Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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The use of calcium channel blockers is usual in cardiology today, but seem to spread to others specialties, particularly in the field of neuropsychiatry. The authors report the major clinical studies in neurology (treatment of migraines, epilepsia, dizziness and ischemic stroke) where flunarizine and nimodipine seem to have an important role. In psychiatry, their introduction is more recent. However, some encouraging results have been noted in the treatment of panic disorder, Gilles de la Tourette disease and mania.
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PMID:[Use of calcium inhibitors in neuropsychiatric pathology]. 219 69

Divalproex sodium is an anticonvulsant agent approved for use either alone or in combination with other antiepileptic drugs for simple and complex absences seizures and mania. Four double-blind placebo-controlled studies have confirmed that divalproex sodium/valproate is an effective migraine treatment. In all of the clinical studies, whether open, retrospective, or placebo-controlled and double-blind, valproate was an effective preventive treatment for migraine. There was a reduction in the number of migraine attacks, and migraine duration and intensity were also reduced in some instances. It is equally as effective in patients with severe frequent migraines as in those with less severe migraines. In clinical trials, the most frequent adverse events reported by patients treated with divalproex sodium were nausea, asthenia, dyspepsia, dizziness, somnolence, and diarrhea, with most adverse events being mild to moderate in severity.
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PMID:Divalproex sodium in headache: literature review and clinical guidelines. 891 63

Moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA) and has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively studied in anxiety disorders. Nearly all meta-analyses and most comparative studies indicated that in the acute management of depression this drug is more efficacious than placebo and as efficacious as tricyclic (or some heterocyclic) antidepressants or selective serotonin reuptake inhibitors (SSRIs). There is a growing evidence that moclobemide is not inferior to other antidepressants in the treatment of subtypes of depression, such as dysthymia, endogenous (unipolar and bipolar), reactive, atypical, agitated, and retarded depression as with other antidepressants limited evidence suggests that moclobemide has consistent long-term efficacy. However, more controlled studies addressing this issue are needed. For patients with bipolar depression the risk of developing mania seems to be not higher with moclobemide than with other antidepressants. The effective therapeutic dose range for moclobemide in most acute phase trials was 300 to 600 mg, divided in 2 to 3 doses. While one controlled trial and one long-term open-label study found moclobemide to be efficacious in social phobia, three controlled trials subsequently revealed either no effect or less robust effects with the tendency of higher doses (600 - 900 mg/d) to be more efficacious. Two comparative trials demonstrated moclobemide to be as efficacious as fluoxetine or clomipramine in patients suffering from panic disorder. Placebo-controlled trials in this indication are, however, still lacking. A relationship between the plasma concentration of moclobemide and its therapeutic efficacy is not apparent but a positive correlation with adverse events has been found. Dizziness, nausea and insomnia occurred more frequently on moclobemide than on placebo. Due to negligible anticholinergic and antihistaminic actions, moclobemide has been better tolerated than tri- or heterocyclic antidepressants. Gastrointestinal side effects and, especially, sexual dysfunction were much less frequent with moclobemide than with SSRIs. Unlike irreversible MAO-inhibitors, moclobemide has a negligible propensity to induce hypertensive crisis after ingestion of tyramine-rich food ("cheese-reaction"). Therefore, dietary restrictions are not as strict. However, with moclobemide doses above 900 mg/d the risk of interaction with ingested tyramine might become clinically relevant. After multiple dosing the oral bioavailability of moclobemide reaches almost 100%. At therapeutic doses, moclobemide lacks significant negative effects on psychomotor performance, cognitive function or cardiovascular system. Due to the relative freedom from these side effects, moclobemide is particularly attractive in the treatment of elderly patients. Moclobemide is a substrate of CYP2C19. Although it acts as an inhibitor of CYP1A2, CYP2C19, and CYP2D6, relatively few clinically important drug interactions involving moclobemide have been reported. It is relatively safe even in overdose. The drug has a short plasma elimination half-life that allows switching to an alternative agent within 24 h. Since it is well tolerated, therapeutic doses can often be reached rapidly upon onset of treatment. Steady-state plasma levels are reached approximately at one week following dose adjustment. Patients with renal dysfunction require no dose reduction in contrast to patients with severe hepatic impairment. Cases of refractory depression might improve with a combination of moclobemide with other antidepressants, such as clomipramine or a SSRI. Since this combination has rarely been associated with a potentially lethal serotonin syndrome, it requires lower entry doses, a slower dose titration and a more careful monitoring of patients. Combination therapy with moclobemide and other serotonergic agents, or opioids, should be undertaken with caution, although no serious adverse events have been published with therapeutic doses of moclobemide to date. On the basis of animal data the combined use of moclobemide with pethidine or dextropropoxyphene should be avoided. There is no evidence that moclobemide would increase body weight or produce seizures. Some preclinical data suggest that moclobemide may have anticonvulsant property.
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PMID:Moclobemide: therapeutic use and clinical studies. 1504 13

Despite therapeutic treatment with lithium or valproate, patients with bipolar I disorder often require adjunctive therapy to treat persistent symptoms. In order to evaluate the effects of quetiapine for bipolar symptoms inadequately responsive to mood stabilizers, a retrospective chart review was undertaken at the Veterans Affairs (VA) Long Beach Mood Disorders Clinic for all bipolar I outpatients who had been prescribed adjunctive quetiapine during an 18-month study period. Among 75 lithium- or valproate-treated patients receiving quetiapine, 16 were identified in whom therapeutic treatment with lithium (> or =0.8 meq/l) or valproate (> or =75 microg/ml) could be verified during the 2-month period prior to quetiapine initiation. Chart notes were utilized by the principal investigator to assign Clinical Global Impression Bipolar ratings (CGI-BP) before and after 30-120 days of quetiapine treatment (mean=173+/-157 mg). Nine of 16 lithium- or valproate-stabilized bipolar patients (56%) were judged much or very much improved in CGI-BP overall ratings following adjunctive quetiapine. In addition, for the entire sample, quetiapine augmentation resulted in significant improvements in clinician-rated bipolar severity scores (CGI-BP) for mania, depression, and overall bipolar illness. The majority of quetiapine-related symptomatic improvement was due to diminished insomnia, agitation, irritability, and mood disturbance. Side effects were mild and transitory including sedation and dizziness. Low-dose quetiapine may be a useful and well-tolerated adjunct for some bipolar patients with incomplete response to lithium or valproate.
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PMID:Adjunctive quetiapine in bipolar patients partially responsive to lithium or valproate. 1292 20

(1) Lithium is the first-line treatment for patients with acute mania. For patients with psychosis or intense agitation, an oral neuroleptic can be added (haloperidol or chlorpromazine, the best-assessed drugs of this class). (2) The licensed indications for oral olanzapine, a neuroleptic, explicitly mention the treatment of acute mania. (3) The clinical evaluation dossier on olanzapine in this setting (10 mg to 15 mg/day) is not particularly impressive. In particular, clinical trials included patients with a variety of associated psychotic symptoms. (4) The only comparative trial against another neuroleptic, haloperidol at a high starting dose (10 mg), showed that olanzapine was no more effective. The same applies to a trial comparing olanzapine with disodium valproate. (5) One placebo-controlled trial tested olanzapine as an additional treatment in patients who did not respond adequately to lithium or valproate disodium. Olanzapine potentiated the antimanic effects of the original treatment but also increased the incidence of adverse effects. (6) In patients with acute mania, the main adverse effects of olanzapine are drowsiness, weight gain, dizziness, and dry mouth. In the trial comparing olanzapine with haloperidol, olanzapine caused fewer extrapyramidal side effects but more weight gain than haloperidol. (7) Olanzapine costs 20 times more than haloperidol in France. (8) In practice, olanzapine is just another neuroleptic approved for the treatment of acute mania in patients with psychotic symptoms and agitation. There is no evidence that olanzapine has the best risk-benefit ratio in this category.
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PMID:Olanzapine: new indication. New indication in acute mania: just another neuroleptic. 1514 54

Despite the considerable burden of bipolar depression, the treatment of this debilitating phase of bipolar disorder is suboptimally addressed by currently available pharmacologic options. Consequently, there is a need for the development of new treatment options with enhanced efficacy and tolerability. Evidence of antidepressant efficacy for some of the atypical antipsychotics in the treatment of bipolar depression has recently emerged. The findings of a large-scale, placebo-controlled, double-blind, randomized clinical study of olanzapine alone and in combination with fluoxetine, and a similar study of quetiapine monotherapy, suggest that some of the atypical antipsychotics may be efficacious in treating depressive symptoms in patients with bipolar I disorder. Subpopulation analyses suggest that quetiapine monotherapy and the olanzapine plus fluoxetine combination appear to be effective in treating depression in patients with a rapid-cycling course. The magnitude of improvement in depressive symptoms in the bipolar I population appears to be larger for quetiapine monotherapy compared with either olanzapine or olanzapine plus fluoxetine; however, the limitations of such a cross-study comparison are acknowledged. Both olanzapine monotherapy and combination therapy, as well as quetiapine monotherapy, were well tolerated. The overall incidence of treatment-emergent mania was low and comparable with placebo in both studies. Somnolence, weight gain, increased appetite and nonfasting glucose and cholesterol levels were more commonly reported in patients treated with olanzapine monotherapy or combination therapy compared with placebo. Dry mouth, sedation/somnolence, dizziness, and constipation were more commonly associated with quetiapine treatment. Large, controlled studies are needed to determine whether other psychotropic agents have antidepressant properties that would make them suitable for use in patients with bipolar depression. In addition, direct comparison of the regimens used in the current study should determine whether the differences evident between them can be confirmed.
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PMID:Clinical highlights in bipolar depression: focus on atypical antipsychotics. 1603 99

Chinese herbal medicines possess the therapeutic potential for mood disorders. This double-blind, randomized, placebo-controlled study was designed to evaluate the efficacy and side effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as an adjunct to carbamazepine (CBZ) in patients with bipolar disorders. One hundred and twenty-four bipolar depressed and 111 manic patients were randomized to treatment with CBZ alone, CBZ plus FEWP, or equivalent placebo for 12 weeks. CBZ was initiated at 300mg/day and FEWP was given at a fixed dose of 36g/day. Efficacy measures included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale , Young Mania Rating Scale, Bech-Rafaelsen Mania Scale, and Clinical Global Impression-Severity (CGI-S). CBZ monotherapy produced significantly greater improvement on manic measures at week 2 through endpoint and CGI-S of depression at endpoint compared to placebo. CBZ monotherapy also yielded significantly higher clinical response rates than placebo on bipolar depression (63.8% vs. 34.8%, p=0.044) and mania (87.8% vs. 57.1%, p=0.012). Compared to CBZ monotherapy, adjunctive FEWP with CBZ resulted in significantly better outcomes on the three measures of depression at week 4 and week 8 and significantly greater clinical response rate in depressed subjects (84.8% vs. 63.8%, p=0.032), but failed to produce significantly greater improvement on manic measures and the response rate in manic subjects. There was a lesser incidence of dizziness and fatigue in the combination therapy compared to CBZ monotherapy. These results suggest that adjunctive FEWP has additive beneficial effects in bipolar patients, particularly for those in depressive phase.
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PMID:Adjunctive herbal medicine with carbamazepine for bipolar disorders: A double-blind, randomized, placebo-controlled study. 1608 Nov 6

In December 2004, an extended-release capsule formulation of carbamazepine was approved by the U.S. Food and Drug Administration for the treatment of acute manic or mixed episodes associated with bipolar I disorder. This formulation allows twice-daily dosing and minimizes plasma carbamazepine fluctuations. The efficacy, safety and tolerability of the product were demonstrated with two pivotal randomized, placebo-controlled, double-blind monotherapy trials. These studies showed efficacy in bipolar I mania in patients with acute manic or mixed episodes. Pooled post hoc analyses documented a significant onset of effect within seven days, an incremental response of about 25% over placebo and a moderate effect size of 0.61 with no treatment-emergent depression. Carbamazepine's mode of action in mania is unknown, but a variety of effects on receptors, neurotransmitters, ion channels and binding sites have been documented. It has a complex pharmacokinetic profile due to autoinduction and a long-acting active metabolite. Carbamazepine's most frequent adverse events comprise dizziness, somnolence, nausea and vomiting, although these tend to diminish over time. It is effectively weight neutral and can provide an acceptable and efficacious treatment option for bipolar I mania.
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PMID:Extended-release carbamazepine for acute bipolar mania: a review. 1680 91

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P <or= 0.001 vs. placebo). Therapeutic effect sizes at Week 8 were 0.61 and 0.54 for quetiapine 300 and 600 mg/d, respectively. Improvements in mean HAM-D scores were also significantly greater with both quetiapine doses than with placebo (P < 0.001) as early as Week 1 and throughout the study. The MADRS response and remission rates were also significantly greater in both quetiapine dose groups compared with placebo. Improvements in primary and secondary outcomes were observed with both 300 and 600 mg/d quetiapine without major differences between the doses. Common adverse events included dry mouth, sedation, somnolence, dizziness, and constipation. The incidence of treatment-emergent mania or hypomania was lower with quetiapine treatment than placebo. This study demonstrates that quetiapine monotherapy is an effective and well-tolerated treatment for depressive episodes in bipolar disorder, confirming the results observed from a previous study (BipOLar DEpRession [BOLDER] I).
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PMID:Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). 1848 Jul 8

A new hazard for adolescents is the negative health effects of energy drink consumption. Adolescents are consuming these types of drinks at an alarming amount and rate. Specific effects that have been reported by adolescents include jitteriness, nervousness, dizziness, the inability to focus, difficulty concentrating, gastrointestinal upset, and insomnia. Health care providers report that they have seen the following effects from the consumption of energy drinks: dehydration, accelerated heart rates, anxiety, seizures, acute mania, and strokes. This article is a comprehensive literature review on the health effects of energy drinks. Findings from this article indicate the need for educational intervention to inform adolescents of the consequences of consuming these popular drinks. School nurses are in a unique position to teach adolescents about the side effects and possible health issues that can occur when energy drinks are consumed.
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PMID:Energy drinks: a new health hazard for adolescents. 2053 66


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