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

Fluoxetine is a new antidepressant which enhances serotoninergic neurotransmission through potent and selective inhibition of neuronal reuptake of serotonin. Metabolism by N-desmethylation occurs in man yielding desmethylfluoxetine, which also inhibits serotonin reuptake. Both the parent compound and metabolite possess elimination half-lives of several days facilitating the maintenance of steady-state plasma concentrations during long term treatment. Fluoxetine has overall therapeutic efficacy comparable with imipramine, amitriptyline and doxepin in patients with unipolar depression treated for 5 to 6 weeks, although it may be less effective than tricyclic antidepressants in relieving sleep disorders in depressed patients. Geriatric patients also responded as well to fluoxetine as to doxepin. The symptomatic improvement in patients with unipolar depression during short term fluoxetine treatment has been satisfactorily maintained when therapy was extended for at least 6 months: the relapse rate was low and similar to that of imipramine. Preliminary data have shown that patients with bipolar depression gained similar therapeutic benefit from fluoxetine or imipramine. Other preliminary trials have indicated that fluoxetine may be useful in obsessive-compulsive disorders. Usual doses of fluoxetine cause significantly fewer anticholinergic-type side effects than tricyclic antidepressants. Nausea, nervousness and insomnia are the most frequently reported fluoxetine-related adverse effects, but these have usually not been severe. Therapeutic doses of fluoxetine do not affect cardiac conduction intervals in patients without pre-existing cardiovascular disease and fluoxetine has been relatively safe in the small number of patients who have taken overdoses. It has not been clearly established whether some types of depression may respond more readily to fluoxetine than other antidepressants, and its overall therapeutic efficacy has not been compared with other second generation antidepressants. Thus, with its different and perhaps improved side effect profile compared with older tricyclic antidepressants, fluoxetine offers properties that could be used to advantage in many patients with depression.
 ...
PMID:Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. 287 98

Selective serotonin-reuptake inhibitors (SSRIs), including fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram, represent an important advance in the pharmacotherapy of mood and other disorders. They are chemically unrelated to tricyclic, heterocyclic, and other first-generation antidepressants. SSRIs are the treatment of choice for many indications, including major depression, dysthymia, panic disorder, obsessive-compulsive disorder, eating disorders, and premenstrual dysphoric disorder, because of their efficacy, good side-effect profile, tolerability, and safety in overdose, as well as patient compliance. A review of the literature was conducted using Medline and the terms "SSRIs," "fluoxetine," "sertraline," "paroxetine," "fluvoxamine," and "citalopram." Articles were limited to those published in English within the last 15 years. The search revealed that indications for antidepressants include unipolar depression, dysthymia, bipolar depression, treatment-resistant depression, depression in the medically ill, panic disorder, obsessive-compulsive disorder, eating disorders, social phobia, and premenstrual dysphoric disorder. One SSRI, fluoxetine, has demonstrated safety in pregnancy. Side effects of SSRIs include gastrointestinal disturbances, headache, sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction.
 ...
PMID:Selective serotonin-reuptake inhibitors: an update. 1047 Dec 45

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.
 ...
PMID:Moclobemide: therapeutic use and clinical studies. 1504 13

The depressive expressions of bipolar disorders have long been neglected. Current data, from both clinical and epidemiologic studies, indicate that such expressions far exceed the manic forms in both cross-section and during follow-up course. Thus, mania occurs in 1% of the population at large; bipolar depression afflicts at least 5 times more people. Much of the new literature on this subject has emphasized its high prevalence, morbidity, and mortality. There has been relatively less attention paid to the phenomenology of bipolar depression as it presents clinically. This special issue (volume 84/2-3, 2005) is devoted to a systematic data-based in-depth examination of the different clinical expressions of bipolar depression including, among others, retarded depression, agitated and/or activated depression, mood-labile depression, irritable-hostile depression, atypical depression, anxious depression, depressive mixed state, and resistant depression. Both bipolar I (BP-I), and the more prevalent yet relatively understudied bipolar II (BP-II), are covered. We trust that this extensive coverage of the "darker" side of bipolarity will set the stage for a much needed renaissance in its complex phenotypic expressions-and its delimitation from unipolar depression (UP). The phenomenology of BP-I depression ranges from depressive stupor to agitated psychosis, whereas UP depression expresses itself in psychic anxiety, and insomnia, as well as retardation. BP-II compared with UP is more likely to have atypical features, mood lability, hostility, activation, biographical instability, multiple anxiety comorbidities, suicidal tendencies, and to be rated as less "objectively" depressed. These findings are complex and do not fully agree with the conventional characterization of BP as retarded and UP as anxious and agitated. The inconsistency between the conventional and the phenomenology described herein is largely due to depressive mixed states, which tend to destabilize BP-II, and may account for the "contradictory" relationships of affect, sleep, drive, and psychomotor activity in mood disorders.
 ...
PMID:The dark side of bipolarity: detecting bipolar depression in its pleomorphic expressions. 1570 7

Antipsychotics are commonly used in bipolar disorder, both for acute mania and in maintenance treatment. The authors review available clinical research concerning the use of both conventional and atypical antipsychotics in bipolar disorder and present recommendations for a number of key clinical situations based on this review. They also consider a number of important related questions, including whether there is evidence for an increased risk of tardive dyskinesia (TD) in patients with bipolar disorder, the potential role for antipsychotics in the treatment of bipolar depression, the role of antipsychotics in maintenance treatment of bipolar disorder, the potential for antipsychotics to induce depression in bipolar illness, and whether antipsychotics can be considered mood stabilizers with a place as monotherapy for bipolar mania. They conclude that standard treatment for acute mania should begin with a mood stabilizer, with benzodiazepines used as an adjunct for mild agitation or insomnia and antipsychotics used as an adjunct for highly agitated, psychotic, or severely manic patients. They also conclude that atypical antipsychotics are preferable to conventional antispychotics because of their more favorable side effect profile and reduced risk of tardive dyskinesia. They review the evidence for using atypical antipsychotics as first-line monotherapy for mania and conclude that more evidence concerning the risk of TD and their efficacy as maintenance treatment in bipolar disorder is needed before a conclusion can be made. Should the eventual risk of TD associated with atypical antipsychotics be found to be minimal and their efficacy in maintenance treatment found to be high, they could eventually be considered first line monotherapy for bipolar disorder. They conclude that treatment with an antipsychotic during bipolar depression should be limited to those patients who have psychosis and that atypical antipsychotics are preferred over conventional antipsychotics in this situation, not only because of their reduced risk of side effects but also because theoretically they may have antidepressant efficacy due to their effects on the serotonin system. The clinical research findings summarized in the article are, for the most part, supported by a recently published guideline based on a consensus of clinical experts.
 ...
PMID:Clinical research on antipsychotics in bipolar disorder. 1599 Apr 92

In bipolar depression, psychomotor agitation is relatively common and often is associated with other noneuphoric hypomanic symptoms and suicidal ideation. Our goal in this retrospective study was to ascertain the co-occurrence of agitation, bipolar features, and suicidal ideation in unipolar disorder. We retrospectively evaluated 314 inpatients with DSM-IV major depressive disorder (MDD) and no other Axis I diagnosis with the National Institutes of Mental Health (NIMH) Life Chart Method and the Operational Criteria for Psychotic Illness (OPCRIT) checklist to ascertain their symptom profiles across all episodes. Univariate and multivariate comparisons were performed between the subgroups with and without psychomotor agitation (OPCRIT item 23> or =1). Agitated depression (AD, a major depressive episode with psychomotor agitation) was present in 19% of the sample. Compared to nonagitated counterparts, patients with AD were older and had lower educational levels and more dysphoria, insomnia, positive thought disorder, and psychotic manifestations. Hypomanic symptoms other than agitation were relatively uncommon (<10%) and more represented in subjects with AD. No significant differences emerged between AD and control groups with respect to most bipolar validators (gender, familiarity, recurrence). Patients with AD had higher levels of suicidal ideation than non-AD controls; however, such a difference was no longer significant after controlling for psychotic features. Excessive self-reproach, early awakening, diurnal changes, poor appetite, and hypomanic symptoms were independently associated with suicidal thoughts in nonpsychotic MDD. Incomplete information on drug treatment, exclusion of patients with Axis I comorbidity, and tertiary care setting were the most important limitations of the study. Although we failed to support the bipolar nature of MDD-AD by common validators, probably because we used a more heterogeneous definition of agitation compared to similar studies, our data confirm the association of agitation with hypomanic symptoms and suicidal thoughts in major depression, and emphasize the complex phenomenology of AD in an inpatient setting.
 ...
PMID:Retrospective analysis of psychomotor agitation, hypomanic symptoms, and suicidal ideation in unipolar depression. 1682 57

This research assesses the development of the night-activity rhythm and quality of sleep during course of treatment among patients with unipolar or bipolar depression and receiving antidepressant treatment plus quetiapine. Twenty-seven patients with major depressive episode were included into a 4-week follow-up study and compared with 27 healthy controls. Motor activity was continuously measured with an electronic wrist device (actigraphy), sleep was assessed with the Pittsburgh Sleep Quality Index, and patients were clinically assessed with the Hamilton depression score. All patients received a standard antidepressant treatment plus quetiapine. Whereas we found a rapid and maintaining improvement of subjective sleep parameters during the 4-week study, we observed a rapid improvement of some objective sleep parameters (actigraph) within the first week, but no further significant change of objective sleep parameters during the rest of the study. Another main finding of this study is that changes of subjectively and objectively assessed sleep parameters do not necessarily reflect clinical improvement of depression during the same timeline. Despite partial clinical remission, objective sleep parameters still showed significantly different patterns compared with controls. This study is the first to examine the effect of quetiapine on locomotor activity alongside with sleep in depression. As the studied patients with depression showed improvement in subjective and objective sleep parameters, quetiapine may be a promising drug for patients with depression and insomnia. Further studies need to investigate in detail the timeline of clinical remission and alterations of objective and subjective sleep parameters.
 ...
PMID:Night locomotor activity and quality of sleep in quetiapine-treated patients with depression. 1711 Aug 22

Although most treatment research on bipolar disorder has focused on mania, depressive episodes occur more frequently among patients with bipolar disorder. Here, we report the results of 2 identically designed, 8-week, multicenter, randomized, double-blind, placebo-controlled studies (CN138-096 and CN138-146) to evaluate the efficacy and safety of aripiprazole monotherapy in outpatients with bipolar I disorder experiencing a major depressive episode without psychotic features. Patients were randomized to placebo or aripiprazole (initiated at 10 mg/d, then flexibly dosed at 5-30 mg/d based on clinical effect and tolerability). The primary end point was mean change from baseline to Week 8 (last observation carried forward) in the Montgomery-Asberg Depression Rating Scale total score. In Studies 1 and 2, respectively, 186 and 187 patients were randomized to aripiprazole, and 188 and 188 to placebo. Although statistically significant differences were observed during Weeks 1 to 6, aripiprazole did not achieve statistical significance versus placebo at Week 8 in either study in the change in Montgomery-Asberg Depression Rating Scale total (primary end point). In addition, despite early statistical separation on the Clinical Global Impressions Bipolar Version Severity of Illness-Depression score (key secondary end point), aripiprazole was not superior to placebo at end point. Aripiprazole was associated with a higher incidence of akathisia, insomnia, nausea, fatigue, restlessness, and dry mouth versus placebo. More patients discontinued with aripiprazole versus placebo in Study 1 (46.8% vs 35.1%) and Study 2 (41.2% vs 29.8%). Aripiprazole monotherapy-as dosed in this study design-was not significantly more effective than placebo in the treatment of bipolar depression at end point (Week 8).
 ...
PMID:Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. 1820 35

Bright light is a treatment of choice for seasonal affective disorder. Other indications for bright light therapy have also been tested. These include non-seasonal depression, bipolar depression, chronic depressive disorder, ante- and postpartum depression, late luteal phase dysphoric disorder, circadian phase sleep disorders, jet lag, shift work problems, and behavioral disturbance and insomnia in organic dementia. Future studies should focus on exploring the use of light therapy in combination with sleep deprivation, other classes of antidepressants, and with psychotherapy and their possible combined effect on subtypes of depression or other mentioned diagnoses, light treatment duration, and the applicability and efficacy of adjunct light treatment for in-patients.
 ...
PMID:Bright light therapy. 1902 78

The purpose of the study was to determine clinical and diagnostic distinctions between the episodes of recurrent depression and bipolar depression. The subjects of the study were 79 patients meeting ICD-10 criteria for either recurrent depressive disorder or bipolar affective disorder. Patient with recurrent depression presented more prominent HDRS symptoms of depressed mood, psychomotor retardation, somatic anxiety, and gastro-intestinal somatic complains. Bipolar patients had more scores related to middle and late insomnia, agitation and suicide. In addition lower length of remission was observed in bipolar depression. The revealed differences should be taken into account in diagnostic and pharmacological treatment of various types of depression.
 ...
PMID:[Comparative study of recurrent and bipolar depression]. 1999 3


1 2 Next >>