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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in dopaminergic tonus have been hypothesized in patients with common migraine, suggesting that prolactin may play a role in the pathogenesis of the migraine. We investigated the prolactin response to domperidone, a dopamine receptor blocker. We tested 22 patients with common migraine (8 men, 7 women in the follicular phase of the menstrual cycle, and 7 women in the luteal phase), and 22 normal subjects adjusted for age, sex and phase of the menstrual cycle. Domperidone produced a significant rise of serum prolactin (p less than 0.01) in migrainous patients (7.77 +/- 3.09 vs 71.06 +/- 9.97 in men, 7.05 +/- 2.3 vs 129.58 +/- 14.15 in women in the follicular phase of the menstrual cycle, and 14.28 +/- 3.51 vs 169.71 +/- 16.63 in women in the luteal phase) and control subjects. The response did not show significant differences between migrainous patients and normal subjects. These data do not suggest changes in the tuberoinfundibular dopaminergic tonus in migrainous patients, in contrast to reports of other authors.
Headache 1990 Apr
PMID:Tuberoinfundibular dopaminergic tonus in common migraine. 235 52

The main treatment of the acute migraine attack remains sleep, sedation, an anti-nauseant and analgesics, and in some patients 1 or 2 mg of ergotamine tartrate. Drugs containing large amounts of caffeine should not be used. Absorption of drugs may be impaired in a migraine attack. Metoclopramide is probably the anti-emetic of choice because it is an effective anti-nauseant and promotes normal gastrointestinal activity. Domperidone has a similar action but is said not to go through the blood-brain barrier, so is less likely to cause extrapyramidal reactions. All drugs, including analgesics such as aspirin and paracetamol, are best given in a soluble or effervescent form. Where vomiting occurs early in the attack, suppositories may be indicated. Ergotamine tartrate is necessary in about one third of attacks and is best given by suppository or by inhalation. Doses higher than 2 mg per attack or 6 mg in one week may cause toxic symptoms, the early signs of which are headache, nausea, vomiting and a feeling of not being very well. The non-drug treatments of an acute attack include pressing on the temporal artery, hot and cold compresses and relaxation.
Cephalalgia 1983 Mar
PMID:Treatment of the acute migraine attack--current status. 640 72

In the treatment of migraine attacks, an antiemetic in combination with an analgesic or ergot alkaloid is widely recommended. Medication should be introduced as early as possible, but only when there is no doubt that the headache is due to migraine. The antiemetic provides relief from the nausea and vomiting and also enhances the resorption of analgesics or ergot preparations. Domperidone 20 mg orally and 20 mg metoclopramide as suppository or 10-20 mg orally are mostly used as antiemetics. Analgesics such as 1000 mg acetylsalicylic acid as effervescent tablets, or 1000 mg paracetamol as effervescent tablets or suppositories should be given 15-20 min later. If this treatment fails, NSAIDs can be tried. In some studies naproxen in doses between 500 and 1000 mg and ibuprofen in doses between 400 and 800 mg have been shown to be effective, as well as NSAIDs like diclofenac, mefenamic acid, ketoprofen, tolfenamic acid and pirprofen. NSAIDs have been found to be superior to placebo and to standard reference drugs in the majority of the reviewed double-blind trials. Nevertheless, these effects are marginal in some studies or even without clinical relevance. Accordingly, there is still a need for further comparative studies.
Cephalalgia 1995 Oct
PMID:Analgesics and NSAIDs in the treatment of the acute migraine attack. 874 41

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypothesis. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D2 receptor antagonist metoclopramide. This drug also has 5HT3 receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D2 receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT4 receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options.
Cephalalgia 1998 Nov
PMID:Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies? 987 82

Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. To further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This single-arm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age >or=18 years) meeting DSM-IV criteria for MDD (n=128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (P<.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by >10% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of 3.1 kg over 2 years of treatment. Results from this study suggest that rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable. Despite weekly escalation, the majority of adverse events were mild and transient and occurred in the first week of duloxetine dosing (at 60 mg once daily). Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of TEAEs and treatment discontinuation due to adverse events. Time course profiles of body weight and heart rate showed modest increases during 2 years of treatment [ClinicalTrials.gov number, NC T000 42575].
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PMID:Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation. 1684 41

An aim of the study was to assess effect of duloxetine, a selective inhibitor of serotonin and noradrenalin reuptake, on chronic daily headache (CDH) and its antinociceptive mechanisms. Duloxetine was administered in dosage 60 mg per day during 8 weeks to 40 patients. The high efficacy of the drug by different clinical indices--decrease of days of headache per month, frequency of headache attacks, reduction of analgetics used--was found, all changes being statistically significant. The therapeutic response was developed from the 2nd month of the treatment. The study of the nociceptive flexion reflex revealed the increase of its threshold and of subjective pain threshold as well. Intensity of comorbid disorders, depression and anxiety, was also significantly decreased. Side-effects were small and transient.
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PMID:[Efficacy of duloxetine in the treatment of chronic daily headache]. 1837 68

Duloxetine (Cymbalta(R)) is a potent serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) in the CNS. It is indicated for the treatment of generalized anxiety disorder (GAD) as well as other indications. In patients with GAD of at least moderate severity, oral duloxetine 60-120 mg once daily was effective with regard to improvement from baseline in assessments of anxiety and functional impairment, and numerous other clinical endpoints. Longer-term duloxetine 60-120 mg once daily also demonstrated efficacy in preventing or delaying relapse in responders among patients with GAD. In addition, duloxetine was generally well tolerated, with most adverse events being of mild to moderate severity in patients with GAD in short- and longer-term trials. Additional comparative and pharmacoeconomic studies are required to position duloxetine among other selective serotonin reuptake inhibitors and SNRIs. However, available clinical data, and current treatment guidelines, indicate that duloxetine is an effective first-line treatment option for the management of GAD. Duloxetine is a potent and selective inhibitor of serotonin and noradrenaline transporters, and a weak inhibitor of dopamine transporters. It has a low affinity for neuronal receptors, such as alpha(1)- and alpha(2)-adrenergic, dopamine D(2), histamine H(1), muscarinic, opioid and serotonin receptors, as well as ion channel binding sites and other neurotransmitter transporters, such as choline and GABA transporters. It does not inhibit monoamine oxidase types A or B. The pharmacokinetics of duloxetine in healthy volunteers were dose proportional over the range of 40-120 mg once daily. Steady state was typically reached by day 3 of administration. Duloxetine may be administered without regard to food or time of day. Duloxetine is highly protein bound and is widely distributed throughout tissues. It is rapidly and extensively metabolized in the liver by cytochrome P450 (CYP) 1A2 and 2D6, and its numerous metabolites, which are inactive, are mainly excreted in the urine. The mean elimination half-life of duloxetine is approximately 12 hours. Duloxetine is a substrate for CYP1A2 and CYP2D6 and a moderate inhibitor of CYP2D6. Concomitant use of duloxetine and potent CYP1A2 inhibitors should be avoided and duloxetine should be used with caution in patients receiving drugs that are extensively metabolized by CYP2D6, particularly those with a narrow therapeutic index. Duloxetine was effective in the short-term treatment of patients with primary GAD of at least moderate severity. In four randomized, double-blind, placebo-controlled, multicentre, phase III trials, duloxetine 60-120 mg once daily for 9 or 10 weeks was significantly more effective than placebo with regard to the primary endpoint of mean change in Hamilton Anxiety Rating Scale (HAM-A) total score from baseline to study endpoint. In addition, all other endpoints were generally improved from baseline to a greater extent with duloxetine 60-120 mg once daily than with placebo. Duloxetine also improved patient role functioning (assessed using Sheehan Disability Scale global impairment functioning scores), health-related quality of life and patient well-being compared with placebo. Duloxetine was effective in patients with GAD who were aged >/=65 years. Pooled results of data from the two short-term efficacy trials that also included an active comparator arm showed that the mean change in HAM-A scores with duloxetine relative to placebo were of the same magnitude as those with venlafaxine extended release versus placebo. Duloxetine 60-120 mg once daily was also more effective than placebo in preventing or delaying relapse in responders to duloxetine in a longer-term study. In this study, patients with GAD received duloxetine during a 26-week, open-label, acute treatment phase and responders were then randomized to continue on duloxetine or receive placebo during a 26-week, double-blind, continuation phase. Time to relapse was significantly longer in duloxetine recipients than in placebo recipients. In addition, significantly fewer duloxetine recipients than placebo recipients relapsed during the double-blind phase of the trial and more duloxetine recipients achieved remission. Short- (9-10 weeks) and longer-term (52 weeks) treatment with duloxetine 60-120 mg once daily was generally well tolerated in patients with GAD, with the majority of adverse events being of mild to moderate severity. Nausea, dry mouth, headache, constipation, dizziness and fatigue were among the most common treatment-emergent adverse events. The adverse event profile of duloxetine did not differ with dose or treatment duration. Significantly more patients receiving short-term duloxetine than placebo discontinued treatment because of an adverse event, with nausea being the only event that resulted in significantly more treatment discontinuations in duloxetine recipients than in placebo recipients. Serious adverse events were uncommon with both short- and longer-term duloxetine treatment. Two episodes of attempted suicide and one episode of completed suicide occurred in duloxetine recipients during the 24-week open-label phase of a longer-term trial. No deaths or suicides were reported in any of the short-term trials. Discontinuation-emergent adverse events, most commonly nausea and dizziness, occurred in up to one-third of duloxetine recipients in the short-term trials.
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PMID:Duloxetine: a review of its use in the treatment of generalized anxiety disorder. 1948 Apr 70

Duloxetine is a serotonin and norepinephrine reuptake inhibitor that possesses antidepressant and pain-relieving properties. Compared with other antidepressants, it has a high affinity for both norepinephrine and serotonin reuptake transporters, which are relatively balanced. Analgesic onset has been observed within the first week of administration in randomized controlled trials and is likely obtained by enhancing the tone of the descending pain inhibition pathways of the central nervous system. Randomized trials have documented significant analgesic effects for managing chronic pain associated with fibromyalgia and diabetic peripheral neuropathic pain. Studies have also suggested that pain associated with major depressive disorder can be reduced with this medication. Modest effects for headache, osteoarthritic pain, and pain secondary to Parkinson disease have also been documented, but data are obtained from single-blinded or open-label trials that require further corroboration with larger randomized studies. Duloxetine has not yet been directly compared with other antidepressants or anticonvulsants for the treatment of pain syndromes.
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PMID:Duloxetine: a review of its pharmacology and use in chronic pain management. 2092 42

Fibromyalgia syndrome (FMS) is a widespread pain condition associated with a wide range of additional symptoms including fatigue, insomnia, depression, anxiety and stiffness. Duloxetine is one of three medications currently FDA approved for use in FMS management. Duloxetine is a mixed serotonin and norepinephrine reuptake inhibitor (SNRI) that functions by increasing central nervous system levels of serotonin and norepinephrine. This review is a primer on use of duloxetine in FMS management and includes information on pharmacology and pharmacokinetics, a review of the three duloxetine FMS treatment trials currently in publication, a discussion of the safety and tolerability of duloxetine, and patient-focused perspectives on duloxetine use in FMS management. Duloxetine has proven efficacy in managing pain and mood symptoms in adult FMS patients with and without major depressive disorder. However, due to side effects, duloxetine must be used with caution in patients with fatigue, insomnia, gastrointestinal complaints, headache, cardiovascular disease, bleeding-risk, and in those 24 years of age and younger due to risk of suicidality. Duloxetine use should be avoided in patients with liver disease or alcoholics. As with all medications, duloxetine is best used as part of an individualized regimen that includes nonpharmacologic modalities of exercise, education and behavioral therapies.
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PMID:Duloxetine for the management of fibromyalgia syndrome. 2119 98

Trigeminal neuralgia (TN) is the most common type of neuralgia affecting facial region and is considered to be one of the most painful conditions. Treatment is often unsatisfactory. Newer treatment modalities are therefore being tried. Duloxetine is FDA approved drug for painful diabetic neuropathy and has been used in painful symptoms of depression as well. Safety and efficacy of duloxetine was evaluated in patients with trigeminal neuralgia; another chronically painful condition, in an open label manner. A total of 15 patients who fulfilled the diagnostic criteria of International Headache Society for Trigeminal Neuralgia were administered duloxetine 40 mg daily. The efficacy of the drug was evaluated by face scale and Likert's numerical scale. Statistically significant pain relief was reported in 9 out of 15 patients of trigeminal neuralgia. The pain relief was reported as early as in one week and was maintained for 16 weeks. The drug was well tolerated and side-effects reported were mild and reversible. No adverse drug reaction requiring hospitalisation or drug discontinuation was reported in the present study. Duloxetine showed statistically significant pain relief in trigeminal neuralgia. Double-blind, placebo-controlled studies are needed to confirm findings at a large scale.
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PMID:Efficacy, safety and tolerability of duloxetine in idiopathic trigeminal neuralgia. 2218 99


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