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At least 19 recordsLinked to original sources
PubMed1992

Reversal of stress-induced anhedonia by the atypical antidepressants, fluoxetine and maprotiline.

Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions. In the present study this effect was reversed by chronic (9 weeks) treatment with the atypical antidepressants, fluoxetine and maprotiline (5 mg/kg/day); the non-antidepressant chlordiazepoxide was ineffective. Stressed animals were also subsensitive to food reward in the place conditioning procedure; however, fluoxetine and maprotiline treated animals showed normal place preference conditioning. Acute pretreatment with raclopride (100 micrograms/kg) selectively reversed the recovery of sucrose drinking in antidepressant-treated stressed animals. These results extend previous reports of the efficacy of tricyclic antidepressants in this paradigm, and support the hypothesis of a dopaminergic mechanism of antidepressant action.

Animals↗
PubMed1986

The effects of some putative antidepressant agents on the schedule-controlled behavior of the pigeon.

Numerous "second-generation" antidepressants with pharmacological profiles and chemical structures different from those of the tricyclic antidepressants have recently been developed. We examined the actions of four of these compounds (mianserin, maprotiline, trazodone and fluvoxamine) on the responding of pigeons under two different multiple (mult) schedules of grain presentation (a mult fixed-interval (FI) 600-s fixed-ratio (FR) 30-response and a mult FI 200-s FI 200-s in which responding in one component was punished by intermittent presentation of a brief electric shock). The rate of FI 600-s responding was greatly increased by several doses of maprotiline and mianserin, which either did not affect or produced only small increases in the rate of FR 30 responding. Fluvoxamine and trazodone did not produce similar differential effects. Relatively low doses of maprotiline, mianserin and trazodone decreased the FI quarter-lives. Fluvoxamine only decreased the FI quarter-life at a dose that largely eliminated responding. Mianserin produced proportionally greater increases in the rate of punished FI 200-s responding than in the rate of unpunished FI 200-s responding. Selective effects on punished responding were not seen with maprotiline, fluvoxamine and trazodone.

Animals↗
PubMed1990

A drug utilization review of prescribing patterns for trazodone versus amitriptyline.

The second-generation antidepressant trazodone has been thought by some clinicians to exert a less robust antidepressant effect than do tricyclic agents. This impression differs from the findings of numerous published clinical trials. In an effort to determine whether this discrepancy may be due to possible inappropriate dosing or use of trazodone for different patient subtypes, a retrospective chart review of 138 depressed inpatients treated with amitriptyline and of 42 depressed inpatients treated with trazodone was performed to compare their respective prescribing patterns. While these two groups did not differ with regard to most demographic variables, results revealed that patient prescribed trazodone were older (trazodone, mean +/- SD age = 54.5 +/- 8.8 years versus amitriptyline, 43.2 +/- 12.9 years; p less than .001), more often had a recurrent depressive disorder (trazodone = 57.1%, amitriptyline = 39.1%, p less than .06), and more frequently had a history of unresponsiveness to other antidepressants (trazodone = 47.6%, amitriptyline = 11.6%; p less than .001). In addition, initially prescribed daily doses of trazodone were below the recommended starting dose of 150 mg/day (mean +/- SD starting dose = 113.7 +/- 42.1 mg/day), while starting daily doses for amitriptyline (mean +/- SD = 69.8 +/- 20.1 mg/day) were judged to be more adequate relative to the recommended daily dose of 75 mg/day. Final trazodone dosage (mean +/- SD final dose = 217.9 +/- 87.5 mg/day) could be judged to have been far short of optimal levels of 250 to 350 mg/day and of up to 600 mg/day for inpatients and 400 mg/day for outpatient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Tolerability of moclobemide, a new reversible inhibitor of monoamine oxidase-A, compared with other antidepressants and placebo.

Moclobemide, a new selective and reversible inhibitor of monoamine oxidase A (RIMA), has been compared with various tricyclic antidepressants (TCAs) in numerous controlled studies. Pooled data from these studies, comprising 1656 patients, as well as the consideration of individual trials, show that moclobemide is far better tolerated than the TCAs. Its side effects mainly comprise mild degrees of nausea and dizziness at the beginning of treatment in a small proportion of patients. Age and sex do not affect the tolerability of moclobemide: it is equally well tolerated by elderly patients. In 2300 patients treated with moclobemide in doses up to 600 mg/day, without dietary restrictions, there was no tyramine-related hypertensive reaction. It is concluded that moclobemide may be the second-generation antidepressant doctors were waiting for--equally effective as the classical antidepressants but far better tolerated.

Adult↗
PubMed1985

Medications to modify at-home behavior of Alzheimer's patients.

Benzodiazepines are used often in elderly, anxious patients with or without dementia. Clearly efficacious and relatively safe, benzodiazepines should be considered the first-line drugs of choice to treat anxiety associated with Alzheimer's disease. "Second-generation" antidepressants, although considerably more expensive than the tricyclics, are of significant benefit in the elderly, primarily because of extremely low anticholinergic side effects.

Aged↗
PubMed1987

Rational use of antidepressants.

The key to the proper treatment of affective illness is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the tricyclic antidepressants for a major depressive episode, electroconvulsive therapy for a major depressive episode with psychotic features, and monoamine oxidase inhibitors for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy or ECT. Second-generation antidepressants are recommended in situations where their adverse effect profiles offer significant advantages over TCAs in an individual patient. Maintenance antidepressant treatment may be necessary to prevent recurrent depressive episodes.

Antidepressive Agents↗
PubMed1988

Antidepressant drug studies in the elderly.

This article reviews the literature on antidepressant drug trials conducted in elderly populations. Only 27 studies of cyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and psychostimulants deal specifically with subjects that were over age 60. Methodologic problems were found in many studies, including lack of diagnostic criteria and inadequate controlling for cognitive impairment, concurrent medical illnesses, and nonpsychotropic medications. Most studies compared second-generation antidepressants against placebo or tricyclic antidepressants (TCAs). Antidepressant drugs are effective treatments for geriatric depression, and limiting side effects are comparable with those seen in younger populations.

Aged↗
PubMed1990

Moclobemide compared with second-generation antidepressants in elderly people.

Two multicentre studies are described here; the first compared moclobemide with mianserin and the second with maprotiline, both in elderly patients with a DSM-III diagnosis of major depressive episode. In the first study, 80 eligible patients were randomized to either moclobemide 300-500 mg or mianserin 75-125 mg per day for 4 weeks. Mean reduction in Hamilton Rating Scale for Depression (HRSD) score was 52% in both groups. The overall assessment of efficacy was good or very good for 60% of the patients, and tolerance was considered good or very good for 85% of the patients in both groups; no significant differences between the 2 treatments were seen. The second study comprised 39 hospitalized patients randomized to either moclobemide 150-300 mg daily or maprotiline 75-150 mg daily for 6 weeks. At the end of treatment, HRSD scores declined 85% in both groups compared with baseline. The overall assessment of efficacy was over 90% good or very good in both groups. Tolerance was rated good or very good for 80% of moclobemide and 75% of maprotiline patients; none of these results differed significantly between the groups, indicating that moclobemide is as effective in elderly patients as the 2 second-generation antidepressants. In view of the safety of moclobemide, it should be considered first-line therapy for depression in elderly people.

Aged↗
PubMed1989

Management of depression in the elderly.

Primary care physicians have a vital role to play in identifying depression in their elderly patients. Diagnosis may be difficult, because symptoms are atypical and frequently include psychomotor agitation, somatic symptoms, and complaints of memory loss. Patients with medical illnesses, such as cancer, postmyocardial infarction, stroke, Parkinson's disease, and early Alzheimer's disease are particularly vulnerable to depression. Drugs that may cause depressive symptoms are digitalis at toxic levels, beta-blockers, centrally acting antihypertensives, immunosuppressants, and nonsteroidal anti-inflammatory agents. Cyclic antidepressants are the drugs of first choice. Selection depends on the patient's physical health and current medications and the side effect profile of the drug. Side effects are more pronounced in old age because of drug accumulation owing to slowed clearance. Troublesome side effects are anticholinergic effects, orthostatic hypotension, sedation, cardiotoxicity, and weight gain. The most useful antidepressants for geriatric patients are the secondary amines, desipramine and nortriptyline. The second-generation drug trazodone has the advantage of causing the least anticholinergic effects, but it is very sedating. Before treatment, the patient should have an electrocardiogram, liver function tests, tonometry, sitting and standing blood pressures, evaluation of urinary symptoms for outflow obstruction, review of current medications, and estimation of suicide risk. Cyclic antidepressants are contraindicated during recovery from myocardial infarction, in heart disease when there is severe impairment of myocardial performance, in seizure disorders, and in the presence of glaucoma or a large prostate. Drug interactions that may cause trouble can occur with epinephrine, MAO inhibitors, thyroid hormone, cimetidine, and centrally acting antihypertensives. Dosage should start low, increasing usually by 25 mg every 4 to 5 days until a therapeutic level is reached. Failure of a noradrenergic antidepressant after 4 to 5 weeks can be followed by a trial of a serotonergic drug. Drug serum level monitoring is useful for imipramine, desipramine, and nortriptyline. Monoamine oxidase inhibitors are effective in many elderly patients who are resistant to TCAs. Sympathomimetic drugs must be avoided with MAOIs. Elderly patients are at high risk of toxicity and drug interactions with lithium. Electroconvulsive therapy is useful for patients who do not respond to drug treatment, but medical complications, particularly cardiovascular, often occur in patients 75 or older. Many patients relapse after ECT. Psychotherapy together with pharmacotherapy may be the optimal treatment for elderly depressives. Older patients are more likely to become chronically depressed than younger patients. The risk of suicide in depressed elderly males is high, particularly in those with psychosocial problems, and depression rises with age.

Aged↗
PubMed1986

Adverse drug reactions to first- and second-generation antidepressants: a critical evaluation of drug surveillance data.

We reviewed data on adverse drug reactions (ADRs) to first- and second-generation antidepressants, recorded by two different drug surveillance systems. The rate of ADRs that led to discontinuation of the drug in the individual case, assessed within a multi-centered hospital-based drug monitoring system (AMUP), was significantly higher in case of exposure to tricyclics (7.4%) than with the second-generation drugs (3.1%). On the basis of voluntary reports to the Medicines Commission of the German Medical Profession (AMK), profiles of ADRs to the drugs under survey were constructed and compared with data compiled by the WHO. The types of ADRs varied more between second-generation drugs than between tricyclics. Special attention was paid to rare but serious ADRs (e.g. seizures during treatment with maprotiline, and blood dyscrasias attributed to mianserin).

Adult↗
PubMed1990

Pharmacotherapy of depression: the American current status.

This paper is a brief review which deals with research findings, clinical issues, and strategies in the pharmacotherapy of clinical depression. The author introduces antidepressants which are currently available in the United States. They include heterocyclic antidepressants (tricyclic antidepressants and second-generation antidepressants), monoamine oxidase inhibitors, lithium, carbamazepine, and others. Under the description of each drug category, therapeutic and side effects are briefly discussed in the context of psychiatric practice in America. Then, the author gives a birds eye view of American pharmacotherapy of using antidepressants in acute, maintenance, and prophylactic treatments of depression.

Antidepressive Agents↗
PubMed1990

Therapy of affective disorders.

The key to the proper treatment of affective disorder is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the TCAs for a depressive episode; ECT for a depressive episode with psychotic features; and MAOIs for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy, an MAOI, or ECT. Second-generation antidepressants are not usually indicated as initial treatments. They are recommended in situations in which their adverse-effect profiles offer significant advantages over TCAs in an individual patient. Second-generation antidepressants have not been extensively studied in patients who do not respond to TCAs. Maintenance antidepressant may be necessary to prevent recurrent depressive episodes. Lithium remains the mainstay of acute treatment of mania and for prophylaxis of subsequent affective episodes. In lithium-refractory or lithium-intolerant patients, carbamazepine is recommended. Valproic acid and verapamil have been useful, primarily in patients who do not respond to lithium and carbamazepine.

Antidepressive Agents, Tricyclic↗
PubMed1991

Antidepressant treatment and side effect considerations.

Many antidepressant drugs are available today, including both the first-generation and second-generation antidepressants. While antidepressants are similar in terms of drug efficacy, onset of action, and latency to treatment response, their potential side effect and toxicity profiles are quite different. These factors must be weighed before treatment of depression is begun in an effort to prescribe the compound that is most beneficial, i.e., clinically effective while exhibiting the fewest negative aspects. Determination of patients' "at-risk" profile for drug side effects is best done by a careful analysis of their medical history and concomitant drug therapies. The relative toxicity index for antidepressants should also be reviewed carefully with the goal of avoiding the unwanted sequelae of antidepressant toxicity.

Antidepressive Agents↗
PubMed1991

Antidepressant drug prescribing in general practice: a 6-year study.

We analysed antidepressant drugs (AD) prescription ratios of the GPs working in Verona, Italy, over a 6-year period (1983-1988). The data, provided by a local drug information system (SIF-USL), were calculated as Defined Daily Dose (DDD), which is the unit of drug consumption recommended by WHO. We found that DDD/1000 patients/day increased over the period, mainly because of an increase in the use of 'second-generation' antidepressants and other non-tricyclic antidepressants. An increase in the levels of prescription of AD was observed over the 6 years. This increase was statistically significant when comparing the first (1983) with the other years. Low correlations were found between DDD/patient/year ratios and GPs' age, sex and list size. Harmonic analysis of the seasonal variations in prescriptions of AD revealed a substantial pattern of seasonality, in which the first four harmonics accounted for the greater part (95.5%) of the seasonality. AD prescribing may be linked more closely to seasonal holiday patterns than to seasonality in the onset of depressive disorders.

Adult↗
PubMed1991

Pharmaco-EEG profile of levoprotiline: second example to discuss the predictive value of pharmaco-electroencephalography in early human pharmacological evaluations of psychoactive drugs.

The present paper forms the second part of a critical evaluation of the use of pharmaco-EEG as an instrument for assessing the profile of action of psychoactive drugs in man based on the trial results of three new psychoactive test substances. Part I described the basic principles and methodological approaches and illustrated the value of pharmaco-EEG in framing hypotheses about the therapeutic efficacy of psychotropic drugs by the example of the neuroleptic drug savoxepine. This chapter illustrates the relevance of pharmaco-EEG in the assessment of psychoactive drugs by reference to the test substance levoprotiline. Levoprotiline is the pure R-(-)-enantiomer of the racemic drug oxaprotiline, a successor to the second-generation antidepressant maprotiline. Only the S-(+)-enantiomer of oxaprotiline inhibits the re-uptake of noradrenaline. In view of the absence of any monoamine-uptake inhibiting action of levoprotiline, this drug was assumed to be devoid of an antidepressive action. This assumption, however, was disproved by observations made in clinical studies with depressive patients, in whom levoprotiline did indeed display antidepressive activity. Investigations of levoprotiline in the pharmaco-EEG model--even though being retrospective in the sequence of events--would have been able to produce objective prediction of antidepressive potential in man. The substance was tested by comparison to placebo and to the standard antidepressant imipramine in nine young, healthy male volunteers. The experimental design was a cross-over uncompleted block design with three consecutive trial days one week apart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression.

Depressive illness among the elderly is an important public health concern. However, treatment of the elderly may be complicated by age-related changes in physiology, general medical status, and susceptibility to side effects. There is therefore a need for improved treatment modalities for depressed elderly patients. Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake. It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants. The authors present the combined data from two similarly designed comparisons of paroxetine and doxepin in outpatients over 60 years of age with major depression. The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression (HAM-D) total score, the Montgomery and Asberg Depression Rating Scale (MADRS), and the Hopkins Symptom Checklist (SCL) depression factor score. Paroxetine was significantly superior to doxepin on the Clinical Global Impressions (CGI) scale for severity of illness, the HAM-D retardation factor, and the HAM-D depressed mood item. Doxepin produced significantly more anticholinergic effects, sedation, and confusion. Paroxetine was associated with more reports of nausea and headache. These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly.

Age Factors↗
PubMed1992

Moclobemide. A review of its pharmacological properties and therapeutic use in depressive illness.

Moclobemide is a reversible and selective inhibitor of the enzyme monoamine oxidase (MAO) subtype A with a broad spectrum of antidepressant activity. Controlled clinical studies suggest that the short term clinical efficacy of moclobemide is significantly superior to that of placebo, and comparable to that of the tricyclic antidepressants clomipramine, amitriptyline, imipramine and desipramine, the irreversible MAO inhibitor tranylcypromine and the second-generation antidepressants maprotiline, mianserin and fluvoxamine in the treatment of major depressive illness. Moclobemide appears to be equally effective in endogenous and nonendogenous depression, producing marked amelioration of clinical features of psychomotor retardation and depressed mood. Moclobemide is well tolerated, being largely devoid of the anticholinergic adverse effects, symptomatic postural hypotension and weight gain variously associated with the tricyclic antidepressants and irreversible MAO inhibitors, and appears considerably safer on overdosage than the tricyclic and second generation antidepressants. Moreover, moclobemide offers the advantage over the older, irreversible MAO inhibitors of causing only minimal potentiation of the pressor response to dietary tyramine (the so-called 'cheese effect'). Consequently, the risk of potentially fatal hypertensive crisis, a major deterrent to the wider acceptance of these earlier compounds, is substantially reduced with moclobemide, and the need for dietary precautions is minimised. With its efficacy against endogenous and nonendogenous depression, relatively rapid onset of antidepressant activity, and absence of carry-over effects on treatment withdrawal, moclobemide is likely to make an important contribution to the treatment of major depressive illness. Its favourable tolerability profile, safety on overdosage and beneficial effect on age-related cognitive impairment may be of particular value in the elderly and those with concurrent physical illness.

Animals↗