dothiepin-hydrochloride and Depressive-Disorder

1. A total of 13,834 depressed patients were exposed to dothiepin most frequently at a dose of 150 mg/day and over 6 weeks, in 116 clinical studies between 1963 and 1990. 2. Overall, 2,066 (15%) patients were withdrawn prematurely from dothiepin for a variety of reasons, the most commonly specified reason being due to drug-related events in 500 (4%) patients. 3. In the remaining 11,768 patients, there were 9,312 reports of unwanted events most typically associated with the pharmacological effects of a tricyclic antidepressant although no serious sequelae were reported. 4. This review indicates that the incidence of serious adverse events associated with dothiepin at therapeutic doses is very low.

Topics: Clinical Trials as Topic; Depressive Disorder; Dothiepin; Humans

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Depressive Disorder; Dothiepin; Fluvoxamine; Humans; Imipramine; Mianserin; Middle Aged; Serotonin Antagonists

Dothiepin is a tricyclic antidepressant that is structurally related to amitriptyline. It appears that the antidepressant activity of dothiepin is mediated through facilitation of noradrenergic neurotransmission by uptake inhibition and possibly also by enhancement of serotoninergic neurotransmission. The overall therapeutic efficacy of dothiepin is very similar to that of amitriptyline. In addition, dothiepin appears to be comparable to imipramine, doxepin, maprotiline, mianserin, fluoxetine, fluvoxamine and trazodone. Dry mouth is the most commonly reported side effect of therapeutic doses but the incidence of this and other anticholinergic side effects is less among patients treated with dothiepin than with amitriptyline. However, the sedative/anxiolytic activity of dothiepin is similar to that of amitriptyline. Dothiepin has not been associated with cardiotoxicity at therapeutic doses. Thus, many years of extensive clinical use have shown that dothiepin is now an established and effective antidepressant in both inpatients and outpatients with depressive symptoms of varying severity and coexisting anxiety. Its therapeutic equivalence to other tricyclics ensures its place as a treatment alternative in these disorders.

Topics: Animals; Depressive Disorder; Dibenzothiepins; Dothiepin; Humans; Rats

Several studies have shown that 20 to 66.2% of patients with rheumatoid arthritis have associated psychiatric comorbidity especially depression. Dothiepin hydrochloride is a well-established and effective antidepressant in patients with depressive symptoms of varying severity and co-existing anxiety. To document the efficacy and tolerability of dothiepin hydrochloride in the management of major depressive disorder (MDD) in rheumatoid arthritis patients a phase IV, open, single arm, prospective study was initiated with dothiepin hydrochloride in the dose of 75 mg/day, duration of therapy was 6 weeks. Twenty-five rheumatoid arthritis patients suffering from co-morbid MDD completed the 6-week dothiepin hydrochoride treatment and were considered for final analysis. There was significant reduction (p < 0.05) in mean HAM-D scores at week 2 (13.92 +/- 5.45), week 4 (9.28 +/- 4.13) and week 6 (5.72 +/- 3.26) compared to baseline (21.64 +/- 5.93). There was significant reduction (p < 0.05) in mean HAM-A scores at week 2 (6.52 +/- 3.34), week 4 (4.0 +/- 2.25) and week 6 (2.76 +/- 1.59) compared to baseline (10.68 +/- 3.68). The global impression of efficacy at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as marked and moderate improvement in 20 (80%) and 5 patients (20%) respectively. Only 2 patients reported dry mouth as an adverse event in the study. The overall assessment of tolerability at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as good and fair in 19 (76%) and 6 patients (24%) respectively. Dothiepin hydrochloride was found to be an effective and well-tolerated drug in the management of MDD and anxiety in patients suffering from rheumatoid arthritis.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Depressive Disorder; Developing Countries; Dose-Response Relationship, Drug; Dothiepin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; India; Male; Maximum Tolerated Dose; Middle Aged; Patient Satisfaction; Prospective Studies; Risk Assessment; Severity of Illness Index; Single-Blind Method; Treatment Outcome

To investigate the efficacy and cognitive and psychomotor effects of venlafaxine and dothiepin in elderly patients with moderate major depression. A prospective, randomized, double-blind, parallel-group, active comparator controlled study was conducted. Eighty-eight patients (aged > or = 60 years) were enrolled. Each patient received either venlafaxine (immediate release formulation) 37.5 mg twice per day or dothiepin 25 mg mane followed by 50 mg nocte for 26 weeks. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. A psychometric test battery to assess cognitive function, activities of daily living and sleep consisted of Critical Flicker Fusion (CFF), Short-term Memory--Kim's Game, Cognitive Failures Questionnaire, Milford Epworth Sleepiness Scale, Leeds Sleep Evaluation Questionnaire, and an Accident Scoring Questionnaire. Quality of Life Questionnaires (Short Form 36 and Quality of Life in Depression Scale) were also administered. Venlafaxine significantly (p < 0.05) raised CFF scores compared to baseline but had no effect on any other measure. Dothiepin significantly (p < 0.05) lowered CFF threshold, and increased ratings of both sedation and difficulty in waking. The results showed that venlafaxine at doses of 37.5 mg b.i.d. in elderly depressed patients is free from disruptive effects on cognitive function and psychomotor performance.

Topics: Aged; Cognition; Cyclohexanols; Depressive Disorder; Disorders of Excessive Somnolence; Dizziness; Dothiepin; Double-Blind Method; Drug Administration Schedule; Female; Flicker Fusion; Humans; Male; Narcolepsy; Nausea; Psychometrics; Psychomotor Performance; Time Factors; Venlafaxine Hydrochloride

The aim of the study was to detect changes of the QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and body surface potential mapping (BSPM) recordings were obtained using Cardiag 112.2 diagnostic system from 27 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings the QTd and the dispersion of heart rate-corrected QT interval QTc were evaluated. These parameters were estimated both from 80 BSPM leads and from 12 standard ECG leads. Acquired data were statistically correlated by Spearman rank order correlation coefficient with dosulepin plasma levels. The average QTd evaluated from BSPM leads (+/-SD) in the dosulepin group was significantly higher [70 (+/-21) ms] than that in the control group [34 (+/-12) ms] (P< 0.001). Moreover, the correlation between QTd and the dosulepin plasma level was statistically significant as well (P< 0.001) with the value of correlation coefficient 0.7871. The QTd evaluated from standard 12 ECG leads was increased in dosulepin group as well [46 (+/-18) ms vs. 28 (+/-10) ms - P< 0.05] but we have not found any significant correlation of the QTd with the dosulepin plasma level. According to the above-mentioned results we can conclude that the QTd estimated from BSPM leads (but not that estimated from 12-lead ECG) could be used as a marker of the dosulepin effect on the myocardium.

Topics: Adult; Antidepressive Agents, Tricyclic; Body Surface Potential Mapping; Depressive Disorder; Dothiepin; Electrocardiography; Female; Heart; Humans; Male

Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium carbonicum (Li) have different cardiovascular side-effects. We compared them in the prophylactic therapy of periodic affective disorder in remission with TCA, SSRI and Li. Our previous papers confirmed the most prominent effects of heart electric field parameters in TCA patients (Slavícek et al., 1998). In the present work we studied for the first time the dose-dependent changes of ECG, body surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40 SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMDŁ10; age 40+/-5 years; treated for depressive disorders or bipolar disorders). The daily doses of dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66+/-0.08 meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were measured and calculated by the Cardiag 112.1 diagnostic system. The results have shown a relation between the dose of dosulepine and extremum (maximum and minimum) of depolarization isoarea map in dosulepine, but not in citalopram patients. The repolarization BSPM changes were most pronounced in SSRI patients. Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM changes. The present results correspond with our previous observations.

Topics: Adult; Analysis of Variance; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Bipolar Disorder; Body Surface Potential Mapping; Cardiovascular Physiological Phenomena; Citalopram; Data Interpretation, Statistical; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Electrocardiography; Heart Rate; Humans; Lithium Carbonate; Middle Aged; Statistics, Nonparametric; Vectorcardiography

Antidepressants, particularly tricyclic (TCA) antidepressants, may have cardiotoxic effects, such as cardiac arrhythmias, especially in patients with cardiovascular diseases. For most of TCA, no exact correlation between dosage, plasma levels and changes of ECG parameters of standard ECG has been found. So far, no relationship between dosulepine plasma levels and heart electric field parameters has been studied. We selected 18 female outpatient subjects diagnosed with recurrent depressive disorders, currently in the remission phase (HAMD < 10), without any cardiovascular disease. Patients were treated with daily dosulepine doses of 25-125 mg for 4-8 weeks. 30 heart electric field parameters were analyzed by Cardiag 128.1 diagnostic system as part of BSPM (Body Surface Potential Mapping). Acquired data were correlated with dosulepine plasma levels by means of Spearman's rank order correlation test. Four ECG parameters showed a significant correlation with dosulepine plasma levels: QRS axis deviation in frontal plane (p=0.01), DIAM 40 max (p<0.05), QRS-STT angle in transversal and left sagittal plane (p<0.05). The demonstrated changes confirmed dosulepine influence on the early myocardium depolarization phase and the correlation of this effect with dosulepine dose (its plasma concentration). The higher the dosulepine level, the more marked are the changes of the QRS-STT angle in transversal and sagittal planes and the changes in the QRS axis deviation in frontal plane. Repeatedly recorded changes in the heart electric field were dosulepine-specific and dependent on its plasma levels.

Topics: Adult; Antidepressive Agents, Tricyclic; Body Surface Potential Mapping; Cardiovascular Physiological Phenomena; Chromatography, High Pressure Liquid; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Electrocardiography; Female; Humans; Middle Aged; Statistics, Nonparametric; Vectorcardiography

Many claims have been made for superior compliance with selective serotonin reuptake inhibitors (SSRIs) compared with tricyclic antidepressants, but to date meta-analyses have not confirmed reduced dropouts in randomized controlled trials. The authors used a randomized study design to evaluate differential compliance with antidepressant medications in a primary care setting.. A total of 152 patients treated in 10 primary care practices in the United Kingdom were included in a randomized, open-label, parallel-group study of fluoxetine and dothiepin at therapeutic doses for 12 weeks. Compliance was assessed by using pill count, patient questionnaires, and the Medication Event Monitoring System.. The level of compliance with fluoxetine was numerically higher than the level of compliance with dothiepin on all three primary outcome measures, although the differences were not significant. In a secondary analysis using data from the Medication Event Monitoring System, both a survival analysis for length of time without a gap in medicine taking and a derived compliance index showed a significant advantage to fluoxetine. Patients in the fluoxetine group reported superior response on the health transition scale of the 36-item Short-Form Health Survey Questionnaire and numerically greater improvement on the Hamilton Depression Rating Scale. In both treatment arms patients with a superior compliance index were more likely to have improved in Hamilton depression scale scores by the last study visit.. This study supports recent meta-analyses of SSRIs versus tricyclic antidepressants in finding no significant differences in crude indices of compliance between fluoxetine and dothiepin, despite marked differences in side effect profile and dose regimen. However, both a survival analysis and a new measure that takes account of prolonged periods of noncompliance distinguished between the treatments and was associated with improvement in both groups.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Tricyclic; Depressive Disorder; Dothiepin; Drug Administration Schedule; Drug Monitoring; Female; Fluoxetine; Humans; Male; Middle Aged; Odds Ratio; Patient Compliance; Primary Health Care; Selective Serotonin Reuptake Inhibitors; Survival Analysis; Treatment Outcome

Topics: Antidepressive Agents, Tricyclic; Arthritis, Rheumatoid; Depressive Disorder; Dothiepin; Humans; Treatment Outcome

The studies made showed that employment of amitriptylinum in patients presenting with depressive disturbances against the background of the organic affection of the brain resulted in origination od side effects, which fact failed to promote the reduction of depressive symptomatology. The use of azaphenum is not very effective. Protiadenum, a new antidepressant, does not induce side effects like amitriptylinum and was noted to be more effective than azaphenum. Protiadenum combined with nootropil and those drugs improving cerebral microcirculation (cavintonum) enhance efficiency of psychopharmacotherapy of depressive disorders in persons with organic affection of brain, who had become victims of the Chernobyl accident, which fact permits recommending such therapy in the complex of curative measures in the given contingent of patients.

Topics: Adult; Antidepressive Agents, Tricyclic; Depressive Disorder; Dothiepin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nootropic Agents; Piracetam; Power Plants; Radioactive Hazard Release; Ukraine; Vinca Alkaloids

Psychomotor retardation is a recognised symptom of depressive illness, and improvement in psychomotor function is associated with the amelioration of the severity of depressive symptoms. Actigraphy permits behavioural activity to be continuously assessed, allowing changes in psychomotor activity to be monitored over time. A randomised, parallel-group, double-blind study was conducted in 14 general practice patients with a diagnosis of major depression. This pilot study was designed to investigate the utility of actigraphy in this patient population and to investigate possible differences between fluoxetine and dothiepin in their effects on 24-hour behavioural activity monitored for the first 10 days of treatment. Patients taking dothiepin (75 mg rising to 150 mg in the second week, nocte) were found to be significantly (p < 0.05) less active over the course of the day compared to those treated with fluoxetine (20 mg, mane). This lower level of behavioural activity in the dothiepin group was particularly noticeable in the early morning (06:00-08:00 h).

Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder; Dothiepin; Double-Blind Method; Female; Fluoxetine; Humans; Male; Middle Aged; Motor Activity; Pilot Projects; Psychiatric Status Rating Scales

This randomised, double-blind study conducted at nine sites in the UK and the Netherlands compared the safety and antidepressant efficacy of venlafaxine and dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression were randomly assigned to receive either venlafaxine or dothiepin for up to 43 days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg per day for the first 15 days, and thereafter could range from 50 to 150 mg per day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p 0.05) for baseline to the end of the study in both groups. A response to therapy was observed in 60% of patients in the venlafaxine group and 53% of patients in the dothiepin group on the MADRS, and in 60% of patients in both groups on the HAM-D. Suicidal ideation scores on the MADRS were significantly (p = 0.042) lower in the venlafaxine group at week 6. Treatment-emergent study events were the primary reasons for withdrawal in only 7% of venlafaxine-treated patients and 8% of dothiepin-treated patients. The results confirm the efficacy and tolerability of venlafaxine for treating major depression in the elderly.

Topics: Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Cyclohexanols; Depressive Disorder; Dothiepin; Double-Blind Method; Female; Humans; Male; Middle Aged; Treatment Outcome; Venlafaxine Hydrochloride

Dothiepin, a well-established antidepressant, has been compared with clomipramine in a single-blind study which demonstrated that dothiepin was better tolerated but there was no difference in efficacy. The present study was performed to recent European guidelines on good clinical practice using a randomised, double-blind, parallel-group methodology. One hundred and one patients suffering from major depressive disorder as defined by DSM-III-R were randomised to receive either clomipramine (25-150 mg daily) or dothiepin (75-150 mg daily) for up to six weeks. The clomipramine group comprised 51 patients, the dothiepin group 50 patients. At baseline, both groups had a mean age of 41-43 years and gave similar mean scores on the Hamilton Depression Rating Scale (23.5 for clomipramine, 23.6 for dothiepin). At endpoint it was reduced in both groups but there were no significant differences between the groups (mean change from baseline for the clomipramine and dothiepin groups was -14.6 and -14.1 respectively). Thirty-one clomipramine patients and 41 dothiepin patients completed six weeks' treatment. Withdrawal from treatment (20 patients for clomipramine, nine for dothiepin) was significantly different (p = 0.0105). When reasons for withdrawal were analysed, 13 clomipramine patients and two dothiepin patients withdrew because of adverse events, this difference being significant (p = 0.002). Thus both treatments were effective in treating patients suffering from major depressive disorder, but patients receiving dothiepin suffered fewer adverse events and were more likely to complete their treatment.

Topics: Adult; Antidepressive Agents, Tricyclic; Clomipramine; Depressive Disorder; Dothiepin; Double-Blind Method; Female; Humans; Male; Middle Aged

This paper reports the results of two studies of depressed patients, evaluating the efficacy and toleration of the selective serotonin reuptake inhibitor (SSRI) sertraline in a general practice setting in the UK. In the first of these studies, 308 patients, with a DSM-III-R diagnosis of major depressive episode, were treated for 6 weeks with either sertraline 50-100 mg/day or the tricyclic antidepressant dothiepin 75-150 mg/day, or placebo. Seventy-six per cent of sertraline-treated patients were maintained on the lower dose (50 mg/day), whereas 81% of dothiepin-treated patients required the higher dose (150 mg/day). Sertraline-treated patients demonstrated a significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) severity scores compared with placebo-treated patients, while dothiepin-treated patients did not show significant improvement compared with placebo. The active drugs were well tolerated, and there were no significant differences in adverse events between the groups. The second study, "Sertraline in General Practice, A Multicenter Assessment", or SIGMA, was a large, multicentre trial with a cohort of 3396 patients recruited to receive 6 weeks of treatment. Patients started on sertraline 50 mg/day, and for 59% of patients this was the final dose; less than 10% of patients reached final doses of more than 100 mg/day. A 50% or greater reduction in MADRS scores was seen in 69% of patients across a wide range of severity of symptoms at baseline, and 87% of patients demonstrated excellent or good toleration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 1-Naphthylamine; Adolescent; Adult; Aged; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Double-Blind Method; Drug Administration Schedule; Family Practice; Female; Humans; Male; Middle Aged; Personality Assessment; Selective Serotonin Reuptake Inhibitors; Sertraline

The socioeconomic impact of major depression is considerable, due to poor patient functioning and increased social impairment, bed disability days, and use of health care resources. Major depression and the side effects of antidepressants medication also adversely affect patients' quality of life (QOL). However, few clinical trials of major depression examine QOL as a measure of treatment outcome. A comprehensive, quantitative QOL instrument for depression was recently tested and validated as conforming to accepted psychometric standards. The sertraline quality of life battery (SQOLB) consists of nine domains measuring health perceptions: energy/vitality, cognitive function, social interaction, alertness behavior, work behavior, home management, life satisfaction, and bed disability days. The SQOLB has been used in two open-label trials of sertraline. In the first study, the SQOLB was administered to 400 patients with major depression at baseline and final visit in a 6 week, open-label, general practice study. At endpoint, mean Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scores were significantly improved. The QOL battery also showed significant (p < 0.001) positive changes from baseline to final visit in all nine domains measured. In the second study, the SQOLB was used as part of an 8 week, open-label trial of sertraline in 308 UK hospital outpatients being treated for depression by psychiatrists. Sertraline was effective in managing the depression and caused statistically significant improvements (p < 0.001) in all QOL domains measured. The QOL scales give a better indication of the effect of pervasive depressive symptoms on a patient's life than rating scales of depressive symptomatology.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 1-Naphthylamine; Adolescent; Adult; Aged; Cost-Benefit Analysis; Depressive Disorder; Disability Evaluation; Dothiepin; Family Practice; Female; Humans; Male; Middle Aged; Quality of Life; Selective Serotonin Reuptake Inhibitors; Sertraline

In a double-blind multi-centre study of general practice patients with DSM-III-R major depressive disorder, sertraline (50 or 100 mg/day) was compared with dothiepin (75 or 150 mg/day) and with placebo. There were 83, 96 and 90 patients evaluated in the respective treatment groups; treatment lasted 6 weeks. Patients were assessed on the MADRS, CGI, and Leeds Self-rating Scales. Statistically significant differences (p < 0.05) between sertraline and placebo were found on MADRS and CGI but not the Leeds Scales. In the mild subgroup analyses, there were no significant differences between sertraline and placebo. However, clear significant differences (p < 0.05) between sertraline and placebo were present in the severe subgroup. Dothiepin failed to achieve a statistically significant difference from placebo on any analyses. Seventy-six per cent of patients were treated with 50 mg sertraline and 81% of patients received 150 mg dothiepin. Both sertraline and dothiepin were generally well tolerated; the most frequent side effects with sertraline were nausea, dizziness and headache; with dothiepin the most frequent side effects were dry mouth, somnolence and headache.

Topics: 1-Naphthylamine; Analysis of Variance; Antidepressive Agents; Depressive Disorder; Dothiepin; Double-Blind Method; Family Practice; Female; Humans; Male; Middle Aged; Sertraline

The tricyclic antidepressant dothiepin is well established in Europe, but clinical experience with the drug in the United States is limited.. In a 10-week, multicenter, randomized, double-blind, placebo-controlled study in the United States, the efficacy and tolerability of dothiepin and doxepin (both administered as a 150-mg nightly dose) were compared in 579 outpatients with major depression.. Patients in both active treatment groups showed significant improvements in depressive symptoms, associated anxiety, and sleep parameters compared with the placebo-treated group. The adverse effect profile of dothiepin was superior to that of doxepin, particularly with respect to drowsiness, weight gain, and increased appetite.. These results confirm that dothiepin is useful when a tricyclic agent is indicated for the treatment of depression.

Topics: Adult; Aged; Ambulatory Care; Depressive Disorder; Dothiepin; Double-Blind Method; Doxepin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Patient Dropouts; Placebos; Psychiatric Status Rating Scales; Treatment Outcome

Plasma concentration-antidepressant response relationships for dothiepin, nordothiepin, dothiepin-S-oxide, and nordothiepin-S-oxide were investigated in 50 patients (33 women and 17 men), who had had a major depressive episode. Depression and anxiety were assessed at the start of therapy and after 2 and 4 weeks by measurement of a Hamilton rating score for depression (HRSD), a Beck depression inventory (BECK), visual analog scores for depression (VASDEP) and anxiety (VASANX), and a physician's global (GLOBAL) score. There were significant (p < 0.001) decreases in both mean depression (32-69%) and mean anxiety (30-44%) scores at weeks 2 and 4, but there were no robust linear or polynomial correlations between percent decrease in depression or anxiety scores and plasma concentrations of dothiepin or its metabolites at week 4. It is suggested that measurement of the nordothiepin/dothiepin ratio may assist in the assessment of compliance.

Topics: Adult; Anxiety; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Female; Humans; Male; Middle Aged; Psychological Tests; Psychotherapy

Of 219 elderly patients with a major depressive disorder (meeting RDC), 69 recovered sufficiently and consented to enter a two-year double-blind placebo-controlled trial of dothiepin. Survival analysis revealed that dothiepin reduced the relative risk of relapse by two and a half times. Past but not current serious physical illness was also associated with a favourable outcome, whereas a prolonged index depressive illness trebled the relative risk of relapse. In the light of previous research on prognosis it is suggested that elderly persons who recover from a major depressive illness should continue with antidepressant medication for at least two years, if not indefinitely.

Topics: Aged; Depressive Disorder; Dothiepin; Double-Blind Method; Female; Follow-Up Studies; Humans; Long-Term Care; Male; Personality Assessment; Recurrence

Repeated assessments of psychopathology, together with personality status, were made over two years on 181 psychiatric out-patients with generalised anxiety disorder (59), panic disorder (66), or dysthymic disorder (56) diagnosed using an interview schedule for DSM-III. Patients were randomly allocated to drug treatment, cognitive and behaviour therapy, or a self-help treatment programme. Although there were no overall differences in compliance rate and efficacy between the three modes of treatment, the psychological treatment methods, particularly self-help, were more effective in patients without personality disorder, and those with personality disorder responded better to drug treatment, primarily antidepressants. The findings suggest that assessment of personality status could be a valuable aid to selection of treatment in neurotic disorders and that self-help approaches are particularly valuable once personality disorder has been excluded.

Topics: Adult; Anxiety Disorders; Cognitive Behavioral Therapy; Depressive Disorder; Diazepam; Dothiepin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurotic Disorders; Panic Disorder; Personality Assessment; Self-Help Groups

A randomized, double-blind, multi-centre, parallel-group study compared the tolerability and efficacy of 450 mg of moclobemide and 75-150 mg of dothiepin in the management of depressed patients in general practice. Patients who fulfilled the DSM-III-R criteria for major depressive disorder and who scored 13 or more on the Hamilton Depression Rating Scale were admitted. The trial lasted six weeks. The dose of moclobemide was 150 mg three times daily and that of dothiepin was 75 mg daily for the first two weeks and 150 mg thereafter. Assessments were made at baseline and after one, three and six weeks using the HDRS, the Zung SRS and the CGI. Adverse events and vital signs were monitored at each visit, and laboratory screening tests performed at the beginning and end of the study. Sixty-four general practitioners from four centres recruited 345 patients: 175 received dothiepin and 170 moclobemide; 265 completed six weeks of treatment. Thirty-eight dothiepin-treated patients (22%) and 42 who received moclobemide (25%) dropped out, most commonly because they experienced adverse events. More patients on dothiepin (24) than on moclobemide (16) dropped out for this reason; the incidence of adverse events was 10% higher in the dothiepin-treated group and of "side effects" more than 10% higher, the latter difference being statistically significant. Both treatments resulted in significant improvement; this was greater in the dothiepin-treated group and the difference was statistically significant, although clinically small.

Topics: Adolescent; Adult; Aged; Benzamides; Depressive Disorder; Dothiepin; Double-Blind Method; England; Family Practice; Female; Humans; Ireland; Male; Middle Aged; Moclobemide; Personality Inventory

The recognition and treatment of psychiatric illness in general practice is a skilled and difficult task and it is estimated that about 30% of psychiatric diagnoses may be missed. Patients whose illness is recognized are more likely to recover at follow-up than those whose illness is missed, demonstrating the importance of adequate training in recognizing psychiatric illness. Many general practitioners find difficulty in using tricyclic antidepressants to treat depression. The usual dose is lower than research evidence accepts as therapeutic and side effects often result in patient refusal to take a full dose. Additionally, the tricyclics are highly toxic in overdose. Many general practitioners in the UK are wary of new treatments because of previous experience of rare side effects leading to withdrawal of some new drugs. However, prescriptions of the selective serotonin reuptake inhibitors (SSRIs) for depression are gradually increasing here and in other countries such as the USA, France and Canada, where the SSRIs as a class account for upwards of 30% of new antidepressant prescriptions. The SSRIs are well suited to general practice; they have a greater therapeutic index than tricyclics, are much safer in overdosage, and have a different range of side effects (mainly nausea) which are better tolerated by patients at therapeutic doses. Furthermore, the SSRIs generally do not require dosage escalation for most patients and evidence indicates that they are effective in the treatment of depression associated with anxiety and insomnia. The safety and efficacy of the new SSRI sertraline has been established in comparative trials versus amitriptyline, imipramine and dothiepin (Reimherr et al., 1990; Cohn et al., 1990; Fontaine, 1991; Langdon, 1991).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 1-Naphthylamine; Adult; Aged; Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Care Team; Personality Inventory; Primary Health Care; Selective Serotonin Reuptake Inhibitors; Sertraline

The validity of the general neurotic syndrome, a combination of anxiety, depression and dependent personality disorder, was examined in a 2-year study of outpatients with dysthymic, panic and generalized anxiety disorder diagnosed using a structured interview schedule. The general neurotic syndrome, found in a third of the patients, was associated with greater mental disorder and a significantly worse outcome than patients without the syndrome. It did not, however, predict response to treatment. Further analysis revealed that the general neurotic syndrome was a better predictor of short- and long-term outcome than any other variable apart from initial psychopathology score. It is argued that the syndrome may represent a personality diathesis that makes the individual more vulnerable to both anxiety and depressive symptoms.

Topics: Adjustment Disorders; Anxiety Disorders; Cognitive Behavioral Therapy; Depressive Disorder; Diazepam; Dothiepin; England; Follow-Up Studies; Humans; Life Change Events; Neurotic Disorders; Panic Disorder; Personality Disorders; Psychiatric Status Rating Scales; Self Care

Topics: Adult; Antidepressive Agents; Antidepressive Agents, Tricyclic; Chronic Disease; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Family Practice; Female; Humans; Male; Referral and Consultation

The 5-HT2 receptor antagonist cyproheptadine significantly increased slow wave sleep in 12 healthy control subjects but not in 12 patients with a history of major depression, maintained on tricyclic antidepressant treatment. Cyproheptadine produced a similar reduction in REM sleep in both groups of subjects. The results are consistent with the hypothesis that tricyclic antidepressant treatment alters brain 5-HT2 receptor sensitivity, but a primary abnormality in slow wave sleep regulation in depressed patients cannot be excluded.

Topics: Adult; Aged; Amitriptyline; Brain; Cyproheptadine; Depressive Disorder; Dothiepin; Double-Blind Method; Electroencephalography; Female; Humans; Male; Middle Aged; Reaction Time; Receptors, Serotonin; Sleep Stages; Sleep, REM

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.

Topics: Anxiety Disorders; Behavior Therapy; Clinical Trials as Topic; Cognitive Behavioral Therapy; Depressive Disorder; Diazepam; Dothiepin; Double-Blind Method; Fear; Follow-Up Studies; Humans; Panic; Personality Assessment; Personality Tests

Topics: Adult; Aged; Alprazolam; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Humans; Male; Middle Aged

Forty-eight healthy volunteers aged between 18 and 61 years, 24 men, 24 women, received dosulepin (Idom) or placebo in a randomized fashion over a period of 16 days. The study was designed as a double-blind, placebo controlled parallel trial. The single daily dose of 75 mg was given in the evening. In order to assess driving ability under medication, the following parameters were examined before the study and on days 3, 10 and 17: visual orientation, concentration stress toleration while performing reaction tasks, eye-hand coordination, vigilance, accuracy and speed of reaction, and sense of wellbeing. Apart from a mild loss of concentration and decrease in the sense of wellbeing, none of the other parameters showed any significant changes as compared with placebo. The results are in good agreement with those of earlier relevant trials with other antidepressants. The results of the present study form the basis for an assessment of the driving ability of the individual patient receiving dosulepin.

Topics: Accidents, Traffic; Adolescent; Adult; Clinical Trials as Topic; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Humans; Male; Middle Aged; Random Allocation

Topics: Aged; Aged, 80 and over; Clinical Trials as Topic; Depressive Disorder; Dibenzazepines; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Humans; Lofepramine; Male

210 psychiatric outpatients with generalised anxiety disorder (71), or panic disorder (74), or dysthymic disorder (65) diagnosed by an interview schedule for DSM-III were allocated by constrained randomisation to one of five treatments: diazepam (28), dothiepin (28), placebo (28), cognitive and behaviour therapy (84), and a self-help treatment programme (42). All treatments were given for 6 weeks and then withdrawn by 10 weeks. Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2, 4, 6, and 10 weeks after randomisation. 18 patients had insufficient data for analysis because of early drop-out. There were no important differences in treatment response between the diagnostic groups, but diazepam was less effective than dothiepin, cognitive and behaviour therapy, or self-help, these three treatments being of similar efficacy. Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period, and those allocated to dothiepin and cognitive and behaviour therapy took the least.

Topics: Adult; Aged; Analysis of Variance; Anxiety Disorders; Behavior Therapy; Clinical Trials as Topic; Cognition; Counseling; Depressive Disorder; Diazepam; Dibenzothiepins; Dothiepin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Panic; Psychotherapy; Random Allocation; Relaxation Therapy; Time Factors

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Prospective Studies; Random Allocation

The response of patients with major depressive illness to fluoxetine or dothiepin was compared in a double-blind multi-centre trial. No differences in efficacy were observed, but the profile of side-effects differed with tremor, rash, nausea and headache occurring with fluoxetine, and drowsiness, dizziness and visual disturbance with dothiepin. It is likely that fluoxetine will be marketed with a proposed dose range lower than the one used here.

Topics: Adult; Aged; Clinical Trials as Topic; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Fluoxetine; Humans; Male; Middle Aged; Propylamines; Psychiatric Status Rating Scales

Dothiepin, a thio analogue of amitriptyline, has been used extensively in Europe during the past 15 years. It is a safe and effective agent for the treatment of major depressive disorder. Although the onset of action is comparable to that of other tricyclic antidepressants, dothiepin may cause fewer intolerable side effects and have less cardiotoxicity than these other compounds. In addition, dothiepin reduces the anxiety associated with some major depressive episodes. These features suggest that dothiepin may be particularly helpful for treating anxious depressed patients and patients who have underlying cardiac disease or who are elderly.

Topics: Adult; Anxiety Disorders; Clinical Trials as Topic; Constipation; Depressive Disorder; Dibenzothiepins; Dothiepin; Female; Humans; Male; Middle Aged; Nausea; Psychiatric Status Rating Scales; Sleep; Xerostomia

A multi-centre controlled trial of amitriptyline, dothiepin and mianserin in the treatment of depressive illness was undertaken in psychiatric inpatients over the age of 65. Despite the co-operation of many of the leading practitioners in this field in Great Britain, it proved impossible to recruit sufficient patients for firm conclusions to be drawn. Forty-five patients were entered into the trial, 13 withdrew because of lack of improvement, 4 because of intercurrent physical illness, 3 because of adverse effects of trial medication and 2 because of lack of compliance. Only 11 of the 23 patients completing had a final score on the Hamilton Depression Rating Scale of 10 or less. No treatment showed a significant superiority over the others, nor was there any difference in tolerance.

Topics: Aged; Amitriptyline; Clinical Trials as Topic; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Humans; Inpatients; Longitudinal Studies; Male; Mianserin; Random Allocation

Topics: Adjustment Disorders; Adult; Aged; Circadian Rhythm; Depressive Disorder; Dibenzazepines; Dibenzothiepins; Dothiepin; Female; Humans; Hypochondriasis; Male; Mianserin; Middle Aged; Obsessive-Compulsive Disorder; Paranoid Disorders; Sleep Initiation and Maintenance Disorders

Electrocardiograms of 65 patients treated with dothiepin, a sulphur substituted tricyclic antidepressant, were compared to those of 57 patients receiving amitriptyline and 62 patients given placebo. Amitriptyline produced an average heart rate increase of 10 beats/minute as compared to 5 beats/minute for dothiepin (p less than .02). Amitriptyline also produced a significant prolongation of the corrected QT interval as compared to both dothiepin and placebo (p less than .01 and p less than .001, respectively). Dothiepin had no significant effect on any index of myocardial conduction (PR interval, corrected QT interval, and QRS duration) as compared to placebo.

Topics: Adult; Amitriptyline; Clinical Trials as Topic; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Placebos

In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.

Topics: Ambulatory Care; Amitriptyline; Clinical Trials as Topic; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Humans; Placebos; Psychiatric Status Rating Scales; Sleep Stages; Vision Disorders; Xerostomia

Ninety three patients took part in a two centre double blind controlled clinical trial designed to assess the efficacy of dothiepin (Prothiaden) as compared with placebo and a soft biteguard in the treatment of psychogenic facial pain. The results showed the superiority of dothiepin over placebo in achieving pain relief; 71% of patients were pain free in the dothiepin group at nine weeks compared with 47% in the placebo group. The biteguard conferred no benefit and compliance in its use was poor. Out of 84 patients followed up for 12 months, 68 (81%) became pain free. An adverse life event before development of pain, minimal previous surgical treatment, and freedom from pain at nine weeks were strong prognostic indicators for successful treatment. These results are clear evidence of the efficacy of dothiepin in psychogenic facial pain, though the drug may be needed for up to a year.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Facial Neuralgia; Female; Humans; Male; Middle Aged; Neurotic Disorders; Prognosis; Temporomandibular Joint Dysfunction Syndrome; Time Factors

Topics: Adult; Aged; Computers; Depressive Disorder; Dibenzazepines; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Humans; Male; Mianserin; Microcomputers; Middle Aged; Psychiatric Status Rating Scales; Self-Assessment

Thirty patients diagnosed as suffering from endogenous depression were entered into a 3-week double-blind trial comparing three times a day dosage of dothiepin with a single night-time dosage in a dosage range of 75 mg to 225 mg per day. The trial was conducted on in-patients and assessments were made pretrial and after 1 and 3 weeks. The patients were assessed by clinician-rated scales for psychomotor and psychic symptoms and by Zung's self-rating scale. Fifteen patients received dothiepin three times a day (day-time group) and fifteen received it as a single night-time dose (nocte group). There were two withdrawals in the day-time group and three in the nocte group. All withdrawals were due to lack of therapeutic effect. Over the 3-week trial 67% of the day-time group and 47% of the nocte group showed a clinical improvement. It was found that there was no statistically significant difference between the two methods of treatment. In the day-time group seven patients and in the night-time group nine patients suffered from side-effects. No particular pattern of side-effects emerged. There were no drug-related changes in the laboratory results. It was concluded that the therapeutic effect of both dosage regimes should be regarded as equivalent. Advantages, due to the specific action of dothiepin, compared with classical antidepressants for reference, could, however, not be presumed by the clinical impression.

Topics: Adult; Aged; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Female; Humans; Male; Middle Aged

Topics: Aged, 80 and over; Antidepressive Agents, Tricyclic; Delirium; Depressive Disorder; Dothiepin; Humans; Male; Substance Withdrawal Syndrome

Topics: Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Cyclohexanols; Depressive Disorder; Dothiepin; Guidelines as Topic; Humans; Primary Health Care; Suicide; Venlafaxine Hydrochloride

The aim of the study was to detect the changes of QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and vectorcardiographic recordings were obtained using Cardiag 112.2 diagnostic system from 28 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings following parameters were evaluated: QTd, spatial QRS-STT angle and amplitude of T-wave. The acquired data were correlated with the dosulepin plasma levels using Spearman's rank order correlation test. The average QTd (+/-S.D.) in the dosulepin group was significantly higher (70+/-21 ms) than that in the control group (34+/-12 ms) (P<0.001). Moreover, the correlation between QTd and the dosulepin plasma levels was highly significant (r = 0.7871, P<0.001). Similar results were obtained when QTc dispersion was used. On the contrary, the QRS-STT space angle did not correlate with the dosulepin plasma levels. Furthermore, the T-wave amplitude was not significantly correlated to the QT-interval. Thus we can conclude that the QT dispersion could be used as a simple marker of the dosulepin effect on the myocardium.

Topics: Adult; Depressive Disorder; Dothiepin; Electrocardiography; Female; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; Statistics, Nonparametric

To demonstrate that when antidepressants are switched, discontinuation symptoms from the first antidepressant may be misdiagnosed as adverse effects of the second antidepressant.. Single case report.. A female patient was switched from paroxetine to dothiepin due to lack of efficacy. Over the next week she developed physical symptoms which she and her doctor regarded as side effects of dothiepin. It was decided to change the dothiepin and a second opinion was obtained regarding a suitable alternative. At that point it was realized that her symptoms represented a paroxetine discontinuation syndrome. The patient was reassured and continued dothiepin. The discontinuation symptoms resolved over the next 3 weeks and her depression subsequently remitted.. Increased professional awareness of discontinuation symptoms is necessary to prevent misdiagnosis and inappropriate treatment.

Topics: Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder; Diagnosis, Differential; Dothiepin; Female; Humans; Middle Aged; Paroxetine; Substance Withdrawal Syndrome

Anorexia nervosa and morbid obesity are popularly considered to be opposite ends of the eating disorder spectrum. Research and clinical experience, however, suggest common psychological factors in a subgroup of obese people. This paper details case reports of two subjects who developed anorexia nervosa following gastric reduction surgery for morbid obesity. Clinical profiles, treatment, and outcome are reported. Psychological similarities between morbid obesity and anorexia nervosa in these subjects are explored. Implications for the selection of subjects for gastric reduction surgery and management after surgery are discussed.

Topics: Adult; Anorexia Nervosa; Antidepressive Agents, Tricyclic; Depressive Disorder; Dothiepin; Female; Gastroplasty; Humans; Middle Aged; Obesity, Morbid

A boy aged 11 years 11 months, with normal premorbid personality, presented with a severe depressive episode with somatic and psychotic features. A clinical response to amitriptyline was complicated by ECG changes leading to the abrupt withdrawal of amitriptyline, with the development of a withdrawal syndrome. Further trials of antidepressant medication were unsuccessful, including paroxetine (clinical deterioration), lofepramine (ECG changes and clinical deterioration), and trazodone (priapism). Finally, a good clinical response to dothiepin augmented with lithium was achieved. ECG changes were assessed as being idiosyncratic responses to medication, rather than ischaemic in nature. A dose/response relationship with dothiepin was observed. All medication was successfully stopped after 26 months of treatment. Clinical phenomena relevant to the development of guidelines for use of tricyclic antidepressants in childhood and adolescence are discussed.

Topics: Amitriptyline; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Child; Depressive Disorder; Dothiepin; Drug Monitoring; Drug Therapy, Combination; Electrocardiography; Humans; Lithium Carbonate; Lofepramine; Male; Paroxetine; Trazodone

Topics: Adult; Antidepressive Agents, Tricyclic; Anxiety; Confusion; Depressive Disorder; Dothiepin; Drug Overdose; Drug Therapy, Combination; Female; Humans; Mianserin; Mirtazapine

This study looks at the outcome of infants exposed to dothiepin in breast milk in an attempt to guide clinicians on the risk-benefit ratio of breast-feeding when on antidepressants.. Thirty women, who had had HDRS scores > 15 within the first five years postpartum from the same women's hospital, were assessed with their children 3-5 years postpartum; half had breast-fed while on dothiepin (study group). Thirty-six non-depressed women were also assessed. Rating scales assessed depression, anxiety, self-esteem, personality, social support, marital relationship, child behaviour and temperament. The children were assessed by the McCarthy Scale.. Comparisons of the two depressed groups showed no significant differences on any measures except marital conflict and child behaviour, which were the most disturbed in the study group (P < 0.001). Overall cognitive scores for the children did not differ between the groups. Higher levels of dothiepin and northiaden were associated with higher cognitive scores on subscales (P = 0.02).. We are cautiously optimistic about the lack of any negative associations between cognitive development and exposure to dothiepin via breast milk.

Topics: Antidepressive Agents, Tricyclic; Breast Feeding; Child Development; Child, Preschool; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Female; Follow-Up Studies; Humans; Infant; Male; Personality Assessment; Personality Development; Puerperal Disorders; Risk Factors

Topics: Adolescent; Antidepressive Agents; Clomipramine; Depressive Disorder; Dothiepin; Drug Administration Schedule; Electroconvulsive Therapy; Female; Humans; Lithium; Phenelzine; Receptors, Serotonin; Recurrence; Self-Injurious Behavior; Substance Withdrawal Syndrome; Suicide; Suicide Prevention; Syndrome

The serotonin reuptake inhibitors (SSRIs) are generally better tolerated than the traditional tricyclic antidepressants (TCAs) in the treatment of major depression. In particular the SSRIs are relatively free from cognitive and psychomotor effects likely to cause behavioural toxicity. Behavioural toxicity is studied using a battery of psychometric assessments. This paper discusses the effects of the TCAs and SSRIs on two such assessments, choice reaction time (CRT) and critical flicker fusion threshold (CFFT). CRT measures psychomotor speed, and CFFT assesses the information processing capacity of the CNS. The behavioural toxicity associated with the traditional TCAs can lead to an increased accident risk, whereas the SSRIs are not associated with such effects. Clinically relevant differences in the behavioural toxicity of the SSRIs are highlighted.

Topics: Accidents, Traffic; Antidepressive Agents, Tricyclic; Automobile Driving; Cognition Disorders; Depressive Disorder; Dothiepin; Flicker Fusion; Fluvoxamine; Humans; Psychomotor Performance; Reaction Time; Selective Serotonin Reuptake Inhibitors; Time Factors

Topics: Depressive Disorder; Dothiepin; Humans; Research

Topics: Aged; Depressive Disorder; Dothiepin; Follow-Up Studies; Humans; Long-Term Care; Middle Aged; Recurrence

A case of post-traumatic stress disorder (PTSD) following a road traffic accident in which the onset of symptoms was delayed for 18 months until a widely reported major disaster occurred is described. A severe major depressive episode was precipitated, requiring treatment in its own right. During psychotherapy sessions, extreme emotions, heightened sensations, and 'organic memories' relating to the original accident were experienced.

Topics: Accidents, Traffic; Arousal; Combined Modality Therapy; Depressive Disorder; Disasters; Dothiepin; Humans; Male; Mental Recall; Middle Aged; Psychiatric Status Rating Scales; Psychotherapy; Railroads; Stress Disorders, Post-Traumatic

This pilot study demonstrated the feasibility of providing practice nurse support as an adjunct to standard general practitioner treatment to patients with depressive disorders prescribed antidepressant medication. With respect to the measures used and pilot study objectives identified, there were no statistically significant differences between the study groups in treatment adherence to the prescription of antidepressant medication or in the incidence and severity of adverse events to medication. Large-scale randomized controlled trials are in progress to assess the effectiveness of practice nurse interventions in the management of depressive illness in general practice.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Dothiepin; Family Practice; Female; Humans; Male; Middle Aged; Nurse Practitioners; Nurse-Patient Relations; Pilot Projects; Workforce

A 32-year-old chronically relapsing depressed male patient with a mild mental handicap had tried different forms of pharmacotherapy which were either not tolerated or failed to prevent recurrences of episodes of psychotic depression. The use of maintenance ECT as the mainstay of the therapeutic regime led to a marked consistent clinical improvement.

Topics: Adult; Child of Impaired Parents; Chronic Disease; Combined Modality Therapy; Depressive Disorder; Dothiepin; Electroconvulsive Therapy; Hospitalization; Humans; Intellectual Disability; Male; Recurrence; Suicide, Attempted

Nineteen mentally handicapped subjects who were referred to the service with clinically significant depression were assessed with a view to determining the value of the dexamethasone suppression test (DST) in clinical diagnosis and in predicting response to antidepressant treatment. They were assessed initially and then 3 months after they had been treated with a tricyclic antidepressant. It was found that a significant proportion had an abnormal DST response which reversed after recovery in some but not in others. Non-reversal was more likely to occur in the more severely handicapped patients. It was concluded that DST was of little value as a diagnostic tool for the detection of depression in mentally handicapped subjects.

Topics: Adolescent; Adult; Antidepressive Agents, Tricyclic; Depressive Disorder; Dexamethasone; Dothiepin; Female; Humans; Hydrocortisone; Intellectual Disability; Male; Middle Aged

Topics: Creutzfeldt-Jakob Syndrome; Depressive Disorder; Diagnosis, Differential; Dothiepin; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Neurocognitive Disorders; Neurologic Examination; Putamen

Topics: Acquired Immunodeficiency Syndrome; Adult; Cognitive Behavioral Therapy; Combined Modality Therapy; Depressive Disorder; Dibenzothiepins; Dothiepin; Humans; Male

Topics: Aged; Depressive Disorder; Dibenzothiepins; Dothiepin; Female; Humans; Pulmonary Fibrosis

Platelet 5-hydroxytryptamine uptake was measured in a group of 28 endogenously depressed patients at three points during the day, before, during and after treatment and in 20 controls at the same three times. Uptake rates varied in control subjects in a manner consistent with the presence of a circadian rhythm in uptake. This variation was absent in depressed subjects. Normal variation was restored in those patients showing a clinical response, irrespective of the effects of treatment on the affinity of the uptake system. This restoration was not found in nonresponders or acutely after treatment was commenced. These findings suggest that depression is associated with a disruption of circadian rhythms, that abnormalities of platelet 5-hydroxytryptamine uptake are secondary to such a disruption and that antidepressants may act to correct this disruption.

Topics: Adult; Aged; Blood Platelets; Combined Modality Therapy; Depressive Disorder; Dothiepin; Electroconvulsive Therapy; Female; Humans; Male; Mianserin; Middle Aged; Serotonin; Trazodone

The affinities of dothiepin and its principal metabolites northiaden, dothiepin sulphoxide and northiaden sulphoxide for [3H]imipramine binding sites in the rat cortical homogenates, and for [3H]spiperone and [3H]serotonin receptor sites in preparations from the rat frontal cortex and hippocampus were studied. As inhibitors of [3H]imipramine binding, the strengths of the drugs are, in terms of their IC50 (concentration corresponding to 50% inhibition): dothiepin 2.8 X 10(-6) M, northiaden 5.0 X 10(-6) M, northiaden sulphoxide 4.0 X 10(-5) M and dothiepin sulphoxide 3.2 X 10(-5) M. The potencies of the drugs in inhibiting serotonergic binding followed a similar trend. Using frontal cortical tissue suspensions and [3H]spiperone, the IC50 values were determined to be: dothiepin 4.2 X 10(-6) M, northiaden 5.0 X 10(-6) M, northiaden sulphoxide 1.6 X 10(-4) M and dothiepin sulphoxide 1.6 X 10(-4) M; whereas in hippocampal suspensions and using [3H]serotonin, the IC50 values were 2.5 X 10(-6) M, northiaden 4.0 X 10(-5) M, dothiepin sulphoxide 2.5 X 10(-4) M and northiaden sulphoxide greater than 10(-3) M. The influence of the drugs on the uptake of [14C]serotonin into human platelets was also investigated. All had an inhibitory effect upon the uptake, the order of potency being dothiepin greater than northiaden greater than northiaden sulphoxide greater than dothiepin sulphoxide. Plots of 1/v versus 1/s showed that the inhibition was competitive for all four compounds.

Topics: Animals; Binding, Competitive; Blood Platelets; Carrier Proteins; Cerebral Cortex; Depressive Disorder; Dibenzothiepins; Dothiepin; Hippocampus; Humans; Imipramine; Rats; Rats, Inbred Lew; Receptors, Drug; Receptors, Serotonin; Serotonin; Spiperone

Ten patients suffering from primary depressive illness were treated with 150 mg/d of dothiepin for 4 weeks. Blood and plasma concentrations of dothiepin and two metabolites, dothiepin S-oxide and northiaden were measured by gas chromatography-mass spectrometry. Severity of depression was assessed using the Hamilton Depression Rating Scale. No significant correlation was found between amelioration score or percentage change and either blood or plasma concentrations of dothiepin, its metabolites or total drug and metabolite concentrations at week 4.

Topics: Adult; Aged; Depressive Disorder; Dibenzothiepins; Dothiepin; Female; Humans; Male; Middle Aged

The therapeutic response to psychotropic drugs was analyzed in 208 patients hospitalized at the Psychiatric Clinic of the Medical Faculty of the Purkinje University (Brno, Czechoslovakia). The patients showed symptoms characteristic of borderline states. The examinations were carried out with the use of modified scale SCL-90 supplemented with 90 additional signs. It was found that the patients with slowly progressing schizophrenia responded to the psychotropic drugs in a way differing from that observed in the patients with the borderline states. It is suggested that patients with slowly progressing schizophrenia have a specific biological background of the disease that determines the type of the response.

Topics: Depressive Disorder; Diagnosis, Differential; Diazepam; Dibenzothiepins; Dothiepin; Humans; Methotrimeprazine; Neurasthenia; Neurotic Disorders; Schizophrenia; Schizotypal Personality Disorder

Topics: Aged; Agranulocytosis; Depressive Disorder; Dibenzothiepins; Dothiepin; Humans; Leukocyte Count; Male; Neutrophils

Topics: Antidepressive Agents, Tricyclic; Anxiety Disorders; Climacteric; Depressive Disorder; Dibenzothiepins; Dothiepin; Female; Humans; Middle Aged

The European clinical experience with dothiepin since 1962 indicates that it is efficacious in the treatment of depression (neurotic, psychotic, and with concomitant anxiety) in dose of 75-200 mg/day. The side effects profile is similar to the tricyclic antidepressant drugs with significantly less anticholinergic side effects and cardiotoxicity then amitriptyline. The result of the current ongoing clinical trails in the United States with several hundred patients will more precisely define the efficacy, dosage and side effect profile of dothiepin.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Aged; Anxiety Disorders; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Drug Administration Schedule; Europe; Female; Humans; Male; Middle Aged