A double blind controlled clinical trial of benzoctamin (Tacitin) and imipramine (Tofranil) in the treatment of 'internal heat' and its association symptoms. Amitriptyline in anxious-depressed outpatients: a controlled study. Tofranil in the treatment of low back pain. [Controlled study of treatment of residual depression by clomipramine versus placebo]. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. Mianserin in the treatment of depression in general practice. [Double-blind clinical study with a new psychotropic agent: doxepin versus placebo]. A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease. A trial of imipramine (Tofranil) in depressed patients with chronic physical disease. Controlled trial of amitriptyline in general practice. The Nottingham Study of Neurotic Disorder: relationship between personality status and symptoms. Effects of amitriptyline on depressive and anxiety states in penitentiary inmates. Plasma levels and therapeutic response with trimipramine treatment of endogenous depression. Doctor-patient concordance in a placebo-controlled trial of limbitrol versus its components [proceedings]. Doxepin: is a single daily dose enough? A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly. Double-blind trial of imipramine in Alzheimer's disease patients with and without depression. Buspirone and imipramine for the treatment of major depression in the elderly. The effect of low dose lofepramine in depressed elderly patients in general medical wards. Amitriptyline in migraine prophylaxis. [Comparative evaluation of the antidepressive properties of opipramol, imipramine and placebo in neurotic depression]. Amytriptyline and chlordiazepoxide (Limbitrol) in depressive states in Nigerians--a double-blind study. Amisulpride versus imipramine and placebo in dysthymia and major depression. Amisulpride Study Group. Amitriptyline in emotional states at the menopause. Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG). Amitriptyline for depressed women with young children in general practice. Chronic tension headache--treated with amitriptyline--a double-blind study. A clinical evaluation of depressives found in a rural survey in India. Antidepressive effect of amitriptyline treatment with plasma drug levels controlled within three different ranges. Trazodone in the treatment of neurotic depression. Cianopramine and amitriptyline in the treatment of depressed patients--a placebo-controlled study. Comparative effects of amitriptyline and amineptine in patients affected by anxious depression. Trimipramine in rheumatoid arthritis: a randomized double-blind trial in relieving pain and joint tenderness. Drug treatment in depressive illness. Imipramine and diet counseling with psychological support in the treatment of obese binge eaters: a randomized, placebo-controlled double-blind study.
nan nan This report describes a double-blind between-group comparison of Tofranil and placebo in fifty-nine patients admitted to the Joint Service Medical Rehabilitation Unit suffering from low back pain. Patients were given 25 mg of either Tofranil or placebo three times a day for four weeks. Fifteen patients were not included in the analysis, nine dropping out for non-trial related reasons, two dropping out complaining of lost libido and four not taking the tablets, or taking additional drugs. One of the patients complaining of lost libido was taking Tofranil and the other was taking placebo. Over the whole sample there was no significant benefit for Tofranil over placebo as regards physical measurements. Both Tofranil and placebo groups showed a significant improvement during the trial on straight leg raise and backward flexion. For lateral flexion the Tofranil group was significantly worse than the placebo group on entering the trial, and during the trial the Tofranil group improved to match the placebo group. The clinician's pain and stiffness assessments and the patients' pain and stiffness assessments show a significant improvement for both the Tofranil and placebo groups during the trial. However, no difference is shown between Tofranil and placebo. The psychological tests show no difference between Tofranil and placebo and only a marinal improvenmet over initial condition. Further analysis according to initial diagnosis showed nothing conclusive. Numerically, the use of Tofranil produced a marked improvement in pain and stiffness in patients with 'disc lesion only' diagnoses, whereas placebo did not produce an improvement. However, this observation was far from reaching statistical significance. Side-effects were not severe for either drug. Additional medication was rarely used. The choice of a new treatment strategy for a patient suffering from residual depression in sometimes difficult; in reality, any change in the prescription involves a risk of losing any benefit, even partial, that has recently been obtained; consequently, can one be sure that a new antidepressant treatment will be beneficial? To attempt to find the answer to this question, the Laboratories Ciba-Geigy have conducted a controlled study versus placebo to evaluate the efficacy of clomipramine in residual depression which has been progressing for more than a year. 207 patients were pre-included in the 7-day wash-out phase and treated with placebo. During this period, a clinical examination and laboratory work-up made it possible to exclude patients with a curable cause of partial resistance to antidepressants (e.g., hypothyroidism) or who were "placebo-responders". After this run-in, 181 patients were included if they complied with the criteria characterizing a major depressive episode in partial remission (according to the DSM III-R), present for at least one year and treated throughout this period with at least two antidepressants at effective dosages. In addition, these patients had to have a score between 15 and 25 on the Montgomery and Asberg Depression Rating Scale (MADRS). The patients included were randomized into two groups, receiving either an clomipramine 75 tablet or a placebo tablet for two weeks; the dosage could be increased to two tablets as at D14 if necessary and maintained for the next six weeks. The only authorized concomitant treatments were tranquillizers (lorazepam or bromazepam) and/or non-barbiturate hypnotics (zopiclone or flunitrazepam).(ABSTRACT TRUNCATED AT 250 WORDS) To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.
                Randomised, double blind, multicentre, parallel group trial for 8 weeks.
                Trained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.
                263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32. 1 and F33.1.
                1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.
                Change from baseline score on the 17 item version of the Hamilton depression scale, the Hamilton anxiety scale, the clinical global impressions scale, Zung's self rating depression scale, and SF-36, and adverse events profile.
                Hypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean -15.4 (SD 8.1), -12.1 (7.4), and -14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).
                At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life. In a double-blind study in general practice, both mianserin ('Bolvidon') in an average dose of 40 mg a day, and imipramine, in an average dose of 100 mg a day, were found to be significantly more effective than placebo after two to three weeks' treatment. No significant differences in antidepressant effect could be demonstrated between mianserin and imipramine. There was no significant difference in side-effects between the three treatments. nan Twenty-one depressed patients with probable Alzheimer's disease (AD) were randomized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design. Main outcome measures were Hamilton Depression, Mini-Mental State (MMSE), and Functional Independence Measure (FIM) scores. Mood improved significantly on both clomipramine and placebo, but clomipramine was significantly more effective than placebo during the first 6-week treatment period. Patients started on clomipramine maintained improvement during the washout and placebo periods, whereas patients started on placebo worsened during the washout period. However, patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo. No significant drug effects were found on FIM scores. Clomipramine proved to be a useful treatment of depression in patients with probable AD. nan A controlled double-blind trial of amitriptyline at two dosage levels (75 and 150 mg/day), amylobarbitone (150 mg/day), and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness. Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups. Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety. Troublesome side effects were equally distributed among the four treatments. Two hundred and ten psychiatric patients with one of three DSM-III diagnoses, generalized anxiety disorder (N = 71), panic disorder (N = 74) or dysthymic disorder (N = 65), were included in a clinical trial in which diazepam, dothiepin or placebo tablets, cognitive and behaviour therapy, or a self-help package were given over ten weeks. Personality status was assessed independently using a structured interview, the Personality Assessment Schedule. One hundred and ninety-eight patients had personality assessments, 89% with a close informant. Thirty-six per cent had a personality disorder and these patients had more severe psychopathology than those with no personality disorder. Personality disorder was more common in patients with dysthymic disorder and this group responded less well to treatment. The category of personality disorder had no apparent influence on symptoms. nan In a 6-week, double-blind study involving 34 endogenously depressed patients, plasma trimipramine levels of two dosage groups, 75-mg/day and 150-mg/day, were compared with regard to clinical efficacy as determined by scores on the Hamilton Rating Scale for Depression, the Clinical Global Impressions scale, and the Zung Self-Rating Depression Scale. Both dosage levels of trimipramine produced prompt, consistent, and progressive antidepressant effects. No correlation between plasma levels and clinical efficacy was found. nan nan The efficacy and safety of alprazolam as compared to imipramine or a placebo added to weekly interpersonal psychotherapy was compared in a 6-week double-blind randomized clinical trial of 35 ambulatory elderly patients with major depression. The average maximum dosage of alprazolam was 2.2 mg and the average maximum dosage of imipramine was 97.5 mg. The findings showed a rapid onset of action of alprazolam within 1 week on symptoms of depression and anxiety. The effects for imipramine were seen later in the study. There were no serious side effects that interfered with treatment. The anticholinergic effects of imipramine were the ones that most commonly interfered with treatment. Alprazolam produced the greatest number of symptoms with discontinuation, most of which were alleviated within a week. We conclude that alprazolam may be useful as an antidepressant for the elderly. More clinical trials are needed to test its efficacy in the depressed elderly with concomitant medical problems, using plasma levels. A double-blind discontinuation study of alprazolam is needed to determine the degree of symptom return. The authors divided 61 subjects with primary degenerative dementia of the Alzheimer's type into a group who also met DSM-III criteria for depression (N = 28) and a group who did not (N = 33). Both groups were randomly assigned to an 8-week double-blind trial of imipramine or placebo. Scores on the Hamilton Rating Scale for Depression, administered at baseline and weeks 2, 4, 6, and 8, indicated significant improvement in both groups. Two measures of cognitive function yielded differing results. The results suggest that moderate depression is a treatable condition in patients with Alzheimer's disease. The current study was designed to assess the safety and efficacy of imipramine and buspirone in the treatment of major depression in elderly depressed attendees of primary care practices.
                177 patients aged 65 and over (mean age = 72 years; range, 65-89) who met DSM-III-R criteria of unipolar major depression with a minimum Hamilton Rating Scale for Depression score of 18 were randomly assigned to 8 weeks of double-blind, placebo-controlled treatment with flexible doses of either imipramine or buspirone.
                Moderate to marked global improvement after 8 weeks of treatment (LOCF analysis) occurred in 70% of patients treated with imipramine, 61% of patients treated with buspirone, and 42% of patients treated with placebo (chi2 = 9.1, df = 2, p < .02). Drug treatment was well tolerated, with 77% of imipramine- and 61% of buspirone-treated patients completing 8 weeks of therapy. Imipramine/placebo differences were present from week 2 on, but buspirone/placebo differences occurred only at week 8. The presence of comorbid medical illness or concomitant use of nonpsychiatric prescription medications was not associated with poorer antidepressant response, increased adverse effects, or study attrition.
                Imipramine and to a lesser extent buspirone were found to be effective and well tolerated in the treatment of elderly depressed outpatients. A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression. In a controlled trial of amitriptyline hydrochloride in migraine prophylaxis, 100 patients received placebo for a four-week baseline period and then were randomized in double-blind fashion to therapy with amitriptyline (47 subjects) or placebo (53 subjects) for another four to eight weeks. Subjects received up to four 25-mg tablets of amitriptyline hydrochloride or identical placebo per day. Comparing the first and second four-week periods for each patient, the conditions of 55.3% of amitriptyline subjects as opposed to 34.0% of placebo subjects were greater than or equal to 50% improved and the difference between amitriptyline and placebo response rates was significant (P less than .05). Nondepressed subjects with severe migraine and depressed subjects with less severe migraine responded best to amitriptyline, whereas depressed subjects with severe migraine had little headache relief. Amitritryline is an effective antimigraine agent and the antimigraine effect seems relatively independent of antidepressant activity. nan nan Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses. In a multicentre, 6 months, placebo-controlled trial, amisulpride (50 mg/daily) was compared to imipramine (100 mg/daily) in the treatment of patients with DSM-III-R criteria for primary dysthymia, dysthymia with major depression or major depression in partial remission. A total of 219 patients were included. Both analyses (intention-to-treat and "per protocol' analysis) detected significant differences between groups (active treatment vs. placebo) on all main rating scales (CGI, MADRS, ERD, and SANS). The number of patients reporting at least one adverse event was higher in the imipramine group than in the two other, mainly due to anticholinergic effects. Endocrine symptoms were more frequent in female patients treated with amisulpride. These results confirm the interest of a drug acting on dopaminergic transmission such as amisulpride in the treatment of depressed patients. nan To examine the problems of establishing dose-effect and concentration-effect relationships of antidepressant therapy with clomipramine.
                This randomized double-blind study compared five fixed doses of clomipramine hydrochloride: 25, 50, 75, 125, and 200 mg/day in hospitalized or day patients at nine clinical centers in Denmark. A 1-week washout period was followed by 6 weeks of active treatment and weekly depression ratings. In total, 151 patients (100 women and 51 men) with major depression scoring > or =18 on the Hamilton Depression Scale (HDS) or > or =9 on the Hamilton Depression subscale (HDSS) before and after the washout period were randomized. The treatment groups (n = 29 to 32) were well balanced with respect to sex, age, and depression rating. Serum concentrations of clomipramine plus metabolites were measured at weekly intervals. A sparteine test was performed before and during drug treatment.
                There was pronounced interpatient variability in response and kinetics at each dose. Drop-outs attributable to adverse events increased with rising doses, whereas drop-outs caused by worsening or lack of effect or nonresponse declined with increasing dose. Completer analyses showed a moderate and statistically significant relationship between depression rating and dose at all ratings after 1 to 6 weeks of treatment (trend analysis). HDS items representing core symptoms of depression showed a particularly consistent dose-effect relationship. Early sustained response occurred more frequently with the two highest doses. Serum levels of clomipramine and desmethylclomipramine showed weak correlation with depression ratings (Rs = -0.18 to -0.27; P < .05 to P < .01). A few blood pressure measurements and a few typical side-effect ratings showed a statistically significant dose-effect and concentration-effect relationship. Serum concentration of clomipramine and desmethylclomipramine showed a pronounced disproportionate increase with increasing dose. Clomipramine inhibited in a dose-dependent fashion CYP2D6 (sparteine oxidation).
                The dose-effect curves, indicating the probability of a certain outcome at a given dose, were flat and overlapping suggesting a narrow therapeutic range. This pattern is similar to that observed with newer antidepressants. nan nan Those who were labelled as depressives in a rural survey were randomly divided into a Medicine group (who received antidepressive drug treatment), a Placebo group (who received placebo) and a Natural Process group (who received no treatment). The depth of their depression was assessed by Hamilton's Depressive Rating Scale before the beginning of the trial, on the 14th day and on the 28th day of trial. They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment. The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics, so far as their response to treatment is concerned. Seventy-four depressed patients were treated with amitriptyline for 4-6 weeks. Their doses were individually adjusted to maintain the sum of the plasma levels of amitriptyline (AT) and nortriptyline (NT) within one of three different ranges, randomly allocated. Allowance was made for individual plasma binding of the drugs. In the 50 patients between 25 and 65 years of age, the antidepressive response at low plasma drug levels was somewhat poorer than at medium or high levels, which were equally effective. In this age group an association was found between outcome and the individual rate of AT metabolism, expressed as "reciprocal clearance" (RC), the steady-state plasma concentration of AT plus NT divided by the daily AT dose. Good antidepressive outcome was associated with high RC. The implications of these findings for patient treatment and for the interpretation of other studies are discussed. The 18 patients between 65 and 80 years of age showed no significant differences between the effectiveness of treatment at different plasma drug levels, and no significant associations between outcome and RC. A double-blind study was conducted to determine the efficacy and safety of trazodone vs. amitriptyline and placebo in 184 patients suffering from neurotic depression. All patients were evaluated for safety and 127 patients who completed 12 to 42 days' therapy were evaluated for efficacy. Trazodone was found to be significantly better than placebo on almost every rating scale, particularly on those items or factors related to depression and associated anxiety. Trazodone was superior to amitriptyline in some patients while amitriptyline was only occasionally better than placebo. Significant improvement was noted in trazodone patients within the first seven days of therapy. Trazodone produced a low level of side effects compared to amitriptyline. 3-Cyano-imipramine (cianopramine) is a potent and selective inhibitor of serotonin uptake into synaptosomes. In a double-blind trial, 60 patients with various types of depression fulfilling the DSM-III criteria of depressive episodes were treated with either cianopramine (n = 20, mean daily dose 3.3 +/- 0.6 mg) amitriptyline (n = 20, mean daily dose 86.4 +/- 21 mg) or placebo (n = 20) orally. According to the ratings of the Hamilton Scale of Depression and clinical global evaluations, both active drugs showed statistical superiority over placebo (P less than 0.02). The frequencies of anticholinergic side effects in the cianopramine group were comparable to those of the placebo group and were less than in the amitriptyline group. The findings suggest that cianopramine is a promising new antidepressant. In a double-blind, placebo-controlled study, the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action, amitriptyline and amineptine, was investigated in patients affected by anxious depression. Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder (DSM-III-R) and meeting additional operational clinical criteria such as anxiety, trepidation, restlessness, early and/or late insomnia, impulsivity, hostility, dysphoria, compulsivity, hyperperspiration, palpitation, pollakiuria and phobias were included. They were randomly assigned to three groups (n = 22) and treated either with placebo, amitriptyline (up to 100 mg/day) or amineptine (up to 200 mg/day) for 6 weeks. Patients showed better response to amitriptyline, a preferential inhibitor of serotonin reuptake, than to amineptine, a selective inhibitor of dopamine reuptake. The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression. The effect of low-dose trimipramine (25 to 75 mg/day) on joint pain and tenderness in 36 patients with rheumatoid arthritis was studied in a randomized double-blind trial carried out over a period of 12 weeks. The patients were pre-selected to include only patients who were depressed on a 'self-rating depression scale' but had no evidence of fibrositic 'trigger-points'. The results showed that joint pain and tenderness were significantly reduced with trimipramine, but depression scores remained unchanged. nan This study with 31 obese binge eaters (body mass index [BMI] 39.5+/-8.6 kg/m(2) [SD]) was designed to assess whether diet counseling with psychological support and imipramine or placebo has an effect on the frequency of binge eating, body weight, and depression during an 8-week treatment phase. This was followed by an open medication-free phase of 6 months of continuous diet counseling with psychological support.
                Randomized double-blind placebo-controlled study of 8 weeks followed by an open phase of 6 months. Patients were evaluated in medical visits by a semistructured videotaped interview, psychometric questionnaires, and hematochemical parameters.
                From Week 0 to 8, a significant reduction in binge frequency occurred in both treatment conditions (7.1+/-4.1 to 2.8+/-3.0 binges per week [imipramine] vs. 7.1+/-4.1 to 5.4+/-5.1 [placebo], p<.01). Patients on imipramine lost -2.2+/-1.8 kg compared to placebo-treated subjects (+0.2+/-3.3 kg, p<.001). On follow-up, only the patients initially treated with imipramine continued to lose weight (-5.1+/-2.8 kg [imipramine] vs. 2.2+/-6.8 kg [placebo], p<.001 [differences to Week 0]). While both treatment conditions were associated with significant improvements on a rater's measure of depressive symptoms (Hamilton Depression Scale) at Week 8, only the patients treated with imipramine still showed a significant improvement at Week 32. Scores on the Self Depression Rating Scale did not show a group difference but a significant reduction at Weeks 8 and 32, compared to baseline.
                These results suggest that adding low-dose imipramine to diet counseling with psychological support helps patients losing weight even for at least 6 months off medication. The effect might include a psychological priming of weight loss during the double-blind phase that continues at least for half a year after stopping the drug.
                Copyright 1999 by John Wiley & Sons, Inc.
Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of varying dosages.