PMID: 

Biochim Biophys Acta. 2015 Oct ;1848(10 Pt B):2756-65. Epub 2015 Feb 19. PMID: 25703814

Abstract Title: 

Investigation of the effects of distance from sources on apoptosis, oxidative stress and cytosolic calcium accumulation via TRPV1 channels induced by mobile phones and Wi-Fi in breast cancer cells.

Abstract: 

TRPV1 is a Ca2+ permeable channel and gated by noxious heat, oxidative stress and capsaicin (CAP). Some reports have indicated that non-ionized electromagnetic radiation (EMR)-induces heat and oxidative stress effects. We aimed to investigate the effects of distance from sources on calcium signaling, cytosolic ROS production, cell viability, apoptosis, plus caspase-3 and -9 values induced by mobile phones and Wi-Fi in breast cancer cells MCF-7 human breast cancer cell lines were divided into A, B, C and D groups as control, 900, 1800 and 2450 MHz groups, respectively. Cells in Group A were used as control and were kept in cell culture conditions without EMR exposure. Groups B, C and D were exposed to the EMR frequencies at different distances (0 cm, 1 cm, 5 cm, 10 cm, 20 cm and 25 cm) for 1h before CAP stimulation. The cytosolic ROS production, Ca2+ concentrations, apoptosis, caspase-3 and caspase-9 values were higher in groups B, C and D than in A group at 0 cm, 1 cm and 5 cm distances although cell viability (MTT) values were increased by the distances. There was no statistically significant difference in the values between control, 20 and 25 cm. Wi-Fi and mobile phone EMR placed within 10 cm of the cells induced excessive oxidative responses and apoptosis via TRPV1-induced cytosolic Ca2+ accumulation in the cancer cells. Using cell phones and Wi-Fi sources which are farther away than 10 cm may provide useful protection against oxidative stress, apoptosis and overload of intracellular Ca2+. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

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PMID: 

J Affect Disord. 2019 05 1 ;250:170-177. Epub 2019 Mar 6. PMID: 30856494

Abstract Title: 

Comparisons of the risk of medication noncompliance and suicidal behavior among patients with depressive disorders using different monotherapy antidepressants in Taiwan: A nationwide population-based retrospective cohort study.

Abstract: 

BACKGROUND: The aim of this study was to assess the association between various classes of antidepressants and the risk of medication noncompliance as well as suicidal behavior among depressed patients.METHODS: A retrospective cohort study was conducted utilizing two nationwide population-based datasets in Taiwan from 2010 to 2016. The outcome measures included the risk of medication noncompliance, attempted suicide, and completed suicide. Cox proportional hazards models with stratification of the propensity score deciles were performed.RESULTS: A total of 447,411 new antidepressant users were identified. Compared to SSRIs, patients who received SARIs [adjusted hazard ratio (aHR) = 1.124, 95% confidence interval (CI) = 1.108-1.142], SNRIs (aHR = 1.049, 95% CI = 1.033-1.065), and other classes of antidepressants (aHR = 1.037, 95% CI = 1.024-1.051) were more likely to exhibit poor medication noncompliance. Patients who received SNRIs had a higher riskof attempted suicide (aHR = 1.294, 95% CI = 1.114-1.513), compared to SSRIs. However, patents in the TCAs group revealed the opposite result (aHR = 0.543, 95% CI = 0.387-0.762). Concerning the risk of completed suicide, this analysis detected no statistical significance across different types of antidepressants.LIMITATIONS: Although the universal coverage of Taiwan's national health insurance program tends to minimize the risk of selection and recall bias, it is difficult to rule out medical surveillance bias by using claim data.CONCLUSIONS: This study demonstrated that classes of antidepressants exert different degrees of impact on the risk of medication noncompliance and attempted suicide, but not completed suicide, among depressed patients.

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PMID: 

Environ Health Toxicol. 2016 ;31:e2016022. Epub 2016 Oct 26. PMID: 27788568

Abstract Title: 

A cross-sectional study of the association between mobile phone use and symptoms of ill health.

Abstract: 

OBJECTIVES: This study analyzed the associations between mobile phone call frequency and duration with non-specific symptoms.METHODS: This study was conducted with a population group including 532 non-patient adults established by the Korean Genome and Epidemiology Study. The pattern of phone call using a mobile phone was investigated through face-to-face interview. Structured methods applied to quantitatively assess health effects are Headache Impact Test-6 (HIT-6), Psychosocial Well-being Index-Short Form, Beck Depression Inventory, Korean-Instrumental Activities of Daily Living, Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index, and 12-item Short Form Health Survey where a higher score represents a higher greater health effect.RESULTS: The average daily phone call frequency showed a significant correlation with the PSS score in female subjects. Increases in the average duration of one phone call were significantly correlated with increases in the severity of headaches in both sexes. The mean (standard deviation) HIT-6 score in the subgroup of subjects whose average duration of one phone call was five minutes or longer was 45.98 (8.15), as compared with 42.48 (7.20) in those whose average duration of one phone call was

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PMID: 

Am J Psychiatry. 2006 May ;163(5):813-21. PMID: 16648321

Abstract Title: 

The risk of suicide with selective serotonin reuptake inhibitors in the elderly.

Abstract: 

OBJECTIVE: The authors explored the relationship between the initiation of therapy with selective serotonin reuptake inhibitor (SSRI) antidepressants and completed suicide in older patients.METHOD: The authors linked population-based coroner's records with patient-level prescription data, physician billing claims, and hospitalization data for more than 1.2 million Ontario residents 66 years of age and older from 1992 to 2000. For each suicide case, four closely matched comparison subjects were selected using propensity score methods. The authors determined the odds ratio for suicide with SSRIs versus other antidepressant treatment, calculated at discrete monthly intervals from the start of treatment.RESULTS: Of 1,329 suicide cases, 1,138 (86%) were each fully matched to four comparison subjects using propensity scores. During the first month of therapy, SSRI antidepressants were associated with a nearly fivefold higher risk of completed suicide than other antidepressants (adjusted odds ratio: 4.8, 95% confidence interval=1.9-12.2). The risk was independent of a recent diagnosis of depression or the receipt of psychiatric care, and suicides of a violent nature were distinctly more common during SSRI therapy. Numerous sensitivity analyses revealed consistent results. No disproportionate suicide risk was seen during the second and subsequent months of treatment with SSRI antidepressants, and the absolute risk of suicide with all antidepressants was low.CONCLUSIONS: Initiation of SSRI therapy is associated with an increased risk of suicide during the first month of therapy compared with other antidepressants. The absolute risk is low, suggesting that an idiosyncratic response to these agents may provoke suicide in a vulnerable subgroup of patients.

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PMID: 

Endocrinology. 2019 Jul 15. Epub 2019 Jul 15. PMID: 31305910

Abstract Title: 

Ancestral fluoxetine exposure sensitizes zebrafish to venlafaxine-induced reductions in cortisol and spawning.

Abstract: 

Due to the prevalence of depression during childbearing, mothers may be prescribed multiple antidepressants, yet little is known about the risk and consequences to the offspring or to the subsequent generations. Fluoxetine (FLX) is usually the first line of pharmacological treatment for affective disorders in pregnant women, and venlafaxine (VEN) may be used as a secondary treatment. Given that FLX and VEN readily cross the placenta, a fetus from a treated pregnant woman is potentially at risk from the endocrine disruptive effects of these chemicals. Pharmaceuticals including FLX and VEN reach aquatic ecosystems through sewage release, so fish may be inadvertently affected. Here, we report that a 6-day FLX exposure during early zebrafish development to an environmentally relevant (0.54µg·L-1 in water) and a concentration detected in the cord blood of FLX-treated pregnant women (54 µg·L-1 in water) reduces the stress response (the arithmetic difference between the stress-induced and unstressed whole-body cortisol levels) in the adult females and males, an effect that persistsfor four generations. To model the possibility of a second antidepressant exposure, the filial generation 4 (F4), was exposed to VEN (5 µg·L-1). We found that FLX exposure sensitizes these descendants to VEN. The VEN treatment further suppresses cortisol production in females and decreases spawning rates in adult pairs. This is an important demonstration that in an animal model, a brief ancestral exposure of great-great-grandparents to the selective serotonin reuptake inhibitor FLX shapes the physiological responses of future generations to the serotonin and norepinephrine reuptake inhibitorVEN.

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PMID: 

J Clin Psychiatry. 2019 Jul 9 ;80(4). Epub 2019 Jul 9. PMID: 31294935

Abstract Title: 

Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis.

Abstract: 

OBJECTIVE: To summarize the effects of antenatal benzodiazepine exposure as monotherapy and in combination with antidepressants on the risk of congenital malformations.DATA SOURCES: MEDLINE, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched from inception to June 30, 2018, using controlled vocabulary and keywords (eg, prenatal, benzodiazepines, malformation).STUDY SELECTION: English-language cohort studies with prospectively collected data on the risk of malformations in benzodiazepine-exposed and -unexposed offspring were evaluated. 23,909 records were screened, 56 studies were assessed for eligibility, and 8 studies were included.DATA EXTRACTION: Quality was assessed by 2 independent reviewers and data extracted. Random-effects models were used for outcomes (≥ 3 studies). Subanalyses examined effect of potential moderators including study quality and timing of exposure, among others.RESULTS: Prenatal benzodiazepine use was not associated with an increased risk of congenital malformations (odds ratio [OR] = 1.13; 95% CI, 0.99 to 1.30, 8 studies, n = 222/5,195 exposed and 64,335/2,082,467 unexposed), including with first trimester exposure specifically (OR = 1.08; 95% CI, 0.93 to 1.25, P = .33; 5 studies, n = 181/4,331 exposed and 64,308/2,081,463 unexposed). There was no significant association with cardiac malformation following exposure (OR = 1.27; 95% CI, 0.98 to 1.65, P = .07; 4 studies, n = 61/4,414 exposed and 19,260/2,033,402 unexposed). However, concurrent use of benzodiazepine and antidepressants during pregnancy was associated with a significantly increased risk of congenital malformations (OR = 1.40; 95% CI, 1.09 to 1.80, P = .008; 3 studies).CONCLUSIONS: Benzodiazepine exposure during pregnancy does not appear to be associated with congenital malformations or with cardiac malformations specifically. There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants, suggesting that caution with this combination is warranted.

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PMID: 

Environ Sci Technol. 2019 May 21 ;53(10):6035-6043. Epub 2019 May 9. PMID: 31034220

Abstract Title: 

Antidepressants in Surface Waters: Fluoxetine Influences Mosquitofish Anxiety-Related Behavior at Environmentally Relevant Levels.

Abstract: 

Pharmaceutical contamination is an increasing problem globally. In this regard, the selective serotonin reuptake inhibitors (SSRIs)-a group of antidepressants-are particularly concerning. By disrupting the serotonergic system, SSRIs have the potential to affect ecologically important behaviors in exposed wildlife. Despite this, the nature and magnitude of behavioral perturbations resulting from environmentally relevant SSRI exposure among species is poorly understood. Accordingly, we investigated the effects of two field-realistic levels of the SSRI fluoxetine (61 and 352 ng/L) on sociability and anxiety-related behaviors in eastern mosquitofish ( Gambusia holbrooki) for 28 days. Additionally, we measured whole-body tissue concentrations of fluoxetine and norfluoxetine. We found that fluoxetine altered anxiety-related behavior but not sociability. Specifically, female fish showed reduced anxiety-related behavior at the lower treatment level, while males showed an increase at the higher treatment level. In addition, we report a biomass-dependent and sex-specific accumulation of fluoxetine and norfluoxetine, with smaller fish showing higher relative tissue concentrations, with this relationship being more pronounced in males. Our study provides evidence for nonmonotonic and sex-specific effects of fluoxetine exposure at field-realistic concentrations. More broadly, our study demonstrated that neuroactive pharmaceuticals, such as fluoxetine, can affect aquatic life by causing subtle but important shifts in ecologically relevant behaviors.

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PMID: 

Ment Illn. 2019 Mar 22 ;11(1):8115. Epub 2019 Jun 11. PMID: 31281608

Abstract Title: 

Interactions between antidepressants, sleep aids and selected breast cancer therapy.

Abstract: 

Depression and insomnia are very significant pathologies in cancer patients as they contribute to the patient's overall cure and quality of life. Moreover, untreated depression and ongoing insomnia are associated with decreased immune responses and lower survival rates. With all disease states and especially with cancer, close attention to drug-drug interactions and the potential impact on the efficacy of therapy is paramount. One area of particular interest due to the lack of well-done clinical trials is drug-drug interaction(s) between antidepressants and cancer treatment. Pharmacokinetics of a certain drug allows for prediction of certain drug interactions based on chemical properties of the agents involved. If the agents depend on their metabolites for activity, active drug level will be decreased through this enzyme inhibition. In this paper, we looked at the cytochrome-P450 drug interactions between antidepressants and sleep aids with Selective Estrogen Receptor Modulators (SERM). Newer SERM metabolisms are less influenced by interactions with medications used to treat depression. However, tamoxifen metabolism could be severely altered by several antidepressants. This has direct consequences as patients on tamoxifen and antidepressant can have double the risk of relapse to cancer in two years. We discussed those interactions and made recommendations for clinical use.

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PMID: 

BMJ Open. 2019 Jun 27 ;9(6):e024886. Epub 2019 Jun 27. PMID: 31248914

Abstract Title: 

Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis.

Abstract: 

OBJECTIVES: To investigate whether the conclusion of a recent systematic review and network meta-analysis (Cipriani) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DESIGN: Reanalysis of a systematic review, with meta-analyses.DATA SOURCES: 522 trials (116 477 participants) as reported in the systematic review by Ciprianiand clinical study reports for 19 of these trials.ANALYSIS: We used the Cochrane Handbook's risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.RESULTS: Several methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Cipriani. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a 'placebo run-in' study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p

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PMID: 

Am J Geriatr Psychiatry. 2019 May 29. Epub 2019 May 29. PMID: 31235427

Abstract Title: 

Exposure to Antidepressant Medication and the Risk of Incident Dementia.

Abstract: 

OBJECTIVE: To test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia.METHODS: A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002-2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes.RESULTS: In the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI = 3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47.CONCLUSION: In this study, monotherapeutic antidepressant exposure in old age was associated with increased incident dementia. Clinicians, caregivers, and patients may wish to consider this potentially negative consequence of antidepressant exposure and aim to balance the costs and benefits of treatment.

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