapse-prevention therapy of rapid- and non-rapid-cycling bipolar II disorder OBJECTIVE We investigated the frequency of quality assessment of r and omized controlled trials within systematic review s and the incorporation of the quality assessment in the analysis . STUDY DESIGN AND SETTING We included new systematic review s of at least five trials of therapeutic or preventive interventions that appeared in issue 2 , 2003 , of the Cochrane Data base of Systematic Review s. All systematic review s in the 2002 issues of the Annals of Internal Medicine , BMJ , JAMA , and Lancet were identified in Pubmed . All review s were assessed under unblinded conditions using preprinted extraction forms . RESULTS Trial quality was assessed in all Cochrane review s and most ( 74 % ) of the paper review s. When we excluded 11 paper review s that were also published as Cochrane review , the percentage remained similar ( 67 % ) . Fifty percent of all Cochrane review s and 61 % of all paper review s incorporated the results of the quality assessment in the analysis . CONCLUSION Half of the review s did not incorporate the results of the quality assessment in the analysis . Authors , peer- review ers , and editors should no longer focus exclusively on whether quality assessment has been performed but should also concentrate on incorporation of quality assessment s in the analysis of the systematic review & NA ; The abrupt discontinuation of antidepressants can result in a syndrome of adverse events , including somatic , mood and psychomotor reactions . This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors ( SSRIs ) on cognitive and psychomotor function . Eighty‐seven patients receiving maintenance therapy with fluoxetine , sertraline , paroxetine or citalopram had their treatment interrupted for 4‐7 days using double‐blind placebo . Assessment s of aspects of cognitive and psychomotor performance , mood and symptoms were carried out at each visit . Following interruption of treatment , significant differences between the groups emerged . Paroxetine treated patients experienced significantly more cognitive failures ( P = 0.007 ) , poorer quality of sleep ( P = 0.016 ) , and an increase in depressive symptoms , as rated both subjectively , using the Zung scale ( P = 0.006 ) and by the clinician , using the Montgomery‐Asberg Depression Rating Scale ( P = 0.0003 ) and Clinical Global Impression ( P = 0.0003 ) , compared to some or all of the other drugs . All changes were reversed on reinstatement of treatment . Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning , which may be related to the antidepressant discontinuation syndrome . These effects are not evident in patients receiving fluoxetine , sertraline and citalopram , suggesting they are not an SSRI class phenomenon . Int Clin Psychopharmacol 15:305‐318 © 2000 Lippincott Williams & Anxious depression , defined as major depressive disorder ( MDD ) accompanied by high levels of anxiety , seems to be both common and difficult to treat , with antidepressant monotherapy often yielding modest results . We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression . We conducted a post-hoc analysis of an existing data set ( N=80 ) , from a 3-week , r and omized , double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD . The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement . Anxious depression status was not found to predict symptom improvement , or serve as a moderator of clinical improvement to cotherapy versus monotherapy . However , the advantage in remission rates in favor of cotherapy versus monotherapy was , numerically , much larger for patients with anxious depression ( 32.2 % ) than it was for patients without anxious MDD ( 9.7 % ) . The respective number needed to treat statistic for these two differences in response rates were , approximately , one in three for patients with anxious depression versus one in 10 for patients without anxious depression . The efficacy of fluoxetine-clonazepam cotherapy  compared with fluoxetine monotherapy  was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression The efficacy and safety of fluoxetine , a new antidepressant agent , were assessed in a double-blind , parallel , r and omized study of 44 out patients with major depressive disorder . Following a 1-week placebo period , patients were r and omly assigned to either fluoxetine or amitriptyline for a period of 5 weeks . The mean maintenance dosages were 55 mg/day for fluoxetine and 159 mg/day for amitriptyline . Both drugs were effective in relieving the symptoms of depression . The most frequently reported side effects were nausea and nervousness for fluoxetine , and dry mouth , dizziness , and drowsiness for amitriptyline Clinicians are faced with the challenge of keeping abreast of the rapidly growing clinical literature . One method that can help clinicians meet this challenge is the provision of synthesis ed evidence by such groups as the Cochrane Collaboration . The Cochrane Library contains the full text of Cochrane review s , which bring together information on controlled studies ( mostly r and omised controlled trials ) in a st and ard format . The first 1000 review s were prepared by early 2001 , and there are now more than 1600 available.1 The task of synthesis ing the clinical literature is a huge undertaking , and in this editorial we will use the number of studies in a typical Cochrane review to provide an estimate of the number of Cochrane review s that are needed to cover all trials currently in the Cochrane Central Register of Controlled Trials ( CENTRAL ) .2–3 CENTRAL is the main source used by Cochrane review ers to locate studies . It contains citations to more than 300 000 reports of studies , which may be eligible for inclusion in Cochrane review s. CENTRAL is reference-based rather than study -based , and therefore multiple references may be included for a single trial . We examined 1000 review s from the Cochrane Data base of Systematic Review s in Issue 1 , 2001 , of the Cochrane Library to determine the average number of studies , and references to the studies , included in a typical Cochrane review . Comparing this with an estimate for the number of relevant references in CENTRAL , it is possible to predict how many more Cochrane review s are needed to cover the healthcare research already in CENTRAL . Of the 1000 review s , 11 had been replaced by notices of withdrawal , leaving 989 complete review s. The included studies in these review s were h and counted by 1 author Background : Maintenance antidepressant ( AD ) medication is the most commonly used preventive strategy in a highly recurrent disease , i.e. depression . Little is known about the discontinuation of maintenance AD use and the association with recurrence in daily clinical practice . The purpose was to examine the discontinuation rate of maintenance AD in daily clinical practice in recurrently depressed patients and the associated risk of recurrence . Methods : Prospect ively AD maintenance medication and recurrence were examined in 172 euthymic patients with recurrent depression .  AD user profiles before recurrence ( nonusers , intermittent users , continuous users ) were examined and related to recurrence over a 2-year follow-up period . Results : Less than half of the patients ( 42 % ) used AD continuously . Taking into account the minimal required adequate used dosage ( ≧20 mg fluoxetine equivalent ) , only 26 % of the patients used AD as recommended by international guidelines . Despite continuous use of AD , 60.4 % relapsed in 2 years . This relapse rate was comparable to the rate of the intermittent users ( 63.6 % ) . In patients who stopped taking AD after remission and who received additional preventive CT , the recurrence rates were significantly lower than in non-AD-using patients treated with usual care ( 8 vs. 46 % ) . Conclusions : The majority of recurrently depressed patients treated with AD  discontinue maintenance AD therapy in daily primary and secondary clinical practice . AD seems to offer poor protection against relapse in this patient group . Patients who stopped using AD experienced less relapse , especially if they were treated with preventive CT . Alternative maintenance treatments ( including preventive cognitive therapy after discontinuation of AD ) should be studied in recurrently depressed patients with intermittent good remission , not only in secondary but also in primary care The effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients . The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment . However , that difference was no longer apparent during the remainder of the study . The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone Background —Acupuncture has recently been studied in assisted reproductive treatment ( ART ) although its role in reproductive medicine is still debated . Objectives —To determine the effectiveness of acupuncture  in the outcomes of ART . Search strategy —All reports which describe r and omised controlled trials of acupuncture in assisted conception were obtained through search es of the Menstrual Disorders and Subfertility Group Specialised Register , CENTRAL , Ovid MEDLINE ( 1996 to August 2007 ) , EMBASE ( 1980 to August 2007 ) , CINAHL ( Cumulative Index to Nursing & Allied Health Literature ) ( 1982 to August 2007 ) , AMED , National Research Register , Clinical Trials register ( www . clinical trials.gov ) , and the Chinese data base of clinical trials . Selection Criteria —R and omised controlled trials of acupuncture for couples who were undergoing ART comparing acupuncture treatment alone or acupuncture with concurrent ART versus no treatment , placebo or sham acupuncture plus ART for the treatment of primary and secondary infertility . Women with medical illness deemed contraindications for ART or acupuncture were excluded . Data Collection and Analysis —Sixteen r and omised controlled trials were identified that involved acupuncture and assisted conception . Thirteen trials were included in the review and three were excluded . Quality assessment and data extraction were performed independently by two review authors . © 2010 Elsevier Inc. All rights reserved . Corresponding author : Eric Manheimer , MS , Research associate , University of Maryl and School of Medicine , Center for Integrative Medicine East Hall , 520 W. Lombard Street Baltimore , MD 21201 , emanheimer@compmed.umm.edu , Telephone : 410 - 706 - 6169 , Fax : 410 - 706 - 6214 . * Both authors contributed equally to this work . The Cochrane Complementary Medicine Field is the group within the Cochrane Collaboration focused on facilitating the conduct of Cochrane systematic review s of CAM therapies . The CAM Field represents an international collaborative effort among research ers , clinicians , consumers , and CAM practitioners from nearly every continent . The Field ’s central office is located at the Center for Integrative Medicine , University of Maryl and School of Medicine , 520 W. Lombard St , Baltimore , MD 21201 . For more information , contact Eric Manheimer at : emanheimer@compmed.umm.edu . Publisher 's Discl aim er : This is a PDF file of an unedited manuscript that has been accepted for publication . As a service to our customers we are providing this early version of the manuscript . The manuscript will undergo copyediting , type setting , and review of the result ing proof before it is published in its final citable form . Please note that during the production process errors may be discovered which could affect the content , and all legal discl aim ers that apply to the journal pertain . NIH Public Mr. B , age 20 , has taken a semester leave from college because of gradually worsening depressed mood . Over the past 2 months he has lost interest in jogging and playing piano -- which he usually enjoys . He reports reduced libido , middle insomnia , loss of appetite , feeling as if his head is " full of cotton , " trouble concentrating , and waking in the morning with a sense of dread . His anxiety dissipates during the day , but he continues to feel sad and sometimes weepy , which is unusual for him . [ ILLUSTRATION OMITTED ] Mr. B reports feeling hopeless at times and has had vague thoughts about life being " not worth it if I continue to feel like this " but denies specific suicide plans . Your initial impression is that Mr. B is in the midst of a major depressive episode and that a selective serotonin reuptake inhibitor ( SSRI ) is indicated . As you finish taking his history , you run through your mind the pros and cons of the recommendation you will make to him . Do SSRIs raise or lower the risk for suicidal behavior in young adults such as Mr. B ? The answer is complicated and goes beyond an " either/or " question , as the FDA acknowledged in May 2007 when it : * extended the black-box warning of increased suicidality risk with antidepressants to cover adults age 18 to 24 as well as children and adolescents * included language in the warning about the benefits of treating depression and the suicide risk associated with untreated depression , given concerns about declining antidepressant prescriptions and rising suicides among youth . ( 1 ) To help you make informed decisions when treating depression in adults , this article review s the studies leading up to and following the FDA 's meta- analysis of antidepressant trial data in patients age 18 and older . Our goal is to provide a framework for clinical treatment of adults age 18 to 24 and those age [ greater than or equal to]25 . First hints of suicidality  SSRIs revolutionized depression treatment . From 1985 to 1999 , annual U.S. antidepressant prescriptions quadrupled , with SSRIs accounting for 70 % of the increase ( see " Antidepressants and suicide risk , 1985 to 2007 , " pages 36 - 37 ) . At the same time , the age-adjusted suicide rate : * dropped 22.5 % for women ( who account for twice as many antidepressant prescriptions as men ) * dropped 12.8 % for men ( without change in the rank order of suicide methods ) . ( 2 ) For many patients , increased antidepressant use improved treatment of major depressive and other antidepressant-responsive disorders . In 1990 , however , case reports suggested SSRIs might cause suicidal thoughts or behavior . ( 3 ) Hypothesized mechanisms included increased aggression ( 4 ) and akathisia . ( 5 ) An FDA review found no proof , and a meta- analysis of data from 17 double-blind , r and omized , controlled trials found no association between fluoxetine and suicidal thoughts or behavior . ( 6 ) The debate rekindled in June 2003 when the British Committee on Safety of Medicines warned against using paroxetine or venlafaxine in children . After conducting its own meta- analysis , the FDA in 2004 ordered a black-box warning about suicidality and the use of  antidepressants in children and adolescents ( Box ) . ( 7 ) After the pediatric ' black box . '  Antidepressant prescriptions for  children and adolescents declined in the years 2003 to 2004 , as did diagnosis of pediatric depression . ( 8 - 10 ) Antidepressant prescribing also showed signs of shifting from general practitioners to psychiatrists . ( 8) At the same time , the suicide rate  among youth age 60 ,  SSRI prescriptions continued to rise and suicide rates fell , ( 9 ) a pattern of change consistent with antidepressants protecting against suicide . An independent meta- analysis by Bridge et al ( 12 ) examined the pediatric trial data used in the FDA meta- analysis plus 7 additional studies . The selective noradrenaline re-uptake inhibitor reboxetine may have advantages over the selective serotonin re-uptake inhibitors fluoxetine and citalopram , in effects on sexual function and satisfaction . The effects of reboxetine and paroxetine on sexual function were compared by examining data from the UK centres in an international double-blind flexible-dose parallel-group multi-centre r and omized controlled trial of acute treatment of patients with DSM-IV major depression . Patients were r and omly assigned to receive reboxetine ( 4 mg b.d . ) or paroxetine ( 20 mg mane ) using a double-dummy technique to preserve the blind . The dosage could be increased at day 28 ( to reboxetine 4 mg mane , 6 mg nocte ; or paroxetine 20 mg b.d . ) . Antidepressant efficacy was assessed by the 21-item Hamilton Rating Scale for Depression ( HAM-D ) and Clinical Global Impression Scale for Severity ( CGI-S ) at all study visits , and the Clinical Global Impression of Improvement ( CGI-I ) at each visit after r and omization . Sexual function and satisfaction was assessed by visual analogue scale ( VAS ) items of the Rush Sexual Inventory completed at baseline and days 28 and 56 . There were no significant differences between groups in demographic or clinical features at baseline . There was a gradual reduction in severity of depressive symptoms  ( reboxetine , 14.3 ; paroxetine , 12.0 : observed case analysis ) , with no significant differences between groups . There were significant differences ( p 0.05 ) , with advantages for reboxetine , at Week 4 and Week 8 on the VAS item assessing ability to become sexually excited , and non-significant trends with advantages for reboxetine , in frequency of sexual thoughts at Week 4 ( p 0.05 ) and Week 8 ( p 0.08 ) ; and in desire to initiate sexual activity at Week 4 ( p 0.09 ) . Exclusion of patients who had ever experienced sexual dysfunction with any medication prior to participation in this study ( n 10 ) reduced the statistical significance of the findings , although there were still numerical advantages for reboxetine .  Sexual function and satisfaction in depressed patients improves during double-blind acute treatment with reboxetine or paroxetine , but this improvement is greater and more rapid with reboxetine Objective : This is a retrospective study to add to the existing body of clinical information regarding male sexual side effects associated with antidepressants . From the chart review , thirty-four out of eighty male patients were identified to have reported loss of libido , erectile difficulty , anorgasmia , and delayed ejaculation while receiving pharmacotherapy of selective serotonin reuptake blockers ( fluoxetine , paroxetine , and sertraline ) ; tricyclic antidepressants ( nortriptyline , imipramine , amitriptyline , desipramine , and clomipramine ) ; and a monoamine oxidase inhibitor ( phenelzine ) . Method : The authors also discussed the management of these sexual side effects by waiting for spontaneous remission , reducing the dosage level , and substituting the offending drug with other antidepressants . Results : This article underscores the underreported nature of antidepressant-associated sexual dysfunction , the high incidence of SSRI-associated sexual side effects , equal potentials in causing sexual side effects among the three SSRI 's , the low incidence rate of sexual adverse effects from bupropion , and the minimal need to add an antidote if the side effects are to be managed systematic ally . Conclusions : Finally , male sexual side effects can occur r and omly and involve any sexual phase r and omly , and the treatment approaches are similar , regardless of the types of sexual dysfunction associated with antidepressants Background : While testosterone 's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature , no placebo-controlled trial selecting for depressive disorders and including a st and ard antidepressant has been conducted . Accordingly , this double-blind trial was design ed to determine whether testosterone , as well as fluoxetine , is superior to placebo for depression , fatigue , or both . Method : One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition depressive disorder entered the 8-week trial and were r and omized to testosterone ( up to 400 mg IM testosterone cypionate biweekly ) , fluoxetine ( up to 60 mg/d ) , or double placebo . Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue , the Hamilton Rating Scale for Depression , and the Chalder Fatigue Scale . Results : Ninety men completed the trial . In intention-to-treat analyses , mood response rates were 54 % , 47 % , and 44 % for fluoxetine , testosterone , and placebo , respectively . Among completers , mood response rates were 70 % , 57 % , and 53 % , respectively ; in neither analysis were differences between treatments statistically significant . In contrast , testosterone was superior to fluoxetine and placebo for completers regarding fatigue . In intention-to-treat analysis , response rates were 39 % , 56 % , and 42 % for fluoxetine , testosterone , and placebo , respectively , and for study completers , 41 % , 63 % , and 52 % , respectively , ( P < 0.05 ) , Conclusion : While over 50 % of patients treated with testosterone reported improved mood , this rate was not statistically superior to placebo . Thus , our findings do not support prescription of testosterone as a first-line treatment for depressive disorders  in HIV-positive men . However , if vali date d in additional studies , testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression Background Research suggests that depressive disorders exist on a continuum , with subthreshold symptoms causing considerable population burden and increasing individual risk of developing major depressive disorder . An alternative strategy to professional treatment of subthreshold depression is population promotion of effective self-help interventions that can be easily applied by an individual without professional guidance . The evidence for self-help interventions for depressive symptoms is review ed in the present work , with the aim of identifying promising interventions that could inform future health promotion campaigns or stimulate further research . Methods A literature search for r and omised controlled trials investigating self-help interventions for depressive disorders or depressive symptoms was performed using PubMed , PsycINFO and the Cochrane Data base of Systematic Review s. Reference lists and citations of included studies were also checked . Studies were grouped into those involving participants with depressive disorders or a high level of depressive symptoms , or non- clinical ly depressed participants not selected for depression . A number of exclusion criteria were applied , including trials with small sample sizes and where the intervention was adjunctive to antidepressants or psychotherapy . Results The majority of interventions search ed had no relevant evidence to review . Of the 38 interventions review ed , the ones with the best evidence of efficacy in depressive disorders were S-adenosylmethionine , St John 's wort , bibliotherapy , computerised interventions , distraction , relaxation training , exercise , pleasant activities , sleep deprivation , and light therapy . A number of other interventions showed promise but had received less research attention . Research in non- clinical sample s indicated immediate beneficial effects on depressed mood for distraction , exercise , humour , music , negative air ionisation , and singing ; while potential for helpful longer-term effects was found for autogenic training , light therapy , omega 3 fatty acids , pets , and prayer . Many of the trials were poor quality and may not generalise to self-help without professional guidance . Conclusion A number of self-help interventions have promising evidence for reducing subthreshold depressive symptoms . Other forms of evidence such as expert consensus may be more appropriate for interventions that are not feasible to evaluate in r and omised controlled trials . There needs to be evaluation of whether promotion to the public of effective self-help strategies for subthreshold depressive symptoms could delay or prevent onset of depressive illness , reduce functional impairment , and prevent progression to other undesirable outcomes such as harmful use of substances BACKGROUND Tricyclic antidepressants and serotonin reuptake inhibitors are considered to be equally effective , but differences may have been obscured by internally inconsistent measurement scales and inefficient statistical analyses . AIMS To test the hypothesis that escitalopram and nortriptyline differ in their effects on observed mood , cognitive and neurovegetative symptoms of depression . METHOD In a multicentre part-r and omised open-label design ( the Genome Based Therapeutic Drugs for Depression ( GENDEP ) study ) 811 adults with moderate to severe unipolar depression were allocated to flexible dosage escitalopram or nortriptyline for 12 weeks . The weekly Montgomery-Asberg Depression Rating Scale , Hamilton Rating Scale for Depression , and Beck Depression Inventory were scored both conventionally and in a more novel way according to dimensions of observed mood , cognitive symptoms and neurovegetative symptoms . RESULTS Mixed-effect linear regression showed no difference between escitalopram and nortriptyline on the three original scales , but symptom dimensions revealed drug-specific advantages . Observed mood and cognitive symptoms improved more with escitalopram than with nortriptyline .  Neurovegetative symptoms improved more with nortriptyline than with escitalopram . CONCLUSIONS The three symptom dimensions provided sensitive descriptors of differential antidepressant response and enabled identification of drug-specific effects
Conclusions : International differences in prescriber behaviour may influence , and in turn be influenced by , the conduct of clinical trials .
Objective : International differences are thought to exist in dosages used by clinicians treating mood disorders .
This study examined international dosage differences in antidepressant clinical trials , using a data base formed and maintained as a component of a Cochrane review of comparative clinical trials of fluoxetine .