Frontotemporal dementia: a randomised, controlled trial with trazodone. A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder. No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients. Trazodone therapy of the post-stroke depression. Experimental examination of trazodone. Trazodone. A comparative clinical and predictive study. Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients. Fluoxetine versus trazodone in depressed geriatric patients.
Behavioural troubles due to frontotemporal dementia (FTD) are difficult to treat. The serotonergic system is associated with frontal lobes, the degeneration of which contributes to FTD. Trazodone increases the extracellular 5-HT levels in the frontal cortex. In a randomised, double-blind, placebo-controlled cross-over study, we investigated the effect of trazodone. There was a significant decrease in the Neuropsychiatry Inventory (NPI) total score with trazodone (p = 0.028) in the 26 evaluable patients. A decrease of more than 50% in the NPI score was observed in 10 patients with trazodone. This improvement was mainly based on the improvement of 4 items of the scale (irritability, agitation, depressive symptoms and eating disorders). The Mini-Mental State Examination was not modified and trazodone was well tolerated. Results of this first placebo-controlled trial suggest that trazodone is an effective treatment for the behavioural symptoms of FTD.
                Copyright 2004 S. Karger AG, Basel The authors compared the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia. Twenty-eight elderly patients with dementia and agitated behaviors were randomly assigned to double-blind treatment with either trazodone (50-250 mg/day) or haloperidol (1-5 mg/day) for 9 weeks. There was no significant difference in improvement between the medication groups. Adverse effects, however, were more common in the group treated with haloperidol. Improvement in individual areas suggested that repetitive, verbally aggressive, and oppositional behaviors responded preferentially to trazodone, whereas symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol. These results indicate that moderate doses of trazodone and haloperidol are equally effective for treatment of overall agitated behaviors in patients with dementia, but specific symptoms may respond preferentially to a particular agent. To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression.
                A total of 122 patients aged 19-64 years were enrolled in this multicenter, double-blind, double-dummy, randomized, comparator-controlled study. Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150-450 mg/day (n = 62) or sertraline 50-100 mg/day (n = 60).
                Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale (HAM-D), Montgomery Asberg Depression Rating Scale, Hamilton Anxiety Rating scale, and the Clinical Global Impression-Global Improvement/Severity scores; and by the rates of patients responding to treatment and considered to be in remission. Time to onset of efficacy and safety were assessed.
                Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission, and had similar onset times. In the Intent-to-Treat population, there were no significant differences in favor of trazodone at study endpoint in all efficacy measures, while a statistically significant difference was detected in the Per-Protocol population on HAM-D and in the percentage of responders. Analysis of HAM-D factors (anxiety/somatization, cognitive disturbance, retardation, and sleep disturbance) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint. Adverse drug reactions, mostly of mild intensity, were reported in 42% of trazodone-treated patients (mainly of the nervous system) and 43% of sertraline-treated patients (mainly gastrointestinal). One event was considered to be serious: a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized. Treatment was discontinued; the patient made a full recovery.
                This study showed that after 6 weeks, trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission. Tolerability profiles reflected the differing pharmacological properties of these antidepressants. Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances. Th determine if teaching caregivers behavior management techniques (BMTs) reduces long-term psychotropic use in Alzheimer's disease (AD) patients, we examined 12-month follow-up data from a 4-month randomized study comparing placebo, BMTs, trazodone, and haloperidol for the treatment of agitated behaviors in persons with AD. After 4 months, treatment was allowed with any agent. Between 42.8% and 51% of AD patients received additional psychotropics between 4 and 12 months. The relative risk of being prescribed any psychotropic drug after the 4-month trial was at or about 1.0 for subjects in each drug arm or placebo arm versus BMTs. We concluded that teaching caregivers BMTs did not diminish long-term prescription of psychotropic drugs. The incidence of depression following a hemispheric stroke ranges from 25 to 60%. The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known. We studied subjects both with and without evidence of depression, as indicated by any one of three criteria: (i) Clinical diagnosis of depression, (ii) Abnormal Zung-depression score. (iii) Abnormal dexamethasone suppression test (DST). Patients in a stroke rehabilitation program (22) were randomized to receive either placebo or 300 mg/day trazodone-HCl, beginning 30 days after the stroke. Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living (ADL) scores, with antidepressant therapy, as compared to patients receiving placebo. An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone, i.e., in post-stroke depression such a treatment seems to be beneficial. To establish the differential indication of trazodone and to find the predictors of its efficacy, we conducted a study in which 45 patients with major depressive disorder and 75 patients with acute schizophrenia were randomly assigned under double-blind conditions to either 400 mg trazodone daily, 150 mg amitriptyline daily, 20 mg haloperidol daily, or placebo daily. At the beginning of the investigations, numerous variables (basic data, MMPI, AMDP, HAM-A, HAM-D) were documented and evaluated on days 3, 7, 14, and 21. In our study, trazodone proved to be as effective an antidepressant drug as amitriptyline. In group comparison, no antipsychotic action of trazodone in schizophrenic patients could be proved. Yet the trazodone treatment was clearly of less risk than the amitriptyline treatment. Under trazodone, provocation of schizophrenic symptoms, which occurred numerously under amitriptyline, was found only in one patient out of 17 schizophrenics. Related to anamnesis and characteristics of the schizophrenic patient, a predictor-variable concerning the antipsychotic effect was not found. It can be assured, however, that patients with depressive symptoms (regarding the entity classification) respond to trazodone. After only 7 days of trazodone treatment, a relatively reliable decision can be established as to whether a therapeutical success can be expected if treatment is continued. The clinical efficacy and tolerability of trazodone and amitriptyline were compared in 74 hospital patients suffering from depressive illness. The daily doses of trazodone and amitriptyline were 150-300 mg and 75-225 mg, respectively, with half-strength capsules for patients over the age of 65 years. Twenty-five and 29 patients receiving trazodone and amitriptyline, respectively, completed the 6 week treatment period. Antidepressant activity was measured using the Hamilton Depression Rating Scale (HDRS), the Zung Scale of Depression, visual analogue scales and a Global Assessment Scale. Trazodone and amitriptyline were both effective but not statistically different from each other in terms of antidepressant action. Moreover, patients with neurotic or endogenous depression responded equally well on either treatment. Trazodone was less troublesome in respect of the persistent dry mouth and severe adverse psychiatric reactions which occurred with amitriptyline. Patients should be advised to take trazodone after meals. We are performing a double-blind trial with inward psychiatric patients. The indication for our psychotropic or psychotherapeutic intervention is mainly severe depression (= major depressive disorders DSM III). For a 3-week trial course trazodone (400 mg daily), amitriptyline (150 mg/die) or placebo capsules were given at random. All patients received the same type of cognitive behaviour therapy. The test battery consists of CGI, BPRS, HAMD, HAMA and AMDP; adverse drug reactions are documented as "free reports" (= freier Nebenwirkungsbericht). The interim results (until March 1987) will be presented. Our investigation indicates that it is probable that the trazodone treatment we used is equivalent to corresponding amitriptyline treatment. A total of 27 subjects began active treatment in this double-blind study comparing the efficacy and safety of trazodone and fluoxetine in geriatric depressed patients, but only 13 completed 6 weeks on study medication. Both agents were effective according to weekly and endpoint analyses, and there was no evidence of significant effects on blood pressure, pulse, or weight. Separate analysis of patients who had received an adequate trial of medication indicated a trend toward relatively more fluoxetine-treated patients meeting clinical criteria for resolved depression.
There is insufficient evidence to recommend the use of trazodone as a treatment for behavioural and psychological manifestations of dementia. In order to assess effectiveness and safety of trazodone, longer-term randomized controlled trials are needed, involving larger samples of participants with a wider variety of types and severities of dementia.