Chemical modulators of lipid abundance and bone development

 My research focussed on the analysing the lipid profile during development. I further studied potential chemicals to modulate lipid abundaces. Furthermore, I explored the effects of SSRIs on bone development.

Effects of antidepressants on postmenopausal bone loss - a 5-year longitudinal study from the OSTPRE cohort

BACKGROUND: Osteoporosis and depression are major health problems worldwide. The association between antidepressants, a treatment for depression, and bone health needs more detailed exploration. OBJECTIVE: The present study investigates antidepressant medication use and postmenopausal bone loss over time. METHODS: A total of 1988 women (aged 57-67) participating in the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) cohort responded to a postal enquiry and had their femoral neck bone mineral density (BMD) measured in 1999 and again in 2004. Data on antidepressant use was obtained from the National Prescription Register. Multiple regression techniques were used to test the associations, before and after adjustment for anthropometric, medical, physical and lifestyle factors. RESULTS: Over the five years of follow-up, 319 (16.0%) women purchased antidepressants. Mean baseline femoral neck BMD for the entire study group was 881mg/cm(2) (SD 123) and mean 5-year bone loss was 6.0mg/cm(2) (SD 4.7). After adjustments, users of tricyclic antidepressants (TCA) had greater annual BMD loss than non-users (-3.6mg/cm(2) vs. -1.1mg/cm(2); P=0.031). Accelerated bone loss was also associated with selective serotonin reuptake inhibitor's (SSRI) use (P=0.001) and use of other antidepressants in a dose-response way, with the latter only among women of low-weight and normal-weight women who had lost weight over the study period. CONCLUSIONS: In conclusion, the use of SSRIs seems to accelerate postmenopausal bone loss in a dose-response manner. Associations between TCA and other antidepressant use and bone loss may also exist. Thus, the possibility of increased risk of osteoporosis should be considered when prescribing antidepressants for postmenopausal women.

Women's preferences for selective estrogen reuptake modulators: an investigation using the time trade off technique

PurposeSelective Estrogen Receptor Modulators (SERMs) reduce the risk of breast cancer for women at increased risk by 38%. However, uptake is extremely low and the reasons for this are not completely understood. The aims of this study were to utilize time trade-off methods to determine the degree of risk reduction required to make taking SERMs worthwhile to women, and the factors associated with requiring greater risk reduction to take SERMs. MethodsWomen at increased risk of breast cancer (N = 107) were recruited from two familial cancer clinics in Australia. Participants completed a questionnaire either online or in pen and paper format. Hierarchical multiple linear regression analysis was used to analyze the data. ResultsOverall, there was considerable heterogeneity in the degree of risk reduction required to make taking SERMs worthwhile. Women with higher perceived breast cancer risk and those with stronger intentions to undergo (or who had undergone) an oophorectomy required a smaller degree of risk reduction to consider taking SERMs worthwhile. ConclusionWomen at increased familial risk appear motivated to consider SERMs for prevention. A tailored approach to communicating about medical prevention is essential. Health professionals could usefully highlight the absolute (rather than relative) probability of side effects and take into account an individual’s perceived (rather than objective) risk of breast cancer.

A survey of combination antidepressant use in Australia

Objective: The aim of this study was to survey doctors working in psychiatry in Australia about the practice of using two antidepressants simultaneously.

Method: A postal survey was sent to all doctors in psychiatry in Australia enquiring about their prescribing history and their attitudes to combination antidepressants and related issues.

Results: Seventy-nine percent of respondents had used combination antidepressants. The most frequently reported combination was a selective serotonin reuptake inhibitor combined with a tricyclic antidepressant. Combinations of mirtazepine with venlafaxine and other antidepressants were the next most frequently used. Seventeen percent of respondents reported having seen a complication from combination antidepressants, 75% believed that Australian GPs should be given information on the use of combination antidepressants, 89% wished for more information on this topic, and 88% believed patients had a right to be informed of this option in their treatment. Use of combination antidepressants was more frequent than exceeding the recommended maximum dose of an individual antidepressant.

Conclusion: Combination antidepressants are used far more frequently in Australia than suspected previously. Research into safe and evidence-based practice is strongly indicated.

Metyrapone and fluoxetine suppress enduring behavioral but not cardiac effects of subchronic stress in rats

In humans, chronic stressors have long been recognized as potential causes for cardiac dysregulation. Despite this, the underlying mechanistic links responsible for this association are still poorly understood. The purpose of this study was to determine whether exposure to a paradigm of subchronic stress can provoke enduring changes on the heart rate of experimental rats and, if so, to reveal the autonomic and neural mechanisms that mediate these effects. The study was conducted on adult male Sprague-Dawley rats instrumented for telemetric recording of heart rate and locomotor activity. Animals were submitted to a subchronic stress protocol, consisting of a 1-h foot shock session on five consecutive days. Heart rate and locomotor activity were recorded continuously for 3 days before and for 6 days after the subchronic stress period. Subchronic foot shock produced significant and enduring reduction in heart rate both during the dark/active [Δ= −23 ± 3 beats per minute (bpm)] and light/inactive (Δ= −20 ± 3 bpm) phases of the circadian cycle, and a reduction in locomotor activity during the dark/active phase [Δ= −54 ± 6 counts per hour (cph)]. The bradycardic effect of subchronic stress was not related to a reduced locomotion. Selective sympathetic (atenolol) and vagal (methyl-scopolamine) blockades were performed to reveal which autonomic component was responsible for this effect. We found that the fall in heart rate persisted after subchronic stress in animals treated with atenolol (active phase Δ= −16 ± 3 bpm, inactive phase Δ= −19 ± 2 bpm), whereas vagal blockade with scopolamine transiently prevented this effect, suggesting that the bradycardia following subchronic stress was predominantly vagally mediated. Fluoxetine (selective serotonin reuptake inhibitor) and metyrapone (inhibitor of corticosterone synthesis) treatments did not affect heart rate changes but prevented the reduction in locomotion. We conclude that subchronic stress exposure in rats reduces heart rate via a rebound in vagal activation and that this effect is serotonin- and corticosterone-independent.

The international society for bipolar disorders (ISBD) task force report on antidepressant use in bipolar diosrders

Objective:
The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders.

Method:  
An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder.

Results:  
There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder.

Conclusions:
Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Application of the gradient boosted method in randomised clinical trials: participant variables that contribute to depression treatment efficacy of duloxetine, SSRIs or placebo

Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-individual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes.

The integrative management of treatment-resistant depression: a comprehensive review and perspectives.

Major depressive disorder is a prevalent and disabling illness. Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment.

Psychological management of unipolar depression

Objective: To be used in conjunction with 'Pharmacological management of unipolar depression' [Malhi et al. Acta Psychiatr Scand 2013;127(Suppl. 443):6-23] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of psychological treatments in depression derived from a literature review. Method: Medical databases including MEDLINE and PubMed were searched for pertinent literature, with an emphasis on recent publications. Results: Structured psychological treatments such as cognitive behaviour therapy and interpersonal therapy (IPT) have a robust evidence base for efficacy in treating depression, even in severe cases of depression. However, they may not offer benefit as quickly as antidepressants, and maximal efficacy requires well-trained and experienced therapists. These therapies are effective across the lifespan and may be preferred where it is desired to avoid pharmacotherapy. In some instances, combination with pharmacotherapy may enhance outcome. Psychological therapy may have more enduring protective effects than medication and be effective in relapse prevention. Newer structured psychological therapies such as mindfulness-based cognitive therapy and acceptance and commitment therapy lack an extensive outcome literature, but the few published studies yielding positive outcomes suggest they should be considered options for treatment. Conclusion: Cognitive behaviour therapy and IPT can be effective in alleviating acute depression for all levels of severity and in maintaining improvement. Psychological treatments for depression have demonstrated efficacy across the lifespan and may present a preferred treatment option in some groups, for example, children and adolescents and women who are pregnant or postnatal. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Citalopram-associated clitoral priapism: a case series.

Priapism is documented to occur in association with treatment with a variety of psychotropic agents. Three cases of clitoral priapism associated with treatment with citalopram are presented.

The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men.

OBJECTIVE: Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men. METHODS: Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression. RESULTS: Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site). CONCLUSIONS: Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men.

Depression as a risk factor for fracture in women: a 10 year longitudinal study

BACKGROUND: Previous research has demonstrated deficits in bone mineral density (BMD) among individuals with depression. While reduced BMD is a known risk for fracture, a direct link between depression and fracture risk is yet to be confirmed. METHODS: A population-based sample of women participating in the Geelong Osteoporosis Study was studied using both nested case-control and retrospective cohort study designs. A lifetime history of depression was identified using a semi-structured clinical interview (SCID-I/NP). Incident fractures were identified from radiological reports and BMD was measured at the femoral neck using dual energy absorptiometry. Anthropometry was measured and information on medication use and lifestyle factors was obtained via questionnaire. RESULTS: Among 179 cases with incident fracture and 914 controls, depression was associated with increased odds of fracture (adjusted odds ratio (OR) 1.57, 95%CI 1.04-2.38); further adjustment for psychotropic medication use appeared to attenuate this association (adjusted OR 1.52, 95%CI 0.98-2.36). Among 165 women with a history of depression at baseline and 693 who had no history of depression, depression was associated with a 68% increased risk of incident fracture (adjusted hazard ratio (HR) 1.68, 95%CI 1.02-2.76), with further adjustment for psychotropic medication use also appearing to attenuate this association (adjusted HR 1.58, 95%CI 0.95-2.61). LIMITATIONS: Potential limitations include recall bias, unrecognised confounding and generalizability. CONCLUSIONS: This study provides both cross-sectional and longitudinal evidence to suggest that clinical depression is a risk factor for radiologically-confirmed incident fracture, independent of a number of known risk factors. If there is indeed a clinically meaningful co-morbidity between mental and bone health, potentially worsened by psychotropic medications, the issue of screening at-risk populations needs to become a priority.

Adjunctive nutraceuticals for depression: a systematic review and meta-analyses

OBJECTIVE: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted. METHOD: A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed. RESULTS: Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta-analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies; funnel plots also revealed asymmetry (reflecting potential study bias). CONCLUSIONS: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.