Mechanisms and treatments of SSRI-induced sexual dysfunction

SSRI-induced sexual dysfunction affects 30% to 50% or more of individuals who take these drugs for depression. Biochemical mechanisms suggested as causative include increased serotonin, particularly affecting 5HT2 and 5HT3 receptors; decreased dopamine; blockade of cholinergic and alpha-1 adrenergic receptors; inhibition of nitric oxide synthetase; and elevation of prolactin levels. Five approaches to treatment include conservative approaches such as wait and see, decrease dosage, and drug holidays. More aggressive strategy for treating SSRI-induced sexual dysfunction are changing antidepressants and augmentation.     

Urinary, faecal and sexual dysfunction in patients with multiple sclerosis

The prevalence and nature of bladder and bowel dysfunction were examined in a population-based study of 221 patients with multiple sclerosis who returned postal questionnaires. This preliminary investigation was supplemented by personal review which also provided information on sexual dysfunction in 174 and laboratory and urodynamic tests in 152 participants. Thirty of 221 (14%) currently used an indwelling catheter, and 84 of the remainding190 (44%) reported symptoms of urinary dysfunction, of which the most common were urgency and frequency. Thirteen of 144 (9%) patients had biochemical evidence of renal dysfunction, and 40 of 132 (30%) had infected urine samples. Eleven of 54 patients in whom investigation of upper urinary tract was thought to be appropriate demonstrated abnormalities. Sixty-four of 221 (29%) patients had experienced faecal incontinence, and 120 of 221 (54%) were constipated. Fifty-six of 68 (82%) men and 55 of 106 (52%) women reported a deterioration in sexual activity, the commonest symptoms being erectile failure in men and fatigue in women. Received: 21 August 1998 Received in revised form: 27 April 1999 Accepted: 16 June 1999     

Instruments to measure sexual dysfunction in community and psychiatric populations

Sexual dysfunction is a significant issue for many individuals. This can be the result of existing disorders, side effects of medications, or both. In order to effectively assess and, if appropriate, manage sexual dysfunction in various populations, it is important to consider the use of validated instruments that can provide a baseline to detect dysfunction and measure change over time. This review will assess the psychometric properties of scales (self-report and interview-based) that have been used in community, psychiatric, and gender-specific populations, with a particular emphasis on depressed patients before and during antidepressant therapy. Key considerations for scale selection and development are also discussed.     

Gender difference in antidepressant-related sexual dysfunction in Taiwan

Objective

Sexual dysfunction accompanied by depression may be altered by antidepressants. The effects of antidepressants on sexual dysfunction among males and females remain to be investigated.

Methods

Three groups of subjects, drug-free patients with depression (N= 125), medicated patients with depression (N= 145) and healthy volunteers (N= 255), were recruited. A Chinese version of the Changes in Sexual Functioning Questionnaire was employed to assess sexual function as the primary outcome.

Results

Drug-free depressed females and medicated depressed males had more sexual dysfunction than healthy controls. The desire for sexual behaviors among healthy females and medicated depressed females was higher than that of drug-free depressed females.

Conclusion

Depression and antidepressants may have different impacts on the sexual function of males and females.     

Mirtazapine augmentation for selective serotonin reuptake inhibitor-induced sexual dysfunction: a retropective investigation

The aim of the present study was to retrospectively identify sexual dysfunction changes in the patients under mirtazapine-augmented serotonin reuptake inhibito (SSRI) treatment. The study comprised medical records of 20 outpatients, under mirtazapine-augmented SSRI treatment for their major depressive disorder, who had been selected among the patients that had developed sexual dysfunction to previous treatment as monotherapy, with SSRI for at least six weeks. These drugs were maintained and mirtazapine were added (15-45 mg/day). There was a significant difference in scores between baseline and week 4 or week 8 on the both Hamilton Depression Rating and Arizona Sexual Experience Scale. According to Clinical Global Impression-Improvement, 68.4% of the patients were responders. The use of low-dose mirtazapine as an add-on treatment to SSRIs appears to be an effective and well-tolerated augmenttaion for sexual dysfunction caused by SSRIs.     

米氮平与文拉法辛治疗抑郁症引起性功能障碍Meta分析

目的评价国内米氮平与文拉法辛治疗抑郁症对照研究引发性功能障碍的差异。方法应用循证医学的Meta分析，采用Peto固定效应模型法，对符合准的12篇对照研究文献性功能障碍的差异进行Meta分析。结果5项研究共313例纳入研究，米氮平治疗组共159例，发生性功能障碍1例，文拉法辛治疗组154例，发生性功能障碍15例，两组性功能障碍的发生率分别是0．63％和9．74％，综合检验两组差异有统计学意义（Z=2．96，P〈0．01；OR=0．10，959，6CI：0．06～0．56）。结论在治疗抑郁症中，文拉法辛比米氮平更容易引发性功能障碍，应特别加以关注。     

Sexual differentiation of the copulatory neuromuscular system in green anoles (Anolis carolinensis): normal ontogeny and manipulation of steroid hormones

The copulatory neuromuscular system of green anoles is sexually dimorphic and differentiates during embryonic development, although details of the process were unknown. In Experiment 1, we determined the time course of normal ontogeny. Both male and female embryos possessed bilateral copulatory organs (hemipenes) and associated muscles until incubation day 13; the structures completely regressed in female embryos by incubation day 19 (total incubation 34 days). In Experiment 2, we treated eggs with testosterone, dihydrotestosterone, estradiol, or vehicle on both incubation days 10 and 13 to determine whether these steroid hormones mediate sexual differentiation. These time points fall between gonadal differentiation, which was determined in Experiment 1 to complete before day 10, and regression of the peripheral copulatory system in females. Tissue was collected on the day of hatching. Gonads were classified as testes or ovaries; presence versus absence of hemipenes and muscles, and the number and size of copulatory motoneurons were determined. Copulatory system morphology of vehicle-treated animals matched their gonadal sex. Hemipenes and muscles were absent in estradiol-treated animals, and androgens rescued the hemipenes and muscles in most females. Both testosterone and dihydrotestosterone treatment also caused hypertrophy of the hemipenes, which were everted in animals treated with these steroids. Copulatory motoneurons, assessed on the day of hatching in both experiments, were not dimorphic in size or number. Steroid treatment significantly increased motoneuron size and number overall, but no significant differences were detected in pairwise comparisons. These data demonstrate that differentiation of peripheral copulatory neuromuscular structures occurs during embryonic development and is influenced by gonadal steroids (regression by estradiol and enhancement by androgens), but associated motoneurons do not differentiate until later in life.     

Sexual dysfunction in multiple sclerosis: a MRI,neurophysiological and urodynamic study

We studied 31 patients with relapsing-remitting (RR) multiple sclerosis (MS) in which we performed an urodynamic study, the pudendal cortical evoked potentials, the tibial cortical evoked potentials and the cranial and cervical spinal cord magnetic resonance imaging (MRI). We calculated the T₁ and T₂ lesion load (LL) and brain parenchymal fraction (BPF) of whole brain, frontal lobes, pons and cervical spinal cord. We also estimated the cross-sectional area at C₂ level. Spearman's rank correlation analysis showed a relationship between symptoms of sexual dysfunction and age (r=0.73, p<0.0001), cognitive performances (r=−0.63, p<0.0001), level of independence (r=−0.63, p<0.0001), disability (r=0.56, p<0.001), symptoms of anxiety (r=0.55, p<0.001) and depression (r=0.50, p<0.005), disease duration (r=0.42, p<0.02) and parenchymal atrophy in the pons (r=−0.38, p=0.031). Sexual dysfunction was not correlated with any other MRI measure, urodynamic patterns or cortical evoked potentials. In multiple regression analysis, sexual dysfunction was predicted only by T₁ lesion load of the pons. In conclusion, we confirmed previous correlations of sexual dysfunction with various clinical variables and demonstrated an association between sexual dysfunction and destructive lesions in the pons, as detected by MRI, in patients with relapsing-remitting multiple sclerosis.     

ICD-11与DSM-5关于性功能失调诊断标准的异同

本文目的是对性功能失调在《精神障碍诊断与统计手册(第5版)》(DSM-5)和《国际疾病分类(第11版)》(ICD-11)中诊断标准的异同进行比较.性功能失调是指成年人难以体验满意的性活动的各种形式.本文对两套诊断系统中性功能失调的诊断要点进行总结和比较,以提高精神心理工作者对相应内容的理解.     

Triiodothyronine, thyroxine, and TSH response to dexamethasone in depressed patients and normal controls

In view of recent investigations concerning alterations of thyroid function in depression, the pre- and postdexamethasone levels of T3, T4, and TSH of 14 patients during depression and after recovery were studied, in addition to those of 27 healthy controls. A reduction of T3 and TSH levels was shown to be dependent on the depressive state, with a tendency to lower T4 levels after recovery. Dexamethasone had a pronounced suppressive effect on TSH levels in healthy controls and in patients after recovery, but not during the depressive episode. These results point to an inadequate suppressibility of the hypothalamo-pituitary-thyroid (HPT) axis to dexamethasone during depression. There are close interrelations between the hypothalamo-pituitary-adrenal (HPA) and the HPT axes that are possibly affected during depressive illness.     

Cortisol response to dexamethasone and noradrenergic function in depression

Positive correlations between measures of hypothalamic-pituitary-adrenal (HPA)-axis activity and noradrenergic turnover have been reported in depression. To investigate this relationship the authors measured peak postdexamethasone cortisol levels (8 a.m., 4 p.m. and 11 p.m.) and the 24-hour urinary 3-methoxy-4-hydroxy-phenylglycol (MHPG) flow in 84 depressed patients. The results show that there is no positive association between those measures of HPA-axis and noradrenergic activity. On the contrary, patients with severe non-suppression (greater than or equal to 10 micrograms/dl or 277 nmol/l) tended to have a lower MHPG-excretion.     

Sexual dysfunction after treatment for testicular cancer: A systematic review

Objectives: We aimed to assess the nature and risk of sexual dysfunction in men after treatment for testicular cancer. Method: Systematic review of sexual dysfunction in men treated for testicular cancer. The odds ratio or proportions of subjects with reduced sexual drive, erectile dysfunction or orgasmic/ejaculatory dysfunction was calculated. Results: A detailed review of 79 of the 227 citations was conducted. The highest level of evidence found, were controlled studies. Six controlled studies examined sexual function in 709 patients after they had received treatment. Seven uncontrolled studies examined sexual function in 337 subjects before and after treatment for testicular cancer. Most studies were limited by low response rates, use of unvalidated questionnaires and inclusion of a variety of treatment modalities. Few assessed psychological function and none examined its possible interaction with sexual dysfunction. Meta-analysis of the controlled studies indicated significantly reduced or absent orgasm (OR=4.62, 95% CI=2.47–8.63) together with erectile (OR=2.47, 95% CI=1.54–3.96) and ejaculatory dysfunction (OR=28.57, 95% CI=1.75–464.78) up to 2 years after treatment. Effects on sexual function were less consistent in the uncontrolled studies. Conclusions: The controlled studies indicate that sexual dysfunction persists for up to 2 years after treatment. However, better evidence is needed in studies that control for the impact of the testicular cancer, the treatment modality and psychological reactions to both.     

A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia

Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning.     

Sexual dysfunction in male multiple sclerosis patients in relation to clinical findings

Seventy-seven consecutive male patients with clinically definite or laboratory supported definite multiple sclerosis were submitted to a questionnaire and a clinical interview in order to assess the frequency, the nature of sexual dysfunction and its relationship with clinical findings. Twenty-six patients (35%) complained of erectile dysfunction: the defect was partial and inconstant in 11 patients (14%), complete and fixed in 15 (21%). Six patients complained of premature ejaculation, in three of whom the symptom was already present before the onset of the disease. Taking the series as a whole, sexual life was poor or not satisfying at all in 34 patients. Erectile dysfunction was associated with the presence and severity of bladder dysfunction and with disability. The relationship with sensory impairment of legs was slight, no relationship was found with motor involvement of legs, type of course, age and disease duration.     

Influence of ethanol and dexamethasone on blood-brain barrier dysfunction to albumin

Stab-wounded ethanol-intoxicated and non-intoxicated rats were studied with respect to the effect of postoperative dexamethasone treatment on blood-brain barrier dysfunction to bovine albumin. In ethanol-intoxicated rats, fluorescence microscopy revealed an increased area of extravasation of fluorescent tracer, compared to non-intoxicated ones. No significant effect of dexamethasone treatment was observed in non-intoxicated rats. In ethanol-intoxicated rats, dexamethasone treatment resulted in a decreased area of extravasation.
Quantitative immuno-electrophoretic measurements of exogeneous bovine albumin confirmed a significant decrease of blood-brain barrier dysfunction to albumin after dexamethasone treatment in ethanol-intoxicated rats, while no significant effect was observed in non-intoxicated ones.     

The long-lasting improvement of sexual dysfunction in patients with advanced, fluctuating Parkinson's disease induced by pergolide: evidence from the results of an open, prospective, one-year trial

Fourteen male patients suffering from Parkinson's disease, each of whom had been treated with L-DOPA, and in whom additional treatment with oral dopamine agonist (DA) was needed, were followed for a period of one year. Pergolide mesylate (Permax^®) was given to each patient, and titrated to a total daily dose of 3 mg. All of the patients were taking L-DOPA. The assessments performed before the start of pergolide treatment consisted of neurological examination, unified Parkinson's disease rating scale (UPDRS) III and IV subscales scoring, mini mental state examination (MMSE) scoring, the neuropsychological examination including Zung scale scoring, biochemical and hematological examinations including prolactine serum levels; and a sexological examination during which the patients filled-in the international index of erectile function (IIEF) questionnaire. These examinations were repeated during the control assessments at months 1, 3, 6 and 12. ANOVA, non-parametric Friedmann's ANOVA and Tukey post hoc tests were used for the statistical analysis. There were statistically significant differences between the values of UPDRS III motor subscale and all subscales of IIEF when months 0 and 1 were compared with the results obtained at months 3, 6 and 12. Pergolide mesylate, when added to L-DOPA, significantly improved all sexual functions in younger male Parkinsonian patients who were still interested in sexual activities. The treatment with pergolide in these cases might be more beneficial than with short-acting PDE-5 inhibitor sildenafile. Nevertheless, the relationship between pergolide treatment and incidence of restrictive valvular heart disease must be considered.     

A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction

We sought to determine whether maca, a Peruvian plant, is effective for selective-serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. We conducted a double-blind, randomized, parallel group dose-finding pilot study comparing a low-dose (1.5 g/day) to a high-dose (3.0 g/day) maca regimen in 20 remitted depressed outpatients (mean age 36 ± 13 years; 17 women) with SSRI-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Ten subjects completed the study, and 16 subjects (9 on 3.0 g/day; 7 on 1.5 g/day) were eligible for intent-to-treat (ITT) analyses on the basis of having had at least one postbaseline visit. ITT subjects on 3.0 g/day maca had a significant improvement in ASEX (from 22.8 ± 3.8 to 16.9 ± 6.2; z =−2.20, P = 0.028) and in MGH-SFQ scores (from 24.1 ± 1.9 to 17.0 ± 5.7; z =−2.39, P = 0.017), but subjects on 1.5 g/day maca did not. Libido improved significantly ( P < 0.05) for the ITT and completer groups based on ASEX item #1, but not by dosing groups. Maca was well tolerated. Maca root may alleviate SSRI-induced sexual dysfunction, and there may be a dose-related effect. Maca may also have a beneficial effect on libido.     

Gonadal steroid control of preprocholecystokinin mRNA expression in the limbic-hypothalamic circuit: Comparison of adult with neonatal steroid treatments

The neuropeptide cholecystokinin (CCK) is involved in the regulation of female, but not male, reproductive behavior. In both sexes, estrogen regulates the expression of CCK in adulthood within the bed nucleus of the stria terminalis and medial amygdaloid nucleus. These areas are parts of an interconnected limbic system-hypothalamic circuit, the development of which is influenced by estrogen during the early postnatal period. This is the same period during which central nervous system (CNS) expression of CCK is dramatically increased, suggesting that the male and female patterns of CCK expression may be the result of early postnatal exposure to estrogen. In the present experiment, the expression of preprocholecystokinin (pCCK) mRNA was determined by in situ hybridization with an isotopically labeled pCCK complementary RNA and emulsion autoradiography in animals whose neonatal and adult gonadal steroid levels had been manipulated. The number of pCCK-expressing cells in animals that were gonadectomized as adults was determined by neonatal estrogen, but stimulation with steroids in adulthood induced a similar number of pCCK-expressing cells in both sexes in the medial amygdala and bed nucleus of the stria terminalis. Neonatal treatment of females with estrogen or testosterone, followed by ovariectomy in adulthood, eliminated the sex difference in pCCK mRNA expression. Males treated neonatally with the aromatase inhibitor androstenedione (to block metabolism of testosterone to estrogen) and orchidectomized in adulthood had a level of pCCK mRNA expression that was similar to that of ovariectomized females. These data suggest that, during neonatal development, estrogen determines the constitutive expression of pCCK mRNA in the medial amygdala and bed nucleus of the stria terminalis, resulting in higher levels of pCCK mRNA expression in males than in females. However, exogenous gonadal steroids induce the same levels of pCCK mRNA expression in adult females, indicating that the levels of gonadal steroids and the patterns of their secretion are the predominant influences on the sexually dimorphic adult levels of pCCK mRNA expression. © 1994 Wiley-Liss, Inc.