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: The authors examined dose-response relationships in 62 agoraphobic patients receiving either imipramine or placebo under double-blind conditions in conjunction with behavioral interventions .  At the end of 12 weeks , patients treated with imipramine had improved significantly more than placebo patients . Results revealed that the beneficial therapeutic effect of imipramine was dose dependent and suggested that optimal response in agoraphobia may require doses of 150 mg/day or more . The results also indicated that side effects can significantly interfere with the buildup of optimal dose in agoraphobic patients treated with imipramine . The authors briefly discuss the implication s of these findings for clinical practice and future research This study examined pretreatment factors associated with attrition from a clinical trial for panic disorder . The study group consisted of 162 patients who began 11-visit treatments .  Six domains ( demography , panic disorder severity , psychiatric comorbidity , illness/treatment attributions , coping styles , and personality styles ) with 52 variables were used to predict attrition . One hundred twenty-two patients completed and 40 dropped out from treatment . Final multivariate regression analyses showed that the following two variables were independently associated with attrition : lower household income and negative treatment attitudes ; attributing the panic disorder to life stressors and greater age were independently associated with attrition at the trend level . Preliminary analyses suggested , in addition , associations between attrition and lower education , shorter length of prior treatment , higher anxiety sensitivity , lower agoraphobic avoidance , and a coping style of seeking social support that were not confirmed by best predictor analysis . Psychiatric comorbidity and personality styles were unrelated to attrition . The implication s of these findings for future research and clinical practice are discussed Among 79 volunteer , unpaid , family doctor-referred psychiatric out patients with DSM III-R panic disorder , with and without agoraphobia , 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months . All subjects received one hour per week concurrent behavioural counselling in the acute phase . Of 13 dropouts in the first 3 weeks , 9 ( of 27 ) were on clomipramine , 2 ( of 26 ) were on lofepramine and 2 ( of 26 ) were on placebo . The high ( 30 % ) early dropout from the clomipramine group was largely due to medication intolerance . Both drugs were superior to placebo by the end of week 6 on several st and ard rating scales but not on panic attack frequency . No significant differences in efficacy were found between the two drugs tested to the end of 6 months . No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24 . The study provides evidence that both drugs , in the dosages used , are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy Objective The present study examined the prevalence of  panic disorder  with or without agoraphobia according to DSM-IV criteria in the Swedish general population . Method Data were obtained by means of a postal survey administrated to 1000 r and omly selected adults . The panic disorder module of the World Health Organization 's Composite International Diagnostic Interview ( CIDI ) was included in the survey . Results 12-month prevalence was estimated at 2.2 % ( CI 95 % 1.02 % – 3.38 % ) . There was a significant sex difference , with a greater prevalence for women ( 5.6 % ) compared to men ( 1 % ) . Conclusion The Swedish panic disorder prevalence is relatively consistent with findings in most other parts of the western world In a controlled- outcome study of phobias , 218 adult phobic patients ( 147 women and 71 men ) received a course of 26 weekly treatment sessions that consisted of behavior therapy ( BT ) and imipramine hydrochloride , BT and placebo , or supportive psychotherapy and imipramine . The BT consisted of systematic desentization using fantasy and assertiveness training .  Patients were classified as agoraphobic , mixed phobic , or simple phobic . Although the conditions of most patients in each group showed moderate to marked improvement , the effects of imipramine were significantly superior to those of placebo in patients with spontaneous panic attacks , ie , patients with agoraphobia or mixed phobia . In patients with simple phobia , who do not experience spontaneous panic , there was not a significant difference between imipramine and placebo . This study clearly distinguished those phobic patients who experienced spontaneous panic from those who did not in terms of pharmacologic benefits Thirty-seven severely-disabled agoraphobics were r and omly assigned to ( 1 ) Imipramine-no exposure . ( 2 ) Imipramine + exposure or ( 3 ) Placebo + exposure groups . To provide a more stringent test of the pharmacological effects of imipramine independent of exposure to phobic stimuli , Ss in the Imipramine-no exposure condition received antiexposure instructions during the first 8 weeks of therapy . Assessment s were conducted at 0 , 8 and 26 weeks . At 8 weeks , the group receiving imipramine combined with exposure therapy displayed more improvement than the other two groups , and was the only group to show a reduction in panic attacks . Ss receiving imipramine with antiexposure instructions showed little improvement on phobic indices , no reduction in panic , but significant improvement in anxiety and dysphoric mood . At 26 weeks Ss receiving the combined imipramine + exposure treatment exhibited further improvement result ing in a significant superiority of Imipramine + exposure over Placebo + exposure across a number of different outcome indices . Ss who had received imipramine with antiexposure instructions showed some improvement during the subsequent 18 weeks in which the antiexposure instructions were no longer in effect . However , neither this group nor the Placebo + exposure group showed a reduction in panic attacks . The results of the present trial provide support for the beneficial effects of combining intensive exposure with imipramine , but call into question the thesis that imipramine exerts its effect through a pharmacological blocking of panic attacks . Alternative hypotheses concerning the mode of action of imipramine are presented We explored a causal sequence between panic and avoidance to provide recommendations for psychotherapy , pharmacotherapy , and their combination in treating agoraphobia . We produced a two-way [ ( imipramine hydrochloride vs placebo ] by [ office-based behavioral therapy vs in vivo exposure ] ) design by amalgamating two studies . We assessed agoraphobic patients for panic and avoidance at these time points : baseline ( week 0 ) , midcourse ( week 13 ) , and termination ( week 26 ) . The causal sequence model was tested by path analysis . Imipramine was superior to placebo in lowering panic and avoidance at both postbaseline time points . Exposure was superior to office-based treatment in lowering avoidance only at week 13 . Exposure appeared to produce quicker improvement of avoidance than office-based therapy , but relapse occurred if this improvement was not supported by medication . Exposure did not benefit panic . We believe patients should be informed that imipramine is superior to exposure in inducing a panic-free state . Exposure without imipramine is of benefit only in reducing avoidance , but adding imipramine to exposure is necessary for panic control and substantially improves exposure and exposure maintenance The issue of panic disorder resistant to treatment ( whether pharmacological or psychological ) has attracted little research attention , despite its clinical frequency and importance . The aim of this study was to compare three treatment modalities , namely exposure alone ( E ) , exposure associated with imipramine ( EI ) and cognitive therapy supplementing exposure ( EC ) , in a sample of 21 patients with DSM‐IV panic disorder and agoraphobia , who failed to respond to a first st and ard course of individual behavioural treatment based on exposure in vivo . Treatments were administered according to a cross‐over , controlled design ( E‐EI‐EC , EI‐EC‐E , EC‐E‐EI ) . Twelve of the 21 patients  achieved remission ( panic‐free status ) during the trial . In 8 cases this occurred after exposure alone ( E ) and in two cases each after the other treatments ( EI and EC ) . The results revealed a significant effect of the factor time on a number of variables , and the superiority of exposure alone compared to other treatment modalities with regard to some variables . These findings suggest that long‐term behavioural treatment based on exposure may be necessary in some patients , and may induce clinical remission . However , patients who do not respond to exposure show poor tolerance of and compliance with pharmacological treatment , and are unlikely to achieve remission  with imipramine or cognitive therapy , even though this may occur in individual cases OBJECTIVE Whereas the fact of attrition during the course of treatment is well documented , little is known about the factors that affect sample selection before the beginning of a study ( " pretreatment attrition " ) . The present study reports on the degree and sources of pretreatment attrition at two sites of a multicenter study on panic disorder that compared treatment outcomes for imipramine and cognitive behavior therapy . METHOD Data were collected at two clinical research sites , one with a pharmacological treatment orientation ( N = 420 ) and one with a psychosocial treatment orientation ( N = 208 ) . RESULTS The main source of pretreatment attrition was participant refusal . At both research sites , eligible patients most often refused participation because they were either unwilling to start treatment with imipramine ( 30.6 % and 47.4 % , respectively ) or discontinue their current medication ( 22.6 % and 35.1 % , respectively ) . CONCLUSIONS Results from comparative treatment outcome studies are limited not only to people who meet the study criteria but also to those who are willing to begin a medication treatment and discontinue their current medication Sixty out- patients with severe agoraphobia took part in a controlled prospect i ve clinical trial of combinations of methohexitone-assisted and st and ard systematic desensitization and monoamine oxidase inhibitor . Severity of agoraphobia in terms of avoidance and anxiety was rated both by the patients themselves and by an independent assessor during the eight weeks of treatment . The monoamine oxidase inhibitor produced a significant reduction in severity of anxiety but not of avoidance .  Methohexitone-assisted systematic desensitization appeared to produce significantly greater improvement than either st and ard systematic desensitization or no systematic desensitization in both anxiety and avoidance . Assessors ' ratings showed that the monoamine oxidase inhibitor used in conjunction with methohexitone-assisted systematic desnsitization produced slightly greater clinical improvement than the other treatment combinations A large number of studies suggest that individual characteristics of psychotherapists affect the outcome of  psychosocial treatments  for psychiatric illness , but little work has been done to see if this is also the case for pharmacotherapy . In the context of a multicenter study that compared psychosocial and medication treatments for panic disorder , we assessed whether such characteristics as age of the psychiatrist , number of years of experience , and gender influence the outcome of treatment with the antipanic drug imipramine . Data were examined by multiple and logistic regression analyses for eight psychiatrists who treated a total of 57 patients with panic disorder . More physician experience , measured as years since completing residency , was associated with better response to imipramine on one of two main dichotomous measures ( the Clinical Global Impression-Improvement Scale ) and on six of nine continuous measure rating scales . Associations between psychiatrist age and outcome and between psychiatrist gender and outcome were also present but on fewer measures . Although these are post-hoc analyses that were not planned when the multicenter study was originally design ed and therefore there are limitations in the information available about the psychiatrists ' characteristics , the findings suggest that even in the context of a clinical trial that employs a specific protocol and single medication , physician experience may influence patient outcome . Depression and Anxiety 17:88 - 93 , 2003 A double-blind study was carried out on 40 agoraphobic and socially phobic patients , matched , then r and omly assigned to one of four treatment groups ; phenelzine-exposure , phenelzine-no exposure , placebo-exposure , and placebo-no exposure . Exposure consisted of encouraging the patient to face the phobic situation a predetermined number of times . Assessment s , made at the beginning and end of 8 weeks of therapy and 8 weeks thereafter , showed that the phobia ratings of groups decreased significantly . The combined exposure group improved significantly more than the combined no exposure group during treatment . At 8 weeks follow-up there was some deterioration in the phenelzine-exposure and placebo-no exposure groups . Exposure , with or without phenelzine , was the superior treatment modality . The antiphobic effect of phenelzine was not supported , although it seemed to reduce subjective anxiety during exposure experiences . The possibility that effect of phenelzine is dose-related is discussed BACKGROUND Panic disorder , with and without agoraphobia , is a prevalent condition which presents primarily in general practice . Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital setting s , and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care . AIM To evaluate the outcome , in a primary care setting , of fluvoxamine versus cognitive behaviour therapy , each used alone and in combination in a double-blind placebo-controlled framework , balanced for therapist contact . METHOD A total of 149 patients satisfying DSMIII-R criteria for panic dis 
    Output:
    
agent
After the acute phase treatment , as long as the drug was continued , the superiority of the combination over either monotherapy appeared to persist .
***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: The authors examined dose-response relationships in 62 agoraphobic patients receiving either imipramine or placebo under double-blind conditions in conjunction with behavioral interventions .  At the end of 12 weeks , patients treated with imipramine had improved significantly more than placebo patients . Results revealed that the beneficial therapeutic effect of imipramine was dose dependent and suggested that optimal response in agoraphobia may require doses of 150 mg/day or more . The results also indicated that side effects can significantly interfere with the buildup of optimal dose in agoraphobic patients treated with imipramine . The authors briefly discuss the implication s of these findings for clinical practice and future research This study examined pretreatment factors associated with attrition from a clinical trial for panic disorder . The study group consisted of 162 patients who began 11-visit treatments .  Six domains ( demography , panic disorder severity , psychiatric comorbidity , illness/treatment attributions , coping styles , and personality styles ) with 52 variables were used to predict attrition . One hundred twenty-two patients completed and 40 dropped out from treatment . Final multivariate regression analyses showed that the following two variables were independently associated with attrition : lower household income and negative treatment attitudes ; attributing the panic disorder to life stressors and greater age were independently associated with attrition at the trend level . Preliminary analyses suggested , in addition , associations between attrition and lower education , shorter length of prior treatment , higher anxiety sensitivity , lower agoraphobic avoidance , and a coping style of seeking social support that were not confirmed by best predictor analysis . Psychiatric comorbidity and personality styles were unrelated to attrition . The implication s of these findings for future research and clinical practice are discussed Among 79 volunteer , unpaid , family doctor-referred psychiatric out patients with DSM III-R panic disorder , with and without agoraphobia , 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months . All subjects received one hour per week concurrent behavioural counselling in the acute phase . Of 13 dropouts in the first 3 weeks , 9 ( of 27 ) were on clomipramine , 2 ( of 26 ) were on lofepramine and 2 ( of 26 ) were on placebo . The high ( 30 % ) early dropout from the clomipramine group was largely due to medication intolerance . Both drugs were superior to placebo by the end of week 6 on several st and ard rating scales but not on panic attack frequency . No significant differences in efficacy were found between the two drugs tested to the end of 6 months . No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24 . The study provides evidence that both drugs , in the dosages used , are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy Objective The present study examined the prevalence of  panic disorder  with or without agoraphobia according to DSM-IV criteria in the Swedish general population . Method Data were obtained by means of a postal survey administrated to 1000 r and omly selected adults . The panic disorder module of the World Health Organization 's Composite International Diagnostic Interview ( CIDI ) was included in the survey . Results 12-month prevalence was estimated at 2.2 % ( CI 95 % 1.02 % – 3.38 % ) . There was a significant sex difference , with a greater prevalence for women ( 5.6 % ) compared to men ( 1 % ) . Conclusion The Swedish panic disorder prevalence is relatively consistent with findings in most other parts of the western world In a controlled- outcome study of phobias , 218 adult phobic patients ( 147 women and 71 men ) received a course of 26 weekly treatment sessions that consisted of behavior therapy ( BT ) and imipramine hydrochloride , BT and placebo , or supportive psychotherapy and imipramine . The BT consisted of systematic desentization using fantasy and assertiveness training .  Patients were classified as agoraphobic , mixed phobic , or simple phobic . Although the conditions of most patients in each group showed moderate to marked improvement , the effects of imipramine were significantly superior to those of placebo in patients with spontaneous panic attacks , ie , patients with agoraphobia or mixed phobia . In patients with simple phobia , who do not experience spontaneous panic , there was not a significant difference between imipramine and placebo . This study clearly distinguished those phobic patients who experienced spontaneous panic from those who did not in terms of pharmacologic benefits Thirty-seven severely-disabled agoraphobics were r and omly assigned to ( 1 ) Imipramine-no exposure . ( 2 ) Imipramine + exposure or ( 3 ) Placebo + exposure groups . To provide a more stringent test of the pharmacological effects of imipramine independent of exposure to phobic stimuli , Ss in the Imipramine-no exposure condition received antiexposure instructions during the first 8 weeks of therapy . Assessment s were conducted at 0 , 8 and 26 weeks . At 8 weeks , the group receiving imipramine combined with exposure therapy displayed more improvement than the other two groups , and was the only group to show a reduction in panic attacks . Ss receiving imipramine with antiexposure instructions showed little improvement on phobic indices , no reduction in panic , but significant improvement in anxiety and dysphoric mood . At 26 weeks Ss receiving the combined imipramine + exposure treatment exhibited further improvement result ing in a significant superiority of Imipramine + exposure over Placebo + exposure across a number of different outcome indices . Ss who had received imipramine with antiexposure instructions showed some improvement during the subsequent 18 weeks in which the antiexposure instructions were no longer in effect . However , neither this group nor the Placebo + exposure group showed a reduction in panic attacks . The results of the present trial provide support for the beneficial effects of combining intensive exposure with imipramine , but call into question the thesis that imipramine exerts its effect through a pharmacological blocking of panic attacks . Alternative hypotheses concerning the mode of action of imipramine are presented We explored a causal sequence between panic and avoidance to provide recommendations for psychotherapy , pharmacotherapy , and their combination in treating agoraphobia . We produced a two-way [ ( imipramine hydrochloride vs placebo ] by [ office-based behavioral therapy vs in vivo exposure ] ) design by amalgamating two studies . We assessed agoraphobic patients for panic and avoidance at these time points : baseline ( week 0 ) , midcourse ( week 13 ) , and termination ( week 26 ) . The causal sequence model was tested by path analysis . Imipramine was superior to placebo in lowering panic and avoidance at both postbaseline time points . Exposure was superior to office-based treatment in lowering avoidance only at week 13 . Exposure appeared to produce quicker improvement of avoidance than office-based therapy , but relapse occurred if this improvement was not supported by medication . Exposure did not benefit panic . We believe patients should be informed that imipramine is superior to exposure in inducing a panic-free state . Exposure without imipramine is of benefit only in reducing avoidance , but adding imipramine to exposure is necessary for panic control and substantially improves exposure and exposure maintenance The issue of panic disorder resistant to treatment ( whether pharmacological or psychological ) has attracted little research attention , despite its clinical frequency and importance . The aim of this study was to compare three treatment modalities , namely exposure alone ( E ) , exposure associated with imipramine ( EI ) and cognitive therapy supplementing exposure ( EC ) , in a sample of 21 patients with DSM‐IV panic disorder and agoraphobia , who failed to respond to a first st and ard course of individual behavioural treatment based on exposure in vivo . Treatments were administered according to a cross‐over , controlled design ( E‐EI‐EC , EI‐EC‐E , EC‐E‐EI ) . Twelve of the 21 patients  achieved remission ( panic‐free status ) during the trial . In 8 cases this occurred after exposure alone ( E ) and in two cases each after the other treatments ( EI and EC ) . The results revealed a significant effect of the factor time on a number of variables , and the superiority of exposure alone compared to other treatment modalities with regard to some variables . These findings suggest that long‐term behavioural treatment based on exposure may be necessary in some patients , and may induce clinical remission . However , patients who do not respond to exposure show poor tolerance of and compliance with pharmacological treatment , and are unlikely to achieve remission  with imipramine or cognitive therapy , even though this may occur in individual cases OBJECTIVE Whereas the fact of attrition during the course of treatment is well documented , little is known about the factors that affect sample selection before the beginning of a study ( " pretreatment attrition " ) . The present study reports on the degree and sources of pretreatment attrition at two sites of a multicenter study on panic disorder that compared treatment outcomes for imipramine and cognitive behavior therapy . METHOD Data were collected at two clinical research sites , one with a pharmacological treatment orientation ( N = 420 ) and one with a psychosocial treatment orientation ( N = 208 ) . RESULTS The main source of pretreatment attrition was participant refusal . At both research sites , eligible patients most often refused participation because they were either unwilling to start treatment with imipramine ( 30.6 % and 47.4 % , respectively ) or discontinue their current medication ( 22.6 % and 35.1 % , respectively ) . CONCLUSIONS Results from comparative treatment outcome studies are limited not only to people who meet the study criteria but also to those who are willing to begin a medication treatment and discontinue their current medication Sixty out- patients with severe agoraphobia took part in a controlled prospect i ve clinical trial of combinations of methohexitone-assisted and st and ard systematic desensitization and monoamine oxidase inhibitor . Severity of agoraphobia in terms of avoidance and anxiety was rated both by the patients themselves and by an independent assessor during the eight weeks of treatment . The monoamine oxidase inhibitor produced a significant reduction in severity of anxiety but not of avoidance .  Methohexitone-assisted systematic desensitization appeared to produce significantly greater improvement than either st and ard systematic desensitization or no systematic desensitization in both anxiety and avoidance . Assessors ' ratings showed that the monoamine oxidase inhibitor used in conjunction with methohexitone-assisted systematic desnsitization produced slightly greater clinical improvement than the other treatment combinations A large number of studies suggest that individual characteristics of psychotherapists affect the outcome of  psychosocial treatments  for psychiatric illness , but little work has been done to see if this is also the case for pharmacotherapy . In the context of a multicenter study that compared psychosocial and medication treatments for panic disorder , we assessed whether such characteristics as age of the psychiatrist , number of years of experience , and gender influence the outcome of treatment with the antipanic drug imipramine . Data were examined by multiple and logistic regression analyses for eight psychiatrists who treated a total of 57 patients with panic disorder . More physician experience , measured as years since completing residency , was associated with better response to imipramine on one of two main dichotomous measures ( the Clinical Global Impression-Improvement Scale ) and on six of nine continuous measure rating scales . Associations between psychiatrist age and outcome and between psychiatrist gender and outcome were also present but on fewer measures . Although these are post-hoc analyses that were not planned when the multicenter study was originally design ed and therefore there are limitations in the information available about the psychiatrists ' characteristics , the findings suggest that even in the context of a clinical trial that employs a specific protocol and single medication , physician experience may influence patient outcome . Depression and Anxiety 17:88 - 93 , 2003 A double-blind study was carried out on 40 agoraphobic and socially phobic patients , matched , then r and omly assigned to one of four treatment groups ; phenelzine-exposure , phenelzine-no exposure , placebo-exposure , and placebo-no exposure . Exposure consisted of encouraging the patient to face the phobic situation a predetermined number of times . Assessment s , made at the beginning and end of 8 weeks of therapy and 8 weeks thereafter , showed that the phobia ratings of groups decreased significantly . The combined exposure group improved significantly more than the combined no exposure group during treatment . At 8 weeks follow-up there was some deterioration in the phenelzine-exposure and placebo-no exposure groups . Exposure , with or without phenelzine , was the superior treatment modality . The antiphobic effect of phenelzine was not supported , although it seemed to reduce subjective anxiety during exposure experiences . The possibility that effect of phenelzine is dose-related is discussed BACKGROUND Panic disorder , with and without agoraphobia , is a prevalent condition which presents primarily in general practice . Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital setting s , and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care . AIM To evaluate the outcome , in a primary care setting , of fluvoxamine versus cognitive behaviour therapy , each used alone and in combination in a double-blind placebo-controlled framework , balanced for therapist contact . METHOD A total of 149 patients satisfying DSMIII-R criteria for panic dis 
    Output:
    