Escitalopram: an open-label study of bereavement-related depression and grief.

BACKGROUND: Approximately 8 million Americans suffer the loss of an immediate family member each year. Chronic depression may develop following bereavement-about 15% of the bereaved are depressed at 1 year. Several studies of psychotropic medications have demonstrated improvement in depression ratings, but little data exists for selective serotonin reuptake inhibitor treatment in bereavement-related depression. METHODS: Thirty adults were treated with escitalopram for 12 weeks in open fashion for a major depressive episode following loss of a close family member (parent, sibling, child, or spouse/significant other). Main outcome measures were the Hamilton Depression Rating Scale, the Montgomery-Asberg Rating Scale, the Texas Revised Inventory of Grief, and the Inventory of Complicated Grief. RESULTS: Twenty-nine of thirty participants returned for at least one set of efficacy measures after starting medication. Nineteen subjects (66%) experienced a 50% or greater improvement on the Hamilton Depression Scale. Fifteen subjects (52%) achieved remission, defined as a final score of 7 or less on the Hamilton Depression Scale. Escitalopram significantly reduced depressive symptoms (P<0.001) over time. Subjects with uncomplicated grief and those with complicated grief improved similarly over time. Subjects with and without PTSD improved to a similar degree. Escitalopram was well tolerated. LIMITATIONS: Open-label design, psychotherapy was not controlled, relatively short treatment period, variation in grief scales make comparisons to other studies difficult, all subjects with complicated grief also were clinically depressed, and gender discrepancy of sample. CONCLUSIONS: Escitalopram improved depressive, anxiety, and grief symptoms in individuals experiencing a major depressive episode related to the loss of a loved one.

Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial.

CONTEXT: Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women. OBJECTIVE: To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women. DESIGN, SETTING, AND PARTICIPANTS: An 8-week prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 1, 2003, and January 1, 2007, at 7 US research centers that included 98 previously sexually functioning, premenopausal women (mean [SD] age 37.1 [6] years) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction. INTERVENTION: Forty-nine patients were randomly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity. MAIN OUTCOME MEASURES: The primary outcome measure was the mean difference in change from baseline to study end (ie, lower ordinal score) on the Clinical Global Impression sexual function scale. Secondary measures included the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale-female version, the University of New Mexico Sexual Function Inventory-female version, a sexual activity event log, and the Hamilton Depression Rating scale. Hormone levels were also assessed. RESULTS: In an intention-to-treat analysis, women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 (95% confidence interval [CI], 1.6-2.3) compared with those taking placebo (1.1; 95% CI, 0.8-1.5), with a mean end point difference of 0.8 (95% CI, 0.6-1.0; P = .001). Assigning baseline values carried forward to the 22% of patients who prematurely discontinued resulted in a mean end point in the sexual function score of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil compared with 0.9 (95% CI, 0.6-1.3) among women taking placebo with a mean end point difference of 0.6 (95% CI, 0.3-0.8; P = .03). Baseline endocrine levels were within normal limits and did not differ between groups. The mean (SD) Hamilton scores for depression remained consistent with remission in both groups (4.0 [3.6]; P = .90). Headache, flushing, and dyspepsia were reported frequently during treatment, but no patients withdrew because of serious adverse effects. CONCLUSION: In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00375297.

Primary sexual disorders: recognition and treatment.

Sexual dysfunction is a common complaint in women across different treatment settings and throughout the lifecycle. Defining normality in sexual response is extremely difficult and little data exists to guide the clinician encountering these complaints. The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) provides a useful classification for sexual dysfunction in both women and men. Female sexual dysfunctions defined in DSM-IV-TR are divided into disorders of desire, arousal, orgasm, and pain. This article defines the scope of the problem of female sexual dysfunction, discusses the diagnosis of various disorders of sexual function, and summarizes available psychological and physiologic treatments.

Treatment of bereavement-related depression and traumatic grief.

In the bereaved, approximately 40% meet criteria for major depression within a month of the death. At a year, approximately 15% of the bereaved are depressed and at 2 years, the figure is approximately 7%. Open-label trials of medication for bereavement-related depression have shown promising results for desipramine, nortriptyline, and bupropion SR. One double-blind controlled trial supports the use of nortriptyline, but interpersonal psychotherapy did no better than placebo. In all these trials, depressive symptoms improve more than bereavement symptoms. Effective open-label treatments for traumatic grief include paroxetine, nortriptyline, and a form of psychotherapy called traumatic grief treatment.

Long-term effectiveness of cognitive therapy in major depressive disorder.

Cognitive therapy of depression, based on the cognitive theory of depression, is an established treatment for major depressive disorder. Although few clinicians expect acute treatment of depression with antidepressant medication to prevent long-term relapse of the illness, some practitioners of cognitive therapy report long-term effectiveness in preventing relapse after short-term treatment. We set out to reanalyze follow-up studies in the literature, using intent-to-treat principles to assess the long-term effects of acute treatment with cognitive therapy. From an initial reference list of 97 citations that met our search criteria (controlled clinical trials of cognitive therapy in depression with follow-up), we found five trials that met our inclusion criteria. This report reviews and reanalyzes these five trials, published between 1981 and 1992, which compare cognitive therapy and tricyclic antidepressant therapy. Overall, the evidence favors a longer-term effect for cognitive therapy over tricyclic antidepressants alone.

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

Review of the long-term effectiveness of cognitive behavioral therapy compared to medications in panic disorder.

Panic disorder is a recurrent and disabling illness. It is believed that Cognitive Behavioral Therapy (CBT) has a long-term protective effect for this disorder. This would offer CBT considerable advantage over medication management of panic disorder, as patients often relapse when they are tapered off their medications. This is a review of the literature about the long-term effectiveness of CBT. We searched for follow-up studies of panic disorder using CBT. Of the 78 citations produced in the initial search, most had major methodological flaws, including ignoring losses to follow-up, not accounting for interval treatment, and unclear reporting. Three papers met strict methodological criteria, and two of these demonstrated a modest protective effect of CBT in panic disorder patients. We make recommendations for well-designed studies involving comparisons of medications and cognitive behavior therapy.

Selective phosphodiesterase type-5 inhibitor treatment of serotonergic reuptake inhibitor antidepressant-associated sexual dysfunction: a review of diagnosis, treatment, and relevance.

Sexual dysfunction related to antidepressants, particularly serotonin reuptake inhibitors is a major cause of premature treatment discontinuation. This places patients at increased risk for recurrence, relapse, chronicity, and mortality (eg, suicide). The clinical assessment requires a comprehensive evaluation of sexual function, including libido, arousal, orgasm, and resolution prior to affective disorder, disturbances associated with the emergence of depression, and changes or dysfunctions associated with antidepressant treatment. Other factors to be included for evaluating sexual dysfunction include inquiry for concurrent medical conditions, somatic treatments, lifestyle risk factors, and response to antidepressants. Current treatment approaches to antidepressant-associated sexual dysfunction have relied on open-label reports, literature reviews, and clinical wisdom. Without double-blind, placebo-controlled studies to support them, too much non-evidence-based treatment may be offered to patients. Advances into nonadrenergic-noncholinergic novel signal transduction, specifically phosphodiesterase type-5 inhibitors, offer new opportunities for developing evidence-based treatments for this side effect and improving depression disease management outcomes.

Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

CONTEXT: Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. OBJECTIVE: To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. DESIGN, SETTING, AND PATIENTS: Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. INTERVENTION: Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). RESULTS: Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. CONCLUSION: In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

SSRI sexual dysfunction: a female perspective.

Women experience two to three times the rate of depression that men do. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for many conditions other than depression, such as anxiety disorders, premenstrual dysphoric disorder, pain syndromes, impulse control disorders, and personality disorders, some of which are more common in women. Increasing awareness of sexual side effects has tempered the initial enthusiasm with which SSRIs were greeted. Men taking SSRIs report higher rates of sexual side effects than women taking them, however, women seem to experience more severe sexual dysfunction. In this article, we discuss the epidemiology of sexual dysfunction and describe treatments with sildenafil.