Low-dose sertraline in the treatment of moderate-to-severe premenstrual syndrome: efficacy of 3 dosing strategies. Escitalopram administered in the luteal phase exerts a marked and dose-dependent effect in premenstrual dysphoric disorder. Citalopram in premenstrual dysphoria: is intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle? Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women. Intermittent luteal phase sertraline treatment of dysphoric premenstrual syndrome. Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder. Treatment of premenstrual syndrome with fluoxetine: a double-blind, placebo-controlled, crossover study. Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study. Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled clinical trial. Fluoxetine in the treatment of premenstrual syndrome. A placebo-controlled, randomized, double-blind study of adjunctive bupropion sustained release in the treatment of SSRI-induced sexual dysfunction. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Luteal phase dosing with paroxetine controlled release (CR) in the treatment of premenstrual dysphoric disorder. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. A clinical trial of the effects of estrogen in acutely psychotic women. Fluoxetine in the treatment of premenstrual dysphoria. Luteal phase sertraline treatment for premenstrual dysphoric disorder. Results of a double-blind, placebo-controlled, crossover study. Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: a randomized, double-blind, placebo-controlled crossover trial. Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients. The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study. Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder. Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial. Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment.
Many studies have demonstrated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of premenstrual dysphoric disorder, but few studies have investigated the efficacy of SSRIs in the treatment of premenstrual syndrome (PMS). The objective of this study was to evaluate the safety and efficacy of sertraline in the treatment of moderate-to-severe PMS using 3 different dosing strategies: luteal phase (2 cycles), followed by continuous dosing throughout the month (1 cycle), followed by dosing begun at the first onset of PMS symptoms, or "symptom-onset" dosing (1 cycle).
                314 women with PMS from 22 U.S. sites were randomly assigned to fixed-dose treatment with sertraline (25 or 50 mg/day) or placebo for 4 menstrual cycles after a single-blind, placebo lead-in cycle. Assessments included the Daily Symptom Report (DSR), the Clinical Global Impressions-Severity of Illness and -Improvement scales, the Patient Global Evaluation scale, the Quality of Life Enjoyment and Satisfaction Questionnaire, and the Social Adjustment Scale-Self Report.
                Intermittent luteal-phase dosing with low doses of sertraline (25 and 50 mg/day) produced significant improvement across 2 menstrual cycles, based on total DSR scores, compared with placebo. Continuous and symptom-onset dosing were also effective in treating PMS symptoms, particularly at the lower dose of 25 mg/day.
                The results of the current study suggest that low doses of sertraline may be a safe, effective, and well-tolerated treatment for moderate-to-severe PMS. This is the first placebo-controlled trial evaluating the efficacy of the selective serotonin reuptake inhibitor (SSRI), escitalopram, in the treatment of premenstrual dysphoric disorder (PMDD). Women with PMDD (intention-to-treat population, n = 151) were treated intermittently for 3 months, during luteal phases only, with 10 mg/d escitalopram, 20 mg/d escitalopram, or placebo. Escitalopram was found to exert a marked and a dose-dependent symptom-reducing effect, 20 mg/d being clearly superior to 10 mg/d. Although the primary outcome parameter, that is, the sum of the symptoms irritability, depressed mood, tension, and affective lability, was decreased by 90% with 20 mg/d escitalopram, the effect of active treatment on breast tenderness, food craving, and lack of energy was more modest and not significantly different from that of placebo; this outcome supports our previous assumption that the former symptoms are more inclined to respond to intermittent administration of an SSRI than are the latter. Although the placebo response was high, the difference between the placebo group and the 20-mg/d escitalopram group with respect to the percentage of subjects displaying 80% or greater reduction in the rating of the cardinal symptom of PMDD, that is, irritability, was considerable: 30% versus 80%. Adverse events were those normally reported in SSRI trials, such as nausea and reduced libido, and were not more common in patients given 20 mg/d of escitalopram than in patients given the lower dose. This study supports the usefulness of escitalopram for the treatment of PMDD and sheds further light on how different components of this syndrome are differently influenced by intermittent administration of an SSRI. In a double-blind trial, the selective serotonin reuptake inhibitor citalopram was administered to women with severe irritability and/or depressed mood in the luteal but not in the follicular phase of the menstrual cycle (premenstrual dysphoria). Treatment continued for three consecutive menstrual cycles. One group (N = 17 completers) was administered citalopram continuously at a constant dosage (20+/-10 mg/day) throughout the menstrual cycle. A second group (N = 17) also received citalopram continuously throughout the cycle, but at a lower dosage in the follicular phases (5 mg/day) than in the luteal phases (20+/-10 mg/day) (semi-intermittent treatment). A third group (N = 18) received citalopram (20+/-10 mg/day) in the luteal phase only and placebo during the follicular phase (intermittent treatment). A fourth group (N = 17) received placebo throughout the cycles. The side effects of active treatment were generally mild and transient. Intermittent administration of citalopram was clearly more effective than placebo with respect to both reduction in self-rated irritability and self-rated global improvement; it is of interest that intermittent treatment with citalopram also seemed more effective than continuous or semi-intermittent administration of the drug. To evaluate the efficacy and safety of intermittent, luteal phase-only administration of paroxetine (10 mg and 20 mg) in the treatment of premenstrual dysphoric disorder (PMDD).
                In this multicenter trial, female outpatients (aged 18-45 years) from 4 Canadian health centers meeting DSM-IV criteria for PMDD were asked to perform daily ratings of their premenstrual symptoms for 2 consecutive menstrual cycles. Those displaying the symptoms of irritability and/or depressed mood in the luteal phases but not in the follicular phases of their menstrual cycles were randomly assigned to intermittent, luteal phase-only treatment with paroxetine 10 mg or 20 mg or placebo for 4 additional cycles. The primary efficacy endpoint was the percent change from baseline at study endpoint on the visual analog scale irritability score. Treatment differences were tested using analysis of covariance ad hoc. Estimated treatment mean differences and their associated 95% confidence intervals were also calculated. Data were collected from May 1999 to November 2002.
                Ninety-nine patients were included in the intention-to-treat population. When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects.
                Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD. These results are consistent with previous studies suggesting that PMDD may be treated effectively by luteal phase-only administration of a selective serotonin reuptake inhibitor.
                clinicaltrials.gov Identifier: NCT00620581. Dysphoric premenstrual syndrome (PMS) has been associated with serotonergic dysregulation, and serotonergic medications have been reported to alleviate the symptoms of PMS. We investigated the effects of the serotonin reuptake inhibitor sertraline given during only the luteal phase in women with dysphoric PMS.
                After baseline ratings were obtained during two menstrual cycles, 15 women with dysphoric PMS who also met DSM-IV criteria for premenstrual dysphoric disorder (PMDD) entered single-blind treatment with sertraline 100 mg/day for one full menstrual cycle. Women who responded to this treatment were randomly assigned to a four-cycle double-blind placebo-controlled crossover study in which sertraline 100 mg/day or placebo was each given only during luteal phases of two consecutive menstrual cycles.
                Eleven (79%) of fourteen women responded to single-blind full-cycle treatment with sertraline and were randomly assigned to the double-blind crossover study. Three patients dropped out of the study while taking placebo owing to nonresponse. For the remaining patients, sertraline given during the luteal phase produced significant improvements in depression, impairment, and global ratings compared with placebo and was equivalent in efficacy to sertraline given during the entire menstrual cycle.
                Women with dysphoric PMS who responded to continuous sertraline treatment responded equally well to sertraline treatment that was restricted to the luteal phase. Luteal phase treatment may have advantages in side effect burden and costs. Larger controlled trials are warranted to confirm this finding. Serotonin reuptake inhibitors (SRIs) do not have to be administered continuously to be effective for premenstrual dysphoric disorder (PMDD), but can be given during luteal phases only. This is of practical importance, but also of theoretical interest since it suggests that the onset of action of SRIs is shorter in PMDD than in, for example depression. In this study, both continuous and intermittent SRI administration was compared with placebo, with the special purpose of analyzing if different PMDD symptoms respond differently depending on the treatment regimen. To this end, women meeting slightly modified DSM-IV criteria for PMDD (mean+/-SD age, 37+/-6.3 years) were treated for three menstrual cycles with paroxetine continuously, paroxetine during the luteal phase only, or placebo, the population completing at least one treatment cycle comprising 55-56 subjects per group. Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%. The effect size was highest for irritability (1.4) and lowest for lack of energy (0.5). Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms. The study indicates that the response rate when treating PMDD with SRIs is high, and that irritability is a key target symptom. Symptoms such as irritability, affect lability, and mood swings appear to be more inclined to respond rapidly to SRIs, enabling intermittent treatment, than are, for example, the somatic symptoms. Although its etiology is unknown, it has been hypothesized that premenstrual syndrome (PMS) is linked to a deficiency of central serotoninergic activity. In the present study, we evaluated the effect of fluoxetine, a specific serotonin uptake inhibitor, on PMS symptoms.
                Following extensive screening, including several psychological inventories, eight women with severe persistent PMS participated in a 6-month double-blind, placebo-controlled, crossover study which included three months each of daily fluoxetine 20 mg or placebo, administered in a randomized order. Symptoms were evaluated using the Calendar of Premenstrual Experiences and other psychometric measures.
                Compared with placebo, treatment with fluoxetine was associated with an improvement in PMS symptoms as judged by highly significant decreases in behavioral (P less than .005), physical (P less than .05), and total (P less than .005) Calendar of Premenstrual Experiences scores; Beck Depression Inventory scores (P less than .005); Profile of Mood States subscales scores including depression (P less than .005), tension (P less than .005), and anger (P less than .01); and State-Trait Anxiety Inventory scores. The use of fluoxetine was associated with a greater mean reduction in behavioral (75%) than in physical scores (40%), with a mean decrease in total Calendar of Premenstrual Experiences scores of 62%, which rendered these scores similar to follicular phase values. Thus, the luteal phase symptomatology of PMS was effectively abolished. At this dose, no significant side effects or complications were noted during treatment.
                Fluoxetine appears to be a highly effective, well-tolerated treatment for the psychological and physical symptoms accompanying severe PMS. A significant number of patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) report sexual dysfunction. SSRI-induced sexual dysfunction adversely affects quality of life and patient adherence to and compliance with treatment regimens. This trial examined the efficacy and safety of adjunctive bupropion in the treatment of SSRI-induced female sexual dysfunction. Sexual function was assessed by using the sexual function domains of the Female Sexual Function Index (primary efficacy outcome measure) and the Clinical Global Impression Scale adapted for sexual function (secondary efficacy outcome measure). End point treatment satisfaction was assessed using a Visual Analog Scale. A total of 218 women (25-45 years old) with SSRI-induced sexual dysfunction were randomized to receive 12 weeks of double-blind fixed dosed treatment with bupropion sustained release 150 mg b.i.d. (n = 109) or placebo (n = 109). The mean (SD) for Female Sexual Function Index total score was higher in the bupropion sustained release group (25.9 (5.12), 95% confidence interval (CI) 22.2-29.4) than in the placebo group (17.2 (4.9), 95% CI 15.8-20.1) (p = 0.001). Mean (SD) Clinical Global Impression Scale score for the bupropion group (2.4 (0.6), 95% CI 2.0-3.6) was significantly lower than that for the placebo group (4.2 (0.8), 95% CI 3.4-5.4) (p = 0.001). At the end of the trial the mean (SD) scores for desire (4.1 (0.7), 95% CI 3.5-4.8) (p = 0.001), arousal (4.4 (0.6), 95% CI 3.7-4.8) (p = 0.01), lubrication (4.4 (0.4), 95% CI 3.3-4.8) (p = 0.001), orgasm (4.4 (0.5), 95% CI 3.7-4.7) (p = 0.001), and satisfaction (4.2 (0.7), 95% CI 3.4-4.8) (p = 0.001) were significantly higher in the bupropion group. The highest improvement was observed in sexual desire, followed by lubrication. Compared with baseline, desire and lubrication domains increased by 86.4% (95% CI 64.9-102.2%, p = 0.001) and 69.2% (95% CI 44.7-82.6%, p = 0.001) in the bupropion group. Adjunctive treatment with bupropion sustained release during a 12-week period significantly improved key aspects of sexual function in women with SSRI-induced sexual dysfunction. Because the symptoms of premenstrual dysphoric disorder (PMDD) are limited to the luteal phase of the menstrual cycle, the potential benefit of luteal-phase dosing has been hypothesized.
                This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated the efficacy and tolerability of enteric-coated fluoxetine 90 mg given once or twice during the luteal phase for the treatment of PMDD.
                Study drug was given 14 and 7 days before expected menses during the luteal phase of 3 menstrual cycles. After a screening period and single-blind placebo lead-in period, eligible women were randomized to I of 3 treatment groups: enteric-coated fluoxetine 90 mg on both days (LPWDx2); placebo 14 days before menses and enteric-coated fluoxetine 90 mg 7 days before menses (LPWDx1); or placebo on both days (PLC). The primary efficacy measure was change from baseline in mean luteal-phase scores on the Daily Record of Severity of Problems (DRSP). Secondary efficacy measures included scores on the Rating Scale for Premenstrual Tension Syndrome, Clinician-Rated (PMTS-C); the Clinical Global Impression (CGI)-Severity scale; and the Patient Global Impression (PGI)-Improvement scale. Quality of life was assessed using the Sheehan Disability Scale.
                Two hundred fifty-seven women were randomized to treatment. At the end of the study, the LPWDx2 group had statistically significant improvements in DRSP total, DRSP mood subtotal, DRSP social functioning subtotal, PMTS-C, CGI-Severity, PGI-Improvement, and Sheehan Disability Scale work and family life scores compared with LPWDx1 and PLC (each measure, P < 0.05). There was also a statistically significant improvement in the score on the social life section of the Sheehan Disability Scale with LPWDx2 compared with PLC (P = 0.037). Across all treatment groups, 5 patients discontinued due to nonserious adverse events. Rates of discontinuation for any reason did not differ between the 3 treatment groups.
                The findings of this study support the efficacy and tolerability of enteric-coated fluoxetine 90 mg given twice during the luteal phase of the menstrual cycle for the treatment of PMDD. Premenstrual syndrome (PMS) is defined as the disabling and cyclic occurrence of emotional and behavioral symptom complex during the latter half of the menstrual cycle. Although its etiology is unknown, it has been speculated that premenstrual syndrome is linked to a deficiency of central serotoninergic activity.
                The study consisted of a double-blind, placebo controlled trial of fluoxetine at a dose of 20 mg/day or placebo for three menstrual cycles. The 440 women who appeared to meet the eligibility criteria were instructed to record the 'Calendar of Premenstrual Experiences' (CPE) scale for two complete menstrual cycles. Of 410 women who successfully completed two cycles of recording their symptoms daily only 35 met the criteria for PMS. These criteria included psychiatric interviews which were made before treatment. Thirty-five PMS patients were randomized into placebo or fluoxetine treatment groups.
                Our study suggests that fluoxetine at a dose of 20 mg per day was significantly superior to placebo in alleviating the symptoms of PMS. The most common side effects were gastrointestinal irritability (15%), insomnia (11%) and sexual dysfunction (8.5%).
                Fluoxetine is an effective and well-tolerated drug and appears to have considerable promise in treating a range of symptoms in women with PMS. Sexual side effects are among the common reasons patients discontinue selective serotonin reuptake inhibitors (SSRIs). While many antidotes have been proposed, few have been subjected to double-blind trials. Some evidence has suggested that bupropion may be an effective antidote for SSRI-induced sexual dysfunction. In this double-blind trial, the efficacy of a standard dose of bupropion sustained release (SR) is evaluated in the treatment of SSRI-induced sexual dysfunction.
                Patients with a history of SSRI-induced sexual side effects were randomly assigned to adjunctive treatment with either bupropion SR 150 mg daily or placebo for 6 weeks. Assessments of sexual function and interest included the Arizona Sexual Experiences Scale (ASEX), Brief Index of Sexual Functioning, and a 10-point visual analogue scale. Efficacy was defined as a 50% improvement on the ASEX at the end of 6 weeks. Data were collected from January 1999 to March 2001.
                Forty-one patients entered the study and completed the 6-week trial. No significant differences were seen between placebo and bupropion SR on the ASEX or on any measure of sexual functioning at the end of the trial.
                A fixed dose of 150 mg/day of bupropion SR taken in the morning does not appear to be effective in the treatment of SSRI-induced sexual dysfunction. Additional trials will be required to define what role, if any, bupropion might have in the treatment of SSRI-induced sexual side effects. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of irritable bowel syndrome (IBS) although evidence of their efficacy is scarce.
                Twenty three non-depressed IBS patients were recruited from a tertiary care centre and included in a crossover trial comparing six weeks of treatment with the SSRI citalopram (20 mg for three weeks, 40 mg for three weeks) with placebo. IBS symptom severity was the primary outcome measure, and depression and anxiety scores were also measured. The effect of acute administration of citalopram on colonic sensitivity and on colonic response to feeding was investigated as a putative predictor of symptomatic response to the drug.
                After three and six weeks of treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life, and overall well being compared with placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement. The effect of acute administration of citalopram during a colonic barostat study did not predict clinical outcome. Analysis of the first treatment period as a double blind parallel arm study confirmed the benefit of citalopram over placebo.
                The SSRI citalopram significantly improves IBS symptoms, including abdominal pain, compared with placebo. The therapeutic effect is independent of effects on anxiety, depression, and colonic sensorimotor function. This clinical trial evaluated luteal phase dosing with paroxetine controlled release (CR) (12.5 mg and 25 mg) in the treatment of premenstrual dysphoric disorder (PMDD).
                A multicenter, randomized, double-blind, placebo-controlled, 3-arm, fixed-dose study of luteal phase dosing with paroxetine CR in the treatment of PMDD. Three hundred seventy-three patients with PMDD were randomly assigned into the study. The primary measure of efficacy was the change from baseline in the mean luteal visual analogue scale (VAS)-Mood score. Secondary efficacy measures included disorder-specific evaluations, global assessments of disease severity, and assessments of functional impairment. Adverse events were recorded throughout the trial.
                Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo.
                For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated. Sexual dysfunction, a frequently reported side effect of many antidepressants, may result in patient dissatisfaction and noncompliance with treatment regimens. This paper describes the results of the first placebo-controlled comparison of the efficacy, safety, and effects on sexual functioning of sustained-release bupropion (bupropion SR) and the selective serotonin reuptake inhibitor sertraline. This randomized, double-masked, double-dummy, parallel-group, multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression. Patients were treated with bupropion SR 150 to 400 mg/d, sertraline 50 to 200 mg/d, or placebo for up to 8 weeks. Patients' depression and sexual functioning were assessed at weekly or biweekly clinic visits; safety was assessed by regular monitoring of adverse events, vital signs, and body weight. Treatment groups were similar at baseline in terms of age, sex, and race, and most patients had a diagnosis of moderate uncomplicated depression. Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points. Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo (P < 0.001). Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group (30% to 40%). Nausea (31%), diarrhea (26%), insomnia (18%), and somnolence (17%) occurred in significantly more patients in the sertraline group than in the bupropion SR group (18%, 7%, 13%, and 3%, respectively) and the placebo group (10%, 11%, 4%, and 6%, respectively). Dry mouth occurred more frequently with bupropion SR (19%) than with sertraline (14%) or placebo (12%), although the differences were not significant. Changes in vital signs were similar in all groups. Similar (small, but not statistically significant) decreases in mean body weight were seen in both the bupropion SR (-1.06 kg) and sertraline (-0.79 kg) groups, whereas the placebo group experienced a minor increase (0.21 kg). Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression, sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo. Therefore, bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients. This study was a preliminary open clinical trial aimed at exploring the hypothesis that estrogen may provide protection against schizophrenia in women. Eleven women with acute psychotic symptoms, as scored on the BPRS, SAPS and SANS, had 0.02 mg estradiol added to neuroleptic treatment for eight weeks. Their response was compared to seven women with similar symptom severity receiving neuroleptic treatment alone. Both groups had baseline hormonal assays of estrogen, progesterone, LH and FSH and underwent regular psychopathology ratings during the eight weeks. The group receiving the estradiol adjunct showed more rapid improvement in psychotic symptoms compared with the group receiving neuroleptics only. This difference was not sustained for the entirety of the trial. Both groups reached similar levels of recovery by the eighth week. These results suggest that estradiol may have antipsychotic properties and/or act as a catalyst for neuroleptic responsiveness in women with schizophrenia. We performed a double-blind, placebo-controlled, crossover trial of fluoxetine in 17 women with prospectively confirmed PMS who also met criteria for premenstrual dysphoric disorder (PMDD). A subset of 10 women with PMDD and an additional 10 controls participated in a single-dose m-chlorophenylpiperazine (m-CPP) challenge during the follicular and luteal phases of the menstrual cycle. We evaluated the ability of the acute behavioral response to luteal phase m-CPP administration to predict therapeutic response to fluoxetine. compared with baseline, fluoxetine, but not placebo, treatment significantly improved both emotional and physical symptoms. We identified 11 (65%) fluoxetine responders who no longer met diagnostic criteria for PMDD during fluoxetine but remained symptomatic during placebo treatment. In addition, acute symptomatic improvement also occurred following m-CPP administration in 7 of 10 women with PMDD. The small number of m-CPP nonresponders did not respond to fluoxetine either. Our findings confirm that fluoxetine is an effective treatment of PMDD. To test the efficacy of late-luteal phase dosing of sertraline hydrochloride in women with moderate-to-severe premenstrual dysphoric disorder. This highly prevalent disorder often causes significant psychosocial impairment.
                Double-blind, crossover trial of each 2-menstrual cycle of baseline, sertraline treatment, and placebo. Randomization to sertraline treatment vs placebo occurred after a 2-cycle, drug-free period.
                A large outpatient multispecialty clinic in central Texas.
                Fifty-seven women aged 19 to 49 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of premenstrual dysphoric disorder.
                Late-luteal phase treatment with sertraline hydrochloride in daily doses of 50 mg (cycle 1) followed by 100 mg (cycle 2) vs placebo.
                The 22-item calendar of premenstrual experiences was completed daily and constituted the primary outcome measure, consisting of a total score and behavioral and physical factor scores.
                A repeated-measures analysis of variance for crossover designs found a significant beneficial effect from sertraline treatment in improving the calendar of premenstrual experiences total (P < .01), behavioral factor (P < .01), and physical factor (P < .04) scores. Most women improved when taking sertraline, 50 mg, although a dose increase to 100 mg yielded further improvement in approximately 25% of women. Use of sertraline was extremely well tolerated; the only adverse event reported by 10% or more of women was insomnia in 8 (14%) of them.
                Luteal phase treatment with sertraline was a safe and effective treatment for moderate-to-severe premenstrual dysphoric disorder. Further controlled studies are needed to confirm the results of this preliminary study. The authors designed a randomized, double-blind, crossover study to assess the efficacy of sertraline in the treatment of premenstrual dysphoric disorder (PMDD) when given only during the luteal phase of the menstrual cycle.
                Thirty-one subjects were selected for a 7-month study period that included an initial 2 months of screening, 2 months of treatment with placebo or sertraline, 1 washout month, and 2 months of crossover treatment with either placebo or sertraline. Eleven subjects completed the study. Symptoms were monitored with daily reports using the Calendar of Premenstrual Experience (COPE). For each study phase, premenstrual COPE scores (7 days prior to menses) were examined using repeated measures analysis of variance. Scores were logarithmically transformed. Comparison of baseline scores between the luteal and follicular phases was examined using the paired t test.
                Analysis of COPE results during the treatment periods of the luteal phase showed a significant treatment effect, with higher scores during the placebo cycles compared with the sertraline-treated cycles (p = .0052 behavioral, p = .014 physical).
                This study is the first to demonstrate a significant response to a serotonin selective reuptake inhibitor used only during the luteal phase. The authors point out the importance of this finding both in terms of economic cost of patients as well as how it may add to the growing understanding of the etiology of PMDD. A sustained-release formulation of bupropion (bupropion SR), developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form, has not been evaluated in active comparator trials. This randomized, double-blind, parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline.
                Outpatients with moderate to severe major depressive disorder (DSM-IV) received bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Clinical Global Impressions scale for Severity of Illness (CGI-S), and for Improvement (CGI-I) were completed, and adverse events were assessed in the clinic periodically throughout treatment. Patients' orgasm function was also assessed.
                Mean HAM-D, HAM-A, CGI-I, and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group; no between-group differences were observed on any of the scales. Orgasm dysfunction was significantly (p < .001) more common in sertraline-treated patients compared with bupropion SR-treated patients. The adverse events of nausea, diarrhea, somnolence, and sweating were also experienced more frequently (p < .05) in sertraline-treated patients. No differences were noted between the two treatments for vital signs and weight.
                This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression. Both compounds were relatively well tolerated, and orgasm dysfunction, nausea, diarrhea, somnolence, and sweating were reported more frequently in sertraline-treated patients. To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined.
                The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period.
                After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age.
                Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design. Many agents have been proposed as potential treatments for SSRI-associated sexual dysfunction, but few placebo-controlled trials have been reported.
                After a 1-month baseline evaluation, pre-menopausal women with moderate to severe sexual dysfunction associated with the institution of fluoxetine therapy were randomized to augmentation therapy with placebo (N=39), mirtazapine (N=36), yohimbine (N=35) or olanzapine (N=38) for a 6-week period. Outcomes were measured using a daily diary, a biweekly self-report assessment, and a computer assisted structured interview.
                At baseline, orgasm was most severely impaired. After 6 weeks, there was statistically significant improvement on most measures for the overall group of patients, however there were few differences between treatment groups. Isolated treatment differences were observed for the patient self-report of overall sexual function (olanzapine superior to placebo) and the structured interview sexual satisfaction item (mirtazapine inferior to placebo).
                No drug assessed was consistently associated with differences from placebo. The results of the study do not support uncontrolled reports of efficacy for these agents in premenopausal women. This study compared the sexual functioning effects as well as the safety and efficacy of bupropion sustained release (bupropion SR) and sertraline. Three hundred sixty-four patients with normal sexual functioning and recurrent major depression were treated with bupropion SR (150-400 mg/day), sertraline (50-200 mg/day), or placebo for 8 weeks in this randomized, double-blind, multicenter study. Patients' depression, sexual functioning, and overall safety were assessed at regular clinic visits. Significantly (P < 0.05) more patients treated with sertraline experienced orgasm dysfunction compared with patients treated with bupropion SR or placebo. Bupropion SR, but not sertraline, was statistically significantly superior to placebo in improving scores on all depression scales by the end of the study. Headache occurred with similar frequency in all groups. Gastrointestinal disturbances occurred more frequently with sertraline; insomnia and agitation occurred more frequently with bupropion SR. Small decreases in mean weight were seen with both active treatments; the placebo group experienced a minor increase in mean weight. Both bupropion SR and sertraline were generally well tolerated, although sertraline was more often associated with sexual dysfunction. Bupropion SR, but not sertraline, was statistically superior to placebo in relieving depression by the end of the study. Bupropion SR may offer advantages over sertraline in treating depressed patients concerned with sexual functioning.
SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.