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Diagnosis and treatment of depression.

In the United States, depression is the most common psychiatric disorder and is the psychiatric problem most often seen by the generalist. Thus, it is essential for the primary-care physician to have a thorough understanding of the diagnosis and management of depression. Patients often present with complaints such as weight loss, appetite changes, sleep disturbances, pain, psychomotor agitation or retardation, decreased sexual drive, loss of energy, and somatic complaints. When depression is suspected, the clinician should first rule out secondary depression attributable to other psychiatric or medical illnesses, or medications. In addition, certain age categories--children, adolescents, and elderly individuals--have characteristic symptoms and behavior patterns suggestive of depression. Identifying the suicidal patient is another important aspect in the treatment of depressed individuals. In addressing this issue, questions have been formulated to help identify patients who may be potentially suicidal. Treatment modalities for depression include exercise regimens, psychotherapy, and pharmacotherapy. The standard pharmacotherapy has been the administration of tricyclic antidepressant agents; newer drugs are currently available that have comparable efficacy, and perhaps better safety profiles than the tricyclic agents.

Antidepressive Agents↗

Physical symptoms comorbid with depression and the new antidepressant duloxetine.

Most general descriptions of depression that date back to Hippocrates, including the DSM-IV, have listed gastrointestinal problems, sleep disturbances, headaches, appetite changes, and aches and pains of a diffuse nature as common features of the disorder. In addition, physical symptoms have a strong association with psychiatric disorders, and the presence of any physical symptom may increase the likelihood of a mood or anxiety disorder by two-fold or three-fold. A growing body of evidence suggests that serotonin and norepinephrine may share neurochemical mechanisms that tie depression and physical symptoms together. Both selective serotonin reuptake inhibitors alone and antidepressant agents that incorporate both serotonin and norepinephrine reuptake inhibition have shown evidence of relieving physical symptoms. Given the additional disease burden caused by physical symptoms in depression, it is vital that antidepressant agents that effectively treat the physical symptoms and chronic pain associated with depression be used.

Adrenergic Uptake Inhibitors↗

Double-blind, placebo-controlled, fixed dose trial of minaprine in patients with major depression.

Minaprine dihydrochloride is a novel psychotropic drug possessing both antidepressant and psycho-stimulant properties. Prior clinical studies have shown minaprine to be as effective as standard antidepressant agents in the treatment of endogenous depression. The present study examined the safety and efficacy of minaprine at four different doses compared to placebo in 190 outpatients with major depression. Overall, minaprine demonstrated a significant antidepressant action compared to placebo, which was most evident at the maximum dose of 400 mg daily. These data, together with a favorable side effects profile, suggest that minaprine may be an effective antidepressant agent for the treatment of major depression.

Adult↗

Pharmacotherapy of adolescent major depression: beyond TCAs.

To date, controlled studies of tricyclic antidepressant (TCA) treatment of adolescent major depression have failed to demonstrate efficacy of these compounds despite multiple lines of evidence suggesting that adolescent major depression is related to the adult form of the disorder. One possible means of increasing the power of such studies is explored: examination of the pattern of response to medication and separation of placebo responders from medication responders using the technique proposed by Quitkin and colleagues (1984). Open label studies of nontricyclic antidepressant agents in adolescents are reviewed, and suggestions are made for future pharmacological trials in this population.

Adolescent↗

Antimuscarinic and other receptor-blocking properties of antidepressants.

Tricyclic antidepressants (for example, amitriptyline) and other types of antidepressants (for example, amoxapine and maprotiline) are competitive antagonists of muscarinic acetylcholine receptors, the predominant class of acetylcholine receptors in the brain. Some evidence suggests that this muscarinic receptor blockade in brain alleviates depression. However, all tricyclic antidepressants appear to be equally effective in treating depression despite having differences in their antimuscarinic potencies while having similar ranges of therapeutic blood levels. It is more likely that the antimuscarinic potency of antidepressants is related mainly to the frequency with which they cause such symptoms as blurred vision, dry mouth, and urinary retention. Information on the antimuscarinic potency and other receptor-blocking potencies of antidepressant agents can be helpful in minimizing or avoiding certain side effects when these drugs are given to patients.

Antidepressive Agents↗

Comparative studies with milnacipran and tricyclic antidepressants in the treatment of patients with major depression: a summary of clinical trial results.

Milnacipran is a novel antidepressant agent which selectively inhibits the reuptake of serotonin and noradrenaline. Seven randomized, double-blind trials with a comparable design have compared the efficacy and tolerability of milnacipran with that of tricyclic antidepressants (TCAs) in patients with major depression. At a dose of 50 mg twice a day, milnacipran therapy is associated with a response rate (50% reduction in Hamilton Depression Rating Scale) of 64%. The rate of response to TCAs in these studies was 67%. In contrast to the TCAs, milnacipran was very well tolerated by the patients. The only adverse event that occurred more frequently in milnacipran-treated patients than in TCA-treated patients was dysuria (2.1% of patients treated with milnacipran). Milnacipran is as effective as TCAs in the treatment of patients with major depression and is better tolerated. Milnacipran's lack of effects on cardiovascular function offers improved safety in cases of overdose.

Adrenergic Uptake Inhibitors↗

Pharmacotherapy of depression in children.

Depression can interfere with the overall functioning of children and adolescents. It can impair normal cognitive and social development. The use of antidepressant medications in children and adolescents has grown in the past decade. Newer antidepressant agents, the selective serotonin reuptake inhibitors, appear very promising, but their safety and efficacy have not been established for children. This review focuses on depression and the design of studies for its treatment with newer antidepressant drugs in children.

Adolescent↗

Lamotrigine inhibits basal and Na+-stimulated, but not Ca2+-stimulated, release of corticotropin-releasing hormone from the rat hypothalamus.

RATIONALE: Corticotropin-releasing hormone (CRH) is a peptide neurotransmitter involved in the pathogenesis of anxiety and depressive disorders; CRH receptor antagonists are currently developed as anxiolytic and antidepressive agents, and several antidepressants negatively modulate CRH in the central nervous system. OBJECTIVES AND METHODS: Originally marketed as an antiepileptic drug, lamotrigine (LTG) was subsequently shown to be effective as a mood stabilizer and an antidepressant. In this study, we used acute rat hypothalamic explants to investigate the effects of LTG on the gene expression and secretion of CRH from the hypothalamus in short-term incubation experiments. RESULTS: We found that LTG reduces basal CRH release in a time- and concentration-dependent manner. LTG also inhibits veratridine-stimulated, but not K+-stimulated, CRH release in 1-h experiments. Moreover, LTG tended to reduce CRH mRNA expression in 1-h experiments, regardless of whether the drug was given alone or in combination with veratridine or high K+ concentrations; such reduction achieved statistical significance after 3 h of incubation. CONCLUSION: In 1-h experiments, LTG reduces CRH release from CRH-containing neurons in the rat hypothalamus by interfering with Na+-driven secretion mechanisms. After 3-h incubations, the reduction in CRH release is also accounted for by LTG-induced decrease in CRH gene expression.

Animals↗

Behavioral effects of HT-90B, a putative novel anxiolytic agent with potent antidepressive activity.

1. HT-90B,((-)-N-[2-(8-methyl-1,4-benzodioxane-2-ylmethyl)am in o]ethyl]tricyclo[3,3,1,1(3,7)] decane-1-carboxamide), is a novel serotonin 5-HT(1A) full agonist with serotonin 5-HT(2) antagonistic action. 2. In a water licking conflict test, HT-90B (3-30 mg/kg, po) was more effective than buspirone in abolishing response suppression. 3. In a forced swim test, HT-90B (3-30 mg/kg, po) reduced the duration of immobility after a single oral dose, which contrasts with the requirement of multiple doses for desipramine (as a standard antidepressant) to produce the effect. 4. These two behavioral effects of HT-90B (20 mg/kg,po) were still evident even 4 hr after oral administration. And no tolerance was observed for these behavioral effects after repeated oral administration (10 mg/kg, b.i.d., 2 weeks). 5. HT-90B hardly produced any diazepam- or buspirone-like side effects. 6. In conclusion, it is suggested HT-90B is a potent anti-depressive anxiolytic with minimal side effects.

Adamantane↗

Possible immunological effects of psychotropic medication.

Psychoactive drugs provide an essential intervention in the care of organ transplant recipients, yet little is known of their effect on immunological function. Human and animal data on immunological effects of neuroleptic (e.g., haloperidol, phenothiazines) and antidepressant agents (e.g., tricyclic antidepressants, fluoxetine) lead to conflicting hypotheses. Lithium carbonate acts through the phosphoinositide system and has a bipolar effect on neuronal activity. Lithium is known to have immune-enhancing properties and is difficult to administer in the peritransplant period but nonetheless deserves study for possible beneficial effects on allograft function.

Humans↗

Amoxapine for the treatment of psychotically depressed subjects. A pilot study.

The treatment of psychotic depression remains controversial, although most studies suggest that the combination of an antipsychotic and an antidepressant agent is most beneficial. The authors describe an open-label study of the treatment of psychotic depression using amoxapine, an agent with both antidepressant and antipsychotic properties. Of the six patients treated, two improved dramatically within the first week of treatment, whereas for the remaining four treatment had to be discontinued due to lack of efficacy or side effects. Amoxapine appears to be effective in some cases of psychotic depression, but side effects and known risks of treatment diminish its usefulness.

Adolescent↗

Geriatric depression and treatment with trazodone.

With the growing number of Americans over the age of 65 years, the high incidence of geriatric depression has become a major concern in the United States. Age-related circumstances--increased incidence of illness, bereavement, financial difficulties, and institutionalization--may contribute to an increased rate of depression in this age group. The signs and symptoms of depression in elderly patients are similar to those seen in younger individuals; therefore, standard Diagnostic and Statistic Manual III (DSM-III) criteria are reliable for making a diagnosis. However, symptoms such as insomnia, obsessional thought, and hypochondriasis may be relatively increased in the elderly patient; and the diagnosis of geriatric depression can be complicated by signs and symptoms of depression that may overlap with those of dementia. In the geriatric group, the mainstay of pharmacotherapy has been the reuptake antidepressant agents. Choice of antidepressant therapy is largely based on the side-effect profile. Thus, the fewer and less severe side effects associated with trazodone make it a suitable drug choice in these patients. Trazodone has been shown to demonstrate comparable efficacy to the other reuptake and monoamine oxidase inhibitors, but has the advantages of a low cardiovascular-risk profile, extremely low suicide toxicity, absence of anticholinergic side effects, and minimal effects on cognition.

Adjustment Disorders↗

Depression: Diagnosis and Management for the Primary Care Physician.

BACKGROUND: Much has been learned in recent years about the diagnosis and treatment of depression, a serious, commonly overlooked psychiatric illness often seen initially by the primary care physician. The objective of this article is to review the diagnosis and treatment of depression in primary care practice. METHOD: Relevant articles on depression were identified by a comprehensive MEDLINE search and classified into the following categories: diagnosis and screening, nonpharmacologic therapy, pharmacologic therapy, newer antidepressant agents, and maximizing antidepressant therapy. The importance to primary care practice was considered in determining the significance of each article reviewed. RESULTS: Because no laboratory tests exist for depression and no biological markers can be measured routinely, the diagnosis of depression must be made with a number of reliable depression scales and questionnaires that can be completed quickly in the primary care setting. The considerable overlap between depressive and anxiety disorders further complicates an accurate diagnosis. Remission (i.e., absence of symptoms) is the ultimate goal of therapy for patients who have depressive symptoms. CONCLUSION: Many patients can be treated safely and effectively for depression in the primary care setting with pharmacologic therapy, which, if completely successful, can lead to full remission of the disorder.

Journal Article↗

[Dementias. Diagnosis and therapy are overwhelmingly the responsibility of the family physician].

The management of elderly patients suffering from dementia is a task mainly for the general practitioner, who is in a favourable position to recognize this condition at an early stage, since he knows the patient, his family and situation. The diagnosis is facilitated by recently developed screening tests. The family doctor may also be confident to make most differential diagnostic decisions. Treatment builds on basic general medical therapy. For pharmacotherapy, modern antidementia agents, antidepressants and neuroleptic agents are available. Pharmacotherapy must be supplemented by adaptation of the patient's surroundings, and counseling of relatives. However, proper treatment of dementia is cost-intensive and puts a strain on the doctor's medications budget.

Aged↗

Lithium and antidepressants: potential agents for the treatment of Rett syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder occurring almost exclusively in females. It is caused by mutations in gene encoding methyl-CpG-binding protein 2 (MECP2) in the majority of cases. MECP2 was originally thought to be a global transcriptional repressor, but recent evidence from studies of animals suggests that it may have a role in regulating neuronal activity-dependent expression of specific genes such as Bdnf. A recent report demonstrated that deletion of Bdnf in Mecp2 mutants caused earlier onset/accelerated disease progression, whereas BDNF overexpression in the Mecp2 mutant brain led to later onset/slower disease progression, suggesting that manipulation of BDNF expression/signaling in the brain could be therapeutic for this disease. Lithium and antidepressants have been demonstrated to increase central BDNF levels or signaling in human as well as animal studies. Thus, it is proposed that these agents could have therapeutic potential for RTT subjects. Several points regarding the use of these agents in RTT are discussed. Further evaluation of the therapeutic effects of these drugs in RTT animal models is needed before clinical trials can begin.

Antidepressive Agents↗

Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein.

alpha 1-Receptor antagonists and antidepressant agents are basic (cationic) drugs that are known to bind to alpha 1-acid glycoprotein (AAG). Since these drugs are frequently co-administered and since they bind to the same protein, this investigation was designed to evaluate the "in vitro" ability of antidepressants, alpha 1-receptor antagonists, and propranolol to displace [3H]imipramine and [3H]prazosin from the AAG binding site(s). Equilibrium dialysis was employed. Of the drugs studied, the following order of potency in displacing [3H]prazosin was found: trazodone greater than prazosin greater than doxazosin greater than propranolol greater than doxepin = amoxapine = trimazosin = amitriptyline greater than imipramine greater than nortriptyline = desipramine = nomifensine greater than bupropion = maprotiline. [3H]lmipramine binding from AAG was displaced with the following potency order: prazosin greater than imipramine greater than propranolol greater than doxazosin greater than nortriptyline greater than desipramine greater than trimazosin. Tricyclic antidepressants produced similar degrees of displacement of both [3H]imipramine and [3H]prazosin from AAG; whereas, alpha 1-receptor antagonists were more effective displacers of [3H]prazosin than of [3H]imipramine. Furthermore, the demethylated metabolites of imipramine and amitriptyline were less potent displacers than their parent compounds. These results suggest that more than a single binding site may be available for binding to AAG and that hydrophobic bonding is important in the binding of drugs to AAG.

Adrenergic alpha-Antagonists↗