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  • Key Points: Presence of residual symptoms of depression was associated with a relapse rate of 76% compared with a relapse rate of 25% among patients who did not have residual symptoms In this study Patients with residual symptoms relapsed almost 3 times faster (median 68 weeks vs. 23 weeks) compared with asymptomatic patients References: Paykel ES. Ramana R. Cooper Z. Hayhurst H. Kerr J. Barocka A. Residual symptoms after partial remission: an important outcome in depression. Psychological Medicine. 25(6):1171-80, 1995 Nov. This paper draws attention to an important adverse outcome in depression, the occurrence of residual symptoms after partial remission. Among patients with definite major depression followed every 3 months to remission and thereafter, residual symptoms reaching 8 or more on the Hamilton Depression Scale 17-item total were present in 32% (19) of the 60 who remitted below major depression by 15 months. The pattern was of mild but typical depressive symptoms. Residual symptoms were more common in subjects with more severe initial illness, but were not related to any other predictors, including longer prior illness, dysthymia, or lower dose of drug treatment during the illness episode. There were weak associations with personality that might have been consequences of symptom presence. Residual symptoms were very strong predictors of subsequent early relapse, which occurred in 76% (13/17) of those with residual symptoms and 25% (10/40) of those without.
  • Key Points: The smaller the number, the more potent the drug Duloxetine is a very potent reuptake inhibitor of both 5-HT and NE The ratio compares the strength of NE binding to 5-HT binding. A ratio of 1 would indicate equa l affinity on NE compared to 5-HT. Study: Chart compares the inhibition of binding to human monamine uptake transporters by various uptake inhibitors, including Cymbalta, a dual reuptake inhibitor (DRI) of 5-HT and NE. Also shown is the SNRI (venlafaxine), various SSRIs, and a classic tricyclic antidepressant. Since this chart shows inhibition of binding, the lower the number, the stronger the binding. The chart suggest that in vitro, duloxetine is a more potent inhibitor of 5-HT and NE uptake than SSRIs or venlafaxine. References: Bymaster FP. Dreshfield-Ahmad LJ. Threlkeld PG. Shaw JL. Thompson L. Nelson DL. Hemrick-Luecke SK. Wong DT. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 25(6):871-80, 2001 Dec.
  • Key Points: Duloxetine produced significantly greater improvement on the core factor subscale of the HAMD17 than placebo, starting at 1 week and continuing at each point throughout the study by MMRM (mixed model repeated measures) analysis. The core factor subscale includes HAMD17 items that represent the core emotional symptoms of depression (item-1, depressed mood; item-2, feelings of guilt; item-3, suicide; item-7, work and activities; item-8, retardation). Background: The data presented here are from one of two identical but independent, 9-week, randomized, double-blind, placebo-controlled studies in adult outpatients who met DSM-IV criteria for major depressive disorder (MDD). None of the patients were considered treatment-refractory. Entry criteria included a DSM-IV diagnosis of major depression with a severity specified by a 17-item Hamilton Depression Rating Scale (HAMD-17) total score > 15 and a Clinical Global Impression of Severity (CGI-S) score of > 4 (indicating at least moderately ill) at baseline for out-patients at least 18 years of age.The relatively low cut-off of 15 on the 17-item HAMD was chosen to minimize encouraging raters to artificially inflate baseline scores, to provide greater accuracy. Note that all patients still had to meet full DSM-IV criteria for MDD and have a CGI-S > 4. References: Data on file, Lilly Research Laboratories. Data: Weeks 0 1 2 3 5 7 9 DLX 60 mg QD (n=121) 0 -1.9 -3.2 -4.04 -4.52 -4.74 -5.26 Placebo (n=115) 0 -1.19 -1.43 -2.22 -2.75 -2.65 -2.76 Study: F1J-MC-HMBH (A)
  • Key Points: Duloxetine produced significantly greater improvement on the HAMD17 anxiety subscale than placebo, starting at 2 weeks and continuing at each point throughout the study by mixed model repeated measures (MMRM) analysis. The anxiety subscale of the HAMD17 includes the following items: item-10, psychic anxiety; item-11, somatic anxiety; item-12, somatic symptoms (GI); item-13, somatic symptoms (general); item-15, hypochondriasis; and item-17, insight. Background: The data presented here are from one of two identical but independent, 9-week, randomized, double-blind, placebo-controlled studies in adult outpatients who met DSM-IV criteria for major depressive disorder (MDD). None of the patients were considered treatment-refractory. Entry criteria included a DSM-IV diagnosis of major depression with a severity specified by a 17-item Hamilton Depression Rating Scale (HAMD-17) total score > 15 and a Clinical Global Impression of Severity (CGI-S) score of > 4 (indicating at least moderately ill) at baseline for out-patients at least 18 years of age.The relatively low cut-off of 15 on the 17-item HAMD was chosen to minimize encouraging raters to artificially inflate baseline scores, to provide greater accuracy. Note that all patients still had to meet full DSM-IV criteria for MDD and have a CGI-S > 4. References: Dunner DL, Goldstein DJ, Mallinckrodt C, Lu Y, Detke MJ . Duloxetine in Treatment of Anxiety Symptoms Associated with Depression. Depression and Anxiety . 2003;18:53-61. Data: Weeks 0 1 2 3 5 7 9 DLX 60 mg QD (n=121) 0 -0.64 -1.58 -2.12 -2.59 -2.91 -3 Placebo (n=115) 0 -0.83 -1 -1.2 -1.43 -1.85 -1.99 Study: F1J-MC-HMBH (A)
  • Key Points: Duloxetine produced significantly greater improvement on HAMD 17 Item 10 (psychic anxiety) than placebo, starting at Week 1 and continuing at each point throughout the study by MMRM (mixed model repeated measures) analysis. These data are pooled from two independent trials. When analyzed separately, the duloxetine group showed significantly greater improvement compared with the placebo group at every post-baseline visit in one trial (p < .01 for all visits), and at Weeks 1, 2, 3, and 7 in the other trial (p<.05). Psychic anxiety is scored on a scale from 0 to 4 and includes “subjective tension and irritability, worrying about minor matters, apprehensive attitude apparent in face or speech, and fears expressed without questioning”. Patients with a primary anxiety disorder were excluded from the clinical trials. Note that the individual trials were not powered for separation on scales other than HAMD 17 total score. Background: Data were pooled from two identical but independent, 9-week, randomized, double-blind, placebo-controlled studies in adult outpatients who met DSM-IV criteria for major depressive disorder (MDD). The primary outcome was change in mean total score of the 17-item Hamilton Depression Rating Scale (HAMD 17 ) . None of the patients were considered treatment-refractory. Entry criteria included a DSM-IV diagnosis of major depression with a severity specified by a HAMD 17 total score > 15 and a Clinical Global Impression of Severity (CGI-S) score of > 4 (indicating at least moderately ill) at baseline. Data from all patients who were assigned to treatment with duloxetine or placebo (trial 1: N = 123 and 122 respectively; trial 2: N = 128 and 139 respectively) contributed to the safety database for this study. Efficacy data were analyzed for all randomized patients who had post-baseline data (trial 1: N = 121 and 115 for duloxetine or placebo respectively; trial 2: N = 123 and 136 for duloxetine or placebo respectively). For the 2 pooled studies, mean baseline HAMD 17 total score was 20.86 among the duloxetine group and 20.78 among the placebo group. Figure is created from data presented in Table 3 in the Hirschfeld 2005 manuscript. The p-values, which are reported in the Hirschfeld ms for Item 10, are p<.05 for all weeks. Actual p-values differ from week to week (p<.001 for weeks 1-7; p=.001 for week 9). P-values shown on the slide reflect the actual values from the data analysis. References: Hischfeld RMA, Mallinckrodt C, Lee TC, and Detke MJ. The Course of Depression-Symptom Improvement During Treatment With Duloxetine. Depression and Anxiety 2005;21:170-177. Brannan SK, Mallinckrodt CH, Detke MJ, Watkin JG, Tollefson GD. Onset and maintenance of antidepressant efficacy for duloxetine 60 mg QD. Presented at the 15 th US Psychiatric and Mental Health Congress; Las Vegas, NV; Oct. 28-31, 2002. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA . Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 2002;63:308-315. Detke MJ, Lu Y, Goldstein DJ, McNamara RK, Demitrack MA. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res 2002;36:383-390. Dunner DL, Goldstein DJ, Mallinckrodt C, Lu Y, Detke MJ. Duloxetine in treatment of anxiety symptoms associated with depression. Depress Anxiety 2003;18:53-61. Studies: F1J-MC-HMBHa, F1J-MC-HMBHb
  • The aim of this study was to examine the longitudinal response for overall and individual symptoms during the treatment of major depressive disorder. Data were pooled from two 9-week trials, which compared duloxetine 60-mg QD (n¼251) with placebo (n¼261) in the treatment of MDD. Changes from baseline in the 17-item Hamilton Depression Rating Scale (HAMD17) and in the Visual Analog Scales for pain were analyzed. Compared to placebo-treated patients, duloxetine-treated patients experienced greater improvement (Po.05) in the HAMD17 total score at Week 2. The individual symptoms showing the most rapid improvements (Week 1) were depressed mood, guilt, suicidal ideation, work/activities, and psychic anxiety as well as VAS back pain and shoulder pain. At subsequent visits, significant improvements were observed in retardation (Week 2); hypochondriasis (Week 3); general somatic symptoms (Week 5); middle and late insomnia (Week 7); and gastrointestinal (GI) symptoms, genital symptoms (level of sexual interest or ease of sexual arousal), insight, and early insomnia (Week 9). Significant advantages for duloxetine were not achieved at any visit for agitation, somatic anxiety, or weight loss. AtWeeks 1 and 2, placebotreated patients had significantly lower GI symptoms and reported less weight loss compared with duloxetine-treated patients; however, differences were not significant at subsequent visits. Furthermore, duloxetine was superior to placebo on GI symptoms at endpoint compared to placebo-treated patients; duloxetinetreated patients had a significantly higher response rate at Week 2 and a higher remission rate at Week 5. These results may help clinicians establish more accurate expectations regarding treatment with duloxetine. Depression and Anxiety 21:170–177, 2005.
  • Key Points: In this pooled analysis of all randomized patients in 6 placebo-controlled, SSRI comparator studies, the remission rates were 43% for duloxetine and 38% for SSRI, and 28% for placebo. In a subset of patients with a higher baseline HAMD17 scores (HAMD17 > 19) more commonly used in antidepressant trials, remission rates for duloxetine were statistically significantly greater than both SSRI and placebo. Remission was defined as a HAMD17 total score of < 7 at 8-weeks. Background: The data presented here are from six randomized, parallel-group, double-blind, placebo-controlled, SSRI-comparator studies in adult outpatients who met DSM-IV criteria for major depressive disorder (MDD). None of the patients were considered treatment-refractory. Entry criteria included a DSM-IV diagnosis of major depression with a severity specified by a 17-item Hamilton Depression Rating Scale (HAMD-17) total score > 15 and a Clinical Global Impression of Severity (CGI-S) score of > 4 (indicating at least moderately ill) at baseline for out-patients at least 18 years of age.The relatively low cut-off of 15 on the 17-item HAMD was chosen to minimize encouraging raters to artificially inflate baseline scores, to provide greater accuracy. Note that all patients still had to meet full DSM-IV criteria for MDD and have a CGI-S > 4. All of the studies used fixed dosing or forced titration dosing protocols. Duloxetine doses ranged from 40-120 mg/day. SSRI doses were within the range of accepted effective dosing (fluoxetine 20 mg, paroxetine 20 mg), but were chosen for purposes other than head-to-head comparisons, such as non-inferiority analyses conducted to satisfy regulatory requirements. Because of this, results must be interpreted in light of the doses used. References: Thase ME, Lu Y, Joliat MJ, and Detke MJ. “Remission in Placebo-Controlled Trials of Duloxetine with an SSRI Comparator.” Presented at the 156 th Annual Meeting of the APA; San Francisco, CA; May 17-22, 2003. Study: F1J-MC-HMAQ, F1J-MC-HMAT, F1J-MC-HMAY
  • Key Points: This slide shows adverse events with frequency more than 5% and at least two times that of placebo in placebo-controlled phase II and phase III MDD studies of duloxetine 40-120 mg/day. Nausea is the most frequently reported adverse event. Cumulative rates from phase II and III MDD studies of duloxetine, showed an average nausea rate of 20% in active drug, compared to 7% for placebo treatment. Background: This slide shows adverse events with frequency more than 5% and at least two times that of placebo. Doses studied include 40 mg/day, 60 mg QD, 80mg/day and 120mg/day. The 40, 80, and 120 mg/day doses were given as twice-daily divided doses of 20, 40 and 60 mg BID. Multiple studies using different study designs are pooled, and patients started in these studies at a variety of doses. Adverse events reported with frequency greater than 5% but not twice the rate of placebo were headache (15% vs. 16.9%), insomnia (9.9% vs. 6.0%), dizziness (8.9% vs. 4.8%), and diarrhea (7.7% vs. 5.5%) for duloxetine vs. placebo respectively. Insomnia and dizziness were statistically significantly (p < .05) more frequent for duloxetine vs. placebo. Dry mouth and constipation are considered to be norepinephrine-mediated events, as duloxetine has no affinity for cholinergic muscarinic receptors (think about the dry mouth one gets from being nervous before giving a speech). References: Data on file, Lilly Research Laboratories. Data: Nausea Dry Mouth Constipation Fatigue Somnolence Increased Decreased Sweating Appetite Duloxetine 40-120 mg/day (n=1139) 19.9 14.6 11.4 8.3 7.1 6.1 5.9 Placebo (n=777) 6.9 6.3 4 3.7 2.7 1.5 1.9 Study: F1J-MC-HMAQ, F1J-MC-HMAT, F1J-MC-HMBH, F1J-MC-HMAY
  • Key Points: In acute phase studies, the incidence of sexual dysfunction among patients receiving duloxetine (40 – 120 mg/day) was significantly lower than that observed for paroxetine (20 mg QD). No dose-related trends in sexual dysfunction were observed for duloxetine-treated patients, possibly due to increased norepinephrine transmission that may mitigate serotonin-induced sexual dysfunction. Background: This was a post-hoc analysis of pooled data from 4 clinical trials. However, the studies were very similar in design, and pooling of data was anticipated in order to support new drug applications. Acute-phase data obtained from four 8-week, double-blind studies, with patients randomized to duloxetine (20-60 mg BID; n=736), paroxetine (20 mg once daily; n=359), or placebo (n=371). These are the only duloxetine/SSRI comparator studies to date in which ASEX data were collected at baseline and endpoint. Long-term data obtained from extension phases in 2 studies, in which acute treatment responders received duloxetine (40 or 60 mg BID; n=297), paroxetine 20 mg QD (n=140), or placebo (n=129) for 26 additional weeks. Patients were > 18 years of age, met DSM-IV criteria for MDD, had scores of > 15 on the 17-item Hamilton Rating Scale for Depression (HAMD 17 ) and > 4 on the Clinical Global Impression of Severity (CGI-S) scale at Visits 1 and 2.   Sexual functioning evaluated using the Arizona Sexual Experience Scale (ASEX). ASEX questions are each scored 1 – 6 and higher scores = greater dysfunction): 1) How strong is your sex drive?, 2) How easily are you sexually aroused?, 3) Females - How easily does your vagina become moist or wet during sex?, Males - How easily can you get and keep an erection?, 4) How easily can you reach an orgasm?, 5) Are your orgasms satisfying? Patients were categorized as having s exual dysfunction if they met any of the following criteria: 1) ASEX total score 19 or greater, 2) Score of 5 or greater on any item, 3) Score of 4 or greater on any 3 items. References: Brannan SK, Detke MJ, Wang F, Mallinckrodt CH, Watkin JG, Tran PV, Delgado PL. “Comparison of Sexual Functioning in Patients Receiving Duloxetine or Paroxetine: Acute and Long-term Data.” Presented at the 156 th Annual Meeting of the APA; San Francisco, CA; May 17-22, 2003. Study: F1J-MC-HMAT and F1J-MC-HMAY
  • Key Points: For female patients without baseline sexual dysfunction, in acute phase studies, the incidence of sexual dysfunction among patients receiving duloxetine (40 – 120 mg/day) was significantly lower than that observed for paroxetine (20 mg QD). For male patients without baseline sexual dysfunction, in acute phase studies, there was no significant difference in the incidence of sexual dysfunction between duloxetine and paroxetine (paroxetine-treated patients; however, had a significantly greater incidence of treatment-emergent sexual dysfunction than placebo-treated patients. Similar trends in the data are observed for male and female patients; statistical significance may vary due to sample size and not drug effect. Background: This was a post-hoc analysis of pooled data from 4 clinical trials. However, the studies were very similar in design, and pooling of data was anticipated in order to support new drug applications. Acute-phase data obtained from four 8-week, double-blind studies, with patients randomized to duloxetine (20-60 mg BID; n=736), paroxetine (20 mg once daily; n=359), or placebo (n=371). These are the only duloxetine/SSRI comparator studies to date in which ASEX data were collected at baseline and endpoint. Long-term data obtained from extension phases in 2 studies, in which acute treatment responders received duloxetine (40 or 60 mg BID; n=297), paroxetine 20 mg QD (n=140), or placebo (n=129) for 26 additional weeks. Patients were > 18 years of age, met DSM-IV criteria for MDD, had scores of > 15 on the 17-item Hamilton Rating Scale for Depression (HAMD 17 ) and > 4 on the Clinical Global Impression of Severity (CGI-S) scale at Visits 1 and 2.   Sexual functioning evaluated using the Arizona Sexual Experience Scale (ASEX). ASEX questions are each scored 1 – 6 and higher scores = greater dysfunction): 1) How strong is your sex drive?, 2) How easily are you sexually aroused?, 3) Females - How easily does your vagina become moist or wet during sex?, Males - How easily can you get and keep an erection?, 4) How easily can you reach an orgasm?, 5) Are your orgasms satisfying? Patients were categorized as having s exual dysfunction if they met any of the following criteria: 1) ASEX total score 19 or greater, 2) Score of 5 or greater on any item, 3) Score of 4 or greater on any 3 items. References: Brannan SK, Detke MJ, Wang F, Mallinckrodt CH, Watkin JG, Tran PV, Delgado PL. “Comparison of Sexual Functioning in Patients Receiving Duloxetine or Paroxetine: Acute and Long-term Data.” Presented at the 156 th Annual Meeting of the APA; San Francisco, CA; May 17-22, 2003. Data: Female Patients Male Patients No baseline dysfunction No baseline dysfunction Placebo 27.69 Placebo 29.97 Duloxetine (40-120 mg/d) 44.05 Duloxetine (40-120 mg/day) 48.5 Paroxetine (20 mg/d) 62.72 Paroxetine (20 mg QD) 59.38 Study: F1J-MC-HMAT and F1J-MC-HMAY
  • KEY POINTS Duloxetine has demonstrated no clinically significant effects on blood pressure. Across all doses, there was no statistically significant difference in the incidence of sustained hypertension in patients treated with duloxetine compared to placebo-treated patients ( P =.371 Fisher’s Exact). Sustained hypertension was defined as 3 consecutive assessments of either systolic blood pressure  140 mm Hg and  10 mm Hg increase from baseline, or diastolic blood pressure  90 mm Hg and  10 mm Hg increase from baseline. There also was no clinically significant effects on pulse or QTc. Because the data reflect a change in mean blood pressure, patients on duloxetine should have their blood pressure taken at initiation of and periodically while on therapy. One patient in each group (duloxetine and paroxetine) met criteria for PCS values QTcF intervals as compared with none in the placebo group. PCS criteria ( > 450 ms for men; and > 470 ms for women with an increase in QTcF of > ms from baseline. BACKGROUND The electrocardiogram/QTc data are from MDD clinical trials of 321 patients treated with duloxetine and 169 placebo-treated patients. The heart rate, blood pressure, and sustained hypertension data are from 8 placebo-controlled MDD studies of duloxetine 40-120 mg/day. REFERENCE Hudson JI, Wohlreich MM, Kajdasz DK, et al., Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placeco-controlled clinical trials. Hum Psychopharmacol Clin Exp . 2005; 20:327-341. Thase ME, Tran PV, Wiltse C , et al., Cardiovascular Profile of Duloxetine, a Dual Reuptake Inhibitor of Serotonin and Norepinephrine. J Clin Psychopharmacol 2005;25(2):132-140. Data on file, Lilly Research Laboratories: CYM20050419B, CYM20050315U, CYM20050419C. Studies: F1J-MC-HMAQa, F1J-MC-HMAQb, F1J-MC-HMATa, F1J-MC-HMATb, F1J-MC-HMAYa, F1J-MC-HMAYb, F1J-MC-HMBHa, F1J-MC-HMBHb
  • Key Points: This slide shows the incidence of sustained hypertension by dose for duloxetine in placebo-controlled studies. The rate was not statistically different from placebo. Background: Sustained Hypertension defined as 3 consecutive assessment of either systolic blood pressure  140 mm/Hg and  10 mm/Hg increase from baseline or diastolic blood pressure  90 mm/Hg and  10 mm/Hg increase from baseline. The duloxetine data presented here are from 8 placebo-controlled phase II and phase III MDD studies of duloxetine 40-120 mg/day. References: Data on file, Lilly Research Laboratories.
  • Two parallel, double-blind studies of duloxetine versus venlafaxine XR in patients with MDD were conducted and the data pooled as specified a priori in the study protocols No significant difference was seen between duloxetine 60 mg daily and venlafaxine XR 150 mg daily as measured by Global Benefit Risk Assessment (the primary outcome measure) Both duloxetine and venlafaxine XR demonstrated substantial antidepressant efficacy as measured by mean change from baseline to endpoint on the HAMD17 total score The rate of study discontinuation was lower with venlafaxine XR compared to duloxetine 60 mg primarily due to a significantly higher discontinuation rate due to adverse events with duloxetine A similar pattern of treatment-emergent adverse events (TEAEs) was seen in duloxetine and venlafaxine XR-treated patients. More nausea and dizziness were reported by duloxetine-treated patients during the first 6 weeks of treatment. Otherwise, no significant differences in TEAE reporting rates were seen during 6 or 12 weeks of treatment There were no significant differences with respect to mean changes in heart rate or blood pressure between the treatment groups; however, more venlafaxine XR-treated patients experienced a statistically significant (p=0.047) sustained elevation of systolic blood pressure during the first 6 weeks of treatment During the taper period, duloxetine demonstrated statistically better tolerability (p<0.05) compared to venlafaxine XR in the incidences of discontinuation-emergent fatigue, insomnia, and vomiting. The venlafaxine-duloxetine head-to-head study does not show that Effexor and Cymbalta are essentially the same. The study showed Cymbalta 60mg and venlafaxine 150 mg both were effective in treating the symptoms of depression. While venlafaxine (starting at 75 mg/day for 2 weeks) was initially better tolerated than duloxetine 60mg, no duloxetine dose titration was permitted; some patients may have benefited from a lower starting dose. Cymbalta is a balanced and potent reuptake inhibitor, and only Cymbalta has proven efficacy in treating both the emotional and painful physical symptoms of depression. Cymbalta is also the only antidepressant with an independent pain indication, for the management of diabetic peripheral neuropathic pain (DPNP). Treating both the emotional and painful physical symptoms of depression leads to high remission rates. How does this cardiovascular profile compare to Effexor (venlafaxine)? Why aren’t there any hypertensive effects? Effexor (venlafaxine) has dose-related rates of hypertension up to 13% per the Physicians Desk Reference (PDR). The rates of hypertension reported by Effexor (venlafaxine) are higher than those seen with Cymbalta (duloxetine). There is no clear explanation for this difference, but there are some hypotheses. Effexor (venlafaxine) is not highly protein-bound (approximately 25% versus duloxetine’s >95%). In one animal study, the CNS levels of duloxetine were up to 15-fold greater than peripheral levels. The relatively low peripheral levels of duloxetine, combined with high protein binding, mean that there is little free duloxetine in the periphery to cause elevated norepinephrine, which might then interact with peripheral adrenergic receptors to raise blood pressure. However, it should be emphasized that this is still a hypothesis requiring further study.
  • Presentación cymbalta ps

    1. 1. Duloxetina: un nuevo antidepresivo
    2. 2. ¿Hay retos todavía en el Tratamiento de la Depresión?
    3. 3. Introducción ♦ El Trastorno Depresivo Mayor (TDM) afecta a mas de 340 millones de personas (Greden, 2001) ♦ El TDM será la segunda causa de morbilidad y discapacidad en el año 2020 (Murray & Lopez 1997, Greden, 2001) ♦ La Investigación en nuevos antidepresivos se centra en mejorar la remisión, rapidez de acción, cumplimiento y efectos adversos de los ya existentes (Greden, 2001)Greden JF, J Clin Psychiatry 2001; 62 suppl 22: 5-9 3Murray & Lopez, Lancet 1997; 349 (9064): 1498-504
    4. 4. Tasas de Respuesta y Remisión con los ISRSs Los pacientes en su mayoría mejoran de sus síntomas pero no vuelven a niveles de normalidad 100% 80% La remisión se 60% produce en la mitad% of Patients 62,5% de los pacientes que experimentan respuesta 40% 33% 20% 0% Response RemissionFawcett J, Barkin RL. J Clin Psychiatry. 1997;58(suppl 6):32-39. 4Keller MB. J Clin Psychiatry 2004; 65 (suppl 4): 53-59.
    5. 5. Implicaciones Clínicas de los Síntomas Residuales Riesgo de recaídas: 75% en pacientes con remisión parcial vs 25 % remisión completaPaykel ES, et al. Psychol Med. 1995;25:1171-1180. 5
    6. 6. Implicaciones Funcionales de los síntomas Residuales Los Síntomas Depresivos Subclínicos producen unos niveles de deterioro en el funcionamiento semejantes a los que produce el Trastorno Depresivo Mayor (Judd et al., 1996) Los pacientes que experimentaron remisión tuvieron mejor funcionamiento en todas las áreas que los pacientes que sólo experimentaron respuesta (Mintz et al., 1993)Judd, Paulus, Wells et al. Am J Psychiatry 1996; 153 (11): 1411-7 6Mintz, Mintz, Arruda et al., Arch Gen Psychiatry 1992; 49 (10): 761-8
    7. 7. Duloxetina 7
    8. 8. DuloxetinaMecanismo de acciónEficaciaSeguridadConclusiones 8
    9. 9. Antidepresivo Dual potente y equilibrado desde el inicio Transportador deEfectos relativamente membrana 5-HT equilibrados sobre (Bloqueado) 5-HT y NA 5-HTPotencia adecuada Transportadordesde la dosis inicial de membrana NA (Bloqueado) ISRNSelectividad sobre 5-HT y NA NA Representación teórica 9
    10. 10. Estudios “in vitro”Eº de radioligandos de unión a transportadores humanos 10Tran PV et al. Dual monoamine modulation for improved treatment of MDD. J Clin Psychopharmacol 2003; 23 (1): 79-96
    11. 11. Estudios “in vitro”:Duloxetina presenta baja afinidad por otros receptores/transportadores 11
    12. 12. Estudios “in vivo”: Microdiálisis cerebralKoch S, Hemrick-Luecke SK, Thompson LK, et al. Neuropharmacology 2003; 45 (7): 935-944 12
    13. 13. Estudios “in vivo”: Microdiálisis cerebral 5-HT NE 500 Dose, mg/kg sc * Vehicle Control 400 1 * * 3% of Basal Levels 15 300 * * 200 *Significantly different from 100 vehicle control, p<.05 (ANOVA/Dunnett’s) 0 Duloxetine Venlafaxine Duloxetine Venlafaxine In vivo microdialysis in rats. Simmons RMA, et al. Presented at the 154th Annual Meeting of the APA; New Orleans, LA; May 5-10, 2001. - 13
    14. 14. Acción Antidepresiva: acción coordinada sobre 5- HT y NA en el cerebro Locus coeruleus α1 adrenoceptor α2 adrenoceptor NA 5-HT1A 5-HT1B Corteza frontal, sistema límbico Neuronas diana 5-HT Núcleos del rafe Artigas F, comunicación personal, 2005 14
    15. 15. DuloxetinaMecanismo de accionEficaciaSeguridadConclusiones 15
    16. 16. Correlación entre Cambios Químicos y Síntomas DepresivosHealy D, McMonagle T. J Psychopharmacol 1997; 11 (4 suppl): S25-S31 16
    17. 17. Acción sobre los dos sistemas neurotransmisores ♦ efecto sinérgico mediado por el aumento simultáneo de laDuloxetina neurotransmisión noradrenérgica y serotoninérgica ♦ espectro de eficacia más amplio REMISIÓN 17
    18. 18. Resumen estudios DuloxetinaENSAYO CLINICO Diseño/ N total Dosis Duloxetina Comparador Duración SemanasPrueba de concepto doble ciego, 120 Placebo 8 N = 167 Fluoxetina 20Búsqueda de dosis doble ciego, 40 y 80 Placebo 8 N = 354 Paroxetina 20Búsqueda de dosis doble ciego, 40 y 80 Placebo 8 N = 353 Paroxetina 20Búsqueda de dosis doble ciego, 80 y 120 Placebo 8 N = 367 Paroxetina 20 + 26 extensiónBúsqueda de dosis doble ciego, 80 y 120 Placebo 8 N = 392 Paroxetina 20 + 26 extensiónDosis diaria única doble ciego, 60 Placebo 9 N = 245Dosis diaria única doble ciego, 60 Placebo 9 N = 267Prevención de recaídas Abierto + doble-ciego, 60 Placebo 12 + 26 N = 533Seguridad 1 año Abierto 80-120 No hay 52 N = 1279> 65 años Doble-ciego, 60 Placebo 8 N = 311 18
    19. 19. Resumen estudios Duloxetina Duloxetina ha sido estudiada en un programa clínico incluyendo a 3158 pacientes (exposición de 1285 pacientes-año) con TDM 1♦ Programa clínico de registro: • 9 Estudios en fase aguda: - 2 EC controlados con placebo y/o comparador activo (Fase II). - 4 EC controlados con placebo y/o comparador activo de búsqueda de dosis (Fase III). - 2 EC controlados con placebo de dosis 60 mg/día (Fase III). - 1 EC controlado con placebo en mayores de 65 años (Fase III). • 1 Estudio de prevención de recaídas del TDM • 1 Estudio de seguridad abierto a un año con más de 1200 pacientes con TDM 191 Ficha técnica de Cymbalta.
    20. 20. Estudios de dosis de Duloxetina ♦ En los ensayos clínicos de búsqueda de dosis el rango estudiado fue de 40-120 mg/día. [1] ♦ Los estudios en fase III muestran que la dosis de 60 mg/día presenta un perfil adecuado de eficacia y seguridad. [2] La dosis inicial eficaz es de 60 mg/día; el rango terapéutico es de 60-120 mg/día. [3][1] Bymaster FP, et al. Curr Pharm Des 2005;11(12):1475-1493.[2] Detke MJ, et al. J Psychiatr Res 202002;36(6):383-390. [3] Ficha técnica de Cymbalta.
    21. 21. ♦ ESPECTRO DE EFICACIA Duloxetina Mecanismo de accion Eficacia Seguridad Conclusiones 21
    22. 22. Duloxetina: Eficacia Global Duloxetina 60 mg vs. Placebo en depresión mayor: HAMD17 Total Weeks 0 1 2 3 4 5 6 7 8 9 0 Mean Change from Baseline -2 Improvement (HAMD17 Total Score) Duloxetine -4 60 mg QD (n=121) -6 * Placebo (n=115) -8 * -10 * *p<.001 * MMRM -12 *Detke MJ, et al. J Clin Psychiatry. 2002;63:308-315. 22
    23. 23. Duloxetina: Eficacia Global HAMD17 subescala de factores nucleares HAMD17 subescala de ansiedad Weeks Weeks 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 Mean Change from Baseline Mean Change from Baseline (HAMD17 Anxiety Subscale) 0 0.0 (HAMD17 Core Subscale) -1 -0.5Improvement Improvement Duloxetine -1.0 -2 60 mg QD Duloxetine * 60 mg QD (n=121) -1.5 -3 (n=121) Placebo * ** (n=115) -2.0 Placebo -4 (n=115) ** ** *p=.007 -2.5 -5 ** ** **p<.001 ** ** MMRM -3.0 ** *p<.05 -6 ** **p<.005 -3.5 MMRM EAV Dolor general Weeks 0 1 2 3 4 5 6 7 8 9 Mean Change from Baseline (mm) Visual Analog Scale for Overall Pain 2 0 Duloxetine Improvement -2 60 mg QD (n=120) -4 Placebo (n=113) -6 -8 * * p=.055 *p<.05 -10 MMRM 23 * * -12
    24. 24. Duloxetina: Eficacia en síntomas emocionales HAMD17 subescala de síntomas nucleares Weeks 0 1 2 3 4 5 6 7 8 9 Mean Change from Baseline 0 (HAMD17 Core Subscale) -1 Improvement Duloxetine -2 60 mg QD * (n=121) -3 Placebo ** (n=115) -4 ** ** *p=.007 -5 ** **p<.001 ** MMRM -6Data on file, Lilly Research Laboratories. 24
    25. 25. Duloxetina: Eficacia en síntomas de ansiedad HAMD17 subescala de ansiedad semanas 0 1 2 3 4 5 6 7 8 9 Mean Change from Baseline (HAMD Anxiety Subscale) 0.0 -0.5 Improvement -1.0 Duloxetine 60 mg QD -1.5 (n=121) * Placebo -2.0 17 (n=115) -2.5 ** -3.0 ** ** *p<.05 ** **p<.005 -3.5 MMRM Los pacientes que presentan una mejoría temprana en los síntomas de ansiedad tienen mayor probabilidad de obtener remisión (Farabaugh et al., Int Clin Psychopharmacology 2005)Dunner DL, et al. Depress Anxiety. 2003;18:53-61. 25
    26. 26. Duloxetina: Eficacia en síntomas de ansiedad Item 10: Ansiedad psíquica de la escala HAMD17 Weeks (HAMD17 Item 10, Psychic Anxiety) 0 1 2 3 4 5 6 7 8 9 Mean Change from Baseline 0.0 Duloxetine 60 mg QD -0.2 (n=244)Improvement Placebo (n=251) -0.4 ***p < .001 *** vs. placebo -0.6 *** MMRM -0.8 Pooled data from 2 *** studies *** *** -1.0 *** Hirschfeld RMA, et al., Depression and Anxiety 2005;21:170-177. 26
    27. 27. Mejoría sintomática desde la primera semanaHirschfeld RM, et al. Depress Anxiety 2005; 21 (4): 170-7 27
    28. 28. Presencia de Síntomas Somáticos en Depresión Mayor Al menos un SS Sin SS Díez o más 12,40% 7% Cuatro o nueve 23% 93% Tres o menos 45% Molestias frecuentes 12,30%PYCASSO study. Submitted to B J Psychiatry 28
    29. 29. Duloxetina: Eficacia en Dolor Duloxetina 60 mg. vs. placebo EAV Dolor global Weeks 0 1 2 3 4 5 6 7 8 9 Mean Change from Baseline (mm) Visual Analog Scale for Overall Pain 2 0 Duloxetine Improvement -2 60 mg QD (n=120) -4 Placebo (n=113) -6 -8 * * p=.055 *p<.05 -10 MMRM * * -12Fava, Mallinckrodt, Detke, et al., J Clin Psychiatry 2004; 65: 521-530 29
    30. 30. Eficacia en síntomas Dolorosos ♦ Los pacientes que presentan una mejoría temprana en los síntomas somáticos generales presentan mayor probabilidad de obtener remisión ♦ Duloxetina mejoró los síntomas dolorosos de forma independiente a la mejoría producida sobre los síntomas emocionalesFarabaugh et al., Int Clin Psychopharmacol 2005; 20 (2): 87-91 30Fava, Mallinckrodt, Detke, et al., J Clin Psychiatry 2004; 65: 521-530Mallinckrodt, Goldstein, Detke et al., Primary Care Companion J Clin Psychiatry 2003; 5: 19-26
    31. 31. ♦ EFICACIA A LARGO PLAZO Duloxetina Mecanismo de accion Eficacia Seguridad Conclusiones 31
    32. 32. Eficacia a largo plazoPerahia, Gilaberte, Wang et al. in press B J Psychiatry 32
    33. 33. Eficacia a largo plazo Duloxetina es eficaz en aquellos pacientes que después de responder al fármaco presentan una recaida al dejar de tomarlo Si un paciente a pesar de seguir el tratamiento con Duloxetina recae, el aumento de la dosis es eficaz en un alto porcentaje de casosPerahia, Gilaberte, Wang et al. in press B J Psychiatry 33
    34. 34. ♦ TASAS DE REMISION Duloxetina Mecanismo de accion Eficacia Seguridad Conclusiones 34
    35. 35. Respuesta y Remisión con Duloxetina Estudio fase III: Eficacia Dosis 60 mg/d 70% 62% 60% 50% 44% 40% Respuesta 29% Remision 30% 20% 16% 10% 0% Duloxetina PlaceboDetke MJ, et al. J Clin Psychiatry. 2002;63:308-315 35
    36. 36. Respuesta y Remisión con Duloxetina Fase Abierta 12 semanas*. Eficacia dosis 60 mg/día 80% 68% 70% 60% 53% 50% Res puesta 40% Remision 30% 20% 10% 0% Duloxetina* Estudio Prevención de Recaidas Hudson, Perahia, Gilaberte et al. in press in “Depression and Anxiety” 36
    37. 37. Remisión Duloxetina vs ISRSs Análisis agrupado de seis estudios clínicos controlados con placebo e ISRS Remisión semana 8 60 Todos los pacientes Pacientes con HAMD>18 randomizados Duloxetine 50 * SSRI 43 * *† Placebo 40 38 38 * 29 *p<.05 30 28 vs. placebo † p<.05 18 vs. SSRI 20 LOCF 10 0 (n=697) (n=423) (n=507) (n=429) (n=245) (n=289)Thase ME, et al. Presented at the 156th Annual Meeting of the APA; San Francisco, CA; May 17-22, 2003. 37
    38. 38. Respuesta y Remisión con Duloxetina NNT para el efecto de Duloxetina vs ISRS Duloxetina NNT (95% CI) ISRS NNT (95% CI) Respuesta 7 (5, 18) 6 (4, 13) Respuesta Remission 7 (5, 20) 11 (5, ∞) Remision 7 (5, 20) Remision 11 (5, ∞) CGI-S Imp. Imp. 8 (5, 20) 7 (5, 23) El numero de pacientes que necesitan ser tratados con Duloxetina para que uno experimente remisión es 7. Mientras que se necesitan 11 pacientes tratados con ISRS para producir la remisión en 1 de ellosAdaptado de Cookson J, Gilaberte I, Desaiah D, et al. Poster presented at the International Forum and 38Mood and Anxiety Disorders, Nov 9-11, 2005. Vienna, Austria
    39. 39. DuloxetinaMecanismo de accionEficaciaSeguridadConclusiones 39
    40. 40. Farmacocinética de Duloxetina 40
    41. 41. Incidencia de acontecimientos adversos Sequedad Aumento de Disminución Náuseas de boca Estreñimiento Fatiga Somnolencia la sudoración del apetito 30 Duloxetina 40-120 25 mg/día (n=1139)Incidencia (%) 20 Placebo (n=777) * 15 * p < 0,001 * frente al placebo para todos los 10 * acontecimientos * 5 * * * 0 Todos los acontecimientos que afectaron a los pacientes tratados con duloxetina, cuya frecuencia alcanzó >5% y representó el doble de la del placebo Hudson JI, et al. Hum Psychopharmacol Clin Exp. 2005; 20:327-341. 41
    42. 42. Tasas de abandono debido a acontecimientos adversos 12 Duloxetina * 9.7% 40-120 10 mg/día % de abandonos (n=1139) 8 Placebo (n=777) 6 4.2% *p < 0,005 4 * 2 1.4% 0.1% 0 Total de acontecimientos adversos Náuseas En los pacientes que experimentaron nausea, en la mayoría de los casos fueron leves (52,9%) o moderadas (41,4%) y se resolvieron de forma espontánea en la primera semana de tratamientoGreist J, McNamara RK, Mallinckrodt CH, et al. Clin Ther 2004; 26: 1146-1455 42
    43. 43. Tolerabilidad de Duloxetina vs ISRSsAdaptado de Swindle RW et al. Presented at 24th CINP Congress; Paris, France, June 20-23, 2004 43
    44. 44. Duloxetina: cambios en el peso Cambios en el peso a las 34 semanas de tratamiento 0 4 8 12 16 20 24 28 32 2 Placebo (n=192) 1.5 * * Duloxetine 80 mg/day 1 * (n=186) Duloxetine 0.5 120 mg/day (n=195) Paroxetine 0 20 mg QD (n=181) -0.5 * * * -1Hudson JI, et al. Hum Psychopharmacol Clin Exp. 2005; 20:327-341. 44Mallinckrodt CH, et al. Presented at the 16th Annual US Psychiatric Congress; Orlando, FL; November 6-9, 2003.
    45. 45. Duloxetina: Incidencia de disfunción sexual Incidencia Disfunción Sexual (%) Placebo (n=127) 29 Duloxetine (40 mg/day; n=71) 44** Duloxetine (80 mg/day; n=124) 50* *p<.01 Duloxetine (120 mg/day; n=46) 39** vs. placebo Paroxetine (20 mg QD; n=107) 62* **p<.05 vs. paroxetineDelgado PL, Brannan SK, Mallinckrodt CH, et al. J Clin Psychiatry 2005; 66: 686-692 45
    46. 46. Probability of Treatment-Emergent Sexual Dysfunction InDepressed Patients Treated with Duloxetine or Paroxetine,Who Did Not Have Dysfunction at Baseline Female Patients, Male Patients, 70 Acute Phase (n=252) Acute Phase (n=223) 70 ** Placebo * Onset of Sexual Dysfunction (%) 60 Onset of Sexual Dysfunction (%) 60 Estimated Probability of Estimated Probability of 50 *† 50Improvement Duloxetine 40 (40-120 40 mg/d) 30 30 Paroxetine (20 mg/d) 20 20 *p<.05 vs. placebo 10 10 ** p<.001 vs. placebo † p<.05 vs. paroxetine 0 0Delgado PL, et al. J Clin Psych. 2005;66(6):686-692. 46
    47. 47. Incidencia de síntomas de discontinuación Incidencia de acontecimientos adversos tras la retirada brusca Mareos Náuseas Cefalea Parestesias Diarrea Vómitos Irritabilidad Insomnio Pesadillas 20 Duloxetina 40-120 mg/día (n=490) Placebo (n=380)Incidencia (%) 15 *p < 0,05 * 10 * * 5 * * * * 0 Acontecimientos sucedidos con duloxetina con una frecuencia >2% y doble de la del placebo Hudson JI, et al. Hum Psychopharmacol Clin Exp. 2005; 20:327-341. 47
    48. 48. Duloxetina: Seguridad CardiovascularEfecto dosis-respuesta de Duloxetina en Tensión arterial y Frecuencia cardiaca Placebo Dlx 40 Dlx 60 Dlx 80 Dlx 120 N= 757 N=174 N=244 N=354 N=344 TAsistólica -1,4 (11,9) 0,8 (12,6) 0,3 (2,5)* 0,2 (12,4) 1,7 (11,4)* TAdiastólica 0,4 (8,7) 1,5 (8,7) 1,3 (9,9) 0,5 (8,2) 0,7 (8,4) Frec Cardiaca -0,6 (9,1) 0,1 (10,2) 1,5 (10,2)* 1,5 (8,9) 1,8 (9,6)* Cambio desde la basal al punto final (analisis de varianza), media (DE) * p<0.01 Thase, Tran, Wiltse, et al., J Clin Psychopharmacol 2005 48
    49. 49. Cardiovascular Effects in Depressed Patients Treatedwith Duloxetine (40-120 mg/day; 8-9 weeks) ♦ Mean change in systolic blood pressure • Duloxetine +0.8 mm Hg • Placebo -1.4 mm Hg • P < .001 ♦ Mean change in diastolic blood pressure • Duloxetine +0.9 mm Hg • Placebo +0.4 mm Hg • P = .099 ♦ Mean change in heart rate • Duloxetine +1.4 bpm • Placebo -0.6 bpm • P < .001 ♦ Mean change in corrected QT interval (QTcF) • Duloxetine -1.46 ms • Placebo +1.00 ms • P = .153 Hudson JI, et al. Hum Psychopharmacol Clin Exp. 2005; 20:327-341. 49
    50. 50. Duloxetina: Seguridad Cardiovascular Desarrollo de hipertensión sostenida n % de la muestra Duloxetina 40 mg/día (N=174) 0 0 Duloxetina 60 mg/día (N=244) 2 0,8 Duloxetina 80 mg/día (N=354) 6 1,7 Duloxetina 120 mg/día (N=344) 6 1,7 Total Duloxetina (N=1116) 14 1,3 Placebo (N=757) 6 0,8La hipertensión sostenida se define como una presión sistólica > 140 mm Hg y un aumento > 10 mmHg con respecto al valor basal, o una presión diastólica > 90 mm Hg y un incremento > 10 mm Hgcon respecto al valor basal durante 3 evaluaciones consecutivasThase, Tran, Wiltse, et al., J Clin Psychopharmacol 2005 50
    51. 51. Duloxetina: Seguridad Cardiovascular♦ El intervalo QT corregido en función de la frecuencia cardiaca que presentaron los pacientes tratados con duloxetina no difirió del observado en los pacientes tratados con placebo1.♦ Duloxetina tiene un perfil cardiovascular semejante al que muestran los ISRS utilizados como comparadores en los EC (Fluoxetina o Paroxetina) Thase, Tran, Wiltse, et al., J Clin Psychopharmacol 2005 51
    52. 52. Eficacia y Seguridad Duloxetina 60 mg en ancianos Weeks Duloxetine 0 1 2 3 4 5 6 7 8 60 mg QD 0 (N=201) MMRM -1 Placebo -2 (N=102)Mejoría HAMD-17 MMRM -3 -4 Duloxetine Mejoría en los síntomas -5 LOCF depresivos -6 *** -7 *** Placebo ***p ≤ .001 LOCF -8 *** vs. placebo -9 -10 Duloxetina Duloxetine Placebo Parámetro Seguridad 60 mg/day (N = 104) (N = 207) Tolerabilidad Abandono por efecto adverso, n, (%) 20 (9.7%) 9 (8.7%) Incidencia de Hipertensión sostenida 0.5% 1.0% Incidencia de Hipotensión ortoestática 15.6% 20.5% 52 Raskin J, et al. Presented at the 18th Annual Meeting of the American Association for Geriatric Psychiatry; San Diego, CA; March 3-6, 2005.
    53. 53. Duloxetina: Seguridad a largo plazo y en ancianos ♦ Duloxetina resultó ser segura y bien tolerada en el tratamiento de depresión mayor a largo plazo a una dosis de hasta 120 mg/día. 1 ♦ Duloxetina resultó ser segura y bien tolerada en el tratamiento de TDM a largo plazo en pacientes de 65 años y mayores. 2 ♦ No es necesario ajustar la dosis en función de la edad. 3(1) Raskin J, et al. J Clin Psychiatry 2003;64:1237-1244. (2) Wohlreich MM, BMC Geriatr. 2004 (3) Ficha Técnica 53
    54. 54. Duloxetina: Dosis y poblaciones especiales ♦ En conjunto, la eficacia de duloxetina ha sido demostrada a dosis diarias entre 60 y 120 mg 1 ♦ No se debe utilizar en insuficiencia hepática 1 ♦ No es necesario un ajuste posológico en pacientes con insuficiencia renal leve o moderada (aclaramiento de creatinina de 30 a 80 ml/min) 1. ♦ No es necesario ajustes de dosis en ancianos 1.(1) Ficha Técnica 54
    55. 55. Interacciones de duloxetina con otros medicamentos ♦ Se aconseja precaución cuando se use duloxetina en combinación con otros fármacos o sustancias de acción central, incluyendo alcohol y medicamentos sedantes. ♦ Está contraindicado el uso de duloxetina en combinación con inhibidores irreversibles no selectivos de la monoaminooxidasa (IMAOs). ♦ Duloxetina no debe utilizarse en combinación con fluvoxamina, ciprofloxacino o enoxacino ( inhibidores potentes de la CYP1A2 ) dado que la combinación da lugar a concentraciones plasmáticas de duloxetina elevadas. 55Ficha técnica de Cymbalta® (duloxetina).
    56. 56. DuloxetinaMecanismo de accionEficaciaSeguridadConclusiones 56
    57. 57. Respuesta y Remisión Datos de Respuesta y Remisión con ISRSsLa Remisión se produce en la mitad de los pacientes que experimentanRespuesta30% de los pacientes tratados con ISRS en EC experimentan Remisión Datos de Respuesta y Remisión con duloxetina 60 mg/dLa Remisión se produce entre el 60-80% de los pacientes queexperimentan RespuestaEntre el 43 y el 57% de los pacientes tratados con Duloxetina 60 mg/dexperimentan Remisión 57
    58. 58. Remisión • La remisión sintomática sostenida es el resultado optimo del tratamiento de un paciente depresivo • La presencia de síntomas residuales es un importante predictor de recaída • Entre el 60 y el 80% de los pacientes que alcanzan respuesta con Duloxetina llegan a alcanzar la RemisiónKeller, MB; J Clin Psychiatry 2004 58Mallinckrodt CH et al., J Clin Psychiatry 2003
    59. 59. Duloxetina: Conclusiones♦ Efecto dual equilibrado sobre la serotonina y la noradrenalina desde la dosis de inicio♦ Amplio espectro de Eficacia con una alta probabilidad de alcanzar Remisión 59
    60. 60. ¿Tiene duloxetina ventajas comparativas con venlafaxina? DULOXETINA VENLAFAXINAIndicación (es) • Tratamiento de los episodios • Tratamiento de la depresión. depresivos mayores. Prevención de las recaídas del • Tratamiento del dolor neuropático episodio depresivo y recurrencias de periférico diabético en adultos. nuevos episodios. • Trastornos de ansiedad generalizada • Fobia social (formas retard)Mecanismo de Inhibidor dual, potente y equilibrado de la Inhibidor de la recaptación de serotonina acción recaptación de serotonina (5HT) y (5HT) y noradrenalina (NA) (IRSN), noradrenalina (NA) (IRSN) con aunque esta última en una proporción aproximadamente la misma afinidad cinco veces menor. Es un inhibidor para unirse a ambos transportadores relativamente selectivo de la de monoaminas. recaptación de 5HT.Eficacia en • Eficaz en el tratamiento de los Mayores tasas de remisión en comparación Depresión vs. síntomas somáticos dolorosos con el tratamiento con ISRS (Thase, ISRS asociados a la depresión en 2001). comparación con el tratamiento con ISRS, que no son eficaces en el tratamiento de estos síntomas. • Mayores tasas de remisión en comparación con el tratamiento con ISRS, en el tratamiento de la depresión moderada o severa (Thase, 2004).Incidencia de Duloxetina no tiene un efecto clínico 3-7 % 60 Hipertensión significativo sobre la tensión arterial Efecto dosis-dependiente

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