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PubMed1979

Combined use of guar and acarbose in reduction of postprandial glycaemia.

Symptoms associated with carbohydrate malabsorption limit the usefulness to diabetics of a powerful glycoside-hydrolase inhibitor (acarbose) which reduces postprandial glycaemia. Addition of a low dose (50 mg) of a acarbose together with 14.5 g guar gum to a breakfast test meal taken by 8 healthy volunteers reduced the mean peak rise in blood-glucose at 30 min by 70%. Areas under the insulin and gastrointestinal-polypeptide response curves were also greatly reduced. No evidence of carbohydrate malabsorption, as assessed by measurement of breath hydrogen, was found during any of the test periods. When acarbose was taken alone, 3 of the 8 subjects had troublesome symptoms and the 30 min rise in blood-glucose was reduced by only 28%. Thus, combination of these two agents effectively reduces the rate of carbohydrate absorption without increasing side-effects and may make combined acarbose and guar acceptable in the management of some diabetics.

Adult↗
PubMed2000

Neuroleptic malignant syndrome after venlafaxine.

A patient developed neuroleptic malignant syndrome after a single dose of venlafaxine with trifluoperazine treatment. A dopamine-inhibition effect induced by one dose of venlafaxine may have augmented dopamine-receptor inhibition by trifluoperazine.

Adult↗
PubMed2000

SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression.

A major goal of antidepressant development is to improve on preceding drug classes with agents with greater specificity (and therefore fewer unwanted side-effects) and with more rapid onset of antidepressant action. To this end, four antidepressants with significantly distinct pharmacological characteristics have been recently introduced: venlafaxine, nefazodone, mirtazapine, and reboxetine. Venlafaxine is the first antidepressant in a new drug class referred to as the serotonin noradrenergic reuptake inhibitors (SNaRIs). Nefazodone is a weaker serotonin and norepinephrine reuptake inhibitor, but a potent serotonin 5-HT2 receptor antagonist. Mirtazapine is a potent antagonist of central 2alpha-adrenergic autoreceptors, and heteroreceptors and is an antagonist of serotonin 5-HT2 and 5-HT3 receptors. The result of these actions is to increase both noradrenergic and specific (5-HT1) serotonergic transmission, and mirtazapine has therefore been termed a noradrenergic and specific serotonergic antidepressant (NaSSA). Reboxetine is the first selective noradrenaline reuptake inhibitor (NaRI) to be introduced since the tricyclics, and lacks immediate serotonergic effects.

Antidepressive Agents↗
PubMed1999

Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors, and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials.

The purpose of this study was to summarize and compare the clinical success rates of extended-release venlafaxine, some selective serotonin reuptake inhibitors (SSRIs), and certain tricyclic antidepressants (TCAs). A meta-analytic approach was used to synthesize outcomes from published randomized controlled trials involving patients scoring > or =15 on the Hamilton Rating Scale for Depression (HAM-D) or > or =18 on the Montgomery-Asberg Depression Rating Scale (MADRS). Searches of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases were performed, as were searches of references from retrieved articles and reviews. Drugs included in the comparison were extended-release venlafaxine (venlafaxine-XR); the SSRIs citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and the TCAs amitriptyline, imipramine, desipramine, and nortriptyline. Therapeutic success was defined as a 50% decrease in the HAM-D or MADRS score. Data were extracted by 2 independent evaluators, with differences resolved through consensus discussions. Weighted mean success rates were calculated for each drug class, using a random-effects model. The resulting data represent 44 trials with 63 study arms and 4033 patients with depression. Venlafaxine-XR demonstrated a 73.7% success rate, which was statistically significantly greater than that of the studied SSRIs (61.1%) and TCAs (57.9%) (P<0.001). Thus this meta-analysis of randomized controlled studies of patients with depression suggests that venlafaxine-XR is clinically superior in efficacy to SSRIs and TCAs. Venlafaxine-XR also had universally lower, though nonsignificant, dropout rates.

Antidepressive Agents, Second-Generation↗
PubMed2002

Efficacy of venlafaxine in patients with major depressive disorder who have unsustained or no response to selective serotonin reuptake inhibitors: an open-label, uncontrolled study.

BACKGROUND: Approximately half of patients who are prescribed selective serotonin re-uptake inhibitors (SSRIs) either do not respond to treatment or do not experience a sustained response. OBJECTIVE: The purpose of this study was to assess the efficacy of venlafaxine immediate-release (IR) and extended-release (XR) in outpatients who either did not respond to SSRI treatment or did not maintain a sustained response. METHODS: Outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depressive disorder who were previously treated with an SSRI (fluoxetine > or = 20 mg/d; sertraline > or = 50 mg/d; paroxetine > or = 20 mg/d) for > or = 6 weeks, but demonstrated an inadequate or unsustained response, were switched to venlafaxine (IR or XR formulation, 50-400 mg/d, titrated from 37.5 mg/d) for > or = 6 weeks. Response at 6 to 8 weeks was defined as total score < or = 10 on the modified 25-item Hamilton Depression (HAM-D25) rating scale or total score > or = 5 on the 21-item Patient Global Improvement (PGI-21) scale. Remission was defined as a HAM-D25 total score < or = 8 or PGI-21 score > or = 7. Tests were administered by an unblinded, board-certified psychiatrist. RESULTS: A total of 73 patients (54 women, 19 men; mean age, 38.6 years) were enrolled and treated with venlafaxine IR (n = 63) or venlafaxine XR (n = 10); 33 were SSRI nonresponders and 36 had an unsustained response to SSRI treatment. Four patients receiving venlafaxine IR discontinued due to drug-related adverse events (agitation, sedation, or nausea). Data from these patients were excluded from the analysis. After 6 to 8 weeks of treatment, 94.2% (65/69) of patients were considered responders (HAM-D25 or PGI-21 criteria); 91.3% (63/69) of patients responded to treatment as assessed by both measures. Eighty-seven percent (60/69) and 85.5% (59/69) of patients achieved remission based on HAM-D,5 and PGI-21 criteria, respectively. Response/remission rates were comparable among patients treated with SSRIs, regardless of whether patients had failed to respond to treatment with 1 or 2 SSRIs. CONCLUSION: Venlafaxine IR/venlafaxine XR may be effective in outpatients with major depressive disorder who do not respond or have an unsustained response to SSRIs. However, randomized, controlled trials are needed before any conclusions can be drawn about the efficacy of this agent in this population.

Adolescent↗
PubMed2003

Venlafaxine: a 2003 update.

BACKGROUND: venlafaxine has been available for use as an antidepressant in the United States for a decade. OBJECTIVE: Comprehensive reviews of venlafaxine have been published elsewhere; thus, this update focuses on newer issues of treatment remission in depression, treatment-resistant depression, and extended-release venlafaxine for generalized anxiety disorder (GAD). METHODS: Relevant clinical literature from 1993 through 2003 was identified from database searches of MEDLINE and International Pharmaceutical Abstracts, and from manual searches of reference lists of the identified papers. Search terms included venlafaxine extended-release, venlafaxine XR, treatment-resistant depression, depressive disorders, anxiety disorders, generalized anxiety disorder, and antidepressive agents second generation. RESULTS: With its dual action of serotonin and noradrenergic reuptake inhibition, venlafaxine has been shown to be superior in efficacy to selective serotonin reuptake inhibitors for severe major depressive disorder, treatment-resistant depression, and depressive symptom remission. Its demonstrated efficacy for both short- and long-term treatment of GAD has led to its use for obsessive-compulsive disorder and chronic pain syndromes, although inadequate clinical literature currently exists to support these latter 2 uses. In the past decade, no new or unexpected adverse events have been identified with venlafaxine therapy, except a possibly greater risk of fatal overdose compared with other serotonergic drugs, suggesting the need for caution in patients with suicidal ideation. Because venlafaxine is a potent serotonin agonist, caution must also be exercised to prevent the possibility of serotonin syndrome when used with other serotonin agonists, and its dose should be tapered very gradually to minimize the risk of a serotonin withdrawal reaction. CONCLUSION: Venlafaxine has emerged as a successful post-SSRI-era antidepressant with an expanded range of uses since it was first marketed.

Antidepressive Agents, Second-Generation↗
PubMedDate not supplied

Cost-effectiveness of venlafaxine for the treatment of major depression in hospitalized patients.

The economic burden of depression is often underestimated, especially when both the direct and indirect costs of treating the disease are considered. The costs associated with antidepressant drug therapy are often the focus of efforts to reduce overall treatment costs, but in actuality they represent only 10% of the overall economic costs of depression. Thus, in analyses of the costs of depression, other factors-including hospitalization, physician costs, monitoring, and indirect costs associated with lost productivity and comorbidity-are important. Economic assessments comparing different antidepressant classes have often found that newer antidepressants are more cost-effective than older, less expensive drugs because of improved tolerability or efficacy. Venlafaxine represents the newest class of antidepressants and offers potential pharmacologic benefits, including early onset of action, dose flexibility, broad range of activity, and improved tolerance. In one analysis that used the results from a study of 67 hospitalized depressed patients, venlafaxine was estimated to result in a cost savings of 11.3% versus fluoxetine. These findings support the concept that the overall costs of depression are more important than the drug costs in determining the cost-effectiveness of therapy.

Antidepressive Agents, Second-Generation↗
PubMedDate not supplied

A randomized, open-label comparison of venlafaxine and fluoxetine in depressed outpatients.

In this randomized, open-label, 8-week comparative study, the efficacy and safety of venlafaxine and fluoxetine were assessed in outpatients with major depression. One hundred forty-five patients were assigned to receive venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily. On day 15, if clinically indicated to improve patient response, the dosage could be increased at the investigator's discretion to venlafaxine 75 mg twice daily or fluoxetine 40 mg once daily. One hundred forty-five patients were evaluated for safety and 110, for efficacy. The mean age was 37 years, and 70% of the patients were female. In both treatment groups, mean scores on the Hamilton Depression Rating Scale decreased significantly between baseline (27.8, venlafaxine; 29.2, fluoxetine) and the end of the study (8.7, venlafaxine; 8.2, fluoxetine). Similarly, mean scores on the Montgomery-Asberg Depression Rating Scale decreased significantly between baseline (31.4, venlafaxine; 31.6, fluoxetine) and the end of the study (8.3, venlafaxine; 7.6, fluoxetine). In venlafaxine patients, the most common adverse events were nausea (44.3%), headache (40.0%), insomnia (31.4%), dizziness (30.0%), and dry mouth (22.9%); in fluoxetine patients, they were headache (32.0%), nausea (28.0%), insomnia (24.0%), anxiety (21.3%), sleepiness (20.0%), and generalized tremor (20.0%). The results of this study indicate that venlafaxine is effective and well tolerated for the treatment of major depression at doses of 37.5 or 75 mg twice daily and not significantly different from fluoxetine 20 or 40 mg once daily.

Adolescent↗
PubMedDate not supplied

Early onset of antidepressant action of venlafaxine: pattern analysis in intent-to-treat patients.

Pattern analysis has been used to distinguish between the true effect of an antidepressant and a placebo effect. The placebo effect constitutes clinical improvement that is attributable to the caregiver, treatment setting, or placebo substance. Pattern analysis allows identification of patients who have early persistent responses, delayed persistent responses, or no responses to a drug. In our study, we used this method to assess the onset and persistence of antidepressant activity of high daily doses of venlafaxine. Our analysis considered scores on the Global Improvement item of the Clinical Global Impressions scale for intent-to-treat patients in two double-masked, placebo-controlled studies of at least 6 weeks' duration. Dosages in both studies were rapidly titrated upward so patients received at least 200 mg/d within the first week of treatment. Improvement within the first 2 weeks was considered early, and improvement not followed by a relapse through the scheduled end of treatment was considered persistent. Significantly greater percentages of patients in the venlafaxine group (27% and 20% in study 1 and study 2, respectively) than in the placebo group (9% and 2%, respectively) had a clinically meaningful drug response within the first 2 weeks of treatment. This early response persisted for the duration of each trial. We concluded that venlafaxine in dosages of at least 200 mg/d demonstrates an early and persistent onset of efficacy compared with placebo.

Adult↗
PubMed1997

Pharmacology of cannabinoid CB1 and CB2 receptors.

There are at least two types of cannabinoid receptors, CB1 and CB2, both coupled to G-proteins. CB1 receptors are present in the central nervous system and CB1 and CB2 receptors in certain peripheral tissues. The existence of endogenous cannabinoid receptor agonists has also been demonstrated. These discoveries have led to the development of selective cannabinoid CB1 and CB2 receptor ligands. This review focuses on the classification, binding properties, effector systems and distribution of cannabinoid receptors. It also describes the various cannabinoid receptor agonists and antagonists now available and considers the main in vivo and in vitro bioassay methods that are generally used.

Animals↗
PubMed2001

Microdialysis in freely moving mice: determination of acetylcholine, serotonin and noradrenaline release in galanin transgenic mice.

In the present study, we describe micro-surgical methods for simultaneous implantation of a microdialysis probe and an intraventricular injection cannula via their respective guide cannulas into the mouse brain. Basal and stimulated release of acetylcholine (ACh), serotonin (5-HT) and noradrenaline (NA) was determined in the ventral hippocampus of freely moving mice. NA and 5-HT were determined in one run by a newly developed HPLC method based on precolumn derivatization with benzylamine and fluorescence detection. The mice with a loss-of-function mutation of the galanin gene (KO) and the mice that over-expressed galanin (OE) were studied. No significant differences in basal, potassium-stimulated or scopolamine-induced extracellular ACh levels were observed in 4-month-old wild-type (WT) and KO mice. In the aged, 10-month-old animals, the basal extracellular ACh levels were significantly reduced in both WT and KO groups. Galanin (1 nmol i.c.v.) caused a significant reduction of basal extracellular NA by about 40% in both WT and galanin OE mice, however, in the latter group the effect was delayed by almost 2 h. A 10-min forced swimming stress caused a higher increase in release of NA and 5-HT in the OE group than in the corresponding WT mice. Finally, venlafaxin (10 mg/kg i.p.) increased extracellular NA to 400% of the control values in the CBA mice, but only to 250% in the C57BL mice. It is concluded that galanin may play an important role in the cholinergic mechanisms underlying cognitive disorders. Furthermore, modulation by galanin and by behavioral activation, of NA and 5-HT neurotransmission in galanin over-expressing mice indicates its possible role in the aetiology of mood disorders.

Acetylcholine↗
PubMed1997

Differential pharmacological treatment response in high angry hostile and low angry hostile depressed patients: a retrospective analysis.

Fava et al., Am. J. Psychiatry 150 (1993)1158-1163, have recently proposed the existence of a sub-type of depressed patients who experience anger attacks. These investigators hypothesized that patients who experience anger attacks will respond better to a specific selective serotonin reuptake inhibitor (SSRI) medication than will depressed patients who do not experience anger attacks. Using a non-randomized, archival treatment methodology, 158 patients were classified as either high angry hostile (n = 83) or low angry hostile (n = 75). These patients had been treated with either a primarily noradrenergic reuptake inhibitor (desipramine) a SSRI (sertraline or paroxetine), or the combined serotonin and norepinephrine reuptake inhibitor (SNRI), venlafaxine. A 2 (high angry hostile/low angry hostile) x 3 (medication type) analysis of variance (ANOVA) was non-significant, indicating no differential treatment effects.

1-Naphthylamine↗
PubMed1997

Breast enlargement during chronic antidepressant therapy.

Recent reports of mammoplasia during selective serotonin re-uptake inhibitor (SSRI) therapy suggested that this side effect may be more common than previously reported. We examined 59 women receiving > or = 2 months treatment with an SSRI or venlafaxine for changes in breast size in relation to menopausal status, weight gain and duration of drug therapy. Serum prolactin, estradiol and beta-hCG were also measured before and during treatment in a subgroup of patients. Twenty-three out of 59 patients (39%) reported some degree of mammoplasia. Significantly more SSRI vs. venlafaxine patients reported mammoplasia (p < 0.01). Eighty-four percent with mammoplasia had weight gain vs. 30% without mammoplasia (p < 0.001). The rate of mammoplasia was unrelated to age, menopausal status or duration of treatment. Serum prolactin increased during treatment in the paroxetine subgroup (p < 0.03). In conclusion, antidepressant-induced mammoplasia may be more common than previously expected.

Breast↗