Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. Efficacy and Tolerability of Reboxetine Compared with Citalopram: A Double-blind Study in Patients with Major Depressive Disorder Citalopram versus desipramine in treatment resistant depression: Effect of continuation or switching strategies. A randomized open study The expert consensus guideline series. Pharmacotherapy of depressive disorders in older patients. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Prediction of the response to citalopram and reboxetine in post-stroke depressed patients Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. Using non-steroidal anti-inflammatory drugs in the treatment of depression. Incidence of sexual side effects in refractory depression during treatment with citalopram or paroxetine. Randomized double-blind comparison of serotonergic (Citalopram) versus noradrenergic (Reboxetine) reuptake inhibitors in outpatients with somatoform, DSM-IV-TR pain disorder. Efficacy of intravenous citalopram compared with oral citalopram for severe depression. Safety and efficacy data from a double-blind, double-dummy trial. Does comorbid substance use disorder impair recovery from major depression with SSRI treatment? An analysis of the STAR*D level one treatment outcomes. 5-HTTLPR modulates antidepressant efficacy in depressed women Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults Notes on the use of fluvoxamine as treatment of depression in HIV-1-infected subjects. A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial. Severity of depression and response to antidepressants: GENPOD randomised controlled trial. GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol 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 Response to an open trial of a second SSRI in major depression. Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model.
Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram , in the treatment of major depressive disorder ( MDD ) . In total , 357 out patients with MDD were r and omized to treatment with reboxetine 8 - 10 mg or citalopram 20 - 40 mg per day during 24 weeks . Primary end-point was change from baseline in the Hamilton Depression Rating Scale ( HAM-D , 21 items ) . Sexual function/dysfunction was measured by the Sexual Function scale ( SF ) . Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores : reboxetine with -21.4 and citalopram with -22.1 points ( NS ) . LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine ( -19.6 vs. -17.8 ; P = 0.034 ) . The response rate was 90.3 % for reboxetine and 92.7 % for citalopram ( NS ) . The most common side effect in the reboxetine group was dry mouth , and in the citalopram group sexual dysfunction . At week 24 , anorgasmia was reported by 5.9 % of the sexually active women in the reboxetine group vs 39 % in the citalopram group . The  dropout number  was 91 in the  reboxetine group , and 54 in the citalopram group . To summarize , both treatments gave a satisfactory antidepressant effect . The side effect profile differed between the groups , with a notably high prevalence of sexual dysfunctions in the citalopram group . The high number of dropouts in the reboxetine group , is considered as a result of the non-titration starting dose of 8 mg reboxetine per day , which gave a high incidence of early side-effects .  Depressive disorders including major depression ( MDD ) is very common , with a lifetime prevalence of at least 15 % in men and 25 % in women.1,2 Depression can be treated effectively by a range of antidepressant agents . Recent review s have suggested that the selective serotonin reuptake inhibitors ( SSRIs ) offer equal efficacy to the older antidepressant agents , such as tricyclic antidepressants , with the advantage of greater tolerability.3 - 5 Other review ers have reported that non-SSRI antidepressants , such as clomipramine , have been found to be significantly more effective than fluoxetine for the treatment of patients with severe depression.6  Reboxetine ( reboxetine mesylate , Edronax ; Pfizer , New York ) is a highly selective noradrenaline reuptake inhibitor , and the efficacy of reboxetine has been independently demonstrated in multiple r and omized , double-blind , placebo-controlled studies .7 - 9 In addition to improvements in depressive symptoms , treatment-associated improvements in social behavior ( measured using the Social Adaptation Self-evaluation Scale [SASS]),10 were noticed in one of these studies .8 In this study , reboxetine was statistically and clinical ly superior to both placebo and fluoxetine in improving social functioning . The primary objective of the current study was to assess efficacy and tolerability of reboxetine  in comparison with those of citalopram ( Cipramil ; H. Lundbeck , Copenhagen , Denmark ) in patients with MDD .  Citalopram is a highly SSRI . The antidepressant mechanism is presumed to be a result of stimulation of serotonergic neurotransmission in the central nervous system as a consequence of higher serotonin levels result ing from inhibition of the serotonin transporter . The therapeutic efficacy of citalopram in patients with MDD has been investigated in several placebo-controlled studies and in long-term and extension studies .11 The underlying rationale for this comparison was to study 2 different drug profiles , 1 drug being pure " adrenergic " and the other pure " serotonergic . " A secondary objective was to analyze the correlation between the types of depression ( ie , degree of melancholia and the efficacy of the 2 drugs ) 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 OBJECTIVES Depression in older patients contributes to personal suffering and family disruption and increases disability , medical morbidity , mortality , suicide risk , and healthcare utilization . The majority of clinical trials of antidepressant treatments are conducted in younger patients . For this reason , clinicians often have to extrapolate from studies in population s that do not present the same problems as older patients . For example , older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment . Older patients as a rule need to be on many medications , some of which may contribute to depression and /or interact with antidepressants . Finally , older adults metabolize medications slowly and are more sensitive to side effects than younger patients . Because of these complexities , we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature . METHOD After review ing the literature and convening a work group of experts , we prepared a written survey with 64 questions that asked about 857 options . 618 of the options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or to check a box to indicate their preferred answer . We sent the survey to 50 national experts on geriatric depression , all of whom completed it . Consensus on each option was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 89 % of the options rated on the 9-point scale . The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment . For unipolar nonpsychotic major depression , the preferred strategy is an antidepressant ( selective serotonin reuptake inhibitor [ SSRI ] or venlafaxine XR preferred ) plus psychotherapy . For unipolar psychotic major depression , the treatment of choice is an antidepressant ( SSRI or venlafaxine XR ) plus one of the newer atypical antipsychotics . Electroconvulsive therapy is also first line . For dysthymic disorder or persistent milder depression , the experts recommend combining an antidepressant ( SSRIs preferred ) and psychotherapy . If the patient has a comorbid medical condition ( e.g. , hypothyroidism ) that is contributing to the depression , the experts recommend treating both the depression and the medical condition from the outset . The SSRIs were the top-rated antidepressants for all types of depression . Among them , the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline . Paroxetine was another first-line option , and fluoxetine was rated high second line . The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy , supportive psychotherapy , problem-solving psychotherapy , and interpersonal psychotherapy . The experts also give strong support to including appropriate psychosocial interventions ( e.g. , psychoeducation , family counseling , visiting nurse services ) in the treatment program . The majority of experts would continue treatment with antidepressant medication for at least 1 year if a patient has had a single episode of severe unipolar major depression , for 1 - 3 years for a patient who has had 2 such episodes , and for longer than 3 years if there is a history of 3 or more episodes . CONCLUSIONS The experts reached a high level of consensus on the appropriateness of including both antidepressant medication , specifically SSRIs , and nonpharmacological modalities in treatment plans for severe depression . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide direction for addressing common clinical dilemmas in older individuals . They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions . Nonetheless , the guidelines can not address the complexities involved in the care of each individual patient and can be most helpful in the h and s of experienced clinicians 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 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 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 BACKGROUND Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters . We wished to investigate whether genetic variation could be used to target or personalise treatment , in a comparison of selective serotonin reuptake inhibitors ( SSRIs ) with noradrenaline reuptake inhibitors ( NARIs ) . AIMS To test the hypothesis that patients homozygous for the long ( insertion ) polymorphism of the serotonin transporter ( 5-HTTLPR ) have an increased response to SSRI antidepressants but not to NARI antidepressants . METHOD In an individually r and omised , parallel-group controlled trial , people meeting criteria for a depressive episode who were referred by their general practitioner were r and omised to receive either citalopram ( an SSRI ) or reboxetine ( an NARI ) . R and omisation was by means of a remote automated system accessed by telephone . The main outcome was depressive symptoms , measured by Beck Depression Inventory ( BDI ) total score 6 weeks after r and omisation . The trial was registered with the International St and ard R and omised Controlled Trials Number registry ( IS RCT N31345163 ) . RESULTS Altogether 298 participants were r and omised to receive citalopram and 303 were r and omised to reboxetine . At 6 weeks follow-up , complete data were available for 258 participants taking citalopram and 262 taking reboxetine . We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment . The interaction term for BDI score at 6 weeks was 0.50 ( 95 % CI -2.04 to 3.03 , P = 0.70 ) , which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype . CONCLUSIONS It is unlikely that the 5-HTTLPR polymorphism alone will be clinical ly useful in predicting response to antidepressants in people with depression 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 OBJECTIVE The incidence of  sexual dysfunction  due to antidepressant drugs reported in pre-marketing clinical efficacy trials is often several times lower than in subsequent clinical experiences and independent reports . Although it is commonly believed that the reason for this discrepancy is that the nonleading questions employed in conventional clinical trials underestimate sexual dysfunction while the direct question ing used in independent trials provides more accurate data , few studies have actually compared these 2 methods . METHOD In this study , 119 patients with a DSM-IV-defined major depressive episode ( 82 women and 37 men ) who had been treated with but not responded to a selective serotonin reuptake inhibitor ( SSRI ; either citalopram or paroxetine )  were assessed regarding sexual functioning by means of open-ended questions and direct question ing at baseline ( after SSRI treatment only ) and after 4 weeks of SSRI treatment plus buspirone or placebo . RESULTS More patients reported sexual dysfunction in response to direct question ing ( 41 % ) as compared with spontaneous report ( 6 % ) ( p < .001 ) . Sexual dysfunction correlated with the duration of the depressive episode , but not with age , dose of SSRI , plasma level of SSRI , duration of SSRI treatment , or any measurement of depression . No statistically significant differences regarding the incidence of sexual dysfunction were found between the citalopram and the paroxetine groups . CONCLUSION Open-ended questions are an insufficient tool to estimate sexual dysfunction , and premarketing clinical trials should therefore include basic explicit assessment s. The failure to find a correlation between treatment duration and sexual dysfunction adds to the notion that sexual side effects due to SSRIs do not abate over time OBJECTIVES Whether the effect of tricyclic antidepressants on Pain Disorder arises from their noradrenergic or serotonergic actions or both remains unclear . We compared the selective serotonin reuptake inhibitor ( SSRI ) citalopram and the noradrenergic reuptake inhibitor ( NARI ) reboxetine in out patients with Pain Disorder . We also distinguished the drugs ' analgesic and antidepressant effects . METHODS In this 8-week , r and omized double-blind study , 35 patients with a DSM-IV-TR diagnosis of Pain Disorder were r and omly assigned to receive either citalopram 40 mg/day ( N=17 patients ) or reboxetine 8 mg/day ( N=18 ) . The  Present Pain Intensity ( PPI ) scale and the Total Pain Rating Index ( tPRI ) of the McGill Pain Question naire were used to measure the effect on pain symptoms . Changes in the Zung Self-Rating Depression Scale ( Zung-D ) scores were evaluated to monitor a possible antidepressant effect . For all patients who had at least one assessment , an intent-to-treat analysis was performed . RESULTS No significant differences were found in the demographic variables or clinical characteristics of the two treatment groups . In the citalopram group , PPI and tPRI scores measured at baseline decreased after treatment ( tPRI : 41.9 vs. 30.0 , p=.004 ; PPI : 3.5 vs. 2.8 , p=.045 ) whereas in the reboxetine group differences were not statistically significant ( tPRI : 35.2 vs. 31.5 ; PPI : 3.7 vs. 3.1 ) . The Zung-D showed no significant changes between baseline and endpoint assessment in either group . CONCLUSIONS Our study suggests that the SSRI citalopram may have a moderate analgesic effect in patients with Pain Disorder , and that this analgesic activity appears to be not correlated to changes in depressive scores . If confirmed in a larger sample , this evidence suggests that patients who are intolerant or resistant to tricyclic antidepressants , may be treated with SSRIs BACKGROUND Intravenous administration is often beneficial in the treatment of severely depressed patients . It is mainly the tri- and tetracyclic antidepressant drugs that can be administered intravenously . However , these drugs have a less favourable safety profile than newer antidepressants , such as the selective serotonin reuptake inhibitors ( SSRIs ) . Citalopram is the only SSRI that is available in a formulation for infusion . This double-blind , r and omised , multicentre trial was design ed to compare the efficacy and tolerability of citalopram infusion ( 40 mg per day ) and citalopram tablet ( 40 mg per day ) . METHODS Patients were r and omised to receive either placebo tablet plus citalopram infusion ( the infusion group ; n=135 ) or citalopram tablet plus placebo infusion ( the tablet group ; n=119 ) . After receiving r and omised treatment for eight days , all patients entered an open treatment phase , during which they received oral citalopram 40 mg per day for five weeks . RESULTS Although there was no difference in Montgomery-Asberg Depression Rating Scale ( MADRS ) scores at the end of the r and omised treatment period , by the end of the open treatment phase the reduction in MADRS scores was significantly greater in the infusion group than in the tablet group ( p=0.015 ) . The infusion group also showed superior efficacy in Clinical Global Impressions assessment s. Citalopram was equally well tolerated in both treatment groups . CONCLUSIONS This trial confirmed the efficacy of citalopram 40 mg per day , and clearly supports the use of citalopram infusion in the treatment of severely depressed , hospitalised patients Many patients with major depressive disorder ( MDD ) present with concurrent substance use disorders ( SUDs ) , which has been thought to impair their response to antidepressants . Clinicians often delay antidepressant treatment until sustained sobriety has been established . Unfortunately , these comorbid subjects are typically excluded from depression treatment trials , leaving a gap in underst and ing the treatment outcomes . In the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) study , 2876 adult out patients diagnosed with nonpsychotic MDD were prospect ively treated with the selective serotonin-reuptake inhibitor ( SSRI ) , citalopram , and returned for at least one post-baseline visit .  Participants with SUD ( 29 % ) and without SUD ( 71 % ) were compared in regard to baseline clinical and sociodemographic features and treatment response . The group with MDD and SUD was further subdivided into those with alcohol only , drug only , and both alcohol and drug use . Despite clear sociodemographic and clinical differences , there were no significant differences between groups in the time to achieve response or rates of response to citalopram ;  however , those who endorsed both alcohol and drug use had significantly reduced rates of remission and significantly increased times to reach remission compared to the MDD group without SUD . In addition , subjects with MDD and SUD had higher risk of psychiatric serious adverse events ( 3.3 % vs. 1.5 % ) and hospitalization ( 2.8 % vs. 1.2 % ) . The results indicate that first-line treatment with citalopram in depressed patients with alcohol or drug use respond as well as those without SUD . More intensive treatment is most likely needed for MDD patients with both drug and alcohol use disorders Background As compared with the long variant ( L ) , the short variant ( S ) of the functional polymorphic region of the serotonin transporter gene ( 5-HTTLPR ) has been associated with a lower antidepressant efficacy in major depression , but some replication studies have evidence d contradictory results . Sex differences may explain these contradictory results . Methods One hundred and three in patients ( 74 women and 29 men ) with a major depressive episode were assessed prospect ively for antidepressant efficacy after 4 weeks of treatment with selective serotonin reuptake inhibitors ( SSRI ) and non-SSRI drugs . Results As compared with LL/LS , the SS genotype of the 5-HTTLPR was associated with a lower antidepressant efficacy in depressed women ( 79 vs. 50 % responders , P = 0.035 ) . This result was shown with both SSRI and non-SSRI antidepressants . The logistic regression performed in women showed that response to treatment was related to genotype ( odds ratio=0.15 ; 95 % confidence interval=0.03–0.85 ; P = 0.03 ) and not to other variables . No effect of 5-HTTLPR was found in depressed men . Conclusion Despite a low power , this study suggests a significant effect of 5-HTTLPR genotype on antidepressant efficacy in depressed women but not in men , with both SSRI and non-SSRI drugs . Further research is needed to confirm this result and investigate its underlying mechanisms OBJECTIVE To compare the emergent sexual effects of moclobemide and selective serotonin reuptake inhibitors ( SSRIs ) during acute and maintenance therapy in routine practice . METHOD 268 patients were evaluated for sexual function  at baseline , 6 weeks , 3 and 6 months of treatment using physician ratings and self-rating question naires . Patients received moclobemide , an reversible monoamine oxidase A inhibitor ( RIMA ) , or a SSRI ( fluoxetine , fluvoxamine , paroxetine , sertraline ) . RESULTS Baseline values were similar in all groups . Incidences of impairments of sexual functioning with treatment , whether clinical ly relevant or not , were 24.3 % with moclobemide and 61.5 % with SSRIs ( physician ratings ) , with no significant tolerance to these effects . There was a suggestion of differences between the SSRIs in their specific dysfunctions they cause . SSRIs ( 21.6 % of patients ) had about ten times the moclobemide rate ( 1.9 % ) of sexual dysfunction reported as adverse events . Antidepressant efficacy was comparable between treatments . CONCLUSION In patients for whom sexual function  is important or sexual dysfunction  is present , moclobemide should be considered a first line antidepressant Fluvoxamine belongs to the class of selective serotonin reuptake inhibitors ( SSRIs ) which have recently gained large popularity as antidepressant agents essentially because they lack the most troublesome adverse effects of older antidepressants ( i.e. tricyclic antidepressants ) such as anticholinergic effects and cardiotoxicity . Recent studies in the literature suggest that HIV-1 infected subjects are affected by depressive episodes with a relatively high frequency , often requiring an antidepressant treatment . Due to its favorable adverse effects profile , we used fluvoxamine as first line treatment for sixteen depressed HIV-1 infected subjects . They were administered the drug at a daily dosage of 100 mg in the evening . Fluvoxamine provided a good clinical efficacy for six of these patients , whereas the other ten had to discontinue the drug because of the presence of severe adverse effects such as acute total insomnia , gastro-intestinal disturbances together with anorexia , aggressive and impulsive behavior and excessive sedation . The observed fluvoxamine side-effects are not typical or specific for this particular patient group since they are also described in seronegative subjects taking fluvoxamine ; however , our findings seem to indicate that they become more frequent and more severe when the drug is administered to HIV-1 infected patients 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 BACKGROUND The cost-effectiveness of tricyclic antidepressants ( TCAs ) and selective serotonin reuptake inhibitors ( SSRIs ) has not been compared in a prospect i ve study in primary care . AIMS To determine the relative cost-effectiveness of TCAs , SSRIs and lofepramine in UK primary care . METHOD An open-label , three-arm r and omised trial with a preference arm . Practitioners referred 327 patients with incident depression . RESULTS No significant differences were found in effectiveness or cost-effectiveness . The numbers of depression-free weeks over 12 months ( on the Hospital Anxiety and Depression Scale ) were 25.3 ( 95 % CI 21.3 - 29.0 ) for TCAs , 28.3 ( 95 % CI 24.3 - 32.2 ) for SSRIs and 24.6 ( 95 % CI 20.6 - 28.9 ) for lofepramine .  Mean health service costs per patient were pound 762 ( 95 % CI 553 - 1059 ) for TCAs , pound 875 ( 95 % CI 675 - 1355 ) for SSRIs and pound 867 ( 95 % CI 634 - 1521 ) for lofepramine .  Cost-effectiveness acceptability curves suggested SSRIs were most cost-effective ( with a probability of up to 0.6 ) . CONCLUSIONS The findings support a policy of recommending SSRIs as first-choice antidepressants in primary care BACKGROUND Antidepressant prescribing is widespread . Nonetheless , response to antidepressants is variable . If it was possible to predict response to medication and thus tailor treatment accordingly , this would not only improve patient outcomes but may also have economic benefits . AIMS To test the hypothesis that individuals with more severe depression would benefit more from noradrenaline reuptake inhibitors ( NARIs ) than selective serotonin reuptake inhibitors ( SSRIs ) compared with individuals with less severe depression . METHOD Individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory ( BDI ) were r and  omised to either an SSRI ( citalopram 20 mg daily ) or a NARI ( reboxetine 4 mg twice daily ) . R and omisation was by means of a remote automated telephone system . The main outcome was depressive symptoms measured by the BDI total score 6 weeks after r and omisation . ( TRIAL REGISTRATION IS RCT N31345163 . ) RESULTS In total , 601 participants were r and omised  ( citalopram : n = 298 , reboxetine : n = 303 ) . Ninety-one per cent were followed up at 6 weeks ( citalopram : n = 274 , reboxetine : n = 272 ) . There was little evidence to support an interaction between treatment and severity of depression ( interaction term : 0.02 , 95 % CI -0.59 to 0.62 , P = 0.96 ) . Adjustment for potential confounders ( age , gender , employment status , history of depression , number of life events and social support ) did not affect the findings ( interaction term : 0.06 , 95 % CI -0.54 to 0.66 , P = 0.85 ) . CONCLUSIONS Treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin ( Selective Serotonin Reuptake Inhibitors – SSRIs ) and noradrenaline ( Noradrenaline Reuptake Inhibitors – NaRIs ) into the presynaptic terminal . There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action . Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs , there are patients who respond to one class of compounds and not another . This suggests that treatment response could be predicted by genetic and /or clinical characteristics . Firstly , this study aims to investigate the influence of a polymorphism ( SLC6A4 ) in the 5HT transporter in altering response to SSRI medication . Secondly , the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs . Methods / design The GenPod trial is a multi-centre r and omised controlled trial . GPs referred patients aged between 18–74 years presenting with a new episode of depression , who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse . Patients were interviewed to ascertain their suitability for the study . Eligible participants ( with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory ( BDI ) score > 14 ) were r and omised to receive one of two antidepressant treatments , either the SSRI Citalopram or the NaRI Reboxetine , stratified according to severity . The final number r and omised to the trial was 601 . Follow-up assessment s took place at 2 , 6 and 12 weeks following r and omisation . Primary outcome was measured at 6 weeks by the BDI . Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments . Discussion The results of the trial will provide information about targeting antidepressant treatment for individual patients ; in turn this may increase prescribing efficacy , thereby speeding recovery and reducing the cost to the NHS . It will also help to underst and the different roles that noradrenaline and serotonin might play in the biology of depression . The trial is expected to report in the autumn of 2008.Trial Registration IS RCT N 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 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 An estimated 30 % to 40 % of patients with depression do not sufficiently respond to treatment with selective serotonin reuptake inhibitors ( SSRIs ) and the period in which treatment efficacy can be assessed is relatively long . Therefore , a test to identify potential nonresponders could be useful in the treatment of depression . Serotonin transporter gene ( SLC6A4 ) variations have been reported to account for differences in the way individuals respond to SSRI treatment . OBJECTIVE A decision-analytic model was used to assess whether pretreatment genetic testing for 5-HTTLPR , a polymorphism of the SLC6A4 genotype , could be an efficient tool in the treatment of depression . METHODS A theoretical clinical decision-analytic model was constructed to compare the current treatment strategy in The Netherl and s with an alternative strategy for the treatment of depression . Under treatment guidelines in The Netherl and s , all patients with depression receive SSRI treatment ( nontesting strategy ) . Under the alternative strategy , genetic testing would be performed to identify which class of antidepressant would be the best choice for initiation of treatment ( genetic testing strategy ) . Probabilities ( predicted results ) for this model were based on data from previous studies and the opinions of experts in the field of psychopharmacology . To test the robustness of the model , 6- and 12-week remission rates for patients treated with SSRIs were varied in a sensitivity analysis using a predetermined range that was established based on expert opinion . Threshold analyses were performed on the parameters of serotonin transporter genotype frequency and response and nonresponse rates for patients receiving SSRIs , serotonin-norepinephrine reuptake inhibitors ( SNRIs ) , and tricyclic antidepressants ( TCAs ) to determine the value for a variable at which it could be concluded that a change in treatment strategy would be preferred . RESULTS When genetic testing was performed before an antidepressant was prescribed , 64.6 % of patients were predicted to be in remission after 6 weeks of treatment compared with 60.0 % of patients who did not receive genetic testing . After 12 weeks , 79.5 % of patients in the testing group who received an SNRI as initial treatment and 83.2 % of those who received a TCA initially were predicted to be in remission compared with 76.7 % of patients in the nontesting group . Sensitivity analyses indicated that the model was robust to variation of probability estimates within their plausible ranges . However , these findings were based on a theoretic model and did not include cost assessment . Pretreatment genetic testing must be evaluated further in r and omized clinical trials and costs must be assessed before implementing this strategy in routine psychiatric practice can be recommended . CONCLUSIONS The findings of this study suggest that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment
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 .