Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety Total score >12 (moderate-to-severe) without meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient-rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model analysis found significantly greater VAS-A improvement slopes for pregabalin (t = -2.47; P = 0.014) and alprazolam (t = -2.39; P = 0.018). There was a significant improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam patients and from 3 h onward in pregabalin patients. Pregabalin produced significantly greater increases in VAS-Sedation versus placebo from 2.5 h through 4 h (2 h onward for alprazolam). Notably, there was a higher correlation between TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = -0.50) on Spearman's analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7, 3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N = 3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0). These results suggest that onset of clinically meaningful anxiolytic effect after single-dose pregabalin occurs within the first 3-4 h. Additional research is needed to determine whether anxiolytic effect occurs in generalized anxiety disorder populations by day 1 or within 3-4 h post-first dose.
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PMID:Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind, placebo- and active-comparator controlled evaluation using a dental anxiety model. 1863 90

Duloxetine, a medication with effects on both serotonin and noradrenaline transporter molecules, has recently been approved for the treatment of generalized anxiety disorder. The evidence for its efficacy lies in a limited number of double blind, placebo controlled comparisons. Statistically significant improvements in the Hamilton Anxiety Rating Scale from baseline were demonstrated in all studies at doses of 60 to 120 mg per day. The significance of such changes in terms of clinical improvements compared to placebo is less certain, particularly when the effect size of the change is calculated. In comparative trials with venlafaxine, duloxetine was as effective in providing relief of anxiety symptoms. In addition to improvements in clinical symptoms duloxetine has also been associated with restitution of role function as measured by disability scales. Duloxetine use is associated with nausea, dizziness, dry mouth, constipation, insomnia, somnolence, hyperhidrosis, decreased libido and vomiting. These treatment emergent side effects were generally of mild to moderate severity and were tolerated over time. Using a tapered withdrawal schedule over two weeks in the clinical trials, duloxetine was associated with only a mild withdrawal syndrome in up to about 30% of patients compared to about 17% in placebo treated patients. Duloxetine in doses of up to 200 mg twice daily did not prolong the QTc interval in healthy volunteers. Like other agents with dual neurotransmitter actions duloxetine reduces the symptoms of generalized anxiety disorder in short term treatments. Further evidence for its efficacy and safety in long term treatment is required.
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PMID:Duloxetine in the treatment of generalized anxiety disorder. 1933 57

A multicenter, double-blind, parallel-group study was designed to assess the efficacy and safety of zolpidem extended-release coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Patients (N = 383) received open-label escitalopram 10 mg/d and were randomized to either adjunct zolpidem extended-release 12.5 mg or placebo. The primary efficacy measure was change from baseline to week 8 in subjective total sleep time. Secondary efficacy measures included subjective sleep onset latency, number of awakenings, wake time after sleep onset, sleep quality, the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, the Sleep Impact Scale, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, and the Sheehan Disability Scale. The last-observation-carried-forward method was used to impute missing values for most efficacy measures. Safety was monitored at each visit. At week 8 and all time points, there was a significant improvement in the zolpidem extended-release/escitalopram group compared with placebo/escitalopram for total sleep time (P < 0.0001). Most of the secondary efficacy measures also significantly favored zolpidem at most visits (P < 0.0001). The most common treatment-emergent adverse events in both groups were nausea, dizziness, headache, fatigue, and dry mouth. Concurrent zolpidem extended-release/escitalopram, compared with placebo/escitalopram, significantly improved insomnia and sleep-related next-day symptoms, but not anxiety symptoms, in patients with comorbid insomnia and generalized anxiety disorder.
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PMID:Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder. 1944 75

There is an increasing interest in the health risks related to the use of herbal remedies. Although most consumers think that phytomedicines are safe and without side effects, interactions between complementary alternative and conventional medicines are being described. The aim of this clinical case report is to highlight the importance of the safe use of herbal remedies by providing a clinical interaction study between pharmaceutical medicines and herbal medicinal products. The case of a patient self-medicated with Valeriana officinalis L. and Passiflora incarnata L. while he was on lorazepam treatment is described. Handshaking, dizziness, throbbing and muscular fatigue were reported within the 32 h before clinical diagnosis. The analysis of family medical history ruled out essential tremor, Parkinson's disease, Wilson's disease and other symptom-related pathologies. His medical history revealed a generalized anxiety disorder and medicinal plant consumption but no neurological disorder. Appropriate physical examination was carried out. An additive or synergistic effect is suspected to have produced these symptoms. The active principles of Valerian and passionflower might increase the inhibitory activity of benzodiazepines binding to the GABA receptors, causing severe secondary effects. Due to the increase in herbal product self-medication, the use of herbal remedies should be registered while taking the personal clinical history. Multidisciplinary teams should be created to raise studies on medicinal plants with impact on medical praxis.
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PMID:Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. 1944 Oct 67

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

The efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) once-daily monotherapy in generalized anxiety disorder (GAD) was assessed. This multicentre, double-blind, randomized, placebo- and active-controlled, phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk (8-wk active treatment, 2-wk post-treatment drug-discontinuation) study period; 873 patients were randomized to 50 mg or 150 mg quetiapine XR, 20 mg paroxetine, or placebo. Primary endpoint was change from randomization at week 8 in Hamilton Rating Scale for Anxiety (HAMA) total score. At week 8, all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR. Significant separation from placebo (-2.90) in HAMA total score was observed at day 4 for 50 mg quetiapine XR (-4.43, p<0.001) and 150 mg quetiapine XR (-3.86, p<0.05), but not for paroxetine (-2.69). Remission (HAMA total score 7) rates at week 8 were significantly higher for 150 mg quetiapine XR (42.6%, p<0.01) and paroxetine (38.8%, p<0.05) vs. placebo (27.2%). The most common adverse events (AEs) were dry mouth, somnolence, fatigue, dizziness, and headache, for quetiapine XR, and nausea, headache, dizziness for paroxetine. A lower proportion of patients reported sexual dysfunction with quetiapine XR [0.9% (50 mg), 1.8% (150 mg)] than with placebo (2.3%) or paroxetine (7.4%). The incidence of AEs potentially related to extrapyramidal symptoms was: quetiapine XR: 50 mg, 6.8%, 150 mg, 5.0%; placebo, 1.8%; and paroxetine, 8.4%. Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD, with symptom improvement seen as early as day 4.
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PMID:Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study. 1969 7

Dizziness and drowsiness are cited as being predictors of dropout from clinical trials for the medicine pregabalin. These adverse events are typically recorded daily on a four point ordinal scale (0 = none, 1 = mild, 2 = moderate, 3 = severe), with most subjects never reporting either adverse event. We modeled the dizziness, drowsiness, and dropout associated with pregabalin use in generalized anxiety disorder using piecewise Weibull distributions for the time to first non-zero dizziness or drowsiness score, after which the dizziness or drowsiness was modeled with ordinal regression with a Markovian element. Dropout was modeled with a Weibull distribution. Platykurtosis was encountered in the estimated random effects distributions for the ordinal regression models and was addressed with dynamic John-Draper transformations. The only identified predictor for the time to first non-zero dizziness or drowsiness score was daily titrated dose. Predictors for dropout included creatinine clearance and maximum daily adverse event score. Tolerance to adverse events over time was modeled by including a non-stationary component for the dizziness ordinal Markov regression while the piecewise Weibull distributions allowed a change point in the median time to first non-zero dizziness or drowsiness score.
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PMID:Joint modeling of dizziness, drowsiness, and dropout associated with pregabalin and placebo treatment of generalized anxiety disorder. 1990 83

The aim and objective of the study is to analyze the data of 145 vertiginous patients aged up to 18 years, which were examined at the Otoneurological Department of the Semmelweis University during the last 5 years. The study design for the analysis: the group of children (66 patients, aged up to 14 years) and group of adolescents (79 patients, ages between 14 and 18 years). Children and adolescents, who sent by otolaryngologists or pediatric neurologists, were examined. The detailed case history and routine physical examinations were followed by cochlear function tests. The vestibular test contained statokinetic test, spontaneous nystagmus with electronystagmographical (ENG) registration, positional and positioning nystagmus with Frenzel's glasses, smooth pursuit eye movement test and caloric test with computer-based ENG. Most of the patients experienced true rotatory vertigo. The ratio of the dizziness (vertigo without direction) was 38% in the children's and 44% in the adolescent group; 21 children and 31 adolescents had headache. Nausea and vomiting were frequent in both the groups: normal hearing was measured in 62% of children and in 82% of adolescents. The vestibular system was normal in 36% of the children's group, and in 39% of the adolescents. In conclusion, it is important to realize that 64% of the children and 61% of the adolescents do have certain vestibular abnormalities. The most frequent cause of dizziness (24%) in the adolescent group is the extravestibular disorder-like panic disease and the anxiety disorder. At younger age, the most frequent disease that can cause vestibular symptoms is the migraine.
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PMID:Vestibular disorders in childhood and adolescents. 2049 Aug 15

Migraine and anxiety disorders are frequently co-morbid with balance disorders. This study examined the relative distribution of subtypes of serotonin (5-HT) receptor in the inner ear of monkeys and rats. Most vestibular ganglion cells were immunoreactive for 5-HT(1B) and 5-HT(1D) receptors in macaques and rats. In the inner ear, 5-HT(1B) and 5-HT(1D) receptor immunopositivity was associated with endothelial cells of the vestibular ganglion, spiral ganglion, vestibulocochlear nerve, spiral ligament and stria vascularis. It was noteworthy that 5-HT(1B) and 5-HT(1D) receptors are expressed in parallel sites in peripheral vestibular and trigeminal systems, which may be a factor underlying the efficacy of triptans in treating migraine and migrainous vertigo. Because the vestibular ganglion and trigeminal ganglion are both within the subarachnoid space, an interaction between 5-HT(1B) and TRPV1 receptors on blood vessel and ganglion cells may also contribute to the vasospasm and the comorbid headache, dizziness, nausea and vomiting that accompany subarachnoid hemorrhage.
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PMID:Distribution of 5-HT1B and 5-HT1D receptors in the inner ear. 2051 Aug 90

Gabapentin (GP) and pregabalin (PB) are structurally related compounds and their predominant mechanism of action is the inhibition of calcium currents via high-voltage-activated channels containing the a2d-1 subunit. A2delta ligands are approved for the treatment of pain of diabetic neuropathy and post-herpetic neuralgia in adults and as adjunctive therapy of partial seizures in children. Recently, pregabalin has been approved for treatment of anxiety disorders in Europe. Besides their already approved indications both drugs are promising treatment options for a number of different serious and debilitating diseases, as fibromyalgia, neuropathic pain of spinal cord injury, hot flushes, and essential tremor. In the present review, the unique mechanism of action of the above drugs is critically analyzed and evidence for their future use is provided. Gabapentin and pregabalin can be treatment options for these disorders, however, a clear comparison between the two drugs can not be performed, since there is no direct comparison study. The most common side effects are dizziness and somnolence which are also the most frequent reasons for withdrawal. Recommendations for future studies should include assessment of ideal titration period for GP and PB to reduce incidence of somnolence and dizziness and increase tolerability, cost-effectiveness and dose-response analysis of PB and GP and direct comparison of the two drugs.
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PMID:A2delta ligands gabapentin and pregabalin: future implications in daily clinical practice. 2059 59


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