Effects of chronic variable stress and antidepressant drugs on behavioral inactivity during an uncontrollable stress: interaction between both treatments.

Rats submitted to a chronic variable stress regime exhibited more inactivity during inescapable shock as compared with unstressed rats. Besides, chronic treatments with desipramine, imipramine, clomipramine, or phenelzine reduce the amount of inactivity exhibited during this aversive experience. Furthermore, the combination of both chronic treatments--stress and antidepressants--resulted in a potentiation of the antidepressant effect alone. This higher antidepressant efficacy may result from the interaction of the neural mechanisms triggered by chronic stress exposure and antidepressant drugs.     

Antidepressant treatment of children: clinical relapse is unrelated to tricyclic plasma concentrations

Plasma concentrations of imipramine and amitriptyline and their desmethylated metabolites were measured in 20 children being treated for major depressive illness 2 wk. and 5 to 10 wk. after achieving drug dosages of 2.25 mg/kg body weight. At 2 wk. all children had exhibited clinical improvement, but by 10 wk. 4 of the 10 children treated with imipramine and 5 of the 10 children treated with amitriptyline had experienced clinical relapse of depressive symptoms. Tricyclic antidepressant plasma concentrations and ratios were comparable in the subgroups of children who maintained their clinical improvement and those who relapsed. There was no evidence of a systematic decline in plasma tricyclic antidepressant concentrations in those children who relapsed.     

Differential indication of trimipramine - results of a controlled multiclinical study]

The antidepressants trimipramine and imipramine were compared within the framework of a multiclinical study performed under the conditions of a controlled clinical experiment. There has been found a time-different remission of affective und psychomotoric symptoms. The panthymoleptic action of trimipramine and other antidepressants is discussed with reference to these results. Trimipramine influences psychotic states, especially if in depression anxiety is combined with agitation, also in hypochondriac forms of depression.     

Treatment of panic disorder with agoraphobia: randomized placebo-controlled trial of four psychosocial treatments combined with imipramine or placebo

Few randomized controlled trials have included panic disorder patients with moderate to severe agoraphobia. Therefore, this population was studied using pharmacotherapy as well as psychotherapy. At the time of the study, imipramine was widely used as a pharmacological treatment. Also, current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy. Therefore, the main objective of this study is to compare four psychosocial treatments-cognitive and graded in vivo exposure treatments, graded in vivo exposure, cognitive treatment, and supportive therapy-to evaluate the benefits of combining cognitive therapy with exposure in vivo. These treatments were combined with imipramine or placebo for a total of eight experimental conditions. Participants presented moderate to severe agoraphobia. The method involved a randomized, double-blind, placebo-controlled trial with 137 participants who completed a 14-session protocol involving the treatments just mentioned. Measures were taken at baseline and posttreatment and at 3-, 6-, and 12-month follow-up. All treatment conditions were statistically and clinically effective in reducing self-reported panic-agoraphobia symptoms over the 1-year follow-up. No statistical differences were observed between imipramine and placebo conditions. This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1-year follow-up period. These surprising results support the need to document the relations among the various components of an intervention. This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole.     

The effect of imipramine and trazodone on the re-uptake of (3H) serotonin by thrombocytes in patients with endogenous depression: changes in antidepressive therapy

The inhibitory potencies of imipramine (IC50-values for IMI) and trazodone (IC50-values for TRA) on platelet [3H]serotonin uptake were measured in depressed patients. The IC50-values for IMI in patients was shown to be higher (P less than 0.01) than in controls. The IC50-values for TRA in patients were lower (P less than 0.01) than found in platelets from controls. These alterations were not accompanied by the significant decrease of a density of platelet [3H]imipramine binding sites. Drug treatment led to the normalization of the IC50-values for IMI and to the partial increase of the IC50-values for TRA. There was a negative correlation of IC50-values for TRA and severity of depressive symptoms evaluated by the Hamilton Depression Rating Scale. The results support the hypothesis that the mechanisms of the regulation of [3H]serotonin uptake sensitivity to IMI and TRA in patients are different.     

Treatment of Panic Disorder with Agoraphobia: Randomized Placebo‐Controlled Trial of Four Psychosocial Treatments Combined with Imipramine or Placebo

Few randomized controlled trials have included panic disorder patients with moderate to severe agoraphobia. Therefore, this population was studied using pharmacotherapy as well as psychotherapy. At the time of the study, imipramine was widely used as a pharmacological treatment. Also, current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy. Therefore, the main objective of this study is to compare four psychosocial treatments—cognitive and graded in vivo exposure treatments, graded in vivo exposure, cognitive treatment, and supportive therapy—to evaluate the benefits of combining cognitive therapy with exposure in vivo. These treatments were combined with imipramine or placebo for a total of eight experimental conditions. Participants presented moderate to severe agoraphobia. The method involved a randomized, double‐blind, placebo‐controlled trial with 137 participants who completed a 14‐session protocol involving the treatments just mentioned. Measures were taken at baseline and posttreatment and at 3‐, 6‐, and 12‐month follow‐up. All treatment conditions were statistically and clinically effective in reducing self‐reported panic–agoraphobia symptoms over the 1‐year follow‐up. No statistical differences were observed between imipramine and placebo conditions. This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1‐year follow‐up period. These surprising results support the need to document the relations among the various components of an intervention. This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole.     

Three years follow-up of panic disorder patients: A naturalistic study

Forty Danish panic disorder patients participating in a placebo controlled study of alprazolam and imipramine (The Cross National Collaborative Panic Study, Phase II) were followed up by a telephone interview three years later, with essentially the same battery of evaluation procedures applied at baseline, end of study, and follow-up. The main finding was that panic disorder is a chronic disorder, but fluctuating in form and severity in the course of time. Twenty-five percent of the patients no longer fulfilled the DSM-III criteria for panic disorder, but had substantial disability due to a variety of symptoms, including panic attacks at infrequent rate, generalized anxiety symptoms, affective symptoms, and phobic avoidance behavior. Nearly three fourths of the patients were under treatment at follow-up. Benzodiazepines were the drugs most often prescribed, usually in combination with supportive psychotherapy. It was concluded that the different types of treatment offered were insufficient. Variables predicting panic disorder or substantial disability at 3-years follow-up were few.     

氟哌啶醇与丙咪嗪交互作用对成本效益决策的影响

本实验采用T迷宫延迟奖赏模型研究多巴胺D2受体拮抗剂氟哌啶醇和5-羟色胺重摄取抑制剂丙咪嗪的交互作用对成本效益决策的影响, 同时探讨了延迟时间对决策的影响。T迷宫两臂分别设置为低成本-低奖赏端和高成本-高奖赏端。实验结果发现：氟哌啶醇能够降低大鼠选择高成本-高奖赏端的次数, 丙咪嗪则能够增加大鼠选择高成本-高奖赏端的次数; 在同时注射这两种药物情况下, 丙咪嗪能够抑制由氟哌啶醇引起的对低成本-低奖赏端的选择倾向。另外, 实验发现, 随延迟时间的增加大鼠选择高成本-高奖赏端的次数相对减少。由此可见, 丙咪嗪能够反转由氟哌啶醇导致的对低成本-低奖赏端的选择倾向, 这可能是由于细胞间5-羟色胺含量的升高部分反转了由多巴胺系统受损导致的行为倾向; 延迟时间的改变可对决策倾向产生逆转, 因此成本的支出即延迟时间也是影响成本效益决策的重要因素。     

Case study: The combined use of imipramine and behavior modification to reduce aggression in an adult male diagnosed as having autistic disorder

The present study examined the behavior decelerative effects of combined imipramine (tofranil) and behavior modification in a severely retarded, depressed autistic man. A simple interrupted time-series design was conducted and the primary data analytic techniques consisted of modified trend analyses and dependent samples t-tests. Consistent with previous theory and scant empirical research, results indicated that combined imipramine and behavior modification significantly reduced daily episodes of self-directed and other-directed aggression. Specifically, controlling for the effects of time, the combined treatment regimen led to significant reductions in both level and slope across three topographies of aggressive behavior. Limitations of the present study and recommendations for future research were discussed. It was concluded that combined imipramine and behavior modification may be an effective strategy for reducing aggression in the developmentally disabled.     

Dietary restraint of bulimic subjects following cognitive-behavioral or pharmacological treatment

The pre and posttreatment self-monitored caloric intake of bulimic subjects treated with either cognitive-behavioral therapy or imipramine was compared. Results indicated that both groups equally and successfully reduced purged calories but that only cognitive-behaviorally treated subjects increased non-purged caloric intake. These results show that cognitive-behavioral treatment lessens dietary restraint whereas imipramine treatment of bulimia nervosa does not. These findings are discussed and it is suggested that they may account for the superior therapeutic maintenance following cognitive-behavioral treatment when compared with pharmacological treatment of bulimia nervosa.     

Do tricyclic responders have different brain laterality?

A previous study showed that depressed patients who improved with tricyclic antidepressant medication had dichotic complex tones test results suggesting right-hemisphere dysfunction relative to nonresponders and controls (G. E. Bruder et al., 1990). A new sample of 68 depressed patients completed dichotic consonant-vowel (CV) and complex tones (CT) tests and then were treated with imipramine or placebo. A significant Ear x Test x Treatment x Response interaction was accounted for by significantly poorer left-ear accuracy for CVs among imipramine responders compared with nonresponders, placebo responders, and controls. CV left-ear accuracy was also significantly greater among placebo responders than placebo nonresponders and controls. The results only partially replicate the prior study in that evidence of right-hemisphere dysfunction in tricyclic responders was seen for the CV test but not the CT test.     

A quantitative interresponse-time analysis of DRL performance differentiates similar effects of the antidepressant desipramine and the novel anxiolytic gepirone.

We describe an interresponse-time analysis of performance on a differential-reinforcement-of-low-rate 72-s schedule. This analysis compares the obtained interresponse-time distribution of individual rats to a corresponding random interresponse-time distribution. The random interresponse-time distribution is a negative exponential probability function; it predicts the relative distribution of interresponse times if the rat emitted the same number of responses randomly (i.e., with a constant probability) with respect to time. The analysis provides quantitative measures of peak location and dispersion of the interresponse times toward random performance. In Experiment 1, an unexpected outcome of this analysis was that the rats would have obtained more reinforcers had they responded at the same rate but randomly. Based on the interresponse-time analysis in Experiment 1, it was shown that rats trained on the differential-reinforcement-of-low-rate 72-s schedule could increase the number of reinforcers obtained in two ways: first, by a coherent shift of the interresponse-time distribution toward longer durations and, second, by dispersal of the interresponse times toward a random interresponse-time distribution. Experiment 2 applied the analysis described in Experiment 1 to the effects of desipramine and gepirone. Both drugs decreased response rate and increased reinforcement rate, but their effects on the distribution of interresponse times were different. The increase in reinforcement rate observed with desipramine was accompanied by a coherent shift of the reinforcement rate observed with gepirone was accompanied by dispersal of the interresponse-time distribution toward the random negative exponential prediction.     

Motor performance in hyperactive children treated with imipramine

The effects of the tricyclic antidepressant imipramine were evaluated in a study of 9 children with Attention Deficit-Hyperactivity Disorder. The study was double-blind, placebo-controlled, with three drug conditions, low, medium, and high doses. The focus was on neuropsychological drug effects. Imipramine exerted negative dose-response effects on motor performance (motor speed, motor pursuit), while it improved hyperactive behavior and attention and raised the heart rate slightly.     

Contrast and inhibition in discrimination learning by the pigeon: Analysis through drug effects

In a series of four experiments, pigeons were trained on either an easy, red/green discrimination with or without a penalty for errors, or a more difficult left/right discrimination with penalty. Some groups of birds were injected with chlorpromazine or desipramine prior to acquisition sessions or to sessions following learning of the discrimination. Drug injection caused substantial impairment of acquisition or retention of the left/right discrimination alone, whereas in all discriminations the behavioral contrast effect was abolished. The results suggest that inhibition of errors depends upon the difficulty of discrimination and the presence of a penalty procedure, and determines both contrast in the saline-injected groups and the extent of impairment in the drug-injected groups.     

Acetylcarnitine reduces the immobility of rats in a despair test (constrained swim)

Male rats forced to swim in a cylinder adopted an immobile posture. Immobility was reduced by acetylcarnitine (5, 10, and 20 mg/kg) and by antidepressant drugs, such as desipramine and iproniazid, injected 24, 5, and, again, 1 h prior to behavioral testing. Acetylcarnitine also potentiated the anti-immobility effect of antidepressant drugs in the despair test. Chronic (10 days) treatment with acetylcarnitine mimicked the effect found after acute administration. It is possible that the action of the acetylcarnitine on the despair test is indicative of an antidepressant activity of this drug that is dependent on a change in the sensitivity of monoamine receptors in the brain.     

Emotion-Focused Therapy for Couples in the Treatment of Depression: A Pilot Study

Emotion-focused therapy (EFT) for couples was compared to pharmacotherapy in the treatment of major depressive disorder. Eighteen distressed couples in which the female partner met diagnostic criteria for major depressive disorder were randomly assigned to 16 weekly sessions of emotion-focused therapy or pharmacotherapy with desipramine, trimipramine, or trazadone. Twelve couples completed the study. Both interventions were equally effective in symptom reduction. There was some evidence that females receiving EFT made greater improvement after the conclusion of treatment than those receiving pharmacotherapy. The results suggest EFT might be useful in the treatment of comorbid major depressive disorder and relational distress.     

Effect of drugs on the cardiac conditioned response of dogs

Dogs were conditioned to an anxiety response characterized by an increase in heart rate upon presentation of a musical tone. Meprobamate, chlordiazepoxide and diazepam effectively prevented the cardiac conditioned response. Phenobarbital and chlorpromazine were less effective. Amphetamine, 1.5 orally, also blocked the cardiac conditioned response. Atropine, meperidine, caffeine, imipramine and -methyl-dopa had no effect on the cardiac conditioned response. Morphine and methyl phenidate were clearly active only in doses producing marked side effects. Ethanol in relatively small doses was mildly effective.     

A delivery system for the treatment of primary enuresis

To illustrate how to deliver underutilized psychological treatments, a comprehensive, low-cost treatment for primary enuresis was developed consisting of bell-and-pad training, cleanliness training, retention control, and overlearning. Sixty primary enuretic children and their parents attended 1-hour group training sessions and implemented treatment in the home. Each case required 15 minutes of professional time, and net cost to each family was $50. Forty-eight (81%) achieved initial arrest of bedwetting and only 11 (24%) relapsed at 1-year follow-up. Significant association between relapse and prior treatment failure with imipramine was noted. The outcome was found to compare favorably with previous treatments that required more professional time.     

DRL interresponse-time distributions: quantification by peak deviation analysis.

Peak deviation analysis is a quantitative technique for characterizing interresponse-time distributions that result from training on differential-reinforcement-of-low-rate schedules of reinforcement. It compares each rat's obtained interresponse-time distribution to the corresponding negative exponential distribution that would have occurred if the rat had emitted the same number of responses randomly in time, at the same rate. The comparison of the obtained distributions with corresponding negative exponential distributions provides the basis for computing three standardized metrics (burst ratio, peak location, and peak area) that quantitatively characterize the profile of the obtained interresponse-time distributions. In Experiment 1 peak deviation analysis quantitatively described the difference between the interresponse-time distributions of rats trained on variable-interval 300-s and differential-reinforcement-of-low-rate 72-s schedules of reinforcement. In Experiment 2 peak deviation analysis differentiated between the effects of the psychomotor stimulant d-amphetamine, the anxiolytic compound chlordiazepoxide, and the antidepressant desipramine. The results suggest that peak deviation analysis of interresponse-time distributions may provide a useful behavioral assay system for characterizing the effects of drugs.     

Rate dependent effects of imipramine: Effects of imipramine on operant behaviour in rats at various levels of water deprivation

The behavioural effects of 1.0, 3.10 and 6.0 mg/kg imipramine injections on lever pressing of rats were studied. Lever pressing was reinforced according to a continuous reinforcement schedule at 0, 24, and 48 h of water deprivation, according to fixed ratio schedules with 22 1/2 h of water deprivation, and according to differential-reinforcement-of-low-rate schedules with 22 1/2 h of water deprivation. The mean rate of responding per min increased significantly at 1.0 mg/kg on the continuous reinforcement schedule at 24 h of deprivation. Otherwise, a dose-related significant reduction in the mean response rate per min occurred on the fixed raito schedules and partly on the differential-reinforcement-of-low-rate schedules, thus lending support to the idea that rate dependent effects may be produced only on schedules of reinforcement such as the fixed ratio, the fixed interval and the variable interval. The results also indicate that depenent effects may be produced only at moderate levels of water deprivation. Some critical comments are made on concepts of rate dependency in view of the results and of previous finding.