A clinical double-blind comparison of maprotiline and amitriptvline in depression

Summary

A double-blind trial was carried out in 30 depressed patients to compare the effectiveness and acceptability of maprotiline and amitriptyline. The study formed part of a multi-national 8-centre trial of the new tetracyclic antidepressant. Fifteen patients were treated with 150?mg. daily of one or other drug over a period of 28 days. The severity of each patient's symptoms was assessed before, during, and at the end of the trial period using the Hamilton Depression Rating Scale, and a note kept of any side-effects. No significant difference was noted in drug effectiveness. Maprotiline, however, produced significantly fewer side-effects than amitriptyline.     

A double-blind controlled study of viloxazine and imipramine in depression

Summary

Fifty-nine depressed patients entered a double-blind, between patient comparison of viloxazine hydrochloride (300?mg./day expressed as base) and imipramine hydro-chloride (150?mg./day expressed as salt). Twenty-nine patients took viloxazine and 30 imipramine. Depression was assessed at weekly intervals, using the Hamilton Scale over a period of 6 weeks, and both drugs produced a statistically significant antidepressant effect. No difference emerged between the response to the two agents. Imipramine was associated with a significantly higher incidence of side-effects than viloxazine and they were more persistent. Imipramine produced a mean increase in weight over 6 weeks of 5.9 kg. whereas viloxazine produced a rise of only 2.4 kg. Viloxazine produced few anticholinergic side-effects; imipramine, on the other hand, was associated with frequent and persistent side-effects such as dry mouth, blurred vision, disturbed micturition and constipation. Drowsiness was not seen with viloxazine but was seen in over half the patients on imipramine. It is concluded that, whereas viloxazine has antidepressant properties equal to those of imipramine, it has a much lower incidence of side-effects, and what side-effects it does have are transient.     

In-patient major depression: is rolipram as effective as amitriptyline?

Summary The antidepressant efficacy and adverse-effects of rolipram (a dialkoxyphenyl-2-pyrrolidone) were compared to those of amitriptyline in the treatment of depressive illness requiring hospital admission in a double-blind study.Fifty patients meeting DSM-III criteria for Major Depression whose scores on the Hamilton Rating Scale for Depression (HRSD) remained above 17 after 5 to 7 days on placebo were randomly allocated to either treatment.The rate of recovery in those patients treated by amitriptyline was substantially greater than in those patients treated by rolipram. Twice as many patients dropped out of treatment by rolipram because of lack of efficacy or adverse-effects compared with patients treated by amitriptyline. Rolipram produced fewer adverse-effects attributable to cholinergic blockade, but more nausea.We conclude that amitriptyline is more effective than rolipram in the treatment of depressed hospital in-patients.     

Bromocriptine in depression

Summary

A double-blind trial was carried out in 9 patients with endogenous depression to compare the effectiveness of bromocriptine (15?mg per day, 4 patients) with that of imipramine (75?mg per day, 5 patients) over a period of 10 weeks. The results of assessments using the Hamilton Rating Scale for Depression showed that both drugs produced comparable reduction in mean scores and there was no significant difference between the two treatment groups. Fewer patients had anticholinergic type side-effects on bromocriptine although some had transient nausea.

Bromocriptine

imipramine

depression     

Real-world effectiveness and safety of aripiprazole augmentation therapy in patients with major depressive disorder

Aims: Augmentation therapy is an option for patients with major depressive disorder who do respond sufficiently to adequate dosages of selective serotonin reuptake inhibitors or serotonin–norepinephrine reuptake inhibitors, but little is known about application of this strategy in everyday practice.

Methods: This prospective, multi-center, observational study investigated the effectiveness and safety of aripiprazole augmentation in Japanese patients with inadequate response to conventional antidepressant therapy in real-world clinical practice. The primary endpoint was mean change in the (Japanese version) Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to study end. Safety was assessed by monitoring adverse events.

Results: There were 1103 patients in the safety population and 1090 patients in the effectiveness population. Mean change in the MADRS total score at study end was –14.9?±?12.3 (p?<?.001 vs baseline). The remission rate increased from 34.5% at Month 6 to 43.3% at Month 12, suggesting additional benefit with continued treatment. The type of primary antidepressant (paroxetine, fluvoxamine, sertraline, milnacipran, duloxetine, mirtazapine, or escitalopram) had no influence on the effectiveness of aripiprazole augmentation therapy. A baseline MADRS total score of <33 points and an elapsed time of <176 days from an episode of depression to the start of aripiprazole treatment increased the likelihood of achieving remission; 24.8% of patients experienced at least one adverse event, but no new safety signals were identified.

Conclusions: Aripiprazole augmentation therapy appears to be effective and safe in Japanese patients with depression/depressive symptoms treated in everyday clinical practice, taking into account factors associated with achieving remission.     

Comparison of adinazolam, amitriptyline, and diazepam in endogenous depressive inpatients exhibiting DST nonsuppression or abnormal contingent negative variation

Adinazolam, a triazolobenzodiazepine that has an action similar to antidepressants in several pharmacological tests, was compared with amitriptyline and diazepam in endogenous depressive inpatients exhibiting dexamethasone suppression test non-suppression and/or abnormal contingent negative variation. Three parallel groups of 22 patients received in double-blind conditions either adinazolam (60-90 mg/day), amitriptyline (150-225 mg/day), or diazepam (30-45 mg/day) over a 4-week period, with weekly assessments by the Hamilton Rating Scale for Depression. Results showed significant superiority of amitriptyline over diazepam on total Hamilton depression scores. On the endogenomorphy subscale, amitriptyline induced significantly better improvement than both diazepam and adinazolam, whereas both amitriptyline and adinazolam exhibited significantly better antidepressant efficacy on the core symptoms of depression. Moreover, the dropout rate for inefficacy after 2 weeks of treatment was higher in the diazepam group. Taken together, these findings suggest that adinazolam has an antidepressant efficacy intermediate between amitriptyline and diazepam. Adinazolam was, however, much better tolerated than amitriptyline, and produced significantly fewer anticholinergic side effects.     

A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression

Background: the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre, randomized, double-blind, amitriptyline-controlled, 5 week clinical study. Method: 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression (HPRSD) score ≥ 18, were randomized to treatment with either mirtazapine 20-60 mg/day or amitriptyline 75-225 mg/day. Results: mirtazapine and amitriptyline were equally effective in reducing depressive symptoms, as assessed by the 17-item HPRSD and MADRS scales. Mirtazapine was better tolerated than amitriptyline, with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial. Conclusion: this study shows that mirtazapine is as effective as amitriptyline in treating major depression, while at the same time better tolerated.     

A comparative study of milnacipran and imipramine in the treatment of major depressive disorder

SUMMARY

The antidepressant efficacy and safety of milnacipran, a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline, was compared with that of the tricyclic antidepressant, imipramine, in a multi-centre, double-blind, randomised, parallel group, comparative trial in 5 hospital centres in Spain. One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association (third revision), with a minimum score of 25 on the Montgomery and Åsberg Depression Rating Scale were treated for 6?weeks with milnacipran (100?mg/day) or imipramine (150?mg/day). Both treatments showed similar efficacy in reducing depressive symptoms. The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group, particularly those related to anticholinergic symptoms. Dysuria and shivering, however, were more common with milnacipran. The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine.     

Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison

Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition.     

Evaluation of rotigotine transdermal patch for the treatment of depressive symptoms in patients with Parkinson’s disease

Objective: To evaluate the dopamine receptor agonist, rotigotine, for improving depressive symptoms in patients with Parkinson’s disease (PD).

Methods: Patients were randomized 1:1 to rotigotine or placebo, titrated for ≤7 weeks, and maintained at optimal/maximum dose for 8-weeks. Primary efficacy variable: 17- item Hamilton Depression Rating Scale (HAM-D 17) total score change from baseline to end-of-maintenance. Secondary variables: changes in Beck Depression Inventory-II, Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living [ADL]) and III (motor) subscores, UPDRS II+III total, patient-rated Apathy Scale (AS), and Snaith-Hamilton Pleasure Scale.

Results: Of 380 patients randomized, 149/184 (81.0%) rotigotine-treated and 164/196 (83.7%) placebo-treated patients completed the study. Patients: mean (±SD) age 65.2 (±8.5) years; time since PD-diagnosis 2.74 (±3.08) years; 42.6% male. The treatment difference (LS mean [95% CI]) in change from baseline HAM-D 17 was ?1.12 (?2.56, 0.33; p = 0.1286). UPDRS II, III, II+III and AS scores improved numerically with rotigotine versus placebo. Common adverse events with higher incidence with rotigotine: nausea, application/instillation site reactions, vomiting, and pruritus. Forty-one (10.8%) patients discontinued owing to adverse events (25 rotigotine/16 placebo).

Conclusions: No statistically significant improvement in depressive symptoms were observed with rotigotine versus placebo. ADL, motor function, and patient-rated apathy improved numerically.

ClinicalTrials.gov: NCT01523301     

A controlled study of mianserin in moderately to severely depressed outpatients

Following a 1-week, single-blind placebo washout, 150 patients were randomized to double-blind treatment with daily doses of either mianserin, 30 mg to 150 mg; amitriptyline, 60 mg to 300 mg; or placebo, 1 to 5 capsules taken at bedtime (qhs). Mianserin and amitriptyline were found to be comparable in efficacy, and both significantly more effective than placebo in the treatment of major depressive illness. Rating instruments, all of which showed significant improvement in the active drug groups over the placebo, included the 17- and 21-item Hamilton Rating Scale for Depression (HAM-D), Montgomery and Asberg Depression Rating Scale (MADRS), Self-rating Depression Scale (SDS) index, and the Clinical Global Impressions (CGI) Severity of Illness and Improvement rating scales. Furthermore, for most efficacy parameters in the efficacy-evaluable group, the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients. The safety profile for mianserin was comparable with placebo with respect to laboratory values, electrocardiogram changes, vital signs, ophthalmologic evaluations, and most adverse clinical experiences. Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups. Mianserin was superior to amitriptyline in terms of vital signs; anticholinergic effects; and complaints of dizziness, dyspepsia, and tremor.     

Clinical Switching Strategies of Various Antidepressants to Vortioxetine in the PREDDICT Trial

BackgroundPartial response to antidepressant medication as well as relapse and treatment resistance are common in major depressive disorder (MDD). Therefore, for most patients with MDD, there will be a need to consider changing antidepressant medication at some stage during the course of the illness. The PREDDICT study investigates the efficacy of augmenting vortioxetine with celecoxib.MethodsWe describe the method used in the PREDDICT study to change participants, who were already taking antidepressant medication at the time of the screening visit, to vortioxetine. We used a cross-titration to change study participants to vortioxetine.ResultsOf a total of 122 study participants who were randomized to receive vortioxetine plus celecoxib or vortioxetine plus placebo at the study baseline visit, 82 were taking antidepressant medication (other than vortioxetine) prior to randomization. These medications were selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants, mirtazapine, or agomelatine. Eighty of these 82 participants completed the changeover to vortioxetine as well as the study baseline visit. We found side effects were generally mild during this changeover period. In addition, there was a reduction in mean total Montgomery-Åsberg Depression Rating Scale score of 2.5 (SD 6.0) from study baseline to week 2 and a further reduction in mean total Montgomery-Åsberg Depression Rating Scale of 2.5 (SD 5.9) from week 2 to week 4.ConclusionChanging other antidepressants to vortioxetine can be done safely and was generally well-tolerated. However, there are some antidepressant classes, in particular monoamine oxidase inhibitors that require a washout period, which were not represented in this study.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR); ID number 12617000527369p; http://www.anzctr.org.au/ACTRN12617000527369p.aspx     

Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial

Twenty-eight elderly inpatients suffering from major depressive episodes (diagnosed according to DSM III) received randomly, on a double-blind basis, amitriptyline (75 mg/die) or fluoxetine (20 mg/die) for five weeks. There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitriptyline group. Weight gain was detected only in patients receiving amitriptyline.     

Cianopramine and amitriptyline in the treatment of depressed patients — a placebo-controlled study

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 Dpression and clinical global evaluations, both active drugs showed statistical superiority over placebo (P<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.     

Amitriptyline,clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients

No longer prescribed only for vegetative signs of depression, tricyclic antidepressants also lessen depressive cognitive distortions. Less clear is whether they ameliorate depressed patients' other cognitive deficits in memory, information processing speed, and psychomotor performance. We tested the alternative hypothesis that amitriptyline, because of its anticholinergic and sedative properties, would exacerbate depressed patients' cognitive disturbances. Depressed outpatients received double-blind placebo (n=15), amitriptyline (n=10), or clovoxamine fumarate (n=10), a serotonin reuptake inhibitor relatively lacking in anticholinergic properties. Depression, memory, and psychomotor performance were assessed at baseline and after 7 and 28 days of drug treatment. Depression was alleviated after all treatments, including placebo. Only amitriptyline impaired performance on tests of memory, producing a significant decrement, relative to placebo, after 4 weeks of treatment. None of the treatments adversely affected performance on psychomotor tasks. These findings add to the evidence that antidepressant drugs with high anticholinergic activity can impair memory, despite alleviation of depression.     

A single-blind comparative study of once daily dothiepin (‘Prothiaden’) and divided daily doses of amitriptyline

Summary

Forty-eight patients took part in a single-blind clinical trial comparing a once daily dose of dothiepin (75?mg)and 25 mg 3-times a day of amitriptyline. The results showed that dothiepin caused a greater improvement than amitriptyline after 4 weeks of treatment as judged by depression scores, total scores and global assessments. The incidence of side-effects was less with dothiepin and in those patients who actually reported side-effects the severity was much less with dothiepin than with amitriptyline.     

The impact of antidepressant treatments on family functioning in adults with major depressive disorder: a post hoc comparison of vortioxetine and agomelatine

Objective: There is limited research on the impact of antidepressant treatment on family functioning. This study examines the impact of vortioxetine and agomelatine on family functioning using the Depression and Family Functioning Scale (DFFS).

Methods: The DFFS was included in REVIVE, a randomized, double-blind study of adults with major depressive disorder with inadequate response to antidepressant treatment who switched to vortioxetine or agomelatine. The prespecified DFFS analyses were performed using change from baseline to weeks 8 and 12, analyzed by mixed models for repeated measurements by treatment groups. Post hoc analyses compared DFFS scores for remitters and nonremitters. Patients were stratified into quartiles using DFFS scores, and scores on other clinical outcome assessments were compared.

Results: Sizeable improvements in DFFS scores were observed from baseline to week 8 (?10.8, ?7.9 for vortioxetine and agomelatine, respectively), with further improvements at week 12 (?13.5, ?11.0). Vortioxetine (n?=?189) was superior to agomelatine (n?=?187) by 2.9 DFFS points at week 8 (p?p?n?=?142) and nonremitters (n?=?233) differed by 11 DFFS points; at week 12, remitters (n?=?183) and nonremitters (n?=?121) differed by almost 12 DFFS points. Patients stratified into baseline DFFS quartiles showed trends on clinical outcomes such that better family functioning was associated with better functional status and depressive symptoms.

Conclusions: Vortioxetine was significantly superior to agomelatine in terms of family functioning and partner relationships, as well as social functioning, health status, and depression symptoms at weeks 8 and 12. Depressed patients with impaired family functioning showed worse overall functioning, health status, and depression symptoms, suggesting that more attention should be given to family functioning of depressed patients.     

A test of the concept of ‘underlying depressive illness’ in the treatment of anxiety states

Summary

In order to test the validity of the concept of anxiety states masking an underlying depressive illness, patients clinically diagnosed as suffering from anxiety or tension states were treated on a random double-blind basis for 4 weeks with either a pure anxiolytic, lorazepam, or an anxiolytic / antidepressant preparation, fluphenazine with nortriptyline. Patients' self ratings were very similar to the physicians' ratings which showed that fluphenazine / nortriptyline was associated with significantly greater overall improvement (p<0.01), as well as significantly greater improvement in the group of symptoms specifically related to depression (p<0.05). These results suggest that a depressive element is present in an appreciable proportion of patients presenting with apparent anxiety states, and antidepressant as well as anxiolytic treatment is required.

Patients selected on the basis that they had improved satisfactorily at the end of the 4-weeks' treatment were followed up for a further 3 months without medication, and the relapse rate was 24%, irrespective of previous treatment. More of the patients treated with lorazepam had to be excluded from the follow-up because of failure to improve, and these probably represented the proportion (19%) of this population with an appreciable depressive element to their illness.     

Comparison of the efficacy of sustained-release amitriptyline with maprotiline in the treatment of depressive illness

Summary

Forty consecutive psychiatric patients referred to hospital with a diagnosis of depressive illness were randomly allocated to double-blind treatment with either 50?mg sustained-release amitriptyline or 75?mg maprotiline in night-time dosage. The dosage was doubled after I week. Rating scale assessments were carried out regularly over a 5-week period. The results indicated that there was a significant improvement with both drugs which occurred at approximately the same speed and to the same extent. Side-effects were complained of by approximately as many patients on both forms of treatment.     

Quetiapine augmentation of treatment-resistant depression: a comparison with lithium

ABSTRACT

Objective: The prevalence of and morbidity associated with treatment-resistant depression has motivated the exploration of treatment alternatives. In this study, quetiapine was compared with lithium in the augmentation of treatment-resistant depression.

Research design and methods: Open-label, comparative study in 20 patients with major depression who had failed to respond after 4 weeks of treatment with an antidepressant at the maximal recommended dose. Patients were randomised to either lithium or quetiapine in addition to the maximally dosed antidepressant and any other concurrent medications. Lithium was initiated at 600?mg/day; quetiapine was titrated to 400?mg by day 7.

Results: Depression, measured by the Hamilton Depression Rating Scale (HAM?D), significantly improved from baseline in both quetiapine (F_1,90 = 25.11, p < 0.0001) and lithium (F_1,90 = 34.54, p < 0.0001). The difference in improvement between the two groups began at day 14 and was seen at all timepoints thereafter (?p < 0.05), with the quetiapine group showing greater improvement than the lithium group. In the Montgomery–Asberg Depression Rating Scale (MADRS) analysis, the difference between the quetiapine and lithium group was significant from day 28 onwards (?p < 0.05), with subjects improving more in the quetiapine group than the lithium group. The treatment by week interaction showed a significant difference overall between the two groups (?p < 0.0001). The severity of psychomotor retardation showed a significant decrease in the Widlocher Psychomotor Retardation Scale scores in the quetiapine (?p < 0.0001) and lithium (?p < 0.0001) groups.

Conclusions: In this pilot study, quetiapine was an effective augmenting agent in treatment-resistant depression.