Efficacy Of Pharmacological Interventions Research Articles

Functional Brain Imaging of Tobacco Exposure in Humans

Cigarette smoking represents a major health problem in the United States. Although most cigarette smokers express a desire to quit, only about 14 to 49% will be successful after 6 or more months of treatment. An improved understanding of the acute and chronic effects of smoking on brain function may lead to more efficacious pharmacological and behavioral treatments for smoking dependence. Many research groups have utilized functional brain imaging to examine the effects of tobacco exposure on brain activity. Acute administration of nicotine and cigarette smoking itself have been found to increase activity in the prefrontal cortex, thalamus, and visual system; reduce global brain activity; and increase dopamine (DA) release in the ventral striatum/nucleus accumbens. Chronic tobacco exposure lead to an overall up-regulation of α4β2 nicotinic acetylcholine receptors (nAChRs) across brain regions (other than thalamus), and reduced monoamine oxidase (MAO) A and B levels in the basal ganglia. Functional brain imaging studies of cigarette craving and withdrawal, too, demonstrate important changes in brain activity. Taken together, current research suggests that smoking enhances neurotransmission through cortico-basal ganglia-thalamic circuits by either direct stimulation of nAChRs, indirect stimulation through DA release of MAO inhibition, or a combination of these, and perhaps, other factors. The purpose of this review is to provide a summary of current functional brain imaging studies of tobacco use and dependence, and use this information to develop a greater understanding of brain function in smokers.

The European Psychiatric Association (EPA) guidance on suicide treatment and prevention

Suicide is a major public health problem in the WHO European Region accounting for over 150,000 deaths per year. Suicidal crisisAcute intervention should start immediately in order to keep the patient alive. DiagnosisAn underlying psychiatric disorder is present in up to 90% of people who completed suicide. Comorbidity with depression, anxiety, substance abuse and personality disorders is high. In order to achieve successful prevention of suicidality, adequate diagnostic procedures and appropriate treatment for the underlying disorder are essential. TreatmentExisting evidence supports the efficacy of pharmacological treatment and cognitive behavioural therapy (CBT) in preventing suicidal behaviour. Some other psychological treatments are promising, but the supporting evidence is currently insufficient. Studies show that antidepressant treatment decreases the risk for suicidality among depressed patients. However, the risk of suicidal behaviour in depressed patients treated with antidepressants exists during the first 10–14 days of treatment, which requires careful monitoring. Short-term supplementary medication with anxiolytics and hypnotics in the case of anxiety and insomnia is recommended. Treatment with antidepressants of children and adolescents should only be given under supervision of a specialist. Long-term treatment with lithium has been shown to be effective in preventing both suicide and attempted suicide in patients with unipolar and bipolar depression. Treatment with clozapine is effective in reducing suicidal behaviour in patients with schizophrenia. Other atypical antipsychotics are promising but more evidence is required. Treatment teamMultidisciplinary treatment teams including psychiatrist and other professionals such as psychologist, social worker, and occupational therapist are always preferable, as integration of pharmacological, psychological and social rehabilitation is recommended especially for patients with chronic suicidality. FamilyThe suicidal person independently of age should always be motivated to involve family in the treatment. Social supportPsychosocial treatment and support is recommended, as the majority of suicidal patients have problems with relationships, work, school and lack functioning social networks. SafetyA secure home, public and hospital environment, without access to suicidal means is a necessary strategy in suicide prevention. Each treatment option, prescription of medication and discharge of the patient from hospital should be carefully evaluated against the involved risks. Training of personnelTraining of general practitioners (GPs) is effective in the prevention of suicide. It improves treatment of depression and anxiety, quality of the provided care and attitudes towards suicide. Continuous training including discussions about ethical and legal issues is necessary for psychiatrists and other mental health professionals.

Antipsychotics, Antidepressants, Anticonvulsants, and Placebo on the Symptom Dimensions of Borderline Personality Disorder

The aim of this study was to quantitatively review randomized controlled trials (RCTs) and open-label trials analyzing the efficacy of antidepressants, mood stabilizers, and antipsychotics for the treatment of the core symptoms of borderline personality disorder (BPD). Using a similar meta-analytic approach, the efficacy of placebo on the same core symptoms of BPD was evaluated. The risk of discontinuation of each of the medication classes reported in the studies was also analyzed to establish the major causes of discontinuation. MEDLINE (1966 to June 2010) and EMBASE (1980 to June 2010) databases were systematically searched to identify relevant RCTs and open studies. The primary outcome was improvement in the specific core symptoms of the disorder: affective dysregulation, impulsive-behavioral dyscontrol, and cognitive-perceptual symptoms. Evidence from RCTs and open studies suggests that drug treatment, especially with mood stabilizers and antipsychotics, may be effective for treating affective dysregulation and impulsive-behavioral dyscontrol. Antipsychotics were also effective in reducing cognitive-perceptual symptoms. Antidepressants failed to show efficacy in treating BPD symptom dimensions other than affective dysregulation. Our analyses of the placebo arm of RCTs showed a significant improvement of symptomatology in these patients also. There were no significant differences in overall dropout rates between patients on medications and those on placebo. In conclusion, the efficacy of pharmacological treatment on the symptom dimensions of BPD has been shown by various independent meta-analyses, with a positive effect of drug treatment on the core symptoms of BPD and some documentable differences in terms of efficacy between different drug classes in each of the symptom domains.

Editorial [Hot Topic: Bringing Drugs Into the Injured Brain and Keeping Them There (Executive Guest Editors: Dirk M. Hermann and Pauline Patak)

The delivery of pharmacological compounds to the injured brain is a huge challenge, which may predispose to drug failure and resistance. Besides the limited passage of drugs across the blood-brain barrier, which is a physical obstacle for the majority of pharmacological compounds, brain capillary cells express ATP-binding cassette (ABC) transporters on their surface, which actively remove drugs from the brain against concentration gradients. Eliminating a large number of pharmacological compounds and endogenous substrates from the brain tissue, ABC transporters play a major role for the maintenance of brain homeostasis and detoxification. The present issue summarizes current knowledge on ABC transporters in the injured brain, outlining how these efflux systems are regulated under pathological conditions, how they impede the brain accumulation of drugs and how they might contribute to the pathogenesis of neurological diseases once they become dysfunctional. This issue analyzes the validity of the concept of multidrug resistance, evaluating how ABC transporters may be modified in order to enable the development of more efficacious pharmacological treatments.

A Systematic Review and Mixed Treatment Comparison of the Efficacy of Pharmacological Treatments for Fibromyalgia

To review the literature on pharmacological treatments for fibromyalgia. Relative efficacy was estimated in terms of outcome measures highlighted by the Outcome Measures in Rheumatology Network using a Bayesian mixed treatment comparison (MTC) meta-analysis. Randomized controlled trials reporting treatments for fibromyalgia were identified by systematically reviewing electronic databases (Cochrane Library, Medline, EMBASE; accessed February 2008) and conducting manual bibliographic searches. Forty-five randomized controlled trials met the prespecified inclusion criteria for the systematic review. There were limited robust clinical data for some therapeutic classes (tricyclic antidepressants, analgesics, sedative hypnotics, monoamine oxidase inhibitors) and only 21 studies met the more stringent criteria for inclusion in the MTC. The majority of studies included in the MTC assessed the anticonvulsant pregabalin (n = 5) or the serotonin norepinephrine reuptake inhibitors (SNRIs) duloxetine (n = 3) and milnacipran (n = 3). Licensed doses of pregabalin and duloxetine were significantly (P < 0.05) more efficacious than placebo in terms of absolute reduction in pain, number of "responders" (≥30% reduction in pain), or change in Fibromyalgia Impact Questionnaire score (pregabalin 450 mg/d only). There was no significant difference between licensed doses of pregabalin and duloxetine for these outcomes. However licensed doses of pregabalin produced significantly greater improvements in sleep compared with milnacipran (as measured by Medical Outcomes Study Sleep Scale). The current study confirms the therapeutic efficacy of pregabalin and the SNRIs, duloxetine and milnacipran, in the treatment of fibromyalgia. Given their different modes of action, combination therapy with pregabalin plus an SNRI should be investigated in future research.

Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis

Conventional meta-analyses have shown inconsistent results for efficacy of pharmacological treatments for acute mania. We did a multiple-treatments meta-analysis, which accounted for both direct and indirect comparisons, to assess the effects of all antimanic drugs. We systematically reviewed 68 randomised controlled trials (16,073 participants) from Jan 1, 1980, to Nov 25, 2010, which compared any of the following pharmacological drugs at therapeutic dose range for the treatment of acute mania in adults: aripiprazole, asenapine, carbamazepine, valproate, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, quetiapine, risperidone, topiramate, and ziprasidone. The main outcomes were the mean change on mania rating scales and the number of patients who dropped out of the allocated treatment at 3 weeks. Analysis was done by intention to treat. Haloperidol (standardised mean difference [SMD] -0·56 [95% CI -0·69 to -0·43]), risperidone (-0·50 [-0·63 to -0·38), olanzapine (-0·43 [-0·54 to -0·32], lithium (-0·37 [-0·63 to -0·11]), quetiapine (-0·37 [-0·51 to -0·23]), aripiprazole (-0·37 [-0·51 to -0·23]), carbamazepine (-0·36 [-0·60 to -0·11], asenapine (-0·30 [-0·53 to -0·07]), valproate (-0·20 [-0·37 to -0·04]), and ziprasidone (-0·20 [-0·37 to -0·03]) were significantly more effective than placebo, whereas gabapentin, lamotrigine, and topiramate were not. Haloperidol had the highest number of significant differences and was significantly more effective than lithium (SMD -0·19 [95% CI -0·36 to -0·01]), quetiapine (-0·19 [-0·37 to 0·01]), aripiprazole (-0·19 [-0·36 to -0·02]), carbamazepine (-0·20 [-0·36 to -0·01]), asenapine (-0·26 [-0·52 to 0·01]), valproate (-0·36 [-0·56 to -0·15]), ziprasidone -0·36 [-0·56 to -0·15]), lamotrigine (-0·48 [-0·77 to -0·19]), topiramate (-0·63 [-0·84 to -0·43]), and gabapentin (-0·88 [-1·40 to -0·36]). Risperidone and olanzapine had a very similar profile of comparative efficacy, being more effective than valproate, ziprasidone, lamotrigine, topiramate, and gabapentin. Olanzapine, risperidone, and quetiapine led to significantly fewer discontinuations than did lithium, lamotrigine, placebo, topiramate, and gabapentin. Overall, antipsychotic drugs were significantly more effective than mood stabilisers. Risperidone, olanzapine, and haloperidol should be considered as among the best of the available options for the treatment of manic episodes. These results should be considered in the development of clinical practice guidelines. None.

Group Releases New Guideline on Options for Treating Painful Diabetic Neuropathy

A NEW GUIDELINE FOR USING EFfective therapies for patients with painful diabetic neuropathy has been issued by the American Academy of Neurology. The guideline, released in April, was established through a systematic review of the literature from 1960 to August 2008 that reported on the efficacy of pharmacological treatments (such as anticonvulsants, antidepressants, and opioids) and nonpharmacological treatments (such as electrical stimulation, magnetic field treatment, low-intensity laser treatment, and Reiki massage). The guideline authors rated the therapies based on the quality of the evidence (Bril V et al. Neurology. 2011; 76[20]:1758-1765). The burning or tingling pain of diabetic neuropathy adversely affects patients’ quality of life. It is estimated that about 16% of patients with diabetes have painful diabetic neuropathy. And while treatments are available, an estimated 39% of cases remain untreated and about 1 in 8 patients do not even report the condition to their physicians. Vera Bril, MD, the lead guideline author and director of the neuromuscular section of the University of Toronto in Toronto, Ontario, Canada, explained why the academy decided to publish the guideline. “We did it because there are new treatments available and people are all over the place in thinking of what works and does not work,” Bril said. What works, at least according to the most rigorous study, is the anticonvulsant pregabalin, which the authors said is effective in lessening the pain of diabetic neuropathy and in improving quality of life; the drug also lessens sleep interference, although the effect size is small. Pregabalin was the only treatment to receive the more rigorous level A recommendation by the authors.

Efficacy and tolerance of systemic steroids in sciatica: a systematic review and meta-analysis

The efficacy of pharmacological interventions in sciatica is limited and the use of systemic steroids is still controversial. We aimed at evaluating the efficacy and tolerance of systemic steroids in sciatica. A systematic literature search was performed in the Medline, Embase and Cochrane databases until February 2010. Randomized placebo-controlled trials evaluating the efficacy and the tolerance of systemic steroids in sciatica were included. Efficacy and tolerance were assessed using the relative risk (RR) and 95% CI with the inverse variance method (RR > 1 means that the event is more likely to occur in the steroid group). We explored the heterogeneity between the studies using subgroup analysis. Seven studies (383 patients) were included. The difference in the rate of responders between both groups was not statistically significant (RR = 1.22, 95% CI 0.96, 1.56). The rate of adverse events was 13.3% for the patients in the steroid group and 6.6% for the placebo group (RR = 2.01, 95% CI 1.06, 3.80). The number needed to harm was 20 (95% CI 10, ∞). Twenty (15.3%) patients in the steroid group and seven (5.7%) patients in the placebo group underwent surgery. A trend towards a higher requirement for spinal surgery was observed in the steroid group (RR = 1.14, 95% CI 0.74, 1.75). The methodological quality slightly influenced the results. We did not find any publication bias. Steroid efficacy is not superior to the placebo in sciatica, but it has more side effects. The tolerance : efficacy ratio indicates against the use of systemic steroids in sciatica.

A cognitive-behavioral treatment for irritable bowel syndrome using interoceptive exposure to visceral sensations

BackgroundIrritable bowel syndrome (IBS) is a chronic and debilitating medical condition with few efficacious pharmacological or psychosocial treatment options available. Evidence suggests that visceral anxiety may be implicated in IBS onset and severity. Thus, cognitive-behavioral treatment (CBT) that targets visceral anxiety may alleviate IBS symptoms. MethodsThe current study examined the efficacy of a CBT protocol for the treatment of IBS which directly targeted visceral sensations. Participants (N = 110) were randomized to receive 10 sessions of either: (a) CBT with interoceptive exposure (IE) to visceral sensations; (b) stress management (SM); or (c) an attention control (AC), and were assessed at baseline, mid-treatment, post-treatment, and follow-up sessions. ResultsConsistent with hypotheses, the IE group outperformed AC on several indices of outcome, and outperformed SM in some domains. No differences were observed between SM and AC. The results suggest that IE may be a particularly efficacious treatment for IBS. ConclusionsImplications for research and clinical practice are discussed.

Efficacy of pharmacological treatment and genetic characterization in early diagnosed patients affected by long QT syndrome with impaired AV conduction

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Pharmacological treatment of sex offenders

Summary Sex offending is a major public health concern due to the potentially serious consequences for the victims (especially in case of rape or paedophilia). All care providers agree that imprisonment alone does not solve the question of repeat offences for these subjects and that a combined medical, psychological and social approach is needed for these offenders. A combination of psychotherapy (especially behavioral therapy) with pharmacological treatment is better than one or other therapy used alone. Two types of medication are used for these subjects; serotonergic antidepressants and antiandrogen treatments. Two antiandrogen treatments have obtained Health Agency approval in different European countries in this indication: cyproterone acetate and depot triptorelin (3-month formulation). Guidelines have been published in France by the National Health Authority and, at the international level, by the World Federation of Societies of Biological Psychiatry ( www.wfsbp.org ). In this paper, we will define the term paraphilia and report some epidemiological data, before summarizing the available literature about the efficacy of pharmacological treatment for paraphilias.

Excessive Daytime Sleepiness in Patients with Parkinsonʼs Disease

Excessive daytime sleepiness (EDS) is described as inappropriate and undesirable sleepiness during waking hours and is a common non-motor symptom in Parkinson's disease, affecting up to 50% of patients. EDS has a large impact on the quality of life of Parkinson's disease patients as well as of their caregivers, in some cases even more than the motor symptoms of the disease. Drug-induced EDS is a particular problem as many dopamine agonists used for the treatment of Parkinson's disease have EDS as an adverse effect. Dopaminergic treatment may also render a subset of Parkinson's disease patients at risk for sudden-onset sleep attacks that occur without warning and can be particularly hazardous if the patient is driving. This demonstrates the need for early recognition and management not only to increase health-related quality of life but also to ensure patient safety. There are many assessment tools for EDS, including the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT), although only the Parkinson's Disease Sleep Scale (PDSS) and the SCales for Outcomes in PArkinson's Disease-Sleep (SCOPA-S) are specifically validated for Parkinson's disease. Polysomnography can be used when necessary. Management comprises non-pharmacological and pharmacological approaches. Non-pharmacological approaches can be the mainstay of treatment for mild to moderate EDS. Advice on good sleep hygiene is instrumental, as pharmacological approaches have yet to provide consistent and reliable results without significant adverse effects. The efficacy of pharmacological treatment of EDS in Parkinson's disease using wakefulness-promoting drugs such as modafinil remains controversial. Further areas of research are now also focusing on adenosine A(2A) receptor antagonists, sodium oxybate and caffeine to promote wakefulness. A definitive treatment for the highly prevalent drug-induced EDS has not yet been found.

Tratamentos farmacológicos para o transtorno de ansiedade social: existem novos parâmetros na atualidade?

CONTEXTO: O transtorno de ansiedade social (TAS), apesar da baixa taxa de detecção e do alto índice de comorbidades associadas, é considerado uma condição tratável. Apesar da resposta estabelecida a diversas classes de medicamentos, os algoritmos para o tratamento do TAS necessitam de atualização constante. OBJETIVO: Realizar revisão sistemática da literatura no que diz respeito à eficácia dos tratamentos farmacológicos relativos ao TAS, a partir de estudos controlados, conduzidos no período de 2005 a 2010. MÉTODO: Foram utilizados os indexadores eletrônicos PsycoInfo, Lilacs e Medline, utilizando-se as palavras-chave: "social phobia or social anxiety and treatment". RESULTADOS: De acordo com critérios de inclusão adotados, 29 artigos foram incluídos e analisados. Mostram-se eficazes para o tratamento do TAS as seguintes drogas, de acordo com a classe: a) ISRSs: escitalopram, fluvoxamina, citalopram, GR205171 e sertralina; b) ISRSN: venlafaxina; c) IMAOs: fenelzina, moclobemina; d) aminoácidos: d-cicloserina; f) anticonvulsivantes: tiagabina. CONCLUSÃO: Os ISRSs e os ISRSNs têm seu uso estabelecido e ainda continuam sendo considerados primeira opção de tratamento. Porém, destaca-se o potencial futuro da d-cicloserina e dos anticonvulsivantes, com necessidade de um número maior de estudos controlados que confirmem os achado iniciais. A ação das diferentes drogas em nível neurobiológico, bem como dos tratamentos associados, necessita ainda ser mais explorada.

Predictors of Persistence of Comorbid Generalized Anxiety Disorder Among Veterans With Major Depressive Disorder

A limited number of randomized clinical trials show that efficacious pharmacologic treatments exist for comorbid major depressive disorder (MDD) and generalized anxiety disorder (GAD). The aims of this effectiveness study were to describe the impact of a depression care management intervention on the persistence of comorbid GAD symptoms in a sample of primary care patients with MDD and to identify risk factors for persistent GAD. Data were collected from April 2003 to September 2005 for the Telemedicine-Enhanced Antidepressant Management (TEAM) study, a multisite, randomized effectiveness trial targeting US Department of Veterans Affairs (VA) primary care patients with depression. Veterans aged 26.59-88.36 years received either the TEAM intervention or usual care in small VA community-based outpatient clinics. The TEAM care management intervention focused on optimizing antidepressant therapy through patient education and activation, symptom monitoring, adherence promotion, and side-effect management. Veterans who screened positive for MDD using the Patient Health Questionnaire-9 (based on DSM-IV criteria) and who met the Mini-International Neuropsychiatric Interview criteria (maintaining consistency with DSM-IV-TR) for comorbid GAD at baseline were selected for the present study (N = 168). The primary outcome was persistence of GAD at 6 months and 12 months. All predictors available in the TEAM study data that were described in the literature to be associated with influencing GAD outcomes were examined. Persistence of depression was the strongest predictor of persistence of comorbid GAD at both 6 months (OR = 5.75; 95% CI, 2.38-13.86; P < .05) and 12 months (OR = 15.56; 95% CI, 6.10-39.68; P < .05). Although the TEAM intervention significantly reduced depression symptom severity, it was not significantly associated with GAD persistence. Insomnia was a significant protective factor for persistence of GAD at 6 months (OR = 0.66; 95% CI, 0.44-0.99; P < .05). Early screening for presence of comorbid GAD among those with MDD may be valuable both for further research and for enhancing clinical management of GAD and MDD comorbidity.

Possible benefits of strontium ranelate in complicated long bone fractures

Osteoporosis drugs are prescribed to prevent fragility fractures, which is the principal aim of the management of osteoporosis. However, if fracture does occur, then it is also important to promote a fast and uneventful healing process. Despite this, little is known about the effect of osteoporosis drugs on bone healing in humans. Strontium ranelate is an osteoporosis agent that increases bone formation and reduces bone resorption and may therefore be beneficial in fracture healing. We report four cases of fracture non-union for up to 20months. Treatment with strontium ranelate (2g/day) for between 6weeks and 6months appeared to contribute to bone consolidation in the four cases. Animal studies support beneficial effects of strontium ranelate on bone healing via improvement of bone material properties and microarchitecture in the vicinity of the fracture. The clinical cases described herein provide new information on these effects, in the absence of randomized controlled studies on the clinical efficacy of pharmacological treatments in osteoporosis in fracture repair. Further studies are necessary. Fracture healing is an important topic in orthopedic research and is also a concern for patients with postmenopausal osteoporosis. Evidence from case reports and animal studies suggests that strontium ranelate improves bone microarchitecture and accelerates fracture healing. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research.

A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity

The efficacy of pharmacological treatment in controlling childhood obesity is controversial. We aimed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification (diet and exercise). This triple-masked randomized clinical trial was conducted among 180 participants aged 10-16 years. They were assigned randomly to 4 groups of equal number to receive metformin, fluoxetine, a combination of the two drugs, or placebo. The trial lasted for 12 weeks and participants were followed up for an additional 12-week period. Overall, 91.1% (n=164) of the enrolled participants completed the trial. After the 12-week trial, the body mass index decreased significantly in all groups receiving medications [approximately -1.2 (0.2) kg/m², P<0.05]. This decrease was not significant in the placebo group. Waist circumference decreased significantly in the groups receiving metformin [-2.1 (0.4) cm, P=0.03)] as well as in the group receiving a combination therapy of metformin and fluoxetine [-2.5 (0.4) cm, P=0.01)]. In the 24-week follow-up study, these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine. No serious drug side-effects were reported. A limited period of such treatment may help weight control, and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs. Our findings should be confirmed in future studies with a longer follow-up period.

Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder

Due to the episodic and chronic nature of bipolar disorder (BD), maintenance therapy represents a critical part of treatment; however, there is a paucity of studies comparing effectiveness of available long-term treatments. The aim of this study is to determine and compare the efficacy of pharmacological treatments for maintenance treatment of BD by means of the number needed to treat (NNT). The efficacy of drugs used for maintenance treatment of BD, as emerging from the results of randomized controlled trials, was assessed using the size effect measure of NNT. PubMed searches were conducted on English-language articles published until May 2010 using the search terms "bipolar disorder," "mania," "mixed episode," or "bipolar depression," cross-referenced with trial characteristic search phrases and generic names of medications. The search was supplemented by manually reviewing reference lists from identified publications. In 15 studies, aripiprazole, olanzapine, quetiapine, risperidone long-acting injection, lithium, lamotrigine, and divalproex proved effectiveness in terms of NNTs (≥ 10% advantage over placebo) for prevention of relapse into any mood episode. Quetiapine, lithium, risperidone long-acting injection, aripiprazole, and olanzapine are effective in manic recurrence prevention. Lamotrigine, quetiapine, and lithium present significant NNTs for prevention of depressive relapses. All of the pharmacological agents assessed were effective in the prevention of any kind of mood episode; however, different efficacy profiles were found for prevention of manic and/or depressive relapses. The comparison of NNT values of the available agents may represent a useful tool in clinical settings, in order to facilitate implementation of long-term pharmacological interventions in patients with BD.

Exercise as a Treatment to Enhance Sleep

The prevalence of sleep-related complaints and the limited efficacy of pharmacological treatments make nonpharmacological alternatives essential. Physical exercise is one such alternative that is inexpensive and affects numerous health systems simultaneously. This article reviews putative mechanisms that have guided exercise and sleep research, including exercise’s antidepressant effects, restorative functions, and circadian effects, and concludes that a number of mechanisms are plausible and likely active in explaining the effects of exercise on sleep. The empirical literature is reviewed, with special emphasis given to randomized controlled trials and experimental studies that help to inform for whom (eg, age, fitness characteristics), under what conditions (eg, light exposure, time of day), and by what means (eg, type, intensity, duration) exercise optimally affects sleep. The review also includes the emerging research using exercise as a treatment of obstructive sleep apnea and restless legs syndrome. The current literature indicates that moderate amounts of exercise, which can be obtained through a variety of means such as brisk walking and resistance training, are sufficient to improve sleep quality. Additional research is warranted in this area, particularly randomized controlled trials that target subgroups at risk for poor sleep such as older adults and persons with sleep disorders.

Leichte kognitive Beeinträchtigung, demenzielle und depressive Erkrankungen – Besondere Maßnahmen im höheren Lebensalter

Depressionen treten im höheren Lebensalter gehäuft auf und weisen als eigenständige Krankheitsentitäten verschiedenartige Auftretensformen und klinische Manifestationen auf. Bei älteren Patienten stehen häufig somatische Beschwerden im Vordergrund, die die rechtzeitige Diagnosestellung und Therapie erschweren. Therapieverfahren sollten unter Berücksichtigung der besonderen Anforderungen des älteren Patienten ausgewählt werden. Die leichte kognitive Beeinträchtigung (LKB) ist mit einem erhöhten Risiko für die spätere Manifestation einer Demenzerkrankung assoziiert. Die unterschiedlichen Konzepte lassen sich hinsichtlich Ätiologie, symptomatischen Schwerpunkten und Verlauf unterteilen. Die Wirksamkeit pharmakologischer Ansätze ist bisher nur unzureichend belegt. Primär- und sekundärpräventive Maßnahmen sollten empfohlen werden. Darüber hinaus werden überblicksartig Demenzen und die wichtigsten diagnostischen Verfahren sowie die Unterscheidung der Alzheimer-Demenz zu LKB und depressiver Pseudodemenz vorgestellt.

Treatment of COPD: from pharmacological to instrumental therapies

The two main goals of the current management of chronic obstructive pulmonary disease (COPD) are: 1) to reduce the impact of the disease on daily activities; and 2) to reduce the risk of future events (exacerbations, lung function decline and death) [1]. The first measure is obviously smoking cessation; however, we will not discuss this. Treatment guidelines are mainly based on randomised clinical trials that include a small and highly selected fraction of the COPD population [2]. Therefore, it is questionable as to whether these evidence-based guidelines can be extrapolated to the overall COPD population in the everyday practice. Indeed, less than one in five or 10 patients with COPD could fit into inclusion or exclusion criteria commonly used in clinical trials evaluating efficacy of pharmacological treatments [2, 3]. In addition, COPD is a heterogeneous disease and patients with similar forced expiratory volume in 1 s (FEV1) may show very different functional status, underlying lung pathology and comorbidities. For most treatments, differences in the responsiveness of COPD subgroups are not yet established and large, long clinical trials, along with high-quality meta-analyses, remain the basis of the current treatment guidelines and the evaluation of the benefit/risk ratio of the main therapeutic classes used in COPD management. However, even the large therapeutic trials may suffer from methodological limitations in the design or analysis [4]. The most important outcomes in clinical trials are patient-centred outcomes. Exacerbations, health-related quality of life and mortality are logical major outcomes in COPD trials [4]. In addition, exercise performance and lung function decline are other important targets for therapeutic intervention in COPD [5]. Lung function and biological markers reliably predicting individual response to treatments would be useful. ### Bronchodilators Bronchodilators are the mainstay of the current pharmacological …