Baldwin DS, Cooper JA, Huusom AK, et al. A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder

Clinical Neuroscience Division, University of Southampton, Royal South Hants Hospital, Southampton, UK.
International Clinical Psychopharmacology (Impact Factor: 2.46). 06/2006; 21(3):159-69. DOI: 10.1097/01.yic.0000194377.88330.1d
Source: PubMed


This multinational, randomized, double-blind, flexible-dose study evaluated the short- and long-term antidepressant tolerability and efficacy of escitalopram and paroxetine. Tolerability was assessed by monitoring adverse events throughout the study, and discontinuation events during brief treatment interruption and tapered withdrawal. Discontinuation-emergent effects were evaluated in two separate double-blind periods. First, to mimic the consequences of non-compliance, patients were randomized to one of two treatment interruption periods (placebo-substitution for 3-5 days). Second, patients were randomized to a 1-2-week tapered withdrawal period randomly scheduled between weeks 28 and 31. The pre-specified primary efficacy endpoint was the mean change from baseline in total Montgomery-Asberg Depression Rating Scale (MADRS) score at week 8, using the principle of last observation carried forward. A total of 323 patients entered 8 weeks of double-blind treatment and received at least one flexible dose of escitalopram (10-20 mg/day) or paroxetine (20-40 mg/day). Patients who demonstrated evidence of a significant clinical improvement (Clinical Global Impression-Improvement of 1 or 2) at week 8 entered a 19-week, double-blind maintenance period during which they were treated with the same dose they received at week 8, followed by a 1-2-week tapered withdrawal period. A total of 89 patients (28%) withdrew during the study; significantly (P<0.01) more patients withdrew from the paroxetine group (34%) than from the escitalopram group (21%), and significantly (P<0.05) more paroxetine patients withdrew due to lack of efficacy. The mean MADRS total score improved for both treatment groups from baseline to week 8, with no statistical difference between groups. In severely depressed patients (baseline MADRS total score >or=30), escitalopram was superior (P<0.05) to paroxetine at week 27 (end of maintenance treatment). There was a high prevalence of sexual dysfunction at baseline: the mean Arizona Sexual Experience Scale (ASEX) score was approximately 20 points in both treatment groups. Mean total ASEX scores increased slightly above baseline values during the acute period and declined slightly below baseline values towards the end of the maintenance period. During taper and cessation of treatment, patients in the paroxetine group demonstrated significantly more discontinuation symptoms relative to escitalopram based on the Discontinuation Emergent Signs and Symptoms scores.

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    • "A relapse prevention study of 325 patients conducted with escitalopram and paroxetine included 8 weeks of initial treatment, followed by a 19-week maintenance treatment period and finally a 1–2 week tapered discontinuation period (Baldwin et al., 2006). Overall, withdrawal of patients for lack of efficacy (normally referred to as relapses) was significantly less common on escitalopram than paroxetine (Baldwin et al., 2006). "
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    ABSTRACT: It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.
    Full-text · Article · Jan 2014 · International clinical psychopharmacology
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    • "Again, the inclusion criteria were more narrowly defined. The authors argued that the decline may have been due to the dropping-out of patients with more severe SD (Baldwin et al. 2006). However, drop-outs in the present study did not differ substantially from subjects who completed the protocol in terms of reported SD. "
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    ABSTRACT: Sexual dysfunction (SD) is a frequently reported side-effect of antidepressant treatment, particularly of selective serotonin reuptake inhibitors (SSRIs). In the multicentre clinical and pharmacogenetic GENDEP study (Genome-based Therapeutic Drugs for Depression), the effect of the serotonin transporter gene promoter polymorphism 5-HTTLPR on sexual function was investigated during treatment with escitalopram (SSRI) and nortriptyline (tricyclic antidepressant). A total of 494 subjects with an episode of DSM-IV major depression were randomly assigned to treatment with escitalopram or nortriptyline. Over 12 weeks, depressive symptoms and SD were measured weekly with the Montgomery-Asberg Depression Rating Scale, the Antidepressant Side-Effect Checklist, the UKU Side Effect Rating Scale, and the Sexual Functioning Questionnaire. The incidence of reported SD after 12 weeks of treatment was relatively low, and did not differ significantly between antidepressants (14.9% escitalopram, 19.7% nortriptyline). There was no significant interaction between the 5-HTTLPR and antidepressant on SD. Improvement in depressive symptoms and younger age were both associated with lower SD. The effect of age on SD may have been moderated by the 5-HTTLPR. In GENDEP, rates of reported SD during treatment were lower than those described in previous reports. There was no apparent effect of the 5-HTTLPR on the observed decline in SD.
    Full-text · Article · Mar 2011 · The World Journal of Biological Psychiatry
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    • "Our aim was to compare the suicide risk of adults over age 50 who stopped redeeming antidepressants at an early stage with those who continued. Given that as many as 85–90% of individuals who discontinue treatment are still depressed (Baldwin et al., 2006), we hypothesized that these individuals have a higher risk of suicide than those who seemingly comply with treatment. Also, we wished to assess if persons who previously have been hospitalized for psychiatric disorders are associated with elevated suicide risks. "
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    ABSTRACT: As many as 47% of adults over age 50 discontinue treatment with antidepressants after redeeming only one prescription. The study aim was to assess the risk of suicide in adults aged 50+ who discontinue antidepressants at an early stage of treatment. Case control study of all individuals aged 50+ living in Denmark and who initiated antidepressant treatment between July 1st 1995 and December 31st 2000 (N=217,123). Hazard ratios were calculated using Cox regression analyses, propensity score matching techniques, and marginal structural models. During the study period, 78,594 men and 138,529 women aged 50+ began treatment with an antidepressant medication, of whom 309 men and 229 women died by suicide. Men aged 50+ who discontinued treatment early had a suicide rate of 167 per 100,000 compared with 175 per 100,000 in those who continued refilling prescriptions; hazard ratio=0.98 [CI-95%: 0.78-1.23]. The suicide rate in women who discontinued treatment was 52 per 100,000 compared with 74 per 100,000 in those who continued refilling; hazard ratio=0.72 [CI-95%: 0.55-0.94]. Although people with previous psychiatric hospitalizations had greater risk of suicide than those without past hospital admissions, the difference was not significant in the adjusted model. Prescriptions redeemed at pharmacies are our only indicator of treatment adherence. Also, information on severity of depression was not available. We did not find a lower suicide risk among people over age 50 who seemingly follow treatment in comparison with those who discontinued treatment with antidepressants at an early stage.
    Full-text · Article · May 2009 · Journal of Affective Disorders
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