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Naturalpathhealthcenter.comEvidence based review of escitalopram in treating majordepressive disorder in primary careThomas R. Einarson The study aimed to summarize clinical data for 43.5%, P = 0.003) but similar to venlafaxine-XR (P = 0.97).
escitalopram in the treatment of major depressive disorder Response rates were superior to placebo (48.7% versus in primary care. Medline, Embase and Cochrane databases 43.1%, P < 0.001) and citalopram (62.5% versus 49.5%, were searched for randomized controlled trials of P = 0.001) but not venlafaxine-XR (P = 0.52). Adverse events escitalopram (10–20 mg/day for 8 weeks) versus other were comparable among active drugs (P > 0.05). Remission antidepressants in therapeutic doses or placebo. Patients and response rates of escitalopram in primary care are were required to have had moderate/severe depression, clinically superior to placebo and citalopram, but similar to venlafaxine-XR. Further head-to-head trials are warranted (MADRS) scores recorded at baseline and 8 weeks.
to verify these findings. A pharmacoeconomic analysis is Outcomes examined were remission rates (MADRS r 12) also required to determine whether these clinical and response rates ( Z 50% decrease from baseline in advantages for the patients translate into economic MADRS at week 8). Data were combined using a random advantages for the health care system. Int Clin effects meta-analytic model. Of the 15 studies identified, 11 were rejected (five not primary care, four duplicate reports, one lacked 8-week MADRS scores, one not depression)and four were accepted (n = 1472 patients). The four International Clinical Psychopharmacology 2004, 19:305–310 studies had nine arms, four for escitalopram (n = 654), two Keywords: Citalopram, escitalopram, major depressive disorder, remission, for citalopram (n = 333), one for venlafaxine-XR (n = 142) and two for placebo (n = 343). Remission rates forescitalopram were superior to placebo (48.7% versus Faculty of Pharmacy, Department of Clinical Pharmacology, Faculty of Medicine,University of Toronto, Toronto, Ontario, Canada.
37.6%, P = 0.003) and citalopram (52.8% versus 43.5%,P = 0.003) but similar to venlafaxine-XR (P = 0.97).
Correspondence and requests for reprints to Dr T. R. Einarson, Leslie Dan Faculty Response rates were superior to placebo (48.7% versus of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2,Canada.
43.1%, P < 0.001) and citalopram (62.5% versus 49.5%, Tel: + 1 416 978 6212; fax: + 1 416 978 1833; P = 0.001) but not venlafaxine-XR (P = 0.52). Adverse events were comparable among active drugs (P < 0.05). Remissionrates for escitalopram were superior to placebo (48.7% Received 31 March 2004 Accepted 6 July 2004 versus 37.6%, P = 0.003) and citalopram (52.8% versus Reviews of the efficacy of escitalopram have been Major depressive disorder is a major health problem in conducted for mixed populations (Auquier et al., 2003; primary care, affecting approximately 10% of the poupla- Gorman et al., 2002; Waugh and Goa, 2003), but none has focused on primary care. Differences in treatment 2003). The consequences of the disease can be patterns and in outcomes have been found between substantial, in terms of morbidity (Wells et al., 1989), primary care and other, more intensive settings, such as mortality (Zheng et al., 1997) and economic impact (Kind secondary or tertiary care (Einarson et al., 1997). It has and Sorenson, 1993). Not all patients respond to even been suggested that patients with major depressive pharmacotherapy and research continues for newer and disorder in primary care have a different aetiology and natural history compared to secondary care patients (Suhand Gallo, 1997; Arya, 1999), although this view has not Escitalopram (Cipralexs, Lexapros) is a selective seroto- been widely accepted. Nonetheless, these patients nin reuptake inhibitor (SSRI). It is the S-enantiomer of constitute an important subgroup that warrants examina- citalopram, and appears to have clinical advantages over tion. However, in their systematic review and meta- citalopram (Montgomery et al., 2001; Auquier et al., 2003; analysis, MacGillivray et al. (2003) concluded that Gorman et al., 2002). The efficacy of escitalopram in ‘evidence on the relative efficacy of selective serotonin treatment of major depressive disorder has been established reuptake inhibitors and tricyclic antidepressants in in randomized controlled trials (Waugh and Goa, 2003).
primary care is sparse and of variable quality’.
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International Clinical Psychopharmacology Therefore, there is a need to examine this clinical area.
was examined using the chi-square test. If more The aim of the present study was to examine the efficacy than one study reported incidences of the same of escitalopram in treating major depressive disorder in adverse event, they were combined in a random effects meta-analytic model to determine overall rates(Einarson, 1997). Outputs were clinical rates weighted by sample size, and also incorporating between-studyvariance.
The population of interest was primary care adultpatients ( Z 18 years of age), either male or female, whohad been diagnosed with major depressive disorder usingany standard criteria. For the purposes of this research, the definition of primary care presented by MacGillivray The initial search identified 15 articles, of which 11 were et al. (2003) was used. They included patients treated by rejected. Five included patients who were not treated in primary care practitioners (i.e. either general or family primary care (Burke et al., 2002; Rapaport et al., 2002; practitioners) in a primary care (ambulatory) setting.
Bielski et al., 2003; Ninan et al., 2003; Rapaport et al., Specialists such as psychiatrists were excluded, as were 2004); four were duplicate reports (Wade et al., 2002a, hospitals and both secondary and tertiary care settings.
2002b; Bothmer et al., 2003; Colonna et al., 2004); in one,MADRS was not measured at 8 weeks (Montgomery et al., Patients were accepted if they had moderate to severe 2001); and one did not deal with depression (Stahl et al., depression, i.e. baseline scores r 18 and ˚sberg Depression Rating Scale (MADRS).
The focus was restricted to primary care patients because That left four studies with 1472 patients (Colonna, 2002; our group has previously found differences in severity, Wade et al., 2002c; Lepola et al., 2003). Table 1 provides treatments and outcomes for those individuals who are clinical and demographic details of the studies, included managed by specialists (e.g. psychiatrists) or in different patients and drugs. Patients had no differences in any settings such as the hospital (Einarson et al., 1997). This parameters across drugs within or between studies. The approach was taken recently by MacGillivray et al. (2003).
majority were females (average proportion in eachstudy = 73 ± 3%), with an average age of 44 ± 3 years, Only randomized controlled trials were included. The and all were recruited from Europe or Canada.
drug of interest was escitalopram, administered in dosesof 10–20 mg daily. Acceptable comparators included other The four studies had a total of nine arms: four for antidepressants in standard therapeutic doses or placebo.
escitalopram (n = 654), two for citalopram (n = 333), one Treatments must have been given for a minimum of for venlafaxine-XR (n = 142) and two for placebo 8 weeks. For the analysis, patients must have had at least (n = 343). Table 2 indicates the disposition of patients one dose of drug and a valid MADRS measurement at in each trial. There were no significant differences in approximately 8 weeks after starting treatment.
overall withdrawal rates among the four comparators (chisquared = 1.75, d.f. = 3, P = 0.63), or in rates of patients Outcomes must have been measured after 6–8 weeks of who completed 8 weeks of treatment (chi squared = 1.53, treatment, and included remission rate (numbers of patients with post treatment MADRS score r 12),response rate (numbers of patients whose MADRS score Clinical results are shown in Table 3. All homogeneity decreased by Z 50%) and adverse event rates. With tests were non-significant, suggesting that it was appro- respect to adverse events, the proportions of patients who priate to pool the data. In terms of remission, escitalo- reported at least one event were calculated, regardless of causality. In addition, adverse events that were reported statistically (P = 0.003) superior to placebo and citalo- for all drugs in at least one study were identified and quantified. The Medline, Embase and Cochrane data- needed-to-treat (NNT) was 9.0 compared to placebo bases (1995 to present) were searched. References were and 10.8 with citalopram. In other words, for every nine searched for further articles, published abstracts, con- ference proceedings, etc. When published data were not with citalopram), there will be one more patient in retrievable, or could not be extracted from published remission. With respect to response rates, escitalopram articles, the manufacturer (H. Lundbeck A/S, Copen- was similarly superior to placebo (difference = 15%, hagen, Denmark) provided the (raw) data.
P = 0.001). The NNTs of 6.7 and 7.8 were slightly lower Data were combined using a random effects model, that with remissions. Rates did not differ from venlafax- weighting studies by sample size and by between-study ine-XR in either response or remission after 8 weeks of variance (Cochran, 1954). Heterogeneity of effects Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Evidence based review of escitalopram Einarson CGI-S, Clinical Global Impression–Severity; DSM, Diagnostic and Statistical Manual; MADRS, Montgomery–A˚sberg Depression Rating Scale.
Disposition of patients in accepted trials ADR, Adverse drug reaction; LOE, lack of efficacy. aReported only total and ADR dropouts.
Rates of adverse events and the proportions of patients (P = 0.005), but did not differ between active drugs reporting them are shown in Table 4. The majority of patients in all studies (meta-analytic average = 57.8%)reported at least one event. However, the rates were similar across the drugs studied. Statistically, event rates for active drugs rates were higher than those for placebo clinically superior to placebo in the general population Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
International Clinical Psychopharmacology Rates of remission and response to escitalopram and its comparators in head-to-head randomized controlled trials *P-value for the difference between groups. NA, Not applicable.
Summary of rates of adverse events reported in accepted studies (Montgomery et al., 2001; Burke et al., 2002; Waugh and outpatients that was 26% higher than that for inpatients Goa, 2003). This meta-analysis supports the efficacy of escitalopram in the population of primary care patients.
Similarly, it confirms that escitalopram also has clinical The rates found in the present study are comparable to advantages over its racemate, citalopram, in these those found in another meta-analysis (Einarson et al., patients. Consequently, primary care practitioners may 1999). For example, the response rate for venlafaxine-XR of 79.6% in 142 patients is similar to the 73.7% found offers clinical advantages to the psychotherapeutic The success rates found here, both for remission It is important that patient populations are separated and response, were clinically relevant and statistically because their clinical courses and responses to treatment can differ substantially. It is to be expected that patients and citalopram. In addition, the NNT was quite treated by a psychiatrist, or who must be treated in an low for escitalopram versus placebo and citalopram, institution, would have more severe symptoms or would respectively, ranging from 6.7 to 10.8. This means that respond less well than those indiviuduals in primary care.
one extra success is obtained when 7–11 (i.e. the For example, in a previous study performed by this numbers are rounded up) more patients are treated with author, it was found that SSRIs had a success rate for escitalopram. These values compare favourably to those Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Evidence based review of escitalopram Einarson presented by Sackett et al. (2000) in their definitive Bielski RJ, Ventura D, Chang CC (2003). A double-blind comparison of escitalopram with venlafaxine-XR in treatment of major depressive disorder[abstract#P.1.207]. Eur Neuropsychopharmacol 13 (suppl 4):S262.
Bothmer J, Montgomery SR, Huusom AKT (2003). Escitalopram: effective and The differences in success rates often can translate into better tolerated than venfalaxine XR in the treatment of depression. Presentedat the 27th Congress of the Nordic Psychiatric Association, Reykjavik, Iceland.
economic advantages. Drugs that truly have a higher Burke WJ, Gergel I, Bose A (2002). Fixed-dose trial of the single isomer SSRI success rate result in a lower utilization of healthcare escitalopram in depressed outpatients. J Clin Psychiatry 63:331–336.
resources, including fewer visits to the physician or Cochran WG (1954). The combination of estimates from different experiments.
psychiatrist, fewer titrations or switching of medica- Colonna L, Reines EH, Andersen HF (2004). Escitalopram is well tolerated and tions, as well as fewer and shortened hospitalizations.
more efficacious than citalopram in long-term treatment of moderately The final result is a lower overall cost and a more http://www.aisc.it/2002/ifmad/abstract/colonna.doc efficient use of healthcare resources (Einarson et al., Colonna L, Reines EH, Andersen HF (2002). Escitalopram is well tolerated and more efficacious than citalopram in long-term treatment of moderatelydepressed patients. Int J Psychiatry Clin Pract 6:243–244.
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i) Biographical Information Current Status: professor, Department of Exercise Science, Researcher, Axe maladies chroniques (groupe santé respiratoire), Centre de recherche, Hôpital du Sacré-Cœur de Montréal Mailing Address: Department of Exercise Science Concordia University 7141 Sherbrooke St. West Science Pavilion Room 165.29 Montréal, Qc H4B 1R6 Phone: (514) 848-2424 Ext. 5