fluvoxamine and Sexual-Dysfunction--Physiological

Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity.

Topics: Antidepressive Agents, Second-Generation; Body Weight; Central Nervous System Diseases; Depressive Disorder; Fluvoxamine; Humans; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Sleep Wake Disorders

Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships, as well as work performance. We report the results of a multicenter, randomized, placebo-controlled trial comparing the efficacy, safety, and tolerability of fluvoxamine controlled release (CR) to placebo in patients with generalized social anxiety disorder.. A total of 279 adult patients meeting all inclusion/exclusion criteria was recruited at 23 United States sites and randomly assigned to receive either fluvoxamine CR (100-300 mg/d) or placebo for 12 weeks. The dose could be increased, based on efficacy and tolerability, in increments of 50 mg/d at weekly intervals. The dosage remained constant during weeks 6 to 12.. Treatment with fluvoxamine CR resulted in statistically and clinically significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement, and at week 6 on the Sheehan Disability Scale, Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale. The most frequent adverse events reported by patients on fluvoxamine CR were headache, nausea, somnolence, and insomnia. No weight gain was observed for either treatment group, and at end point, there were no differences between treatments on overall sexual function, as measured by the Arizona Sexual Experience Scale.. Both physician and patient-rated scales indicate that fluvoxamine CR is effective and safe for the treatment of generalized social anxiety disorder.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Anxiety; Delayed-Action Preparations; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychometrics; Sample Size; Sexual Dysfunction, Physiological; Social Behavior Disorders; Treatment Outcome

Sexual dysfunction is a major side effect of selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). We conducted a genome-wide association study to identify the genetic factors contributing to the risk of SSRI/SNRI-induced sexual dysfunction by testing 186 320 single nucleotide polymorphism (SNP) markers in a cohort of 201 Japanese major depression patients including 36 with sexual dysfunction induced by SSRI (paroxetine or fluvoxamine) or SNRI (milnacipran). The Cochran-Armitage trend test showed that 11 SNPs, tightly clustered in a distinct region on chromosome 14q21.3, were associated with SSRI/SNRI-induced sexual dysfunction at a genome-wide significance level after false discovery rate (FDR) correction, and the strongest SNP association was with rs1160351 (P=3.04 × 10(-7), risk ratio=2.92, 95% confidence interval (CI)=1.79-4.76). These SNPs mapped to the intronic region of the MDGA2 gene. A Manhattan plot showed that the strong association peak remained in MDGA2 after adjustment for sex and age in a multivariable logistic regression analysis although P values increased slightly and became non-significant. Replication studies with larger sample sizes are required to validate this exploratory study, but our findings may provide insights into the genetic basis of sexual dysfunction induced by SSRI/SNRI.

Topics: Adrenergic Uptake Inhibitors; Adult; Aged; Aged, 80 and over; Asian People; Cohort Studies; Cyclopropanes; Depressive Disorder, Major; Female; Fluvoxamine; Genome-Wide Association Study; Genotype; GPI-Linked Proteins; Humans; Male; Middle Aged; Milnacipran; Neural Cell Adhesion Molecules; Paroxetine; Polymorphism, Single Nucleotide; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological

The intravaginal ejaculation latency time (IELT) behaves in a skewed manner and needs the appropriate statistics for correct interpretation of treatment results.. To explain the rightful use of geometrical mean IELT values and the fold increase of the geometric mean IELT because of the positively skewed IELT distribution.. Linking theoretical arguments to the outcome of several selective serotonin reuptake inhibitor and modern antidepressant study results.. Geometric mean IELT and fold increase of geometrical mean IELT.. Log-transforming each separate IELT measurement of each individual man is the basis for the calculation of the geometric mean IELT. A drug-induced positively skewed IELT distribution necessitates the calculation of the geometric mean IELTs at baseline and during drug treatment. In a positively skewed IELT distribution, the use of the "arithmetic" mean IELT risks an overestimation of the drug-induced ejaculation delay as the mean IELT is always higher than the geometric mean IELT. Strong ejaculation-delaying drugs give rise to a strong positively skewed IELT distribution, whereas weak ejaculation-delaying drugs give rise to (much) less skewed IELT distributions. Ejaculation delay is expressed in fold increase of the geometric mean IELT.. Drug-induced ejaculatory performance discloses a positively skewed IELT distribution, requiring the use of the geometric mean IELT and the fold increase of the geometric mean IELT.

Topics: Antidepressive Agents; Coitus; Data Interpretation, Statistical; Ejaculation; Fluoxetine; Fluvoxamine; Humans; Male; Mianserin; Mirtazapine; Models, Biological; Piperazines; Reaction Time; Research Design; Selective Serotonin Reuptake Inhibitors; Sensitivity and Specificity; Sertraline; Sexual Dysfunction, Physiological; Treatment Outcome; Triazoles

It has been reported that selective serotonin reuptake inhibitor (SSRI) may cause sexual dysfunction.. To determine the relationship between serotonin and sexual function, we investigated the role of serotonergic receptors on changes in intracavernous pressure (ICP) and systemic blood pressure (BP) in conscious and free-moving rats.. ICP and BP were measured in male Sprague-Dawley rats after catheters were inserted into the crus corpus cavernosum and carotid artery, respectively. Pressures were recorded 2 hours after catheterization. In other rats, this procedure was performed 2 weeks after spinal cord transection (spinal cord injury [SCI]) between the eighth and ninth thoracic vertebrae. To investigate the role of serotonergic receptors, fluvoxamine (an SSRI), WAY100635 (a 5-HT(1A)-receptor antagonist), and SB242084 (a 5-HT(2C)-receptor antagonist) were administered by intravenous (i.v.) or intracerebroventricular (i.c.v.) routes.. BP and parameters of ICP were measured in conscious and free-moving rats.. Administration of fluvoxamine (1- to 30-micromol/kg i.v. and 1- to 30-nmol i.c.v.) induced a transient increase in the ICP. The ICP parameters responded in a dose-dependent manner, especially the time to first response (TFR), which was significantly shortened. BP also increased in response to fluvoxamine. In contrast, ICP in SCI rats did not change after fluvoxamine administration. WAY100635 (10 or 30-nmol i.c.v.) induced an increase in the ICP. In combination with fluvoxamine, it significantly shortened the TFR in comparison with WAY100635 or fluvoxamine alone. However, SB242084 (10 or 30-nmol i.c.v.) actually had an inhibitory effect on fluvoxamine-induced ICP responses.. These findings demonstrated that ICP is regulated at the supraspinal level when endogenous serotonin is increased by fluvoxamine. Furthermore, ICP is facilitated by 5-HT(2C)-receptors and inhibited by 5-HT(1A)-receptors in the rat brain.

Topics: Aminopyridines; Animals; Blood Pressure; Dose-Response Relationship, Drug; Fluvoxamine; Indoles; Injections, Intraventricular; Male; Penis; Piperazines; Pyridines; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Sexual Dysfunction, Physiological