Standard Tricyclic Antidepressants Research Articles

A comparative study on efficacy of amitriptyline and escitalopram in the treatment of depression

Background: Several generations of antidepressant medication which act by distinct pharmacological mechanisms have been introduced for the treatment of depression; tricyclic antidepressants (TCAs) were first line of treatment for many years. However, over the last decade, selective serotonin reuptake inhibitors (SSRIs) have displaced TCAs, mainly because of better side effect profile. There are no references in literature on comparison of efficacy of TCAs and SSRIs in Nepalese population. This study attempted to compare the efficacy of amitriptyline, a reference standard TCA with escitalopram, a newer SSRI in Nepalese population.Methods: An open level, randomised, prospective study was conducted for one year duration. Eighty outpatients suffering from major depression who met inclusion and exclusion criteria were randomly assigned to either amitriptyline or escitalopram group for four week study. Seventy one patients (amitriptyline N: 36, escitalopram N: 35) completed the study. Hamilton Depression Rating Scale (HDRS) was used to measure the antidepressant effect. Antidepressant efficacy was evaluated on reduction of HDRS score before and after therapy (End of four weeks).Results: In amitriptyline group, mean percentage reduction in HDRS score was 58.29% (13.5 points), while in escitalopram group was 60.78% (14.03 points). Both the drugs significantly improved the HDRS score at the end of the study (p<0.05). On intergroup comparison, antidepressant efficacy of amitriptyline and escitalopram did not differ significantly from each other (p>0.05).Conclusions: This study suggests that escitalopram is effective in the treatment of depression and its efficacy appears to be comparable to amitriptyline at the end of four weeks.

Treatment patterns in inpatient depression care.

This study aimed to identify latent patterns of treatment combinations in inpatient depression care. A secondary analysis of routinely collected data on inpatient depression treatment from 2133 patients was conducted. Exploratory latent class modeling was used to identify distinct classes of treatment combinations based on antidepressant medication, psychotherapeutic interventions, and additional treatments. The classes were compared with regard to patient characteristics and treatment outcomes. Eight different classes of inpatient treatment combinations could be identified: 22.8% of the patients were treated with a combination labelled "standard modern antidepressants", 14.6% with "standard tricyclic antidepressants", 12.2% with "high intensity innovative strategies", 12.1% with "standard selective-reuptake-inhibitors", and 11.6% with "low intensity", 9.6% with "somatic", 8.8% with "high intensity traditional", and 8.3% with "high intensity psychosocial" care, respectively. Patients treated with different patterns of interventions differed statistically significantly regarding demographic and clinical characteristics. Responder rates ranged from 68.4% to 86.6% across treatment classes. The presented attempt of empirical modeling of a complex multifactorial intervention by means of latent class analysis proved to be a promising way of capturing the complexity of routine inpatient depression treatment. The identified classes of treatment combinations may provide relevant information for a re-evaluation and improvement of inpatient depression treatment strategies.

Will tricyclic antidepressants make a comeback for depressed Parkinson disease patients?

Neurologists and psychiatrists were willing to embrace the revolution of the serotonin reuptake inhibitor (SSRI) which in most offices replaced the standard tricyclic antidepressants (TCA) for treatment of depression in patients with Parkinson disease (PD). It is not hard to imagine how such a drastic transition occurred so rapidly, as there was a desire for a more refined and targeted therapy with fewer side effects (such as dry mouth, dry eyes, constipation, and confusion). The switch occurred, however, in the absence of a prospective, randomized, head-to-head comparison between SSRIs and TCAs. Menza et al.1 offer a true evidence-based comparison in this issue of Neurology ®. With depression reported to occur in 40% or more of patients with PD,2,3 this is an important clinical study. The authors presented a simple study design that compared paroxetine CR, nortriptyline, and placebo in a 52-patient randomized trial. The doses were escalated up to three times, based on the clinician’s discretion, up to a top …

Efficacy and safety of citalopram versus amitriptyline in the treatment of major depression

Background:Double-blind clinical trials comparing citalopram with amitriptyline or other tricyclic antidepressants are lacking in India.Aim:To evaluate the efficacy and safety of the newer antidepressant citalopram in the treatment of major depression.Methods:The clinical acceptability and safety profile of citalopram was assessed and compared with that of amitriptyline in 40 patients in an outpatient set-up. Patients aged 18 to 65 years who fulfilled the diagnostic criteria for a single or recurrent major depressive disorder (as defined by DSM-IV) for a minimum of 2 weeks were enrolled. Patient assessment was done at screening, baseline, end of week 1, week 2, week 3, week 4, week 5 and week 6 for efficacy and safety parameters such as Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI) Scale, adverse event follow up, blood pressure and pulse. Three-level statistical analysis including ANOVA was performed on all efficacy measures.Results:On the HDRS the percentage reduction in the mean score for the citalopram group (Group 1) was 72.12%, while that for the amitriptyline group (Group 2) was 67.93%. On the CGI-Improvement Scale, the percentage reduction at the end of the study for the citalopram group was 56.79% while in the amitriptyline group it was 44.70%. Twenty per cent of patients in Group 1 reported adverse events compared to 75% in Group 2.Conclusions:Citalopram is effective in the treatment of major depression at the dosages range of 20–60 mg/day and its efficacy is equivalent to that of standard tricyclic antidepressants such as amitriptyline, with a substantially better tolerability profile.

Efficacy of the dietary supplement S-adenosyl-L-methionine.

To review existing published clinical evidence surrounding the dietary supplement SAMe (S-adenosyl-L-methionine). The majority of information was obtained from primary published literature identified through MEDLINE search (1966-February 2001). Information was also obtained through secondary and tertiary sources when available. All articles identified from data sources were evaluated and all relevant information included in this review. The majority of clinical trial evidence surrounds the application of SAMe for various depressive disorders, osteoarthrits, and fibromyalgia. Sample sizes of these trials and the dose employed have varied considerably. Several reviews and at least two meta-analyses have examined the available evidence surrounding SAMe in the therapy of depression for trials completed prior to 1994 and concluded that SAMe was superior to placebo in treating depressive disorders and approximately as effective as standard tricyclic antidepressants. Much of this information exists in the form of isolated case reports or solitary clinical trials. SAMe appears to be well tolerated, with the majority of adverse effects presenting as mild to moderate gastrointestinal complaints. However, it is apparent that this agent is not without risk of more significant psychiatric and cardiovascular adverse events. Information documenting drug or food interactions with SAMe is very limited. Consumers should be instructed to avoid unmonitored consumption of this dietary supplement until sufficient discussion has taken place with their primary healthcare provider. Although there exists significant potential for therapeutic application of SAMe, its uncertain risk profile precludes definitive recommendation at this time. Healthcare providers and consumers should likely temper their enthusiasm for this dietary supplement until sufficient information becomes available.

SAMe targets consumers via the Web.

Touted as one of the most promising supplements ever introduced, S-adenosyl-L-methionine, or SAMe (pronounced “Sammy”), is found advertised on the Internet, in health and drug stores, and even in direct-to-consumer television ads since its introduction in the United States last year. Discovered in the 1950s, SAMe has been used widely in Europe for a variety of maladies, including depression, osteoarthritis, and liver disorders. This dietary supplement has been sought by US consumers primarily for its mood-enhancing effects. SAMe is a natural compound endogenously produced from adenosine triphosphate and the amino acid methionine. It then becomes a ubiquitous methyl donor to a wide variety of acceptor molecules and is involved in numerous metabolic pathways.1 The exact mechanisms of action of SAMe for its purported health applications, principally as treatment of depression, are unknown. Limited animal and human data suggest that SAMe may play a role in alleviating depression by mechanisms such as modulating the monoaminergic systems and enhancing the neurotransmission resulting from the increase in neuronal membrane fluidity when modified by SAMe supplementation. The proposed neuropharmacologic effects of SAMe on depression have been extensively reviewed by several authors.1,2,3 Most early studies evaluating SAMe for depression were generally small and varied greatly in the patient population. A metaanalysis of selected clinical trials conducted for depression between 1973 and 1992 attempted to pool available data to assess the efficacy of SAMe compared with placebo (6 trials) and standard tricyclic antidepressants (7 trials). This study concluded that SAMe was more effective than placebo and comparably as effective as low to moderate dosages of tricyclic antidepressants.4 However, the substantial heterogeneity among these individual trials—patient populations, sample sizes, variable dosage regimens, and treatment durations—may limit the results found in this analysis. More recently, additional small double-blind trials have yielded positive results.5,6 Overall, trials testing parenteral doses have shown SAMe to be effective for clinical depression. Most trials have found the antidepressant effect to appear fairly rapidly (sometimes within 1 week) after the start of treatment. However, given the lack of large controlled trials and SAMe's questionable oral bioavailability, more data are needed to support its use orally. SAMe may be administered orally, intravenously, or intramuscularly, but only the oral formulation is commercially available in the United States. Most controlled studies of oral SAMe have employed a daily divided dose of 1,600 mg—but marketed supplements often recommend lower doses. Besides mild gastrointestinal distress, SAMe is generally well tolerated and does not appear to possess cardiac, anticholinergic, or orthostatic effects that may limit the clinical utility of many prescriptive antidepressants.7,8 Agitation and manic reactions have been reported to appear soon after SAMe administration.9,10,11,12 For this reason, its use should be avoided in patients with a history of mania or bipolar disorders. There are no known confirmed drug interactions with SAMe. One case of serotonin syndrome in an elderly woman taking SAMe (intramuscularly) concurrently with clomipramine hydrochloride has been documented.13 The safety of concurrent use with the commonly prescribed selective serotonin reuptake inhibitors has not been evaluated. The coadministration of SAMe (intramuscularly) with imipramine hydrochloride (to hasten the onset of response to imipramine) did not reveal significant adverse effects.6 Consumers should be aware that the nutritional supplement industry is not well regulated and that the question of purity and potency remain. For instance, a company that conducts independent analyses of herbal, vitamin, and mineral supplements recently found disturbing discrepancies between the labeled amount and the actual amount of SAMe contained in various brand products selected for testing. Nearly half of the products evaluated did not pass testing.14 Consumers and clinicians should also consider the cost of therapy. The monthly cost of SAMe, depending on the dose used, may be well over $200, exceeding that of most prescription antidepressants. The antidepressant potential of SAMe has generated much enthusiasm in this country lately, especially through the lay press. However, its claims of efficacy and safety for the treatment of depression need to be further justified through large controlled trials and by formal evaluation by the Food and Drug Administration. Follow-up studies to assess long-term tolerability and relapse rates are also needed.

Transmethylation and affective disorders

S-adenosyl-L-methionine (SAMe) is a naturally occurring metabolite and a major source of methyl groups in the brain. Methylation processes are important in the expression of mood and the failure of methylation may underlie some affective disorders. The administration of SAMe is associated with an increase in both 5-OH-indoleacetic acid and homovanillic acid, being the metabolites of serotonin and dopamine, respectively. SAMe indices mood elevation in depressed patients. Until 1995, 1,400 patients treated with SAMe were investigated in open or controlled trials. The efficacy of SAMe in treating depressive disorders is superior to placebo and comparable to standard tricyclic antidepressants. SAMe demonstrates a particularly low side effect profile. The increase of anxiety is the most common side effect. The addition of SAMe to standard antidepressants may shorten the time of treatment response compared to the use of antidepressants alone, especially in parenteral use (400–800 mg/day, iv.).

Section Review Central & Peripheral Nervous Systems: New antidepressant agents: Recent pharmacological developments leading to improved efficacy

The disadvantages of the standard tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), in terms of side-effects and fatal overdose, led to the development and release of seven new antidepressants in the USA in the past eight years with approximately another ten in various stages of development. This paper will focus on how recent advances in biochemistry and kinetics have led to improved efficacy. In particular, the more specific 5-HT agents appear effective for ‘typical’ depression and pain; the less specific ones for depression associated with obsessive-compulsive disorder. The selective serotonin reuptake inhibitors (SSRIs) are particularly suited for treatment of depression associated with diabetes mellitus; the serotonin and norepinephrine reuptake inhibitor (SNRI), venla-faxine, for resistant depression; and bupropion, for atypical depression. The serotonin receptor modulator (SRM), nefazodone, in contrast, is particularly suited for the treatment of depression associated with ...

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

Since the early 1950s, when imipramine was first introduced, a whole series of antidepressants with differences in structures, neurochemical effects and pharmacokinetics have been developed. Structurally or functionally, they have been classified as tricyclic antidepressants (TCAs), tetracyclic antidepressants, monoamine oxidase inhibitors (MAOIs), or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). In addition, there is a series of antidepressants with unique structures. Many of the newer TCAs appear to have shorter half-lives than the standard TCAs (e.g. imipramine), allowing for the possibility of a more rapid response, but requiring the drugs to be given in multiple daily doses, which may reduce patient compliance. The short time to peak plasma concentration (tmax) can also lead to rapid onset of adverse effects. The tetracyclic antidepressants have longer elimination half-lives (t1/2) than the TCAs, but there is only very minimal evidence for a relationship between drug concentrations in the blood and clinical response. The triazolopyridines, like the newer TCAs, show pharmacokinetic evidence for rapid onset of adverse effects and the need for multiple daily doses due to short tmax and t1/2. The newer MAOIs are a significant addition to therapy, as the rapid binding action of these medications increases their safety margin with regard to tyramine interactions. Further information in this area is required. In addition, moclobemide has pharmacokinetic features that are clinically beneficial (e.g. aging and renal dysfunction have little effect on the elimination of the drug), but also features that are not beneficial (e.g. nonlinear pharmacokinetics). Among the SSRIs, there are a range of t1/2 values for the parent drugs, from relatively short t1/2 values of less than 24 hours (paroxetine, fluvoxamine) to among the longest found (e.g. 2 days for fluoxetine). Only 2 of the agents (sertraline and citalopram) have linear pharmacokinetics, and 1 drug has nonlinear pharmacokinetics within the usual therapeutic range (fluvoxamine). Once a therapeutic blood concentration is established, linearity is helpful in avoiding the small dose changes and repeated rechecking of concentrations of medications that would be required for those agents with nonlinear pharmacokinetics. Sertraline stands out as having the best effects on behaviour among all antidepressants. However, fluoxetine and fluvoxamine are least likely to penetrate into breast milk. All 3 of the structurally unique newer antidepressants [amfebutamone (bupropion), viloxazine venlafaxine] have relatively short tmax values (1 to 2 hours), which may relate to the early onset of adverse effects. Amfebutamone has the benefits of linear pharmacokinetics with potential for defined therapeutic blood concentrations, lack of effect of liver enzymes on metabolism of the drug, and lack of significant effects of either aging or hepatic dysfunction on elimination of the drug. Thus, the antidepressants best suited for pharmacokinetic optimisation of therapy are the following: desipramine, sertraline, fluvoxamine, citalopram and amfebutamone.

Klinische Wirkungen von Serotonin-Wiederaufnahmehemmern - eine Übersicht

The SSRIs are a new class of effective antidepressant agents which have proven efficacy in a wide range of psychiatric applications. They are as effective as the tricyclic antidepressants and are better tolerated. The SSRIs are safe in overdose and have minimal drug interactions, and are suitable for once-daily dosing. Newer members of the class, such as paroxetine, have shorter half-lives and no active metabolites, and are likely to be safer than other members of the class. Paroxetine has been compared with the standard tricyclic antidepressants in a range of studies, and the efficacy and tolerability data from these studies have been collected together in the worldwide database on paroxetine. Paroxetine was shown to be at least as effective as active comparators in melancholic depression (DSM-III). In a comparative study of paroxetine and fluoxetine, both drugs were effective in reducing depressive symptoms and paroxetine showed a faster onset of action than fluoxetine. A higher incidence of side-effects was obtained in fluoxetine patients. In a long-term comparative study of paroxetine and placebo, fewer patients relapsed while on paroxetine for one year than on placebo - 15 and 38 %, respectively.

Comparative Tolerability Profiles of the Newer versus Older Antidepressants

Although the standard tricyclic antidepressants (TCAs) are generally effective in the treatment of depression, they can cause several troublesome adverse effects. Chief among these are their anticholinergic actions, which range from annoying dryness of the mouth and constipation to potentially dangerous urinary retention and confusion or delirium in the ill and elderly. Cardiovascular effects of TCAs include orthostatic hypotension, tachycardia and cardiac conduction slowing. Many TCAs are sedating and promote weight gain. Also problematic is the potential lethality of TCAs in overdose. The continual introduction of a host of new antidepressants over the past 15 years has provided an opportunity to improve the benefit-risk ratio for many patients by reducing medication-related toxicity. Selective serotonin reuptake inhibitors (SSRIs) and amfebutamone (bupropion), among others, are examples of effective antidepressants free of tricyclic-like anticholinergic, cardiovascular, sedating and appetite/weight-increasing effects. However, the new-generation drugs also present adverse effects of their own, including gastrointestinal distress, agitation and drug-drug interactions in the case of the SSRIs, and the risk of seizures or psychosis in amfebutamone recipients. Monoamine oxidase (MAO) inhibitors have also been refined; reversible inhibitors of MAO-type A afford protection against the usually feared hypertensive reaction to indirect sympathomimetic substances. The availability of new-generation antidepressants thus increases the likelihood of clinical response with a reduction in unwanted toxicity.

Dose-effect relationships for tricyclic antidepressants: the basis for rational clinical testing of new antidepressants.

The dose-effect relationship is a basic element in all research in experimental pharmacology. In clinical pharmacology, the central role of the dose-effect concept has usually been acknowledged, but the actual demonstration of dose-effect relationships in clinical drug research is often extremely difficult. In the early years after the introduction of imipramine and subsequently other tricyclic antidepressants (TCA), the dose-effect problems were not infrequently discussed in the clinical reports, usually on the basis of uncontrolled clinical assessments (Delay and Deniker 1959; Ayd 1959). However, towards the end of the 1960s, the question of appropriate dosing appeared to receive little attention, clinically or in research trials. In a larger review attempting to identify variables important for the therapeutic efficacy of TCA, the dose was not even considered (Smith et al. 1969). At that time, the demonstration of pronounced variations in steady state levels in patients on standard TCA (Sjoqvist et al. 1968) gave rise to a series of studies on concentration-effect relationships during the following two decades. For the introduction of new antidepressants, there is an increasing demand for data on the dose-effect relationship. In this situation, it seems awkward that our knowledge about the dose-effect relationship for the usual control therapy, TCA, is rather limited. Also for the clinical use of TCA, the dose-effect issue has been reintroduced by some authors in the 1980s (Quitkin 1985; Roose et al. 1986; Goethe et al. 1988). However, in clinical trials, this problem is seldom even discussed as a source of bias or variability.

New Aspects in the Treatment of Depression

Because of the limitations in efficacy and safety of the older tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAOI) a number of new approaches have been made in recent years to the treatment of depression to obtain more effective, more rapidly acting, better tolerated and safer drugs. One tactic has been to develop compounds with greater neuropharmacological selectivity in inhibiting the neuronal reuptake of 5-HT. Most of these are as effective as TCA but with fewer side-effects and greater safety. Another development has been 'reversible' MAOI which reduce the risk of interaction with tyramine-containing foods. For resistant depression the addition of lithium (and/or tryptophan) may be effective, possibly through promoting 5-HT neurotransmission. Continuous treatment with a selective 5-HT reuptake inhibitor can reduce the relapse rate in patients with recurrent depression. Unfortunately, these new approaches, despite their advantages in terms of side-effects and safety, have thus far not proved to be more effective or faster acting than the standard TCA. That remains a challenge for the future.

Clinical overview of serotonin re-uptake inhibitors

The SSRIs are a new class of effective antidepressant agents which have proven efficacy in a wide range of psychiatric applications. They are as effective as the tricyclic antidepressants and are better tolerated. The SSRIs are safe in overdose and have minimal drug interactions, and are suitable for once-daily dosing. Newer members of the class, such as paroxetine have shorter half-lives and no active metabolites and are likely to be safer than other members of the class. Paroxetine has been compared with the standard tricyclic antidepressants in a range of studies, and the efficacy and tolerability data from these studies have been collected together in the worldwide database on paroxetine. Paroxetine was shown to be at least as effective as placebo and active comparators in melancholic depression (DSM-III). In a comparative study of paroxetine and fluoxetine, both drugs were effective in reducing depressive symptoms and paroxetine showed a faster onset of action than fluoxetine. A higher incidence of side-effects was obtained in fluoxetine patients. In a long-term comparative study of paroxetine and placebo fewer patients relapsed while on paroxetine for one year than on placebo - 15 and 38%, respectively.

Comparative Effects of Antidepressants, Amitriptyline, and Maprotiline on Intraventricular Conduction, Effective Refractory Period, and Incidence of Ventricular Arrhythmias Induced by Programmed Stimulation in Dog Hearts After Myocardial Infarction

The effects of amitriptyline and maprotiline, standard tricyclic and tetracyclic antidepressants, on intraventricular conduction, the effective refractory period (ERP), and the incidence of ventricular arrhythmias induced by programmed stimulation were studied and compared in dog hearts after myocardial infarction. Amitriptyline at doses of 1-3 mg/kg significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and dose-dependent manner. Amitriptyline at doses of 2 and 3 mg/kg slowed conduction slightly in normal zones. The ERP was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Maprotiline at doses of 1-3 mg/kg slowed conduction in infarcted zones to a lesser extent as compared with amitriptyline, although severely depressed conduction in the infarcted zone was obviously slowed by maprotiline. Maprotiline did not increase the incidence of ventricular arrhythmias significantly. From the present results, maprotiline appears to have less cardiac toxicity than amitriptyline, although maprotiline produces a slight decrease in conduction of infarcted zones.

MAOIs in Adolescent Major Depression Unresponsive to Tricyclic Antidepressants

Abstract Many adolescents with major depressive disorder have at most partial response to standard tricyclic antidepressants despite appropriate dosage and adequate length of treatment. This paper reports a series of 23 such adolescents who were treated with monoamine oxidase inhibitors (MAOIs). Seventy-four percent of this group achieved good or fair antidepressant response, 57% had both good or fair response and continued dietary compliance. There were few serious side effects. Special attention must be paid to subject selection for treatment with MAOIs because of the risk of impulsive or accidental dietary transgression. This retrospective chart review strongly suggests the need for controlled studies of MAOI treatment in adolescents with tricyclic antidepressant refractory major depression.

Cardiovascular effects of the standard tricyclic antidepressants.

Cardiovascular effects of the standard tricyclic antidepressants.

Recent Studies on Selective Serotonergic Antidepressants

In recent years, the role of serotonin in the pathophysiology of depressive disorders has been intensively studied. These studies have been complemented by the development of newer antidepressant agents that exert specific effects on serotonin systems. This paper reviews the pharmacology of these newer compounds and contrasts it with those of the standard tricyclic antidepressants. The current status of various serotonergic agents is discussed. Results are reviewed from recent double-blind studies comparing three compounds (trazodone, fluoxetine, and fluvoxamine) to a standard tricyclic antidepressant. Relative efficacy, dropout rates, optimal dosages, and side effects are emphasized. Data from studies on trazodone and fluoxetine suggest that lower dosages may prove as effective (if not more effective) than very high dosages. Implications of these data are discussed. Side effects of fluoxetine and fluvoxamine include primarily nausea, weight loss, insomnia, and anxiety. Possible application of specific serotonin reuptake blockers in the treatment of obsessive-compulsive disorder and in the reduction of alcohol consumption is also reviewed.

Amoxapine: a review of its pharmacology and efficacy in depressed states.

Amoxapine is an N-demethylated dibenzoxazepine closely related in the neuroleptic loxapine. Its tricyclic structure appears to give it antidepressant properties resembling imipramine and amitriptyline. In uncontrolled trials it was shown to have antidepressant activity in usual doses up to 200 to 400mg daily. In placebo and double-blind controlled studies comparing amoxapine with the standard tricyclic antidepressants imipramine and amitriptyline, it was shown to be comparable in efficacy with a possibly somewhat faster onset of improvement of selected symptoms of depression in some studies. Because of the small study groups and lack of placebo control, many reports do not show statistically significant differences of treatment over standard drugs. To date there have been no studies comparing amoxapine with electroconvulsive therapy. Side effects were qualitatively similar to standard drugs with a suggestion that in standard doses or overdose myocardial effects are mild. However, the final place of amoxapine in the therapy of depressed states is still to be decided.

Efficacy of Trazodone: Data from European and United States Studies

Combined results of approximately two dozen studies of the efficacy of trazodone, conducted in the United States and Europe, indicate that trazodone is superior to placebo in alleviating depression. Moreover, trazodone is at least as effective as standard tricyclic antidepressants. Possible biases introduced by combining results obtained with different methodologies are minimized by including, with one exception, only double-blind, random assignment, controlled studies.