human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Prevention of relapse following depression is a pressing research problem . The authors tested the efficacy of the tricyclic antidepressant amitriptyline and psychotherapy , alone and in combination , in preventing the relapse of 150 neurotic depressed female patients . They found that patients receiving amitriptyline and little psychotherapy had a 12-percent relapse rate , compared to a 16-percent rate for those receiving more psychotherapy and no medication . There was no significant difference between drug therapy alone or drug therapy in combination with psychotherapy . However ,  psychotherapy was beneficial to patients with problems of social adjustment and interpersonal relations .  The need for further research and implication s for treatment are discussed Adinazolam , a triazolobenzodiazepine , was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives . Forty-eight patients entered the study , and 35 completed 6 weeks of evaluation . Patients were well matched in each of the groups . Initially , the adinazolam group showed more improvement than the placebo group , but this trend did not persist beyond day 7 . The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups , and final scores were significantly better for amitriptyline . Depressive symptoms in the amitriptyline dropout group appeared improved , whereas in the adinazolam and placebo dropout groups they were unchanged or worse . Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo . Thus , amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo The present report examines the predictors and modifiers of response to amitriptyline in an effort to : identify variables whose effects on drug response are general enough to apply to a range of patient types and treatment setting s , isolate predictors , and evaluate the extent to which contrasting conditions across treatment setting s may lead to contrasting predictors of treatment effects . The sample comprised moderately depressed neurotic out patients from three treatment setting s : 84 clinic patients from an outpatient clinic in a city hospital , 95 patients from the private practice of general practitioners , and 78 patients from the private practice of a group of psychiatrists . Potential predictors from which regressors in a step search multiple regression procedure could be selected were : patient demographic and attitudinal characteristics , assessment s of presenting illness and its history , and evaluations of aspects of the patient-therapist interaction Summary : To establish the differential indication of trazodone and to find the predictors of its efficacy , we conducted a study in which 45 patients with major depressive disorder and 75 patients with acute schizophrenia were r and omly assigned under double‐blind conditions to either 400 mg trazodone daily , 150 mg amitriptyline daily , 20 mg haloperidol daily , or placebo daily . At the beginning of the investigations , numerous variables ( basic data , MMPI , AMDP , HAM‐A , HAM‐D ) were documented and evaluated on days 3 , 7 , 14 , and 21 . In our study , trazodone proved to be as effective an antidepressant drug as amitriptyline . In group comparison , no antipsychotic action of trazodone in schizophrenic patients could be proved . Yet the trazodone treatment was clearly of less risk than the amitriptyline treatment . Under trazodone , provocation of schizophrenic symptoms , which occurred numerously under amitriptyline , was found only in one patient out of 17 schizophrenics . Related to anamnesis and characteristics of the schizophrenic patient , a predictor‐variable concerning the antipsychotic effect was not found . It can be assured , however , that patients with depressive symptoms  ( regarding the entity classification ) respond to trazodone . After only 7 days of trazodone treatment , a relatively reliable decision can be established as to whether a therapeutical success can be expected if treatment is continued This report examines the hypothesis that for phenelzine to be more effective than placebo it is necessary to achieve at least 80 % inhibition of platelet MAO activity . This hypothesis was examined in the context of a double-blind comparison of phenelzine , amitriptyline and placebo in depressed patients . When phenelzine became significantly more effective than placebo at 4 weeks , the average MAO inhibition was 85 % . By the 5th week , with MAO inhibition greater than 90 % , phenelzine was significantly more effective than amitriptyline . A highly significant correlation was noted between improvement and MAO inhibition within the phenelzine group The cardiovascular effects of trazodone ( TZD ) , amitriptyline ( AMT ) and placebo were studied in out- patients with major depression .  AMT was shown to have the expected effects on the electrocardiograph and on systolic time intervals consistent with its proven anticholinergic and quinidine-like properties . TZD , in contrast , had no quinidine-like effects and minor effects on systolic time intervals . However , it was not without any cardiovascular effects . Although TZD was shown to be a safer preparation than the reference drug AMT , long-term monitoring is needed to explain the minor effect on heart rate and T wave changes A controlled double-blind trial of amitriptyline at two dosage levels ( 75 and 150 mg/day ) , amylobarbitone ( 150 mg/day ) , and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness . Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups . Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety . Troublesome side effects were equally distributed among the four treatments Following a 1-week , single-blind placebo washout , 150 patients were r and omized 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 MIA is an effective antidepressant , comparable in therapeutic efficacy to the TCAs . Further , because of its weak antimuscarinic effects . Further , because of its weak antimuscarinic effects , MIA produces no significant cognitive impairment , alteration of cardiovascular function of anticholinergic side effects compared to the TCA 's . While drowsiness is the most frequently reported adverse reaction with MIA , an h.s . dosing schedule can provide relief of insomnia and improve the quality of sleep ( 47,61 ) . Therefore , because of MIA 's advantageous pharmacodynamic profile , it offers an improvement in therapeutic index over the TCAs in the treatment of depression in the elderly SIR,-We wish to record a further instance of fatal paraquat poisoning . So far as we can ascertain , this is the tenth reported fatality caused by this widely used herbicidal preparation."q In December 1965 a 42-year-old male accidentally drank a small quantity of " weed-killer "  from an  unlabelled stout bottle . It was later estimated that the quantity of fluid consumed was about threequarters of a teaspoonful . The nature of the substance could not be immediately ascertained , but it was subsequently identified as Gramaxone 19 % ' w/w paraquat ion ) by the laboratories of I.C.I. Ltd. On admission to hospital a few hours after taking the poison , the patient complained of a  burning sensation in the throat and repeated -vomiting . Despite immediate gastric lavage , prophylactic penicillin , and abundant oral and intravenous fluids , there was progressive clinical deterioration . At three days the tongue was severely ulcerated and two days later haemoptysis occurred . On the eighth day jaundice , pyrexia , tachycardia , and a blood urea of 375 mg./100 ml . were recorded . The patient died some hours later . The outst and ing necropsy findings included focal myocardial necrosis , -severe pulmonnary haemorrhage and oedema , dense eosinophilic alveolar membrane , and proliferation of fibroblast-like cells in the alveolar septa . It is apparent from this and other reports that the lethal dose of paraquat may be very small . Further fatalities will -nly be avoided by proper , care in the storage and use of this valuable -but potentially dangerous compound . A detailed and illustrated clinico-pathological report is being prepared for publication.-We are , etc . Eighty-five female depressed patients were treated for 4 weeks with amitriptyline in a flexible dose ( median , 150 mg daily ) . Predictive analyses of outcome were carried out , using both typological and regressional models based on the same 29 predictor variables . The typological prediction utilized a previously described four-group typology derived by multivariate cluster analysis and comprising psychotic depressives , anxious depressives , hostile depressives , and young depressives with personality disorder . Patients were assigned to groups by discriminant functions on the basis of scores on the predictor variables . The four groups were found to predict outcome significantly . Psychotic depressives , initially the most severely depressed , improved the most ; anxious depressives , a little less severely ill initially , showed the least improvement and the most residual illness at 4 weeks ; hostile depressives and young depressives with personality disorders , initially the least severely ill , showed intermediate improvement and were least ill , by a small margin , at 4 weeks . The 29 predictor variables also predicted outcome significantly in linear multiple regression analyses . Five variables showed regression weights significantly different from zero : high initial severity predicted high improvement but more residual illness ; initial insomnia , more previous depressions , longer illness , and hypochondriasis all predicted low improvement and more residual illness . Predictions by using typological and regression models were compared , and their interrelationships were examined . The regression prediction accounted for more variance in outcome measures than did the typology , but the statistical significance s of the regression and typological predictions were of the same order . Two variables appeared particularly important — high initial severity of illness which characterized the psychotic depresives and increased number of previous depressions which characterized the anxious depressives . Typological prediction was not solely due to these two variables in linear regression model sicne it remained significant when the outcome measure was adjusted for both by analysis of covariance . Both typological and regressional models provide useful approaches to prediction , with only limited overlap . The typological approach , which has been relatively neglected in recent years , warents more frequent application as an alternative to multiple regression Summary Forty-five patients suffering from a major depression were administered zimeldine , amitriptyline or placebo ( 15 patients in each group ) in a double-blind controlled study . In the zimeldine group , seven of the 14 patients treated for more than one week presented a toxic syndrome consisting in a severe prostration , fever , myalgias and arthralgias . In all patients presenting this syndrome , laboratory analyses revealed an elevation of alkaline phosphatase and of aspartate and alanine aminotransferases and a decrease in white blood cell and platelet counts . Three patients presented a mild proteinuria and hematuria . Although an immunological mechanism can not be ruled out , several characteristics of this reaction suggest the formation of a metabolite of zimeldine with direct cellular toxicity . The relatively high starting dose of 200 mg/day of zimeldine administered in the present study and the increment to 300 mg/day after only seven days might have contributed to the high incidence of toxic reactions observed One hundred and fifteen patients from 5 general practice s participated in a 12-week , double-blind study comparing L-tryptophan , amitriptyline , L-tryptophan-amitriptyline combination and placebo in the treatment of depression . Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo . Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups . Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups , but this difference was not significant . Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups . St and ard haematological and biochemical profiles did not alter significantly in any group , but mean heart rate was significantly increased in patients receiving amitripty 
    Output:
    
agent
Amitriptyline is an efficacious antidepressant drug .
It is , however , also associated with a number of side effects .
Degree of placebo response and severity of depression at baseline may moderate drug-placebo efficacy differences
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Prevention of relapse following depression is a pressing research problem . The authors tested the efficacy of the tricyclic antidepressant amitriptyline and psychotherapy , alone and in combination , in preventing the relapse of 150 neurotic depressed female patients . They found that patients receiving amitriptyline and little psychotherapy had a 12-percent relapse rate , compared to a 16-percent rate for those receiving more psychotherapy and no medication . There was no significant difference between drug therapy alone or drug therapy in combination with psychotherapy . However ,  psychotherapy was beneficial to patients with problems of social adjustment and interpersonal relations .  The need for further research and implication s for treatment are discussed Adinazolam , a triazolobenzodiazepine , was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives . Forty-eight patients entered the study , and 35 completed 6 weeks of evaluation . Patients were well matched in each of the groups . Initially , the adinazolam group showed more improvement than the placebo group , but this trend did not persist beyond day 7 . The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups , and final scores were significantly better for amitriptyline . Depressive symptoms in the amitriptyline dropout group appeared improved , whereas in the adinazolam and placebo dropout groups they were unchanged or worse . Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo . Thus , amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo The present report examines the predictors and modifiers of response to amitriptyline in an effort to : identify variables whose effects on drug response are general enough to apply to a range of patient types and treatment setting s , isolate predictors , and evaluate the extent to which contrasting conditions across treatment setting s may lead to contrasting predictors of treatment effects . The sample comprised moderately depressed neurotic out patients from three treatment setting s : 84 clinic patients from an outpatient clinic in a city hospital , 95 patients from the private practice of general practitioners , and 78 patients from the private practice of a group of psychiatrists . Potential predictors from which regressors in a step search multiple regression procedure could be selected were : patient demographic and attitudinal characteristics , assessment s of presenting illness and its history , and evaluations of aspects of the patient-therapist interaction Summary : To establish the differential indication of trazodone and to find the predictors of its efficacy , we conducted a study in which 45 patients with major depressive disorder and 75 patients with acute schizophrenia were r and omly assigned under double‐blind conditions to either 400 mg trazodone daily , 150 mg amitriptyline daily , 20 mg haloperidol daily , or placebo daily . At the beginning of the investigations , numerous variables ( basic data , MMPI , AMDP , HAM‐A , HAM‐D ) were documented and evaluated on days 3 , 7 , 14 , and 21 . In our study , trazodone proved to be as effective an antidepressant drug as amitriptyline . In group comparison , no antipsychotic action of trazodone in schizophrenic patients could be proved . Yet the trazodone treatment was clearly of less risk than the amitriptyline treatment . Under trazodone , provocation of schizophrenic symptoms , which occurred numerously under amitriptyline , was found only in one patient out of 17 schizophrenics . Related to anamnesis and characteristics of the schizophrenic patient , a predictor‐variable concerning the antipsychotic effect was not found . It can be assured , however , that patients with depressive symptoms  ( regarding the entity classification ) respond to trazodone . After only 7 days of trazodone treatment , a relatively reliable decision can be established as to whether a therapeutical success can be expected if treatment is continued This report examines the hypothesis that for phenelzine to be more effective than placebo it is necessary to achieve at least 80 % inhibition of platelet MAO activity . This hypothesis was examined in the context of a double-blind comparison of phenelzine , amitriptyline and placebo in depressed patients . When phenelzine became significantly more effective than placebo at 4 weeks , the average MAO inhibition was 85 % . By the 5th week , with MAO inhibition greater than 90 % , phenelzine was significantly more effective than amitriptyline . A highly significant correlation was noted between improvement and MAO inhibition within the phenelzine group The cardiovascular effects of trazodone ( TZD ) , amitriptyline ( AMT ) and placebo were studied in out- patients with major depression .  AMT was shown to have the expected effects on the electrocardiograph and on systolic time intervals consistent with its proven anticholinergic and quinidine-like properties . TZD , in contrast , had no quinidine-like effects and minor effects on systolic time intervals . However , it was not without any cardiovascular effects . Although TZD was shown to be a safer preparation than the reference drug AMT , long-term monitoring is needed to explain the minor effect on heart rate and T wave changes A controlled double-blind trial of amitriptyline at two dosage levels ( 75 and 150 mg/day ) , amylobarbitone ( 150 mg/day ) , and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness . Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups . Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety . Troublesome side effects were equally distributed among the four treatments Following a 1-week , single-blind placebo washout , 150 patients were r and omized 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 MIA is an effective antidepressant , comparable in therapeutic efficacy to the TCAs . Further , because of its weak antimuscarinic effects . Further , because of its weak antimuscarinic effects , MIA produces no significant cognitive impairment , alteration of cardiovascular function of anticholinergic side effects compared to the TCA 's . While drowsiness is the most frequently reported adverse reaction with MIA , an h.s . dosing schedule can provide relief of insomnia and improve the quality of sleep ( 47,61 ) . Therefore , because of MIA 's advantageous pharmacodynamic profile , it offers an improvement in therapeutic index over the TCAs in the treatment of depression in the elderly SIR,-We wish to record a further instance of fatal paraquat poisoning . So far as we can ascertain , this is the tenth reported fatality caused by this widely used herbicidal preparation."q In December 1965 a 42-year-old male accidentally drank a small quantity of " weed-killer "  from an  unlabelled stout bottle . It was later estimated that the quantity of fluid consumed was about threequarters of a teaspoonful . The nature of the substance could not be immediately ascertained , but it was subsequently identified as Gramaxone 19 % ' w/w paraquat ion ) by the laboratories of I.C.I. Ltd. On admission to hospital a few hours after taking the poison , the patient complained of a  burning sensation in the throat and repeated -vomiting . Despite immediate gastric lavage , prophylactic penicillin , and abundant oral and intravenous fluids , there was progressive clinical deterioration . At three days the tongue was severely ulcerated and two days later haemoptysis occurred . On the eighth day jaundice , pyrexia , tachycardia , and a blood urea of 375 mg./100 ml . were recorded . The patient died some hours later . The outst and ing necropsy findings included focal myocardial necrosis , -severe pulmonnary haemorrhage and oedema , dense eosinophilic alveolar membrane , and proliferation of fibroblast-like cells in the alveolar septa . It is apparent from this and other reports that the lethal dose of paraquat may be very small . Further fatalities will -nly be avoided by proper , care in the storage and use of this valuable -but potentially dangerous compound . A detailed and illustrated clinico-pathological report is being prepared for publication.-We are , etc . Eighty-five female depressed patients were treated for 4 weeks with amitriptyline in a flexible dose ( median , 150 mg daily ) . Predictive analyses of outcome were carried out , using both typological and regressional models based on the same 29 predictor variables . The typological prediction utilized a previously described four-group typology derived by multivariate cluster analysis and comprising psychotic depressives , anxious depressives , hostile depressives , and young depressives with personality disorder . Patients were assigned to groups by discriminant functions on the basis of scores on the predictor variables . The four groups were found to predict outcome significantly . Psychotic depressives , initially the most severely depressed , improved the most ; anxious depressives , a little less severely ill initially , showed the least improvement and the most residual illness at 4 weeks ; hostile depressives and young depressives with personality disorders , initially the least severely ill , showed intermediate improvement and were least ill , by a small margin , at 4 weeks . The 29 predictor variables also predicted outcome significantly in linear multiple regression analyses . Five variables showed regression weights significantly different from zero : high initial severity predicted high improvement but more residual illness ; initial insomnia , more previous depressions , longer illness , and hypochondriasis all predicted low improvement and more residual illness . Predictions by using typological and regression models were compared , and their interrelationships were examined . The regression prediction accounted for more variance in outcome measures than did the typology , but the statistical significance s of the regression and typological predictions were of the same order . Two variables appeared particularly important — high initial severity of illness which characterized the psychotic depresives and increased number of previous depressions which characterized the anxious depressives . Typological prediction was not solely due to these two variables in linear regression model sicne it remained significant when the outcome measure was adjusted for both by analysis of covariance . Both typological and regressional models provide useful approaches to prediction , with only limited overlap . The typological approach , which has been relatively neglected in recent years , warents more frequent application as an alternative to multiple regression Summary Forty-five patients suffering from a major depression were administered zimeldine , amitriptyline or placebo ( 15 patients in each group ) in a double-blind controlled study . In the zimeldine group , seven of the 14 patients treated for more than one week presented a toxic syndrome consisting in a severe prostration , fever , myalgias and arthralgias . In all patients presenting this syndrome , laboratory analyses revealed an elevation of alkaline phosphatase and of aspartate and alanine aminotransferases and a decrease in white blood cell and platelet counts . Three patients presented a mild proteinuria and hematuria . Although an immunological mechanism can not be ruled out , several characteristics of this reaction suggest the formation of a metabolite of zimeldine with direct cellular toxicity . The relatively high starting dose of 200 mg/day of zimeldine administered in the present study and the increment to 300 mg/day after only seven days might have contributed to the high incidence of toxic reactions observed One hundred and fifteen patients from 5 general practice s participated in a 12-week , double-blind study comparing L-tryptophan , amitriptyline , L-tryptophan-amitriptyline combination and placebo in the treatment of depression . Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo . Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups . Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups , but this difference was not significant . Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups . St and ard haematological and biochemical profiles did not alter significantly in any group , but mean heart rate was significantly increased in patients receiving amitripty 
    Output:
    