Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care. Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial. Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression. A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. Efficacy of paroxetine in treating major depressive disorder in persons with multiple sclerosis. Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy. Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity. The relationship between pain and depression in a trial using paroxetine in sufferers of chronic low back pain.
Major depression with high levels of anxiety (anxious depression) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment. It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors. For this reason, using head-to-head acute treatment comparison, we compared efficacy and tolerability of fluoxetine, sertraline, and paroxetine among depressed patients with high levels of anxiety.
                Patients (N = 108) with DSM-IV major depression and high levels of anxiety (a HAM-D-Anxiety/Somatization Factor score > or =7) were randomized to fluoxetine, sertraline, or paroxetine treatment in a double-blind fashion. Changes in overall depression and anxiety were assessed.
                Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores. Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores, except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score. There were no significant differences across treatments in percentages of patients with substantial emergence, any worsening, or improvement at endpoint in individual HAM-D Items 9 (agitation), 10 (psychic anxiety), and 11 (somatic anxiety). Overall, all treatments were well tolerated.
                These data showed no significant differences in efficacy and tolerability of fluoxetine, sertraline, and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression. Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression. Primary care patients with a major depressive disorder and 17-item Hamilton Rating Scale for Depression (17-HAM-D) score >18 were randomized to 24 weeks of treatment with mirtazapine 30-45 mg/day (n=99) or paroxetine 20-30 mg/day (n=98). Both treatments were efficacious in improving depressive symptomatology, as assessed by group mean 17-HAM-D scores, percentages of HAM-D responders and remitters and Clinical Global Improvement responders. The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17-HAM-D scores at weeks 1, 2 and 4, and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4. Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment. Both treatments were well tolerated. The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue. Statistically significantly more paroxetine-treated patients complained of increased sweating, headache and nausea. The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care. An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine, and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors. Drugs influencing monoaminergic pathways are of potential use in the treatment of pain. A serotonin re-uptake inhibitor, paroxetine (20-30 mg daily), and a dopamine antagonist, sulpiride (200-400 mg daily) were compared in a randomized, double-blind, response-conditional cross-over pilot study in 50 non-depressed patients with chronic tension-type headache. Headache was scored daily on a 5-point verbal scale during 4-weeks baseline and during 8 weeks of treatment for each drug. A 5-point 'Global' assessment was obtained for each drug. In both treatment groups headache score decreased compared to baseline. Group comparison of 24 patients first treated with paroxetine and 24 patients first treated with sulpiride showed a non-significant trend in favor of sulpiride by 'Global' evaluation and by evaluation of the available diary records (18 paroxetine-treated and 19 sulpiride-treated). Cross-over analysis of 'Global' records from 20 patients treated with paroxetine followed by sulpiride and 17 patients treated in the reverse order showed better relief from sulpiride compared to paroxetine in patients having tested both drugs (P = .03). A similar difference was reflected in available headache scores (13 and 10 patients respectively; P = .03). Predominant side effects were sedation and depression, for paroxetine also nausea and head pain. None of the drugs improved headache more than one score-point on average. A placebo controlled trial of sulpiride may be warranted. Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews 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, randomized, 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.
                (c) 2008 Movement Disorder Society. This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV.
                In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score.
                Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups.
                The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance. 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. The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder (MDD) in persons with multiple sclerosis (MS).
                In this double-blind trial, 42 participants with MS and MDD were randomly assigned to one of two parallel 12-week treatment arms: paroxetine or placebo. The participants started at an initial dose of 10 mg/day paroxetine or placebo, titrated up to 40 mg daily based on symptoms response and side effects. The primary outcome measure was the Hamilton Rating Scale for Depression (HAM-D). Secondary outcomes included fatigue, anxiety and self-reported quality of life.
                Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment. Although the treatment group improved more than the control group on most measures, few differences were statistically significant. For the primary outcome, 57.1% of participants in the treatment arm had at least a 50% reduction in HAM-D score, compared with 40% in the control group (nonsignificant). Treatment effects were greater among the participants who completed the study; 78.6% of completers had a treatment response compared with 42.1% of controls (P=.073).
                Although paroxetine may not be efficacious for all persons with MS and MDD, it appears to benefit some individuals. Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors. The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine. However, most data were collected in samples of outpatients. To overcome this restriction, a six-week double-blind control-group study, comparing 30 mg paroxetine with 150 mg amitriptyline per day, was performed in a sample of inpatients suffering from major depression. Generally speaking, the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline, either with respect to the total score on the Hamilton Depression Scale (HAMD) and the Clinical Global Impressions or with respect to the subscores of the HAMD. One exception was the retardation subscore, in which amitriptyline showed a greater degree of reduction. Both drugs had a characteristic side-effect profile. Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea. reuptake inhibitors (SSRIs) during continuation therapy. This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression, quality of life, and personality outcomes. Outpatients with unipolar major depression (DSM-III-R) were randomly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine (20-40 mg) or sertraline (50-150 mg). Assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale, the Battelle Quality of Life Questionnaire, and the Structured Clinical Interview for DSM-III-R Personality Disorders screen questionnaire. One hundred seventy-six patients (mean age, 43 years; 64% female; baseline MADRS, 30.3) were treated with sertraline and 177 patients (mean age, 42 years; 71% female; MADRS, 30.7) with paroxetine. Antidepressant efficacy during continuation therapy was sustained, with only 2% of patients receiving sertraline and 9% of patients receiving paroxetine suffering a relapse. Continuation therapy resulted in a substantial conversion of responders during short-term treatment to full remission: remitter rates increased from 52% to 80% for sertraline and from 57% to 74% for paroxetine. The improvements in quality of life were related to a reduced depression score. SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality. A logistic regression analysis identified early response (25% reduction in MADRS scores at week 2) as the most important predictor of treatment response, whereas high severity, chronicity, and poor baseline quality of life had no effect. Both treatments were well-tolerated, with sertraline having a somewhat lower side effect profile. Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy. Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology. To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors. Previous studies have shown a positive association between pain and depression, though evidence supporting a direct link between these two variables is less robust. Using a placebo-controlled trial, the authors examined the analgesic and antidepressant efficacy of paroxetine (20 mg) in chronic low back pain sufferers. The authors examined the associations among pain, depression, disability, and illness attitudes. Paroxetine showed no effects on pain or depression compared with placebo; however, subjects randomized to paroxetine were more likely to reduce concomitant analgesic medication. The cross-sectional association of depression and pain at baseline (r = 0.2, P = 0.02) was weaker than the association between depression and disability (r = 0.3, P = 0.004). Similarly, the association of change in depression scores with change in pain (r = 0.25, P = 0.016) was weaker than change between depression and disability (r = 0.49, P<0.0005). Whereas the relationship between pain and depression became nonsignificant when disability and illness attitudes were controlled, the relationship between depression and disability remained highly significant when pain and illness attitudes were controlled. These data are consistent with the association between pain and depression being wholly modulated by disability and illness attitudes, with no direct relationship between pain and depression.
Both desipramine and paroxetine show a trend towards efficacy in depression in MS the short term, but both treatments were associated with adverse effects, with significantly more patients treated with paroxetine suffering from nausea or headache. Further clinical research on the treatment of depression in MS is clearly needed. Future trials should address the efficacy and tolerability in the long term and compare antidepressant treatments head-to-head.