Abstract:
:Treatment-resistant depression (TRD) presents major challenges for both patients and clinicians. There is no universally accepted definition of TRD, but results from the US National Institute of Mental Health's (NIMH) STAR*D (Sequenced Treatment Alternatives to Relieve Depression) programme indicate that after the failure of two treatment trials, the chances of remission decrease significantly. Several pharmacological and nonpharmacological treatments for TRD may be considered when optimized (adequate dose and duration) therapy has not produced a successful outcome and a patient is classified as resistant to treatment. Nonpharmacological strategies include psychotherapy (often in conjunction with pharmacotherapy), electroconvulsive therapy and vagus nerve stimulation. The US FDA recently approved vagus nerve stimulation as adjunctive therapy (after four prior treatment failures); however, its benefits are seen only after prolonged (up to 1 year) use. Other nonpharmacological options, such as repetitive transcranial stimulation, deep brain stimulation or psychosurgery, remain experimental and are not widely available. Pharmacological treatments of TRD can be grouped in two main categories: 'switching' or 'combining'. In the first, treatment is switched within and between classes of compounds. The benefits of switching include avoidance of polypharmacy, a narrower range of treatment-emergent adverse events and lower costs. An inherent disadvantage of any switching strategy is that partial treatment responses resulting from the initial treatment might be lost by its discontinuation in favour of another medication trial. Monotherapy switches have also been shown to have limited effectiveness in achieving remission. The advantage of combination strategies is the potential to build upon achieved improvements; they are generally recommended if partial response was achieved with the current treatment trial. Various non-antidepressant augmenting agents, such as lithium and thyroid hormones, are well studied, although not commonly used. There is also evidence of efficacy and increasing use of atypical antipsychotics in combination with antidepressants, for example, olanzapine in combination with fluoxetine (OFC) or augmentation with aripiprazole. The disadvantages of a combination strategy include multiple medications, a broader range of treatment-emergent adverse events and higher costs. Several experimental pharmaceutical treatment alternatives for TRD are also being explored in combination with antidepressants or as monotherapy. These less studied alternative compounds include pindolol, inositol, CNS stimulants, hormones, herbal supplements, omega-3 fatty acids, S-adenosyl-L-methionine, folic acid, lamotrigine, modafinil, riluzole and topiramate. In summary, despite an increasing variety of choices for the treatment of TRD, this condition remains universally undefined and represents an area of unmet medical need. There are few known approved pharmacological agents for TRD (aripiprazole and OFC) and overall outcomes remain poor. This might be an indication that depression itself is a heterogeneous condition with a great diversity of pathologies, highlighting the need for careful evaluation of individuals with depressive symptoms who are unresponsive to treatment. Clearly, more research is needed to provide clinicians with better guidance in making those treatment decisions--especially in light of accumulating evidence that the longer patients are unsuccessfully treated, the worse their long-term prognosis tends to be.
journal_name
CNS Drugsjournal_title
CNS drugsauthors
Shelton RC,Osuntokun O,Heinloth AN,Corya SAdoi
10.2165/11530280-000000000-00000subject
Has Abstractpub_date
2010-02-01 00:00:00pages
131-61issue
2eissn
1172-7047issn
1179-1934journal_volume
24pub_type
杂志文章,评审相关文献
CNS DRUGS文献大全abstract::L-Dopa-induced dyskinesias (LID) are the most common adverse effects of long-term dopaminergic therapy in Parkinson's disease (PD). However, the exact mechanisms underlying dyskinesia are still unclear. For a long time, nigrostriatal degeneration and pulsatile stimulation of striatal postsynaptic receptors have been h...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-014-0205-z
更新日期:2014-12-01 00:00:00
abstract::Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone. The epilepsy syndromes at high risk of this are a disparate group of condition...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-013-0041-6
更新日期:2013-03-01 00:00:00
abstract::Given the high heritability of the disorder, attention-deficit hyperactivity disorder (ADHD) is common among parents of children with ADHD. Parental ADHD is associated with maladaptive parenting, negative parent-child interaction patterns and a diminished response to behavioural parent training. We describe our previo...
journal_title:CNS drugs
pub_type: 杂志文章
doi:10.2165/11633910-000000000-00000
更新日期:2012-09-01 00:00:00
abstract:OBJECTIVE:To determine the efficacy and tolerability of zolmitriptan 2.5 mg oral tablet as an acute treatment for menstrual migraine attacks. METHODS:This was a two-phase, multicentre, randomised, double-blind, placebo-controlled, parallel-group outpatient study (Phase I is reported here). The study was conducted at 2...
journal_title:CNS drugs
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/00023210-200620120-00005
更新日期:2006-01-01 00:00:00
abstract::Alzheimer's disease affects nearly 5 million Americans currently and, as a result of the baby boomer cohort, is predicted to affect 14 million Americans and 22 million persons totally worldwide in just a few decades. Alzheimer's disease is present in nearly half of individuals aged 85 years. The main symptom of Alzhei...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/00023210-200317090-00004
更新日期:2003-01-01 00:00:00
abstract::Glutamatergic, noradrenergic, serotonergic, and cholinergic systems play a critical role in the basal ganglia circuitry. Targeting these non-dopaminergic receptors remains a focus of ongoing research to improve Parkinson's disease (PD) motor symptoms, without the potential side effects of dopamine replacement therapy....
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-020-00754-0
更新日期:2020-10-01 00:00:00
abstract::Electroconvulsive therapy (ECT) is used in the treatment of severe psychiatric disorders. It involves the induction of a seizure for therapeutic purposes by the administration of a variable-frequency electrical stimulus via electrodes applied to the scalp. The original application of ECT in non-anaesthetised patients ...
journal_title:CNS drugs
pub_type: 指南,杂志文章,实务指引,评审
doi:10.2165/00023210-200519090-00002
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Thrombolytic therapy reduces stroke size and disability by reperfusion and salvage of ischaemic penumbra. Emerging evidence suggests that retrieved penumbra may be the site of ongoing inflammatory pathology that includes extensive microglial activation. Microglial activation may be associated with excessive ...
journal_title:CNS drugs
pub_type: 杂志文章
doi:10.2165/11588400-000000000-00000
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:No head-to-head clinical trials have been published comparing guanfacine extended release (GXR) and atomoxetine (ATX): two nonstimulants approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, other study designs or methods could be used to indirectly compare these two medicat...
journal_title:CNS drugs
pub_type: 杂志文章
doi:10.1007/s40263-013-0102-x
更新日期:2013-11-01 00:00:00
abstract::Teriflunomide is a once-daily oral agent that has been licensed in the EU since August 2013 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). More recently (September 2014), the EU summary of product characteristics (SmPC) was updated to include data from patients with a first cli...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-015-0299-y
更新日期:2016-01-01 00:00:00
abstract::Female hypoactive sexual desire disorder (HSDD) may occur in up to one-third of adult women in the US. The essential feature of female HSDD is a deficiency or absence of sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty. The evaluation of female HSDD generally requ...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/00023210-200216110-00003
更新日期:2002-01-01 00:00:00
abstract::Benzodiazepine hypnotic agents were the mainstream pharmacotherapy for insomnia from the 1960s to the 1980s, but their safety profile proved to be not quite as perfect as originally expected with regard to daytime performance and cognition, and above all the risk of dependence. These risks are substantially diminished...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/00023210-200418001-00005
更新日期:2004-01-01 00:00:00
abstract::The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative lysosomal storage disorders caused by mutations in at least 13 different genes and primarily affect the brain and the retina of children or young adults. The disorders are characterized by progressive neurological deterioration with dementia, epi...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-019-00620-8
更新日期:2019-04-01 00:00:00
abstract::Despite the established efficacy of chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies, translating CAR T therapy to solid tumors has remained investigational. Glioblastoma, the most aggressive and lethal form of primary brain tumor, has recently been among the malignancies being trialed clinic...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-019-00687-3
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:When otherwise unexplained, syncope in patients with Alzheimer's disease may be attributed to bradycardia caused by cholinesterase inhibitors. We studied prospectively the clinical events and cardiovascular changes occurring during treatment with donepezil in patients with Alzheimer's disease. METHODS:Conse...
journal_title:CNS drugs
pub_type: 临床试验,杂志文章
doi:10.2165/00023210-200620050-00005
更新日期:2006-01-01 00:00:00
abstract::Ursolic acid is a pentacyclic triterpenoid found in several plants. Despite its initial use as a pharmacologically inactive emulsifier in pharmaceutical, cosmetic and food industries, several biological activities have been reported for this compound so far, including anti-tumoural, anti-diabetic, cardioprotective and...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-017-0474-4
更新日期:2017-12-01 00:00:00
abstract::In this article, we review the evidence that tocopherol (vitamin E) may have a role to play in the prevention and treatment of Alzheimer's disease and other neurological diseases. The theoretical rationale for the effectiveness of tocopherol as treatment and/or prevention of Alzheimer's disease is based on its antioxi...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/00023210-200418120-00005
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVE:To assess the relationship between the sustained pain free (SPF) and adverse event (AE) rates associated with six oral serotonin 5-HT(1B/1D) receptor agonists (triptans) used for the treatment of acute migraine, employing data from a previous meta-analysis (that included almotriptan, eletriptan, naratriptan, ...
journal_title:CNS drugs
pub_type: 杂志文章
doi:10.2165/00023210-200721010-00006
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Earlier commencement of clozapine has been related to a better response in treatment-resistant schizophrenia. OBJECTIVES:To identify variables that predict clozapine use after a first episode of schizophrenia (FES). METHODS:Patients with FES and ≤15 days of lifetime antipsychotic treatment were followed up...
journal_title:CNS drugs
pub_type: 杂志文章
doi:10.1007/s40263-016-0358-z
更新日期:2016-10-01 00:00:00
abstract::Major depressive disorder (MDD) is a chronic, recurrent mental disease that causes serious disability. Because currently available antidepressants have limited efficacy with respect to response and remission in patients with MDD, clinicians must choose the best available treatment interventions for patients who do not...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-012-0032-z
更新日期:2013-05-01 00:00:00
abstract::Varenicline (Chantix, Champix) is an orally administered alpha4beta2 nicotinic acetylcholine receptor partial agonist that is indicated as an aid to smoking cessation. Varenicline was an effective aid to smoking cessation and was generally well tolerated in clinical trials, although more data are needed regarding the ...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/11204710-000000000-00000
更新日期:2010-09-01 00:00:00
abstract::Postherpetic neuralgia, which occurs most typically in older persons, is one of the most common and serious complications of herpes zoster (or shingles). It is a chronic neuropathic pain syndrome and remains one of the most difficult pain disorders to treat. Known beneficial agents include antidepressants, antiepilept...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/00023210-200317110-00001
更新日期:2003-01-01 00:00:00
abstract::Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symp...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/00023210-200216030-00006
更新日期:2002-01-01 00:00:00
abstract::NEDA was evaluated as the proportion of patients free of relapses, 3-month confirmed disability progression, and free of new or newly enlarging T2 lesion and Gadolinium enhancing lesions. ...
journal_title:CNS drugs
pub_type: 已发布勘误
doi:10.1007/s40263-018-0595-4
更新日期:2019-01-01 00:00:00
abstract::Premature mortality due to cardiovascular disease in those with schizophrenia is the largest lifespan disparity in the US and is growing; adults in the US with schizophrenia die, on average, 28 years earlier than those in the general population. The rate of smoking prevalence among individuals with schizophrenia is es...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-017-0438-8
更新日期:2017-06-01 00:00:00
abstract::Clinically relevant movement disorders are identified in 3% of patients with HIV infection seen at tertiary referral centres. In the same setting, prospective follow-up shows that 50% of patients with AIDS develop tremor, parkinsonism or other extrapyramidal features. Hemiballism-hemichorea and tremor are the most com...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.2165/00023210-200216100-00002
更新日期:2002-01-01 00:00:00
abstract::The development of an intervention to slow or halt disease progression remains the greatest unmet therapeutic need in Parkinson's disease. Given the number of failures of various novel interventions in disease-modifying clinical trials in combination with the ever-increasing costs and lengthy processes for drug develo...
journal_title:CNS drugs
pub_type: 杂志文章,评审
doi:10.1007/s40263-018-0548-y
更新日期:2018-08-01 00:00:00
abstract::The original article can be found online. ...
journal_title:CNS drugs
pub_type: 杂志文章,已发布勘误
doi:10.1007/s40263-018-0561-1
更新日期:2018-09-01 00:00:00
abstract:SYNOPSIS:Mirtazapine is a tetracyclic antidepressant with a novel mechanism of action; it increases noradrenergic and serotonergic neurotransmission via blockade of central α2-adrenergic auto- and heteroreceptors. The increased release of serotonin (5-hydroxytryptamine; 5-HT) stimulates serotonin 5-HT1 receptors becaus...
journal_title:CNS drugs
pub_type: 杂志文章
doi:10.2165/00023210-199605050-00007
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND:Few studies examine predictors of seizures in medically treated patients with epilepsy receiving antiepileptic monotherapy using a large patient population. OBJECTIVE:Our objective was to identify clinical, medication, and demographic factors associated with seizure recurrence in medically treated patients ...
journal_title:CNS drugs
pub_type: 杂志文章
doi:10.1007/s40263-014-0191-1
更新日期:2014-11-01 00:00:00