[NEW TRENDS IN MODERN PHARMACOLOGY].
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Anesthetics↗
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[Obsessive-compulsive disorders in general practice. How the obsessive-compulsive neurotic is revealed by skin and hair].
Obsessive-compulsive disorder (OCD) is characterized by obsessions, compulsions, or both, which cause significant personal distress or social dysfunction. OCD is a common psychiatric illness with a prevalence of 1-2%. Because most people have regular contact with primary health care services, the patient with OCD is likely to see their general practitioner even though psychological problems may not be the main reason for consultation. Early recognition of the disorder facilitates early intervention. This reduces distress, disability and burden of illness. Pharmacological treatment with serotonin reuptake inhibitors (SRI) and cognitive-behavioral therapy have both been proven to be effective and are evidence based.
Adolescent↗
[Panic attacks and panic disorder. Checklist for the diagnosis].
After looking for possible organic factors, other psychiatric disorders must be considered, e.g. depression or other anxiety disorders. With respect of the different neurobiologic and psychologic factors of panic attacks the therapy should be complex. Psychotherapy (e.g. behavior therapy) and psychopharmacologic treatments were proved very well. For the general practitioner the treatment with SSRI is very helpful. This approach provides a 60% full remission. For an uncomplicated disorder prophylactic treatment is necessary.
Adult↗
Are all antidepressants the same?
Historically, the clinician's choice of antidepressant agent has been determined largely by consideration of tolerability, given the perception that the therapeutic efficacy of the various antidepressants was broadly comparable. However, with the advent of the newer, more selective antidepressants, indications of variation in clinical efficacy have begun to emerge. The advent of the selective serotonin reuptake inhibitors has been welcomed by patients, largely owing to their superior tolerability profile compared with older antidepressants. However, severely depressed patients appear to benefit particularly from agents that include a noradrenergic mode of action, such as tricyclic antidepressants and the modern dual-action antidepressants mirtazapine, venlafaxine (at higher doses), and milnacipran. In addition, a noradrenergic component may offer superior efficacy in social functioning. The recent development of a novel, selective norepinephrine reuptake inhibitor (reboxetine) with proven efficacy in a range of depressed patients will permit the investigation of the relevance of the noradrenergic approach. Clinical observations of the effects of the newer, more selective antidepressants are important in our understanding of precise mode of action, variation in efficacy and tolerability, and comparative usefulness in clinical practice.
Antidepressive Agents↗
Pharmacological treatment of adolescent major depression.
Antidepressant agents are widely prescribed for adolescents, although specific data regarding their efficacy in this age range are limited. The aims of the present article are to review research findings regarding the use of antidepressant drugs for adolescent depression and to discuss the main results in light of our clinical experience. Only 13 controlled trials on the use of antidepressant drugs for adolescent major depression are available in the literature. Six studies evaluated the efficacy of tricyclic antidepressants, yet they only included 196 adolescents altogether. Seven studies, including a total of 1,403 patients, evaluated the efficacy of three specific serotonin reuptake inhibitors: fluoxetine, paroxetine, and sertraline. Based on published data, serotonin reuptake inhibitors appear to be the first-line psychopharmacologic treatment for adolescent depression, as three compounds (fluoxetine, paroxetine, and sertraline) appeared to be effective in this indication. Conversely, all published studies failed to demonstrate that the tricyclic antidepressants were superior to placebo. Several questions remain open and are discussed: How should we use available scientific data in clinical practice? Are there nonspecific factors implicated in treatment response? Is there a serotonin hypothesis for juvenile depression? What are the priorities for future research?
Adolescent↗
Recognition and management of depression in the elderly.
Depression is probably the most common psychiatric disorder of the elderly. Societal stereotypes and atypical clinical features are contributing factors to inadequate diagnosis and treatment. Somatic complaints without an obvious mood defect and a syndrome of pseudodementia are commonly encountered. Treatment strategies rest firmly on a comprehensive evaluation that considers the biological, psychologic, and social factors involved. Psychotherapy is a valuable tool in some elderly persons. When antidepressant agents are used, it should be recognized that lower than usual dosage may be effective and that the elderly person is particularly sensitive to the autonomic side effects of these chemical agents. Electroconvulsive therapy remains a helpful and sometimes lifesaving resource when other methods have failed.
Aged↗
Effects of antidepressants and anticholinergics in a mouse "behavioral despair" test.
A new "behavioral despair" test previously asserted to be selectively sensitive to antidepressant treatments was examined for specificity. The results of the present study demonstrate that, in addition to antidepressants, agents with anticholinergic properties such as scopolamine, danitracin, benactyzine, benztropin, clozapine and cyproheptadine also reduce immobility in this test. These results indicate that the swim test in mice cannot be considered selectively sensitive to antidepressants.
Animals↗
Antidepressant medication use and restless legs syndrome in patients presenting with insomnia.
BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a movement disorder that frequently results in significant complaints of insomnia. Based on published case reports, it is commonly believed that RLS can be caused or exacerbated by antidepressant agents, thus complicating the treatment of depressed patients who are already prone to sleep disturbances. However, there are no systematic studies demonstrating an association between the clinical diagnosis of RLS and the use of antidepressant medication. PATIENTS AND METHODS: Retrospective chart review of 200 consecutive patients presenting for evaluation of sleep initiation insomnia at an accredited freestanding sleep disorders center that is part of an integrated health care system. RESULTS: Mean age (+/-SD) of patients was 51.1+/-14.8 years; 60% were women. Fifty-six percent carried a diagnosis of depression, 38% were being treated with antidepressant medication at presentation and 45% met clinical diagnostic criteria for RLS. There were no statistical associations, either by chi(2) analysis or odds ratios, between RLS and antidepressant use or use of any specific class of antidepressant. Positive associations with RLS were found for patients receiving treatment for hypothyroidism and those taking estrogens; a significant negative association was found for patients receiving beta adrenergic antagonists. CONCLUSIONS: Although there are anecdotal reports of antidepressant use causing or exacerbating RLS, systematic study of this issue fails to corroborate an association.
Adult↗
Do adenosine receptors play a role in amitriptyline-induced cardiovascular toxicity in rats?
OBJECTIVE: The aim of the our study was to investigate the role of adenosine receptors on cardiovascular toxicity induced by amitriptyline, a tricyclic antidepressant agent. Therefore, the hypothesis of this study was that adenosine receptor antagonists would improve and/or prevent amitriptyline-induced hypotension and conduction abnormalities in an anesthetized rat model of amitriptyline intoxication. METHODS: Two separate experimental protocols were performed. Amitriptyline intoxication was induced by the infusion of amitriptyline 0.94 mg/kg/min until 40-45% reduction of mean arterial pressure (MAP). Sodium cromoglycate (10 mg/kg) was injected i.v. to inhibit the A3 receptor-mediated activation of mast cells. In protocol 1, after amitriptyline infusion, while control animals (n=8) were given dextrose solution, treatment groups received a selective adenosine A1 antagonist DPCPX (8-cyclopentyl-1,3-Dipropylxanthine, 20 microg/kg/min, n=8) or a selective A2a antagonist CSC (8-(3-chlorostyryl) caffeine, 24 microg/kg/min, n=8) for 60 minutes. In protocol 2, after the sodium cromoglycate, while control group of rats (n=8) recevied a dextrose solution, treatment groups of rats were administered DPCPX (20 microg/kg/min, n=8) or CSC (24 microg/kg/min, n=8) infusion to block adenosine A1 and A2a receptors for 20 minutes before amitriptyline infusion. After pretreatment with adenosine antagonists, all rats were given a dose of 0.94 mg/kg/min of amitriptyline infusion during 60 minutes. Outcome measures were mean arterial pressure (MAP), heart rate (HR), QRS duration and survival rate. RESULTS: In protocol 1, amitriptyline infusion significantly reduced MAP and prolonged QRS within 15 minutes. HR was not changed significantly during the experiments. While dextrose did not improve MAP and QRS prolongation, DPCPX or CSC administration developed a significant improvement in MAP compared to the dextrose group within 10 min (88.5 +/- 2.8%, 75.6 +/- 4.7% and 50.1 +/- 14.7%, p<0.01, p<0.05, respectively). Both DPCPX and CSC decreased QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.00001). In protocol 2, pretreatment with DPCPX or CSC prevented the reduction in MAP due to amitriptyline toxicity compared to rats administered dextrose infusion (99.5 +/- 2.6%, 102.4 +/- 2.6%, 81.8 +/- 5.4, p<0.01 at 30 min; 98.0 +/- 2.9%, 93.5 +/- 6.0%, 64.9 +/- 4.7, p<0.001, p<0.01 at 40 min, respectively). Pretreatment with DPCPX or CSC also prevented the QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.0001). CONCLUSION: Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline-induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results suggest that adenosine receptors may have a role in the pathophysiology of amitriptyline-induced cardiovascular toxicity. Adenosine A1 and A2a receptor antagonists may be promising agents for reversing amitriptyline-induced cardiovascular toxicity.
Amitriptyline↗
Antidepressant-type effect of the NK3 tachykinin receptor agonist aminosenktide in mouse lines differing in endogenous opioid system activity.
The influence of the tachykinin NK3 receptor agonist, aminosenktide on the immobility in the forced swimming test was studied in mouse lines selectively bred for divergent magnitudes of stress-induced analgesia. The high analgesia (HA) line is known to display enhanced, and the low analgesia (LA) line displays reduced activity of the opioid system. Aminosenktide at doses of 125 microg/kg or 250 microg/kg intraperitoneally (IP) reduced, in naltrexone-reversible manner, the immobility more of opioid receptor-dense HA than of unselected mice, but was ineffective in the opioid receptor-deficient LA line. The effect of aminosenktide was quite similar to the antiimmobility action of desipramine (10 mg/kg IP), a prototypic antidepressant agent. None of the compounds increased animals' locomotion as found with an open field test; therefore their antiimmobility effect cannot be attributed to a change in general motility. The results claim that aminosenktide causes an antidepressant effect, and endogenous opioids are involved in this process.
Analgesia↗
The phenomenon of rapid cycling in bipolar mood disorders: a review.
OBJECTIVE: To review the various pharmacological and nonpharmacological factors associated with the induction of rapid cycling in bipolar mood disorder, and to introduce the idea that parturition may also have a role. Factors known to contribute to bipolar mood disorder rapid cycling include antidepressant agents, female gender and middle age. Currently, there is evidence that hypothyroidism may also play a role. METHOD: A critical review of the literature was undertaken. CONCLUSION: Caution should be exercised in the use of antidepressants in patients with bipolar mood disorders.
Adult↗
[Modern aspects of mood disorders].
Mood disorders, particularly depression, now represent a major world health problem which will most likely continue increasing. From a clinical standpoint, the synthesis of new antidepressant agents of various chemical structures and the advent of the thymoregulators (lithium salts) has allowed a more flexible, better individualized, therapeutic approach to the affective disorders. However, the widespread use by general practitioners of the antidepressants, alone or in combination with other psychotropic drugs, often with mitigated success, brings to psychiatric consultation patients whose symptomatology has become less characteristics, is more difficult to identify rapidly, requiring thus greater diagnositc refinement. Moreover, greater attention is currently given to depressive affects that can occur during organic illnesses or at various periods of life, particularly at senescence. Besides sustained concerns concerning suicide, the attitude of man confronted with his death arouses great interest and a depressive phase constitutes one of the steps towards this ending. Finally, during the last two decades, some psychoanalysts have reexamined the psychodynamic concepts of mood disorders, whereas from behavioral and cognitive theories new techniques of treatment of depression have emerged. In brief, if no revolution has occurred, there has been evolution. Mood disorders and their approach have known modifications and some concepts pertinent to this are considered here from various angles, particularly from the clinical (association with organic illnesses, with respect to death), therapeutic (psychopharmacological, behavioral and cognitive therapies), sociological (including suicide) and psychoanalytic viewpoints.
Antidepressive Agents, Tricyclic↗
Clinical options for imipramine in the management of urinary incontinence.
Urinary incontinence is a common disorder in both childhood and adulthood. Proper treatment depends on insight into the pathophysiology and pharmacology of the lower urinary tract. This article reviews the mechanism of action of an old but commonly used drug, the tricyclic antidepressant agent imipramine, in nocturnal enuresis and stress and urge incontinence with reference to neuropharmacology and the relevant pathophysiology.
Antidepressive Agents, Tricyclic↗
Depression and chronic medical illness.
Major depression is the most common clinical problem primary care physicians are called upon to diagnose and treat. Depression is associated with high medical care utilization, amplification of somatic symptoms and disability, poor self-care and adherence to medical regimens, and increased morbidity and mortality from medical illness. Despite the high prevalence and the maladaptive effects of major depression on patients' lives, this affective illness is often not accurately diagnosed or effectively treated. Double-blind, placebo-controlled studies have increasingly demonstrated efficacy of the antidepressant agents in primary care patients, patients with chronic pain, and patients with comorbidity--chronic medical illness and major depression.
Antidepressive Agents↗
Mirtazapine for treatment-resistant depression: a preliminary report.
OBJECTIVE: To describe the effectiveness and tolerability of mirtazapine, a noradrenergic and specific serotonergic antidepressant, in the open-label treatment of patients with depression who were resistant to other antidepressant agents. METHODS: The charts of 24 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria for major depressive disorder and were treated with mirtazapine after partial or nonresponse to standard antidepressants were reviewed for clinical response. Outcome was determined by using the Clinical Global Impressions of Improvement (CGI-I) Scale. RESULTS: Symptomatic improvement was observed in 9 (38%) of 24 patients during an average of 14.1 months of mirtazapine treatment at a mean dose of 36.7 mg/day. Five (21%) patients discontinued mirtazapine because of side effects such as fatigue, weight gain and nausea. Five (21%) patients were receiving combination therapy with another antidepressant when mirtazapine treatment was initiated. CONCLUSIONS: This open-label study suggests that a subgroup of patients with treatment-resistant depression may benefit from mirtazapine treatment. Further controlled studies are required to demonstrate the efficacy of mirtazapine in treatment-resistant depression.
Adrenergic alpha-Antagonists↗
The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications.
Various classes of antidepressant drugs with distinct pharmacologic actions are differentially effective in the treatment of classic melancholic depression--characterized by pathological hyperarousal and atypical depression--associated with lethargy, hypersomnia, and hyperphagia. All antidepressant agents exert their therapeutic efficacy only after prolonged administration. In situ hybridization histochemistry was used to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of 3 different classes of activating antidepressant drugs which tend to be preferentially effective in treating atypical depressions, on the expression of central nervous system genes thought to be dysregulated in major depression. Daily administration (5 mg/kg, i.p.) of the selective 5-hydroxytryptophan (5-HT) reuptake inhibitor fluoxetine, the selective alpha 2-adrenergic receptor antagonist idazoxan, and the nonspecific monoamine oxidase A and B inhibitor phenelzine increased tyrosine hydroxylase mRNA levels by 70-150% in the locus coeruleus after 2 weeks of drug and by 71-115% after 8 weeks. The 3 drugs decreased corticotropin-releasing hormone mRNA levels by 30-48% in the paraventricular nucleus of the hypothalamus. The decreases occurred at 8 weeks but not at 2 weeks. No consistent change in steroid hormone receptor mRNA levels was seen in the hippocampus with the 3 drugs, but fluoxetine and idazoxan increased the level of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA, respectively, after 8 weeks of drug administration. Proopiomelanocortin (POMC) mRNA levels in the anterior pituitary and plasma adrenocorticotropic-hormone (ACTH) levels were not altered after 2 or 8 weeks of drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Antagonists↗
Antidepressants versus placebo for the treatment of bulimia nervosa: a systematic review.
OBJECTIVE: The objective of this study was to valuate the effectiveness, tolerability and acceptability of various classes of antidepressants compared with placebo in the treatment of bulimia nervosa. METHOD: A meta-analysis including 16 randomised controlled trials and 1300 bulimic patients was performed. Dichotomous outcomes were analysed by calculating relative risks, and continuous outcomes by calculating effect sizes. Methodological quality, heterogeneity in the results and selective publication were assessed. RESULTS: Short-term remission in bulimic symptoms was statistically more likely on antidepressants than placebo (Relative Risk=0.88, 95% CI=0.83-0.94, p<0.0001). Drop-out rates were high but no statistical difference was found between treatment groups (34.6% and 31.4% for drug and placebo; RR=1.03, 95% CI=0.80-1.32, p=0.8). No difference in efficacy could be demonstrated among different classes of antidepressants. CONCLUSIONS: The use of a single antidepressant agent was clinically effective for the treatment of bulimia nervosa when compared with placebo, with an overall greater remission rate and a higher rate of drop-outs. No differential effect regarding efficacy and tolerability among the various classes of antidepressants could be demonstrated.
Antidepressive Agents↗
The influence of different relapse criteria on the assessment of long-term efficacy of sertraline.
The treatment of depression with antidepressant agents must be continued beyond the acute phase, until the response is complete. The precise length of this continuation phase is still debated, but most authors estimate that it should last for between 4-6 months after apparent recovery. If antidepressants are withdrawn sooner, the original depression will return (relapse) in a proportion of patients. Relapse rates on placebo are high, whether patients are first-time or recurrent depressives. Most depressions are recurrent and long-term treatment therefore ensures that the changes of a new episode of illness developing are reduced. The importance of this aspect of efficacy is recognized and new antidepressants are being tested in long-term prophylactic studies. A long-term efficacy study has shown that sertraline was significantly more effective than placebo in preventing both relapse and recurrence.
1-Naphthylamine↗