Emotional blunting with antidepressant treatments: A survey among depressed patients.

BACKGROUND: Emotional blunting is regularly reported in depressed patients on antidepressant treatment but its actual frequency is poorly understood. We have previously used qualitative methods to develop an appropriate scale, the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA). METHODS RESULTS: Six hundred and sixty nine depressed patients on treatment and 150 recovered (formerly depressed) controls (aged ≥18 years) participated in this internet-based survey. The rate of emotional blunting in treated depressed patients was 46%, slightly more frequent in men than women (52% versus 44%) and in those with higher Hospital Anxiety and Depression (HAD) scale scores. There was no difference according to antidepressant agent, though it appeared less frequent with bupropion. Depressed patients with emotional blunting had much higher total blunting scores on OQESA than controls (42.83 ± 14.73 versus 25.73 ± 15.00, p < 0.0001) and there was a correlation between total blunting score and HAD-Depression score (r = 0.521). Thus, those with HAD-D score >7 (n = 170) had a higher total questionnaire score, 49.23±12.03, than those with HAD-D score ≤7 (n = 140), 35.07 ± 13.98, and the difference between the two groups was highly significant. However, patients with HAD-D score ≤7 (n = 140) had a higher total score (35.07 ± 13.98) than the recovered controls (n = 150) (25.73 ± 15.00), and the difference between the two groups was significant. Among the patients with emotional blunting, 37% had a negative perception of their condition and 38% positive. Men reported a more negative perception than women (p=0.008), and patients with a negative perception were more likely to have higher HAD scores. Higher levels of emotional blunting are associated with a more negative perception of it by the patient (r = -0.423). LIMITATIONS: Include self-evaluation and the modest size of the sample for detection of differences between antidepressants. CONCLUSIONS: Emotional blunting is reported by nearly half of depressed patients on antidepressants. It appears to be common to all monoaminergic antidepressants. The OQESA scores are highly correlated with HAD depression score; emotional blunting cannot be described simply as a side-effect of antidepressants, but also as a symptom of depression. A higher degree of emotional blunting is associated with a poorer quality of remission. The OQESA scale allows the detection of this phenomenon.

Early effect on general interest, and short-term antidepressant efficacy and safety of agomelatine (25-50mg/day) and escitalopram (10-20mg/day) in outpatients with Major Depressive Disorder. A 12-week randomised double-blind comparative study.

BACKGROUND: A double-blind, randomized, study was conducted in 29 centers in Romania to evaluate the effect of agomelatine 25-50mg/day (n=144 patients) on general interest, overall clinical efficacy, and functionality in comparison with escitalopram 10-20mg/day (n=143 patients) in out-patients diagnosed with moderate to severe Major Depressive Disorder (MDD). METHODS: The primary endpoint of the study was the score difference between agomelatine and escitalopram were assessed on the item 13 of the Quick Inventory of Depressive Symptomatology (16-Item) Self-Report (QIDS-SR16) over the first week period. Secondary measures include the primary criterion on the 12-week period, the within-group evolution over 12 weeks of the 17-item Hamilton Depression Scale (HAM-D17) total score, CGI severity of illness (CGI-S) and CGI-I scores, and functionality by using the self-rated Sheehan Disability Scale (SDS). RESULTS: After one week, the mean General Interest score showed no statistically significant difference between treatments. Over 12 weeks, patients felt more and more interested in other people and activities than before having taken medication. Both agomelatine and escitalopram improved depressive symptoms and symptom-related functional impairment of patients. Both agomelatine and escitalopram were well-tolerated by patients. LIMITATIONS: The strength of our results would benefit from additional data from trials using a similar design and other active comparators. CONCLUSION: There was no difference in week 1 changes of interest between agomelatine and escitalopram. The relatively good tolerability of agomelatine and escitalopram is confirmed.

Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties.

Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors and as a neutral antagonist at 5-HT2C receptors. Accumulating evidence in a broad range of experimental procedures supports the notion that the psychotropic effects of agomelatine are due to the synergy between its melatonergic and 5-hydroxytryptaminergic effects. The recent demonstration of the existence of heteromeric complexes of MT1 and MT2 with 5-HT2C receptors at the cellular level may explain how these two properties of agomelatine translate into a synergistic action that, for example, leads to increases in hippocampal proliferation, maturation and survival through modulation of multiple cellular pathways (increase in trophic factors, synaptic remodelling, glutamate signalling) and key targets (early genes, kinases). The present review focuses on the pharmacological properties of this novel antidepressant. Its mechanism of action, strikingly different from that of conventional classes of antidepressants, opens perspectives towards a better understanding of the physiopathological bases underlying depression.

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

[Value of tianeptine in treating major recurrent unipolar depression. Study versus placebo for 16 1/2 months of treatment]. / Intérêt de la tianeptine dans le traitement des dépressions majeures unipolaires récurrentes. Etude versus placebo sur 16 mois et demi de traitement.

OBJECTIVES: The aim of this study was to assess the efficacy of tianeptine vs placebo in the long-term treatment of unipolar major recurrent depression. METHOD: 286 patients who met DSM-III-R criteria for major depression with a Hamilton Depression Rating Scale (HDRS-21 items) score > or = 17, and with a history of at least one previous episode within the last 5 years, were treated in an open trial with tianeptine for 6 weeks. 185 patients who responded to treatment at day 42 (intent-to-treat) were randomly assigned to tianeptine 37.5 mg/day (n = 111), or placebo (n = 74). Among these patients 173 were strict responders to tianeptine (per-protocol-population), as defined in the present study by a 50% reduction in the HDRS score, a global score lower than 15 and confirmation by clinical evaluation. Both groups were comparable except for the severity of the depressive episode (significantly more severe in the tianeptine group (33%) than in the placebo group (18%)) (p = 0.018). Relapses and recurrences were defined by a HDRS score > or = 15, and/or a CGI score > or = 4, the recurrences being confirmed by the clinician. Patients were subsequently evaluated at day 63, and the 3rd, 6th, 9th, 12th, 15th and 18th month. RESULTS: Special attention was given to the number of relapses and recurrences, and to the delay of onset (Kaplan Meier Method). Between day 42 and 18th month (intent-to-treat group), the rate of relapses and recurrences was significantly higher in the placebo group (36%), than in the tianeptine group (16%) (p = 0.002). Long term comparison of the rate of patients without recurrence or relapse, also showed a significant difference in favour of tianeptine (p < 0.001). The difference between teh 2 groups increased within time. Secondary analysis of relapses and recurrence in the intent-to-treat group showed a significantly higher rate of relapses for the placebo group (p = 0.002); the rate of patients without recurrences in the long term appeared to be at the limit in the intent-to-treat group (p = 0.067) but significant in the per-protocol-group, in favour of tianeptine (p = 0.36). Furthermore, no difference was observed between the 2 groups, in terms of tolerance. Secondary effects attributed to treatment by investigators were rare and benign in each group. CONCLUSIONS: These data support the use of tianeptine in the long term treatment of unipolar major recurrent depression. Relapses and recurrences were 2 to 3 times less frequent with tianeptine as compared to placebo. Furthermore, prolonged treatment with tianeptine appeared to be very well tolerated.

[Major depressive episodes in patients over 70 years of age. Evaluation of the efficiency and acceptability of tianeptine and mianserin]. / Episodes dépressifs majeurs de sujets âgés de plus de 70 ans. Evaluation de l'efficacité et de l'acceptabilité de la tianeptine et de la miansérine.

OBJECTIVES: The aim of this multicenter study was to compare the efficacy, acceptability and impact on quality of life of tianeptine (T) and mianserine (M) in patients over 70 years of age with major depression. METHODS: Fulfilment of the DSM IIIR criteria for major depression with a total Montgomery and Asberg depression rating scale (MADRS) of at least 25 and a Hamilton anxiety rating scale (HARS) of at least 18 were required for inclusion. The 315 men and women enrolled in the study were given, by double blind assignment, either T: 37.5 mg/day, T: 25 mg/day or M: 30 mg/day. Treatment duration was 6 months in all three groups and follow-up continued for 3 months after withdrawal of tianeptine or mianserine. The main efficacy criterion was the MADRS score evaluated at each of 6 visits at day 15 (D15) and month 1 (M1), M2, M4, M4.5 and M6. The HARS score was another efficacy criterion. Overall assessment of efficacy and acceptability was done at each visit by the patient and the investigator. Both the patient and the physician estimated global effectiveness on a quality of life scale at M1, M3, M6 and M9. RESULTS: In the intention-to-treat population (n = 299), the antidepressant efficacy of tianeptine and mianserine was not significantly different, whether assessed as effect on anxiety or on quality of life. Scores however tended to be better in the T: 37.5 mg group. Acceptability was good as shown by the low number of adverse events in all 3 groups, but at D15, the incidence of impaired vigilance or equilibrium was significantly lower in the T: 25 mg group than in the M: 30 mg group, emphasizing the advantage of tianeptine in decreasing the risk of falling. Physician-assessed tolerance and acceptability was significantly different at M3 (p = 0.014) and at M6 (p = 0.028) in favor of T: 37.5 mg, indicating that though increasing dosage does not improve efficacy, there is no risk of poorer acceptability. CONCLUSION: These findings reconfirm the antidepressive efficacy, acceptability and safety of tianeptine. They also confirm the anxiolytic aspect associated with the antidepressive effect of tianeptine without any sedative effect. Tianeptine is particularly well indicated in the treatment of depression in elderly or very elderly subjects.

[Anxiety-related and depressive disorders in women during the premenopausal and menopausal period. Study of the efficacy and acceptability of tianeptine versus maprotiline]. / Etats anxio-dépressifs de la femme en période préménopausique et ménopausique. Etude de l'efficacité et de l'acceptabilité de la tianeptine versus maprotiline.

This study was conducted to evaluate the effectiveness and acceptability of Tianeptine (T) versus Maprotiline (M) in the management of anxiodepressive disorders in menopausal and premenopausal women. Anxio-depressive women with a Montgomery Asberg Depression score (MADRS) > 20 and a Hamilton Anxiety score (HARS) > 15 were included in the study. T or M were the only psychotropes taken by the patients during the study. Eighty-three women were enrolled and given, by double blind assignment T 37.5 mg/day or M 75 mg/day (T n = 42; M n = 41). The effectiveness of therapy was assessed on D5, D15, D30 and D60 by the MADRS, HARS, CGI and CHESS scores; acceptability was assessed by the CHESS scale. To exclude placebo responders, the patients were treated with a placebo for 7 days prior to enrollment. A significant improvement in the MADRS score, compared with the previous score, remained until D60 for the T group and M group (p < 0.01). The improvement in the MADRS score was higher (p = 0.025) in the T group than in the M group. At D60, there was a statistically significant difference between T and M in favour of T (p = 0.04). Similar results were obtain with HARS and CGI (item 1). The incidence of side effect was significantly lower in the group treated with T than in the group treated with M. At any time point, there were more patients in the M group (p < 0.001) who complained of side effects than in the T group. The patients were divided into subgroups according to whether or not they were also receiving Hormone Replacement Therapy (HRT). The group taking HRT and T had a more significant reduction in HARS (p = 0.038) and CHESS (p = 0.015) than the group taking T only. T administrated as a single psychotropic agent showed an improvement in the symptoms of anxio-depression which were significantly more important than in the control group with better control of associated complaints.