Antidepressants and suicidal thought

The association of antidepressants with suicidal thought in people aged up to 25 year is a thorny issue. Balancing risk with benefit must always be at the core of any decision to treat and when the risk is an increased risk of suicide then a balanced decision can be difficult to make. Some clinicians who have been successfully treating patients using antidepressants have felt skepticism with these studies, finding them to be not reflective of their personal clinical experience. It may be wondered by some whether highlighting the link between suicidal thoughts and antidepressants may paradoxically lead to an increase in suicide by reducing the number of cases treated, however there is no evidence that this has occurred.

The association between antidepressants and suicidal thought may be unpalatable, but as with all new research the only way it can be judged is by the evidence to support it. The weight of evidence to demonstrate the association between antidepressants and suicidal thought in young people is convincing although the risk is low, estimated at one case of emerging suicidal ideation or suicide attempt for every 143 pediatric patients treated [1]. This risk is too low to displace antidepressants as the first line of treatment for depression but is too high a risk to be ignored. The risk is also too low to be recognized based on clinical experience alone as it is low enough to be imperceptible amongst suicides which occur due to depressive illness independent of antidepressant treatment. Only large studies are sufficiently powered to detect suicidal thought associated with antidepressant treatment. Clearly further studies would be helpful, especially if they can help characterize those at greatest risk. This is why the study by Lucy Goldsmith and Joanna Moncrieff in this issue of Current Drug Safety is an important step towards improving our understanding of antidepressant safety. These researchers find a link between increased suicidal impulses and emotional blunting and emotional instability.

Treating clinicians are urged to monitor for risk of suicide after initiation of antidepressant treatment, typically more frequently for the first four weeks of treatment and as indicated thereafter. However, if there is no history of suicidal thought or attempt and the patient does not admit to suicidal thought, suicidality may be missed by the treating clinician, ending in tragedy. Studies that provide new insights into this serious problem may lead to improvements in the effectiveness of monitoring patients for suicide risk, ultimately leading to better outcomes for patients.

Antidepressants and breast-feeding : a review of the literature

For every antidepressant so far investigated in the breast milk of mothers prescribed these medications, findings indicate that some amount of drug will be excreted into the breast milk. Nursing infants will be exposed to some, usually a very low, amount of drug and drugmetabolites. Levels of drug exposure to infants for the many antidepressants available are examined, discussing milk to plasma drug concentration ratios and the infant dose as a percentage of thematernal dose. Drug concentrations in infant plasma and adverse effects of drug exposures to infants are reviewed. Factors influencing the decision on whether to breast or bottle feed an infant nursed by a mother taking antidepressants are discussed, concluding that the decision needs to be made on an individual basis. The lactating mother, in consultation with her doctor, should be in a position to make an informed decision on whether or not to breast feed. Under certain circumstances the decision to bottle feed may be wise, but more commonly the advantages of breast-feeding will outweigh the very low risk of an adverse event from drug exposure to the infant.

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.

Combination antidepressants : use by GPs and psychiatrists

Background : Current treatment of depression fails to achieve remission in 50% of patients. Combinations of two antidepressants are used by some Australian psychiatrists.

Objective : This article investigates the pros and cons of combination antidepressant therapy and provides suggestions for when to consider their use, which combinations to choose, and how to introduce combination antidepressant therapies.

Discussion : Combining two antidepressants is a controversial strategy, with supporters and critics arguing its efficacy and safety from opposing perspectives. The use of combination antidepressant therapies may facilitate remission from depression. However, there is limited evidence supporting these treatments, and safety concerns are often cited. There is some support for combination therapies in selected cases from international bodies. After considering risks and benefits on a case-by-case basis, careful use of selected combination antidepressant therapy may be one of a range of effective treatments for some individuals suffering from depression.

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.

The association between use of antidepressants and bone quality using quantitative heel ultrasound.

Osteoporosis and depression are major public health problems worldwide. Studies have reported an association between antidepressant use, mainly selective serotonin reuptake inhibitors (SSRIs), and bone mineral density (BMD), but the issue remains unclear.

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.

Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression

Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high prevalence. Selective serotonin reuptake inhibitors (SSRIs), first-line agents in the pharmacological treatment of mood and anxiety disorders, have also been shown to negatively affect bone metabolism. SSRIs are the most prescribed antidepressants worldwide and a large number of persons at risk of developing osteoporosis, including older patients, will receive these antidepressants. Therefore, a proper musculoskeletal evaluation of individuals who are being targeted for or using SSRIs is a priority. The aim of this article is to review the evidence regarding the effects of depression and serotonergic antidepressants on bone and its implications for clinical care.