Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gabapentin (Neurontin) has been successfully used in the treatment of both epilepsy and neuropathic pain. Despite its widespread clinical use, its mechanism of action is very poorly understood. Indeed, the only protein it is known to interact with is the alpha2delta subunit of the voltage-gated Ca(2+) channel complex. In a recent article, gabapentin was reported to inhibit synaptic transmission in the spinal cord through an inhibitory effect on presynaptic P/Q-type Ca(2+) channels in both glutamatergic primary afferents and glycinergic interneuones. To examine if such inhibition of P/Q-channel-mediated synaptic transmission by gabapentin generalised to other synaptic pathways, we tested the actions of gabapentin of P/Q-type Ca(2+) channel-mediated synaptic responses in the CA1 subfield of the hippocampus. We found that gabapentin was completely inactive on such synaptic responses even at 10 times the maximally effective concentration used in the spinal cord. A small ( approximately 10%) but consistent depression of control synaptic responses was elicited by 10 microM gabapentin. No greater response was observed at a 10 times higher concentration. From these data we conclude that gabapentin is not a generic inhibitor of presynaptic P/Q-type channels and its actions at the spinal level must represent a feature of the P/Q-type channel not present in the hippocampus. Given the known interactions of this compound, the best candidate for this is the presence, subtype, or state of the alpha2delta subunit.
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PMID:Gabapentin fails to alter P/Q-type Ca2+ channel-mediated synaptic transmission in the hippocampus in vitro. 1566 86

Twenty-four adults with phantom limb pain (PLP) and/or residual limb pain (RLP) participated in a double-blind crossover trial. Participants were randomly assigned to receive gabapentin or placebo and later crossed over to the other treatment, with a 5-week washout interval in which they did not receive medication. Gabapentin was titrated from 300 mg to the maximum dose of 3,600 mg. Measures of pain intensity, pain interference, depression, life satisfaction, and functioning were collected throughout the study. Analyses revealed no significant group differences in pre- to posttreatment change scores on any of the outcome measures. More than half of the participants reported a meaningful decrease in pain during the gabapentin phase compared with about one-fifth who reported a meaningful decrease in pain during the placebo phase. In this trial, gabapentin did not substantially affect pain. More research on the efficacy of gabapentin to treat chronic PLP and RLP is needed.
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PMID:Efficacy of gabapentin in treating chronic phantom limb and residual limb pain. 1658 90

Using a large US health insurance claims database, we identified all persons aged > or =18 years with > or =2 medical encounters with diagnoses of cancer and > or =2 medical encounters with diagnoses of painful neuropathies in calendar year (CY) 2000; persons with seizure disorders or depression were excluded. We then examined the use of antiepileptics (AEDs), tricyclic antidepressants (TCAs) and other pain-related pharmacotherapy among these selected persons, as proxied by pharmacy dispenses. A total of 956 persons were identified who met all entry criteria; 17% received AEDs in CY2000 and 14% received TCAs. Gabapentin was the most widely used AED (92% of all AED patients); amitriptyline was the most widely used TCA (79% of all TCA patients). Patients who received AEDs and/or TCAs were similar in age, gender and the presence of metastases to those who had not received these medications; they were more likely to have received other pain-related therapies, however, including short-acting opioids (73% vs. 53%; P < 0.01) and long-acting opioids (23% vs. 8%; P < 0.01). Use of AEDs and TCAs appears to be relatively low among cancer patients with painful neuropathies. Further research is needed to better understand reasons for this finding, as well as its potential implications for pain management in this patient population.
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PMID:Use of antiepileptics and tricyclic antidepressants in cancer patients with neuropathic pain. 1664 61

Ten newer antiepileptic drugs have been developed since 1990s. These drugs have wider therapeutic spectra, fewer side-effects, and lesser drug-to-drug interactions compared with the older typical antiepileptic drugs. Among them, zonisamide was developed in Japan and has been used from 1989. Gabapentin was at length approved in 2006. The other newer antiepileptic drugs are not approved yet in Japan. Felbamate can not be used in Europe because it may induce lethal hepatic toxicity and aplastic anemia. Vigabatrin is not approved in USA because it may induce permanent visual field deficit. The USA guideline for epilepsy treatment recommends that patients with newly diagnosed epilepsy can be treated with gabapentin, lamotrigine, topiramate, and oxcarbazepine. In contrast, based on epilepsy treatment guideline in England, newer antiepileptic drugs are considered only when patients with newly diagnosed epilepsy are unable to use the older antiepileptic drugs for some reasons. All newer antiepileptic drugs are used for intractable partial epilepsies, and lamotrigine and topiramate can also be used for idiopathic generalized epilepsies. The response rate (seizure reduction rate with 50% or more) and drop-out rate are overlapping among all newer antiepileptic drugs. Gabapentin, levetiracetam, and pregabalin are eliminated from kidney, and they had no drug-to-drug interactions and can be titrated rapidly. The serum concentration of lamotrigine is decreased with co-administration of hepatic enzyme inducing drugs and is increased with co-administration of valproic acid. Hypersensitivity reactions are rare with gavapentin, levetiracetam, topiramate, and tiagabin. Psychoses are reported to be induced with zonisamide, however, they can be induced with the other newer drugs (topiramate, levetiracetam, etc.). Drug-induced psychiatric symptoms, especially depression, may be often underdiagnosed. Many of these newer drugs (gabapentine, lamotrigine, levetiracetam, oxycarbazepine, etc.) have effects on chronic neuropathic pain. Some newer drugs show mood stabilizing effects (lamotrigine, oxycarbazepine, etc.), or antianxiety effect (gabapentin, topiramate, levetiracetam, pregavalin, etc.). Wide range of action to central nervous system of these newer antiepileptic drugs may serve not only for clinical seizure suppression, but also for neuroprotection.
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PMID:[Newer antiepileptic drugs]. 1731 56

Ten newer antiepileptic drugs have been developed since 1990s. These drugs have wider therapeutic spectra, fewer side-effects, and lesser drug-to-drug interactions compared with the older typical antiepileptic drugs. Among them, zonisamide was developed in Japan and has been used from 1989. Gabapentin was at length approved in 2006. The other newer antiepileptic drugs are not approved yet in Japan. Felbamate can not be used in Europe because it may induce lethal hepatic toxicity and aplastic anemia. Vigabatrin is not approved in USA because it may induce permanent visual field deficit. The USA guideline for epilepsy treatment recommends that patients with newly diagnosed epilepsy can be treated with gabapentin, lamotrigine, topiramate, and oxcarbazepine. In contrast, based on epilepsy treatment guideline in England, newer antiepileptic drugs are considered only when patients with newly diagnosed epilepsy are unable to use the older antiepileptic drugs for some reasons. All newer antiepileptic drugs are used for intractable partial epilepsies, and lamotrigine and topiramate can also be used for idiopathic generalized epilepsies. The response rate (seizure reduction rate with 50% or more) and dropout rate are overlapping among all newer antiepileptic drugs. Gabapentin, levetiracetam, and pregabalin are eliminated from kidney, and they had no drug-to-drug interactions and can be titrated rapidly. The serum concentration of lamotrigine is decreased with co-administration of hepatic enzyme inducing drugs and is increased with co-administration of valproic acid. Hypersensitivity reactions are rare with gavapentin, levetiracetam, topiramate, and tiagabin. Psychoses are reported to be induced with zonisamide, however, they can be induced with the other newer drugs (topiramate, levetiracetam, etc.). Drug-induced psychiatric symptoms, especially depression, may be often underdiagnosed. Many of these newer drugs (gabapentine, lamotrigine, levetiracetam, oxycarbazepine, etc.) have effects on chronic neuropathic pain. Some newer drugs show mood stabilizing effects (lamotrigine, oxycarbazepine, etc.), or antianxiety effect (gabapentin, topiramate, levetiracetam, pregavalin, etc.). Wide range of action to central nervous system of these newer antiepileptic drugs may serve not only for clinical seizure suppression, but also for neuroprotection.
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PMID:[Newer antiepileptic drugs]. 1738 Jul 79

Anticonvulsants are showing to be helpful in the treatment of Borderline Personality Disorder and are widely used in clinical settings, although few studies have been published and their role in different borderline patients is not completely outlined. Gabapentin pharmacologic profile and its documented efficacy in anxiety disorders and drug abuse withdrawal were the basis for this open label multicenter six-month follow-up trial in borderline patients not enough responsive to previous therapies. DSM-IV Borderline Personality diagnosis was confirmed by the Diagnostic Interview for Borderlines-Revised. Outcome measures were changes in scores on Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Beck Depression Inventory, Barratt Impulsivity Scale and Clinical Global Impression Scale of Severity and Improvement. A global improvement, especially in anxious and depressive symptomatology, was observed; no adverse events were reported. Gabapentin showed to be efficacious and safe in Borderline Personality Disorder's treatment.
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PMID:[Efficacy and safety of gabapentin in Borderline Personality Disorder: a six-month, open-label study]. 1827 30

The treatment of dysphoric mania is challenging given the need to treat symptoms of both depression and mania simultaneously without provoking any clinical exacerbation. The newer antiepileptic drugs such as gabapentin, lamotrogine, and carbamazepine are often used as adjuncts to either lithium or valproic acid in the treatment of bipolar disorder. We decided to undertake a monotherapy trial because previous evidence suggested mixed states may be more responsive to anticonvulsants than more traditional antimanic agents. 51 patients with a DSM IV diagnosis of dysphoric mania were randomized to three groups comprising gapbapentin, lamotrogine or carbamazepine and followed for 8 weeks. Psychiatric diagnosis was verified by the structural clinical interview for the DSM-IV (SCID). The MMPI-2 in full was used to assess symptoms at baseline and 8 weeks. All three groups showed significant changes in MMPI-2 scores for depression and mania subscales. Gabapentin showed the greatest change in depression symptom improvement relative to lamotrogine and carbamazepine, respectively. Although manic symptoms improved overall, here were no differences between groups in the degree of manic symptom improvement.
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PMID:Anticonvulsant treatments of dysphoric mania: a trial of gabapentin, lamotrigine and carbamazepine in Iran. 1872 2

Cognitive deficits, including memory deficiencies, are currently deemed one of key symptoms of psychopathologic mental disorders or epilepsy. The impairment of neurocognitive processes could be due to the administered therapy, in particular combined therapy or therapy using antiepileptics of older type. Gabapentin (GBP) is one of new antiepileptics with normothymic properties. It is known that epileptic patients run a significant risk of developing depression and mood changes. Smoking may also have a negative effect on memory processes and efficacy of administered drugs. Note that smoking in pregnant women also leads to neurobehavioral changes in their children. The objective of our research was to evaluate the effect of GBP on memory functions and antidepressant effect in rats not exposed and exposed to tobacco smoke in fetal life. We were also intent on finding whether GBP has an anticonvulsant effect in contact and without contact with tobacco smoke, and whether it affects motor coordination in animals if administered in the dose of 25 mg/kg. Spatial memory of the animals was assessed in the Morris test and the antidepressant effect in the Porsolt test. The ED(50) value was determined in the Swinyard maximum electric shock test, and the effect on motor coordination was assessed in the chimney test. GBP administered in the dose of 25 mg/kg intraperitoneal (i.p.) significantly reduced the immobility time on days 1 and 7 of the test in animals exposed to tobacco smoke, and on days 7 and 14 of the test in rats not exposed to tobacco smoke. Upon single and multiple administration of GBP to animals not exposed to tobacco smoke, the spatial memory improved, whereas in animals exposed to tobacco smoke in fetal life tolerance for procognitive effect was observed on day 21 of the test. It has been found that in rats not exposed to tobacco smoke, ED(50) of GBP was 28.73 mg/kg, whereas in animals exposed to tobacco smoke in fetal life, ED(50) was 46.2 mg/kg. Upon 14 and 21 days of drug administration, motor coordination was impaired in both GBP receiving animal groups. In conclusion, GBP beside its anticonvulsant efficacy also improves memory processes and has antidepressant effect. We also proved that GBP may reverse cognitive deficits concerning working memory induced by prenatal exposure to tobacco smoke and may have antidepressant effect in rats exposed to tobacco smoke.
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PMID:Effect of gabapentin on cognitive processes in rats not exposed and exposed to tobacco smoke during fetal life. 1927 43

Gabapentin (Neurontin) is approved by the US Food and Drug Administration for treatment of epilepsy and post-herpetic neuralgia. Despite lack of strong evidence, gabapentin is also often prescribed off-label for psychiatric conditions. The case described here involved a 38-year-old male physician with substance intoxication delirium and psychoactive substance dependence due to high self-administered doses of gabapentin, which had been prescribed at lower doses in combination with buspirone and bupropion for depression and anxiety. This unusual case of gabapentin dependence and abuse involved toxic delirium, intense cravings, and a prolonged post-withdrawal confusional state reminiscent of benzodiazepine withdrawal. Gabapentin is a central nervous system inhibitory agent with likely gamma-aminobutyric acid (GABA)-ergic and non-GABAergic mechanisms of action. The similarity between benzodiazepine withdrawal and what this patient experienced with gabapentin suggests a common role for GABA-related effects. The case reported here suggests the need for heightened concern regarding the off-label prescription of this drug to vulnerable individuals with psychiatric conditions.
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PMID:Gabapentin-induced delirium and dependence. 1962 87

Benign, self-limited hiccups are more of a nuisance, but persistent and intractable hiccups lasting more than 48 hours and 1 month, respectively, are a source of significant morbidity in the patient with advanced malignancy.The hiccup reflex is complex, but stimulation of vagal afferents followed by activation of efferent phrenic and intercostal nerve pathways results in contraction of the diaphragm and intercostal muscles, respectively.The etiology of hiccups in the cancer and palliative care population may include chemotherapy, electrolyte derangements, esophagitis, and neoplastic involvement of the central nervous system (CNS), thorax, and abdominal cavity. Prolonged hiccups can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration syndromes. Evaluation should be symptom-directed, focusing mainly upon the CNS and thoracoabdominal cavities as well as assessment of medications and serum chemistries. Most patients with ongoing hiccups require pharmacotherapy, with chlorpromazine being the only US Food and Drug Administration-approved agent. However, numerous other medications have been reported to be efficacious for treating intractable hiccups. Gabapentin has recently been shown to terminate hiccups effecitvely in cancer patients and may emerge as a therapy of choice in the palliative setting due to favorable tolerability, pain-modulating effects, minimal adverse events, and lack of drug interactions.
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PMID:Diagnosis and management of hiccups in the patient with advanced cancer. 1973 77


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