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: BACKGROUND Posttraumatic stress disorder ( PTSD ) frequently co-occurs with alcohol use disorders . This study investigated the use of sertraline , a serotonin reuptake inhibitor , in treating co-occurring symptoms of alcohol dependence and PTSD . METHODS A total of 94 individuals with current alcohol dependence and PTSD were r and omly assigned to receive sertraline ( 150 mg/day ) or placebo for 12 weeks . Post hoc cluster analysis of baseline characteristics was used to define subgroups of participants . RESULTS There was a significant decrease in alcohol use during the trial in both the sertraline and the placebo groups . Cluster analysis revealed significant medication group by cluster interactions for alcohol-related outcomes . Sertraline-treated participants with less severe alcohol dependence and early-onset PTSD had significantly fewer drinks per drinking day ( p < 0.001 ) . For participants with more severe alcohol dependence and later onset PTSD , the placebo group had significantly greater decreases in drinks per drinking day ( p < 0.01 ) and average number of drinks consumed per day ( p < 0.05 ) . CONCLUSIONS There may be subtypes of alcohol-dependent individuals who respond differently to serotonin reuptake inhibitor treatment . Further investigation of differential responders may lead to improvements in the pharmacological treatment of co-occurring alcohol dependence and PTSD Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder ( PTSD ) symptoms , we conducted a 10-week , double-blind , placebo-controlled evaluation in which 15 patients were r and omized 2 : 1 to either  olanzapine or placebo . The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day . Eleven patients completed the study . Patients in both groups showed improvement in PTSD symptoms , but no between-group differences in treatment response were observed and a high placebo response rate was found . Both treatments were tolerated well , although the olanzapine treatment group had more weight gain . Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD . The lack of difference between olanzapine and placebo may in part be due to olanzapine 's not being effective in PTSD or , alternatively , a small sample size , a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients Nefazodone is a unique serotonergic antidepressant that acts as both a presynaptic serotonin reuptake inhibitor and a postsynaptic 5-hydroxytryptamine 2A receptor antagonist . Based on the positive results of open-label trials of nefazodone , including one from our group , we tested nefazodone 's efficacy in the treatment of posttraumatic stress disorder ( PTSD ) under placebo-controlled conditions . Forty-one patients with chronic PTSD , predominantly male combat veterans , were enrolled in a r and omized , double-blind , placebo-controlled 12-week trial of nefazodone . The primary outcome measure was the Clinician-Administered PTSD Scale .  Fifteen patients were r and omized to placebo and 26 were r and omized to nefazodone .  In a repeated- measures analysis of variance with last observation carried forward , patients on nefazodone showed a significant improvement in the percentage change of Clinician-Administered PTSD Scale Total score from baseline compared with those on placebo ( P = 0.04 ; effect size = 0.6 ) . Sample size was not powered to test group differences in the Clinician-Administered PTSD Scale criterion B , C , or D subscale . However , the criterion D subscale showed significant improvement in patients treated with nefazodone compared with those treated with placebo ( P = 0.007 ) . In addition , the Hamilton Rating Scale for Depression showed significant improvement compared with placebo ( P = 0.008 ) . The nefazodone group also reported an improvement on the PTSD Checklist ( self-report scale ; P = 0.08 ) and the Clinician-Administered Dissociative States Scale ( P = 0.06 ) . This pilot study supports the efficacy of nefazodone for the treatment of PTSD . However , larger placebo-controlled studies in more diverse patient population are warranted OBJECTIVE This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder ( PTSD ) . METHOD Out patients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale , part 2 , were r and omly assigned to take placebo ( N=186 ) , 20 mg/day of paroxetine ( N=183 ) , or 40 mg/day of paroxetine ( N=182 ) for 12 weeks . Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale , part 2 , and rates of response ( " very much improved " or " much improved " ) for global improvement on the Clinical Global Impression scale . RESULTS Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis . Moreover , paroxetine treatment result ed in statistically significant improvement compared to placebo on all three PTSD symptom clusters ( reexperiencing , avoidance/numbing , and hyperarousal ) , social and occupational impairment , and comorbid depression .  Paroxetine was effective for both men and women . Treatment response did not vary by trauma type , time since trauma , or severity of baseline PTSD or depressive symptoms . Both doses were well tolerated . CONCLUSIONS Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD Eighteen male U.S. veterans meeting DSM-III criteria for posttraumatic stress disorder ( PTSD ) completed a 4-week double-blind , crossover study comparing administration of 200 mg/day of desipramine with placebo . Response was measured by using the Beck Depression Inventory , the Hamilton Rating Scale for Depression , the Hamilton Rating Scale for Anxiety , and the Impact of Event Scale . Overall , the only apparent response to desipramine was in some symptoms of depression ; there were no changes in anxiety and other PTSD symptoms BACKGROUND The anticonvulsant , lamotrigine , may be useful for symptom management in PTSD . METHODS Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo .  Patients were r and omized 2:1 to either lamotrigine or placebo . Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated . RESULTS Fifteen subjects entered treatment , fourteen of whom returned for subsequent visits . Of 10 patients who received lamotrigine , 5 ( 50 % ) responded according to the DGRP , compared to 1 of 4 ( 25 % ) who received placebo . Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients . Treatments were generally well tolerated . CONCLUSIONS Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD . These promising results warrant further large sample double-blind , placebo-controlled trials BACKGROUND The objective of this double-blind , placebo-controlled study was to investigate the efficacy and safety of paroxetine in out patients with posttraumatic stress disorder ( PTSD ) . METHOD Male and female out patients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale ( CAPS-2 ) were r and omly assigned to treatment with paroxetine ( 20 - 50 mg/day ) or placebo for 12 weeks . The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale ( CGI-1 ) . Additional key outcome measures were the change from baseline in the reexperiencing , avoidance/ numbing , and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale ( SDS ) . Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale . The proportion of patients achieving response and remission was also determined . RESULTS 307 patients constituted the intent-to-treat population . At week 12 , compared with the placebo group ( N = 156 ) , the paroxetine group ( N = 151 ) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures . Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 ( p < .05 ) , and significantly greater proportions of paroxetine-treated patients achieved response ( p < .001 ) and remission ( p = .008 ) by week 12 . The improvement in PTSD symptoms was similar in male and female patients . Functional improvement at the study endpoint was significantly greater ( p < .05 ) in the paroxetine group in all 3 domains of the SDS ( work , social life , family life ) . Treatment with paroxetine was well tolerated , with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication . CONCLUSION Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD . Improvement is obtained for all 3 symptom clusters ( reexperiencing , avoidance/numbing , hyperarousal ) and is associated with significant reduction in disability after 12 weeks of treatment Effects of double-blind treatment of chronic posttraumatic stress disorder ( PTSD ) with 2 SSRIs and placebo on emotional symptoms and autonomic reactivity were assessed prospect ively . PTSD subjects received citalopram ( n=25 ) , sertraline ( n=23 ) , or placebo ( n=10 ) for 10 weeks , with psychophysiologic assessment s performed before and after treatment . Intent-to-treat analysis showed that all treatment groups improved significantly in total symptoms of PTSD ( as measured by the Clinician Administered PTSD Scale ) , all 3 PTSD symptom clusters , and sleep time . However , subtle differences in improvements in PTSD symptom clusters , physiologic reactivity , and reported adverse events were identified . Citalopram treated subjects significantly lowered systolic and diastolic blood pressures , while sertraline and placebo treated patients significantly lowered only systolic blood pressure reactivity to individualized trauma scripts . The sertraline group showed significantly more improvement in avoidance/numbing symptoms than both other groups . Considering side effects , subjects on sertraline reported more gastrointestinal problems , with early terminators having more insomnia . Early terminators on citalopram reported more fatigue and appetite changes than other treatment groups , with completers reporting more sexual dysfunction . Results support a class effect of SSRIs in treating PTSD symptoms , but suggest a possible differential effect of drugs on symptom clusters , physiologic parameters , and side effects that may have clinical relevance . Implication s of symptom reduction noted in the smaller placebo group are discussed relative to recent concerns about increasing placebo response in clinical trials BACKGROUND Based on an earlier pilot study , as well as a theoretical consideration of its mechanism of action , we undertook a placebo-controlled , double-blind trial of mirtazapine in posttraumatic stress disorder . METHODS Twenty-nine patients were r and omized to receive  drug  up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks , with data being available for analysis in 26 . Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview ( SPRINT ) Global Improvement item and total score . Secondary measures comprised the Davidson Trauma Scale , Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale . Adverse events were also measured . RESULTS On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure , rates of response were 64.7 % and 20.0 % for mirtazapine and placebo . Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global , Structured Interview for Posttraumatic Stress Disorder , and Hospital Anxiety Depression Scale anxiety subscale scores . The drug was well tolerated . CONCLUSIONS Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms This was a multicenter , r and omized , double-blind , parallel trial conducted in out patients in three countries . Following screening and placebo washout , patients received brofaromine ( a combined MAO-A inhibitor/5-HT transport inhibitor ) or placebo in a flexible dosing design . Based upon the CAPS , a st and ardized post-traumatic stress disorder ( PTSD ) interview , findings from a cohort involving both subchronic and chronic traumatic stress margin 
    Output:
    
agent
Of the medication classes , evidence of treatment efficacy was most convincing for the SSRIs .
In addition , medication was superior to placebo in reducing  comorbid depression and disability .
Medication was also less well tolerated than placebo .
A narrative review of the 3 maintenance trials suggested that long-term medication may be required in treating PTSD .
CONCLUSION Medication treatments can be effective in treating PTSD , acting to reduce its core symptoms , as well as associated depression and disability , and should be considered as part of the treatment of this disorder .
The findings of this review support the status of SSRIs as first-line agents in the pharmacotherapy of PTSD , as well as their value in longterm treatment .
***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: BACKGROUND Posttraumatic stress disorder ( PTSD ) frequently co-occurs with alcohol use disorders . This study investigated the use of sertraline , a serotonin reuptake inhibitor , in treating co-occurring symptoms of alcohol dependence and PTSD . METHODS A total of 94 individuals with current alcohol dependence and PTSD were r and omly assigned to receive sertraline ( 150 mg/day ) or placebo for 12 weeks . Post hoc cluster analysis of baseline characteristics was used to define subgroups of participants . RESULTS There was a significant decrease in alcohol use during the trial in both the sertraline and the placebo groups . Cluster analysis revealed significant medication group by cluster interactions for alcohol-related outcomes . Sertraline-treated participants with less severe alcohol dependence and early-onset PTSD had significantly fewer drinks per drinking day ( p < 0.001 ) . For participants with more severe alcohol dependence and later onset PTSD , the placebo group had significantly greater decreases in drinks per drinking day ( p < 0.01 ) and average number of drinks consumed per day ( p < 0.05 ) . CONCLUSIONS There may be subtypes of alcohol-dependent individuals who respond differently to serotonin reuptake inhibitor treatment . Further investigation of differential responders may lead to improvements in the pharmacological treatment of co-occurring alcohol dependence and PTSD Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder ( PTSD ) symptoms , we conducted a 10-week , double-blind , placebo-controlled evaluation in which 15 patients were r and omized 2 : 1 to either  olanzapine or placebo . The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day . Eleven patients completed the study . Patients in both groups showed improvement in PTSD symptoms , but no between-group differences in treatment response were observed and a high placebo response rate was found . Both treatments were tolerated well , although the olanzapine treatment group had more weight gain . Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD . The lack of difference between olanzapine and placebo may in part be due to olanzapine 's not being effective in PTSD or , alternatively , a small sample size , a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients Nefazodone is a unique serotonergic antidepressant that acts as both a presynaptic serotonin reuptake inhibitor and a postsynaptic 5-hydroxytryptamine 2A receptor antagonist . Based on the positive results of open-label trials of nefazodone , including one from our group , we tested nefazodone 's efficacy in the treatment of posttraumatic stress disorder ( PTSD ) under placebo-controlled conditions . Forty-one patients with chronic PTSD , predominantly male combat veterans , were enrolled in a r and omized , double-blind , placebo-controlled 12-week trial of nefazodone . The primary outcome measure was the Clinician-Administered PTSD Scale .  Fifteen patients were r and omized to placebo and 26 were r and omized to nefazodone .  In a repeated- measures analysis of variance with last observation carried forward , patients on nefazodone showed a significant improvement in the percentage change of Clinician-Administered PTSD Scale Total score from baseline compared with those on placebo ( P = 0.04 ; effect size = 0.6 ) . Sample size was not powered to test group differences in the Clinician-Administered PTSD Scale criterion B , C , or D subscale . However , the criterion D subscale showed significant improvement in patients treated with nefazodone compared with those treated with placebo ( P = 0.007 ) . In addition , the Hamilton Rating Scale for Depression showed significant improvement compared with placebo ( P = 0.008 ) . The nefazodone group also reported an improvement on the PTSD Checklist ( self-report scale ; P = 0.08 ) and the Clinician-Administered Dissociative States Scale ( P = 0.06 ) . This pilot study supports the efficacy of nefazodone for the treatment of PTSD . However , larger placebo-controlled studies in more diverse patient population are warranted OBJECTIVE This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder ( PTSD ) . METHOD Out patients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale , part 2 , were r and omly assigned to take placebo ( N=186 ) , 20 mg/day of paroxetine ( N=183 ) , or 40 mg/day of paroxetine ( N=182 ) for 12 weeks . Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale , part 2 , and rates of response ( " very much improved " or " much improved " ) for global improvement on the Clinical Global Impression scale . RESULTS Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis . Moreover , paroxetine treatment result ed in statistically significant improvement compared to placebo on all three PTSD symptom clusters ( reexperiencing , avoidance/numbing , and hyperarousal ) , social and occupational impairment , and comorbid depression .  Paroxetine was effective for both men and women . Treatment response did not vary by trauma type , time since trauma , or severity of baseline PTSD or depressive symptoms . Both doses were well tolerated . CONCLUSIONS Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD Eighteen male U.S. veterans meeting DSM-III criteria for posttraumatic stress disorder ( PTSD ) completed a 4-week double-blind , crossover study comparing administration of 200 mg/day of desipramine with placebo . Response was measured by using the Beck Depression Inventory , the Hamilton Rating Scale for Depression , the Hamilton Rating Scale for Anxiety , and the Impact of Event Scale . Overall , the only apparent response to desipramine was in some symptoms of depression ; there were no changes in anxiety and other PTSD symptoms BACKGROUND The anticonvulsant , lamotrigine , may be useful for symptom management in PTSD . METHODS Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo .  Patients were r and omized 2:1 to either lamotrigine or placebo . Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated . RESULTS Fifteen subjects entered treatment , fourteen of whom returned for subsequent visits . Of 10 patients who received lamotrigine , 5 ( 50 % ) responded according to the DGRP , compared to 1 of 4 ( 25 % ) who received placebo . Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients . Treatments were generally well tolerated . CONCLUSIONS Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD . These promising results warrant further large sample double-blind , placebo-controlled trials BACKGROUND The objective of this double-blind , placebo-controlled study was to investigate the efficacy and safety of paroxetine in out patients with posttraumatic stress disorder ( PTSD ) . METHOD Male and female out patients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale ( CAPS-2 ) were r and omly assigned to treatment with paroxetine ( 20 - 50 mg/day ) or placebo for 12 weeks . The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale ( CGI-1 ) . Additional key outcome measures were the change from baseline in the reexperiencing , avoidance/ numbing , and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale ( SDS ) . Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale . The proportion of patients achieving response and remission was also determined . RESULTS 307 patients constituted the intent-to-treat population . At week 12 , compared with the placebo group ( N = 156 ) , the paroxetine group ( N = 151 ) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures . Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 ( p < .05 ) , and significantly greater proportions of paroxetine-treated patients achieved response ( p < .001 ) and remission ( p = .008 ) by week 12 . The improvement in PTSD symptoms was similar in male and female patients . Functional improvement at the study endpoint was significantly greater ( p < .05 ) in the paroxetine group in all 3 domains of the SDS ( work , social life , family life ) . Treatment with paroxetine was well tolerated , with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication . CONCLUSION Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD . Improvement is obtained for all 3 symptom clusters ( reexperiencing , avoidance/numbing , hyperarousal ) and is associated with significant reduction in disability after 12 weeks of treatment Effects of double-blind treatment of chronic posttraumatic stress disorder ( PTSD ) with 2 SSRIs and placebo on emotional symptoms and autonomic reactivity were assessed prospect ively . PTSD subjects received citalopram ( n=25 ) , sertraline ( n=23 ) , or placebo ( n=10 ) for 10 weeks , with psychophysiologic assessment s performed before and after treatment . Intent-to-treat analysis showed that all treatment groups improved significantly in total symptoms of PTSD ( as measured by the Clinician Administered PTSD Scale ) , all 3 PTSD symptom clusters , and sleep time . However , subtle differences in improvements in PTSD symptom clusters , physiologic reactivity , and reported adverse events were identified . Citalopram treated subjects significantly lowered systolic and diastolic blood pressures , while sertraline and placebo treated patients significantly lowered only systolic blood pressure reactivity to individualized trauma scripts . The sertraline group showed significantly more improvement in avoidance/numbing symptoms than both other groups . Considering side effects , subjects on sertraline reported more gastrointestinal problems , with early terminators having more insomnia . Early terminators on citalopram reported more fatigue and appetite changes than other treatment groups , with completers reporting more sexual dysfunction . Results support a class effect of SSRIs in treating PTSD symptoms , but suggest a possible differential effect of drugs on symptom clusters , physiologic parameters , and side effects that may have clinical relevance . Implication s of symptom reduction noted in the smaller placebo group are discussed relative to recent concerns about increasing placebo response in clinical trials BACKGROUND Based on an earlier pilot study , as well as a theoretical consideration of its mechanism of action , we undertook a placebo-controlled , double-blind trial of mirtazapine in posttraumatic stress disorder . METHODS Twenty-nine patients were r and omized to receive  drug  up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks , with data being available for analysis in 26 . Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview ( SPRINT ) Global Improvement item and total score . Secondary measures comprised the Davidson Trauma Scale , Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale . Adverse events were also measured . RESULTS On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure , rates of response were 64.7 % and 20.0 % for mirtazapine and placebo . Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global , Structured Interview for Posttraumatic Stress Disorder , and Hospital Anxiety Depression Scale anxiety subscale scores . The drug was well tolerated . CONCLUSIONS Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms This was a multicenter , r and omized , double-blind , parallel trial conducted in out patients in three countries . Following screening and placebo washout , patients received brofaromine ( a combined MAO-A inhibitor/5-HT transport inhibitor ) or placebo in a flexible dosing design . Based upon the CAPS , a st and ardized post-traumatic stress disorder ( PTSD ) interview , findings from a cohort involving both subchronic and chronic traumatic stress margin 
    Output:
    