title: Treatment of Panic Disorder with Agoraphobia: Randomized Placebo‐Controlled Trial of Four Psychosocial Treatments Combined with Imipramine or Placebo Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Stress hormones during flooding therapy and their relationship to therapy outcome in patients with panic disorder and agoraphobia. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. Therapeutic response to benzodiazepine in panic disorder subtypes. Is there a hypersensitive visual alarm system in panic disorder? 2nd year maintenance and discontinuation of imipramine in panic disorder with agoraphobia. Serotonergic modulation of the balance system in panic disorder: An open study Placebo-controlled study of gabapentin treatment of panic disorder. Comparison of the treatment with paroxetine and reboxetine in panic disorder: a randomized, single-blind study. Glucocorticoids enhance extinction-based psychotherapy Crossover trial of pagoclone and placebo in patients with DSM-IV panic disorder Double-blind clonazepam vs placebo in panic disorder treatment. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. Do antidepressants selectively suppress spontaneous (unexpected) panic attacks? A replication. Improvement of quality of life in panic disorder with escitalopram, citalopram, or placebo. D-cycloserine does not improve but might slightly speed up the outcome of in-vivo exposure therapy in patients with severe agoraphobia and panic disorder in a randomized double blind clinical trial. Interactive Model of Therapeutic Response in Panic Disorder: Moclobemide, a Case in Point Double-Blind, Controlled, Crossover Trial of Inositol Versus Fluvoxamine for the Treatment of Panic Disorder Antipanic Drug Modulation Of 35% CO2 Hyperreactivity and Short-Term Treatment Outcome The use of the Panic and Agoraphobia Scale (P & A) in a controlled clinical trial. A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. Time to response in panic disorder in a naturalistic setting: combination therapy with alprazolam orally disintegrating tablets and serotonin reuptake inhibitors compared to serotonin reuptake inhibitors alone. A randomized trial of cognitive-behavioral therapy or selective serotonin reuptake inhibitor or both combined for panic disorder with or without agoraphobia: treatment results through 1-year follow-up. Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder Duration of Imipramine Therapy and Relapse in Panic Disorder With Agoraphobia A randomized, controlled trial of aerobic exercise in combination with paroxetine in the treatment of panic disorder A randomized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder. A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. Controlled trials of inositol in psychiatry
abstract: Few r and omized 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 grade d in vivo exposure treatments , grade d 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 r and omized , 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 clinical ly 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 BACKGROUND Traditional pharmacological approaches to treating psychiatric disorders focus on correcting presumed biochemical abnormalities . However , some disorders , particularly the anxiety-related disorders exemplified by specific phobia , have an emotional learning component to them that can be facilitated with psychotherapy . OBJECTIVE To determine whether D-cycloserine ( DCS ) , a partial agonist at the N-methyl-d-aspartate receptor that has previously been shown to improve extinction of fear in rodents , will also improve extinction of fear in human phobic patients undergoing behavioral exposure therapy . DESIGN R and omized , double-blind , placebo-controlled trial examining DCS vs placebo treatment in combination with a precisely controlled exposure paradigm . SETTING Participants were recruited from the general community to a research clinic . PARTICIPANTS Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical Interview for DSM-IV were enrolled . INTERVENTIONS After we obtained pretreatment measures of fear , subjects were treated with 2 sessions of behavioral exposure therapy using virtual reality exposure to heights within a virtual glass elevator . Single doses of placebo or DCS were taken prior to each of the 2 sessions of virtual reality exposure therapy . Subjects , therapists , and assessors were blind to the treatment condition . Subjects returned at 1 week and 3 months posttreatment for measures to determine the presence and severity of acrophobia symptoms . MAIN OUTCOME MEASURES Included were measures of acrophobia within the virtual environment , measures of acrophobia in the real world , and general measures of overall improvement . An objective measure of fear , electrodermal skin fluctuation , was also included during the virtual exposure to heights . Symptoms were assessed by self-report and by independent assessors at approximately 1 week and 3 months posttreatment . RESULTS Exposure therapy combined with DCS result ed in significantly larger reductions of acrophobia symptoms on all main outcome measures . Subjects receiving DCS had significantly more improvement compared with subjects receiving placebo within the virtual environment ( 1 week after treatment , P</=.001 ; 3 months later , P</=.05 ) . Subjects receiving DCS also showed significantly greater decreases in posttreatment skin conductance fluctuations during the virtual exposure ( P</=.05 ) . Additionally , subjects receiving DCS had significantly greater improvement compared with subjects receiving placebo on general measures of real-world acrophobia symptoms ( acrophobia avoidance [ P</=.02 ] , acrophobia anxiety [ P</=.01 ] , attitudes toward heights [ P</=.04 ] , clinical global improvement [ P</=.01 ] , and number of self-exposures to real-world heights [ P</=.01 ] ) ; the improvement was evident early in treatment and was maintained at 3 months . CONCLUSION These pilot data provide initial support for the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to accelerate the associative learning processes that contribute to correcting psychopathology In spite of excessive fear during a panic attack , studies have found no or little evidence for an activation of cortisol during natural panic attacks . Whether this phenomenon is related to psychopathology or outcome of psychotherapy is unknown . In this study , 10 patients with panic disorder and agoraphobia were treated with cognitive behavioural therapy including 3 in-vivo exposures ( flooding ) to individual phobic situations . Before , during and after exposure , the level of subjective fear was assessed and blood was collected simultaneously . Cortisol and ACTH were analysed from plasma . Ten matched healthy control subjects went through the same procedure . Fear and stress hormones during exposure were compared in patients and controls as well as related to therapy outcome at the end of therapy and 2 follow-ups in patients . Results showed that the concentrations of cortisol and ACTH did not significantly increase during exposure . Patients ' cortisol concentrations were higher than those of controls at baseline and during exposure , while ACTH concentrations were comparable before and during exposure , and even lower than those of controls at recovery . Cortisol concentrations were moderately but consistently correlated to therapy outcome , i.e. patients with least cortisol release during exposure profited least from therapy . The study showed that a lack of stimulation of the HPA system at repeated confrontation with the phobic situation was related to therapeutic outcome . Mechanisms of action via the influence of cortisol on extinction learning or the inhibition of central excitatory neurotransmission are conceivable BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p < /=.05 ) , as measured by the Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder CONTEXT This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam , a benzodiazepine . OBJECTIVES To evaluate the clinical efficacy of clonazepam in a fixed dosage ( 2 mg/day ) , compared to placebo , in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes . TYPE OF STUDY R and omized study with clonazepam and placebo . SETTING Outpatient Anxiety and Depression Unit of the Institute of Psychiatry , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil . PARTICIPANTS 34 patients with a diagnosis of panic disorder with agoraphobia , between 18 and 55 years old . PROCEDURES Administration of clonazepam or placebo for 6 weeks , in panic disorder patients , after they were classified within two subtypes of panic disorder : respiratory and non-respiratory . MAIN MEASUREMENTS Changes in the number of panic attacks in comparison with the period before the beginning of the study ; Hamilton Anxiety Scale ; Global Clinical Impression Scale ; and Patient 's Global Impression scale . RESULTS In the group that received clonazepam , by the end of the 6th week there was a statistically significant clinical improvement , shown by the remission of panic attacks ( p < 0.001 ) and decrease in anxiety ( p = 0.024 ) . In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder , regarding the therapeutic response to clonazepam . CONCLUSION Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder , suggesting there is no difference in the therapeutic response between the two subtypes Agoraphobia in panic disorder ( PD ) has been related to abnormal balance system function . Vision influences balance and behavioural adaptations ; peripheral vision influences orienting and fast defensive reactions whereas central vision analyzes details of objects . We have hypothesized that the abnormal balance function in PD could be mainly related to peripheral vision as part of a defensive alarm system in the brain . In 25 patients with PD and agoraphobia and 31 healthy controls we assessed , by posturography ,  balance system reactivity to video-films projected in peripheral and central visual fields ( r and omized sequence ) . Length , velocity and surface of body sway were calculated . Patients increased their body sway during peripheral stimulation , whereas controls did not ; the two groups showed a similar increase of body sway during central stimulation . Anxiety levels during peripheral stimulation significantly influenced the postural response in the group of patients . These preliminary results suggest that the higher visual sensitivity to peripheral stimulation in patients with PD and agoraphobia may be linked to a more active " visual alarm system " involving visual , vestibular and limbic areas that might influence the development of agoraphobia in situations where environmental stimuli are uncertain BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients Experimental evidence suggests that panic disorder is characterized by abnormalities in the balance system function and that these abnormalities might be related to the severity of agoraphobic avoidance . Since the balance system can be modulated by the serotonergic system , we investigated the effect of a 6‐week treatment with citalopram on the balance system function in patients with panic disorder . Fifteen patients with panic disorder with/without agoraphobia underwent static posturography on days 0 and 42 . Static posturography and clinical assessment s were carried out by different investigators who were blind to each other . Static posturography showed high percentages of abnormal scores . Patients with no or low agoraphobic avoidance showed less abnormal posturographic measures than those with moderate to severe agoraphobia . After 6 weeks of treatment with citalopram there was a significant decrease of four out of six posturography measures in eyes‐closed and neck extension conditions , whereas no significant effect was found in the eyes‐open condition . This is the first report that suggests that the modulation of the serotonergic system can improve the balance system function in patients with panic disorder , particularly when visual information is lacking . In addition , our findings confirm the observation that many patients with panic disorder have abnormalities in their balance system function , supporting the idea that these abnormalities are mainly related to agoraphobic avoidance . Depression and Anxiety 17:101–106 , 2003 . © 2003 Wiley‐Liss , A r and omized , double-blind , placebo-controlled , parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of  panic disorder . One hundred three patients were r and omly assigned to receive double-blind treatment with either gabapentin ( dosed flexibly between 600 and 3,600 mg/day ) or placebo for 8 weeks . No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale ( PAS ) ( p = 0.606 ) . A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure ( PAS score > or = 20 ) . In this population , the gabapentin-treated patients showed significant improvement in the PAS change score ( p = 0.04 ) . In patients with a PAS score of 20 or greater , women showed a greater response than men regardless of treatment . Adverse events were consistent with the known side effect profile of gabapentin and included somnolence , headache , and dizziness . One patient experienced a serious adverse event during the study . No deaths were reported . The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder INTRODUCTION Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder ( PD ) . However preliminary studies suggested that reboxetine might be effective in the treatment of PD . We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD . METHODS Sixty-eight patients with PD were assigned to treatment groups in a single-blind , r and omized design . Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Side effects were also recorded . RESULTS Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one . Vice versa we did not find any significant differences for other outcome measures . Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group . CONCLUSIONS The results showed a greater effect of paroxetine on panic attacks than reboxetine , while no differences for anticipatory anxiety and avoidance were found , suggesting a different role of noradrenaline and serotonin in the treatment of PD Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction . Because pre clinical studies have shown that glucocorticoids can promote extinction processes , we aim ed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy . In a r and omized , double-blind , placebo-controlled study , 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights . Cortisol ( 20 mg ) or placebo was administered orally 1 h before each of the treatment sessions . Subjects returned for a posttreatment assessment 3–5 d after the last treatment session and for a follow-up assessment after 1 mo . Adding cortisol to exposure therapy result ed in a significantly greater reduction in fear of heights as measured with the acrophobia question naire ( AQ ) both at posttreatment and at follow-up , compared with placebo . Furthermore , subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up . The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy Pagoclone is a cyclopyrrolone that is believed to act as a partial agonist at the γ-aminobutyric acid ( GABA ) A/benzodiazepine ( BDZ ) receptor . In theory , such partial agonists should be anxiolytic but lack the adverse side-effects of sedation , tolerance and withdrawal associated with full GABA-A/BDZ agonists . The objective of the r and omized double-blind crossover study was to assess whether pagoclone was an effective anti-panic agent and also to assess its side-effect profile . Patients recruited had a diagnosis of Panic Disorder ( DSM-IV ) with at least one panic attack per week . Following a 2-week screening period , patients entered a 6-week trial consisting of two 2-week treatment periods , each followed by a 1-week washout . Patients were r and omly assigned to receive either pagoclone 0.1 mg t.d.s . or placebo on their first treatment period and the converse on their second . The primary measure was daily panic attack dairy . Fourteen patients completed the study , the mean number of panic attacks during screening was 5.8 ± 0.8 ( SEM ) , this fell to 3.6 ± 0.5 during treatment with pagoclone ( p = 0.05 ) and 4.3 ± 0.8 with placebo ( p = 0.14 ) . There was no significant difference on direct comparison of pagoclone with placebo or in any of the secondary measures ( including Rickels withdrawal scale ) or the adverse event profiles . The study provides preliminary evidence that pagoclone has anxiolytic properties in the absence of typical BDZ side-effects . This is consistent with its theoretical mode of action as a partial agonist at the GABAA/BDZ receptor OBJECTIVE To assess the effectiveness of clonazepam , in a fixed dose ( 2 mg/day ) , compared with placebo in the treatment of panic disorder patients . METHOD 24 panic disorder patients with agoraphobia were r and omly selected . The diagnosis was obtained using the structured clinical interview for DSM-IV . All twenty-four subjects were r and omly assigned to either treatment with clonazepam ( 2 mg/day ) or placebo , during 6 weeks . Efficacy assessment s included : change from baseline in the number of panic attacks ; CGI scores for panic disorder ; Hamilton rating scale for anxiety ; and panic associated symptoms scale . RESULTS At the therapeutic endpoint , only one of 9 placebo patients ( 11.1 % ) were free of panic attacks , compared with 8 of 13 ( 61.5 % ) clonazepam patients ( Fisher exact test ; p=0,031 ) . CONCLUSION the results provide evidence for the efficacy of clonazepam in panic disorder patients OBJECTIVE Because they found in an earlier study that inositol , an important intracellular second-messenger precursor , was effective against depression in open and double-blind trials , the authors studied its effectiveness against panic disorder . METHOD Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind , placebo-controlled , 4-week , r and om-assignment crossover treatment trial of 12 g/day of inositol . RESULTS The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more after inositol than after placebo administration . Side effects were minimal . CONCLUSIONS The authors conclude that inositol 's efficacy , the absence of significant side effects , and the fact that inositol is a natural component of the human diet make it a potentially attractive therapeutic for panic disorder The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a small therapeutic study : ( 1 ) the pathogenesis of panic disorder includes at least two identifiable components : a biological component represented by spontaneous ( unexpected ) panic attacks , and a cognitive component represented by situational attacks and especially by phobias ; ( 2 ) these components respond differently to treatment ; ( 3 ) many biological processes respond to an effective intervention in proportion to their deviance from " normal " prior to treatment ( " Law of Initial Value " ) ; and ( 4 ) the response of spontaneous panic attacks to an effective treatment conforms to that model . Previously , the authors reanalyzed an 8-week therapeutic study of panic disorder that included groups treated with  placebo  and with  imipramine ( 225 mg daily ) . The criteria of response were spontaneous panic attacks ( biological component ) , situational panic attacks ( both components ) , and agoraphobia ratings ( cognitive component ) . The analyses compared the regression lines for posttreatment status on pretreatment status in the imipramine and placebo groups . The effect of imipramine on spontaneous panic attacks fitted the hypothesized model : the pre-post slope in the placebo group was approximately 1 ( 45 degrees ) , whereas the slope in the imipramine group was approximately 0 . There was no significant difference in pre-post slopes between the imipramine and placebo groups for situational panic attacks or agoraphobia ratings . For this report , the authors applied the same approach to another larger data set from a study using a similar design , but a different antidepressant . In this multicenter , double-blind study , patients with panic disorder were r and omly assigned to receive 10 weeks of treatment with  placebo ( N = 78 ) or fluoxetine 10 mg ( N = 84 ) or 20 mg ( N = 81 ) daily . Spontaneous and situational panic attacks were registered in a daily diary , and agoraphobia was rated at each visit . Using baseline and endpoint data , fluoxetine had a statistically significant , dose-dependent , suppressive effect on spontaneous panic attacks , as measured by the pre-post slopes in the three treatment groups . The placebo group showed some response ( slope = 0.69 ) . There were no significant drug effects on situational panic attacks . On ratings of agoraphobia , the slopes in the placebo and the fluoxetine 20 mg groups did not differ , but the slope in the fluoxetine 10 mg group was significantly less than that in the placebo group , suggesting a therapeutic drug effect on agoraphobia only at the lower dose . These results are consistent with the stated hypotheses . They suggest that the therapeutic effects of antidepressants on panic disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings . Implication s of these results for concepts of pathogenesis , clinical practice , and therapeutic research regarding panic disorder are discussed BACKGROUND It has been argued that measurement of outcome in panic disorder should not be limited to monitoring the number of panic attacks , but should include all domains that affect patient quality of life . METHODS Data from a r and omized prospect i ve comparison of escitalopram , citalopram , and placebo in patients with DSM-IV panic disorder were analyzed with regard to measurements of impairment of quality of life . The subscales of the Panic and Agoraphobia Scale ( P&A ) ( Panic Attacks , Agoraphobic Avoidance , Anticipatory Anxiety , Functional and Social Disability , and Worries about Health ) and the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) were analyzed . RESULTS Treatment with escitalopram was associated with significant improvement on all 5 subscales of the P&A.  Citalopram was significantly different from placebo in 3 subscales . Escitalopram and citalopram were significantly better than placebo in improving quality of life ( measured by the total score of the Q-LES-Q Scale ) . Escitalopram was superior to placebo on 12 of 16 items of the Q-LES-Q , while citalopram was superior on 7 items . CONCLUSION The P&A scale was more robust than measurement of panic frequency in differentiating medication from placebo . Escitalopram treatment was associated with improvement on all assessed domains that impair quality of life in panic disorder . Measurement of clinical improvement should not be solely based on panic attack frequency , but should also include assessment of a broad range of domains that affect patient quality of life D-cycloserine (DCS)-augmented exposure therapy has proven efficacy in the treatment of acrophobia , social phobia , panic disorder and OCD . Here we studied whether DCS can also improve the effect of cognitive behavioral therapy ( CBT ) in patients with agoraphobia and panic disorder . To this end , 39 patients with the diagnoses of agoraphobia and panic disorder were treated with 11 sessions of CBT including three individual in-vivo exposure sessions ( flooding ) , augmented with either 50 mg of DCS ( N=20 ) or placebo ( N=19 ) in a r and omized double blind design . Primary outcome was the total score of the panic and agoraphobia scale . Both groups profited considerably from therapy and DCS did not significantly improve this outcome ( p=0.475 ; η(2)p = 0.01 ) . However , there was a statistical trend ( p=0.075 ; η(2)p = 0.17 ) in the more severely ill patients  that DCS accelerated symptom reduction in the primary outcome at post-therapy . No serious adverse effects occurred during the trial . We conclude that in patients with agoraphobia and panic disorder  , DCS seems to lack an additional benefit to efficient cbt , probably due to a floor effect . Nonetheless , the acceleration of symptom reduction in severely ill patients might represent a valuable treatment option deserving further investigation It was proposed that pre-post regression slopes be used to index treatment response when the effect of baseline scores differed among treatments ( interaction between treatment and baseline score ) . Reanalyses of two studies using imipramine and fluoxetine in panic disorder showed doserelated decreases in pre-post slopes for the frequency of unexpected panic attacks , but not for the frequency of situational panic attacks or measures of agoraphobia . This report presents similar analyses of data from a study using moclobemide .  Patients ( N = 452 ) with panic disorder were r and omized to placebo  or a fixed dose of moclobemide ( 75 , 150 , 300 , 600 , or 900 mg/day ) . They were treated double-blindly and evaluated at baseline and 1 , 2 , 3 , 4 , 6 , and 8 weeks later . The authors analyzed the frequency of unexpected and situational panic attacks compiled from a daily diary , and fear and avoidance ratings based on the patient ’s main phobia using baseline ( pre ) and end-point ( post ) values for all r and omized patients . Adjoining dose groups were combined . Both unexpected and situational panic attacks showed systematic doserelated suppression of pre-post treatment slopes . Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance differed reliably between treatment arms . This study replicates the authors ’ earlier findings , except for situational panic attacks , which probably were not reliably identified . Antidepressants selectively suppress panic attacks , especially unexpected attacks , but not agoraphobia . The findings are consistent with the hypothesis that panic disorder with agoraphobia has clinical ly separable biologic and cognitive components that respond differentially to treatment . Antidepressants benefit primarily patients with many unexpected panic attacks . Investigators should evaluate pre-post treatment slopes before comparing adjusted posttreatment means ( analysis of covariance ) Only 70 % of patients respond to current treatments for panic disorder , and many discontinue drugs because of side effects . myo-Inositol , a natural isomer of glucose and a precursor for the second-messenger phosphatidyl-inositol system , has previously been found superior to placebo in the treatment of depression , panic disorder , and obsessive-compulsive disorder ( OCD ) , but a direct comparison with an established drug has never been performed . A double-blind , controlled , r and om-order crossover study was undertaken to compare the effect of inositol with that of fluvoxamine in panic disorder . Twenty patients completed 1 month of inositol  up to 18 g/day and 1 month of fluvoxamine up to 150 mg/day . Improvements on Hamilton Rating Scale for Anxiety scores , agoraphobia scores , and Clinical Global Impressions Scale scores were similar for both treatments . In the first month , inositol reduced the number of panic attacks per week ( mean and SD ) by 4.0 ( 2 ) compared with a reduction of 2.4 ( 2 ) with fluvoxamine ( p = 0.049 ) . Nausea and tiredness were more common with fluvoxamine ( p = 0.02 and p = 0.01 , respectively ) . Because inositol is a natural compound with few known side effects , it is attractive to patients who are ambivalent about taking psychiatric medication . Continuing reports of inositol ’s efficacy in the treatment of depression , panic disorder , and OCD should stimulate replication studies Carbon dioxide ( CO2 ) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder ( PD ) . Anti-panic drugs decrease CO2 reactivity after the first days of treatment ; however , the clinical meaning of this finding has not yet been established . This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors ( SSRIs ) on CO2 reactivity and compared the relationships between 35 % CO2 hyperreactivity modulation and short-term clinical outcome .  One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were r and omly assigned to treatment groups with imipramine , clomipramine , paroxetine , sertraline , or fluvoxamine . A double-blind , r and omized design was applied . Each patient received the 35 % CO2 challenge on days 0 , 7 , and 30 . The severity of clinical symptomatology was measured on days 0 and 30 . Decreased hyperreactivity to 35 % CO2 in all five treatment groups was already evident after the first week . The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement . Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month . The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity . They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “ respiratory ” PD BACKGROUND A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia , the Panic and Agoraphobia Scale ( P & A ) . The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients ( panic attacks , avoidance , anticipatory anxiety , disability and worries about health ) . The application of this scale in a double-blind placebo-controlled panic disorder trial is described . At the same time , the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy . METHODS Patients with Panic disorder ( DSM-IV ) were r and omly assigned to three treatment modalities : running ( n=45 ) , clomipramine ( n=15 ) or placebo ( n=15 ) . Treatment efficacy was measured with the Panic and Agoraphobia Scale ( P & A ) and other rating scales . RESULTS According to the P & A and other scales , both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment . Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise . The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability . CONCLUSIONS The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments . Analysis of the scales five subscores may help to underst and mechanisms of action of panic disorder treatments To date , no large-scale , controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported . This double-blind study compares the efficacy of venlafaxine extended-release ( ER ) and paroxetine with placebo . A total of 664 nondepressed adult out patients who met DSM-IV criteria for panic disorder ( with or without agoraphobia ) were r and omly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER ( 75 mg/day or 150 mg/day ) , or paroxetine 40 mg/day . The primary measure was the percentage of patients free from full-symptom panic attacks , assessed with the Panic and Anticipatory Anxiety Scale ( PAAS ) . Secondary measures included the Panic Disorder Severity Scale , Clinical Global Impressions -- Severity ( CGI-S ) and --Improvement ( CGI-I ) scales ; response ( CGI-I rating of very much improved or much improved ) , remission ( CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks ) ; and measures of depression , anxiety , phobic fear and avoidance , anticipatory anxiety , functioning , and quality of life . Intent-to-treat , last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo . No significant differences were observed between active treatment groups . Panic-free rates at end point with active treatment ranged from 54 % to 61 % , compared with 35 % for placebo . Approximately 75 % of patients given active treatment were responders , and nearly 45 % achieved remission . The placebo response rate was slightly above 55 % , with remission near 25 % . Adverse events were mild or moderate and similar between active treatment groups . Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder OBJECTIVE This study evaluated time to response in the treatment of panic disorder with a selective serotonin reuptake inhibitor ( SSRI ) or serotonin norepinephrine reuptake inhibitor ( SNRI ) combined with alprazolam orally disintegrating tablets ( ODT ) , or SSRI/SNRI alone . DESIGN Subjects were r and omized to eight weeks open-label treatment with alprazolam ODT ( 4 weeks treatment followed by 3 - 4 week taper ) combined with an SSRI or SNRI , or treatment with SSRI/SNRI alone . SETTING The study was conducted under naturalistic conditions at 62 primary care and 34 psychiatric practice s. PARTICIPANTS Male or female subjects ≥18 years of age diagnosed with panic disorder , with or without agoraphobia . MEASUREMENTS The primary efficacy measure was time to response , defined as ≥50-percent decrease from baseline Hamilton Rating Scale for Anxiety ( HAM-A ) total score . Secondary measures included change from baseline in HAM-A scores and the Clinical Global Impression of Improvement ( CGI-I ) and Patient Global Impression ( PGI ) scales . RESULTS The intent-to-treat ( ITT ) population comprised 245 subjects . There was no statistical difference between treatment groups in time to response in the ITT population ; however , a prospect ively defined per protocol analysis revealed a statistically significant earlier onset of effect in subjects receiving SSRI/SNRI plus alprazolam ODT ( P<0.05 ) . Mean change from baseline in HAM-A total score and clinician and patient measures of global improvement also showed statistically significant early advantages for combination therapy compared with SSRI/SNRI monotherapy . CONCLUSION Combined treatment of panic disorder with alprazolam ODT and an SSRI/SNRI may be associated with more rapid improvement in anxiety symptoms compared with an SSRI/SNRI alone OBJECTIVE To establish the long-term effectiveness of 3 treatments for DSM-IV panic disorder with or without agoraphobia :  cognitive-behavioral therapy ( CBT ) , pharmacotherapy using a selective serotonin reuptake inhibitor ( SSRI ) , or the combination of both ( CBT + SSRI ) . As a secondary objective , the relationship between treatment outcome and 7 predictor variables was investigated . METHOD Patients were enrolled between April 2001 and September 2003 and were r and omly assigned to treatment . Academic and nonacademic clinical sites participated . Each treatment modality lasted 1 year . Pharmacotherapists were free to choose between 5 SSRIs currently marketed in The Netherl and s. Outcome was assessed after 9 months of treatment ( posttest 1 ) , after discontinuation of treatment ( posttest 2 ) , and 6 and 12 months after treatment discontinuation ( follow-up 1 and follow-up 2 ) . RESULTS In the sample ( N = 150 ) , 48 % did not suffer from agoraphobia or suffered from only mild agoraphobia , while 52 % suffered from moderate or severe agoraphobia . Patients in each treatment group improved significantly from pretest to posttest 1 on the primary outcome measures of level of anxiety ( P < .001 ) , degree of coping ( P < .001 ) , and remitter status ( P < .001 ) , as well as on the secondary outcome measures of depressive symptomatology ( P < .001 ) , and from pretest to posttest 2 for health-related quality of life ( P < .001 ) . Gains were preserved from posttest 2 throughout the follow-up period . Some superiority of CBT + SSRI and SSRI as compared with CBT was observed at posttest 1 . However , at both follow-ups , differences between treatment modalities proved nonsignificant . Client satisfaction appeared to be high at treatment endpoint , while patients receiving CBT + SSRI appeared slightly ( P < .05 ) more satisfied than those receiving CBT only . CONCLUSIONS No fall-off in gains was observed for either treatment modality after treatment discontinuation . SSRIs were associated with adverse events . Gains produced by CBT were slower to emerge than those produced by CBT + SSRI and SSRI , but CBT ended sooner . TRIAL REGISTRATION Netherl and s Trial Register ( www.trialregister.nl ) Identifier : IS RCT N8156869 BACKGROUND Traditional combination strategies of cognitive-behavior therapy plus pharmacotherapy have met with disappointing results for anxiety disorders . Enhancement of cognitive-behavior therapy with d-cycloserine ( DCS ) pharmacotherapy represents a novel strategy for improving therapeutic learning from cognitive-behavior therapy that remains untested in panic disorder . METHOD This is a r and omized , double-blind , placebo-controlled augmentation trial examining the addition of isolated doses of 50 mg d-cycloserine or pill placebo to brief exposure-based cognitive-behavior therapy .  R and omized participants were 31 out patients meeting DSM-IV criteria for panic disorder with or without agoraphobia , who were offered five sessions of manualized cognitive-behavior therapy emphasizing exposure to feared internal sensations ( interoceptive exposure ) but also including informational , cognitive , and situational exposure interventions . Doses of study drug were administered 1 hour before cognitive-behavior therapy sessions 3 to 5 . The primary outcome measures were the Panic Disorder Severity Scale ( PDSS ) and Clinicians ' Global Impressions of Severity . RESULTS Results indicated large effect sizes for the additive benefit of d-cycloserine augmentation of cognitive-behavior therapy for panic disorder . At posttreatment and 1 month follow-up , participants who received d-cycloserine versus placebo had better outcomes on the PDSS and global severity of disorder and were significantly more likely to have achieved clinical ly significant change status ( 77 % vs. 33 % ) . There were no significant adverse effects associated with DCS administration . CONCLUSIONS This pilot study extends support for the role of d-cycloserine in enhancing therapeutic learning from exposure-based cognitive-behavior therapy and is the first to do so in a protocol emphasizing exposure to feared internal sensations of anxiety in panic disorder It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse . This study further explores the relationship between relapse and duration of imipramine treatment in this population . Fifty-one patients , all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and r and omized to double-blind maintenance or placebo substitution , discontinued imipramine treatment eventually and were followed over a 12-month risk period : 27 during first year placebo substitution , 7 after 12 months of imipramine maintenance in placebo substitution , and 17 after variable duration s of imipramine maintenance in open discontinuation . There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation . Duration of imipramine treatment , the method of discontinuation ( open versus placebo substitution ) , or any of the 9 variables from the demographic , clinical , and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse . The rate of relapse after only 6 months of treatment ( 10 out of 27 , 37 % ) was identical to the rate of relapse after 12 to 30 months of treatment ( 9 out of 24 , 37.5 % ) . The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients . Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction Abstract Objectives . Regular aerobic exercise ( running ) has been shown to be superior to a pill placebo in the treatment of panic disorder . Combined drug and exercise treatment has not been investigated in r and omized controlled studies to date . Methods . This is a r and omized , 10-week , controlled , parallel group , pilot study . A total of 75 out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 ) received either ( 1 ) exercise plus paroxetine 40 mg/day ( n=21 ) , ( 2 ) relaxation plus paroxetine ( n=17 ) , ( 3 ) exercise plus pill placebo ( n=20 ) , or ( 4 ) relaxation plus pill placebo ( n=17 ) . Changes in the Panic and Agoraphobia Scale ( P&A ) , and the Clinical Global Impression Scale ( CGI ) underwent repeated measure analysis . Results . Effects sizes were large for all groups ( d=1.53–3.87 ) , however not significantly different . Paroxetine-treated patients were significantly more improved than placebo-treated patients . On the CGI , patients in the exercise groups ( plus paroxetine or placebo ) had a trend toward better improvement compared to relaxation ( P=0.06 ) . Response and remission rates were higher in the paroxetine compared to pill placebo groups . Conclusions . While paroxetine was superior to placebo , aerobic exercise did not differ from relaxation training in most efficacy measures Hendriks G‐J , Keijsers GPJ , Kampman M , Oude Voshaar RC , Verbraak MJPM , Broekman TG , Hoogduin CAL . A r and omized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder BACKGROUND Tricyclic antidepressants and selective serotonin reuptake inhibitors ( SSRIs ) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder . The introduction of SSRIs has enabled a greater underst and ing of the role of serotonin in the etiology of panic disorder ; however , the role of norepinephrine has been more challenging to ascertain . The aim of this study was to determine the efficacy and tolerability of reboxetine , a novel selective norepinephrine reuptake inhibitor , in patients with panic disorder with and without agoraphobia . METHOD Eighty-two patients ( aged 18 - 65 years ) with DSM-III-R panic disorder , with or without agoraphobia , were r and omly assigned to receive 6 to 8 mg/day of reboxetine ( 42 patients ) or placebo ( 40 patients ) for 8 weeks in this placebo-controlled , parallel-group , double-blind clinical trial . RESULTS Of the 82 patients enrolled in the trial , 75 were considered in the analysis ( 37 patients in the reboxetine group and 38 patients in the placebo group ) . At last assessment , there was a significant reduction in the mean number of panic attacks ( range , 9.3 - 1.2 ) and phobic symptoms ( range , 8.1 - 3.2 ) in the reboxetine group compared with the placebo group ( ranges , 8.5 - 5.8 and 7.7 - 5.2 , respectively ; p < .05 ) . Improvement in Hamilton Rating Scale for Depression , Hopkins Symptom Checklist-90 , and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group . Adverse events reported more frequently with reboxetine than placebo included dry mouth ( 36 % vs. 16 % ) , constipation ( 27 % vs. 22 % ) , and insomnia ( 26 % vs. 22 % ) . CONCLUSION Reboxetine was effective and well tolerated in the treatment of panic disorder BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs OBJECTIVE Several classes of medications have demonstrated efficacy in panic disorder , but direct comparison of 2 proven treatments is still uncommon . The purpose of this study was to compare sertraline and paroxetine in the acute treatment of panic disorder . METHOD Adult out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 criteria ) were r and omly assigned in double-blind fashion to 12 weeks of treatment with flexible doses of sertraline ( titrated up to 50 - 150 mg/day ; N = 112 ) or paroxetine ( titrated up to 40 - 60 mg/day ; N = 113 ) . Patients were then tapered off medication over 3 weeks . The primary analysis was a noninferiority analysis of Panic and Agoraphobia Scale ( PAS ) scores . Secondary measures included panic attack frequency and the Clinical Global Impressions-Improvement scale ( CGI-I ) ( with responders defined as those with a CGI-I score < or = 2 ) . Data were collected from January 2000 to June 2001 . RESULTS Sertraline and paroxetine were associated with equivalent levels of improvement on the PAS total score , as well as on all secondary outcome measures . Eighty-two percent of patients taking sertraline versus 78 % of those taking paroxetine were CGI-I responders at endpoint . Numerically more patients on paroxetine treatment compared with sertraline treatment discontinued due to adverse events ( 18 % vs. 12 % ; NS ) , and a significantly higher proportion of paroxetine patients showed > or = 7 % weight gain ( 7 % vs. < 1 % ; p < .05 ) . During the taper period , the proportion of panic-free patients increased by 4 % with sertraline but decreased by 11 % with paroxetine ( p < .05 ) . CONCLUSION Sertraline and paroxetine had equivalent efficacy in panic disorder , but sertraline was significantly better tolerated and was associated with significantly less clinical worsening during taper than paroxetine Inositol is a simple polyol precursor in a second messenger system important in the brain . Cerebrospinal fluid inositol has been reported as decreased in depression . A double-blind controlled trial of 12 g daily of inositol in 28 depressed patients for four weeks was performed . Significant overall benefit for inositol compared to placebo was found at week 4 on the Hamilton Depression Scale . No changes were noted in hematology , kidney or liver function . Since many antidepressants are effective in panic disorder , twenty-one patients with panic disorder with or without agoraphobia completed a double-blind , placebo-controlled , four week , r and om-assignment crossover treatment trial of inositol 12 g per day . Frequency and severity of panic attacks and severity of agoraphobia declined significantly with inositol compared to placebo .  Side-effects were minimal . Since serotonin re-uptake inhibitors benefit obsessive compulsive disorder ( OCD ) and inositol is reported to reverse desensitization of serotonin receptors , thirteen patients with OCD completed a double-blind controlled crossover trial of 18 g inositol or placebo for six weeks each . Inositol significantly reduced scores of OCD symptoms compared with placebo . A controlled double-blind crossover trial of 12 g daily of inositol for a month in twelve anergic schizophrenic patients , did not show any beneficial effects . A double-blind controlled crossover trial of 6 g of inositol daily vs. glucose for one month each was carried out in eleven Alzheimer patients , with on clearly significant therapeutic effects . Antidepressant drugs have been reported to improve attention deficit disorder ( ADDH ) with hyperactivity symptomatology . We studied oral inositol in children with ADDH in a double-blind , crossover , placebo-controlled manner . Eleven children , mean age 8.9 + /- 3.6 years were enrolled in an eight week trial of inositol or placebo at a dose of 200 mg/kg body weight . Results show a trend for aggravation of the syndrome with myo-inositol as compared to placebo . Recent studies suggest that serotonin re-uptake inhibitors are helpful in at least some symptoms of autism . However a controlled double-blind crossover trial of inositol 200 mg/kg per day showed no benefit in nine children with autism . Cholinergic agonists have been reported to ameliorate electroconvulsive therapy (ECT)-induced memory impairment . Inositol metabolism is involved in the second messenger system for several muscarinic cholinergic receptors . Inositol 6 g daily was given in a crossover-double-blind manner for five days before the fifth or sixth ECT to a series of twelve patients , without effect . These results suggest that inositol has therapeutic effects in the spectrum of illness responsive to serotonin selective re-uptake inhibitors , including depression , panic and OCD , and is not beneficial in schizophrenia , Alzheimer 's ADDH , autism or ECT-induced cognitive impairment
target: Paroxetine , sertraline , citalopram , escitalopram , and clomipramine showed the most consistent results , while fluvoxamine , fluoxetine , and imipramine showed limited efficacy .
  Preliminary results suggested the potential efficacy of inositol ; D-cycloserine showed mixed results for its ability to improve the outcome of exposure-based cognitive behavioral therapy .
  No studies have been specifically oriented toward evaluating the effect of drugs on AG ; in the available studies , the improvement of AG might have been the consequence of the reduction of panic attacks .
background: BACKGROUND Although there are controversial issues ( the " American view " and the " European view " ) regarding the construct and definition of agoraphobia ( AG ) , this syndrome is well recognized and it is a burden in the lives of millions of people worldwide .
  To better clarify the role of drug therapy in AG , the authors summarized and discussed recent evidence on pharmacological treatments , based on clinical trials available from 2000 , with the aim of highlighting pharmacotherapies that may improve this complex syndrome .