Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine

In a previous study, of 41 depressed patients who had not responded to fluoxetine 20 mg/day, 53% were treated with high-dose fluoxetine (40-60 mg/ day) and responded (i.e., their 17-item Hamilton Rating Scale for Depression [HAM-D-17] score was <7) versus 29% and 25% of patients treated with fluoxetine plus lithium (300-600 mg/day) or fluoxetine plus desipramine (25-50 mg/day), respectively. We wanted to assess whether these findings could be replicated in a larger sample of depressed outpatients. We identified 101 outpatients with major depressive disorder (52 men and 49 women; mean age, 41.6 + 10.6 years) who were either partial responders (n = 49) or nonresponders (n = 52) to 8 weeks of treatment with fluoxetine 20 mg/ day. These patients were randomized to 4 weeks of double-blind treatment with high-dose fluoxetine (40-60 mg/day), fluoxetine plus lithium (300-600 mg/day), or fluoxetine plus desipramine (25-50 mg/day). In the overall group of patients (N = 101), there was no significant difference in response rates across the three treatment groups (high-dose fluoxetine, 42.4%; fluoxetine plus desipramine, 29.4%; fluoxetine plus lithium, 23.5%). Dropout rates were also comparable, ranging from 9.1% (high-dose fluoxetine) to 14.7% (fluoxetine plus desipramine and fluoxetine plus lithium). There were also no significant differences in response rates across the three treatment groups among partial responders (high-dose fluoxetine, 50.0%; fluoxetine plus desipramine, 33.3%; fluoxetine plus lithium, 33.3%) and nonresponders (high-dose fluoxetine, 35.3%; fluoxetine plus desipramine, 26.3%; fluoxetine plus lithium, 12.5%). At the end of the study, the mean lithium level was 0.37 + 0.15 mEq/L (n = 27; range, 0.1-0.8 mEq/L) among lithium-treated patients, and the mean desipramine level was 104.7 + 58.8 ng/mL (n = 22; range, 25-257 ng/mL). There were no significant relationships between lithium or desipramine blood levels and degree of improvement (as measured by the change in HAM-D-17 score). We found no significant differences in efficacy among these three treatment strategies among patients who had failed to respond adequately to 8 weeks of treatment with fluoxetine 20 mg/day, although the high-fluoxetine group was associated with nonsignificantly higher response rates in both partial responders and nonresponders.     

Escitalopram prevents relapse of obsessive-compulsive disorder.

To examine the efficacy and tolerability of escitalopram in the prevention of relapse in patients with OCD, 468 patients with OCD were treated with open label escitalopram (10 mg or 20 mg) for 16 weeks, after which the 320 responders (Y-BOCS total score decrease > or =25%) were randomised to placebo or escitalopram (at the assigned dose) for 24 weeks double-blind treatment. The primary analysis (time to relapse) showed a significant advantage for escitalopram (p<0.001, log-rank test). The proportion of patients who relapsed was statistically significantly higher in the placebo group (52%) than in the escitalopram group (23%) (p<0.001, chi(2)-test). The risk of relapse was 2.74 times higher for placebo compared to escitalopram. Escitalopram was well tolerated and improvements in obsessive-compulsive symptoms reported during the open label period were sustained during the double-blind extension of treatment with active drug. These results demonstrate that escitalopram is effective for long-term treatment and relapse prevention in OCD.     

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.     

A double-blind, placebo controlled study of trazodone in patients with obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) have been shown to be preferentially responsive to serotonin (5-HT) uptake-inhibiting antidepressants including clomipramine, fluoxetine, fluvoxamine, and sertraline. The nontricyclic antidepressant, trazodone, also possesses serotonin reuptake inhibiting properties and has been reported to be efficacious in OCD in several case reports and open trials. In order to investigate trazodone's potential antiobsessive efficacy in a controlled fashion, 21 patients with OCD were entered into a double-blind, parallel design comparison of trazodone and placebo. There were no significant differences in baseline rating scores of OCD or depressive symptoms between those who entered the trazodone phase (N = 13) versus those who entered the placebo phase (N = 8). As measured by standardized OCD and depression rating scales, there was no significant difference in OCD or depressive symptoms in the 17 patients who completed 10 weeks of trazodone (N = 11, mean daily dose, 235 +/- 10 mg) versus 10 weeks of placebo (N = 6) administration. In comparison to clomipramine and fluoxetine treatment which we have found to be associated with greater than 95% reduction in platelet 5-HT concentration, there was only a 26% mean reduction in platelet 5-HT concentration after 10 weeks of trazodone administration. These results indicate that trazodone lacks substantial antiobsessive effects and is associated with only modest reductions in platelet 5-HT concentrations.     

Assessing the efficacy of 2 years of maintenance treatment with venlafaxine extended release 75-225 mg/day in patients with recurrent major depression: a secondary analysis of data from the PREVENT study

The objective of this study was to evaluate the long-term efficacy of venlafaxine extended release (ER) < or =225 mg/day in patients with recurrent major depressive disorder (MDD). In this double-blind trial, outpatients with recurrent MDD (N=1096) were randomized to 10 weeks of acute-phase treatment with venlafaxine ER (75-300 mg/day) or fluoxetine (20-60 mg/day) followed by a 6-month continuation phase and two consecutive 12-month maintenance phases. At the start of each maintenance period, venlafaxine ER responders were randomized to double-blind venlafaxine ER or placebo. In this analysis, data from responders to acute and continuation treatment were analyzed during the combined maintenance phases while receiving venlafaxine ER < or =225 mg/day. Failure to maintain response was defined as an increase in maintenance dose to 300 mg/day or recurrence. Differences were calculated using Kaplan-Meier methods and compared using log-rank tests. Continuation-phase responders (n=114) receiving venlafaxine ER < or =225 mg/day comprised the analysis population (venlafaxine ER: n=55; placebo: n=59). The estimated probability for remaining well across 24 months of maintenance treatment was 67% for venlafaxine ER and 41% for placebo (P=0.007). Venlafaxine ER effectively maintained response at doses < or =225 mg/day for up to 2.5 years in patients with recurrent MDD. The findings are consistent with those of the full data set.     

Placebo-controlled continuation treatment with mirtazapine: acute pattern of response predicts relapse.

Pattern of response to antidepressants has been proposed as a method to identify patients whose improvement is more likely due to drug vs those whose improvement on drug is more likely to be a placebo effect. It is hypothesized that those with 'true-drug initial response pattern' are most likely to benefit from continuation treatment. The relationship between acute patterns of response and subsequent placebo-controlled continuation treatment with the antidepressant mirtazapine is examined. A total of 410 outpatients were treated openly with mirtazapine for 8-12 weeks. Patients who remitted in the acute phase were randomized to continue the same dose of mirtazapine or switched to placebo. Acute phase responders were classified as 'placebo initial response pattern' (early responders and nonpersistent responders) and 'true-drug initial response pattern' (delayed and persistent responders). Of those with a 'true-drug initial response pattern,' 10/40 (25.0%) relapsed with continuation mirtazapine, and 23/41 (56.1%) relapsed when switched to placebo. The difference (31.1%) is significant. Of those with a 'placebo initial response pattern,' 5/36 (13.9%) relapsed with continuation mirtazapine, and 12/39 (30.8%) relapsed with placebo substitution. This difference (16.9%) is not statistically significant. Moreover, the relapse rate for 'true-drug initial response pattern' patients switched to placebo (56.1%) was also significantly greater than for 'placebo initial response pattern' patients switched to placebo (30.8%). It has been suggested that patients with late onset and persistence are more likely to have improved because of drug. This hypothesis gains support from this study because of the different relapse rates of 'true-drug' responders on drug and placebo. The low relapse rate for patients with an acute placebo pattern switched to placebo suggests specific drug effect played a smaller role in their initial improvement.     

Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression

The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy. Relapse rates were significantly lower for patients randomized to continued nefazodone treatment than for patients switched to placebo. Kaplan-Meier estimates of relapse rates 9 months (36 weeks) after the end of acute treatment were 1.8% for nefazodone versus 18.3% for placebo (P = 0.009) by the Hamilton Depression Scale and 17.3% versus 32.8% (P = 0.028) by discontinuation for lack of efficacy. The mean modal dose of nefazodone was 412 mg/day at study endpoint. These results demonstrate the clinical effectiveness of up to 1 year's treatment (16 weeks acute and 36 weeks continuation) with nefazodone in depressed patients. Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment.     

A 1-year,double-blind,placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study

We evaluated relapse in patients with stable, chronic schizophrenia over a 1-year period; inpatients were randomized to ziprasidone 40 mg/day (n = 72), 80 mg/day (n = 68), 160 mg/day (n = 67) or placebo (n = 71). The probability of relapse (Kaplan-Meier) at 1 year was significantly lower in the ziprasidone 40, 80, and 160 mg/day groups (43%, 35% and 36%, respectively) compared to placebo (77%; P = 0.002, P < 0.001 and P < 0.001, respectively). In those patients who remained on treatment for at least 6 months, only 9% subsequently relapsed on ziprasidone compared to 42% on placebo (P = 0.001). All three doses of ziprasidone were significantly superior to placebo on Positive and Negative Syndrome Scale (PANSS) efficacy variables (all P < 0.05). Ziprasidone was associated with a significantly greater mean improvement in the PANSS negative symptom subscale compared to placebo (P < 0.05). Discontinuation due to adverse events was similar with ziprasidone and placebo. Ziprasidone treatment was indistinguishable from placebo in assessments of movement disorders and was not associated with weight gain or cardiovascular abnormalities. These results demonstrate that ziprasidone was effective in reducing the frequency of relapse and was associated with long-term improvement in negative symptoms. Ziprasidone was well tolerated in this population of patients with chronic, stable schizophrenia.     

Once-weekly fluoxetine.

The relatively long half-life of the selective serotonin reuptake inhibitor fluoxetine has allowed the development of a delayed-release (enteric-coated) formulation containing 90 mg fluoxetine per capsule for once-weekly oral administration. The cumulative relapse rate in patients switched to once-weekly fluoxetine 90 mg for 25 weeks (after responding to 13 weeks of fluoxetine 20 mg/day) was similar to that in patients continuing to receive fluoxetine 20 mg/day and significantly lower than seen in patients switched to placebo. The efficacy of the once-weekly formulation was also similar to that of the daily formulation in other assessment parameters (modified 17-item Hamilton Rating Scale for Depression, Clinical Global Impressions - Severity of Illness Scale). Patient compliance (measured using an electronically monitored tablet bottle) was maintained at 87.5% in evaluable patients receiving once-weekly fluoxetine 90 mg for 12 weeks from a baseline of 85.4% after responding to 4 weeks of fluoxetine 20 mg/day; in contrast, compliance declined significantly (from 87.3% at baseline to 79.4%; p < 0.001) in patients continuing to receive 20 mg/day for 12 weeks. Once-weekly fluoxetine is well tolerated, with a tolerability profile similar to that of the immediate-release formulation.     

Duloxetine treatment for relapse prevention in adults with generalized anxiety disorder: A double-blind placebo-controlled trial.

The objective was to examine duloxetine 60-120 mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (>/=50% reduction in Hamilton Anxiety Rating Scale total score to /=2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P相似文献   

Impact of study design on the results of continuation studies of antidepressants

Antidepressant continuation studies have used 2 different designs. In the placebo substitution design, all patients are initially treated with active medication in an open-label fashion, and then treatment responders are randomized to continue with medication or switch to placebo in a double-blind manner. In the extension design, patients are randomized to a double-blind placebo-controlled acute study at the outset, and responders to active treatment and placebo are continued on the treatment to which they initially responded. We hypothesized that the design of antidepressant continuation studies would impact on the likelihood of relapse. In the extension design, there is no change in treatment. Whether patients responded to placebo or medication, the treatment that produced the response is continued. In contrast, in the placebo substitution design, there is an obvious change in treatment protocol upon initiation of the continuation phase. Patients are aware that they initially received active medication, and there is now a chance that they will be switched to placebo. We speculated that the expectation of a continued positive response is lower in patients treated using the placebo substitution design than the extension design and therefore predicted that relapse rates would be higher. We conducted a meta-analysis of antidepressant continuation studies and compared the relapse rates in continuation studies using these 2 different designs. As predicted, for both the active medication and placebo groups, the frequency of relapse was lower in studies using an extension design. We also found that the difference in relapse risk between antidepressants and placebo was greater with the extension design. Thus, the design of continuation studies of antidepressants was associated with the absolute percentage of patients who relapse on both active medication and placebo, as well as estimates of differential relapse risk between antidepressants and placebo.     

Efficacy of pregabalin in preventing relapse in patients with generalized social anxiety disorder: results of a double-blind, placebo-controlled 26-week study

The objective of this study was to evaluate the efficacy and safety of pregabalin in preventing relapse in generalized social anxiety disorder (SAD). Patients with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) generalized SAD, who met responder criteria after 10 weeks of open-label treatment with fixed-dose pregabalin (450 mg/day; n=153), were randomly assigned to 26 weeks of double-blind treatment with pregabalin (450 mg/day) or placebo. The primary a-priori outcome of time to relapse was analyzed using the Kaplan-Meier method and the log-rank test. Double-blind treatment with pregabalin was associated with significant delay in time to relapse versus placebo (P=0.035), and with significantly greater maintenance of symptomatic improvement over 26 weeks on the Liebowitz Social Anxiety Scale total (P=0.012) and subscale scores and on the Marks Fear Questionnaire total phobia (P=0.010) and social phobia (P=0.014) subscales. Pregabalin was generally well tolerated. During the double-blind phase, the adverse events that occurred more frequently with pregabalin compared with placebo were dizziness (11.3 vs. 4.1%) and infection (21.3 vs. 16.4%). The results of this study suggest that pregabalin (450 mg/day) is safe, well tolerated, and has significant relapse-prevention efficacy over 26 weeks in patients with SAD who responded to an initial course of the pregabalin treatment.     

Fluoxetine: relationships among dose, response, adverse events, and plasma concentrations in the treatment of depression

Data from two large, fixed-dose trials support the efficacy of a fixed 20 mg/day dose of fluoxetine in the treatment of depression. Data pooled from these two studies suggest a dose relationship for adverse events during fluoxetine therapy. At a fixed 20 mg/day dose, only nausea and insomnia were reported by a significantly greater percentage of patients (p less than .05) than those treated with placebo. However, at 60 mg/day, nausea, anxiety, dizziness, and insomnia were reported by a significantly greater percentage of patients (p less than .05) than those treated with placebo. The potential relationship of response rate [Hamilton Rating Scale for Depression (HAM-D) total decrease greater than or equal to 50%] to plasma concentrations of fluoxetine, norfluoxetine, and fluoxetine plus norfluoxetine was evaluated in one study which excluded early responders (less than or equal to 3 weeks of therapy). No significant relationship was found. Furthermore, adverse events were not related to plasma concentrations.     

A double-blind, randomized, placebo-controlled trial of olanzapine in the prevention of psychotic relapse

Sustained response to antipsychotic therapy is an important outcome measure for patients with psychotic disorders. Placebo control in studies of relapse prevention contributes valuable information yet provokes much debate. This study, using placebo as a control, evaluated olanzapine's efficacy in preventing a psychotic relapse. Participants were stable minimally symptomatic outpatients with schizophrenia or schizoaffective disorder. The study included 4 phases: (1) 4-day to 9-day screening/evaluation (N = 583), (2) 6-week conversion to open-label olanzapine (N = 493; 10-20 mg/d), (3) 8-week stabilization on olanzapine (N = 458; 10-20 mg/d), and (4) 52-week randomized (2:1), double-blind maintenance with olanzapine (N = 224; 10-20 mg/d) or placebo (N = 102). Primary relapse criteria were clinically significant changes in the Brief Psychiatric Rating Scale (BPRS) positive item cluster or rehospitalization due to positive symptoms. Statistical methodology allowed sequential real-time estimation of efficacy across blinded treatment groups and multiple interim analyses, which permitted study termination when efficacy was significantly different between treatments. A significant between-treatment difference emerged 210 days after first patient randomization to double-blind treatment. Thus, 151 (46.3%) of the randomized patients were discontinued early and 34 (10.4%) of the planned patient enrollment were not required. The olanzapine group had a significantly longer time to relapse (P < 0.0001) than the placebo group. The 6-month cumulative estimated relapse rate (Kaplan-Meier) was 5.5% for olanzapine-treated patients versus 55.2% for placebo-treated patients. The design of this study enabled appropriate statistical testing of the primary hypothesis while minimizing exposure of patients to a less effective treatment than olanzapine. In remitted stabilized patients with schizophrenia or schizoaffective disorder, olanzapine demonstrated a positive benefit-to-risk profile in relapse prevention.     

Dose correspondence between olanzapine long-acting injection and oral olanzapine: recommendations for switching

Oral-to-depot dose correspondence was explored in a 24-week study of olanzapine long-acting injection (LAI). Patients with schizophrenia stabilized on oral olanzapine of 10, 15, or 20 mg/day (n=1065) were randomized to continue their oral treatment or switch directly to a fixed dose of olanzapine LAI [(mg/weeks) 45/4, 150/2, 405/4, or 300/2] without oral supplementation. Six-month relapse rates for each LAI-dose group stratified by earlier oral dose were analyzed using a Cox proportional hazard model assessing risk of relapse relative to each oral dose. Relapse rates for the therapeutic LAI doses (≥ 150 mg) varied depending on earlier oral dose, ranging from 1.5% (patients switched from 10 mg/day to 300 mg/2 weeks) to 18.8% (patients switched from 20 mg/day to 150 mg/2 weeks). Switching from 10 mg/day to 405 mg/4 weeks produced a comparable risk of relapse as remaining on that oral dose [Hazard ratio (HR)=1.03]. Switching from 15 or 20 mg/day to 300 mg/2 weeks produced comparable risk of relapse as remaining on those oral doses (HR=0.68 and 1.13, respectively). Pharmacokinetic modeling was conducted to evaluate the resulting dosing recommendations. Findings suggest that patients can be switched directly from oral to olanzapine LAI without the need for oral supplementation and with a low risk of relapse when initiated on an appropriate LAI dose.     

Is quality of life among minimally symptomatic patients with schizophrenia better following withdrawal or continuation of antipsychotic treatment?

This secondary report from our 52-week, double-blind, relapse prevention trial tested whether stable patients with schizophrenia who were taken off active drug treatment would experience greater improvements in long-term quality of life than those who were continued on antipsychotic treatment. On average, Heinrichs-Carpenter Quality-of-Life Scale total scores improved by 4.3 +/- 10.6 points during treatment with olanzapine (10-20 mg/d; n = 212), but decreased by 7.1 +/- 14.6 points during treatment with placebo (n = 92; P < 0.001). Mean Quality-of-Life Scale total scores worsened in both treatment groups for the relapsing patient subgroup, whereas for nonrelapsing patients, those treated with olanzapine had significantly improved mean Quality-of-Life Scale total scores compared with those given placebo. For a subset of nonrelapsing patients who were considered "nonexacerbating" on the basis of minimal non-clinically relevant increases in psychopathology, Quality-of-Life Scale total mean change was no better (P = 0.066) for those given placebo (2.7 +/- 11.0; n = 40) than those treated with olanzapine (5.7 +/- 8.9; n = 174). Path analysis indicated a direct effect of treatment (approximately 29%) on quality of life that was not accounted for by differential changes in psychopathology. In conclusion, stable patients with schizophrenia who were taken off active drug treatment experienced no greater improvements in long-term quality of life than those who were continued on antipsychotic treatment, even in the absence of psychotic symptoms.     

Reboxetine,a new noradrenaline selective antidepressant,is at least as effective as fluoxetine in the treatment of depression

The clinical profile of reboxetine, a selective noradrenaline reuptake inhibitor, was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind, multicenter, parallel-group clinical trial of patients with major depression. Among the 381 patients treated with reboxetine 8 to 10 mg/day, fluoxetine 20 to 40 mg/day, or placebo for up to 8 weeks, a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression (21-item HAM-D) total score (the primary efficacy variable) was seen for both active treatment groups compared with placebo (p < 0.024). A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response (>or=50% reduction in HAM-D) or remission (HAM-D 相似文献   

Long-term efficacy of pregabalin in generalized anxiety disorder

A multicenter, randomized, placebo-controlled, double-blind study was conducted to evaluate the efficacy of pregabalin in preventing relapse of generalized anxiety disorder (GAD) after response to short-term treatment. Outpatients (n=624) with GAD for > or =1 year received open-label pregabalin (450 mg/day) for 8 weeks and, if a clinical response was observed, were randomized to receive either pregabalin (450 mg/day; n=168) or placebo (n=170) for 24 weeks. The primary efficacy parameter was time to relapse. Among responders to open-label acute treatment with pregabalin, time to relapse of GAD was significantly longer for patients treated with pregabalin compared with placebo (P<0.0001). Fifty per cent of the placebo group had relapsed by day 23, and at study endpoint, 65% had relapsed. In the pregabalin group, only 42% had relapsed by study end. Total attrition during double-blind treatment was somewhat higher on pregabalin compared with placebo (21.4 vs. 15.3%); attrition owing to adverse events (AEs) was also somewhat higher on pregabalin (6.0 vs. 2.4%). AEs were relatively low in the double-blind phase; only three AEs occurred with an incidence of more than 5% on pregabalin and placebo, respectively: infection (14.9 vs. 11.2%), headache (10.1 vs. 11.2%), and somnolence (6.0 vs. 0%). No safety concerns were identified with long-term treatment. The study indicates that pregabalin is an effective treatment for the prevention of relapse in patients with GAD.     

Paroxetine: an update of its use in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or =60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Lu AA21004, a multimodal psychotropic agent, in the prevention of relapse in adult patients with generalized anxiety disorder

The purpose of this study was to investigate the long-term maintenance of the efficacy of Lu AA21004 5 or 10 mg/day in the prevention of relapse in patients with generalized anxiety disorder (GAD). Patients (n = 687) with a primary diagnosis of GAD (DSM-IV criteria) and a baseline Hamilton Anxiety (HAM-A) total score of at least 20 underwent a 20-week, open-label Lu AA21004 treatment. In all, 459 patients responded and were randomized to 24-56 weeks of a double-blind treatment with Lu AA21004 (n = 229) or placebo (n = 230). The predefined primary efficacy endpoint was time to relapse (HAM-A total score ≥ 15) using a Cox model; the key secondary efficacy endpoint under multiplicity control was time to relapse for patients responding to treatment for at least 12 weeks. The primary analysis showed a statistically significant effect of Lu AA21004 relative to the placebo on the time to relapse of GAD, with a hazard ratio of 2.71 (P < 0.001). There was a statistically significant effect of Lu AA21004 in the stable responders (hazard ratio = 3.06, P < 0.001). Lu AA21004 was well tolerated, with withdrawal rates due to adverse events of 9% (open-label) and 3% (placebo) and 4% (Lu AA21004) in the double-blind period. In this study, Lu AA21004 5 or 10 mg/day was efficacious in preventing relapse and was well tolerated in the maintenance treatment of GAD.