Trimipramine in physical illness with depression. Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression. A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression. Cognitive behavior therapy, relaxation training, and tricyclic antidepressant medication in the treatment of depression. A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. Tricyclic antidepressants in the treatment of depressions. A double-blind clinical comparison of clomipramine (Anafranil) and amitriptyline. Tricyclic antidepressant education program and its evaluation. Venlafaxine in the treatment of children and adolescents with major depression. A double-blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients. Changes in weight during treatment for depression. A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. Reduced REM latency predicts response to tricyclic medication in depressed outpatients. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice.
To assess whether tricyclic antidepressants are useful in patients with a serious physical disorder who develop symptoms of major depression, 42 medically ill outpatients who met RDC criteria for endogenous major depression and had a Raskin depression score of at least 7 were studied. The patients were randomly assigned to a 6-week trial of trimipramine or placebo under double-blind conditions. In the placebo group, depressive symptoms improved when the physical disorder improved; in the trimipramine group, improvement was seen in the depressive symptoms even when there was no concomitant improvement in physical condition. To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD).
                Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo.
                There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL.
                No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD. To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD).
                Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures.
                Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size.
                No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD. Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another. This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy. To test the uniqueness hypothesis, relaxation training, a nonpharmacologic, noncognitive treatment, was chosen as a comparison for cognitive behavioral therapy as well as drug therapy. Treatment duration was 16 weeks. The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied. For both cognitive behavioral therapy and relaxation training, outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis. The posttreatment scores on the Beck Depression Inventory of 82% of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score < or = 9 which was not significantly greater than that for the group receiving relaxation training (73%), so a unique effect was not demonstrated for cognitive behavioral therapy. The outcome for tricyclic antidepressant medication (29% improved to criteria) was significantly worse than that for cognitive behavioral therapy. The patient's pretreatment initial expectancy was not predictive. Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression. The clinical efficacy of oral clomipramine and amitriptyline treatment (50--125 mg/day) was compared over a period of 2 months in 72 depressive patients visiting a psychiatric out-patient clinic. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression. According to a nurse's independent evaluation of 13 items the two drugs were equipotent in relieving depressive symptoms and no statistically significant differences between the treatment groups were found in the global evaluation by the investigator and the patient. A trend in favour of clomipramine was, however, seen in several parameters. The declines in the Hamilton Rating Scale scores and the nurse's evaluation scores were highly significant during the first 2 weeks of treatment (P less than 0.001) in both groups and the scores continued to decrease during the 2nd month of the study. The most common unwanted effects were dryness of the mouth and fatigue. The frequency of side effects was 51% in the clomipramine group and 43% in the amitriptyline group. The side effects were generally mild and transient and called for discontinuation of treatment in only one case in each group. The objectives of this study were (1) to develop an individualized tricyclic audiovisual education program and (2) to compare the program's effectiveness with that of traditional education. The program is designed to increase short-term and long-term knowledge about tricyclic antidepressants and depression. The patient's dose was stabilized, and then a pretest was given. If the patient was in the study group, he received the seven-minute slide-tape program and a posttest within 72 hours. The control group received the posttest within five days of the pretest. Both groups were given knowledge tests at approximately four weeks. Statistical analysis of the data from this small study group revealed significance at the 95% confidence level for the following statement: the study group showed a greater increase in factual short-term and long-term knowledge about its tricyclic therapy as shown by differences in pretest, posttest, and scores of tests at four weeks. This study demonstrates an effective standardized alternative to traditional education which can be used to educate the majority of patients about tricyclic antidepressants and depression with a minimum time investment. Major depression is commonly found in the child and adolescent population. Venlafaxine, a new antidepressant, has been used successfully in adults; however, its use in children and adolescents has been very limited. This study evaluated the efficacy and side effect profile of venlafaxine in the treatment of depression in children and adolescents. In a double-blind, placebo-controlled, 6-week study, 33 subjects between the ages of 8 and 17, who met DSM-IV criteria for major depression, were treated with either venlafaxine and therapy or placebo and therapy. Patient progress data were obtained by weekly rating assessments. Data on side effects were also obtained weekly. The statistical analysis indicated a significant improvement over time, but it could not be attributed to venlafaxine drug therapy. These findings are consistent with other studies where the efficacy of antidepressants in the treatment of major depression in this age population remains unproven. Low dosage and short length of treatment may account for the lack of efficacy. The findings did, however, suggest a low side-effect profile. Further studies are recommended to assess efficacy and to corroborate its safety in children and adolescents. The results of a double-blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil) and a conventional tricyclic, amitriptyline (Elavil), in 67 ambulatory depressives are reported. Hamilton's Rating Scale for Depression was the main outcome criterion. No statistically significant differences were found between the drugs in onset of action, efficacy, side effects or predictors of response. Patients on either drug showed a significant reduction in symptoms after 1 week of treatment and at the end of the trial. Both drugs were tolerated well. A review of double-blind comparisons of maprotiline and tricyclic antidepressants, spanning 13 countries, and including over 900 patients, both ambulatory and inpatient, shows essentially similar results. The main outcome criterion in all these studies was manifest psychopathology assessed on the Hamilton Rating Scale for Depression by the treating physician. The absence of additional types of outcome criteria or assessment techniques, which may have detected differences in motor activity or drive as originally postulated, may have obscured results which were expected to be subtle. Changes in appetite and weight were examined in a group of 47 carefully diagnosed primary depressives who were treated in a random design with either placebo (N = 17) or amitryptyline (N = 30) over a 35-day protocol. While the amitriptyline treated group as a whole showed a greater gain in weight than did the placebo group (4.5 vs. 0.5 lb, p less than 0.05), no differential effects could be demonstrated between drug responders and nonresponders. Likewise, while a consistent relationship between the self-report of decreased appetite and final weight change was noted in the placebo group, no simple relationship between final weight change and self-reported changes in appetite were apparent in the drug-treated patients. There was, however, a relationship between the report of decreased appetite and clinical severity of depression in the drug nonresponder subgroup despite significant weight gain during the protocol. Thus, weight change during this study period did not appear to show a simple relationship to corresponding clinical change. The clinical lore that has supported the notion that increased appetite and weight gain in patients being treated with tricyclic antidepressants are "good" signs cannot be confirmed by our findings. Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression.
                An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7-11) and adolescents (ages 12-17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4 if clinically indicated. The primary outcome measure was score on the Children's Depression Rating Scale-Revised; the response criterion was defined as a score of < or =28.
                The overall mean citalopram dose was approximately 24 mg/day. Mean Children's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group, beginning at week 1 and continuing at every observation point to the end of the study (effect size=2.9). The difference in response rate at week 8 between placebo (24%) and citalopram (36%) also was statistically significant. Citalopram treatment was well tolerated. Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis, nausea, and abdominal pain were the only adverse events to occur with a frequency exceeding 10% in either treatment group.
                In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated. Forty-two outpatients with major depressive disorder entered a double-blind, randomized trial of either desipramine or amitriptyline for a minimum of 6 weeks. Pretreatment polysomnographic and clinical measures were used to predict response. Response was defined as a 17-item Hamilton Rating Scale for Depression score less than or equal to 9 at the end of treatment. There was a 61.1% response rate for patients treated with amitriptyline and a 66.7% response rate for patients treated with desipramine. Reduced REM latency (2-night mean less than or equal to 65.0 min) predicted a positive response to these tricyclic antidepressants. REM latency did not differentiate between desipramine or amitriptyline responders. More patients with reduced REM latency (80%) responded to treatment compared with patients with nonreduced REM latency (50%). The 80% response rate in reduced REM latency depressed patients confirms our previous findings in a mixed inpatient and outpatient sample. Contrary to our hypothesis, in this sample, endogenous depression was not associated with a good response to tricyclic medication. Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline (median dose 125 mg). The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice. Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment. The effects of the antidepressant were on the core symptoms of depression, and were apparent in all but the most mildly ill patients. The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice.
Data suggest tricyclic drugs are not useful in treating depression in children. There is marginal evidence to support the use of tricyclic drugs in the treatment of depression in adolescents.