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PubMed1990

TCA poisoning treated in the intensive care unit.

Intoxication with tricyclic antidepressants (TCA) is a common cause of admission to an intensive care unit and a major cause of death due to drug overdose. It is difficult to identify at an early stage those patients for whom toxic events are likely. There is a poor correlation between the plasma concentration of TCAs and the risk of developing toxic symptoms. A better predictor of complications following tricyclic overdose is the level of consciousness on admission to hospital. It has been claimed that "newer" antidepressant agents are less toxic then the classic antidepressants when taken in overdoses. In Sweden, two of these "newer" antidepressants, maprotiline and lofepramine, have been marketed. Of these, only lofepramine is less toxic than the classic TCAs. Maprotiline has the same cardiotoxicity as the TCAs, convulsions are seen more often and a longer plasma half-life leads to longer time spent on a ventilator and longer time in an ICU when it is taken in overdose.

Antidepressive Agents, Tricyclic↗
PubMedDate not supplied

Self-report of depressed mood and depression in women with type 2 diabetes.

The purpose of this cross-sectional analysis (N = 53) was to (a) describe the self-reported prevalence of depressed mood and depression in women with type 2 diabetes; (b) to describe the antidepressive agents and dosages prescribed for depression treatment in women with type 2 diabetes; and (c) to examine differences in diabetes-related health outcomes (physiologic, psychosocial, and health functioning variables) with respect to depressed mood. Forty-four percent of women in this sample reported a depressed mood and 34% of the sample reported a history of depression. The majority of women with a history of depression were taking an antidepressive agent at the time of assessment (94%). Most women were treated with selective serotonin reuptake inhibitors (SSRIs). Women with depressed mood demonstrated poorer psychosocial adjustment and health functioning compared to women without a depressed mood; however, no differences in physiological outcomes were demonstrated. Only 18% of the participants were currently being treated with psychotherapy in conjunction with medication. Further research on this understudied population is indicated.

Adult↗
PubMed1987

The current status of monoamine oxidase and its inhibitors.

The enzyme monoamine oxidase (MAO) plays an important role in the inactivation of both dietary amines and also of neurotransmitter amines. A study of the properties of irreversible inhibitors of this enzyme suggests that the enzyme exists in two broad types--MAO-A and MAO-B. Although irreversible inhibitors of MAO were once widely used as antidepressant agents, they fell from favour because of adverse reactions after the ingestion of amine-containing foodstuffs ("the cheese reaction"). However, these inhibitors (phenelzine and tranylcypromine) are probably best for the treatment of atypical depression providing the patient is aware of dietary reactions. A new series of reversible, MAO-A selective inhibitors are being developed which do not exhibit serious dietary interactions. These reversible inhibitors show promise as rapidly acting antidepressant agents. An atypical irreversible MAO-B selective inhibitor, selegiline (deprenyl) does not exhibit an adverse reaction on the ingestion of amine-containing foods. This drug has been used as an adjuvant in the treatment of Parkinson's disease since it allows the dose of L-dopa to be reduced by approximately 25%. More important, selegiline may slow the degeneration of dopaminergic neurons that is characteristic of Parkinson's disease.

Allylamine↗
PubMed1982

Amoxapine (Asendin, Lederle Laboratories).

Amoxapine is a tricyclic antidepressant agent, which is chemically related to the antipsychotic agent loxapine, but which appears to block selectively the neuronal reuptake of norepinephrine; it is qualitatively similar to desipramine. In studies of patients with mixed depressive illnesses, amoxapine is at least as effective as amitriptyline and imipramine and probably more effective than placebo in ameliorating depressive symptoms. Claims of more rapid onset of therapeutic effects are based on group mean data obtained from small samples of depressed patients with heterogeneous and imprecisely defined diagnostic types. Amoxapine has yet to be compared with desipramine or maprotiline, the most pharmacologically similar antidepressants. Biopharmaceutical and pharmacokinetic data are limited, and a relationship between serum concentrations and efficacy has not yet been shown. Acute toxicity and drug interaction documentation are also lacking. At this time, amoxapine represents a chemical alternative to traditional tricyclic antidepressants. There are no consistent data indicating superiority of amoxapine over any other antidepressant agent for any specific symptom constellation, in rate or extent of improvement, or in any particular diagnostic or demographic population. Studies in which amoxapine is compared with pharmacologically similar agents at therapeutically equivalent doses in diagnostically homogeneous groups are needed to establish the drug's true place in the treatment of depressions.

Amoxapine↗
PubMed2000

Depression: the case for a monoamine deficiency.

The monoamine hypothesis of depression predicts that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin, norepinephrine, and/or dopamine in the central nervous system. This hypothesized pathophysiology appears to be supported by the mechanism of action of antidepressants: agents that elevate the levels of these neurotransmitters in the brain have all been shown to be effective in the alleviation of depressive symptoms. However, intensive investigation has failed to find convincing evidence of a primary dysfunction of a specific monoamine system in patients with major depressive disorders. Understanding of the etiology of depression has been hampered by the absence of direct measurements of monoamines in humans. However, the monoamine depletion paradigm, which reproduces the clinical syndrome, allows a more direct method for investigating the role of monoamines. Results from such studies show that antidepressant responses are transiently reversed, with the response being dependent on the class of antidepressant. In contrast, monoamine depletion does not worsen symptoms in depressed patients not taking medication, nor does it cause depression in healthy volunteers with no depressive illness. In conclusion, it is clear that antidepressant agents in current use do indeed require intact monoamine systems for their therapeutic effect. However, some debate remains as to the precise role that a deficiency in monoamine system(s) may play in depression itself.

Depressive Disorder↗
PubMed2004

Serotonin regulates osteoclast differentiation through its transporter.

UNLABELLED: 5-HTT mediates antidepressant-sensitive clearance of 5-HT after its release into neural synapses. We found increased expression of 5-HTT in RANKL-induced osteoclast-like cells. Fluoxetine, an inhibitor of 5-HTT, reduced osteoclast differentiation but not activation. Reserpine, an inhibitor of 5-HT intracellular transport, potentiated differentiation. These results indicate a role for 5-HTT in osteoclast function and suggest that commonly used antidepressive agents may affect bone mass. INTRODUCTION: Interactions between the serotonergic and skeletal systems are suggested by various clinical observations but are poorly understood. MATERIALS AND METHODS: Using gene microarrays, we found that the serotonin transporter (5-HTT) was strongly expressed in RANKL-induced osteoclasts. Using RANKL stimulation of RAW264.7 cells and mouse bone marrow cells as a model system for osteoclast differentiation, we studied the possible role/s of the different components of the serotonin (5-HT) system on the differentiation process. RESULTS: Osteoclast 5-HTT exhibited typical 5-HT uptake activity that was inhibitable by fluoxetine (Prozac). Fluoxetine reduced osteoclast differentiation but did not inhibit the activation of preformed osteoclasts, whereas the addition of 5-HT itself enhanced differentiation. Fluoxetine-treated osteoclast precursors had reduced NF-kappa B activation and elevated inhibitory protein kappa B alpha (I kappa B alpha) levels compared with untreated cells. 5-HT, on the other hand, resulted in activation of NF-kappa B. Reserpine inhibition of intracellular transport of 5-HT into cytoplasmic vesicles potentiated RANKL-induced osteoclast formation, suggesting the importance of intracellular 5-HT in regulating osteoclast differentiation. Reserpine also modestly enhanced the expression of the osteoclast marker TRACP in the absence of RANKL. CONCLUSIONS: Taken together, these data suggest that the 5-HT system plays an important role in bone homeostasis through effects on osteoclast differentiation and implies that commonly used antidepressive agents may affect bone mass.

Animals↗
PubMed1992

A population-wide profile of prescription drug use in Saskatchewan, 1989.

OBJECTIVE: To measure the prevalence of prescription drug use in Saskatchewan in 1989. DESIGN: Retrospective study. PARTICIPANTS: A total of 961,203 Saskatchewan residents (including those who died or were born during the study year) who were eligible for coverage under the Saskatchewan Prescription Drug Plan. The study population represented 94% of the province's total population; those excluded were mostly status Indians (for whom a federal plan is available). MAIN RESULTS: At least one prescription was received by 66.0% of the study population in 1989. The mean number of prescriptions per patient was 8.2, and the mean cost of drug material per prescription was $13.95. Females received substantially more prescriptions than males; the difference was particularly notable for cardiovascular agents, antidepressants and benzodiazepines. In the senior population 80.8% received at least one prescription; the mean number of prescriptions per patient was 18.4. The most commonly dispensed drug for the entire study population was amoxicillin (290 prescriptions per 1000 people); triazolam was the most frequently dispensed central nervous system drug (74 prescriptions per 1000 people). Regional variation in overall drug use was remarkably small, although it increased at the drug-class level, especially for tranquillizers. The use of cardiovascular drugs was 27% to 32% higher (depending on how use was measured) per Regina resident than per Saskatoon resident. Benzodiazepines were commonly used on a long-term basis, despite recommendations to the contrary. CONCLUSIONS: The results quantify the prevalence of prescription drug use, underscore the importance of careful management of drug therapy by physicians and pharmacists (especially for seniors), illustrate substantial variation in drug therapy strategies and raise questions about utilization of benzodiazepines and cardiovascular drugs.

Age Factors↗
PubMed1987

Pharmacological properties of EXP 561, a potential antidepressant drug.

The compound EXP 561 (1-amino-4-phenylbicyclo-[2,2,2]-octane), an inhibitor of the noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) uptake, a potential antidepressant agent, was studied in tests for evaluation of antidepressant drugs (AD). In most experiments (the apomorphine and reserpine hypothermia, the behavioural despair test, the blood pressure increases induced by NA and 5-HT) EXP 561 revealed similar activities as tricyclic AD. EXP 561 evoked stimulation of the hind limb flexor reflex in spinal rats, blocked by prazosin, metergoline and clomipramine. EXP 561 administered repeatedly in mice (twice daily for 14 days) did not evoke the adaptive changes induced by AD inhibiting the amine uptake, i.e. it did not enhance the amphetamine locomotor hyperactivity, did not potentiate the clonidine aggressiveness (at a lower dose, while at a higher one it acted less potently than when given acutely) or did not change the reserpine effect on the locomotor activity. EXP 561 showed a poor affinity to alpha 1-adrenoceptor (IC50 was 135,000 nM). The results indicate that the inability to induce adaptive changes is a feature which differentiates EXP 561 from tricyclic AD.

Aggression↗
PubMed2000

[Serotonin syndrome during fluoxetine poisoning in a patient taking moclobemide].

PURPOSE: To present a case of delayed serotonin syndome (SS), a less well-known adverse effect of fluoxetine intoxication. CLINICAL PRESENTATION: A 21-yr-old woman was admitted following voluntary intoxication with fluoxetine and benzodiazepines. At the time of admission, she was slightly drowsy and hypotonic but, eight hours later, she developed severe hypertonic coma despite blood concentrations of fluoxetine within the therapeutic range. Repeated toxicological analyses revealed the presence of moclobemide at non-measurable concentrations, suggesting earlier ingestion of this monoamine oxydase inhibitor. Having excluded all other likely causes of the neurological syndrome observed, a SS was postulated. Treatment was symptomatic with mechanical ventilation, sedation with thiopental and fentanyl, and neuromuscular block with pancuronium bromide. The patient recovered spontaneously 20 hr later. CONCLUSION: Physicians managing patients presenting with fluoxetine intoxication must be aware of the potential risk of SS. Treatment is symptomatic, but SS may be severe and require vital support in the intensive care environment. Review of published reports does not allow the authors to recommend a specific anesthetic management.

Adult↗
PubMed1996

Lateralized neuropsychological functioning in depressive patients before and after drug therapy.

Several decades of research have led to different hypotheses about cognitive functioning in depression; one of the hypotheses states that there is altered functioning of the hemispheres during a depressive episode. Lateralization studies have found diminished neuropsychological functioning in depressive patients; especially right-hemisphere functions seem impaired. In our study we used conventional neuropsychological tests to study shifts in hemispheric functioning. Neuropsychological testing before and after therapy in 52 (for the most part therapy-resistant) depressives showed no substantial effects in lateralized functioning. None of the measures enabled prediction of response to treatment; however 17 different interaction variables were identified, five of which make an unique contribution.

Adult↗
PubMed1999

Non-nicotine pharmacotherapy for smoking cessation.

The selection of a non-nicotine treatment is based on the acceptability of various treatments with smokers, the ability to address the specific neurobiology of nicotine addiction, and the option to provide treatment for co-morbid conditions of nicotine-dependent patients. The search for effective treatments for nicotine dependence has generated a wide variety of non-nicotine approaches based on the neuropharmacologic and sensory basis for tobacco use. The only non-nicotine, FDA-approved medication is bupropion, an amino-ketone agent that is believed to work on the dopaminergic and noradrenergic neurotransmitters involved in perpetuating nicotine dependence. This article reviews other unapproved medications, mechanisms of action, and their effectiveness in clinical trials.

Adrenergic alpha-Antagonists↗
PubMed2001

Long-term naturalistic treatment of depressive symptoms in bipolar illness with divalproex vs. lithium in the setting of minimal antidepressant use.

OBJECTIVE: Risks have been associated with the long-term use of antidepressant in the treatment of bipolar disorder. We review our naturalistic experience with divalproex versus lithium in treating depressive symptoms of bipolar illness. METHOD: All patients with bipolar disorder treated with lithium or divalproex were identified in a university outpatient psychiatry clinic sample over one year (n=38 patients, 41 treatment trials). Treatment response was based on standard prospective symptom rating scales. Mean duration of follow-up was 90 weeks. RESULTS: Lithium and divalproex were equally effective and tolerated in the total sample. Antidepressant effects were noted despite sparing use of standard antidepressant agents (19% received them). Lithium non-responders responded well to divalproex (50%), and vice versa (44%). Divalproex monotherapy (24%) was more common than lithium monotherapy (7%, P=0.07) and was notably effective in treating depressive symptoms, with a 7/10 response on the CGI-BP and improvement on the HDRS (14.8+/-9.2 to 7.6+/-7.8, P=0.003, duration of prospective follow up 26.7 weeks). CONCLUSIONS: Lithium and divalproex were equally effective and tolerated in this naturalistic sample, but responders may represent distinct subgroups. Both agents, but particularly divalproex, demonstrated long-term antidepressant effects, with limited adjunctive standard antidepressant use.

Adult↗
PubMed1999

Anxiety with depression: a treatment need.

In the community, depression and anxiety are highly prevalent. The relationship between these two conditions is often unclear and has been the subject of much discussion. The classical viewpoint considered depression and anxiety to be two disorders with separate treatment options: anxiolytic agents for anxiety and antidepressant agents for depression. Depression and anxiety may occur together representing comorbid 'pure' conditions, or anxiety may predispose depression (or vice versa), or symptoms of anxiety and depression may be external manifestations of one underlying cause, or there may be an overlap of classifications. It is also possible that a mixed anxiety and depressive disorder exists: the association of subthreshold depressive symptoms and subthreshold depressive anxiety. This review examines the relationship of co-occurring depression and anxiety. The socioeconomic burden and the need for effective treatment of comorbid anxiety and depression are highlighted. The SSRIs, e.g. paroxetine, are discussed in particular as appropriate pharmacological therapy for anxiety with depression.

Anxiety↗
PubMed1995

Burning mouth syndrome.

BACKGROUND AND OBJECTIVES: Burning mouth syndrome (BMS) is a frequent process that produces marked oral dysesthetic symptoms. There is controversy over its etiopathogenesis and diagnosis. Therapeutic results are unsatisfactory. The objectives of this study were: (1) to analyze a possible agreement on the definition of BMS; (2) to analyze its cause; (3) to propose a therapeutic scheme that has been shown to be highly effective in our experience and has not been previously reported. METHODS: Five hundred patients with symptomatology of BMS were retrospectively evaluated with a study protocol, specially designed for this disease. Patients with local or general disease processes that could cause secondary asymptomatic stomatodynia were excluded from the study. RESULTS: Most of the patients evaluated were women over 60 years of age with oral symptoms, including a sensation of heat and burning, and pain, lasting for months or years, and a history of multiple unsuccessful treatments. The patients showed depression associated with anxiety, with evidence of psychiatric disorders in the family. Based on these findings and eliminating symptomatic painful conditions of the mouth that may stimulate this syndrome, we diagnosed a genuine or basic BMS of psychosomatic origin. Therapies used in the treatment of these neurotic conditions were not always useful. Tranylcypromine associated with anxiolytics and hypnotics in low doses plus the support of psychotherapy by the stomatologist were the most effective treatments. CONCLUSIONS: The BMS should be defined as a psychosomatic process causing oral dysesthesias for months or years.

Adult↗
PubMed2005

Newer antidepressants and other nonhormonal agents for the treatment of hot flashes.

The reluctance to use estrogen in breast cancer survivors with hot flashes has extended to its use in healthy women since the 2002 publication of the Women's Health Initiative study. This article reviews the clinical development of nonhormonal agents as alternatives to hormonal therapy for the management of hot flashes.

Adrenergic alpha-Agonists↗
PubMed2005

Selective serotonin re-uptake inhibitors and the risk of bleeding.

Despite their safety, selective serotonin re-uptake inhibitors (SSRIs) are associated with bleeding. The authors critically reviewed the medical literature on SSRIs to identify subgroups of patients at risk of bleeding complications. The authors performed a literature search using MEDLINE from 1966 to 1st September 2004 using; 'haemorrhage, serotonin uptake inhibitors and antidepressive agents' as search terms and followed up on citations in each paper that was relevant to SSRI associated bleeding. The authors reviewed 7 retrospective analytical studies and 24 case reports of bleeding in 43 different people. Analytical studies support an association between SSRI consumption and upper gastrointestinal (GI) bleeding and perioperative bleeding. Little evidence links SSRI use with intracerebral haemorrhage. The risk of GI bleeding appeared to be highest among patients consuming SSRIs with NSAIDs. Combining aspirin or NSAIDs with SSRIs may further increase the risk of bleeding. Clinicians should caution patients about combining SSRIs with aspirin or NSAIDs. Pharmacotherapy to reduce the risk of GI bleeding should be considered in high risk patients.

Adult↗