Do antidepressants reduce the burden imposed by depression on employers?

The ability to perform paid or unpaid work is integral to an individual's quality of life. Therefore, we performed a systematic literature review to examine the impact of depression and its treatment on occupational outcomes. This review found absenteeism from work to be markedly higher among depressed employees and productivity to be dramatically undermined by some symptoms of depression. Gaps in the published literature point to the need for future economic and clinical analyses to include work-related outcomes. Published studies showed that antidepressants can enhance work-related outcomes by alleviating affective symptoms. However, the pharmacological properties of antidepressants may produce differential effects that influence work-related outcomes in other ways. For example, TCAs, but not SSRIs, produce sedation and impair cognitive function in ways that could undermine work-related outcomes. Formal analyses are required to quantify whether the improved social functioning, motivation and vigilance that may be associated with some newer antidepressants translate into improved work-related outcomes. Although few published studies have directly quantified the cost benefit of managing depression and associated lost productivity, existing studies that directly assessed work-related outcomes have suggested that treating depression is cost effective. Gaps in the published literature imply that the impact of depression and antidepressants on occupational outcomes has been understudied. This reflects, in part, the fact that antidepressant studies lasting 4 or 6 weeks are unlikely to capture the impact of treatment on work-related measures. In addition, the current evidence base is fraught with other methodological limitations. The effect of depression on non-paid employment also requires further assessment. In conclusion, the efficacy of antidepressants on work-related outcomes should be measured in clinical trials that have an adequate design and a suitable follow-up period, and included in health technology assessments. Until such studies are available, the evidence base supporting the use of antidepressants will remain incomplete.     

Comparative studies on the efficacy of psychotherapy, pharmacotherapy, and their combination in depression: was adequate pharmacotherapy provided?

Pharmacotherapy and psychotherapy, separately or in combination, have been used successfully in the treatment of depression. Recent studies have compared the two modes of treatment and their combination with respect to relative efficacy and have found psychotherapy, alone or combined with medication, to be the preferential treatment approach for depressive disorders. However, the adequacy of pharmacotherapy administered in these trials remains in question. The last decade's major comparative studies are systematically reviewed in order to evaluate the nature and specifics of pharmacotherapy. Special emphasis is placed on essential requirements of pharmacotherapy, methods of treating refractory cases, and details of treatment provision. Most of the studies used inadequate antidepressant doses, did not measure tricyclic plasma concentrations systematically, neglected the use of accepted strategies for response enhancement in refractory cases, and at times provided pharmacotherapy in nonspecialized settings or by inexperienced physicians. Findings indicate that pharmacotherapy administered in these studies does not fulfill requirements for adequacy and thereby precludes any definite conclusions regarding relative efficacy. The authors propose the term "optimization" of treatment to reflect maximized pharmacotherapy, discuss its essential requirements, and submit that such optimization be assured in future comparative trials.     

Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon

Introduction: Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns.

Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the ‘San Antonio NIPS model’, we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly.

Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician’s focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.     

Pharmacokinetic/pharmacodynamic considerations for epilepsy – depression comorbidities

Introduction: Epilepsy may be frequently associated with psychiatric disorders and its co-existence with depression usually results in the reduced quality of life of patients with epilepsy. Also, the efficacy of antiepileptic treatment in depressed patients with epilepsy may be significantly reduced.

Areas covered: Results of experimental studies indicate that antidepressants co-administered with antiepileptic drugs may either increase their anticonvulsant activity, remain neutral or decrease the protective action of antiepileptic drugs in models of seizures. Apart from purely pharmacodynamic interactions, pharmacokinetic mechanisms have been proven to contribute to the final outcome. We report on clinical data regarding the pharmacokinetic interactions of enzyme-inducing antiepileptic drugs with various antidepressants, whose plasma concentration may be significantly reduced. On the other hand, antidepressants (especially selective serotonin reuptake inhibitors) may influence the metabolism of antiepileptics, in many cases resulting in the elevation of plasma concentration of antiepileptic drugs.

Expert opinion: The preclinical data may provide valuable clues on how to combine these two groups of drugs – antidepressant drugs neutral or potentiating the anticonvulsant action of antiepileptics are recommended in this regard. Avoidance of antidepressants clearly decreasing the convulsive threshold or decreasing the anticonvulsant efficacy of antiepileptic drugs (f.e. bupropion or mianserin) in patients with epilepsy is recommended.     

Neuronal and immunological basis of action of antidepressants in chronic pain – clinical and experimental studies

The current knowledge of the pharmacological actions of the tricyclic antidepressants (TCAs) has slowly evolved through their over 40-year history. Chronic pain represents one of the most important public health problems, and antidepressants are an essential part of the therapeutic strategy in addition to classical analgesics. This article reviews the available evidence on the efficacy and safety of antidepressants in chronic pain conditions; namely, headaches, low back pain, fibromyalgia, cancer pain and especially neuropathic pain. TCAs are traditionally the main type of depression medication used to treat chronic pain. Recently, new antidepressants were introduced into clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs that are effective for chronic pain belong to the tetracyclic antidepressants (TeCAs) group (amoxapine, maprotiline), the serotonin and noradrenaline reuptake inhibitors (SNRIs) group (duloxetine, venlafaxine, milnacipran) and the atypical antidepressants group (bupropion, trazodone, mirtazapine, nefazodone). In this review, we present the available publications on TCAs (amitriptyline, doxepin, imipramine, desipramine, nortriptyline), TeCAs (amoxapine, maprotiline), selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluoxetine, paroxetine), SNRIs (duloxetine, venlafaxine, milnacipran) and atypical antidepressants (bupropion) for the treatment of neuropathic pain.We also review analgesics acting as both opioid receptor agonists and also acting as aminergic reuptake inhibitors. Existing data are insufficient to conclude which of these new classes of antidepressants has the best clinical profile and will be the most effective in the treatment of neuropathic pain; in addition, a lower incidence of side effects should be considered. Increased experimental and translational research is a key for further improvement of the treatment of chronic pain with antidepressants. However, evidence from basic science is needed to improve our understanding of the mechanisms of action and their possible pharmacodynamic interactions.     

Sleep changes during long-term treatment of depression with fluvoxamine – a home-based study

Rationale: The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice. Objectives: To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies. Methods: We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients’ own homes, using the Oxford Medilog system. Results: At 12 weeks, 7/12 patients had responded (HAM-D decreased by >50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed non- significant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the HAM-D) showed a progressive improvement over time, especially in the responders. Conclusions: The effects of the SSRI fluvoxamine on objective sleep measures are in the direction predicted by its pharmacological actions and some persist for at least 12 weeks. In addition subjective appraisal of sleep is strongly affected by mood state. All patients found the home recording procedure acceptable and only minimally disruptive. Received: 5 July 1999 / Final version: 22 November 1999     

Postoperative nausea and vomiting – a narrative review of pathophysiology,pharmacotherapy and clinical management strategies

Introduction: Postoperative nausea and vomiting (PONV) are common complications concerning patients undergoing general anesthesia. Intensive research was performed during the last two decades in order to develop therapeutic and prophylactic strategies to prevent this complication.

Areas covered: This article reviews the pathophysiology as well as pharmacological aspects of PONV prophylaxis and treatment. Relevant strategic aspects for pharmacological prophylaxis of PONV are discussed and clinical standard operating procedures are presented.

Expert opinion: The expert opinion focuses on poor implementation of actual PONV guidelines and future considerations.     

An immune gate of depression – Early neuroimmune development in the formation of the underlying depressive disorder

The prevalence of depression worldwide is increasing from year to year and constitutes a serious medical, economic and social problem. Currently, despite multifactorial risk factors and pathways contributing to depression development, a significant aspect is attributed to the inflammatory process. Cytokines are considered a factor activating the kynurenine pathway, which leads to the exhaustion of tryptophan in the tryptophan catabolite (TRYCAT) pathway. This results in the activation of potentially neuroprogressive processes and also affects the metabolism of many neurotransmitters.The immune system plays a coordinating role in mediating inflammatory process. Beginning from foetal life, dendritic cells have the ability to react to bacterial and viral antigens, stimulating T lymphocytes in a similar way to adult cells. Cytotoxicity in the prenatal period shapes the predisposition to the development of depression in adult life. Allostasis, i.e. the ability to maintain the body’s balance in the face of environmental adversity through changes in its behaviour or physiology, allows the organism to survive but its consequences may be unfavourable if it lasts too long.As a result, Th lymphocytes, in particular T helper 17 cells, which play a central role in the immunity of the whole body, contribute to the development of both autoimmune diseases and psychiatric disorders including depression, as well as have an impact on the differentiation of T CD4+ cells into Th17 cells in the later development of the child’s organism, which confirms the importance of the foetal period for the progression of depressive disorders.     

Current status in research of dengue vaccine candidates based on domain Ⅲof E protein

The ideal dengue vaccines should be low reactogenic, induce life-long protection against infection with any of the four serotypes of dengue viruses, and be affordable. The envelope protein domain Ⅲ of dengue virus has been implicated in receptor binding, and it is also the target of specific neutralizing antibodies.In this article, the current state of knowledge on vaccine candidates based on domain Ⅲ is reviewed.     

Health and medication literacy and the desire to participate in pharmacotherapy decision making – comparison of two countries

Background

Health and medication literacy may be important factors in the outcomes of medical treatment. Similarly, shared decision making or lack of it may influence patient's behavior and adherence to medications.