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

Available evidence suggests that antidepressants need to be continued on a long-term basis after the acute response. Premature discontinuation soon after symptomatic response is associated with the return of depression (relapse) in many patients. One efficacy measure of an antidepressant required by many regulatory authorities prior to approval of the agent is the ability of the antidepressant to continue the acute response compared with a placebo control. The reference tricyclic antidepressants (TCAs) amitriptyline and imipramine both have been shown to be effective in this continuation phase, but there is surprisingly little evidence on the efficacy of the other TCAs. The serotonin selective reuptake inhibitors paroxetine, fluoxetine, sertraline, and citalopram, as well as nefazodone, a new antidepressant with a dual mechanism of action that is classified as a serotonin receptor modulator, are effective compared with placebo. Placebo appears to be a good comparator in assessing the long-term efficacy of antidepressants. For example, in an assessment of the long-term efficacy of citalopram, patients who responded while taking placebo and were continued on placebo treatment were compared with patients who responded to drug and were transferred to placebo. The relapse rates in both cases were similar, validating placebo as a useful control. Most studies of long-term efficacy use the discontinuation design in which patients are treated with an active drug until response is obtained and then are either continued on the active drug or switched to placebo in a random and blinded manner. Alternatively, studies with nefazodone have used the double-blind continuation design, which may be preferred because it avoids any confounding effects of the discontinuation of drug in a drug-responsive patient. For example, in acute studies, responders to treatment with nefazodone, imipramine, or placebo were continued on the same treatment under double-blind conditions for 1 year; both antidepressants were effective compared with placebo. This study design may be useful in providing an estimate of long-term efficacy that can be obtained relatively early in a drug development program. The length of treatment in the continuation phase of therapy is also of interest. The separation of drug and placebo efficacy is sharpest in the first 4 months, which is consistent with the recommendation that all treatment for depression should continue for a minimum of 4 to 6 months to prevent relapse after symptomatic response of the acute episode. After the continuation phase (relapse prevention), evolving evidence strongly indicates that antidepressant treatment should be continued in patients at risk for recurrence. Depending on the number of recurrences, lifelong prophylactic therapy may be warranted.
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PMID:Efficacy in long-term treatment of depression. 862 60

Thirty-three years ago, Gaddum and Picarelli classified the serotonin receptors in the guinea pig ileum into D and M types based on the activity of dibenzyline (D) and morphine (M) to block contractions of intestinal smooth muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification of 14 serotonin receptor sub-types in rat brain. The cloning of these receptor sub-types has been of importance in enabling them to be classified as specific-protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub-types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub-types in sleep, anxiety states, schizophrenia and depression. A summary of the relationship between these receptor sub-types and their possible involvement in the aetiology of schizophrenia, depression, anxiety and sleep disorders.
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PMID:Serotonin receptors and their function in sleep, anxiety disorders and depression. 871 Oct 84

Serotonergic mechanisms are involved in gender-related behaviors and psychiatric conditions like aggression, eating disorders, depression, impulsivity or suicide. We studied gender differences in the living human brain type-2 serotonin receptor (5HT2r). Twenty-two healthy age-matched men and women were investigated using positron emission tomography and the selective radiotracer, 18F-labeled altanserin. Binding was quantified using a non-linear least-squares minimization procedure. We found significantly higher 5HT2r binding capacity in men than in women, especially in the frontal and cingulate cortices. Distinct liability for men and women to suffer from some psychiatric disorders responding to serotonergic agents may be related to differences in brain serotonin receptors.
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PMID:Sex difference in 5HT2 receptor in the living human brain. 892 69

Serotonin is a neurotransmitter involved in a large number of psychophysiological processes including the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth and importantly, appetitive functions. Alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including depression, anxiety, eating disorders, schizophrenia etc. Hence, genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and therefore are of great pharmacogenetic relevance. Knockout mice deficient of a functional 5-HT2C receptor have implicated a potential role of this receptor subtype in the serotonergic control of appetite. A Cys23Ser mutation in the human 5-HT2C receptor gene discovered recently prompted us to investigate this mutation with regard to the development of human obesity. We have evaluated this mutation in 241 obese children and adolescents (mean BMI > or = 97th percentile), 80 normal weight children (BMI 5th-85th percentile) and 92 underweight probands (BMI < or = 15th percentile) for a possible association with obesity. The frequencies of the mutant allele in all three weight groups (obese subjects: 0.1597; normal weight: 0.168; underweight: 0.1575) were very similar. Association as well as linkage studies were negative. Therefore it is unlikely that this receptor mutation plays a direct role in the development of human obesity.
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PMID:Evaluation of a Cys23Ser mutation within the human 5-HT2C receptor gene: no evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults. 920 Jun 73

Serotoninergic system is involved in the regulation of diverse biological and psychological functions and a variety of serotonin receptor subtypes represent a possible target for a new generation of medications. 5-HT receptors play an important role in both schizophrenia and depression. Modern strategies for treating schizophrenia profit from the existence of interaction between serotonin and dopamine systems. New drugs called serotonin-dopamine antagonists (SDAs) offer wider spectra of activity and lower extrapyramidal side effects liability. The principle of the SDAs is that the drug should be a potent serotonin 5-HT 2A antagonist, with slightly less potent dopamine D2 receptor-blocking properties. New pharmacological agents with great therapeutic potential and fewer side effects were recently developed also for the treatment of depression. Among these new antidepressives the serotonin selective reuptake inhibitors (SSRIs) currently play the most important role.
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PMID:[Serotonin and treatment of mental disorders. Present status and future perspectives]. 934 Jan 86

We present the case of a 35-year-old woman who developed serotonin syndrome after receiving a single dose of the cyclic antidepressant imipramine (Tofranil). She was already being treated for depression with paroxetine (Paxil), a selective serotonin reuptake inhibitor. Two hours after receiving imipramine, the patient developed tachycardia, delirium, bizarre movements, and myoclonus, all classic findings of serotonin syndrome. Her antidepressants were discontinued and she was treated with intravenous fluids, sedation, and a short course of cyproheptadine, a serotonin receptor antagonist. All symptoms resolved completely within 24 hours. In this case report, we review the drug interactions that can precipitate serotonin syndrome, and give recommendations for the diagnosis and treatment of this potentially fatal disorder.
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PMID:Serotonin syndrome: case report and review of the literature. 941 60

Over the past several years, remarkable advances have been made both in our understanding of the central nervous system (CNS) and in the pathophysiology of the major psychiatric disorders, resulting in major break-throughs in our capacity to treat these devastating illnesses. Since the seminal work of Ramon Y Cajal and Golgi at the turn of the century, new techniques such as fluorescence histochemistry have evolved into immunohistochemical and more recently in situ hybridization. These techniques have permitted, for the first time, the elucidation of chemically defined neural circuits. Such advances in the mapping of neural systems and the visualization of monoaminergic and peptidergic neurons and their receptors in tissue sections have provided the tools for the burgeoning field of neurochemical pathology of psychiatric disorders. Data provided from such studies has served as the basis for the development of novel pharmacological approaches to the treatment of affective and anxiety disorders, as well as schizophrenia. This review focuses on two major neural systems implicated in the pathophysiology of depression, serotonin and corticotropin-releasing factor (CRF). Development of novel agents are described including selective serotonin receptor agonists, combined selective serotonin receptor antagonists and serotonin reuptake inhibitors, CRF receptor antagonists, and the use of an antisense strategy.
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PMID:Psychopharmacology of affective disorders in the 21st century. 978 75

A growing body of literature describes the effects of estrogen and other gonadal steroids on the central nervous system. The ability of estrogen to modulate serotonergic function, in particular, raises the possibility that sex steroids may play a role in the mechanisms associated with depression and its treatment. This review will focus on those aspects of the estrogen-serotonin interaction that relate to possible increased vulnerability to affective disorders and on hormonal treatments that may be clinically applicable to women. After a discussion of the potential relationship between estrogen and mood disorders across the female life cycle, a model is proposed in which differential sensitivity to mood disorders explains the differential response by some women to periods of normal hormonal changes. Possible serotonin receptor-mediated and intracellular mechanisms by which estrogen may exert its effects on mood are also reviewed. These are compared to putative mechanisms of standard antidepressant effect. Lastly, treatment studies in which estrogen has been used as 1) monotherapy for depression, 2) an augmentation strategy, or 3) a prophylactic intervention against recurrence of depression are reviewed.
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PMID:Estrogen, serotonin, and mood disturbance: where is the therapeutic bridge? 980 36

Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder. However, such treatment may decrease serotonin receptor responsivity. We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients. Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterwards. Ten unmedicated patients underwent the same procedures. Symptoms improved 4 h after both metergoline and placebo. The day after metergoline but not placebo, fluoxetine-treated patients had significantly increased anxiety, obsessions and compulsions, abating over several days. Depression was unchanged. Metergoline had no similar delayed effects in unmedicated patients. Metergoline levels were higher in fluoxetine-treated patients. These results, consistent with less conclusive earlier findings, suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder.
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PMID:Delayed obsessive-compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients. 988 19

A role for serotonin in migraine has been supported by changes in circulating levels of serotonin and its metabolites during the phases of a migraine attack, along with the ability of serotonin-releasing agents to induce migraine-like symptoms. The development of serotonin receptor agonists with efficacy in the clinic for the alleviation of migraine pain further implicates serotonin as a key molecule in migraine. Several theories regarding the etiology of migraine have been proposed. The vasodilatory theory of migraine suggested that extracranial arterial dilation during an attack was related to migraine pain; a theory supported when vasoconstrictors such as sumatriptan alleviated migraine pain. The neurological theory of migraine proposed that migraine resulted from abnormal firing in brain neurons. Cortical spreading depression, one facet of the neurological theory, could explain the prodrome of migraine. The neurogenic dural inflammation theory of migraine supposed that the dural membrane surrounding the brain became inflamed and hypersensitive due to release of neuropeptides from primary sensory nerve terminals. Substance P, calcitonin gene related peptide and nitric oxide are all though to play a role in the dural inflammatory cascade. Animal models of migraine have been utilized to study the physiology of migraine and develop new pharmaceutical therapies. One model measures the shunting of blood to arteriovenous anastomoses based on a proposal that migraine primarily involves cranial arteriovenous vasodilation. Another model utilizes electrical stimulation of the trigeminal ganglion to induce neurogenic dural inflammation quantified by the resulting extravasation of proteins. Pharmacological agents such as meta-chlorophenylpiperazine (mCPP) and nitroglycerin have also been used to induce dural extravasation in animals. Both compounds also induce migraine attacks in individuals with a history of migraine. In addition, Fos, a protein produced by activation of the c-fos gene, has been measured as an index of migraine-like pain transmission to the CNS following chemical or electrical stimulation of the trigeminal nerve. A role for serotonin in migraine is further supported by the efficacy of serotonin receptor ligands. Sumatriptan is an agonist at 5-HT1D and 5-HT1B receptor subtypes, and effective in treating migraine pain and associated symptoms. Recently, selective 5-HT1F agonists have been proposed for the treatment of migraine, without the side effects associated with the present 5-HT1D and 5-HT1B receptor agonists. A role for 5-HT2B receptors has also been suggested the initiation of migraine, supporting use of selective 5-HT2B receptor antagonists in migraine. Thus, agents that modulate 5-HT1B, 5-HT1D, 5-HT1F and 5-HT2B receptors either have or may have clinical utility in the therapy of migraine headache.
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PMID:Serotonin in migraine: theories, animal models and emerging therapies. 994 63


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