Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome. Symptoms of PMDD occur during the last week of the luteal phase of the menstrual cycle and usually abate at the onset of menses. About 3-8% of all menstruating women experience PMDD, which can lead to significant functional impairment. Several randomized, controlled trials have assessed the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of PMDD. The SSRIs were found to significantly improve symptoms, particularly psychological or behavioral symptoms, during the luteal phase in women with PMDD. Also, SSRIs were found to improve the quality of life in women with PMDD. Headache, fatigue, insomnia, and anxiety were often reported as adverse effects. A decrease in libido or sexual dysfunction also was reported. In recent studies, intermittent SSRI therapy was found to be effective treatment for PMDD and allows a woman to take the drug for only 14 days each month. Intermittent SSRI therapy should be recommended before continuous daily dosing of SSRIs in the treatment of PMDD.
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PMID:Treatment of premenstrual dysphoric disorder with selective serotonin reuptake inhibitors. 1452 45

Effects of double-blind treatment of chronic posttraumatic stress disorder (PTSD) with 2 SSRIs and placebo on emotional symptoms and autonomic reactivity were assessed prospectively. PTSD subjects received citalopram (n=25), sertraline (n=23), or placebo (n=10) for 10 weeks, with psychophysiologic assessments performed before and after treatment. Intent-to-treat analysis showed that all treatment groups improved significantly in total symptoms of PTSD (as measured by the Clinician Administered PTSD Scale), all 3 PTSD symptom clusters, and sleep time. However, subtle differences in improvements in PTSD symptom clusters, physiologic reactivity, and reported adverse events were identified. Citalopram treated subjects significantly lowered systolic and diastolic blood pressures, while sertraline and placebo treated patients significantly lowered only systolic blood pressure reactivity to individualized trauma scripts. The sertraline group showed significantly more improvement in avoidance/numbing symptoms than both other groups. Considering side effects, subjects on sertraline reported more gastrointestinal problems, with early terminators having more insomnia. Early terminators on citalopram reported more fatigue and appetite changes than other treatment groups, with completers reporting more sexual dysfunction. Results support a class effect of SSRIs in treating PTSD symptoms, but suggest a possible differential effect of drugs on symptom clusters, physiologic parameters, and side effects that may have clinical relevance. Implications of symptom reduction noted in the smaller placebo group are discussed relative to recent concerns about increasing placebo response in clinical trials.
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PMID:Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo. 1460 46

BACKGROUND: Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is characterized by a unique receptor-specific pharmacologic profile and tolerable side-effect profile in comparison to other antidepressants. It has been reported to have a low incidence of agitation, anxiety, and insomnia, which may be due to blockade of 5-HT(2) and 5-HT(3) receptors. This unique multireceptor-mediated clinical pharmacologic profile may reduce the need for polypharmacy in selected patients. CASE REPORTS: Three cases are presented. In case 1, mirtazapine was able to rapidly treat anxiety and agitation in a 90-year-old woman. This was confirmed with 3 consecutive challenges with mirtazapine. In case 2, both a mood disorder and insomnia were successfully treated with rapid resolution in a patient by using mirtazapine. In case 3, the patient experienced sexual dysfunction while receiving sertraline and developed insomnia with the addition of bupropion. The addition of mirtazapine and the discontinuation of sertraline and bupropion resolved the sexual dysfunction and insomnia. Polypharmacy interventions were decreased in these patients through receptor-specific events from mirtazapine. CONCLUSION: The new antidepressant mirtazapine appears to be an effective strategy for treating anxiety, agitation, and insomnia and for diminishing SSRI-related sexual dysfunction without compromising the patient's therapeutic response to the medication while decreasing the need for additional pharmacotherapies. More than 70% of patients with major depression will have anxiety symptoms. The 5-HT(2) receptor seems to play a major role in the regulation of anxiety. The anxiolytic properties of mirtazapine may be due to its antagonism of 5-HT(2) receptors and can appear as early as the first week of treatment.
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PMID:A Trilogy Case Review Highlighting the Clinical and Pharmacologic Applications of Mirtazapine in Reducing Polypharmacy for Anxiety, Agitation, Insomnia, Depression, and Sexual Dysfunction. 1501 75

Selective Serotonin Reuptake Inhibitors (SSRIs) have been accused of causing bleeding problems as a side effect. Theories about the mechanism are still being discussed. We report a case, presenting bleeding problems, during sertraline treatment. The SSRIs are widely used to treat depression and many other psychiatric disorders. Their lower severity of side effects and being markedly safer in overdose are some of the reasons of their preference as primary choice in most of the cases. Besides their common side effects like, agitation, headache, insomnia, weight gain or loss, and sexual dysfunction, SSRIs also have been suspected of increasing the risk of bleeding. A population-based cohort study supported the hypothesis of an increased risk of upper gastrointestinal bleeding during the use of SSRIs, and they also indicated that this effect is potentiated with concurrent use of NSAIDs or low-dose aspirin. We would like to report our recent experience with one patient who was on sertraline, 50 mg/day.
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PMID:Bleeding induced by SSRIs. 1633 93

Agomelatine is a new agent with a unique pharmacological profile, as the first melatonergic antidepressant. Its antidepressant efficacy has been demonstrated in the treatment of major depressive disorder (MDD) at a dose of 25 mg/day. Expectations from antidepressant therapies now go beyond efficacy alone, to include advantages in tolerability and safety. Due to its pharmacological profile, agomelatine does not induce the side-effects typical of other therapies, such as selective serotonin reuptake inhibitors (i.e. gastrointestinal disorders, weight gain, serotonergic syndrome and insomnia). Moreover, a placebo-controlled trial in MDD comparing the effects of agomelatine and venlafaxine on sexual dysfunction (another significant side-effect with current antidepressant medications) indicated the very favourable profile of agomelatine; in the same study, there was similar antidepressant efficacy in the same two groups. A double-blind, placebo-controlled trial investigating the effect of abrupt cessation of treatment demonstrated the absence of discontinuation symptoms with agomelatine, which was in contrast with the results observed with paroxetine. The ability of an antidepressant to relieve sleep complaints with no sedative effects is a key advantage because sleep complaints are a major presenting feature of depression. Again due to its unique pharmacological profile, agomelatine has been shown to positively influence disturbed circadian rhythms in depressed patients by significantly improving all phases of disturbed sleep and the overall quality of sleep, with a favourable impact on daytime alertness. In conclusion, experience with agomelatine across a range of clinical studies suggests that this compound offers a novel approach to the treatment of depression combining efficacy, even in severe depression, with an extremely favourable side-effect profile and sleep regulation. These properties give agomelatine a definite clinical advantage in the treatment of depression.
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PMID:Efficacy and tolerance profile of agomelatine and practical use in depressed patients. 1643 38

Our objective was to assess the effectiveness and safety of the combination of duloxetine and bupropion for treatment-resistant major depressive disorder (TRD). A retrospective chart review was conducted to identify patients with major depressive disorder (MDD) who had not experienced full remission of symptoms following an adequate trial of either duloxetine (n = 3) or bupropion (n = 7), and who then received the combination of these two antidepressants for TRD. Ten patients [37.2 +/- 11.3 years of age, five women, baseline Clinical Global Impressions (CGI) scale score 4.4 +/- 1.1], seven of whom had not remitted following treatment with bupropion (330 +/- 67 mg, 20.5 +/- 12.2 weeks), and three of whom had not remitted following treatment with duloxetine (90 +/- 30 mg, 18 +/- 2 weeks) received at least 4 weeks of combination treatment. The CGI was administered when the combination was first prescribed, and following 8.8 +/- 4.0 (range, 4-16) weeks of treatment. There was a significant decrease in CGI-S (Severity) scores (4.4 +/- 1.1 to 2.1+/-0.9, P <.0001) following combination treatment. Three (30%) patients were remitters at follow-up, and six (60%) were responders who did not achieve full symptom remission. The mean maximum adjunctive duloxetine and bupropion doses were 60.0 +/- 17.3 mg and 175.0 +/- 114.5 mg, respectively. Side effects reported during combination treatment were nausea (n = 2), dry mouth (n = 2), jitteriness/agitation (n = 2), fatigue/drowsiness (n = 2), increased blood pressure (n = 1), increased sweating (n = 1), insomnia (n = 1), pruritus (n = 1), headache (n = 1), sexual dysfunction (n = 1), and weight gain (n = 1). Although preliminary, these results suggest a possible role for the combination of duloxetine and bupropion for TRD.
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PMID:The combination of duloxetine and bupropion for treatment-resistant major depressive disorder. 1652 1

A total of 17 years after its introduction, bupropion remains a safe and effective antidepressant, suitable for first-line use. Bupropion undergoes metabolic transformation to an active metabolite, 4-hydroxybupropion, through hepatic cytochrome P450-2B6 (CYP2B6) and has inhibitory effects on cytochrome P450-2D6 (CYP2D6), thus raising concern for clinically-relevant drug interactions. Common side effects are nervousness and insomnia. Nausea appears slightly less common than with the SSRI drugs and sexual dysfunction is probably the least of any antidepressant. Bupropion is relatively safe in overdose with seizures being the predominant concern. The mechanism of action of bupropion is still uncertain but may be related to inhibition of presynaptic dopamine and norepinephrine reuptake transporters. The activity of vesicular monoamine transporter-2, the transporter pumping dopamine, norepinephrine and serotonin from the cytosol into presynaptic vesicles, is increased by bupropion and may be a component of its mechanism of action. Bupropion is approved for use in major depression and seasonal affective disorder and has demonstrated comparable efficacy to other antidepressants in clinical trials. Bupropion is also useful in augmenting a partial response to selective serotonin reuptake inhibitor antidepressants, although bupropion should not be combined with monoamine oxidase inhibitors. It may be less likely to provoke mania than antidepressants with prominent serotonergic effects. Bupropion is effective in helping people quit tobacco smoking. Anecdotal reports indicate bupropion may lower inflammatory mediators such as tumor necrosis factor-alpha, may lower fatigue in cancer and may help reduce concentration problems.
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PMID:Bupropion: pharmacology and therapeutic applications. 1700 13

Although older monoamine oxidase inhibitors (MAOIs) are effective in the treatment of depressive disorders, they are underutilized in clinical practice due to main concerns about interaction with tyramine-containing food, and side effects. Efforts to address these safety issues led to the development of a transdermal formulation of selegiline, called selegiline transdermal system (STS). STS has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depression. Transdermal administration of selegiline bypasses gastrointestinal absorption and first-pass metabolism. Therefore, STS permits inhibition of monoamine oxidase (MAO)-A and MAO-B enzymes in the brain while preserving the activity of MAO-A in the gastrointestinal system, thereby minimizing the risk of possible interactions with tyramine-rich foods. Tyramine challenge tests have confirmed that dietary modifications are not required with the 6 mg STS. The FDA has required dietary modifications with the 9 mg and 12 mg STS. Compared to oral administration, transdermal selegiline leads to sustained (minimal peak-trough fluctuations) plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain. The efficacy of STS has been established in several short-term and one long-term randomized controlled trials. In clinical trials, application site reactions and insomnia were observed more frequently with STS than placebo. Rates of orthostatic hypotension, sexual dysfunction and weight gain were comparable between STS and placebo. STS is a new generation of MAOI with superior safety profile to older MAOIs. It increases the pharmacological options available to treat depressive disorders and may benefit patients with major depression with atypical features and resistant depression. It is important for health-care professionals to be informed about the properties of STS.
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PMID:Transdermal selegiline. 1761 8

Antidepressant side effects may have implications with regard to patient safety as well as the overall tolerability of treatment. Side effects relevant to patient safety can contribute to an increased risk of morbidity and mortality, but may or may not result in patient distress or discomfort. In contrast, side effects related to tolerability can contribute to patient discomfort but are not associated with an immediate increase in risk of morbidity or mortality. Common tolerability-related side effects of modern antidepressants include nausea, insomnia, somnolence, fatigue, sexual dysfunction, and weight gain. Because these side effects can result in patient discomfort and distress, they can lead to poor compliance or noncompliance with treatment that, in turn, may result in an increased risk of depressive relapse or recurrence. Modern antidepressants have varying tolerability profiles, and clinicians should be vigilant about balancing treatment efficacy with side effects when choosing antidepressants. This article compares the rates of common tolerability-related side effects among the newer (post-tricyclic era) antidepressants with the selective serotonin reuptake inhibitors, the most popular contemporary first-line treatment for depression.
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PMID:Tolerability of modern antidepressants. 1849 38


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