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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present in vivo microdialysis study evaluates the possible existence of a differential regulation of serotonergic transmission by the antinarcoleptic drug modafinil [(diphenyl-methyl)-sulfinyl-2-acetamide; Modiodal] among various brain regions of the awake rat. The results show that, in the cerebral cortex, the central amygdala, and the dorsal raphe nucleus, modafinil in the dose range of 10-100 mg/kg i.p. dose-dependently increases dialysate serotonin (5-HT) levels. In other brain areas, such as the medial preoptic area and the posterior hypothalamus, the modafinil-induced increase in dialysate 5-HT levels is observed only at tenfold higher doses (100 mg/kg), 10-30 mg/kg being ineffective. Together these data suggest that, in the frontal cortex, the amygdala, and the dorsal raphe, modafinil is more potent in enhancing extracellular 5-HT levels and presumably 5-HT transmission than in the medial preoptic area and the posterior hypothalamus. In view of the role of ascending 5-HT pathways in arousal and depression, it seems likely that the antinarcoleptic drug modafinil may also have an antidepressant potential in addition to its wakefulness-promoting action, both actions involving enhancement of 5-HT neurotransmission.
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PMID:Differential enhancement of dialysate serotonin levels in distinct brain regions of the awake rat by modafinil: possible relevance for wakefulness and depression. 1193 55

Modafinil is a novel stimulant approved by the FDA for use in the management of excessive sleepiness associated with narcolepsy. Utility for other indications includes attention deficit-hyperactivity disorder (ADHD), depression, and management of cocaine dependence. To investigate the pharmacokinetics of modafinil in these patients, the authors improved and validated an HPLC method to separate and quantitate the separate enantiomers of modafinil in human serum. d- and l-Modafinil and the internal standard 3,3-diphenylpropylamine were extracted from serum, separated by gradient elution on a beta-cyclodextrin column, and then detected by UV absorbance at 225 nm. The elution gradient was developed to eliminate interferences by other drugs used to manage narcolepsy, ADHD, and stimulants of abuse, and endogenous substances in human serum. Validation studies included determination of stability, selectivity, precision, accuracy, and recovery. The method was used to investigate the pharmacokinetics of d- and l-modafinil in a volunteer after receiving 400 mg twice daily of racemic modafinil for 5 days. Interday and intraday assay variability (CV) typically ranged from 3% to 4%. The limits of detection (0.01 microg/mL) and quantitation (0.5 microg/mL) were well below the concentration expected in serum from patients receiving therapeutic doses of modafinil. The method was free from interference by methylphenidate, cocaine, commonly used antidepressants, and amphetamines. An example of apparent stereoselective disposition is presented as d-modafinil was eliminated more rapidly than l-modafinil from human serum. The validation data support the use of this method for human pharmacokinetic studies of modafinil in patients with known or suspected use of common antidepressants, psychostimulants, and drugs of abuse.
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PMID:Chiral analysis of d- and l-modafinil in human serum: application to human pharmacokinetic studies. 1265 14

Modafinil is a wake-promoting agent approved by the Federal Drug Administration for the treatment of narcolepsy. Preliminary evidence indicates that modafinil may improve fatigue and excessive sleepiness associated with a variety of conditions. The purpose of this study was to investigate the utility of modafinil as an adjunctive treatment of depressed patients. Subjects with a history of major depression with partial response on a stable therapeutic dose of an antidepressant were eligible to participate. All subjects endorsed complaints of significant fatigue and/or excessive sleepiness on clinical assessment. Modafinil was added to their existing regimen at a dose of 100 to 400 mg/d for 4 weeks. Subjects were assessed at 2-week intervals for improvement using the standard depression scales (HDRS, BDI, CGI), fatigue scales (VASF, FSI), and a neuropsychologic battery. Thirty-five subjects were entered and 31 subjects completed the 4-week trial. Significant improvements were seen across all 3 measures of depression (HDRS, BDI, CGIS) and both measures of fatigue (VASF, FSI). On the neurocognitive battery, significant gains in the Stroop Interference Test were seen at 4 weeks, whereas the other cognitive tests showed no change. Modafinil may be a useful and a well-tolerated adjunctive agent to standard antidepressants in the treatment of major depression.
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PMID:A prospective trial of modafinil as an adjunctive treatment of major depression. 1470 53

The wake-promoting agent modafinil (PROVIGIL) may prove useful as an adjunctive treatment in patients with suboptimal responses to antidepressant regimens. This retrospective chart review describes the use of modafinil as an adjunct to antidepressant therapy in 78 outpatients in a general psychiatric practice and discusses in detail treatment outcomes for 3 patients. Statistically significant improvements in mean Carroll Depression Rating Scale scores (p < 0.01), Visual Analog Scale scores for overall feeling (p < 0.003), and Clinical Global Impression of Severity ratings (p < 0.001) were demonstrated following treatment with modafinil. Treatment with modafinil rapidly improved wakefulness, fatigue, and everyday functioning in individual cases. Modafinil was well tolerated in combination with antidepressants and other medications. These findings suggest that adjunctive modafinil may improve treatment outcomes when used with antidepressant therapy in depressed patients, particularly in those with problematic sleepiness or fatigue.
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PMID:Modafinil as adjunctive therapy in depressed outpatients. 1551 45

In view of a postulated role of the vigilance-promoting drug modafinil in depression, the interaction of modafinil and two classical antidepressant drugs, fluoxetine and imipramine, were studied in 5-HT levels in the dorsal raphe-cortical system using dual-probe microdialysis. Fluoxetine (1-10 mg/kg) dose-dependently increased dorsal raphe-cortical 5-HT levels. Modafinil at a very low dose (3 mg/kg), by itself ineffective, enhanced the fluoxetine (5 mg/kg)-induced increases of 5-HT levels in both brain areas. A synergistic interaction was observed in the prefrontal cortex with fluoxetine (1 mg/kg) in terms of 5-HT release, but not in the dorsal raphe. Imipramine (1.3 mg/kg) increased 5-HT levels in the dorsal raphe, but not in the prefrontal cortex, while the higher doses (10.9-21.8 mg/kg) caused substantial increases in both brain areas. Modafinil (3 mg/kg), injected before imipramine (1.3 mg/kg), which by itself was ineffective on cortical 5-HT levels, increased cortical 5-HT levels. On other hand, modafinil failed to affect the high-dose imipramine (10.9 mg/kg)-induced increase of 5-HT levels in the prefrontal cortex and the imipramine (1.3; 10.9 mg/kg)-induced increase of 5-HT levels in the dorsal raphe nucleus. These results demonstrate that modafinil in low doses enhances the acute effects of fluoxetine and imipramine on 5-HT levels in the dorsal raphe nucleus (fluoxetine only) and especially in the prefrontal cortex of the awake rat. These findings suggest a therapeutic potential of low doses of modafinil in the treatment of depression when combined with low doses of classical antidepressants, especially by increasing 5-HT transmission in cortical regions.
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PMID:Modafinil enhances the increase of extracellular serotonin levels induced by the antidepressant drugs fluoxetine and imipramine: a dual probe microdialysis study in awake rat. 1566 7

Major depression is often refractory to antidepressants, and it is important to explore alternative medication treatments. Among the symptoms common with depression are energy loss/fatigue and anxiety. Modafinil has a novel mechanism of action and may have antidepressant properties. In a single outpatient clinic, data were systematically collected on all patients including those who began modafinil treatment for major depression. This clinician (C.P.) had used modafinil to treat major depression in patients who failed one or more adequate antidepressant treatments. To monitor changes during treatment, charting had included four rating scales: the Beck Depression Inventory, the Zung Self-Rating Depression Scale, and the Hamilton Depression and Hamilton Anxiety Rating Scales. A follow-up chart review identified 45 patients whose major depression was treated with modafinil over a 9-month period. The mean dose of modafinil was 184.3+/-100.0 mg/day (range=50-450 mg/day). For these 45 patients, all four rating scales showed significant improvement following 2 weeks and following 3 months of modafinil treatment. Fifteen of these patients were on modafinil monotherapy, and the remaining 30 on modafinil as an augmenting agent. For both subgroups, all three depression rating scales showed a significant improvement following 2 weeks and 3 months of modafinil treatment. This chart review provides preliminary evidence that modafinil treatment may be beneficial to those with major depression, even when unresponsive to other treatments.
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PMID:A retrospective chart review of the effects of modafinil on depression as monotherapy and as adjunctive therapy. 1603 49

Treatment-resistant depression, i.e. partial or non response to antidepressants in spite of various treatment attempts with optimized doses and combinations, is rather common. With residual symptoms such as tiredness, anhedonia and concentration disturbances, the treatment strategy has often been to use monoamino-oxidase inhibitors (MAOIs). Their use, however, is limited due to interaction problems. Modafinil is recently developed wake-promoting drug with only minor side-effects. Pilot studies indicate that it appears to have an augmentation effect in treatment-resistant depression. This open-label study performed in the private psychiatric practice setting is the first to make a comprehensive evaluation of the target patient profile based on patient-reported symptoms. Modafinil in doses of 100-400 mg was administered as augmentation to ongoing antidepressant therapy in patients with partial response and suffering from hypersomnia. The total number of patients was 21 and 43% of these were responders (i.e. had a score reduction of >50% on the Major Depression Inventory (MDI) as well as remitters, i.e. the remission rate was 43%. At endpoint, the responders had psychological distress scores on the Symptom Checklist (SCL-92) on the level of the general Danish population. Baseline characteristics for responders were lower scores on depression, hostility, anxiety, somatization, obsession and psychoticism. Modafinil thus appears to be an appropriate augmentation to antidepressant treatment, leading to a remission rate of 43%. However, the results from this open-label study need ot be confirmed in a placebo-controlled trial.
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PMID:Modafinil augmentation in depressed patients with partial response to antidepressants: a pilot study on self-reported symptoms covered by the Major Depression Inventory (MDI) and the Symptom Checklist (SCL-92). 1620 39

Atypical depression, with features of hypersomnia, hyperphagia, anergia, and rejection sensitivity, is a common presentation of major depressive disorder. There are few available effective therapies for this disorder. We test modafinil, a novel wake-promoting agent, as monotherapy for atypical depression in a double-blind, placebo-controlled, relapse prevention trial after open-label treatment. We found that modafinil significantly improved atypical depression symptoms during 12 weeks of open-label treatment (mean +/- SD Hamilton Depression Scale (29-item version) score changed from 34 +/- 8.2 at baseline to 9.7 +/- 9.3, P < 0.0001), and that benefits were maintained alike in both the continuation and placebo arms during the double-blind treatment phase (P = 0.92). Modafinil was well tolerated and the drug was associated with significant weight loss compared with placebo (P = 0.01).
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PMID:Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment. 1685 54

In this article, we highlight recent Bipolar Collaborative Network data. We found that childhood-onset bipolar illness is common, often goes untreated for more than a decade, and carries a poor prognosis. During randomized studies of adjunctive medications in depression: 1) Venlafaxine showed higher switch rates than bupropion or sertraline; 2) Tranylcypromine was as well tolerated as lamotrigine; and 3) Modafinil was more effective than placebo. Finally, in treatment of overweight and obesity, topiramate and sibutramine showed equal efficacy but poor tolerability, and zonisamide data showed that it may be useful for mood and weight loss.
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PMID:New findings from the Bipolar Collaborative Network: clinical implications for therapeutics. 1716 30

Modafinil, a medication for the excessive sleepiness associated with narcolepsy, has been hypothesized to improve not just alertness but mood as well. The purpose of this study was to determine how treatment with modafinil affects mood in healthy volunteers. Normal healthy volunteers (n = 12, 10 men and 2 women; 30-44 years) underwent a 3-day, counterbalanced, randomized, crossover, inpatient trial of modafinil (400 mg daily) versus placebo with 4-day washout period between 2 treatments. Mood was assessed daily using both the Positive and Negative Affect Schedule and a general mood scale, which consisted of 10 bipolar adjective ratings based on a severity scale ranging from 1 to 10. Modafinil increased general mood and Negative Affect scales relative to placebo and had a significant effect on Positive Affect scales. These results suggest that modafinil may have general mood-elevating effects accompanied by increased negative affect (anxiety). The findings may have implications for clinical practice, in particular for the adjunctive use of modafinil in treatment-resistant depression.
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PMID:A randomized, double-blind, crossover trial of modafinil on mood. 1722 18


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