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 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study compared the stabilized duloxetine dose through approximately 12 weeks of treatment in patients initiating duloxetine therapy with that in patients switching to duloxetine from selective serotonin reuptake inhibitors or venlafaxine. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder. Patients (n = 112) exhibiting suboptimal response or poor tolerability to their current antidepressant medication (citalopram, escitalopram, fluvoxamine, paroxetine, sertraline, or venlafaxine) were switched to duloxetine 60 mg once daily (QD) without intermediate tapering or titration ("switching" group). A comparator group (n = 137), comprising patients not currently receiving antidepressant medication, was randomized to receive duloxetine 30 or 60 mg QD ("initiating" group). At the end of week 1, patients receiving 30 mg QD had their dose increased to 60 mg QD. During the remainder of the study, each patient's duloxetine dose could be titrated on the basis of degree of response within a range from 60 to 120 mg QD, with 90 mg QD as an intermediate dose. At the study end point, approximately one third of the patients in each treatment group were stabilized at each of the 3 studied duloxetine doses (60, 90, and 120 mg QD), and the distribution of stabilized doses among patients initiating duloxetine therapy did not differ significantly from that observed in patients switching to duloxetine. The efficacy of duloxetine in patients switching from selective serotonin reuptake inhibitor/venlafaxine did not differ significantly from that observed in untreated patients initiating duloxetine therapy (baseline-to-end point mean changes: 17-Item Hamilton Rating Scale for Depression total score, -13.1 vs. -13.5; Hamilton Rating Scale for Anxiety, -10.6 vs. -10.3; and Clinical Global Impression of Severity, -2.22 vs. -2.38, respectively). The rate of discontinuation caused by adverse events among patients switched to duloxetine was significantly lower than that in patients initiating duloxetine therapy (6.3% vs. 16.1%, P = 0.018). Treatment-emergent adverse events occurring in more than 10% of patients in both treatment groups were nausea, headache, dry mouth, insomnia, diarrhea, and constipation. In the first week of therapy, patients switched to duloxetine reported significantly lower rates of headache and fatigue compared with patients initiating duloxetine. Thus, the efficacy of duloxetine in switched patients was comparable to that observed in patients initiating duloxetine therapy. Immediate switching from a selective serotonin reuptake inhibitor or venlafaxine to duloxetine (60 mg QD) was well tolerated.
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PMID:An open-label study of duloxetine for the treatment of major depressive disorder: comparison of switching versus initiating treatment approaches. 1628 37

Our objective was to assess the effectiveness and safety of the combination of duloxetine and bupropion for treatment-resistant major depressive disorder (TRD). A retrospective chart review was conducted to identify patients with major depressive disorder (MDD) who had not experienced full remission of symptoms following an adequate trial of either duloxetine (n = 3) or bupropion (n = 7), and who then received the combination of these two antidepressants for TRD. Ten patients [37.2 +/- 11.3 years of age, five women, baseline Clinical Global Impressions (CGI) scale score 4.4 +/- 1.1], seven of whom had not remitted following treatment with bupropion (330 +/- 67 mg, 20.5 +/- 12.2 weeks), and three of whom had not remitted following treatment with duloxetine (90 +/- 30 mg, 18 +/- 2 weeks) received at least 4 weeks of combination treatment. The CGI was administered when the combination was first prescribed, and following 8.8 +/- 4.0 (range, 4-16) weeks of treatment. There was a significant decrease in CGI-S (Severity) scores (4.4 +/- 1.1 to 2.1+/-0.9, P <.0001) following combination treatment. Three (30%) patients were remitters at follow-up, and six (60%) were responders who did not achieve full symptom remission. The mean maximum adjunctive duloxetine and bupropion doses were 60.0 +/- 17.3 mg and 175.0 +/- 114.5 mg, respectively. Side effects reported during combination treatment were nausea (n = 2), dry mouth (n = 2), jitteriness/agitation (n = 2), fatigue/drowsiness (n = 2), increased blood pressure (n = 1), increased sweating (n = 1), insomnia (n = 1), pruritus (n = 1), headache (n = 1), sexual dysfunction (n = 1), and weight gain (n = 1). Although preliminary, these results suggest a possible role for the combination of duloxetine and bupropion for TRD.
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PMID:The combination of duloxetine and bupropion for treatment-resistant major depressive disorder. 1652 1

In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores < or =2) and Montgomery Asberg Depression Rating Scale (MADRS) (> or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%).
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PMID:A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder. 1750 98

Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. To further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This single-arm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age >or=18 years) meeting DSM-IV criteria for MDD (n=128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (P<.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by >10% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of 3.1 kg over 2 years of treatment. Results from this study suggest that rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable. Despite weekly escalation, the majority of adverse events were mild and transient and occurred in the first week of duloxetine dosing (at 60 mg once daily). Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of TEAEs and treatment discontinuation due to adverse events. Time course profiles of body weight and heart rate showed modest increases during 2 years of treatment [ClinicalTrials.gov number, NC T000 42575].
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PMID:Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation. 1684 41

A total of 17 years after its introduction, bupropion remains a safe and effective antidepressant, suitable for first-line use. Bupropion undergoes metabolic transformation to an active metabolite, 4-hydroxybupropion, through hepatic cytochrome P450-2B6 (CYP2B6) and has inhibitory effects on cytochrome P450-2D6 (CYP2D6), thus raising concern for clinically-relevant drug interactions. Common side effects are nervousness and insomnia. Nausea appears slightly less common than with the SSRI drugs and sexual dysfunction is probably the least of any antidepressant. Bupropion is relatively safe in overdose with seizures being the predominant concern. The mechanism of action of bupropion is still uncertain but may be related to inhibition of presynaptic dopamine and norepinephrine reuptake transporters. The activity of vesicular monoamine transporter-2, the transporter pumping dopamine, norepinephrine and serotonin from the cytosol into presynaptic vesicles, is increased by bupropion and may be a component of its mechanism of action. Bupropion is approved for use in major depression and seasonal affective disorder and has demonstrated comparable efficacy to other antidepressants in clinical trials. Bupropion is also useful in augmenting a partial response to selective serotonin reuptake inhibitor antidepressants, although bupropion should not be combined with monoamine oxidase inhibitors. It may be less likely to provoke mania than antidepressants with prominent serotonergic effects. Bupropion is effective in helping people quit tobacco smoking. Anecdotal reports indicate bupropion may lower inflammatory mediators such as tumor necrosis factor-alpha, may lower fatigue in cancer and may help reduce concentration problems.
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PMID:Bupropion: pharmacology and therapeutic applications. 1700 13

We examined the efficacy and tolerability of augmentation with an extended release formulation of methylphenidate (OROS MPH, Concerta) in patients with major depression who were nonresponders or partial responders to antidepressants. Sixty subjects with treatment-resistant depression (TRD) participated in a 4-week, randomized, double-blind, placebo-controlled study of augmentation with methylphenidate (18-54 mg/d). The preexisting antidepressant dose was unchanged. The primary efficacy measure was change in the 21-item Hamilton Depression Rating Scale from randomization to end of treatment. Data were analyzed with intent-to-treat with last observation carried forward approach. There were no statistically significant differences between the methylphenidate (n = 30) and placebo (n = 30) groups in reduction in 21-item Hamilton Depression Rating Scale scores (drug, -6.9; placebo, -4.7) from baseline to end of treatment (F1,47 = 1.24, P = 0.22), although responders were numerically higher in the extended-release methylphenidate group (40.0%) than in the placebo group (23.3%). On the secondary efficacy measures of changes in Clinical Global Impression-Improvement and Severity scores and Beck Depression Inventory-Second Edition, the drug failed to separate from placebo, although the proportion of responders in the drug group were numerically higher than placebo. There were no significant differences in weight, heart rate, and blood pressure changes between the 2 groups. The common adverse events were loss of appetite, nausea, headache, and anxiety. The mean dose of drug was 34.2 mg/d. The study did not demonstrate a statistically significant benefit for augmentation with methylphenidate in TRD. Combination of methylphenidate with antidepressants was well tolerated. Adequately powered, randomized, controlled trials are necessary to fully evaluate the efficacy of extended-release methylphenidate in TRD.
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PMID:A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression. 1820 60

Bupropion was initially developed and licensed for the treatment of major depressive disorder in the United States in 1989. It was licensed as a pharmacotherapy for smoking cessation in the United States in 1997 and in the United Kingdom in 2000, and for the prevention of seasonal major depressive episodes in patients with seasonal affective disorder in the United States in 2006. Its main mechanism of action is believed to be via dopamine and noradrenalin reuptake inhibition. In addition to proven clinical efficacy for the treatment of major depression, the prevention of depressive episodes in patients with seasonal affective disorder, and as an aid to smoking cessation treatment, bupropion has demonstrated efficacy for attenuation of symptoms of attention deficit hyperactivity disorder, and more recently it has shown anti-inflammatory action against proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may be implicated in a number of inflammatory diseases such as Crohn's disease. The twice-daily sustained-release formulation has been extensively evaluated for smoking cessation and has shown continuous smoking abstinence rates at one year of the order of 20% across many clinical groups including healthy smokers, and smokers with cardiovascular disease, chronic obstructive airways disease, depression and schizophrenia. Bupropion is well tolerated with side effects including insomnia, headache, dry mouth, dizziness and nausea. Bupropion is a cytochrome p450 2D6 inhibitor and care must be taken when coprescribing with drugs cleared by this enzyme and when coprescribing with drugs that lower seizure threshold. Despite the clinical effectiveness and cost-effectiveness of bupropion as an aid to smoking cessation, its uptake for this indication remains low when compared with nicotine replacement therapy.
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PMID:Bupropion. 1713 26

Duloxetine (Cymbalta is an antidepressant of the class of serotonin noradrenaline reuptake inhibitors. The efficacy of duloxetine 60 mg/day has been well demonstrated in the acute and long term treatment of major depression. The level of effectiveness of duloxetine is particularly high and associated with a shorter latency of action. Duloxetine also exhibits antinociceptive properties independently of the antidepressant effect. The side-effect profile of duloxetine is particularly good and similar to selective serotonin reuptake inhibitors with mainly nausea. In total, duloxetine represents a real progress in the pharmacological treatment of major depression.
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PMID:[Medication of the month. Duloxetine (Cymbalta)]. 1719 49

Duloxetine is a newly introduced drug. It is being prescribed for the management of diabetic neuropathic pain and major depressive disorder. The most frequently observed adverse events with duloxetine are nausea, dry mouth and somnolence, constipation, diarrhea, decreased appetite, weight loss, feeling of fatigue, dizziness, somnolence, hypohidrosis, decreased libido and erectile dysfunction. One of the patients being prescribed the drug developed bleeding gums on being started with the drug which resolved on stopping it. We hereby report this case.
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PMID:Bleeding gums: duloxetine may be the cause. 1724 71

Escitalopram is the newest selective serotonin reuptake inhibitor (SSRI) available for use in the United States. It has been approved for the treatment of major depression and generalized anxiety disorder. It is the S-enantiomer of the SSRI citalopram and is highly serotonin specific as it has minimal effect on the reuptake of dopamine or norepinephrine. It is also a well-tolerated medication, with a side-effect profile comparable to the other SSRIs. While a number of side effects have been seen during escitalopram therapy, such as insomnia, nausea, and increased sweating, there are no reported cases of serotonin syndrome associated with escitalopram therapy to date. We present the case of a 24-year-old woman who developed serotonin syndrome after an increase in her escitalopram to 30 mg/day. We will review the diagnostic criteria of serotonin syndrome and the clinical scenarios in which serotonin syndrome can develop. We will also discuss the proposed treatments and role that polypharmacology may play in the development of this clinical entity.
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PMID:Serotonin syndrome associated with the use of escitalopram. 1742 64


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