Selective serotonin reuptake inhibitors and treatment of premenstrual dysphoric disorder

TOPIC: Premenstrual dysphoric disorder (PMDD) has reentered the spotlight following the FDA's recent approval of fluoxetine hydrochloride to treat its symptoms. Although the diagnosis and treatment of PMDD has long been a source of contention, the FDA move has heightened the debate over this diagnostic category and the most appropriate treatment. PURPOSE: To explore several diagnoses related to PMDD and review recent research findings pertaining to the effectiveness of SSRIs to treat PMDD. SOURCES OF INFORMATION: Published literature. CONCLUSIONS: Advanced practice nurses need to remain well informed about premenstrual conditions and emerging evidence-based treatment alternatives. In particular, they need to remember that the FDA has approved fluoxetine for the treatment of a very small subset of women with premenstrual complaints, among whom treatment efficacy is limited.     

Comparison of treatment adherence between selective serotonin reuptake inhibitors and moclobemide in patients with social anxiety disorder

Objective

With respect to the pharmacotherapy of social anxiety disorder (SAD), it has been suggested that treatment duration is an important factor that can significantly predict responses. The present study aimed to compare the treatment adherence of SAD patients who were taking either SSRIs or reversible inhibitors of MAO-A (moclobemide) by measuring treatment duration and all-cause discontinuation rates of pharmacotherapy in a natural clinical setting.

Methods

We retrospectively analysed the data of 172 patients diagnosed with SAD. Depending on their medication, we divided the patients into two groups, SSRI (n=54) or moclobemide (n=118). The expected number of all-cause discontinuation every 2 weeks after starting treatment was calculated by life table survival methods. A multi-variable Cox proportional hazard regression was used to analyze the potential influence of explanatory variables.

Results

Treatment duration was significantly longer in the SSRI group [46.41±56.96, median=12.0 (weeks)] than in the moclobemide group [25.53±34.74, median=12.0 (weeks), Z=2.352, p=0.019]. Overall, all-cause discontinuation rates were significantly lower with SSRIs (81%) than moclobemide (96%, χ²=4.532, p=0.033).

Conclusion

The SSRI group had a longer treatment duration and lower all-cause discontinuation rate than moclobemide. Further, only the type of medication had a significant effect on all-cause discontinuation rates and therefore, we could predict better treatment adherence with the SSRIs in the treatment of SAD.     

The impact of premenstrual dysphoric disorder among 92 bipolar patients

ObjectivesTo evaluate the impact of Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV)-defined premenstrual dysphoric disorder (PMDD) lifetime co-morbidity among 92 bipolar patients.MethodNinety-two women with a lifetime diagnosis of DSM-IV-defined Bipolar Disorder (BD) either type I or type II were consecutively enrolled to determine co-morbidity rates with PMDD and associated clinical features. Measures included the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I) and the Clinical Global Impression (CGI) rating scale.ResultsIn our sample, 25 (27.2%) patients reported a lifetime history of PMDD according to DSM-IV criteria (PMDD+). PMDD+ reported higher rates of Cyclothymia and BP-II than PMDD? (respectively 72% vs. 36% and 88% vs. 60%). On the contrary, the carbohydrate-craving feature was more represented among PMDD? than PMDD+ (25% vs. 4%). PMDD was also significantly associated with post-partum depression (36% vs. 15%), Obsessive-Compulsive (24% vs. 7.5%) and Body Dysmorphic Disorders (24% vs. 6%). Finally, PMDD+ reported higher total number of Axis I co-morbid disorders than PMDD?.ConclusionsIn our cohort of BD women, PMDD is a frequent co-morbid condition, in particular among patients with BD-II or Cyclothymia. Multiple co-morbidities also represent a clinical variable associated with PMDD. Further perspective studies are necessary to better define the relationships between PMDD and BD.     

SSRIs治疗强迫症对照分析

目的：比较５羟色胺回收抑制剂（ＳＳＲＩｓ）与氯丙咪嗪对强迫症的临床疗效及副反应。方法：对３５例强迫症患者应用ＳＳＲＩｓ（１８例）与氯丙咪嗪（１７例）进行对照分析。采用Ｙａｌｅ－Ｂｒｏｗｎ强迫量表（Ｙ－ＢＯＣＳ）、汉密尔顿抑郁量表（ＨＡＭＤ）、副反应量表（ＴＥＳＳ）和临床疗效评定标准评定疗效及副反应。结果：ＳＳＲＩｓ与氯丙咪嗪疗效相似,两组显效率和有效率无显著差异。ＳＳＲＩｓ组副反应较氯丙咪嗪组少且     

Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder

BACKGROUND: Due to their favorable side effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Aripiprazole, an atypical antipsychotic agent with partial dopaminergic and serotonin 1A receptor agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study was to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: 12 patients (mean +/- SD age = 46.6 +/- 11.3 years, 66.7% female) with major depressive disorder (MDD) diagnosed by use of the Structured Clinical Interview for DSM-IV-Axis I Disorders, who had failed to experience a clinical response following an adequate trial of an SSRI, were treated with open-label aripiprazole in addition to their SSRI for 8 weeks. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline-endpoint) as measured by the 17-item Hamilton Rating Scale for Depression total score. Data were collected from August 2003 to July 2004. RESULTS: 9/12 (75.0%) patients completed the trial. Using a completer analysis, 5/9 (55.6%) patients were classified as responders. An intent-to-treat (ITT) analysis resulted in 7 responders (58.3%). The overall proportion of remitters was 3/9 (33.3%) using a completer analysis and 5/12 (41.7%) using the ITT analysis. Aripiprazole administration appeared safe, with no severe adverse events observed in any of the study participants. CONCLUSIONS: These results suggest a possible augmentation role for aripiprazole when used in conjunction with SSRIs in SSRI-resistant MDD.     

Triiodothyronine augmentation of selective serotonin reuptake inhibitors in posttraumatic stress disorder

BACKGROUND: There is considerable comorbidity of major depression and posttraumatic stress disorder (PTSD), and antidepressants have been reported to be effective in treating PTSD. Addition of triiodothyronine (T3) to ongoing antidepressant treatment is considered an effective augmentation strategy in refractory depression. We report the effect of T3 augmentation of antidepressants in patients with PTSD. METHOD: T3 (25 microg/day) was added to treatment with a selective serotonin reuptake inhibitor (SSRI) (paroxetine or fluoxetine, 20 mg/day for at least 4 weeks and 40 mg/day for a further 4 weeks) of 5 patients who fulfilled DSM-IV criteria for PTSD but not for major depressive disorder (although all patients had significant depressive symptoms). The Clinician-Administered PTSD Scale, the 21-item Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Severity of Illness scale were administered every 2 weeks, and self-assessments were performed with a 100 mm visual analog mood scale. RESULTS: In 4 of the 5 patients, partial clinical improvement was observed with SSRI treatment at a daily dose of 20 mg with little further improvement when the dose was raised to 40 mg/day. This improvement was substantially enhanced by the addition of T3. Improvement was most striking on the Hamilton Rating Scale for Depression. CONCLUSION: T3 augmentation of SSRI treatment may be of therapeutic benefit in patients with PTSD, particularly those with depressive symptoms. Larger samples and controlled studies are needed in order to confirm this observation.     

Combined psychoeducation and treatment with selective serotonin reuptake inhibitors for youth with generalized social anxiety disorder

Treatment outcome data for childhood social anxiety are scant. Studies that do exist support the efficacy of both pharmacological and psychotherapeutic interventions. Aside from case reports, studies assessing the efficacy of combined treatment approaches are even more limited. In the current study, we present preliminary findings from a combined psychoeducational and pharmacological treatment program for children and adolescents (ages 8-17 years) with generalized social anxiety disorder. Twelve participants received 12 weeks of citalopram treatment (maximum dose 40 mg/day) and eight brief counseling sessions (15 minutes each). Counseling sessions included education about social anxiety, skills coaching, and behavioral exercises; parents were included in these sessions. Based on clinician global ratings of change, 10 of 12 (83.3%) youths reported improvement: 41.7% (n = 5) of the participants were very much improved, and 41.7% (n = 5) were much improved. Significant changes were also found on self-report ratings of social anxiety, depression, and parents' perceptions of children's social skills during the course of treatment. Findings support the need for double-blind, placebo-controlled studies of combined treatments for youth with generalized social anxiety disorder.     

Clinical predictors of response to pharmacotherapy with selective serotonin reuptake inhibitors in obsessive-compulsive disorder

The objective of this study was to investigate the clinical predictors of response to treatment with selective serotonin reuptake inhibitors (SSRI) in a sample of patients with obsessive-compulsive disorder (OCD). A total of 55 patients diagnosed as OCD according to revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders criteria underwent a 12-week standardized SSRI treatment. According to 'treatment response', defined as at least a 35% drop in the Yale-Brown Obsessive-Compulsive Scale total score, OCD patients were divided into two groups. A total of 32 (58.2%) patients who responded to treatment and 23 (41.8%) who did not, were compared in terms of sociodemographic and clinical characteristics. The authors' findings demonstrated that the severity of obsession-compulsions and disability in work, social and family lives at the beginning of treatment were significantly higher in OCD patients who did not respond to treatment in comparison to those who did. Linear regression analysis, however, revealed that Sheehan Disability Scale-work score at baseline was a predictor of response to SSRI treatment. The higher levels of disability at the beginning of treatment in patients with OCD are associated with a poorer response to SSRI.     

Cost-utility of selective serotonin reuptake inhibitors for depression in primary care in Catalonia

OBJECTIVE: To determine the cost-utility of selective serotonin reuptake inhibitors (SSRIs) for treating depressive disorders prescribed in primary care (PC). METHOD: A total of 301 participants beginning antidepressant treatment with an SSRI were enrolled in a prospective 6-month follow-up naturalistic study. Incremental cost-utility ratios (ICUR) were obtained for several comparisons among different SSRIs. To address uncertainty in the ICUR's sampling distribution, non-parametric bootstrapping was carried out. RESULTS: Taking into account adjusted total costs and incremental quality of life gained, fluoxetine dominated paroxetine and citalopram with 63.4% and 79.3% of the bootstrap replications in the dominance quadrant, respectively. Additionally, fluoxetine was cost-effective over sertraline with 83.4% of the bootstrap replications below the threshold of 33,936 US$/quality-adjusted life year (30,000 euro/QALY). CONCLUSION: Fluoxetine seems to be a better cost-utility SSRI option for treating depressive disorders in PC.     

Decreased suicidal ideation in depressed patients with or without comorbid posttraumatic stress disorder treated with selective serotonin reuptake inhibitors: an open study

Comorbidity of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is associated with higher morbidity including suicidal ideation and behavior. Selective serotonin reuptake inhibitors (SSRIs) are a known treatment for PTSD, MDD and comorbid PTSD and MDD. Since the patients with comorbid MDD and PTSD (PTSD-MDD) are sicker, we hypothesize a poorer response to treatment compared to patients with MDD only. Ninety-six MDD patients were included in the study: 76 with MDD only and 20 with PTSD-MDD. Demographic and clinical parameters at baseline were assessed. We examined clinical parameters before and after 3 months of open SSRI treatment in subjects with PTSD-MDD and compared this group to individuals with MDD only. At baseline, PTSD-MDD patients had higher Hamilton Depression Rating Scale and Buss-Durkee Hostility Scale scores compared with MDD only subjects. There was a significant decrease in scores on the Hamilton Depression Rating Scale, Beck Depression Inventory, Beck Hopelessness Scale, and Beck Scale for Suicidal Ideation after 3 months of treatment with SSRIs in both groups. The magnitude of improvement in Beck Scale for Suicidal Ideation scores was greater in the PTSD-MDD group compared to the MDD only subjects. Symptoms of depression including suicidal ideation improved in MDD patients with or without comorbid PTSD after 3 months of treatment with SSRIs but improvement in suicidal ideation was greater in the PTSD-MDD group. Our finding has not supported the hypothesis that a response to treatment is poorer in the PTSD-MDD group which may indicate that sicker patients benefit more from the treatment.     

Preliminary experience with adjunctive quetiapine in patients receiving selective serotonin reuptake inhibitors

Treatment of depression and anxiety disorders with selective serotonin reuptake inhibitors (SSRIs) has been shown by numerous studies to be generally effective. Less well understood is how clinically to address the residual anxiety symptoms a significant minority of such patients treated with SSRIs continue to experience. We assessed quetiapine as adjunctive therapy to SSRIs for patients with anxiety symptoms complicating a depressive or anxiety disorder. Patients receiving a stable dosage of an SSRI for at least 6 weeks who also had persistent anxiety symptoms (Hamilton Anxiety scale [HAM-A] > or =16), were enrolled in a 9-week, open-label, variable dose study. Changes in clinical status were assessed with the Hamilton Depression Rating Scale (HAM-D), HAM-A, and State Anxiety Inventory (SAI). Statistically and clinically significant reductions of > or =50% in the HAM-D and HAM-A occurred by the second week of treatment in 10 of the 11 patients. These improvements continued throughout the study along with a significant improvement on the SAI scale. The most frequent side effects reported were mild dry mouth, constipation, and transient drowsiness with dose escalation. The results provide evidence that quetiapine may be an effective adjunctive treatment for recalcitrant anxiety symptoms in individuals treated with SSRIs for either anxiety or depressive disorders. Given the open-label design of the trial, more rigorous studies are clearly indicated.     

A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic illness associated with substantial morbidity; it often requires long-term medication. The best-studied therapeutic agent in the treatment of this disorder is the tricyclic antidepressant clomipramine. Since other tricyclic antidepressants appear to lack efficacy in OCD, that of clomipramine has been linked to its potent effects on serotonin. Consequently, agents that selectively inhibit serotonin reuptake have been the focus of several large-scale, placebo-controlled studies of OCD. Their efficacy in OCD is the focus of our review. DATA SOURCES: MEDLINE search (1966 to present) of OCD treatment with clomipramine or SSRI antidepressant medication using the key words obsessive-compulsive disorder, serotonin reuptake inhibitors, clomipramine, and pharmacology. STUDY FINDINGS: The selective serotonin reuptake inhibitors fluoxetine, sertraline, fluvoxamine, and paroxetine have, in separate multicenter trials, demonstrated efficacy and tolerability in the treatment of OCD. In contrast, clomipramine, though efficacious, is often associated with substantial adverse events, particularly anticholinergic side effects. While 2 recent meta-analyses support the superior efficacy of clomipramine over selective serotonin reuptake inhibitors in the treatment of OCD, 5 of 6 head-to-head comparisons of either fluoxetine or fluvoxamine versus clomipramine have found similar efficacy but a lower incidence of side effects with the selective serotonin reuptake inhibitor. A recently completed multicenter, 12-week, double-blind trial of paroxetine versus clomipramine versus placebo showed paroxetine to be as effective as clomipramine. With significantly fewer dropouts due to adverse effects than clomipramine, paroxetine was also associated with superior tolerability. CONCLUSION: The suggestion that selective serotonin reuptake inhibitors possess efficacy similar to that of clomipramine, but have a superior side effect profile, may have important implications for patients with OCD who require long-term treatment.     

文拉法辛对选择性5-羟色胺再摄取抑制剂治疗无效的抑郁症患者的疗效

目的研究文拉法辛对选择性5羟色胺再摄取抑制剂(SSRI)治疗无效的抑郁症患者的治疗效果。方法对经SSRI治疗8周而无明显疗效的34例抑郁症患者以文拉法辛治疗6周(研究组),剂量为(100±20)mg/d。在文拉法辛治疗前及治疗后第1,2,4,6周末评定汉密尔顿抑郁量表(17项,HAMD),并进行临床疗效评定,监测血压,记录不良反应。选择同期门诊34例年龄、诊断与研究组相匹配的患者作为对照组,给予文拉法辛治疗6周,剂量为(99±25)mg/d。结果两组患者的HAMD评分均从第1周末起明显下降(P<005或P<001),且一直持续至治疗第6周末。研究组治疗第6周末的有效率达68%(23/34),临床治愈率达53%(18/34);对照组分别为77%(26/34)和59%(20/34)。两组间的差异无统计学意义(P>005)。研究组口干、恶心、呕吐的发生率高于对照组,差异有统计学意义(P<005)。结论文拉法辛对SSRI治疗8周而无明显疗效的抑郁症患者有较好的疗效。     

Continuous or intermittent dosing with sertraline for patients with severe premenstrual syndrome or premenstrual dysphoric disorder

OBJECTIVE: The authors compared the efficacy and acceptability of continuous versus intermittent treatment with a selective serotonin reuptake inhibitor in women with severe premenstrual syndrome and determined the effects of postmenstrual symptom severity and depression history as covariates of the treatment response. METHOD: Patients who met symptom criteria and reported impaired functioning after three screening cycles were randomly assigned to three cycles of double-blind, placebo-controlled treatment with continuous (full-cycle dosing) or intermittent (luteal-phase dosing) sertraline. The design was stratified for severity of postmenstrual symptoms and history of major depression. Flexible sertraline dose was 50-100 mg/day. Outcome measures were the Daily Symptom Rating Form score and patient global ratings of functioning. RESULTS: Both sertraline groups improved significantly more than the placebo group as assessed by total premenstrual Daily Symptom Rating Form scores for 3 treatment months. Daily Symptom Rating Form factors that were significantly more improved in the sertraline groups were mood and physical symptoms. Sertraline improvement occurred swiftly in the first month of treatment. Gradual placebo improvement was similar to sertraline in the third month. Subjects with higher postmenstrual symptoms before treatment remained more symptomatic regardless of the dosing regimen. A history of major depression was not associated with treatment response. More sertraline-treated subjects reported improved functioning in the domains of family relationships, social activities, and sexual activity. CONCLUSIONS: Premenstrual dosing does not differ from continuous dosing with sertraline in premenstrual syndrome treatment. Higher levels of postmenstrual symptoms limit treatment response and are important to define in treatment of premenstrual syndrome.     

Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder

BACKGROUND: Due to their favorable side-effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Ziprasidone, an atypical antipsychotic agent with strong 5-HT(1A) agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study is to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: Twenty patients with major depressive disorder (MDD) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002. MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline to endpoint), as measured by the HAM-D-17 total score. RESULTS: Thirteen of 20 patients (65.0%) completed the trial. Using a completer analysis, 8 patients (61.5%) were classified as responders. An intent-to-treat (ITT) analysis resulted in 10 responders (50.0%). The overall proportion of remitters was 5 of 13 (38.5%) using a completer analysis and 5 of 20 (25.0%) using the ITT analysis. Ziprasidone administration appeared to be safe, with no clinically significant QTc prolongation or severe adverse events observed in any of the study participants. CONCLUSION: These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD.     

Treatment of severe depression with the selective serotonin reuptake inhibitors

The selective serotonin reuptake inhibitors (SSRIs) are recognized as effective as and better tolerated than older antidepressant therapies and have become the drugs of choice in the treatment of mild to moderate depression. However, there is a clinical impression that the SSRIs are less effective than older therapies in the severely depressed patient. A limited number of trials have attempted to address this issue. This review assesses 16 controlled studies of SSRIs in severe depression. The findings from a majority of studies found the SSRIs to be superior to placebo and as effective as but better tolerated than the tricyclic antidepressants (TCAs) in severely depressed patients. Although future studies are needed to corroborate and elaborate on these data, studies still support the use of SSRIs in this patient population. Depression and Anxiety 4:182–189, 1996/1997. © 1997 Wiley-Liss, Inc.