Controlled comparison of two different doses of milnacipran in major depressive outpatients

We compared the antidepressant efficacy and patient tolerance of two different doses of milnacipran (75 mg and 150 mg daily) in 66 outpatients with major depression, using the 17-item Hamilton Depression Rating Scale (HDRS). Only new patients who had never experienced frank depressive episodes before, or those who had remained free from thymoregulators for more than 1 year without recurrence of depressive symptoms, were recruited. Subjects were randomly selected to receive a daily dose of milnacipran that reached either 75 mg or 150 mg within 2-3 weeks and then remained stable over an 8-week period. The results showed a significant superiority of milnacipran at 150 mg/day over 75 mg/day at the end of the study period in both response (50% or more decrease in total score from baseline, P=0.026) and remission (total HDRS score lower than 7 points, P=0.034). A response was recorded for 56.0% of the patients treated with 75 mg of milnacipran and for 84.6% of those treated with 150 mg after the 8-week study period. No significant difference was seen between the treatment groups for either individual or total incidence of adverse events. Notably, nausea and vomiting occurred most often immediately after the first visit, when subjects in both groups started with a daily dose of 50 mg. We conclude that additional comparisons between different doses of milnacipran should be performed to confirm or deny the linear dose/efficacy relationship observed in the present study.     

Citalopram in the treatment of dysthymic disorder

This study aimed to provide preliminary data on the tolerability and effectiveness of citalopram for patients with dysthymic disorder. Twenty-one adult subjects meeting DSM-IV criteria for dysthymic disorder were enrolled in this 12-week open-label study, of whom 15 had pure dysthymia (e.g. no major depression in the past 2 years). Citalopram was initiated at 20 mg/day, and increased to a maximum of 60 mg/day. Response was defined as 50% or greater drop in score on the Hamilton Depression Rating Scale (HDRS) and a Clinical Global Impressions-I score of 1 ('very much improved') or 2 ('much improved'). Of these 15 pure dysthymic disorder subjects, all completed the trial, and 11 (73.3%) were treatment responders. All paired sample t-tests were highly significant, demonstrating significant average improvement on all measures of symptomatology and functioning. Scores on the 24-item HDRS decreased from 22.3+/-4.3 at baseline to 9.1+/-7.8 at week 12 [t(14)=6.1, P<0.001]. In addition, improvement was noted in self-reported measures of temperament and social functioning. The average final dose of citalopram was 39 mg/day. Side-effects were reported by nine of 15 subjects (60%), most frequently gastrointestinal symptoms (n=5), dry mouth (n=5) and sexual side-effects (n=3). These findings suggest the effectiveness and tolerability of citalopram in treating dysthymic disorder. Double-blind prospective studies are needed comparing citalopram both to placebo and to other medications, assessing both initial and sustained response to treatment.     

Milnacipran plasma levels and antidepressant response in Japanese major depressive patients

The relationship between antidepressant effects and plasma levels of milnacipran was studied in 49 cases of major depression without psychotic features during 6 weeks of milnacipran treatment. The daily dose of milnacipran was 50 mg/day for the first week, and up to 100 mg/day thereafter. Depressive symptoms were evaluated by the Montgomery and Asberg depression rating scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of this study. Thirty-four patients (69.4%) were responders (defined as a 50% or greater decrease in the baseline MADRS score). Significant differences of MADRS scores were seen from 1 week after the beginning of this study (p=0.004, unpaired t-test) between responders and nonresponders. The mean plasma milnacipran level of responders, 82.0 +/- 29.4 ng/ml, was similar to that of non-responders, 78.6+/-23.1 ng/ml; there was no significant difference between responders and nonresponders. Neither a significant linear nor a curvilinear relationship was obtained between the final MADRS score and the plasma levels of milnacipran. Although there was no significant relationship between the plasma levels of milnacipran and the antidepressant response, milnacipran should be considered an efficacious agent in the treatment of major depressive patients.     

Differential effects of milnacipran and fluvoxamine, especially in patients with severe depression and agitated depression: a case-control study

We attempted to compare the antidepressant efficacy of milnacipran and fluvoxamine in 202 outpatients with major depression, using the 17-item Hamilton Depression Rating Scale (HDRS). Special attention was paid to the difference of responsiveness as a function of the severity of depression and individual HDRS factors. As a result, while no significant difference between the treatment groups was found overall, a positive response (50% or more decrease in total score from the baseline) was recorded significantly more often with milnacipran than fluvoxamine recipients whose baseline HDRS total score was greater than 19 points. Furthermore, there was a significant difference of response for the 'agitation' and 'insomnia' factors in favour of milnacipran. In both treatment groups, the incidence of adverse events, characteristic of tricyclic antidepressants such as dry mouth, constipation, somnolence and postural hypotension, was low. While complaints concerning the upper intestinal tract, such as epigastric distress, were predominant in the fluvoxamine group, urological complications and palpitations were reported only in the milnacipran group. In conclusion, we suggest that milnacipran is preferred to selective serotonin reuptake inhibitors for the treatment of depressed patients with agitation as well as severely depressed patients.     

Alprazolam: an antidepressant? Alprazolam, desipramine, and an alprazolam-desipramine combination in the treatment of adult depressed outpatients

The antidepressant efficacy of alprazolam (ALP) was tested in a double-blind controlled comparison with desipramine (DMI) and an ALP-DMI combination in outpatients diagnosed with major depressive disorder by Research Diagnostic Criteria (90% met criteria for endogenous subtype). Following a placebo period of at least 1 week, subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale (HDRS) scores were administered oral doses of the active medication (N = 79), in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI. Treatment continued for 6 weeks, and all subjects who completed at least 2 weeks (N = 69) were included in endpoint analyses. Following the placebo baseline, symptoms were rated again at day 5 and at the end of weeks 1, 2, 4, and 6. Final doses averaged 4.6 +/- 1.3 mg for the ALP group, 230 +/- 61 mg for the DMI group, and 4.6 +/- 1.2 mg ALP + 229.5 +/- 1.2 mg DMI for the combination group. The final outcome was a comparable degree of improvement at the endpoint among the three treatment groups on measures of depression (HDRS and Beck Depression Inventory), anxiety (Hamilton Anxiety Rating Scale), and global improvement (Global Assessment Scale, and Physician and Patient Global Impressions). A similar outcome was found for the subgroup of patients who completed all 6 weeks (N = 56). Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression, anxiety, and global status. These results suggest that ALP alone is as effective as a standard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication. Side effect profiles were compared among treatment groups and are discussed, as are other clinical studies that have investigated ALP's potential antidepressant efficacy.     

Clinical utility of milnacipran in comparison with other antidepressants

The utility of milnacipran in the treatment of major depression has been the subject of an extensive clinical development programme. Comparative studies with tricyclic antidepressant drugs have demonstrated equivalent efficacy, with improved tolerability, in particular with respect to autonomic effects. In comparison with selective serotonin reuptake inhibitors (SSRIs), milnacipran shows similar good tolerability. It appears superior to such drugs in the treatment of severe depression, but equivalent to them for mild to moderate depression. In contrast to treatment with SSRIs, treatment response to milnacipran appears to be associated with the degree of psychomotor retardation. The good tolerability of milnacipran makes it safe in overdose. This drug also has a beneficial effect on suicidal ideation. Maintenance therapy with milnacipran has been demonstrated to reduce the recurrence of depressive episodes.     

Efficacy and tolerability of milnacipran in the treatment of major depression in comparison with other antidepressants : a systematic review and meta-analysis

BACKGROUND: Milnacipran, a dual serotonin-noradrenaline reuptake inhibitor, is one of the newer antidepressants that clinicians use for the routine care of patients with major depression. We undertook a systematic review and meta-analysis of randomized controlled trials that compared the efficacy and tolerability of milnacipran with other antidepressants. OBJECTIVE: To assess the efficacy and tolerability of milnacipran in comparison with TCAs, SSRIs and other drugs in the acute phase of treatment for major depression. METHODS: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials registers, journals, conference proceedings, trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished randomized controlled trials that compared the efficacy and adverse events of milnacipran versus any other antidepressant. The search was conducted in December 2006 and updated in May 2007. No language restrictions were applied. All relevant authors were contacted to supplement any incomplete reporting in the original papers. Randomized controlled trials comparing milnacipran with any other active antidepressants as monotherapy in the acute phase of treatment for major depression were selected. Participants were aged > or =18 years, of both sexes and with a primary diagnosis of unipolar major depression. Studies were excluded when the participants had specific psychiatric and medical co-morbidities.Two independent reviewers assessed the quality of trials for inclusion, and subsequently extracted data. Disagreements were resolved by consensus. Meta-analyses were conducted for efficacy and tolerability outcomes. Sixteen randomized controlled trials (n = 2277) were included in the meta-analyses. RESULTS: No differences were found in achieving clinical improvement, remission or overall tolerability when comparing milnacipran with other antidepressants. However, compared with the TCAs, fewer patients taking milnacipran were early treatment withdrawals due to adverse events (number needed to harm (NNH) = 15; 95% CI 10, 48). Significantly more patients taking TCAs experienced adverse events compared with milnacipran (NNH = 4; 95% CI 3, 7). CONCLUSIONS: The overall effectiveness and tolerability of milnacipran versus other antidepressants does not seem to differ in the acute phase of treatment for major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of premature withdrawal due to adverse events and the rates of patients experiencing adverse events. Milnacipran may benefit some patient populations who experience adverse effects from other antidepressants in the acute phase of treatment for major depression.     

Milnacipran: new preparation. Tricyclics remain first-line antidepressants

Several placebo-controlled trials have shown that milnacipran, 100 mg/day in two doses, is an effective antidepressant in both the ambulatory and hospital settings. Comparative trials against tricyclic antidepressants (imipramine and clomipramine) failed to show that milnacipran was any more effective. Milnacipran has not been compared with specific or non specific MAOI antidepressants. As regards non tricyclic-non MAOI antidepressants, milnacipran has been compared only to two specific serotonin reuptake inhibitors, fluvoxamine and fluoxetine. The trials cannot convince us of a difference in efficacy between the two types of treatment. The claimed superiority of milnacipran over serotonin reuptake inhibitors is not based on firm evidence of better efficacy or fewer adverse effects. The overall tolerability of milnacipran is similar to that of fluoxetine and fluvoxamine. Relative to the tricyclic antidepressants, milnacipran has fewer atropinic effects (sedation and sweating). In contrast, it cause more dysuria, and cannot, therefore, replace tricyclics in elderly men with prostate disorders. Tricyclics remain the preferred first-line antidepressant drugs. When they are contraindicated or poorly tolerated, many other antidepressants with well-documented risk-benefit ratios are available.     

Milnacipran, a new specific serotonin and noradrenaline reuptake inhibitor

Milnacipran is a new antidepressant which inhibits equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo with no effect on dopamine reuptake. Microdialysis studies have shown increased extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor. In particular, and unlike tricyclic antidepressants (TCAs), it has no activity at noradrenergic, muscarinic or histaminergic receptors. Contrary to TCAs, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. Milnacipran has a high bioavailability, low plasma protein binding, and is largely eliminated in the urine as the parent drug or as a glucuronide. These features suggest that interactions with other drugs given concurrently are unlikely. Studies in patients with liver dysfunction and in the elderly suggest that dose adjustment is not necessary. In patients with renal impairment, decreased elimination of milnacipran is correlated to the degree of renal impairment allowing an easy dosage adjustment. An intermediate half-life of approximately 8 h is compatible with twice-daily administration. Clinical studies comparing milnacipran, placebo and other antidepressants provide evidence of its efficacy in moderate to severe depression in both hospitalized and outpatient settings. Meta-analyses of the original data of controlled trials comparing milnacipran with imipramine or selective serotonin reuptake inhibitors (SSRIs) show that milnacipran provides antidepressant efficacy similar to that of TCAs and significantly superior to that of SSRIs. An analysis of a database of over 3300 patients shows that both the general and cardiovascular tolerability of milnacipran are superior to those of TCAs with notably less cholinergic side effects. The tolerance of milnacipran was comparable to that of SSRIs with a higher incidence of dysuria with milnacipran but a higher frequency of nausea and anxiety with the SSRIs. Milnacipran represents an interesting new therapeutic option in depression, being as well tolerated as the SSRIs but offering clinical efficacy similar to the TCAs.     

A comparative study of milnacipran and imipramine in the treatment of major depressive disorder

The antidepressant efficacy and safety of milnacipran, a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline, was compared with that of the tricyclic antidepressant, imipramine, in a multi-centre, double-blind, randomised, parallel group, comparative trial in 5 hospital centres in Spain. One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association (third revision), with a minimum score of 25 on the Montgomery and Asberg Depression Rating Scale were treated for 6 weeks with milnacipran (100 mg/day) or imipramine (150 mg/day). Both treatments showed similar efficacy in reducing depressive symptoms. The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group, particularly those related to anticholinergic symptoms. Dysuria and shivering, however, were more common with milnacipran. The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine.     

Antidepressant therapy with moclobemide in primary care practice

A Swiss, open, multicentre clinical study was conducted in collaboration with 176 general practitioners and internists to evaluate the efficacy and tolerability of moclobemide, an antidepressant belonging to a class of novel reversible MAO-A inhibitors called RIMAs. Six hundred and fifty-four outpatients satisfying the DSM-III criteria of major depression were recruited and treated for at least four weeks. Efficacy was assessed with the Hamilton Depression Rating Scale (HDRS) and the Hospital Anxiety and Depression (HAD) self-rating scale. Subjects were grouped according to depression subtype, history, age and seveerity of depression and were evaluated individually. The global efficacy was assessed by the HDRS and Clinical Global Impression (CGI). The HDRS-score was reduced significantly after four weeks of treatment (p < 0.001). Moclobemide was effective in depression associated with anxiety or psychomotor retardation, in neurotic and agitated depression, in recurrent and chronic depression as well as initial depressive episodes, and in both young and old patients. According to the patients' self-ratings (HAD), moclobemide provided rapid relief of depressive and anxiety symptoms. The drug was well tolerated, as evidenced by the low incidence of side-effects.     

A comparative study of milnacipran and imipramine in the treatment of major depressive disorder

SUMMARY

The antidepressant efficacy and safety of milnacipran, a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline, was compared with that of the tricyclic antidepressant, imipramine, in a multi-centre, double-blind, randomised, parallel group, comparative trial in 5 hospital centres in Spain. One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association (third revision), with a minimum score of 25 on the Montgomery and Åsberg Depression Rating Scale were treated for 6?weeks with milnacipran (100?mg/day) or imipramine (150?mg/day). Both treatments showed similar efficacy in reducing depressive symptoms. The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group, particularly those related to anticholinergic symptoms. Dysuria and shivering, however, were more common with milnacipran. The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine.     

Efficacy of tianeptine vs placebo in the long-term treatment (16.5 months) of unipolar major recurrent depression*

To compare the efficacy and acceptability of tianeptine vs placebo in the long-term treatment of unipolar major recurrent depression, 268 hospitalized and ambulatory patients meeting DSM III-R criteria for major depression with a 21-item Hamilton depression rating scale (HDRS) score >/= 17 and at least one episode in the previous 5 years received tianeptine in a 6-week multicenter open study. At D42, 185 responders (intention-to-treat population) were randomized for ethical reasons into two unbalanced groups to receive tianeptine 37.5 mg/day (n= 111) or placebo (n= 74) for 16.5 months; 173 of the 185 responders were defined as strict responders (per-protocol population) by an HDRS score which was both < 15 and at least halved vs D1, combined with clinical confirmation by the investigator. The groups were similar at baseline except in the severity of the depressive episode (greater in the tianeptine group: 33 vs 18%, p= 0.018). Relapse (before 6 months) and recurrence (after 6 months) were defined by an HDRS score >/= 15 and/or clinical global impression score >/= 4, and clinical confirmation by the investigator. Visits were at D63 and M3, M6, M9, M12, M15, and M18. Efficacy was measured by the number of relapses and recurrences and their time of onset (Kaplan-Meier survival curve analysis). Between D42 and M18 (intention-to-treat population), relapse and recurrence were less frequent on tianeptine vs placebo (16 vs 36%, p= 0.002). Comparison over time also showed a higher proportion of patients without relapse or recurrence on tianeptine (p< 0.001); the intergroup difference increased with follow-up duration. Secondary analysis of relapse in the intention-to-treat group showed a higher proportion on placebo (p= 0.002); secondary analysis of recurrence over time showed that the difference in the percentages of recurrence-free patients was nonsignificant in the intention-to-treat population (p= 0.067) but significant in the per-protocol population (p= 0.036) in favor of tianeptine. Acceptability did not differ between the groups. Treatment-induced adverse events were rare and mild in both groups. These data support the use of tianeptine in the long-term treatment of unipolar major recurrent depression. Relapse and recurrence were decreased two- to threefold on tianeptine vs placebo with no difference in acceptability between the two groups. Copyright 1997 Doin Editeurs     

Fluoxetine in the prevention of depressive recurrences: a double-blind study

Optimal outcomes from depression treatment are long-term recovery and, in the case of recurrent depression, prevention of new episodes. However, few data are available concerning the long-term efficacy of antidepressants in prophylactic treatment to prevent recurrences of depression. The efficacy and safety of fluoxetine 20 mg/day was evaluated in reducing the number of depressive episodes and in extending the time free of symptoms in patients with recurrent unipolar major depression. Patients with recurrent unipolar major depression according to DSM-III-R criteria and who responded to 32 weeks of open-label fluoxetine were randomly assigned to receive fluoxetine 20 mg/day (N = 70) or placebo (N = 70) for 48 weeks of double-blind maintenance treatment. Outcome measures were the percentage of recurrences and time to recurrence. Safety assessments included treatment-emergent adverse events, reasons for discontinuation, vital signs, and laboratory measures. Fluoxetine was associated with a statistically significantly smaller percentage of patients who had a recurrence compared with placebo (20% vs. 40%; chi2 analysis, p = 0.010). The symptom-free period was significantly longer for patients treated with fluoxetine versus placebo (295 vs. 192 days; Kaplan-Meier estimates, log-rank test, p = 0.002). Treatments were well tolerated during maintenance treatment. The only statistically significant difference in adverse events between treatment groups was anxiety, which was more frequent in the placebo group (fluoxetine, 12.9% vs. placebo, 30%; chi2 analysis, p = 0.013). Two placebo-treated patients and no fluoxetine-treated patients were withdrawn because of adverse events. In conclusion, fluoxetine at 20 mg/day was effective and well tolerated for the prophylactic treatment of recurrent unipolar major depression.     

Efficacy and safety of amisulpride 50 mg versus paroxetine 20 mg in major depression: a randomized, double-blind, parallel group study.

The efficacy of amisulpride in depressive disorders has been demonstrated in dysthymia and in double depression. Limited data are available in major depression. A randomized, double-blind, parallel group, multicentre study was set up to compare the efficacy and tolerability of amisulpride (50 mg o.d.) and paroxetine (20 mg o.d.) for 8 weeks in 272 patients with major depression (DSM-IV and baseline Hamilton Depression Rating Scale (HAMD) score > or = 18). The study was designed as a non-inferiority trial based on the proportion of responders (> or = 50% decrease in HAMD total score) at end-point, with a maximal allowable difference of 15%; secondary end-points included HAMD total and cluster scores, Montgomery and Asberg Depression Rating Scale score and responders rates and Clinical Global Impression improvement. The tolerability evaluation was based on incidence of adverse events and routine laboratory tests. The results did not disclose statistically significant differences between treatments, although the hypothesis of an efficacy difference between the two treatments within the set limit at day 56 could not be accepted. The issue of non-inferiority trials is discussed.     

Fluoxetine response: endpoint vs pattern analysis

A 6-week double-blind trial of fluoxetine treatment of unipolar major depressive disorder in 49 patients was evaluated in terms of improvement in the Hamilton Depression Rating Scale (HDRS) and Clinical Global Improvement (CGI) scores. A relationship was found between change in HDRS (absolute and percentage decrease from baseline) and final CGI ratings. However, because of a few placebo-responders, endpoint analysis with both the HDRS and CGI showed no differences between active drug and placebo. Pattern analysis of persistent response did successively separate active drug from placebo (less than 0.05).     

Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine

The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression.     

Spotlight on sertraline in the management of major depressive disorder in elderly patients

Sertraline is a selective serotonin reuptake inhibitor (SSRI) with well established antidepressant and anxiolytic activity. Results from several well designed trials show that sertraline (50-200 mg/day) is effective in the treatment of major depressive disorder in elderly patients (> or =60 years of age). Primary endpoints in most studies included the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression score and the Montgomery-Asberg Depression Rating Scale. Sertraline was significantly more effective than placebo and was as effective as fluoxetine, nortriptyline and imipramine in elderly patients. During one trial, amitriptyline was significantly more effective than sertraline (mean reduction from baseline on one of six primary outcomes [HDRS]), although no quantitative data were provided. Subgroup analysis of data from a randomised, double-blind trial in elderly patients with major depressive disorder suggests that vascular morbidity, diabetes mellitus or arthritis does not affect the antidepressant effect of sertraline. Secondary endpoints from these clinical trials suggest that sertraline has significant benefits over nortriptyline in terms of quality of life. In addition, significant differences favouring sertraline in comparison with nortriptyline and fluoxetine have been recorded for a number of cognitive functioning parameters. Sertraline is generally well tolerated in elderly patients with major depressive disorder and lacks the marked anticholinergic effects that characterise the adverse event profiles of tricyclic antidepressants (TCAs). The most frequently reported adverse events in patients aged > or =60 years with major depressive disorder receiving sertraline 50-150 mg/day were dry mouth, headache, diarrhoea, nausea, insomnia, somnolence, constipation, dizziness, sweating and taste abnormalities. The tolerability profile of sertraline is generally similar in younger and elderly patients. Sertraline has a low potential for drug interactions at the level of the cytochrome P450 enzyme system. In addition, no dosage adjustments are warranted for elderly patients solely based on age. CONCLUSION: Sertraline is an effective and well tolerated antidepressant for the treatment of major depressive disorder in patients aged > or =60 years. Since elderly patients are particularly prone to the anticholinergic effects of TCAs as a class, SSRIs such as sertraline are likely to be a better choice for the treatment of major depressive disorder in this age group. In addition, sertraline may have advantages over the SSRIs paroxetine, fluoxetine and fluvoxamine in elderly patients because of the drug's comparatively low potential for drug interactions, which is of importance in patient groups such as the elderly who are likely to receive more than one drug regimen.     

Sertraline: a review of its use in the management of major depressive disorder in elderly patients

Sertraline is a selective serotonin reuptake inhibitor (SSRI) with well established antidepressant and anxiolytic activity. Results from several well designed trials show that sertraline (50 to 200 mg/day) is effective in the treatment of major depressive disorder in elderly patients (> or =60 years of age). Primary endpoints in most studies included the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI) score and the Montgomery-Asberg Depression Rating Scale (MADRS). Sertraline was significantly more effective than placebo, and was as effective as fluoxetine, nortriptyline and imipramine in elderly patients. During one trial, amitriptyline was significantly more effective than sertraline [mean reduction from baseline on one of six primary outcomes (HDRS)], although no quantitative data were provided. Subgroup analysis of data from a randomised, double-blind trial in elderly patients with major depressive disorder suggests that vascular morbidity, diabetes mellitus or arthritis does not affect the antidepressant effect of sertraline. Secondary endpoints from these clinical trials suggest that sertraline has significant benefits over nortriptyline in terms of quality of life. In addition, significant differences favouring sertraline in comparison with nortriptyline and fluoxetine have been recorded for a number of cognitive functioning parameters. Sertraline is generally well tolerated in elderly patients with major depressive disorder, and lacks the marked anticholinergic effects that characterise the adverse event profiles of tricyclic antidepressants (TCAs). The most frequently reported adverse events in patients aged > or =60 years with major depressive disorder receiving sertraline 50 to 150 mg/day were dry mouth, headache, diarrhoea, nausea, insomnia, somnolence, constipation, dizziness, sweating and taste abnormalities. The tolerability profile of sertraline is generally similar in younger and elderly patients. Sertraline has a low potential for drug interactions at the level of the cytochrome P450 enzyme system. In addition, no dosage adjustments are warranted for elderly patients solely based on age. CONCLUSION: Sertraline is an effective and well tolerated antidepressant for the treatment of major depressive disorder in patients aged > or =60 years. Since elderly patients are particularly prone to the anticholinergic effects of TCAs as a class, SSRIs such as sertraline are likely to be a better choice for the treatment of major depressive disorder in this age group. In addition, sertraline may have advantages over the SSRIs paroxetine, fluoxetine and fluvoxamine in elderly patients because of the drug's comparatively low potential for drug interactions, which is of importance in patient groups such as the elderly who are likely to receive more than one drug regimen.     

Controlled comparison of two doses of milnacipran (F 2207) and amitriptyline in major depressive inpatients

A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran (50 mg and 100 mg/day) and amitriptyline (150 mg/day) in three parallel groups of 45 major depressive inpatients defined by Research Diagnostic Criteria. After a wash-out period of 4–7 days on placebo with lorazepam and/or nitrazepam if necessary, patients were randomly assigned to a daily dose of milnacipran 50 mg, milnacipran 100 mg or amitriptyline 150 mg reached on the 5th day and then stable over a 4-week period, with weekly assessments by means of the Montgomery and Asberg depression scale, the Hamilton depression scale, the Clinical Global Impressions (CGI) and the Target Emergent Signs and Symptoms. Results showed significant superiority of both milnacipran 100 mg/day and amitriptyline over milnacipran 50 mg/day at the end of the treatment period. However, amitriptyline induced a nonsignificant trend toward more rapid improvement after 2 weeks of treatment, mainly based on items related to insomnia, supporting more sedative properties of amitriptyline as compared to milnacipran. Anticholinergic side-effects were significantly lower with milnacipran than with amitriptyline, explaining why milnacipran 100 mg exhibited at the end of the treatment period, a nonsignificantly better efficacy index on the CGI. Moreover, in contrast to milnacipran, amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain.