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)

The aim of prophylactic treatment of migraine is to reduce the frequency and severity of migraine attacks. Identifying relevant trigger factors can help reduce the frequency of migraine attacks. The headache diary is useful to identify trigger factors and pattern of headaches and to assess the efficacy of medication. Prophylactic drugs should be considered when attacks are frequent or severe and the acute treatments such as triptans or NSAIDs are not effective. Lomerizine, propranolol, valproate and amitriptyline are useful. Lomerizine is recommended as the first-line prophylactic drug because it is licensed as a preventive drug for migraine in Japan. If attacks has not improved after using a prophylactic drug for 2 months, the drug can be changed to another drug. Propranolol is particularly useful if a patient has hypertension. Amitriptyline is useful if there is associated depression and/or tension-type headache. Valproate is considered if attacks are frequent. Patients should be informed benefits and potential side-effects of the medicine.
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PMID:[Prophylactic treatment of migraine]. 1621 95

Amitriptyline is a tricyclic antidepressant that is historically indicated and used to manage depression. More recently, due to clinical evidence demonstrating efficacy, it is often prescribed in the management of painful neuropathic disorders (PNDs). However, the amitriptyline label contains numerous preclusions (contraindications, warnings/precautions, drug interactions). Our objective was to measure the frequency of amitriptyline prescriptions in PND patients using the U.K. General Practice Research Database and assess whether any prescriptions were given to patients with preclusions listed in the product label. We identified a total of 13,546 patients (mean age 59 +/- 16.2 years; 66.7% female) who had a diagnosis of a PND and received > or =1 prescription for amitriptyline between July 1998 and June 2001. Nearly half (46.7%) of PND patients prescribed amitriptyline had > or =1 preclusion for its use; 3.5% had > or =1 contraindication; 22% had > or =1 warning/precaution; and 33% received > or =1 medication with a potential for drug interactions with amitriptyline. Preclusions were more likely in women than in men (48.3% vs. 43.4%, P < 0.0001); their incidence increased with age (42.8%, 50.4%, 55.1%, and 52.3% among those ages <65, 65-74, 75-84, and 85+ years, P < 0.0001), and the number of patients with preclusions was the highest in the phantom limb pain group (67.4%) and lowest in the atypical facial pain group (42.9%), P < 0.001. The average daily amitriptyline doses (starting: 33.6 +/- 32.4 mg; maintenance: 42.1 +/- 39.9 mg) were low compared to those used for the treatment of depression. Results indicate that, in a significant number of cases, the existence of preclusions did not prevent the prescribing of amitriptyline. Our findings raise a potential concern about the way this medication is being used. However, the clinical significance of these data is, as yet, unclear. Although, in theory, adverse outcomes may have been associated with this practice, we could not confirm this with this database analysis.
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PMID:Prevalence of contraindicated medical conditions and use of precluded medications in patients with painful neuropathic disorders prescribed amitriptyline. 1712 7

Amitriptyline is a tricyclic antidepressant widely used in the treatment of depression. Antidepressant drugs are among the most commonly encountered causes of self-poisoning, as illustrated by several published cases in the literature. This investigation reports a case of massive amitriptyline intoxication, involving a 44-year old female found dead in bed. The presence of this tricyclic antidepressant was revealed by a routine screening procedure. The concentration was calculated by gas chromatography/ electron ionization-mass spectrometry in the selected ion monitoring mode after solid-phase extraction using proadifen as internal standard and was in the post-mortem whole blood sample 85.9 mug/mL. This value was much higher than the reported toxic values ever found in the literature, and may therefore have caused the victim's death. Nortriptyline was also detected in the toxic concentration range, as well as therapeutic levels of diazepam and nor-diazepam. Taking into account both the available circumstantial information and toxicological results, it is very likely that death was caused by self-poisoning. Human & Experimental Toxicology (2007) 26, 667-670.
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PMID:Massive intoxication involving unusual high concentration of amitriptyline. 1788 55

Neuropathy is common in patients receiving vinca alkaloids, platinum derivatives, or taxanes. This double-blind, randomized, placebo-controlled study assessed the efficacy of low-dose amitriptyline to relieve chemotherapy-induced symptoms in 44 patients (age 20-65 years) who had neuropathic symptoms (numbness, tingling, pain) with a severity of > or =3/10. They were treated with amitriptyline for eight weeks (10mg/day to start, then dose elevation of 10mg/week up to 50mg/day if tolerated, followed by a stable dose > or =4 weeks). The patients completed a diary twice weekly, noting the intensity of pain, numbness and tingling, global improvement, and adverse effects. Neurological examination was performed at each visit (baseline, four, and eight weeks). The patients assessed both intensity and relief of pain, and overall discomfort. They also completed the Neuropathic Pain Scale and validated measures of anxiety and depression, and quality of life (QoL). The results demonstrated that amitriptyline did not improve sensory neuropathic symptoms, although there was a trend toward global improvement and improved QoL in favor of the amitriptyline group. No statistical significance was reached, probably due to the small number of patients and too low dose of amitriptyline. Amitriptyline was well tolerated.
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PMID:Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. 1798 May 50

The paper presents a study devoted to endogenous depression with a pronounced element of anxiety. The subjects, 66 patients, received antidepresive therapy with either amitriptyline or remeron. The study lasted 6 months, during which the symptoms were assessed using Hamilton Depression and Anxiety Scales. Three variants of anxious depressive conditions were revealed: anxious melancholic, anxious hypochondriac and anxious adynamic ones. Amitriptyline proved to be more efficient in treatment of patients with anxious melancholic depression. No difference in time to and the degree of symptom reduction was observed between amitriptyline and remeron in patients with anxious adynamic depression. Remeron proved to be more efficient in patients with anxious hypochondriac depression.
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PMID:[Differentiated approach to the therapy of endogenous anxious depression]. 1822 7

Migraine prophylaxis is a stepwise procedure with lifestyle advice followed by consideration of medications. Patients should be advised to try to maintain a regular lifestyle, with regular sleep, meals, exercise, and management of stress, perhaps through relaxation techniques or other ways that are sensible for them. If this regimen does not adequately control their migraines, preventatives are indicated. Patients can choose between evidence-based nutraceuticals such as riboflavin, feverfew, butterbur, or coenzyme Q10, or more traditional pharmacotherapeutics. Medicine choices are somewhat limited by what is available in each country, but from the full range, the medicines of first choice are beta-adrenoceptor blockers, flunarizine, topiramate, and valproic acid. Beta-adrenoceptor blockers are particularly useful in patients also suffering from hypertension or tachycardia. Following recent studies, topiramate has become a first choice for episodic as well as chronic migraine. It is the only prophylactic drug that may lead to weight loss, but it is sometimes associated with adverse cognitive effects. Valproic acid and flunarizine also have very good prophylactic properties. However, valproic acid is often associated with adverse effects, and flunarizine is unavailable in many countries, including the United States. If sequential monotherapies are ineffective, combinations of first-line drugs should be tried before advancing to drugs of second choice, which are associated with more adverse effects or have less well-established prophylactic properties. Amitriptyline should be used carefully because of its anticholinergic effects, although it is useful in comorbid tension-type headache, depression, and sleep disorders. Methysergide is very effective, but it has been supplanted or even made unavailable in many countries because of its well-described association with retroperitoneal fibrosis. Pizotifen has a slightly better safety profile but is unavailable in the United States. Aspirin is particularly useful in patients needing platelet inhibitors for other medical conditions, but the risk of gastrointestinal bleeding must be considered. The prophylactic properties of magnesium, riboflavin, and coenzyme Q10 are low at best, but their lack of severe adverse effects makes them good treatment options. Magnesium may be particularly useful during pregnancy. Lisinopril and candesartan were shown to be effective in single trials and are preferable in patients with hypertension. Acupuncture may be another alternative; although controlled trials have failed to differentiate its effect from placebo, it is at least innocuous. Botulinum toxin A is not effective in the prophylaxis of episodic migraine.
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PMID:Update on the prophylaxis of migraine. 1832 96

Comorbid chronic pain is common in depressed patients. It is predictive of a poor prognosis for depression and is a major risk factor for suicidal behavior. Depression and chronic pain may result from a common neurobiological dysfunction of monoamine cell bodies in the basal ganglia. Amitriptyline, which inhibits both serotonin and norepinephrine reuptake, is a preferred treatment of chronic pain although it is not officially indicated for this condition. Chronic pain can be modeled in animals where amitriptyline has been shown to be highly effective. Similar effects are obtained with the serotonin norepinephrine reuptake inhibitors milnacipran, duloxetine, and venlafaxine, whereas selective serotonin reuptake inhibitors (SSRIs) are only weakly active. Both animal and clinical studies of chronic pain show that dual-acting reuptake inhibitors are more active than selective norepinephrine reuptake inhibitors, which are, in turn, more active than SSRIs. A meta-analysis of placebo-controlled studies confirmed that dual-action antidepressants, but not SSRIs, were effective in reducing chronic lower-back pain. Milnacipran, duloxetine, and venlafaxine, have all been reported to be effective in a number of chronic pain conditions, including the treatment of fibromyalgia where their analgesic effects are independent of comorbid depression.
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PMID:Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. 1862 71

Treatment of depression may ameliorate the cognitive disability and motor slowness in Parkinson's disease. It has been shown that antidepressants, including fluoxetine, may attenuate or exacerbate neuronal cell death. The present study assessed the effect of antidepressants (amitriptyline, tranylcypromine and fluoxetine) against the toxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in relation to the mitochondria-mediated cell death process in differentiated PC12 cells. Amitriptyline and tranylcypromine attenuated the MPP(+)-induced cell death that may be associated with mitochondrial membrane permeability change and oxidative stress. Both compounds prevented the loss of the mitochondrial transmembrane potential, over-expression of Bax, reduction in Bcl-2 level, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH. The inhibitory effect of tranylcypromine was greater than that of amitriptyline on the basis of concentration. In contrast, fluoxetine revealed a toxic effect and exhibited an additive effect against the toxicity of MPP(+). Results show that amitriptyline and tranylcypromine may attenuate the MPP(+) toxicity by suppressing the mitochondrial membrane permeability change that leads to cytochrome c release and subsequent caspase-3 activation. The effects seem to be associated with the inhibitory action on the formation of reactive oxygen species and the depletion of GSH. In contrast, fluoxetine seems to exert an additive toxic effect against neuronal cell damage by increasing mitochondrial damage and oxidative stress.
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PMID:Antidepressants reveal differential effect against 1-methyl-4-phenylpyridinium toxicity in differentiated PC12 cells. 1913 49

An in vitro inhibition study was performed to investigate potential drug-drug interactions on glucuronidation of buprenorphine (BUP) and norbuprenorphine (NBUP), which represents the major elimination pathway of the drug using cDNA-expressed uridine 5'-diphosphate glucuronosyltransferases (UGTs) and human liver microsomes (HLMs). Following identification of major UGT enzymes for BUP and NBUP glucuronidation, substrates were incubated with drugs (amitriptyline, nortriptyline, lamotrigine, oxazepam, and temazepam), which are extensively cleared by glucuronidation as well as are often used during maintenance treatment. To evaluate the inhibitory potential, the half maximal inhibitor concentration (IC(50)), the inhibition constant (K (i)), and the inhibitor concentration (K (I)) that yield half the maximum rate of inactivation and the enzyme inactivation rate constant (k (inact)) were determined, if appropriate. Amitriptyline and temazepam are inhibitors of NBUP glucuronidation (UGT1A3, HLMs), whereas BUP glucuronidation was affected by amitriptyline (HLMs), oxazepam, and temazepam (UGT2B7). Additionally, BUP inhibits NBUP glucuronidation (UGT1A1, 1A3, HLMs) and vice versa (UGT1A3). A decrease in the metabolic clearance of NBUP may increase the risk of adverse effects such as respiratory depression. Further investigations are needed to evaluate whether inhibition of BUP and NBUP glucuronidation contributes to adverse events.
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PMID:An in vitro approach to estimate putative inhibition of buprenorphine and norbuprenorphine glucuronidation. 2011 69

Amitriptyline (AMI) is widely used for migraine prophylaxis, but its mechanism is undetermined. Cortical spreading depression (CSD), reflected by alterations in calcium, sodium, and Na(+)-K(+)ATP channels, has been implicated in migraine and as a headache trigger. Evidences indicate that mutations in sodium and calcium channels are involved in migraine. Sodium channels are critical for the electrical excitability of sensory neurons and play a key role in pain sensation by controlling afferent impulse discharge. To investigate the mechanism underlying AMI effectiveness for migraine prophylaxis, we studied the effects of AMI on voltage-gated sodium channels in cultured rat cortical neurons by the whole-cell patch clamp recording and real-time reverse transcription polymerase chain reaction (RT-PCR). We found that AMI blocked sodium channel current (I(Na)) in a concentration-dependent, not voltage-dependent manner. AMI also altered the activation and steady-state inactivation of I(Na) toward hyperpolarization. Results of real-time RT-PCR indicated that AMI inhibited the expression for sodium channels in a concentration-dependent manner; inhibition of expression of the Na(V)1.1 and Na(V)1.6 sodium channels was more than that of Na(V)1.2. From these results, we speculate that AMI may reduce CSD by inhibiting I(Na) and mRNA expression of sodium channels. This may contribute to strategies for migraine prophylaxis.
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PMID:Amitriptyline inhibits currents and decreases the mRNA expression of voltage-gated sodium channels in cultured rat cortical neurons. 2039 37


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