Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants.

BACKGROUND: Sexual dysfunction is a common side effect of Serotonergic antidepressants (SA) treatment, and persists in some patients despite drug discontinuation, a condition termed post-SSRI sexual dysfunction (PSSD). The risk for PSSD is unknown but is thought to be rare and difficult to assess. This study aims to estimate the risk of erectile dysfunction (ED) and PSSD in males treated with SAs. METHODS: A 19-year retrospective cohort analysis was conducted using a computerized database of the largest HMO in Israel. ED was defined by phosphodiesterase-5 inhibitors prescriptions. 12,302 males aged 21-49 met the following criteria: non-smokers, no medical or psychiatric comorbidities or medications associated with ED, no alcohol or substance use. Logistic regression was used for estimation of ED risk in SA-treated subjects compared to non-SA-treated controls, assessed with and without the effects of age, body mass index (BMI), socioeconomic status (SES), depression and anxiety, yielding crude and adjusted odds ratios (cOR and aOR, respectively). RESULTS: SAs were associated with an increased risk for ED (cOR = 3.6, p < 0.000001, 95% CI 2.8-4.8), which remained significant after adjusting for age, SES, BMI, depression and anxiety (aOR = 3.2, p < 0.000001, 95% CI 2.3-4.4). The risk for PSSD was 1 in 216 patients (0.46%) treated with SAs. The prevalence of PSSD was 4.3 per 100,000. CONCLUSIONS: This work offers a first assessment of the small but significant risk of irreversible ED associated with the most commonly prescribed class of antidepressants which should enhance the process of receiving adequate informed consent for therapy.

Risk factors for postpartum depression among sexual minority and heterosexual parents.

OBJECTIVE: Postpartum depression (PPD), a major depressive episode with postpartum onset, develops in 15% of mothers. Although findings suggest sexual minority parents may be at risk for PPD, research among this population is scarce. We evaluated risk factors for PPD in a sample of sexual minority and heterosexual parents. METHOD: Four hundred and twenty seven heterosexual and one hundred and eleven sexual minority parents responded to a questionnaire distributed via social media that included demographics, the Edinburgh Postnatal Depression Scale, and the Multidimensional Scale of Perceived Social Support. RESULTS: Sexual minority identity was not associated with increased risk for PPD. Pregnancy had no significant effect on the likelihood for PPD. Social support was negatively and significantly associated with probability for PPD. CONCLUSIONS: Our data suggest that sexual minority parents are not at increased risk for PPD, contrary to previous findings. The parental role, a psychosocial factor, is a more dominant risk factor than pregnancy itself, in the development of PPD.

A Nationwide Study Comparing Mental Health Professionals' Willingness to Try Hallucinogenic Drugs in Basic Research or Clinical Practice.

This study explored whether personal attitudes toward drug users are associated with professional approaches and whether the association between personal and professional attitudes varies across different mental health professions. Participants (N = 347) included medical (psychiatrists and psychiatric nurses) and other (clinical psychologists and social workers) mental health professions from all 13 mental health centers in Israel. They completed questionnaires aimed to assess familiarity with medical usage of hallucinogenic drugs, personal attitudes toward recreational drug users and willingness to use five hallucinogens in research of clinical practice. Hypotheses were tested using multiple-group structural equation modeling (SEM). Psychiatrists reported the highest levels of familiarity with and willingness to use all types of hallucinogenic drugs, as compared to other mental health professionals. Psychiatrists held the strongest belief in the potential utility of hallucinogenic drugs; yet, their personal attitudes toward drug users affected negatively their willingness to try hallucinogenic drugs in clinical practice. This was the only significant association that was found. Future research and treatment programs should address the topic of hallucinogenic drug therapy, and specifically the need to separate between individual beliefs and professional clinical decision-making.

'An Apple a Day'?: Psychiatrists, Psychologists and Psychotherapists Report Poor Literacy for Nutritional Medicine: International Survey Spanning 52 Countries.

Nutritional interventions have beneficial effects on certain psychiatric disorder symptomatology and common physical health comorbidities. However, studies evaluating nutritional literacy in mental health professionals (MHP) are scarce. This study aimed to assess the across 52 countries. Surveys were distributed via colleagues and professional societies. Data were collected regarding self-reported general nutrition knowledge, nutrition education, learning opportunities, and the tendency to recommend food supplements or prescribe specific diets in clinical practice. In total, 1056 subjects participated in the study: 354 psychiatrists, 511 psychologists, 44 psychotherapists, and 147 MHPs in-training. All participants believed the diet quality of individuals with mental disorders was poorer compared to the general population (p < 0.001). The majority of the psychiatrists (74.2%) and psychologists (66.3%) reported having no training in nutrition. Nevertheless, many of them used nutrition approaches, with 58.6% recommending supplements and 43.8% recommending specific diet strategies to their patients. Only 0.8% of participants rated their education regarding nutrition as 'very good.' Almost all (92.9%) stated they would like to expand their knowledge regarding 'Nutritional Psychiatry.' There is an urgent need to integrate nutrition education into MHP training, ideally in collaboration with nutrition experts to achieve best practice care.

Possible Age-Related Progression of Attentional Impairment in ADHD and Its Attenuation by Past Diagnosis and Treatment.

Objective: The aim of the study is to evaluate attentional impairment in different age groups with ADHD. Method: In all, 58 children, 73 adolescents, and 104 adults with ADHD were evaluated using the Test of Variables of Attention (TOVA). Subjects with comorbidities or psychotropic treatment were not included. Results: Considering Response Time Variability (RTV), adults were 10.6 and 4.0 times more likely to be severely impaired (standard score < 40) than children and adolescents, respectively. Adults were twice as likely as adolescents to be very impaired (standard score< 70) in Omissions. Considering d' (decrement of attentional performance over time), all severely impaired participants were adults. Age predicted impairment in Attention Performance Index (API), RTV, and d', but not Omissions or Commissions. Past treatment with stimulants predicted less impairment in d', past diagnosis predicted less impairment in RTV, and each predicted less impairment in Omissions and API. Conclusion: Adults had more attentional impairment than children and adolescents. Past diagnosis and treatment were associated with less ADHD-related attentional impairment.

The Placebo Response in Adult ADHD as Objectively Assessed by the TOVA Continuous Performance Test.

Objective: We compared the placebo response (PR) as measured by the Test of Variables of Attention (TOVA) and the Conners' Adult ADHD Rating Scale (CAARS) scores. Method: A retrospective data analysis from a double-blind placebo-controlled study of metadoxine-ER in adults with ADHD. An additional database was used for comparison to TOVA response after methylphenidate challenge (TOVA-MPH-R). Results: PR was highest when calculated from the TOVA-Attention Composite Score (ACS). The PR showed significantly fewer variables improving concomitantly compared with MPH-R. The most prominent correlation between the CAARS-PR and the TOVA-PR was in the Omissions score (p = .032), which was age-dependent (b = .0007, p <.001). Discussion: TOVA-PR has an index-specific profile compared with CAARS-PR and TOVA-MPH-R. The partial correlation of TOVA-PR with CAARS-PR suggests that a composite score of TOVA specific indices and CAARS could have a synergic impact to improve the reliability of the response assessment in adult ADHD.

Characterizing the Placebo Response in Adults With ADHD.

Objective: Several ADHD pharmacological trials reported high placebo response (PR) rates. This study aims to characterize the PR in adult ADHD. Method: A retrospective cohort analysis of the placebo arm (140 adults with ADHD, 18-55 yrs, M:F 46.4%-53.6%) of a 6-week randomized, multicenter, double-blind metadoxine study, using Conners' Adult ADHD Rating Scale (CAARS) and the Adult ADHD Self-Report Scale (ASRS), was conducted. Results: Pre-post changes in placebo-treated adults were significant for both the CAARS and ASRS, F(2.9, 404.5) = 61.2, p < .00001, F(2.8, 383.0) = 43.1, p < .00001, respectively. Less than half of the participants had a PR which began early in treatment and persisted; almost 50% had a variable, inconsistent PR. Conclusion: In the current sample, PR in adult ADHD was prominent on both symptom scales and the investigator-rater instrument. Therefore, using investigator ratings as a primary endpoint does not necessarily attenuate PR. Of note, about half of the PR is variable, suggesting unreliable determination of efficacy.

Apparent lack of practice effects in the Test of Variables of Attention (TOVA) in adult ADHD.

The test of variables of attention (TOVA) is a continuous performance test commonly used as an aid for diagnosis of ADHD and assessment of treatment response. It has been studied and standardized in both children and adults. As a repetitive measurement of treatment efficacy, used both in research and in the clinic, it's important to disprove a practice effect. A retrospective cohort analysis was done, using only the placebo-arm participants from two different randomized, multicenter, double-blind clinical trials on the efficacy of a non-stimulant (metadoxine-XR). In order to reveal the practice effects, only the participants that showed no placebo effect (< 25% improvement), in the Conners' Adult ADHD Rating Scale-investigator rated (CAARS-Inv), the gold standard, were included. Demographic data, CAARS-Inv baseline and TOVA results during each visit were recorded and analyzed. Ninety-one participants from two studies were pooled (2014 n = 24, 2016 n = 67). They did not differ significantly in any demographic parameter, most side effect frequencies, and CAARS-Inv baseline scores. The baseline TOVA performances demonstrated similarity in the degree of inattention, variability, impulsivity, and response time. The TOVA scores were not altered significantly between visits, as assessed by repeated-measures analysis of variance. No significant differences were detected between the TOVA baseline-to-endpoint scores as assessed by paired t test. No practice effects were detected, in both clinical trials, suggesting that the results of the TOVA are likely to represent genuine changes in attentional performance. Further studies are needed to replicate these findings.

The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells.

Commonly used pharmaceutical drugs might alter the epigenetic state of cells, leading to varying degrees of long-term repercussions to human health. To test this hypothesis, we cultured HEK-293 cells in the presence of 50 µM citalopram, a common antidepressant, for 30 days and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array. A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation (p < 0.01); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control. Using Ingenuity Pathway Analysis, we found that the chief gene networks and signaling pathways that are differentially regulated include those involved in nervous system development and function and cellular growth and proliferation. Genes implicated in depression, as well as genetic networks involving nucleic acid metabolism, small molecule biochemistry, and cell cycle regulation were significantly modified. Involvement of upstream regulators such as BDNF, FSH, and NFκB was predicted based on differential methylation of their downstream targets. The study validates our hypothesis that pharmaceutical drugs can have off-target epigenetic effects and reveals affected networks and pathways. We view this study as a first step towards understanding the long-term epigenetic consequences of prescription drugs on human health.

Psychiatric disorders and compliance with prenatal care: A 10-year retrospective cohort compared to controls.

BACKGROUND: Inadequate prenatal care has been associated with adverse perinatal outcomes. We sought to compare compliance with prenatal care visits (PCV), oral glucose tolerance test (OGTT) and serum alfa-fetoprotein (aFP) in women with psychiatric disorders (PD) and healthy controls. METHODS: Subjects were 5395 women (1043 PD and 4352 controls), members of Clalit Health Services (Tel-Aviv district, Israel), who gave birth during 2004-2014. We used Generalized Estimating Equations with binary-logistic models, considering consecutive pregnancies as repeated measures with unbalanced design. The diagnostic subgroup was the main independent, assessed once with and once without age, socioeconomic status and multiple gestation variables. RESULTS: Risk for non-compliance with OGTT was increased in women with depression (aOR = 1.4, 95% CI = 1.1-1.7) and schizophrenia (aOR = 1.8, 95% CI = 1.1-2.9), but not anxiety. Risk for non-compliance with aFP was decreased in women with anxiety (aOR = 0.6, 95% CI = 0.5-0.8), but women with depression and schizophrenia did not differ from controls. PD were at risk for both absence of PCV (aOR = 4.6, 95% CI = 2.7-8.0) and high utilization of PCV (>20 visits, aOR = 2.8, 95% CI = 2.1-3.7). Psychopharmacological treatment during pregnancy was associated with high utilization of PCV (OR = 2.2, 95% CI = 1.7-2.9), increased compliance with aFP tests (OR = 1.4, 95% CI = 1.1-1.7) and marginally-significant increased compliance with OGTT (OR = 0.82, 95% CI = 0.67-1.01). CONCLUSION: PD under-utilized tests perceived for the wellbeing of the mother (OGTT) and over-utilize tests for the wellbeing of the fetus (aFP). PD exhibited patterns of both very low and very high utilization of PCV. Psychopharmacological treatment during pregnancy may improve some measures of compliance with prenatal care.

Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship.

Emerging evidence suggests that sexual dysfunction emerging during treatment with selective serotonin reuptake inhibitors (SSRIs) and/or serotonin-norepinephrine reuptake inhibitors (SNRIs) persists in some patients beyond drug discontinuation (post-SSRI sexual dysfunction [PSSD]). We sought to identify and characterize a series of such cases and explore possible explanatory factors and exposure-response relationship. Subjects who responded to an invitation in a forum dedicated to PSSD filled out a survey via online software. Case probability was defined according to the following 3 categories of increasing presumed likelihood of PSSD. Noncases did not meet the criteria for possible cases. Possible cases were subjects with normal pretreatment sexual function who first experienced sexual disturbances while using a single SSRI/SNRI, which did not resolve upon drug discontinuation for 1 month or longer as indicated by Arizona Sexual Experience Scale scores. High-probability cases were also younger than 50-year-olds; did not have confounding medical conditions, medications, or drug use; and had normal scores on the Hospital Anxiety and Depression Scale. Five hundred thirty-two (532) subjects completed the survey, among which 183 possible cases were identified, including 23 high-probability cases. Female sex, genital anesthesia, and depression predicted current sexual dysfunction severity, but dose/defined daily dose ratio and anxiety did not. Genital anesthesia did not correlate with depression or anxiety, but pleasureless orgasm was an independent predictor of both depression and case probability. Limitations of the study include retrospective design and selection and report biases that do not allow generalization or estimation of incidence. However, our findings add to previous reports and support the existence of PSSD, which may not be fully explained by alternative nonpharmacological factors related to sexual dysfunction, including depression and anxiety.