(S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD). Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features. Citalopram versus desipramine in treatment resistant depression: Effect of continuation or switching strategies. A randomized open study Using non-steroidal anti-inflammatory drugs in the treatment of depression. Response to an open trial of a second SSRI in major depression. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor Design and Rationale for a Randomized, Controlled Trial of Interpersonal Psychotherapy and Citalopram for Depression in Coronary Artery Disease (CREATE) Prediction of the response to citalopram and reboxetine in post-stroke depressed patients Faster Onset of Antidepressant Effects of Citalopram Compared With Sertraline in Drug-Naïve First-Episode Major Depressive Disorder in a Chinese Population: A 6-Week Double-Blind, Randomized Comparative Study The treatment of SSRI-resistant depression in adolescents (TORDIA): in search of the best next step. A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Reboxetine and citalopram in panic disorder: a single-blind, cross-over, flexible-dose pilot study Citalopram versus fluoxetine: a double‐blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. A Naturalistic Long-Term Comparison Study of Selective Serotonin Reuptake Inhibitors in the Treatment of Panic Disorder
Major Depressive Disorder ( MDD ) is a common illness that affects > 40 million people worldwide , and antidepressants are one of the top 5 leading classes of pharmaceuticals with annual sales in excess of $ 20 billion ( 1,2 ) . The current st and ard of care focuses on serotonin−norepinephrine reuptake inhibitors ( SNRI ) and selective serotonin reuptake inhibitors ( SSRI ) ; however , patients often respond poorly . In fact , the National Institute of Mental Health conducted a large-scale STAR*D study and found that 63 % of patients did not achieve remission with the SSRI Citalopram ( 1,3−5 ) . Citalopram was originally developed in Lundbeck in the late 1980s and sold as a racemate . Lundbeck , in collaboration with Forest Laboratories , has recently released an up date d version called Escitalopram ( also known as Lexapro ) , which is the single (S)-enantiomer of the racemic Citalopram , which provided new patent life . In 2009 , Lexapro garnered ∼$2.7 billion in sales in the US ( Figure ​(Figure1)1 ) ( 2 ) . Figure 1 Structures of Citalopram , Escitalopram , and TC-5214 . An alternative hypothesis for depression emerged over 30 years ago and suggests that a cholinergic imbalance ( hypercholinergic tone ) is a major factor in depression , and both clinical and pre clinical studies have implicated neuronal nicotinic cholinergic receptors ( NNRs ) rather than muscarinic receptors ( 5 ) . On the basis of these data , AstraZeneca and Targacept have explored the role of NNR antagonism in depressive disorders and recently announced the initiation of a phase III trial of TC-5214 , (S)-(+)-mecamylamine , as an adjunct therapy with Citalopram . TC-5214 is a low molecular weight ( 167.3 as free base , 203.8 as the HCl salt ) , basic ( pKa = 11.5 ) compound , freely soluble in water . While TC-5214 displays modest selectivity among the NNRs , its antidepressive properties are presumed to be the result of inhibition of the α4β2 NNRs . Pre clinical ly , TC-5214 demonstrated robust efficacy in rodent models of depression ( forced swim and behavioral despair ) and anxiety ( social interaction and light/dark chamber ) . The (S)-enantiomer showed a superior preclincial safety profile compared to that of either the racemic compound or the (R)-enantiomer . Furthermore , TC-5214 was well tolerated in both acute and chronic toxicity tests , displayed no mutagenic potential , and possessed pharmacokinetic properties suitable for development ( 3−5 ) . In 2009 , Targacept conducted a double blind , placebo controlled phase IIb trial in MMD patients with TC-5214  , as an adjunct treatment with Citalopram demonstrated superiority to placebo in both primary and secondary outcome measures ( 3−5 ) . This positive outcome led to a license agreement in December of 2009 with AstraZeneca for the global development and commercialization of TC-5214 . On June 23 , 2010 , AstraZeneca and Targacept announced the enrollment of the first patients in the phase III trial of TC-4214 . Coined the Renaissance Program , the trial will include two fixed dose and two flexible dose phase III studies of TC-5214 as an adjunct treatment for patients with poor response to st and ard SSRI or SNRI therapy . Each fixed dose and flexible dose phase III study will employ an initial open label phase wherein patients diagnosed with MDD receive one of seven marketed SSRIs or SNRIs for eight weeks to assess therapeutic response . Patients that respond poorly will then be r and omized into a double blind , placebo controlled second phase to receive a fixed or a flexible dose of TC-5214 or placebo , twice daily , while continuing the SSRI or SNRI therapy . A change from double blind baseline for TC-5214 on the Montgomery−Asberg Depression Rating Scale ( MADRS ) as compared to placebo is the primary outcome measure . The program will also include a double blind , placebo controlled study for long-term safety . The companies plan completion of the trial in time to file an IND with the FDA in late 2012 ( 3−5 ) . MMD is the leading cause of disability in the US for people 15−44 , and the burden for MDD in the US in 2000 was in excess of $ 83 billion ( 6 ) . When broken down , the workplace burden for lost time is ∼62 % , treatment costs account for ∼31 % , and suicide related costs average 7 % ( 6 ) . For those suffering from MDD with poor response to SSRIs and SNRIs , the phase III data is anxiously awaited CONTEXT Little is known about selecting among second-step medications for major depressive disorder after intolerance or lack of remission with an initial selective serotonin reuptake inhibitor . OBJECTIVE To determine whether sociodemographic , clinical , or first-step treatment features predict remission with or intolerance overall or differentially to any 1 of 3 second-step medications after an unsatisfactory outcome with citalopram hydrobromide . DESIGN An equipoise stratified r and omized study . Participants were recruited from July 17 , 2001 , through April 20 , 2004 . SETTING Public or private sector primary care ( n = 18 ) and psychiatric care ( n = 23 ) setting s across the United States . PARTICIPANTS Representative out patients aged 18 to 75 years with nonpsychotic major depressive disorder ( N = 727 ) . INTERVENTIONS Sustained-release bupropion hydrochloride was started at 150 mg/d and incrementally increased to 400 mg/d . Sertraline hydrochloride was started at 50 mg/d and incrementally increased to 200 mg/d . Extended-release venlafaxine hydrochloride was started at 37.5 mg/d and incrementally increased to 375 mg/d . MAIN OUTCOME MEASURES The 16-item Quick Inventory of Depressive Symptomatology , Self-Rated and the Frequency , Intensity , and Burden of Side Effects Rating . RESULTS Remission was more likely among participants who were white , employed , cohabiting or married , or privately insured or who had prior intolerance to citalopram or at least a response to citalopram , and no prior suicide attempts . Remission was less likely among participants with concurrent generalized anxiety , obsessive-compulsive , panic , or posttraumatic stress disorders ; social phobia ; anxious or melancholic features ; or more severe depression . Intolerance was less likely for Hispanic participants , but more likely for participants with previous suicide attempts or intolerance to citalopram . Participants with concurrent substance use were less likely to remit ( odds ratio , 0.37 ) and more likely not to tolerate extended-release venlafaxine . Intolerance to citalopram was associated with intolerance to sertraline ( P = .04 ) . CONCLUSIONS Clinical , demographic , and treatment history were of little value in recommending 1 medication vs another as a second-step treatment for major depressive disorder . Participants most likely to remit in the second step had less Axis I psychiatric disorder comorbidity , less social disadvantage , and at least a response to citalopram in the first step . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00021528 Abstract Objectives . Evidence in favour of switching between selective serotonin reuptake inhibitor ( SSRI ) and tricyclic ( TCA ) antidepressants in treatment resistant depression has been tested in a few studies only , consequently a prospect i ve study was undertaken to evaluate the impact of switching strategies . Methods . One hundred eighty-nine patients who failed to respond to a previous antidepressant were r and omised to four arms : firstly they received citalopram or desipramine for a 4-week period ; secondly , those who failed to respond were treated for a further 4-week period with the same antidepressant ( citalopram-citalopram and desipramine-desipramine arms ) or switched to the alternate one ( citalopram-desipramine and desipramine-citalopram arms ) . Results . There was no difference in the first 4-week phase between patients receiving citalopram versus desipramine in Hamilton Rating Scale for Depression ( HRSD ) , Montgomery – Asberg Depression Rating Scale ( MADRS ) , and Clinical Global Impression ( CGI ) scores . In the second 4-week phase remitter rates were higher among non-switched patients ( P = 0.04 ) . Moreover , considering HRSD and MADRS , switched patients reported significantly higher scores ( P ≤ 0.02 for both scales at each time-point ) . Conclusions . This study supports the thesis that switching from an SSRI to a TCA ( and vice versa ) in non-responders to a 4-week trial of an SSRI/TCA is not associated with improved response . The result goes in the opposite direction to that predicted by current guidelines BACKGROUND clinicians have long noticed a correlation between physiological markers of inflammation and depression . The best-known example is the activation of the hypothalamus-pituitary-adrenal axis and cortisol secretion ; however more recent studies have demonstrated increased salivary prostagl and ins and plasma acute phase proteins in depressed patients . To date four r and omised controlled trials have used celecoxib or rofecoxib as adjuncts to serotonin selective reuptake inhibitors in the treatment of depression . These suggested a statistically significant decrease in depressive symptoms in the patients taking NSAIDs and SSRIs , compared to patients taking SSRIs alone . Interpretation of these results is limited by the small sample size and short duration of these preliminary studies . The research only considers depressed patients receiving treatment in secondary care ; no study has examined the effectiveness of NSAIDs as an adjunct in primary care , even though most cases of depression in the UK are managed in the community by general practitioners . PROPOSAL we propose a multi-centre double-blinded r and omised controlled trial with two objectives : to determine whether citalopram plus celecoxib dual therapy achieves a greater reduction in depressive symptoms ( quantified using the Hamilton Depression Rating Scale ( HDRS ) ) within four weeks , compared to citalopram monotherapy ; and to determine whether citalopram plus celecoxib dual therapy is more likely to achieve remission ( HDRS score ? 7 ) of moderate to severe depression within six months , compared with citalopram monotherapy . The endpoints will be the reduction in HDRS score after 4 weeks of treatment , and the HDRS score after 26 weeks of treatment . The study will enrol 452 participants from general practice s who have a moderate or severe , current or recurrent major depressive episode when medication with an SSRI is considered . The study population will be stratified according to age , sex , HDRS score , age of onset of first episode , number of previous depressive episodes and duration of current episode . The population will then be r and omised into two groups . Subjects will be interviewed to determine HDRS score , measure blood pressure , count pills and discuss side-effects . This will occur weekly for the first four weeks , and every four weeks thereafter 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 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 Findings from the National Institute of Mental Health 's Sequenced Treatment Alternatives to Relieve Depression trial indicate that approximately 50 % of patients with major depressive disorder do not experience a treatment response after adequate first-line treatment with a selective serotonin reuptake inhibitor ( SSRI ) . This study was design ed to test the hypothesis that , after treatment failure with an SSRI , switching to venlafaxine extended release ( ER ) would offer advantages over switching to another SSRI , citalopram . The objectives of this trial were to compare the efficacy and safety of venlafaxine ER and citalopram in the treatment of moderate-to-severe depression in patients who did not experience a treatment response to an SSRI other than citalopram  and to investigate the effects of severity of depression by categorizing treatment groups according to baseline severity . This was a 12-week , double-blind , r and omized , parallel-group , multicenter study . Participants were adult out patients who , following 8 weeks of monotherapy with an adequate dosing regimen of an SSRI other than citalopram  and had not responded , met the diagnostic criteria for depression as described in the Diagnostic and statistical manual of mental disorders , fourth edition , and had a score ≥20 on the 21-item Hamilton Rating Scale for Depression ( HAM-D21 ) . After a 7-day screening period , patients were r and omly assigned to receive venlafaxine ER 75 mg/day or citalopram 20 mg/day for the first 2 weeks . Doses could be increased every 2 weeks through week 6 . Treatment lasted 12 weeks and was followed by a 1-week tapering period . Maximum dosages were venlafaxine ER 300 mg/day or citalopram 60 mg/day . The primary end point was the final on-therapy total HAM-D21 score . To investigate the treatment effects of the severity of depression on efficacy , a subgroup analysis was performed for baseline HAM-D21 total score ≤31 and > 31 . The analyses for HAM-D21 , Montgomery – Åsberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions – Severity ( CGI-S ) , and Clinical Global Impressions – Improvement scores were based on intent-to-treat ( ITT ) population , for both the primary analysis and subgroup analysis according to baseline HAM-D21 total scores ≤31 or > 31 . Safety assessment s included the recording of adverse events ( AEs ) . A total of 406 patients ( 200 venlafaxine ER , 206 citalopram ) were r and omly assigned and 396 patients were included in the ITT population ( 194 venlafaxine ER , 202 citalopram ) . Treatment groups were similar in terms of demographics and baseline psychiatric assessment s. Two hundred and eighty-four patients ( 137 venlafaxine ER , 147 citalopram ) were present in the ITT population with a baseline HAM-D21 total score ≤31 and 112 patients ( 57 venlafaxine ER , 55 citalopram ) in the > 31 group . In the primary analysis , there was no statistical difference between groups . The group with a baseline HAM-D21 total score of 20–31 did not differ significantly in any efficacy parameters . In the group with a baseline HAM-D21 total score > 31 , the venlafaxine ER group differed significantly from the citalopram group on the primary end point HAM-D21 total score ( P=0.0121 ) . The secondary end point CGI-S score was statistically significant ( P=0.0359 ) , although the MADRS total score ( P=0.0930 ) was not . AEs were reported by 57.8 and 63.4 % of venlafaxine ER and citalopram patients , respectively . Overall discontinuation rates were 24.5 % for venlafaxine ER and 20.9 % for citalopram  . Discontinuation rates owing to an AE as a primary or secondary reason were 5.5 % for venlafaxine ER and 5.3 % for citalopram . Overall , venlafaxine ER and citalopram showed similar efficacy in patients who had an inadequate response to an SSRI . In the subset of more severely depressed patients , venlafaxine ER was significantly more effective on a number of efficacy measures . Patients who remain severely depressed following treatment with an SSRI may gain more benefit from the dual-action drug venlafaxine , rather than switching to another SSRI Objective : Recognition that depression is associated with increased morbidity and mortality in coronary artery disease ( CAD ) patients has augmented the need for evidence -based treatment guidelines . This article presents the design of a multisite , Canadian trial of the efficacy , safety , and tolerability of interpersonal psychotherapy ( IPT ) , an empirically supported , depression-focused therapy , and the selective serotonin reuptake inhibitor citalopram , alone or in combination , in the treatment of major depression in CAD patients . Methods : Two hundred eighty stable CAD patients with a current major depressive episode of at least 4 weeks ’ duration , based on the Structured Clinical Interview for Depression ( SCID ) , and who have a baseline score > 19 on a central ized , telephone-administered , 24-item Hamilton Depression Rating Scale ( HAM-D ) will be r and omly assigned to receive 12 weekly IPT sessions or 12 weekly sessions of st and ardized clinical management ( CM ) . Patients are also r and omly assigned to receive 20 to 40 mg per day of citalopram or pill-placebo . This results in a 2-by-2 factorial design with four groups : IPT plus pill-placebo , IPT plus citalopram , CM plus pill-placebo , and CM plus citalopram . This permits the evaluation of both IPT and citalopram . Blinded , central ized , 24-item , HAM-D telephone ratings constitute the primary outcome variable . The self-report Beck Depression Inventory-II is the secondary outcome . Analyses will involve the intent-to-treat principle with last observation carried forward for incomplete assessment s. Results : Not applicable . Conclusions : The results of this trial will contribute to the development of evidence -based clinical guidelines for managing depression in the context of CAD . CREATE = Canadian Cardiac R and omized Evaluation of Antidepressant and Psychotherapy Efficacy ; IPT = interpersonal psychotherapy ; CAD = coronary artery disease ; SCID = Structured Clinical Interview for Depression ; HAM-D = Hamilton Depression Rating Scale ; CM = clinical management ; SADHART = Sertraline Antidepressant Heart Attack R and omized Trial ; ENRICHD = Enhancing Recovery in Coronary Heart Disease ; SSRI = selective serotonin reuptake inhibitor ; ECG = electrocardiogram ; NIMH = National Institute of Mental Health ; TDCRP = Treatment of Depression Collaborative Research Program ; MMSE = Mini-mental Status Exam ; STAR*D = Sequenced Treatment Alternatives to Relieve Depression ; IDS = Inventory for Depressive Symptomatology ; BDI-II = Beck Depression Inventory-II ; IPRI = Interpersonal Relationship Inventory ; FPI = Functional Performance Inventory ; SAE = serious adverse event ; LOCF = last observation carried forward ; DSMB = data safety monitoring board Rationale and objective Depression is a significant complication of stroke . The effectiveness of antidepressant drugs in the management of post-stroke depression ( PSD ) has been widely investigated . However , the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies . Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor ( SSRI ) , citalopram , and a noradrenaline reuptake inhibitor ( NARI ) , reboxetine , in post-stroke patients affected by anxious depression or retarded depression . Methods This was a r and omized double-blind study . Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table . R and omisation was planned so that 50 % of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50 % were assigned to treatment with reboxetine . The Beck Depression Inventory ( BDI ) , the Hamilton Depression Rating Scale ( HDRS ) and a synoptic table were used to score depressive symptoms . Results Both citalopram and reboxetine showed good safety and tolerability . Citalopram exhibited greater efficacy in anxious depressed patients , while reboxetine was more effective in retarded depressed patients . Conclusions Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects . In addition , PSD patients should be classified according to their clinical profile ( similarly to patients affected by primary depression ) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients Several previous studies , including a meta- analysis , reported no significant differences between various selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of major depressive disorder . However , because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups , a head-to-head comparative study between SSRIs in different population s may be enlightening . We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded r and omized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder . Fifty-one patients were r and omly assigned to citalopram or sertraline treatment . The Montgomery-Åsberg Depression Rating Scale ( MADRS ) was used as the primary outcome . Efficacy and adverse effects were analyzed in an intent-to-treat population . Efficacy was analyzed using a last-observation-carried-forward method for early terminators . There were no significant differences in demographic characteristics at baseline . No significant differences were found in MADRS scores between citalopram and sertraline at baseline ( 36.6 ± 5.5 vs 38.2 ± 4.9 ; P = 0.322 ) or at the end of treatment ( week 6 ; 10.8 ± 10.0 vs 16.7 ± 11.3 ; P = 0.082 ) . However , MADRS scores in the citalopram group were significantly lower at week 1 ( 25.2 ± 8.5 vs 30.4 ± 6.1 ; P = 0.029 ) and week 3 ( 15.9 ± 10.0 vs 22.1 ± 8.7 ; P = 0.037 ) . Overall , treatment-emergent adverse effects were reported by 14.3 % and 28.6 % of patients in the citalopram and sertraline groups , respectively . In conclusion ,  citalopram  and sertraline were both efficacious and well tolerated . However , citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment , although the statistic was not significant The Treatment of SSRI-Resistant Depression in Adolescents study ( TORDIA ) was design ed to inform clinicians as to the best next step in the treatment after a depressed adolescent has not responded to an adequate trial with a selective  serotonin re-uptake inhibitor (SSRI).[1 ] In this six-site study , conducted from 2000 to 2006 , 334 treatment-resistant adolescents with major depressive disorder ( MDD ) were r and omized to one of the four treatment strategies in a two-by-two balanced factorial design : ( a ) switch to another SSRI ; ( b ) switch to venlafaxine ; ( c ) switch to another SSRI and add cognitive behavioral therapy ( CBT ) ; or ( d ) switch to venlafaxine and add CBT . The SSRI switch options were fluoxetine , and for the first half of the trial ( n = 181 ) , paroxetine . Because of the concerns about the safety and efficacy of paroxetine , citalopram was used instead during the second half of the trial ( n = 153 ) . All enrolled youth had not responded to an “ adequate trial ” with an SSRI , defined as treatment for at least 8 weeks , with the last 4 weeks at a dosage that was the equivalent of 40 mg of fluoxetine . This communication focuses on acute treatment , which was 12 weeks in duration 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 enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants ( TCAs ) , and the frequency and type of adverse events , have made the treatment of depression in this group difficult . The selective serotonin reuptake inhibitors ( SSRIs ) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs . We compared the therapeutic actions and side effects produced by citalopram , the most selective SSRI available , with amitriptyline in a group of elderly patients ( aged 65 and older ) diagnosed with major depression . In a double-blind , double-dummy , parallel-group , multicenter comparison of citalopram ( 20 or 40 mg/day ) and amitriptyline ( 50 or 100 mg/day ) , patients who did not respond to placebo during a 1-week single-blind phase were r and omly assigned to receive citalopram or amitriptyline for 8 weeks . Efficacy measures included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Depression Scale ( HAMD ) , and Clinical Global Impressions . Both drug treatments produced equivalent time-related declines in severity of depression , so that by 8 weeks slightly more than 50 % of the patients in each group experienced marked recovery , defined as MADRS scores < or = 12 . Amitriptyline produced a greater overall incidence of adverse events , including a significantly higher ( P < 0.001 ) percentage of patients reporting dry mouth ( 34 % vs. 7 % ) , as well as a significantly higher ( P < 0.02 ) incidence of somnolence . Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group . For only one event ( nausea ) did the citalopram group report a significantly greater ( P = 0.012 ) incidence ( 12.8 % vs. 4.8 % ) . On the basis of these results , it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly . Because of its low incidence and low magnitude of side effects , citalopram seems especially useful in private practice Both noradrenergic and serotonergic systems have been implicated in the pathophysiology of panic disorder . The advent of selective serotonin ( 5-HT ) reuptake inhibitors ( SSRIs ) ( e.g. citalopram ) and , more recently , selective noradrenergic ( NA ) reuptake inhibitors ( NRIs ) ( e.g. reboxetine ) has provided potentially important avenues of treatment for the disorder . To date , the comparative efficacy of selective NA and 5-HT reuptake inhibitors for panic disorder remains unresolved . Nineteen patients with panic disorder were r and omized in a single-blind , cross-over design to either citalopram or reboxetine for 8 weeks and after a 2-week washout were switched to the other study drug . At week 18 , seven of 13 patients ( 54 % ) in the intent-to-treat sample responded to reboxetine and nine of 11 patients responded to citalopram ( 82 % ) . Both citalopram and reboxetine led to significant improvements in panic attack severity with no apparent between-drug differences in efficacy . However , citalopram demonstrated superior efficacy in treating depressive symptoms . One non-responder to citalopram responded to reboxetine and three non-responders to reboxetine responded to citalopram . Although SSRIs are viewed as a first-line treatment for panic disorder , these results suggest that a NA agent such as reboxetine may also have a role . These data also suggest an advantage for citalopram in treating comorbid depressive symptoms , although some patients may respond preferentially to an SSRI and other patients to an NRI & NA ; Two selective serotonin reuptake inhibitors ( SSRIs ) , citalopram and fluoxetine , both at a daily dose of 20 mg , were compared in patients with unipolar major depression treated in general practice . This was a multicentre , double‐blind , r and omized trial carried out in France . The duration of treatment was 8 weeks . Patients were assessed by means of the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) , the 17 items Hamilton Depression Rating Scale ( HAMD ) and the investigator 's Clinical Global Impressions ( CGI ) . Observed and spontaneously reported adverse events were also recorded . A total of 357 patients of both sexes , aged between 21 and 73 years , entered the double‐blind phase of the trial . A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments . Apart from back pain recorded more frequently in the citalopram group , no significant difference was found between the two treatment groups with regard to adverse events , and both citalopram and fluoxetine were considered to be well tolerated . It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression . Citalopram showed an earlier onset of recovery than fluoxetine STAR*D is a multisite , prospect i ve , r and omized , multistep clinical trial of out patients with nonpsychotic major depressive disorder . The study compares various treatment options for those who do not attain a satisfactory response with citalopram , a selective serotonin reuptake inhibitor antidepressant . The study enrolls 4000 adults ( ages 18 - 75 ) from both primary and specialty care practice s who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode . After receiving citalopram ( level 1 ) , participants without sufficient symptomatic benefit are eligible for r and omization to level 2 treatments , which entail four switch options ( sertraline , bupropion , venlafaxine , cognitive therapy ) and three citalopram augment options ( bupropion , buspirone , cognitive therapy ) . Those who receive cognitive therapy ( switch or augment options ) at level 2 without sufficient improvement are eligible for r and omization to one of two level 2A switch options ( venlafaxine or bupropion ) . Level 2 and 2A participants are eligible for r and om assignment to two switch options ( mirtazapine or nortriptyline ) and to two augment options ( lithium or thyroid hormone ) added to the primary antidepressant ( citalopram , bupropion , sertraline , or venlafaxine ) ( level 3 ) . Those without sufficient improvement at level 3 are eligible for level 4 r and om assignment to one of two switch options ( tranylcypromine or the combination of mirtazapine and venlafaxine ) . The primary outcome is the clinician-rated , 17-item Hamilton Rating Scale for Depression , administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments . Secondary outcomes include self-reported depressive symptoms , physical and mental function , side-effect burden , client satisfaction , and health care utilization and cost . Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessment 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
Some statistically significant differences between citalopram and other antidepressants for the acute phase treatment of major depression were found in terms of efficacy , tolerability and acceptability .
Citalopram was more efficacious than paroxetine and reboxetine and more acceptable than tricyclics , reboxetine and venlafaxine , however , it seemed to be less efficacious than escitalopram .
BACKGROUND Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode .
Systematic review s have already highlighted some differences in efficacy between second-generation antidepressants .
Citalopram , one of the first selective serotonin reuptake inhibitors ( SSRI ) introduced in the market , is one of these antidepressant drugs that clinicians use for routine depression care .
OBJECTIVES To assess the evidence for the efficacy , acceptability and tolerability of citalopram in comparison with tricyclics , heterocyclics , other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression .