A double‐blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients

Abstract

A randomized, double-blind, parallel-group, 6-week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine. After a 1-week placebo wash-out, patients suffering from DSM-III major depression and with a score of 18 or more on the 21-item Hamilton Rating Scale for Depression (HRSD) received either paroxetine or fluoxetine. The patients were assessed for efficacy using the HRSD, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression; for tolerability, adverse events were elicited by the use of a non-leading question and a side effects checklist. The groups of patients were comparable on entry to the study. One hundred patients were recruited into the study, of whom 78 were evaluable for the efficacy analysis. Paroxetine and fluoxetine showed comparable efficacy at the end of the 6-week treatment period, but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed. This could suggest an earlier onset of action with paroxetine. Also, associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3. Patients on paroxetine reported fewer adverse events than those on fluoxetine. The most commonly reported adverse events were nausea and vomiting in both groups.

A comparison of the post‐marketing safety of four selective serotonin re‐uptake inhibitors including the investigation of symptoms occurring on withdrawal

“…Only three direct comparisons of different SSRIs in 4 The question on whether additional treatment was the same clinical study have been published [1][2][3]. given was completed by 181 respondents (93.2%).…”

“…Only three small scale review and compare the safety profiles of all four SSRIs. Spontaneous adverse drug reaction (ADR) reports are clinical studies allowing comparison of the safety of SSRIs have been published [1][2][3]. We have previously made by UK doctors through the 'yellow card' system.…”

The effect of study sponsorship on a systematically evaluated body of evidence of head-to-head trials was modest: secondary analysis of a systematic review

“…Twenty studies were clearly funded by the pharmaceutical industry [40,41,43,44, 46,47,50e52,54,56e61,63,65,67,68]. Six studies were probably funded by the industry [42,45,48,55,62,66]. One study reported a mixed funding source of public and industry monies [49].…”

“…Most trials were funded by the following: H. Lundbeck A/S, the manufacturer of citalopram and escitalopram (seven studies, 2,691 patients) [43,46,54,55,58,59,62]; Pfizer, Inc., New York, NY, USA, the manufacturer of sertraline (six studies, 1,520 patients) [40e42, 61,66,68]; and Glaxo Smithkline, London, United Kingdom, the [44,45,48,50,65,67]. Eli Lilly and Company, Indianapolis, IN, USA, the producer of fluoxetine [51,52,57], and Solvay Pharmaceuticals, Brussels, Belgium, the producer of fluvoxamine [47,56,60,63], financially supported three and four RCTs each (1,169 and 439 patients, respectively).…”

Selective Serotonin Reuptake Inhibitors

“…To date, all data regarding the rapidity of the SSRIs onset of action have been drawn from the retrospective subanalysis of clinical trials that were not designed to evaluate onset of action (Blier 2001), and there is need for prospective studies to examine comparative onset of action using sensitive designs and adequate sample sizes (Thase 2001) to clearly differentiate between the different SSRIs. However, several randomized, double-blind studies have suggested that fluoxetine may have a slower onset of action than other antidepressants, including citalopram (Patris et al 1996), moclobemide (Gattaz et al 1995), paroxetine (De Wilde et al 1993), and venlafaxine (Clerc et al 1994). The delayed onset of antidepressant action with fluoxetine may be due to the long half-lives of fluoxetine and norfluoxetine and the fact that it therefore takes 35-75 days to reach steady state in healthy young individuals and an average of 105 days in healthy individuals over the age of 65.…”