Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suicidal patients often report problems with their sleep. Although sleep-related complaints and EEG (electroencephalographic) changes have been seen widely across the spectrum of psychiatric disorders, sleep complaints such as insomnia, hypersomnia, nightmares, and sleep panic attacks are more common in suicidal patients. The subjective quality of sleep as measured by self-rated questionnaires also appears to be more disturbed in suicidal depressive patients. Sleep studies have reported various polysomnographic findings including increased REM (rapid eye movement) time and REM activity in suicidal patients with depression, schizoaffective disorder, and schizophrenia. One mechanism responsible for this possible association between suicide and sleep could be the role of serotonin (5HT). Serotonergic function has been found to be low in patients who attempted and/or completed suicide, particularly those who used violent methods. Aggression dyscontrol appears to be an intervening factor between serotonin and suicide. Additionally, agents that enhance serotonergic transmission decrease suicidal behavior. Serotonin has also been documented to play an important role in onset and maintenance of slow wave sleep and in REM sleep. CSF 5-HIAA levels have been correlated with slow wave sleep in patients with depression as well as schizophrenia. Moreover, 5HT2 receptor antagonists have improved slow wave sleep. Further studies are needed to investigate the possible role of sleep disturbance in suicidal behavior.
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PMID:Sleep and suicide in psychiatric patients. 1153 31

Mirtazapine is an antidepressant that has a receptor-binding profile that may suit it for use in controlling the nausea and insomnia of highly emetic cancer chemotherapy. Mirtazapine binds to and is antagonistic at the 5HT3 receptor, as are the group of medicines related to ondansetron. Mirtazapine is anxiolytic by virtue of its antagonism of the 5HT2 receptor, and is strongly sleep inducing. The resulting sleep quality tends to be superior to that induced by benzodiazapines. There has been concern about mirtazapine's potential to suppress bone marrow function, so that further study is required before routine use in chemotherapy can be adopted.
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PMID:Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy. 1158 76

There is extensive evidence to implicate dysregulation of noradrenergic, serotonergic, and dopaminergic neurotransmission in the pathophysiology of mood disorders. The receptor profile for risperidone, an atypical antipsychotic with demonstrated efficacy in schizophrenia, is consistent with possible antidepressant activity. Specifically, risperidone is a potent antagonist of central 5-HT2A receptors, addressing symptoms such as insomnia, agitation, and weight loss and may indirectly enhance 5-HT1A-mediated neurotransmission. A search of the worldwide medical literature published through December 2000 revealed 24 publications pertinent to the clinical use of risperidone in the treatment of patients with depressive symptomatology. In schizophrenia, in which depression is a common comorbid condition, the results of eight randomized, blinded, and controlled trials consistently demonstrated that treatment with risperidone significantly reduced scores on various measures of depressive symptoms. Moreover, these effects were distinct from improvements in negative and positive symptoms. Antidepressant effects also were observed in two large meta-analyses of trials in patients with schizophrenia or schizoaffective disorder. Observations from uncontrolled studies and case reports of risperidone therapy of other psychiatric disorders were similarly suggestive of antidepressant activity. Collectively, the evidence we present in this review indicates that risperidone's therapeutic benefits in psychiatric medicine extend beyond potent and effective antipsychotic activity and may include effectiveness in treating depression and related affective disorders. Systematic studies are now needed to evaluate the utility of concomitant therapy with an atypical antipsychotic in psychotic, bipolar, and treatment-resistant depressive syndromes.
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PMID:Risperidone: review of its therapeutic utility in depression. 1239 61

Depression is a frequent symptom in psychiatry, either isolated (major depression) or entangled with other psychiatric symptoms (psychotic depression, depression of bipolar disorders). Many antidepressant drugs are available with different pharmacological profiles from different classes: tricyclic antidepressants, monoamine oxydase inhibitors, selective serotonin reuptake inhibitors (SSRI). However, there are some limitations with these drugs because there is a long delay before relief for symptoms, some patients with major depression are resistant to treatment, there is a risk to induce manic symptoms in patients with bipolar disorders and these drugs have no effect on the psychotic symptoms frequently associated to major depression. The leading hypothesis for the search of more efficient new antidepressants has been the amine deficit hypothesis: noradrenaline and/or serotonin deficit and more recently dopamine deficit. Moreover, a dopamine deficit has been also hypothesized as the central mechanism explaining the negative symptoms of schizophrenia. These symptoms are the consequence of a deficit of normal behaviours and include affective flattening, alogia, apathy, avolition and social withdrawal. There is thus a great overlap between symptoms of depression and negative symptoms of schizophrenia. Atypical antipsychotics, in contrast with conventional neuroleptics, have been shown to decrease negative symptoms, most probably through the release of dopamine in prefrontal cortex, thus improving psychomotor activity, motivation, pleasure, appetite, etc. The dopamine deficit in cortical prefrontal areas was thus an unifying hypothesis to explain both some symptoms of depression and negative symptoms of schizophrenia. Studies in animal confirm this view and show that the association of an atypical antipsychotic drug and an SSRI (olanzapine plus fluoxetine) increases synergistically the release of dopamine in prefrontal areas. Moreover, most of the atypical antipsychotics have a large action spectrum, beyond the only dopamine receptors: their effects on the serotonin receptors--particularly the 5-HT2A and 5-HT2C receptors--suggest that their association to SSRI could be a promising treatment for depression. Indeed, SSRI act mainly by increasing the serotonin level in the synapse, thus leading to a non specific activation of all pre- and post-synaptic serotonin receptors. Among them, 5-HT2A/2C receptors have been involved in some of the unwanted effects of SSRI: agitation, anxiety, insomnia, sexual disorders, etc. The inhibition of these receptors could be thus beneficial for patients treated with SSRI. Amisulpride is an unique atypical antipsychotic that selectively blocks dopamine receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission. The antidepressant effect of amisulpride was shown in dysthymia in many clinical studies versus placebo, tricyclic antidepressants, SSRI or others. However, a shorter delay for symptom relief was not demonstrated for amisulpride as compared to comparative antidepressants. Other atypical antipsychotics (clozapine, olanzapine), which act on a large variety of receptors, have shown antidepressant effects--mainly in association with SSRI--in different psychiatric diseases: treatment-resistant major depression, major depression with psychotic symptoms and depression of bipolar disorders, with no increase of manic symptoms in this latter case. Moreover, the delay for symptom relief was greatly shortened. More comparative double-blind studies are required to confirm and to precise the antidepressant effects of atypical antipsychotics. Nevertheless, these studies suggest that atypical anti-psychotics could be of great value in depressive conditions reputed for their resistance to treatment with usual antidepressants. Particularly, new strategies emerge that combine atypical antipsychotics and antidepressants for greater efficacy and more rapid relief of depression symptoms.
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PMID:[Efficacy of atypical antipsychotics in depressive syndromes]. 1573 62

Incorporation of fluorine at the 4-position of an existing series of sulfonyl piperidine 5-HT2A antagonists gave compounds with increased selectivity over the IKr potassium channel. This work led to the identification of 3b, a compound that gave no increase in QTc in the anesthetized dog up to plasma levels as high as 148 microM. Furthermore, 3b has been shown to increase slow-wave sleep bout duration and to decrease the number of awakenings in rats, indicating the potential utility of 5-HT2A antagonists in the treatment of insomnia.
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PMID:4-Fluorosulfonylpiperidines: selective 5-HT2A ligands for the treatment of insomnia. 1599 98

There are three different approaches in the pharmacological treatment of posttraumatic stress disorder (PTSD) in the published data. The most frequently implemented approach is to treat patients suffering from the diagnosis of PTSD. Both short-term acute and long-term relapse prevention treatments represent a curative paradigm: with an intention to diminish the symptoms associated with the disorder. Data about efficacy of monoamine oxidase inhibitors and selective serotonin reuptake inhibitors (SSRIs) in the treatment of PTSD are heterogeneous. Data are relatively consistent with regards of efficacy of SSRIs in the treatment of civilian, predominantly female population, regardless of the type of trauma: interpersonal or non-interpersonal trauma. Placebo controlled trial data in the treatment of combat-related PTSD are inconclusive or negative. Three recently published studies provide new approaches to the treatment of male patients, suffering from combat-related PTSD. A relatively young, recently traumatized male, combat-related population showed significant improvement for fluoxetine compared to placebo. An adjuvant 5HT2 antagonist profile may improve the SSRI effect in the treatment of PTSD: nefazodone was significantly superior compared to placebo in the treatment of combat-related PTSD, and risperidone treatment add-on to antidepressants showed significant benefits compared to antidepressant monotherapy in the treatment of combat-related PTSD. The goal of sedative paradigm is to minimize the immediate consequences of the traumatic stress, decrease the fear, anxiety and sleeplessness. Data published about benzodiazepines failed to show effectiveness in the acute management of post-traumatic mental consequences. The intention of the third treatment paradigm is characterized by the secondary prevention of PTSD. Benzodiazepines administered shortly after the traumatic event, failed to prevent the mental consequences of traumatic stress. Two small trials with propranolol administration after the trauma have been shown some benefits compared to placebo or no treatment. PTSD represents a complex disregulation of numerous neurotransmitters and neuromodulators, therefore the complex pharmacological treatment has to consider approaches beyond the current treatment regimens characterized by modulation of monoamine neurotransmission.
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PMID:[Three paradigms in the treatment of posttraumatic stress disorder]. 1616 63

ACADIA Pharmaceuticals is developing ACP-103, lead compound in a series of 5-HT2A inverse agonists, as a potential antipsychotic agent and for the potential treatment of insomnia. Phase II clinical trials in treatment-induced psychosis in Parkinson's disease (PD) patients and in schizophrenic patients are ongoing, as are phase II trials evaluating the effects of the drug on PD symptoms and dyskinesias.
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PMID:ACP-103, a 5-HT2A receptor inverse agonist. 1686 20

A variety of molecules with novel mechanisms of action are currently being evaluated for their potential as treatments for sleep disorders. The GABA-A receptor complex remains an important target for hypnotic drugs (eg gaboxadol, indiplon). However, drugs acting through histamine, calcium channels and serotonin receptors may also be of interest for the treatment of insomnia. In the case of the 5HT2A subtype of serotonin receptors, several molecules which improve sleep maintenance and modify sleep architecture by increasing slow wave sleep are currently being tested (eg eplivanserin). Two new drugs with efficacy in excessive sleepiness (modafinil, sodium oxybate) have improved the treatment of this condition. However, the mechanisms of action of these agents are poorly understood. The recent discovery of the hypocretin arousal system in the hypothalamus may aid the identification of additional new drugs. An agonist at receptors for the pineal hormone melatonin is available in some countries (ramelteon) but is currently used only for the treatment of insomnia associated with difficulties of sleep onset. Additional melatonin receptor agonists are being developed and may have potential for treating several conditions including circadian rhythm disorders and depression.
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PMID:New perspectives for the treatment of disorders of sleep and arousal. 1765 96

Insomnia is a disorder that affects a large part of the population. Agents that are used to treat this sleep disorder have evolved: benzodiazepines replaced barbiturates, but there is still concern about their residual effects and about the development of dependence and the risk of withdrawal symptoms. Currently the benzodiazepines receptor agonists (zolpidem, zaleplon, zopiclone and eszopiclone) are the agents most widely prescribed. Pharmaceutical technology and the advances in the knowledge of sleep physiology have led to the availability of some novelties like modified release zolpidem (indicated not only to initiate but also to maintain sleep., ramelteon and agomelatine (melatonine receptors agonists). This article summarises these subjects as well as the pharmacology of investigational drugs, such as indiplon (another benzodiazepine receptor agonist), gaboxadol ( a selective extrasynaptic GABAA agonist -SEGA-), and some anticonvulsant drugs that could be useful as hypnotics: tiagabine ( a GABA transporter inhibitor), pregabaline and gabapentine (GABA analogs). The possible usefulness of 5-HT2A/2C antagonists is also addressed.
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PMID:[New hypnotics: perspectives from sleep physiology]. 1826 73

The popularity of antidepressants in the treatment of insomnia is not supported by a large amount of convincing data, but rather by opinions and beliefs of the prescribing physicians on the advantages of these agents compared with drugs acting on the benzodiazepine receptor or other drugs used for the treatment of insomnia. The existing data do not allow for clear-cut, evidence-based recommendations concerning the use of antidepressants in insomnia. Our conclusions result from a few short-term studies on single agents, clinical experience and inferences from knowledge on the effect of antidepressants in other indications. At present, prescribing antidepressants for short-term treatment of insomnia can be useful if there is some amount of concomitant depressive symptomology or a history of depression, raising the impression that the present insomnia may be a prodromal sign for a new depressive episode. In all other cases, benzodiazepine receptor agonists, especially the nonbenzodiazepines among them (the so-called 'z drugs') should be the drugs of choice. For long-term treatment, antidepressants are among the pharmacological options, in addition to other groups of psychotropics. Off-label use of antidepressants may be considered for chronic insomnia if there is a concomitant depressive symptomalogy (which is not so pronounced that an antidepressant treatment with adequate higher doses would be required) and if there is no specific indication for one of the other groups of psychotropics (e.g. dementia-related nocturnal agitation, in which case an antipsychotic would be preferred, or circadian problems, in which case melatonin or a melatonin agonist would be favoured). If antidepressants are used to treat insomnia, sedating ones should be preferred over activating agents such as serotonin reuptake inhibitors. In general, drugs lacking strong cholinergic activity should be preferred. Drugs blocking serotonin 5-HT2A or 5-HT2C receptors should be preferred over those whose sedative property is caused by histamine receptor blockade only. The dose should be as low as possible (e.g. as an initial dose: doxepin 25 mg, mirtazapine 15 mg, trazodone 50 mg, trimipramine 25 mg). Regarding the lack of substantial data allowing for evidence-based recommendations, we are facing a clear need for well designed, long-term, comparative studies to further define the role of antidepressants versus other agents in the management of insomnia.
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PMID:Antidepressants for the treatment of insomnia : a suitable approach? 1901 70


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