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PubMed1998

Pharmacologic management of depression in the elderly.

Depression, the most common geriatric psychiatric disorder, is a disabling mood disorder that impairs one's well-being and may even threaten a sufferer's life. Severely depressed elderly persons are more likely to kill themselves than individuals in any other age group. However, geriatric depression is, for the most part, a treatable and manageable illness. Antidepressant medication can be very effective in treating major depressive disorder (MDD). Because age-related physical changes in the elderly produce pharmacokinetics that are often different than that experienced by younger adults, different doses are often necessary. This article summarizes recommendations for selecting and initiating appropriate antidepressant therapy in elderly persons suffering from MDD. The benefits and drawbacks of tricyclic antidepressant agents, and other atypical antidepressant agents are discussed. Phases of treatment, drug selection, dosing, and educational tips for pharmacotherapy are presented.

Aged↗
PubMed2003

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression.

There is growing evidence from neuroimaging and ostmortem studies that severe mood disorders, which have traditionally been conceptualized as neurochemical disorders, are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that recent preclinical studies have shown that critical molecules in neurotrophic signaling cascades (most notably cyclic adenosine monophosphate [cAMP] response element binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen activated protein [MAP] kinases) are long-term targets for antidepressant agents and antidepressant potentiating modalities. This suggests that effective treatments provide both trophic and neurochemical support, which serves to enhance and maintainnormal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning. For many refractory patients, drugs mimicking "traditional" strategies, which directly or indirectly alter monoaminergic levels, may be of limited benefit. Newer "plasticity enhancing" strategies that may have utility in the treatment of refractory depression include N-methyl-D-aspartate antagonists, alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) potentiators, cAMP phosphodiesterase inhibitors, and glucocorticoid receptor antagonists. Small-molecule agents that regulate the activity f growth factors, MAP kinases cascades, and the bcl-2 family of proteins are also promising future avenues. The development of novel, nonaminergic-based therapeutics holds much promise for improved treatment of severe, refractory mood disorders.

Animals↗
PubMed1996

Neurobiological and psychopharmacological basis in the therapy of bulimia and anorexia.

1. Eating disorders can be found in several psychiatric pathologies: schizophrenia, delusional disorder (somatic type), bipolar disorders, major depressive disorder, borderline personality disorder, generalized anxiety disorder, body dysmorphic disorder, somatization disorder and conversion disorder. 2. Although their clinical features have been defined, relatively little is known about the role of neurobiological patterns in the pathogenesis of these disorders. Several CNS neurotransmitters and neuromodulators are involved in the regulation of eating behavior in animals and have been implicated in symptoms such as depression and anxiety often observed in patients with eating disorders. The authors will review some studies on NA, DA, 5-HT, beta-endorphins, CRH, VP, OT, CCK, NPY and PYY involved in eating disorders. Furthermore, we will highlight some of the studies on drug therapy of eating disorders taking into account the effects of these agents on neurotransmitters and neuromodulators. 3. Antidepressant drugs have long been used for anorexia nervosa and bulimia, these disorders been claimed to be affective equivalent. Antidepressant agents seem to be effective in reducing the frequency of binge-eating episodes, purging behavior and depressive symptomatology. It is notable that antidepressant agents have been proved to be effective in patients with chronic bulimic symptoms, even in cases persisting for many years and in patients who had repeatedly failed courses of alternative therapeutic approaches. In all of the positive studies, antidepressant agents appeared effective even in bulimic subjects who did not display concomitant depression. 4. Few controlled studies on use of medications for anorexia nervosa have been published. Central serotonergic receptor-blocking compounds such as cyproheptadine cause marked increase in appetite and body weight. Zinc supplementation or cisapride could be a therapeutic option in addition to psychological and other approaches in anorexia nervosa. 5. There is no therapy as yet which is fully effective in alimentary disorders. Psychotropic drugs give some relief from symptoms, but they cannot cure the disorders. An integrated approach, either pharmacological or psychological, is still recommendable.

Anorexia↗
PubMed2001

Tianeptine: a review of its use in depressive disorders.

UNLABELLED: Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for tianeptine but dothiepin appeared superior in another study. Extended treatment with tianeptine decreases the incidence of relapse/recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to tianeptine. The adverse effects associated with tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. CONCLUSIONS: The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism.

Aged↗
PubMed1999

Therapeutic drug monitoring of antidepressants: cost implications and relevance to clinical practice.

Despite evidence to support its potential benefit in clinical practice, therapeutic drug monitoring (TDM) is under-utilised and underdeveloped in the field of psychiatry. In antidepressant pharmacotherapy drug dose is emphasised as the critical treatment variable. However, dose in, and of, itself can be a strikingly misleading predictor of drug concentration and, hence, treatment effect. For antidepressant drugs, plasma concentrations at a given dose have been shown to vary in excess of 40-fold. The clinical relevance of this variability is that at a standard antidepressant dosage only some patients will have tissue drug concentrations associated with an optimal response whereas others will have either low, ineffective drug concentrations or unnecessarily high concentrations which may be poorly tolerated. Among clinicians and healthcare agencies there is an under-appreciation of the degree of pharmacokinetic variability found in patients and how that might impact on the patients response to pharmacotherapy. Hence there is a perception that TDM is an unnecessary, complicated and costly procedure. This is actually unfounded. There are data to suggest that TDM can favourably affect the outcome of antidepressant treatment by providing a rational alternative to the inherently slower, trial and error practice of dosage titration based on clinical response. It is unlikely that TDM will become a standard of care for all antidepressant agents and all patients. Therefore the question becomes for which antidepressant agents, for which patients and under what circumstances, is TDM more cost-effective than traditional dose titration. The use of TDM to optimise the efficient use of selected antidepressant agents could potentially free up healthcare resources to fund other equally deserving treatments. This article provides a discussion of the major classes of antidepressant drugs with regard to their pharmacological features that predict the utility of TDM in clinical practice. Recommendations are made for the practical application of TDM and the directions for further research.

Antidepressive Agents↗
PubMed2001

Using a computerized patient database to evaluate guideline adherence and measure patterns of care for major depression.

This study examined the translation of recommendations from the Agency for Health Care Policy and Research (AHCPR) guidelines for major depression into measures derived from a computerized database to assess guideline conformance and patterns of care for major depression. Patients (n = 208) were identified who were hospitalized for major depression and had two or more outpatient mental health appointments within 6 months of discharge from an academically affiliated Veterans Affairs Medical Center. Measures were based on AHCPR guideline recommendations or developed independently. Conformance could be measured for three guideline recommendations. Of patients on single-agent antidepressant therapy, 87% received dosages within the recommended range. Sixty-nine percent received the recommended number of follow-up visits. Specific condition-related treatment interventions were identified in 32% of patients with concurrent alcoholism. Dual diagnoses of depression and drug or alcohol abuse were not deterrents to prescribing benzodiazepines. Despite its limitations, computerized database analyses provided efficient measures of guideline adherence.

Adult↗
PubMed2006

The relationship between body weight and drug costs: An Italian population-based study.

OBJECTIVES: This study determined the prevalence of 3 categories of body mass index (BMI)--normal weight, overweight, and obesity--in a sample of subjects from general clinical practice in Ravenna, Italy, and evaluated the impact of comorbidities associated with overweight and obesity on the costs of drug treatment from the perspective of the Italian national health system. METHODS: This was a cross-sectional study conducted in a sample of subjects aged > or =18 years from 10 general practices in the Ravenna local health unit (LHU) in 2001-2002. Subjects were invited to attend a screening visit at which weight and height were measured for determination of BMI, blood pressure was measured, and a fasting blood sample was obtained for laboratory tests. The screening examinations were conducted by 2 physicians at a dedicated practice. Normal weight, overweight, and obesity were defined as a BMI < or =24.9, between 25 and 29.9, and > or =30 kg/m2, respectively. The costs of classes of drug treatment that were reimbursable to the LHU in the 12 months before the screening examination were evaluated using the Ravenna LHU administrative databases. Drug treatments were classified as antihypertensive agents, statins, NSAIDs, gastroprotective drugs, antidiabetic agents, respiratory drugs, antiplatelet agents, antidepressants, and all other drugs. The data were analyzed by age group. RESULTS: Of the 2622 subjects in the sample, 1256 (47.9%) had a normal BMI, 918 (35.0%) were overweight, and 448 (17.1%) were obese. The prevalence of overweight and obesity increased in relation to age up to 50-59 years (P < 0.001), after which it remained stable. Overweight and obese subjects had significantly more exposure to individual and multiple drug treatments compared with subjects with normal weight (P < 0.001). By type of drug treatment, 16.7% of normal-weight subjects, 35.6% of overweight subjects, and 51.8% of obese subjects were exposed to antihypertensives; 4.1%, 8.7%, and 12.1%, respectively, to statins; 14.2%, 22.0%, and 29.0% to NSAIDs; and 1.0%, 4.7%, and 9.4% to antidiabetics. The mean annual cost of drugs was Euro 132.71 in normal-weight subjects, Euro 246.19 in overweight subjects, and Euro 335.64 in obese subjects (P < 0.001). After adjustment for differences in age distribution between the study sample and the overall population of Ravenna, the estimated excess drug costs associated with overweight and obesity in Ravenna were Euro 5,661,126.20 and Euro 6,688,099.85, respectively. CONCLUSIONS: In this study sample, the prevalence of overweight increased by approximately 10% and the prevalence of obesity increased by approximately 5% with each decade of age up to 60 years, after which it remained stable at approximately 40% and approximately 20%, respectively. Overweight and obesity were associated with increased drug exposure and costs in all age groups considered.

Antidepressive Agents↗
PubMed1997

The management of coexisting depression in patients with dementia: potential of calcium channel antagonists.

Depression frequently coexists with dementia, although in many cases the depression is not recognized clinically. Depression represents a major additional burden in dementia, not only for the patients but also for families, caregivers, and, economically, society as a whole. However, depression in patients with dementia does respond to treatment, and appropriate therapy can significantly improve the well-being of these patients. Depression in patients with dementia is currently treated with a variety of standard antidepressive agents (tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors), but none is free from significant side effects. Moreover, the use of these drugs is often complicated by a number of age-related factors or effects on the cholinergic neurotransmitter system. Consequently, an antidementia treatment with concomitant antidepressive properties and an acceptable benefit/risk ratio would represent an attractive therapeutic option. The pathogenesis of depression in patients with dementia is not well understood, but may be related to increased intracellular calcium ions in the CNS, the so-called "calcium hypothesis." This hypothesis may explain why some calcium antagonists exert psychotropic effects, including putative antidepressant activity. Animal models and clinical data provide support for the use of calcium channel antagonists for the treatment of depression, with the potential for good tolerability. The latter aspect is especially important for elderly patients with dementia. Although antidepressive effects have been seen with a number of calcium channel antagonists, the dihydropyridine derivative nimodipine shows particular potential for clinical use, perhaps because nimodipine is one of the most lipophilic of these drugs and therefore achieves high concentrations in the CNS, and because of the unique biochemical properties of the dihydropyridine compounds compared with other L type calcium channel blockers. Nimodipine also increases somatostatin levels in CSF, one of the cardinal biochemical deficits in Alzheimer's disease. Data obtained incidentally from the use of nimodipine in the treatment of elderly demented patients clearly demonstrate significant antidepressant activity by the drug in this patient group. Formal clinical evaluation is therefore recommended to establish more clearly the therapeutic benefits offered by nimodipine in patients who suffer from both dementia and depression.

Aged↗
PubMed2003

Treatment of bipolar disorder.

Management strategies for bipolar disorder often entail relatively long-term, complex medication regimens that combine primary mood stabilizers, antipsychotic agents, antidepressants, and other medications, such as benzodiazepines. New strategies for the management of bipolar disorder have recently been evaluated in controlled clinical trials, including using newer anticonvulsants, replacing conventional antipsychotics with atypical antipsychotics, and using novel combination treatments. This article provides an overview of current management strategies for patients with bipolar disorder and describes how these approaches can be incorporated into clinical practice.

Algorithms↗
PubMed2004

Late-life anxiety disorders.

The prevalence, natural course, risk profile, and treatment of anxiety disorders in the elderly are remarkably understudied. Anxiety disorders are less prevalent in the elderly than in younger adults, but rates of subsyndromal anxiety disorders in elderly persons are nearly as high as in their younger cohorts. The most common late-life anxiety disorders are mixed anxiety-depression and generalized anxiety disorder. Though the benzodiazepines are widely used in this population and are considered relatively safe given appropriate dosing and safety monitoring, important liabilities remain with the use of these agents. Antidepressants also are widely used in elderly patients, but there are no randomized controlled anxiety disorder treatment trials in this population. Gabapentin and low-dose atypical antipsychotics are beginning to be used and studies of the atypical antipsychotics are ongoing. Until studies are completed, treatment of late-life anxiety will continue to be guided by extrapolating data from the general adult population. Psychopharmacology Bulletin. 2004;38(Suppl 1): 25-30.

Antidepressive Agents↗
PubMed2002

Differential modulation of efficiency in a food-rewarded "differential reinforcement of low-rate" 72-s schedule in rats by norepinephrine and serotonin reuptake inhibitors.

RATIONALE: The differential reinforcement of low-rate 72-s (DRL 72-s) schedule, in which rats must withhold a response for at least 72 s to obtain a reward (generally water), is an attractive procedure for the characterisation of potential antidepressant agents. Indeed, several antidepressants have been shown to improve efficiency (ratio of reinforcement rate to response rate) in this model, either by decreasing response rates and/or by increasing reinforcement rates. OBJECTIVE: Herein, we compared the actions of antidepressants known to inhibit serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) reuptake in a food-rewarded DRL 72-s schedule. METHODS: Rats trained in a food-rewarded DRL 72-s schedule and showing stable baseline performance were administered with drugs i.p. once a week. In independent experiments, the influence of drugs on food intake, spontaneous locomotor activity and extracellular levels of monoamines in the frontal cortex was evaluated. RESULTS: In confirmation of previous studies, the tricyclic agent imipramine (10.0 mg/kg) and the "atypical" agent mianserin (40.0 mg/kg) significantly increased efficiency. In analogy, the selective NE reuptake inhibitors (NARIs) desipramine (20.0 mg/kg), nortriptyline (2.5 mg/kg) and reboxetine (0.63 mg/kg) all displayed marked enhancements in efficiency. In contrast, the selective 5-HT reuptake inhibitors (SSRIs) citalopram (10.0 mg/kg), fluvoxamine (10.0 mg/kg) and paroxetine (10.0 mg/kg) all significantly decreased efficiency. The mixed 5-HT/NE reuptake inhibitors (SNRIs) venlafaxine (2.5 mg/kg, 10.0 mg/kg) and S33005 (0.16-10.0 mg/kg), likewise, did not increase efficiency. Further, the DA reuptake inhibitors (DARIs) bupropion (0.16-10.0 mg/kg) and GBR12935 (0.63-10.0 mg/kg) had no effect on DRL 72-s performance. All drug classes exerted a similar, mild inhibitory influence on food intake and locomotor behaviour. Imipramine, mianserin and NARIs markedly increased extracellular levels of NE, and SSRIs elevated levels of 5-HT, while SSRIs augmented levels of both. CONCLUSIONS: The present experimental procedure demonstrates, in analogy to imipramine and mianserin, robust and consistent increases in efficiency with NARIs. Their effects may be distinguished from a decrease in efficiency elicited by SSRIs, and a lack of activity of SNRIs and DARIs. While the reasons underlying the ineffectiveness of SSRIs (in contrast to previous studies) remain to be clarified, these data underline the importance of adrenergic mechanisms in the control of behaviour under conditions of delayed responding. Further, they support the interest of DRL 72-s procedures for the characterisation of diverse classes of antidepressant agent.

Adrenergic Uptake Inhibitors↗
PubMed2006

[Antidepressives and antidepressive interactions with other drugs].

During the therapy with antidepressive agents, for the reason of its duration, numerous drug-drug interactions may occur. Antidepressive agents inhibit P450 enzyme activity and interfere with other drug metabolism. Many interactions are acceptable from the clinical point of view, and some are seriously dangerous indicating a need for their better knowledge. The aim of this work is to point out the possible interactions between antidepressive agents and other drugs.

Antidepressive Agents↗
PubMed1983

Monoamine metabolites as predictors of antidepressant response: a critique.

Monoamine metabolite measurements are being increasingly used for making nosological, symptomatological and pharmacological profiles of the affective disorders. A number of unresolved methodological issues question the validity of using baseline metabolite levels for predicting treatment response. Some studies show correlations between baseline metabolite levels and response to treatment with specific antidepressant agents. Effects of antidepressant treatment on metabolite levels may be useful in predicting drug response.

Antidepressive Agents↗
PubMedDate not supplied

[Adverse drug reactions in patients attending in emergency service].

OBJECTIVE: Describing adverse drug reactions (ADR) and analyzing the factors associated with their appearance in patients attending two hospitals' emergency services. METHODS: Descriptive, medicine-surveillance study of people consulting the emergency service at the Rosales hospital and the basic total health attention unit in Pereira, Colombia, between July and September 2005 for any symptom related to taking medicine. Naranjo's Adverse Drug Reaction probability scale was used. RESULTS: A total of 91 patients were found; 62,6 % were women having an average age of 36,3+/-22,4 (range 0-85). Antibiotics (24,2 %) NSAIDs (17,6 %), analgesics (9,9 %) and antidiabetic agents (8,8 %) were the most used drugs. 39,6 % of the patients only used one medicine; the average of drugs per patient was 2,4+/-1,5. Self-medication was present in 25,3 %. The most common ADRs arose from urticaria (31,9 %), hypoglycaemia (8,8 %), gastritis (6,6 %), angioedema (5,5 %) and anaphylaxis (4,4 %). 13,2 % of ADRs were serious and 54,9 % were avoidable. 14,3 % of ADRs were classified as being definite and 75,8 % probable. Only 14,3 % of patients had a past history of ADR. The average cost of being attended was US$ 78,1 dollars. Analgesic use was associated with anaphylaxis, antibiotics with urticaria whilst NSAIDs was associated with gastritis and gastrointestinal bleeding, antidiabetic agents with hypoglycaemia, antipsychotic and antidepressants agents with neurological symptoms and warfarin with bleeding. CONCLUSIONS: The most important ADR-associated risk factors in patients attending emergency services were determined. Special care must be paid to patients using NSAIDs, warfarin, metoclopramide, metamizole, antipsychotic and antidepressants agents, antidiabetic agents and antibiotics, having a past history of ADR, being more than 55 years old and presenting urticaria, digestive and/or neurological symptoms

Adolescent↗
PubMed1990

Desipramine relieves postherpetic neuralgia.

Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressant agents, but its pain-relieving potential has received little study. Other antidepressant agents--notably amitriptyline--are known to ameliorate postherpetic neuralgia, but those agents are often toxic. In a randomized double-blind crossover design, we gave 26 postherpetic neuralgia patients 6 weeks of treatment with desipramine (mean dose, 167 mg/day) and placebo. Nineteen patients completed both treatments; 12 reported at least moderate relief with desipramine and two reported relief with placebo. Pain relief with desipramine was statistically significant from weeks 3 to 6. Psychiatric interview at entry into the study produced a diagnosis of depression for 4 patients; pain relief was similar in depressed and nondepressed patients and was statistically significant in the nondepressed group alone. We conclude that desipramine administration relieves postherpetic neuralgia and that pain relief is not mediated by mood elevation. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressant agents that have relieved neuropathic pain, may be involved in relief of postherpetic neuralgia.

Adult↗