Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The past decade has witnessed the advent of selective serotonin reuptake inhibitors (SSRIs) as first-line treatments for major depression. Still, there is considerable debate as to whether these agents are as effective or as potent as the first-generation tricyclic antidepressants (TCAs) or the mixed reuptake inhibitor, venlafaxine, all of which exert considerable effect on norepinephrine (NE) reuptake. Recently, reboxetine, a selective NE reuptake inhibitor (selective NRI), has been introduced in Europe. This drug has only a minimal affinity for muscarinic acetylcholine receptors and therefore causes less dry mouth, constipation, or other such effects than do the TCAs. Reboxetine does not block serotonin reuptake or alpha1 receptors and, thus, does not appear to produce significant nausea, diarrhea, or hypotension. Unlike other antidepressants, reboxetine appears to be nonsedating. Data on acute and long-term clinical efficacy and safety from double-blind, placebo-controlled, and active comparator studies with reboxetine are reviewed. These studies indicate that reboxetine is significantly more effective than placebo and as effective as fluoxetine in reducing depressive symptoms. Improvements in social adjustments were reported to be more favorable with reboxetine than with fluoxetine. Further, data from controlled clinical trials have shown that the side effect profile for reboxetine is relatively benign. The clinical implications of studies on reboxetine are discussed with an eye toward understanding the potential role NE reuptake blockers may play in the treatment of patients with major depression.
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PMID:Clinical efficacy of reboxetine in major depression. 1091 15

Depression in the elderly is often not recognised and is frequently under-treated. Reboxetine is a selective noradrenaline reuptake inhibitor (selective NRI) which is effective and well tolerated in the treatment of depressed adult patients. This prospective, uncontrolled, multicentre study was designed to assess the efficacy and tolerability of reboxetine as maintenance therapy for major depressive disorder or dysthymia in 160 elderly patients (aged 65-94 years). One hundred and thirty-nine patients completed the 6-week run-in period and entered the long-term phase; 104 patients completed the 52-week treatment period. The proportion of patients with CGI-global improvement ratings assessed as 'much' and 'very much' improved increased from 15.1% at week 2 to 88.7% at week 6 and to 95.2% at week 52. The mean HAM-D total score showed a reduction from 24.0 at baseline to 10.4 at week 6 and 7.5 at week 52. Twenty-five patients discontinued treatment due to adverse events. The most frequently reported adverse events were nausea (11.9%), insomnia (11.9%), headache (10.0%) and dry mouth (9.1%), and these were of mild or moderate severity. In summary, results from this study show reboxetine to be effective, and well tolerated in both the short- and long-term treatment of elderly depressed or dysthymic patients.
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PMID:Reboxetine in the maintenance therapy of depressive disorder in the elderly: a long-term open study. 1098 24

Geriatric patients with major depression present clinical challenges not encountered in younger individuals, including a greater incidence of medical comorbidity, higher rates of multiple medication use, changes in drug metabolism due to age or physical illness, and increased sensitivity to antidepressant side effects. Nevertheless, successful treatment of depressive disorders in the elderly improves mental and physical functioning, decreases morbidity and perhaps mortality, and enhances quality of life. Recent research indicates that newer antidepressants are effective for late life depression and safer for older individuals. Among newer antidepressants, venlafaxine has a pharmacological profile that makes it an attractive choice for geriatric patients. It has limited potential to interact with other medications because it only weakly inhibits the cytochrome P450 system and binds to plasma proteins at a low level. Dosing may have to be adjusted for patients with renal failure, but typically not for those with liver disease or other medical conditions. Data from three double-blind and four open clinical trials support the safety and efficacy of venlafaxine for geriatric depression. Patients may experience transient, generally tolerable side effects such as insomnia, nausea, agitation, or dry mouth early in treatment, but more serious problems such as falls or cardiac rhythm disturbances seem to be rare. Treatment emergent hypertension occurs in a small percentage of older patients, generally at doses above 150 mg/day. Finally, emerging data suggest that venlafaxine may be effective for conditions such as stroke, anxiety, and neuropathic pain that frequently accompany depressive disorders in the elderly.
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PMID:Efficacy of venlafaxine in geriatric depression. 1109 16

The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score > or = 18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with > or = 1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58-69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD = 170), also within the range of previous trials (321-472 mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by > 6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21-33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports.
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PMID:Open trial of nefazodone among Hispanics with major depression: efficacy, tolerability, and adherence issues. 1138 31

1. Men and women may differ in their pharmacokinetic responses to tricyclic antidepressants (TCAs), in a number of autonomic indices, and in various adrenergic receptor mediated responses. Emerging evidence also suggests that women may have a lower rate of serotonin synthesis in brain and a greater sensitivity to the depressant effects of tryptophan depletion, relative to men. However, sex-related differences in TCA-induced side-effects, including increases in heart rate (HR), dry mouth, constipation, and difficulty urinating, has not been systematically investigated. 2. The authors examined potential sex-related differences in the pattern of side-effects during treatment with nortriptyline (NT), a TCA that is still widely used. Seventy-eight healthy outpatients who met Research Diagnostic Criteria and DSM-III-R criteria for major depression participated in a double-blind, randomized parallel trial of NT versus placebo. 3. Each subject was acutely challenged with either placebo or 50 mg NT prior to and after a 6-week treatment with NT. NT doses were adjusted weekly to maintain therapeutic plasma levels. Patients were assessed at multiple time points to detect the presence of NT-induced side-effects. 4. The initial, single (50 mg) dose of NT significantly increased supine HR. Six-week treatment with NT was found to significantly increase supine and sitting HRs, irrespective of sex. In rechallenge with the single NT dose, there were no significant effects on HR. 5. When sex-related differences were examined, HR increases were greater in men than women during weeks 4 through 6 of the NT treatment, although no sex-related differences were present in plasma NT levels or metabolites. In addition, there was a significant NT to placebo difference in self-rated dry mouth for women during all 6-weeks of treatment, whereas men showed a significant NT-placebo difference during weeks 3 and 5. 6. The results suggest the presence of sex-related differences in elevated supine HR response during the course of 6-week NT treatment. Depressed men may be more susceptible to NT-induced increases in supine HR than women.
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PMID:Sex-related differences in nortriptyline-induced side-effects among depressed patients. 1144 76

The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action. Mirtazapine is extensively metabolized in the liver. The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for its metabolism. Using once daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in the elderly. In vitro studies suggest that mirtazapine is unlikely to cause clinically significant drug-drug interactions. Dry mouth, sedation, and increases in appetite and body weight are the most common adverse effects. In contrast to selective serotonin reuptake inhibitors (SSRIs), mirtazapine has no sexual side effects. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. In major depression, its efficacy is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, or venlafaxine. Mirtazapine also appears to be useful in patients suffering from depression comorbid with anxiety symptoms and sleep disturbance. It seems to be safe and effective during long-term use.
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PMID:A review of the pharmacological and clinical profile of mirtazapine. 1160 47

We attempted to compare the antidepressant efficacy of milnacipran and fluvoxamine in 202 outpatients with major depression, using the 17-item Hamilton Depression Rating Scale (HDRS). Special attention was paid to the difference of responsiveness as a function of the severity of depression and individual HDRS factors. As a result, while no significant difference between the treatment groups was found overall, a positive response (50% or more decrease in total score from the baseline) was recorded significantly more often with milnacipran than fluvoxamine recipients whose baseline HDRS total score was greater than 19 points. Furthermore, there was a significant difference of response for the 'agitation' and 'insomnia' factors in favour of milnacipran. In both treatment groups, the incidence of adverse events, characteristic of tricyclic antidepressants such as dry mouth, constipation, somnolence and postural hypotension, was low. While complaints concerning the upper intestinal tract, such as epigastric distress, were predominant in the fluvoxamine group, urological complications and palpitations were reported only in the milnacipran group. In conclusion, we suggest that milnacipran is preferred to selective serotonin reuptake inhibitors for the treatment of depressed patients with agitation as well as severely depressed patients.
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PMID:Differential effects of milnacipran and fluvoxamine, especially in patients with severe depression and agitated depression: a case-control study. 1189 Jan 86

Sertraline (SRT) has been shown to be an effective antidepressant in extensive clinical trial programs but data on plasma concentrations regarding clinical outcome and tolerability are lacking. Twenty-one out-patients of both sexes, with mean age of 50.23 years (S.D. = 17.37), affected by major depressive disorder, recurrent (Diagnostic and Statistical Manual of Mental Disorder--IV, DSM-IV), were treated with 25-150 mg of SRT once a day (mean=66.26 mg, S.D.=30.50) for 30 days. Clinical evaluation was assessed at baseline (T0), after 15 days (T15), and then after 30 days (T30). Plasma samples for SRT level determination were collected at T30. Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale for Depression (HRS-D), and Hamilton Rating Scale for Anxiety (HRS-A) showed a significant improvement during the study (P<.01 vs. T0). The most commonly reported side effects were nausea (19%), cephalalgia (9.5%), dry mouth (9.5%), decreased libido (9.5%), tremor (4.7%), and tachycardia (4.7%). SRT plasma levels ranged from 2.82 to 112.20 ng/ml (mean=40.42 ng/ml, S.D.=26.93). No correlation between SRT plasma levels and clinical improvement or side effects were observed. Drug plasma level determination does not seem be strictly necessary from a clinical point of view but further research seems advisable in patients at risk like elderly and during long-term studies.
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PMID:Clinical outcome and tolerability of sertraline in major depression: a study with plasma levels. 1199 14

Escitalopram oxalate (S-citalopram, Lexapro), a selective serotonin re-uptake inhibitor antidepressant which is the S-enantiomer of citalopram, is in clinical development worldwide for the treatment of depression and anxiety disorders. Preclinical studies demonstrate that the therapeutic activity of citalopram resides in the S-isomer and that escitalopram binds with high affinity to the human serotonin transporter. Conversely, R-citalopram is approximately 30-fold less potent than escitalopram at this transporter. Escitalopram has linear pharmacokinetics, so that plasma levels increase proportionately and predictably with increased doses and its half-life of 27 - 32 h is consistent with once-daily dosing. In addition, escitalopram has negligible effects on cytochrome P450 drug-metabolising enzymes in vitro, suggesting a low potential for drug-drug interactions. The efficacy of escitalopram in patients with major depressive disorder has been demonstrated in multiple short-term, placebo-controlled clinical trials, three of which included citalopram as an active control, as well as in a 36-week study evaluating efficacy in the prevention of depression relapse. In these studies, escitalopram was shown to have robust efficacy in the treatment of depression and associated symptoms of anxiety relative to placebo. Efficacy has also been shown in treating generalised anxiety disorder, panic disorder and social anxiety disorder. Results also suggest that, at comparable doses, escitalopram demonstrates clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram. Analysis of the safety database shows a low rate of discontinuation due to adverse events, and there was no statistically significant difference between escitalopram 10 mg/day and placebo in the proportion of patients who discontinued treatment early because of adverse events. The most common adverse events associated with escitalopram which occurred at a rate greater than placebo include nausea, insomnia, ejaculation disorder, diarrhoea, dry mouth and somnolence. Only nausea occurred in > 10% of escitalopram-treated patients.
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PMID:Escitalopram. 1238 7

Existing therapies for major depressive disorder (MDD) have either limited efficacy and/or poor tolerability. The present study examined the effects of duloxetine, a potent and balanced dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE), in patients with MDD. Adult patients (N = 267) with MDD were randomly assigned to receive duloxetine (60 mg/day) or placebo in this 9-week, multi-center, double-blind, parallel-group clinical trial. Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD(17)), Visual Analog Scales (VAS) for pain, Clinical Global Impression of Severity (CGI-S), Patient's Global Impression of Improvement (PGI-I), and Quality of Life in Depression Scale (QLDS). Safety was evaluated by assessing discontinuation rates, adverse event rates, vital signs, and laboratory tests. Duloxetine (60 mg QD) significantly reduced the HAMD(17) total score compared with placebo at the end of 9-week therapy. Estimated probabilities of response and remission were 65 and 43%, respectively, for duloxetine compared with 42 and 28% for placebo. Duloxetine also reduced overall pain, back pain, shoulder pain and time in pain while awake significantly more than placebo. Global measures of improvement, including PGI-I and QLDS, were significantly improved by duloxetine compared with placebo. Discontinuations due to adverse events were more frequent for duloxetine-treated patients (12.5%) than for placebo-treated patients (4.3%). Nausea, dry mouth, dizziness, and constipation were more frequent for duloxetine than placebo. There was no significant incidence of hypertension, nor any other safety issues. Duloxetine 60 mg administered once daily appears to be a safe and effective treatment for MDD.
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PMID:Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. 1239 7


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