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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty major depressed patients, resistant to multiple pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess tolerability. There were 188 adverse events: insomnia, dizziness, headache, nausea, dry mouth and myoclonic jerks were the most common. Many events were rated as severe. The high rate of adverse events suggest that there are clinically significant pharmacodynamic interactions between moclobemide and SSRIs. However the uncontrolled data on effectiveness is encouraging and the combination deserves further consideration as a strategy for treating intractable depression.
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PMID:Safety and tolerability of combined treatment with moclobemide and SSRIs: a systematic study of 50 patients. 892 97

In drug development the move from tricyclic antidepressants (TCAs) to selective serotonin reuptake inhibitors (SSRIs) involved not only the loss of the direct receptor interactions responsible for the adverse side effects of TCAs, but also the ability to inhibit the reuptake of noradrenaline. Selectivity for the single neurotransmitter, serotonin, may explain why SSRIs tend to be less efficacious than the TCAs, especially in more serious forms of depression. The advent of selective serotonin and noradrenaline reuptake inhibitors (SNRIs) has tended to confirm the idea that an action on both monoamine systems is important for maximal antidepressant efficacy. This paper reviews clinical trials comparing the new SNRI milnacipran with the SSRIs fluoxetine and fluvoxamine. A meta-analysis of the principal trials shows greater response rates (the proportion of patients with a decrease in symptom scores of 50% or more) with milnacipran (50 mg twice a day) than with fluoxetine (20 mg once a day), or fluvoxamine (100 mg twice a day) (milnacipran: 64%; SSRIs: 50%). Remission rates (the proportion of patients with Hamilton Depression Rating Scores of 7 or below) were also higher with milnacipran than with SSRIs (39 versus 28%). In one study, in which 100 mg milnacipran was given once a day in the evening, the higher response rate obtained with fluoxetine appears to be largely attributable to an inappropriate milnacipran dosage regimen. Data from a pharmacovigilance database including all patients participating in clinical trials with milnacipran (n = 5732) showed that, compared with the SSRIs, milnacipran produced fewer gastrointestinal side effects, such as nausea, and less anxiety. Milnacipran was, however, associated with a higher incidence of headache, dry mouth and dysuria. The results of these studies suggest that milnacipran is superior in efficacy to SSRIs and is equally well tolerated. Milnacipran, therefore, appears to offer a therapeutic advantage over the SSRIs.
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PMID:Milnacipran and selective serotonin reuptake inhibitors in major depression. 892 26

The clinical trial development programme of mirtazapine (Org 3770), performed in Europe and the United States, demonstrated an outstanding safety profile of this compound. The evaluation of the safety was based on data from all patients who took at least one dose of study medication during studies comparing mirtazapine with placebo, amitriptyline or other active comparators. A general indication of mirtazapine's safety is the significantly lower percentage of patients (65%) who complained of any adverse clinical experiences compared with the placebo- (76%) or amitriptyline-treated group (87%). Moreover, drop-out rates due to adverse clinical experiences were significantly lower than in the amitriptyline-treatment group. Mirtazapine has virtually no anticholinergic, adrenergic or typical selective serotonin reuptake inhibitor (SSRI) side effects. The only significantly higher incidences versus placebo were seen in the adverse clinical effects of drowsiness (23% versus 14%), excessive sedation (19% versus 5%), dry mouth (25% versus 16%), increased appetite (11% versus 2%) and weight increase (10% versus 1%). These complaints were typically mild and transient in nature, and decreased over time despite increased doses of mirtazapine. In contrast, significantly higher incidences of headache (5% versus 10%) and weight decrease (2% versus 6%), symptoms commonly seen in depressed patients, were recorded in the placebo-treated patients. Also, typical SSRI adverse events, such as nausea, vomiting, diarrhoea and insomnia, and symptoms of sexual dysfunction were registered less frequently in mirtazapine-treated patients than in the placebo-treated patients. Approximately 10% of the mirtazapine-treated patients in the clinical trial programme were older than 65 years. The pattern of adverse clinical experiences seen in this group of patients is fully in line with that seen in the overall patient population. The analysis of vital sign indices, i.e. blood pressure and heart rate, showed that no changes occurred with mirtazapine treatment; this pattern was fully comparable to that seen with placebo. Furthermore, very low incidences of clinically relevant changes in laboratory indices, such as the liver enzymes alanine aminotransferase and aspartate aminotransferase or neutropenia, were recorded in each treatment group. Mirtazapine has a very low seizure-inducing potential: only one case was recorded in a patient with a history of seizures during previous treatment with clomipramine. The low seizure-inducing potential combined with a lack of cardiotoxic properties allows safety in an overdose of mirtazapine, even in elderly patients. The only symptom seen in the patients taking an overdose of mirtazapine alone or in combination with other drugs was excessive but transient somnolence, which resolved spontaneously within a few hours. In conclusion, the new antidepressant mirtazapine offers clinicians a unique combination of strong efficacy and good safety.
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PMID:Safety of mirtazapine: a review. 893 8

The objective of the present study was to compare the safety and efficacy of moclobemide versus fluoxetine in adult patients with major depressive disorder. The design of the study was a multicenter, double-blind, comparative, and randomized trial. A 1- to 2-week single-blind placebo washout phase was followed by 6 weeks of double-blind treatment with moclobemide or fluoxetine. A total of 150 patients were enrolled in the study. There were 128 patients eligible to be randomized, with 66 patients receiving moclobemide and 62 patients receiving fluoxetine. At the termination of the study, patients in the moclobemide group were receiving a mean dose of 440 mg +/- 123 mg, while the mean dose in the fluoxetine group was 35 mg +/- 8 mg. No significant treatment differences were found for any of the efficacy parameters. Headache and nausea were the most frequently reported adverse events in both treatment groups. Headache and blurred vision were reported significantly more often (P < 0.05) in the fluoxetine group, whereas significantly more dry mouth was reported (P < 0.05) in the moclobemide group. These results provide supporting evidence of the comparable efficacy of moclobemide and fluoxetine and the better tolerability of moclobemide when used in the treatment of major depressive disorder.
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PMID:Moclobemide versus fluoxetine in the treatment of major depressive disorder in adults. 907 6

The pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of tramadol are reviewed. Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake. It is rapidly and extensively absorbed after oral doses and is metabolized in the liver. Analgesia begins within one hour and starts to peak in two hours. In patients with moderate postoperative pain, i.v. or i.m. tramadol is roughly equal in efficacy to meperidine or morphine; for severe acute pain, tramadol is less effective than morphine. Oral tramadol can also be effective after certain types of surgery. Tramadol and meperidine are equally effective in postoperative patient-controlled analgesia. In epidural administration for pain after abdominal surgery, tramadol is more effective than bupivacaine but less effective than morphine. In patients with ureteral calculi, both dipyrone and butylscopolamine are more effective than tramadol. For labor pain, i.m. tramadol works as well as meperidine and is less likely to cause neonatal respiratory depression. Oral tramadol is as effective as codeine for acute dental pain. In several types of severe or refractory cancer pain, tramadol is effective, but less so than morphine; for other types of chronic pain, such as low-back pain, oral tramadol works as well as acetaminophen-codeine. Common adverse effects of tramadol include dizziness, nausea, dry mouth, and sedation. The abuse potential seems low. The recommended oral dosage is 50-100 mg every four to six hours. Tramadol is an effective, if expensive, alternative to other analgesics in some clinical situations.
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PMID:Tramadol: a new centrally acting analgesic. 907 93

Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term clinical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline. The optimum therapeutic dosage of nefazodone appears to be between 300 and 600 mg/day. Limited long term data suggest that nefazodone is effective in preventing relapse of depression in patients treated for up to 1 year. Analyses of pooled clinical trial results indicate that nefazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo in patients with major depression. Short term tolerability data indicate that nefazodone has a lower incidence of adverse anticholinergic, antihistaminergic and adrenergic effects than imipramine. Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointestinal effects (nausea, diarrhoea, anorexia) and adverse effects on sexual function, but is associated with more dizziness, dry mouth, constipation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures, priapism or significant sleep disruption, and appears to be relatively safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 isoenzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of major depression. Nonetheless, available data suggest that nefazodone is a worthwhile treatment alternative to tricyclic antidepressants and SSRIs in patients with major depression.
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PMID:Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. 921 Oct 88

Venlafaxine, a phenylethylamine, and nefazodone, a phenylpiperazine compound, are the newest antidepressants to receive approval of the Food and Drug Administration and to be marketed in the United States. Both strongly inhibit serotonin (5-HT) reuptake; venlafaxine also inhibits norepinephrine reuptake, and nefazodone also exhibits 5-HT2-receptor antagonism. Venlafaxine inhibits the cytochrome P-450 2D6 isozyme to a lesser extent than the selective serotonin reuptake inhibitors (SSRIs) and is 27% protein bound. Structurally, the drugs are unrelated to SSRIs and have some clinically important differences in side effect profiles. Nausea, headache, somnolence, and dry mouth are the most frequently reported side effects with both. Sustained hypertension was reported by a limited number of venlafaxine-treated patients.
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PMID:Venlafaxine and nefazodone, two pharmacologically distinct antidepressants. 916 54

We investigated symptoms suggestive of swallowing problems in patients with primary biliary cirrhosis, some of whom displayed features of sicca complex. A prospective study of 95 consecutive patients with primary biliary cirrhosis was conducted at a single teaching hospital using a questionnaire administered over the telephone. Some symptoms of sicca complex (dry mouth and/or dry eyes) were found in 65 patients (68.4%). Subjective xerostomia alone was present in 45 patients (47.4%). The questionnaire revealed an increase in incidence of dysphagia in xerostomia subjects, affecting 21 of 45 patients, compared with 6 of 50 non-xerostomia patients. Multivariate logistic regression analysis showed that confounding factors such as age, obesity, cigarette smoking, and medications associated with a dry mouth could not explain these findings. Twenty-eight patients complained of hoarseness, 23 of coughing, and 14 of wheezing, all of which were significantly more frequent than in the 50 patients without xerostomia. Heartburn affected 17 xerostomia patients and 15 non-xerostomia patients, indicating no difference in frequency between these two groups, even after age, obesity, cigarette smoking, and medications associated with heartburn were considered in the multivariate analysis. Acid regurgitation, nausea, and vomiting were also similar in frequency between patients with and without xerostomia. Swallowing problems, manifested primarily as dysphagia, are common in primary biliary cirrhosis patients who have subjective xerostomia.
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PMID:Primary biliary cirrhosis, sicca complex, and dysphagia. 919 Jan 3

This article presents a summary of drug safety data concerning the use of tramadol hydrochloride and an outline of the specific aspects of this analgesic in particular with regard to respiratory depression and dependence potential. Information from phase II to IV clinical studies, postmarketing surveillance studies (covering safety data from a total of more than 21,000 patients) and the spontaneous reporting system have been taken into consideration. The data from the spontaneous reporting system covers the period between 1977 and 1993, during which more than one billion single dose units were distributed throughout the world. The phase II to IV studies compare acute intravenous, acute intramuscular, acute oral and multiple dose oral administration Postmarketing surveillance studies provide a picture of everyday use of tramadol in general medical practice. Further analyses were performed to provide information about the gender-, age- and dose-related distribution of adverse reactions The prevalence of side effects was calculated by comparing the number of symptoms with the number of patients. The pooled data from the clinical studies and the postmarketing surveillance studies reveal that the most commonly observed side effects were nausea, dizziness, drowsiness, tiredness, sweating, vomiting and dry mouth, with an overall incidence of between 1 and 6%. In the postmarketing surveillance studies on long term and acute administration, the profile of adverse events was qualitatively almost identical to that in the phase II to IV studies. However, there were distinct quantitative differences it favour of the long term studies. In the postmarketing surveillance study on acute parenteral administration, the incidences of nausea and vomiting were only 4.2 and 0.5% respectively, which is significantly lower than the 20.7 and 11.4% in the patient-controlled analgesia studies. Nevertheless, it is important to take into consideration the different conditions in these studies. All the postmarketing surveillance studies were outpatient studies, whereas almost all of the phase II to IV studies were carried out in hospitals. The studies with intravenous and intramuscular administration were mainly postoperative, which explains the relatively high incidence of nausea and vomiting, 17.8 and 7.0%, respectively, with intramuscular administration. The different conditions in the phase II to IV studies and the postmarketing surveillance studies are also reflected in the occurrence of dizziness and postural hypotension: The incidence of dizziness in the postmarketing surveillance studies is slightly higher than that observed in the phase II to IV studies. Particularly in the studies with intravenous and intramuscular administration, the patients were confined to bed and were therefore much less sensitive to dizziness than those in the long term oral and postmarketing surveillance studies, who were all outpatients. On the other hand, postural hypotension played almost no role in the multiple dose studies, in which the oral formulation were used most frequently. It is interesting to note that diarrhoea, pruritus and gastrointestinal disorder (except nausea and vomiting) are mainly reported in the multiple dose studies in the groups receiving oral tramadol, and also in the postmarketing surveillance studies. Once again, the study conditions may well be the explanation. The adverse effects reported in both clinical and postmarketing surveillance studies are similar to those in the spontaneous reports. The most frequently documented adverse effects in clinical and postmarketing surveillance studies, i.e. nausea/vomiting, dizziness, drowsiness, tiredness, sweating and dry mouth, are noted very infrequently in spontaneous reports, since in medical practice these side effects are usually known and are described in the product information. Almost all reports referring to abuse/dependence are connected with pain therapy; they give no reason to suspect any pro
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PMID:[Tolerance and safety of tramadol use. Results of international studies and data from drug surveillance]. 919 Mar 25

Major depressive disorder and dysthymia are twice as prevalent in women as in men, and the lifetime risk of a woman's developing a major depressive disorder is about 20%. Yet depression is often unrecognized or misdiagnosed in women, and only about one quarter of women who meet criteria for major depressive disorder receive appropriate therapy. Until recently, women were generally excluded from clinical drug trials because of concerns of inadvertent pregnancy and risk of teratogenicity. Thus, information on safety and efficacy in those most likely to require antidepressant therapy is lacking. Studies have shown that the antidepressant fluoxetine, a selective serotonin reuptake inhibitor (SSRI) has a more tolerable side effect profile than do tricyclic amine (TCA) antidepressants, but few data have been reported on the efficacy and tolerability of fluoxetine or other SSRIs in female patients. In this study, a retrospective analysis of 11 randomized, double-blind, well-controlled trials was done to compare data from 427 female patients on fluoxetine and 423 female patients on TCAs. Both fluoxetine and TCAs significantly reduced the HAMD17 total mean score from baseline to end point, week 5 (fluoxetine, 24.35 to 14.37; TCAs, 24.57 to 14.43; p < 0.001). Both treatment groups were associated with significant reductions in the HAMD17 anxiety/somatization and insomnia subfactor scores. Abnormal vision, constipation, dizziness, dry mouth, and somnolence occurred more frequently (p < 0.05) in the TCA group. Insomnia and nausea were the only adverse events more common (p < 0.05) in the fluoxetine group. This study demonstrates that fluoxetine is an effective and tolerable agent for the treatment of major depressive disorder in women.
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PMID:Fluoxetine vs. tricyclic antidepressants in women with major depressive disorder. 920 68


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