Angel L. Montejo

Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline.

OBJECTIVE This study evaluates the efficacy of agomelatine, the first antidepressant to be an agonist at MT(1)/MT(2) receptors and an antagonist at 5-HT(2C) receptors, versus sertraline with regard to the amplitude of the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder (MDD). METHOD Outpatients with DSM-IV-TR-defined MDD received either agomelatine 25 to 50 mg (n = 154) or sertraline 50 to 100 mg (n = 159) during a 6-week, randomized, double-blind treatment period. The study was conducted from 2005 to 2006. The main outcome measure was the relative amplitude of the individual rest-activity cycles, expressed as change from baseline to week 6 and collected from continuous records using wrist actigraphy and sleep logs. Secondary outcome measures were sleep efficiency and sleep latency, both derived from actigraphy, and efficacy on depression symptoms (17-Item Hamilton Depression Rating Scale total score and Clinical Global Impressions scale scores) and anxiety symptoms (Hamilton Anxiety Rating Scale total score and subscores). RESULTS A significant difference in favor of agomelatine compared to sertraline on the relative amplitude of the circadian rest-activity cycle was observed at the end of the first week (P = .01). In parallel, a significant improvement of sleep latency (P <.001) and sleep efficiency (P <.001) from week 1 to week 6 was observed with agomelatine as compared to sertraline. Over the 6-week treatment period, depressive symptoms improved significantly more with agomelatine than with sertraline (P <.05), as did anxiety symptoms (P <.05). CONCLUSIONS The favorable effect of agomelatine on the relative amplitude of the circadian rest-activity/sleep-wake cycle in depressed patients at week 1 reflects early improvement in sleep and daytime functioning. Higher efficacy results were observed with agomelatine as compared to sertraline on both depressive and anxiety symptoms over the 6-week treatment period, together with a good tolerability profile. These findings indicate that agomelatine offers promising benefits for MDD patients. TRIAL REGISTRATION www.isrctn.org: ISRCTN49376288.

Sexual function in chronic illness

INTRODUCTION Direct and indirect effects of chronic disease on sexual health are frequent and complex, but guidelines for their optimal management are lacking. With improved surgical and medical treatment of the underlying disease, the numbers of men and women needing assessment and management of associated sexual dysfunction are increasing. AIM To provide recommendations/guidelines for the clinical management of sexual dysfunction within the context of chronic illness. METHODS An international consultation in collaboration with the major sexual medicine associations assembled 186 multidisciplinary experts from 33 countries into 25 committees. Nine experts from four countries compiled the recommendations of sexual dysfunction in chronic illness and cancer with four focusing on neurological, renal, and psychiatric disease and lower urinary tract symptoms (LUTS). Searches were conducted using Medline, Embase, Lilacs, and Pubmed databases. MAIN OUTCOME MEASURES Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. RESULTS Some conclusions concerning prevalence and pathophysiology of sexual dysfunction in the context of neurological disorders, end-stage renal failure, LUTS, and psychiatric disease were made. Optimal assessment of the multiple factors affecting sexuality when one or both partners are chronically ill is outlined. Evidence-based recommendations for management are presented. Comorbid depression is frequent and independently determines prevalence of sexual dysfunction in many conditions. CONCLUSIONS There is need for more research and scientific reporting on prevalence, pathophysiology, and optimal treatment of sexual dysfunction associated with chronic illness. Screening for and managing comorbid depression is strongly recommended.

Prescribing patterns of antidepressants in Europe: results from the Factors Influencing Depression Endpoints Research (FINDER) study

Antidepressant prescribing patterns and factors influencing the choice of antidepressant for the treatment of depression were examined in the Factors Influencing Depression Endpoints Research (FINDER) study, a prospective, observational study in 12 European countries of 3468 adults about to start antidepressant medication for their first episode of depression or a new episode of recurrent depression. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly prescribed antidepressant (63.3% patients), followed by serotonin-norepinephrine reuptake inhibitors (SNRIs, 13.6%), but there was considerable variation across countries. Notably, tricyclic and tetracyclic antidepressants (TCAs) were prescribed for 26.5% patients in Germany. The choice of the antidepressant prescribed was strongly influenced by the previous use of antidepressants, which was significantly associated with the prescription of a SSRI (OR 0.64; 95% CI 0.54, 0.76), a SNRI (OR 1.49; 95% CI 1.18, 1.88) or a combination of antidepressants (OR 2.78; 95% CI 1.96, 3.96). Physician factors (age, gender, speciality) and patient factors (severity of depression, age, education, smoking, number of current physical conditions and functional syndromes) were associated with initial antidepressant choice in some models. In conclusion, the prescribing of antidepressants varies by country, and the type of antidepressant chosen is influenced by physician- as well as patient-related factors.

Psychometric Properties of the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) in Patients with Schizophrenia and Other Psychotic Disorders

Sexual dysfunction is a disturbing and often underrecognized problem associated with schizophrenia and its treatment. The Psychotropic-Related Sexual Dysfunction (PRSexDQ-SALSEX) is a brief and relatively nonintrusive questionnaire that has shown adequate psychometric properties in patients with depression. This study examined the psychometric properties of the PRSexDQ-SALSEX in a sample of patients with schizophrenia or other psychotic disorders who were experiencing anti-psychotic-induced sexual dysfunction and were switched to olanzapine. The PRSexDQ-SALSEX was very feasible and its internal reliability was satisfactory. In addition, this questionnaire showed a good convergent validity and sensitivity to tracking changes in sexual functioning.

Quality of life outcomes among patients with depression after 6 months of starting treatment: Results from FINDER

BACKGROUND Health-related quality of life (HRQoL) data in depression are limited. We studied the impact of antidepressant (AD) treatment on HRQoL outcomes in depressed patients and investigated factors associated with these outcomes in routine practice settings. METHODS The Factors Influencing Depression Endpoints Research (FINDER) study was a 6-month, European, prospective, observational study, designed to estimate HRQoL in 3468 adult patients with a clinically diagnosed episode of depression at baseline and at 3 and 6-months after commencing AD treatment. HRQoL was assessed by the Medical Outcome Short-Form (36) Health Survey (SF-36) and European Quality of Life-5 Dimensions (EQ-5D). Regression analysis identified baseline and treatment variables independently and significantly associated with HRQoL outcomes. RESULTS Most HRQoL improvement occurred within 3 months of starting treatment. Better HRQoL outcomes were strongly associated with fewer somatic symptoms at baseline, AD treatment taken and not switching within AD groups. Education and occupational status were also important. Depression variables (number of previous depressions and current episode duration) were consistently associated with worse HRQoL outcomes. Self-rated depression severity was associated with poorer outcomes on the SF-36 mental component only. LIMITATIONS As this was an observational study, the important finding that between and within AD group switching impacted HRQoL will need to be investigated in more controlled settings. CONCLUSIONS Receiving an AD treatment was associated with large improvements in HRQoL, but switching within AD groups was consistently associated with poorer outcomes. Somatic symptoms, including painful symptoms, are often present in depressed patients and appear to negatively impact HRQoL outcomes.

Generalized anxiety disorder, with or without co-morbid major depressive disorder, in primary care: Prevalence of painful somatic symptoms, functioning and health status

BACKGROUND Painful physical symptoms (PPS) have received little attention in patients with generalized anxiety disorder (GAD). The objective of the present study was to assess the prevalence of PPS in patients with GAD vs patients with GAD and co-morbid major depressive disorder (MDD) and a control group (patients neither with GAD nor MDD). METHODS This is a cross-sectional, multi-center, epidemiological study, in primary care. Patients were screened for GAD (HADS-A), followed by a diagnosis confirmation (MINI). Patients were considered to have PPS when VAS overall pain score >30. Functioning and health status was assessed (SDS, EUROQoL-5D). Relationships between the presence of PPS and functioning and health status was analyzed (ANCOVA models). Results were adjusted for confounding factors. RESULTS Of 7152 patients, 1546 (22%) screened positive for GAD, 981 (14%) had confirmed GAD diagnosis, of whom 559 (8%) had GAD with co-morbid MDD and 422 (6%) had GAD alone. Of the 5292 (74%) patients screened negative for GAD, 336 (5%) were confirmed as controls. PPS in patients with GAD were twice as prevalent as in the control group: 59.0% vs. 28.3%; p<0.001. The presence of co-morbid MDD was associated with a significantly higher prevalence of PPS: 78.0% vs. 59.0%; p<0.001. PPS were significantly associated with functioning and health status impairment (p<0.001) both in GAD alone and in GAD and co-morbid MDD compared with controls. LIMITATIONS Results do not prove causal relationships. CONCLUSIONS Our results support the clinical relevance of PPS in patients suffering from GAD; therefore they need to be considered when evaluating the patient.

Switching to duloxetine in selective serotonin reuptake inhibitor non- and partial-responders: Effects on painful physical symptoms of depression

Painful physical symptoms (PPS) are common in patients with depression. Our objective was to evaluate the presence of PPS in a sample of SSRI non- or partial-responders with MDD and examine the effect of a switch to duloxetine on those PPS. Outpatients who met criteria for MDD despite having taken an SSRI antidepressant for at least 6 weeks, and who had a Hamilton depression rating scale total score of at least 15 and a clinical global impression of severity score of at least 3, were randomized to switch to duloxetine by either a direct switch or a start-taper switch method. PPS were assessed at baseline and at the study endpoint using various measures including six visual analog scales (VAS) for pain (overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake), the pain subscale of the symptom questionnaire-somatic subscale, and the bodily pain subscale of the short form-36 item health survey. Clinically significant levels of pain (mean baseline VAS scores >30 mm) were seen across all VAS pain measures prior to switching. Switch to duloxetine was associated with significant improvements on all pain measures regardless of switch method, and there was evidence for an earlier reduction in pain in the start-taper switch group. In summary, MDD patients who were non- or partial-responders to SSRI treatment were found to have clinically significant pain which improved significantly following switch to duloxetine regardless of the switch method utilized.

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%; χ 2 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%; χ 2 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.

Sexual side-effects of antidepressant and antipsychotic drugs.

Purpose of review Psychotropic-related sexual dysfunction is a quite frequent issue in clinical practice, mainly in chronic treatments affecting both quality of life and compliance. Recent findings In the last decade fortunately antidepressants and antipsychotic compounds have been deeply screened in order to identify sexual adverse events that were commonly underdiagnosed and previously underestimated by clinicians and perhaps by pharmaceutical companies as well. Some differences in the mechanism of action are the nucleus of this poorly tolerated adverse event. All antidepressants with serotonergic activity can cause mild to severe sexual dysfunction such as decreased libido and delayed orgasm frequently (>60%) or anorgasmia and arousal difficulties sometimes (30%). In contrast, noradrenergic, dopaminergic, or melatonergic antidepressants do not cause sexual dysfunction but perhaps the clinical profile of patients receiving these compounds could be different. Antipsychotics that highly increase prolactin levels and strongly block dopamine receptors could be related to sexual dysfunction as well. Unfortunately, these dysfunctions are present during the long term after the antipsychotic onset to provide continued symptom control and enable recovery. Young patients suffering psychosis and concomitant sexual dysfunction (erectile and/or orgasmic difficulties) tend to show poor compliance in chronic treatments affecting the outcomes. Summary The implications of psychotropic-related sexual dysfunction in clinical practice are relevant mainly in patients under long-term treatment with previous satisfactory sexual life. Implications for future research about sexual dysfunction in all new treatments should be strongly taken into account.

The effects of agomelatine on sexual function in depressed patients and healthy volunteers

Selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor antidepressants are associated with high rates of treatment‐emergent sexual dysfunction (TESD) due to stimulation of serotonin receptors.