Two-year follow-up of exposure and imipramine treatment of agoraphobia

Sixty-two agoraphobic patient who had completed a controlled study of therapist-assisted in vivo exposure (flooding) and imipramine were assessed 1 month, 6 months, 1 year, and 2 years later. Overall, improvement during treatment was maintained throughout follow-up. At 1 month but not subsequently, imipramine and flooding had significant effects on central measures of agoraphobia. Patients who were marked treatment responders had a favorable clinical course and did not experience secondary depression, unlike patients who had not responded markedly to treatment. These findings suggest that treatments which evoke maximum therapeutic benefit initially are likely to foster long-term maintenance and reduce subsequent depressive sequelae.     

Imipramine and chlordiazepoxide in depressive and anxiety disorders. I. Efficacy in depressed outpatients

We randomly assigned 425 outpatients, independently classified as primarily depressed by two trained psychiatrists, to double-blind treatment with Imipramine hydrochloride, chlordiazepoxide hydrochloride, or placebo. Those patients who remained at least moderately depressed (following a two-week placebo washout period) were treated for an additional eight weeks. An endpoint analysis of 387 patients who completed two or more weeks of medication disclosed early therapeutic advantages of chlordiazepoxide. By week 4 of treatment, however, imipramine produced more improvement than did placebo and chlordiazepoxide. By six and eight weeks a general, marked therapeutic advantage was found for imipramine relative to placebo and to chlordiazepoxide on measures of depression, anxiety, anger-hostility, interpersonal sensitivity, and global improvement. Chlordiazepoxide-treated patients generally did significantly better on sleep difficulty but significantly worse on anger-hostility and interpersonal sensitivity than did imipramine- or placebo-treated patients.     

Gender differences in treatment response to sertraline versus imipramine in chronic depression

OBJECTIVE: The authors examined gender differences in treatment response to sertraline, a selective serotonin reuptake inhibitor (SSRI), and to imipramine, a tricyclic antidepressant, in chronic depression. METHOD: A total of 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were randomly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout. RESULTS: Women were significantly more likely to show a favorable response to sertraline than to imipramine, and men were significantly more likely to show a favorable response to imipramine than to sertraline. Gender and type of medication were also significantly related to dropout rates; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study. Gender differences in time to response were seen with imipramine, with women responding significantly more slowly than men. Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications. CONCLUSIONS: Men and women with chronic depression show differential responsivity to and tolerability of SSRIs and tricyclic antidepressants. The differing response rates between the drug classes in women was observed primarily in premenopausal women. Thus, female sex hormones may enhance response to SSRIs or inhibit response to tricyclics. Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient.     

Depressed in-patients respond differently to imipramine and mirtazapine.

Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression. After a previous report of a marked difference in the response to mirtazapine compared to imipramine, we report here an analysis of different symptom clusters. One hundred seven consecutive in-patients with major depression (Diagnostic and Statistical Manual III-R, DSM-III-R) and a Hamilton Rating Scale for Depression (HRS-D) score of 18 points or more were randomly assigned to double-blind treatment. Two and four weeks after predefined blood levels had been obtained, the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine, the latter being in excess of the 15-45 mg/day range currently advised. Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients (79%) who were not receiving any co-medication. Imipramine was more effective against the clusters related to core symptoms of depression: "depression and guilt", "retardation", and "melancholia", respectively. Mirtazapine showed a biphasic response with regard to the clusters "sleep" and "anxiety/agitation", respectively, which consisted of a marked response after two weeks of predefined blood level, but with a waning of this effect at four weeks. Imipramine produced a more gradual response on these clusters, which was more pronounced at four weeks than with mirtazapine. Two aspects of the present study could be related to this finding: blood level control resulted in optimal treatment with imipramine but not mirtazapine, and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication. These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in-patients.     

Agoraphobia: relative and combined effectiveness of therapist-assisted in vivo exposure and imipramine

Sixty-two chronically agoraphobic patients completed a controlled study to assess the effects of 1) imipramine up to 200 mg/day (mean = 130 mg/day), 2) 12 weekly therapist-assisted in vivo exposure sessions (flooding), and 3) imipramine plus flooding. The control group received systematic therapeutic instructions for self-directed in vivo exposure (programmed practice). Clinical measures of global severity, phobia, panic, anxiety, depression, and behavioral performance tests were administered before treatment and at Weeks 4, 8, and 12 of treatment. Results revealed significant improvement in all groups on all measures over the course of treatment; almost a third of the control patients showed marked improvement. Imipramine had significant effects on improvement of phobias and markedly increased clinical response rates in patients receiving 150-200 mg/day. Less chronicity and severity of condition also predicted better clinical outcome. Flooding had limited effects above and beyond programmed practice, and no imipramine-flooding interactions effects were found.     

Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination

In a double-blind, long-term follow-up study, 117 bipolar patients received lithium carbonate, imipramine hydrochloride, or both and 150 unipolar patients received lithium carbonate, imipramine, both lithium carbonate and imipramine, or placebo. With bipolar patients, lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes. The combination treatment provided no advantage over lithium carbonate alone. With unipolar patients, imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences. The combination treatment provided no advantage over imipramine alone. The lithium carbonate-treated group had fewer manic episodes than the other groups. Treatment outcome, which was evaluated primarily in terms of the occurrence of major depression or manic episodes, was significantly related to characteristics of the index episode, ie, the episode that brought the patient into the study.     

A double-blind comparison study of nomifensine and imipramine in treating depressed patients

Nomifensine was compared to imipramine in treatment of 40 patients with endogenous major depressive disorder. After one week washout, patients were randomly assigned to 5 weeks treatment with Nomifensine or Imipramine. Mean scores for HAM-D, HAM-A, GAS were significantly improved in both treatment groups (P less than 0.01). Two agents were similar in antidepressant efficacy and rapidity of action. Nomifensine treatment group had fewer side effect, whereas the Imipramine group had more adverse experiences. Effects of Nomifensine on the ECG were compared to those of imipramine. Both drugs increased heart rate. Nomifensine less than imipramine. QT measurement interval revealed a statistically significant decrease in imipramine group. Plasma Nomifensine and imipramine concentrations were not correlated with clinical response, side effects or electrocardiographic parameters. The steady-state plasma concentration 105 +/- 47ng/ml for nomifensine, 860 +/- 773ng/ml for imipramine were offaimed respectively at the fixed dose (225mg/day) during the 35 treatment day.     

Response of postpsychotic depression to adjunctive imipramine or amitriptyline

Case histories were reviewed of 25 patients with RDC diagnoses of schizophrenia or schizoaffective disorder who developed a clinical syndrome of depression subsequent to the resolution of their psychotic episodes. Of these patients, 14 were then treated with imipramine and 11 with amitriptyline in addition to their neuroleptic drugs. As a group, the patients did well--48% had a remission of depressive symptoms and an additional 32% improved. Psychotic exacerbation was noted in only one patient. Imipramine seemed more beneficial than amitriptyline in these patients.     

Cardiovascular and antidepressant effects of imipramine in the treatment of secondary depression in patients with ischemic heart disease

The authors report on 12 men with ischemic heart disease who developed secondary depression following myocardial infarction or coronary artery bypass-graft surgery and were treated with imipramine hydrochloride for 4 weeks. Imipramine had an antiarrhythmic effect, manifested by reduction in premature ventricular contractions during treatment. This drug did not produce clinically significant disturbances in cardiac conduction, but orthostatic hypotension led to early termination of the drug treatment in 1 subject. Imipramine treatment was associated with significant improvement in both observer-rated and patient-rated depression scales.     

Six-year follow-up after exposure and clomipramine therapy for obsessive compulsive disorder

To determine whether gains from exposure therapy are lasting in patients with chronic obsessive compulsive disorder, the authors followed up 34 (85%) of 40 such patients who had been treated 6 years earlier with exposure therapy for 3 or 6 weeks and with clomipramine or placebo for 36 weeks. Severity of obsessive compulsive disorder was assessed by rating the discomfort caused by the time devoted to four target rituals, the Behavioral Avoidance Test, and the Compulsion Checklist. Mood was assessed by the 17-item Hamilton Rating Scale for Depression, the Wakefield Self-Assessment Depression Inventory, and the Anxiety scale. In addition, the patients' general adjustment was assessed. The authors found that the group as a whole remained significantly improved on obsessive compulsive symptoms, work and social adjustment, and depression; however, the group returned to pretreatment levels (slight to moderate) of general anxiety. They found that neither clomipramine nor placebo affected long-term outcome and that the majority of patients who were taking clomipramine or other antidepressants at follow-up were no more improved that those who were not taking antidepressants. Better long-term outcome correlated with more exposure therapy (6 weeks of therapy vs. 3 weeks) and with better compliance with the exposure therapy homework. The best predictor of long-term outcome was improvement at the end of treatment. Subjects who had initially been most depressed were more likely to receive psychotropic medication during follow-up. Initial severity of illness did not preclude benefit from exposure therapy.     

Imipramine binding in depressed patients with psychogenic pain

Imipramine binding to platelet membranes from depressed patients was analyzed. The patients were divided into two groups: one with depression alone, another with depression and psychogenic pain. The depressed patients with psychogenic pain had lower imipramine binding than the depressed patients without pain.     

Imipramine and brief therapists-aided exposure in agoraphobics having self-exposure homework

Forty-five chronic agoraphobics were randomly assigned to treatment by placebo or imipramine in doses up to 200 mg/day for 28 weeks. All patients also had systematic self-exposure homework with an instruction manual. In addition, half of each drug group had therapist-aided exposure and half had therapist-aided relaxation, each totalling three hours. Patients in both drug groups improved substantially and maintained their gains for one year of follow-up. Imipramine had no significant therapeutic effect despite satisfactory plasma levels and significant drug side effects. Patients' low initial Hamilton depression scores might explain the absence of any drug effect. Antidepressants may be ineffective for agoraphobics who have normal mood. Brief therapist-aided exposure improved phobias and panics to a significant but limited extent, and is a useful adjuvant to self-exposure homework, which can be a powerful therapeutic agency by itself.     

Which tricyclic for depressed outpatients, imipramine pamoate or amitriptyline?

Fifty-seven neurotically depressed outpatients with sleep disturbance were randomly assigned to treatment with either imipramine pamoate or amitriptyline given in a single dose at bedtime in a double-blind study for four weeks. The results indicate that both imipramine pamoate and amitriptyline are equally effective in treating neurotic depression. The clinical lore that imipramine is more effective for retarded depression and amitriptyline for anxious, agitated depression was not supported by this study. Of special interest is the fact that the imipramine pamoate group had significantly earlier rising times, and a trend toward better quality of sleep. The side effect profiles of the two drugs were also remarkably similar in this population though more patients complained of side effects on amitriptyline than on imipramine.     

Agoraphobics 5 years after imipramine and exposure. Outcome and predictors

Five years after treatment in a controlled trial, in which all had received self-exposure homework, a group of 40 agoraphobic outpatients retained marked improvement in agoraphobia, mood, and free-floating anxiety. Frequency of spontaneous panics decreased as much in those who had placebo and self-exposure as in those who received imipramine and self-exposure. Few patients, however, were completely well at 5 years and over half had received further treatment for agoraphobia during the follow-up. Patients who were still highly phobic at the end of the clinical trial were more often prescribed psychotropic medication during follow-up and remained phobic at 5 years. Phobic improvement had generalized more in those patients with very low than in those with moderate pretreatment Hamilton depression scores. Frequency of initial spontaneous panics did not predict outcome. Improvement in agoraphobia was associated with improved marital adjustment. Those who began with the best marital, work, and social adjustment were more improved in their phobias 5 years later.     

Antidepressant specificity in atypical depression

One hundred nineteen patients who met specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 71% with phenelzine, 50% with imipramine, and 28% with placebo. Phenelzine was widely superior to placebo and also showed superiority to imipramine. Phenelzine superiority appeared even greater after an additional six-week continuation phase. Imipramine was only moderately effective in this atypical depressive sample. Unexpectedly, the superiority of either phenelzine or imipramine to placebo was largely confined to patients in subsets of the study sample who were prospectively judged to also have a history of spontaneous panic attacks and/or show hysteroid dysphoric features. This is consonant with some but not other recent findings and requires replication. Overall, the concept of atypical depression as a subtype that is preferentially responsive to monoamine oxidase inhibitors is supported.     

Long-term outcome of endovascular therapy for acute basilar artery occlusion

The long-term functional outcome of acute basilar artery occlusion (BAO) patients who received modern endovascular therapy (EVT) is unclear. We sought to assess the long-term functional outcome of BAO patients treated with EVT and determine the prognostic factors associated with favorable outcome. We enrolled consecutive BAO patients who received EVT between December 2012 and December 2018 in this observational study. Baseline characteristics and outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long-term outcome. Among the 177 BAO patients included in this study, 80 patients (45.2%) obtained favorable outcome and 97 patients (54.8%) had unfavorable outcome at long-term follow-up with a median observation time of 12 months (interquartile range, 3–19). A total of 67 patients (37.9%) died. National Institutes of Health Stroke Scale (NIHSS), posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS), time from stroke onset to recanalization, and recanalization condition were identified as independent predictors for long-term outcome. Over 40% of BAO patients who were treated with modern EVT achieved favorable outcome at long-term follow-up. NIHSS, pc-ASPECTS, time from stroke onset to recanalization, and recanalization condition were identified as independent prognostic factors of long-term outcome.     

Imipramine treatment for chronic depression

Antidepressant drugs in the treatment of chronic depressions have received little systematic study. We used a two-week, single-blind placebo washout followed by a six-week, double-blind comparison of imipramine hydrochloride and placebo in a sample of 76 outpatients with DSM-III dysthymic disorder entered into a trial at two centers. Subjects were preponderantly female, had insidious onset at an early age, and had depressions of moderate severity; 96% also met the DSM-III criteria for major depressive disorder at the time of presentation. Sixty percent had a history of persistent depressive symptoms sufficient to meet criteria for major depression for longer than two years. Markedly favorable responses occurred in 45% of imipramine-treated (n = 29) and 12% of placebo-treated (n = 25) patients and, respectively, 59% and 13% of those who completed the study. Imipramine produced significant advantage in measures of depressive symptoms, global severity of illness, and self-rated social and vocational function. Recovered patients experienced remission from both long-standing symptoms and deficits as well as more recently exacerbated aspects of their syndrome. Patients with pure dysthymic disorder of a mild, subsyndromal type were uncommon in these clinical settings. However, anti-depressant medication was effective for many moderately severe chronic depressions, which had previously been untreated or undertreated, presumably related to misdiagnosis.     

Factors associated with premature medication discontinuation among responders to an MAOI or a tricyclic antidepressant

The charts of 80 outpatients who responded to antidepressants were reviewed to determine if there was a higher rate of premature medication discontinuation with phenelzine than with imipramine. The phenelzine responders had a significantly (p less than .01) higher rate of drug discontinuation, mainly because of side effects. Controlled studies of long-term use are needed to better explain the problem of attrition.     

Imipramine and buspirone in treatment of patients with generalized anxiety disorder who are discontinuing long-term benzodiazepine therapy

OBJECTIVE: Patients with generalized anxiety disorder (N=107) who had been long-term benzodiazepine users (average duration of use=8.5 years) were enrolled in a benzodiazepine discontinuation program that assessed the effectiveness of concomitant imipramine (180 mg/day) and buspirone (38 mg/day) compared to placebo in facilitating benzodiazepine discontinuation. METHOD: After a benzodiazepine stabilization period taking either diazepam, lorazepam, or alprazolam, patients were treated for 4 weeks with imipramine, buspirone, or placebo under double-blind conditions while benzodiazepine intake was kept stable (treatment phase). Patients then entered a 4-6 week benzodiazepine taper and a 5-week posttaper phase with imipramine, buspirone, and placebo treatment being continued until 3 weeks into the posttaper phase, at which time all patients were switched to placebo for 2 weeks. Benzodiazepine plasma levels were assayed weekly. Benzodiazepine-free status was assessed 3 and 12 months posttaper. RESULTS: Study subjects were long-term benzodiazepine users with an average of three unsuccessful prior taper attempts. The success rate of the taper in this study was significantly higher for patients who received imipramine (82.6%), and nonsignificantly higher for patients who received buspirone (67.9%), than for patients who received placebo (37.5%). The imipramine effect remained highly significant even after the analysis adjusted for three other independent predictors of taper success: benzodiazepine dose, level of anxious symptoms at baseline, and duration of benzodiazepine therapy. CONCLUSIONS: Management of benzodiazepine discontinuation can be facilitated significantly by co-prescribing imipramine before and during the benzodiazepine taper. Daily benzodiazepine dose, severity of baseline symptoms of anxiety and depression, and duration of benzodiazepine use were additional significant predictors of successful taper outcome.