title: Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder Open‐Label Support for Duloxetine for the Treatment of Panic Disorder Sertraline treatment of panic disorder: results of a long‐term 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. Mirtazapine versus fluoxetine in the treatment of panic disorder. Double-blind clonazepam vs placebo in panic disorder treatment. The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study. Olanzapine Augmentation in Treatment-Resistant Panic Disorder: A 12-Week, Fixed-Dose, Open-Label Trial Efficacy and tolerability of controlled-release paroxetine in the treatment of panic disorder. Imiprmaine vs. Sertraline in Panic Disorder: 24-Week Treatment Completers Clomipramine and fluoxetine effects in the treatment of panic disorder. A three-year follow-up study of patients with the respiratory subtype of panic disorder after treatment with clonazepam Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder. Combined Paroxetine and Clonazepam Treatment Strategies Compared to Paroxetine Monotherapy for Panic Disorder Double-Blind, Controlled, Crossover Trial of Inositol Versus Fluvoxamine for the Treatment of Panic Disorder Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial. A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. The effect of mirtazapine in panic disorder: an open label pilot study with a single-blind placebo run-in period Relapse prevention of panic disorder in adult outpatient responders to treatment with venlafaxine extended release. Aripiprazole as augmentation treatment of refractory generalized anxiety disorder and panic disorder. Effects of the GABA-reuptake inhibitor tiagabine on panic and anxiety in patients with panic disorder. Specific Side Effects of Long-Term Imipramine Management of Panic Disorder World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder. Efficacy of open-label nefazodone treatment in patients with panic disorder. A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. The 35% CO 2 Hyperreactivity and Clinical Symptomatology in Patients With Panic Disorder After 1 Week of Treatment With Citalopram: An Open Study Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. Double-blind comparison of 30 and 60 mg tranylcypromine daily in patients with panic disorder comorbid with social anxiety disorder
abstract: 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 RATIONALE Few r and omized , placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder . OBJECTIVES The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release ( ER ) with placebo in treating panic disorder . Secondary objectives included comparing paroxetine with venlafaxine ER and placebo . METHODS Out patients aged > or = 18 years ( placebo , n = 157 ; venlafaxine ER 75 mg , n = 156 ; venlafaxine ER 225 mg , n = 160 ; paroxetine , n = 151 ) , with a primary diagnosis of panic disorder ( + /-agoraphobia ) based on the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) criteria for > or =3 months were r and omly assigned to receive venlafaxine ER ( titrated to 75 mg/day or 225 mg/day ) , paroxetine ( titrated to 40 mg/day ) , or placebo for 12 weeks . The primary efficacy measure was the percentage of patients free of full-symptom panic attacks ( > or = four symptoms ) at endpoint . Key secondary outcomes included the Panic Disorder Severity Scale ( PDSS ) mean score change and response . RESULTS At endpoint , all active treatment groups showed a significantly ( P < 0.01 ) greater proportion of patients free of full-symptom panic attacks , compared with placebo , and were superior ( P < 0.05 ) on most secondary measures . The venlafaxine ER 225 mg group had significantly ( P < 0.05 ) greater mean PDSS score improvement than the paroxetine group ( -12.58 vs -11.87 ) and a significantly higher proportion of patients free of full symptom panic attacks ( 70.0 vs 58.3 % ) . Both drugs were generally well tolerated . CONCLUSION Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted Objective : To investigate the long‐term efficacy , prevention of relapse and safety of sertraline in the treatment of panic disorder 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 Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents ( selective serotonin reuptake inhibitors ) used in the treatment of panic disorder . The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind , r and omized , flexible-dose trial conducted with out patients . After a 1-week single-blind placebo run-in , 27 patients entered an 8-week double-blind phase in which they were r and omly assigned to treatment with either mirtazapine or fluoxetine . Both groups improved significantly in all but one efficacy measure ( P < or = 0.01 ) . ANOVA showed no significant differences between the two treatment groups in number of panic attacks , Hamilton Anxiety Scale or Sheehan Phobic Scale , whereas measures of patient global evaluation of phobic anxiety were significantly different between groups ( F1,20 = 6.91 , P = 0.016 ) favoring mirtazapine . For the 22 patients who completed the study , the mean daily dose of mirtazapine was 18.3 + /- 1.3 vs 14.0 + /- 1.0 mg for fluoxetine at the endpoint . Weight gain occurred more frequently in the mirtazapine group ( 50 vs 7.7 % , P = 0.04 ) and nausea and paresthesia occurred more often in the fluoxetine group ( P = 0.01 ) . Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder 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 BACKGROUND AND OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are currently the first-line treatment for panic disorder , although up to 30 % of patients either do not respond to SSRIs or withdraw due to adverse events . Reboxetine , a selective norepinephrine reuptake inhibitor ( selective NRI ) , is effective in treating depression and may alleviate depression-related anxiety . This study aim ed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs . METHOD In this 6-week , open-label study , 29 adult out patients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day , titrated to a maximum of 8 mg/day over the first 10 days .  Efficacy was assessed using the Panic Self- Question naire ( PSQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the 17-item Hamilton Rating Scale for Depression ( HRSD ) and the Global Assessment of Functioning ( GAF ) Scale . RESULTS The 24 patients who completed the study responded well to reboxetine treatment . Significant improvement ( p < 0.001 ) was observed in the number of daily panic attacks , and on the scales measuring anxiety , depression and functioning . Reboxetine was generally well tolerated . Five patients withdrew due to  adverse events . CONCLUSIONS Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI .  Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness . No extrapyramidal symptoms were reported . Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD , but study limitations must be considered and placebo-controlled studies are needed OBJECTIVE To assess the efficacy and tolerability of controlled-release paroxetine ( paroxetine CR ) in the treatment of adults with panic disorder . METHOD  Paroxetine CR ( 25 - 75 mg/day ; N = 444 ) was compared with  placebo ( N = 445 ) in patients with DSM-IV panic disorder with or without agoraphobia in 3 identical , double-blind , placebo-controlled , 10-week clinical trials that were pooled for analysis . RESULTS Paroxetine CR was statistically superior to placebo in the primary outcome measure , percentage of patients who were free of panic attacks in the 2 weeks prior to endpoint . Of the total population that completed or prematurely terminated treatment , 63 % and 53 % of paroxetine CR- and placebo-treated patients , respectively , were panic-free during the final 2 weeks ( p < .005 ; odds ratio [ OR ] = 1.63 ; 95 % CI = 1.21 to 2.19 ) . For week 10 completers ( 72 % of total ) , 73 % and 60 % of paroxetine CR- and placebo-treated patients , respectively , were panic-free at week 10 ( p < .005 ; OR = 2.11 ; 95 % CI = 1.45 to 3.07 ) . Paroxetine CR was also statistically superior to placebo on the global improvement and severity items of the Clinical Global Impressions scale and in reducing anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety total score and total fear and avoidance on the Marks-Sheehan Phobia Scale . Adverse events leading to study withdrawal were minimal and occurred in 11 % of the paroxetine CR group and 6 % of the placebo group . Most of the treatment-emergent adverse events were rated as mild to moderate in severity and occurred early in the study . There were no unexpected adverse events , and serious adverse events were uncommon ( 10 [ 2.3 % ] of the 444 patients treated with paroxetine CR vs. 8 [ 1.8 % ] of the 445 patients treated with placebo ) . CONCLUSION Paroxetine CR is an effective and well-tolerated treatment for panic disorder . Paroxetine CR is associated with low rates of treatment-emergent anxiety as well as low dropout rates from adverse events Despite the acknowledged favorable side effects profile of selective serotonin reuptake inhibitors ( SSRIs ) , comparative studies have not found significant differences in efficacy between tricyclics ( TCAs ) such as imipramine and clomipramine , and SSRIs in the treatment of panic disorder . The present study focuses on treatment completers to inform patients who adhere to a recommended course of treatment on the possible differential patterns of improvement and of change in side effects between sertraline and imipramine . From an intent to treat consecutive sample of patients participating in the 24-week open phase protocol ized treatment of a long-term controlled maintenance/discontinuation study , 20 imipramine completers and 16 sertraline completers with moderate to severe baseline symptomatology were compared using primarily repeated measures analysis of variance on measures of symptom severity , on 15 side effects systematic ally elicited using an inventory and on heart rate and weight . The results revealed greater early improvement with imipramine compared to sertraline but no enduring differences beyond week 8 of treatments . Side effects , in particular dry mouth , constipation , tremors , sweating , and cardiovascular complaints increased more in severity and were more frequent and persistent during imipramine than sertraline but , except for the 10 beats/min increase in heart rate , side effects were clinical ly insignificant at the end of both treatments . Change in sexual complaints and weight did not differ between the treatments . The more favorable side effect profile of SSRIs versus TCAs was demonstrated even in the best case scenario of treatment completers . The more rapid improvement with imipramine needs replication but , tentatively , it may be attributed to the greater motivational effects toward action observed with noradrenergic or dual action antidepressants compared to SSRIs Panic disorder ( PD ) is an acute psychobiologic reaction manifested by intense anxiety and panic attacks , that occur unpredictably with subjective sense of intense apprehension or terror , accompanied by temporary loss of the ability to plan , think , or reason and the intense desire to escape or flee the situation . Panic attacks may last from a few seconds to an hour or longer . Symptoms typically include , among others , palpitations , tachycardia , hypertension , chest pain , dyspnoea , and fear of loosing control or going crazy and vague feeling of imminent doom or death . Since pharmacotherapy of PD includes the administration of selective serotonin reuptake inhibitors and tricyclic antidepressants , the objective of this study was to perform a pilot double blind clinical trial design ed to compare the effects of two studied drugs in the treatment of PD . A total number of 40 patients with a history of panic disorder were r and omly assigned into two groups of 20 patients each . Hamilton anxiety rating scale and St and ard Psychiatric Interview were methods for PD assessment . One group was treated with clomipramine hydrochloride ( ANAFRANIL ) 75 mg/day and the other with fluoxetine ( OXETIN ) 60 mg/day . Both drugs were administrated by mouth ( PO ) two times-a-day in equally divided doses for 6 weeks . Both studied agents produced similar antipanic effectiveness . Favourable response was achieved in 95 % of patients treated with fluoxetine and 90 % of patients treated with clomipramine . The onset of antipanic effects was quicker in all clomipramine treated patients , while fluoxetine produced more-favourable response in male patients . The duration of treatment with both antidepressants studied should be at least 10 weeks , instead of 6 weeks The demographic , clinical and therapeutic features of the respiratory subtype of panic disorder ( PD ) versus the non-respiratory subtype were studied in a prospect i ve design . Sixty-seven PD out patients ( DSM-IV ) , who had previously been categorized into respiratory ( n=35 ) and non-respiratory ( n=32 ) subgroups , were openly treated with clonazepam for a 3-year period . The principal measure of efficacy was the number of panic attacks , obtained from the Sheehan Panic and Anticipatory Anxiety Scale . In the first 8 weeks of treatment ( acute phase ) , the respiratory subtype group had a significantly faster response to clonazepam . During the follow-up ( weeks 12 - 156 ) , the two subgroups did not differ significantly in the number of panic attacks experienced from baseline to end point . Patients in the respiratory subtype were characterized by a later onset of disorder and a family history of PD . Patients in the non-respiratory subgroup had a significantly higher number of past depressive episodes than those in the respiratory subgroup . The respiratory subgroup had a faster response after 8 weeks of treatment and an equivalent response in the 3-year follow-up period . Clonazepam had a sustained therapeutic effect over the entire treatment period OBJECTIVE To evaluate the efficacy and tolerability of sertraline and imipramine in patients with comorbid panic disorder and major depressive disorder . METHOD Out patients meeting a DSM-IV diagnosis of panic disorder and concurrent major depressive disorder were r and omized in a 2:1 ratio to 26 weeks of double-blind treatment with either sertraline , in daily doses of 50 to 100 mg , or imipramine , in daily doses of 100 to 200 mg . Primary outcome measures were panic attack frequency ( derived from patient diaries ) and the Montgomery-Asberg Depression Rating Scale ( MADRS ) . RESULTS 138 patients were treated with sertraline ( 76 % female ; mean age = 40 years ) and 69 with imipramine ( 70 % female ; mean age = 40 years ) . The symptoms of both major depressive disorder and panic disorder responded significantly and equivalently to both drugs . Endpoint improvement with sertraline versus imipramine , respectively , on the MADRS was 11.1 + /- 10.8 versus 11.2 + /- 10.4 , and on the Clinical Global Impressions-Improvement scale ( CGI-I ) was 2.1 + /- 1.3 versus 2.4 + /- 1.6 . Among study completers , CGI-I responder rates were 88 % with sertraline and 91 % with imipramine . Treatment outcome was concordant for both diagnoses in approximately 70 % of patients and discordant in approximately 30 % . Overall , sertraline was significantly better tolerated with significantly fewer discontinuations due to adverse events ( 11 % vs. 22 % ; chi(2 ) = 4.39 , df = 1 , p = .04 ) . CONCLUSION Both sertraline and imipramine were found to be highly effective treatments for both major depressive disorder and panic disorder , with sertraline showing significantly greater tolerability and compliance during long-term treatment than imipramine Despite the widespread application of combined selective serotonin reuptake inhibitors ( SSRI ) and benzodiazepine treatment for panic disorder , there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy . Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment , this study is the first to address the critical question of whether continued combined treatment confers superior efficacy . This study is a r and omized , double-blind , three-arm study in patients with panic disorder ( n = 60 ) , comparing the efficacy and safety of paroxetine and placebo ( PP ) , paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase ( PC-D ) , and ongoing combination treatment ( PC-M ) . All treatment groups demonstrated significant improvement by endpoint . There was a significant advantage for the combined treatment groups early in treatment but , subsequently , outcome in all three groups was similar . A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered . The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout . Combined treatment with paroxetine and clonazepam result ed in more rapid response than with the SSRI alone , but there was no differential benefit beyond the initial few weeks of therapy . Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy 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 The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder ( PD ) . Twenty-five out patients having PD with or without agoraphobia were included . These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day . Treatment-resistant PD was defined as a less than 20 % reduction in score on the Panic Self- Question naire ( number of attacks per week ) ( PSQ ) and the Clinical Anxiety Scale With Panic Attacks ( CAS+PA ) . These patients continued to receive fluoxetine 20 mg/day and were r and omly assigned to additionally receive either pindolol ( 2.5 mg three times daily ) or placebo for the following 4 weeks . Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety , the Hamilton Rating Scale for Depression ( HAM-D ) , the CAS+PA , the NIMH Anxiety Scale , the PSQ , and the Clinical Global Impression Scale . The data were analyzed using a repeated- measures analysis of variance ( ANOVA ) and a t-test for independent sample s. Patients treated with the combination of pindolol and fluoxetine ( N = 13 ) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales , with the exception of HAM-D. The statistical differences were shown using the repeated- measures ANOVA ( baseline , week 2 , week 4 ) and also with t-tests from the second week of the trial . These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD 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 In this open label pilot study , we studied the efficacy of mirtazapine ( Remeron ) in panic disorder . Twenty-eight patients with a DSM-IV diagnosis of panic disorder , with or without agoraphobia ( 10 males/18 females ) , were included and 19 patients completed the study . The 15-week trial started with a 3-week single-blind placebo run-in period . After this run-in period , the 12-week active treatment phase started . As primary efficacy measures , we studied the decrease in the number of full symptom panic attacks and the number of patients completely free of panic during the last 3 weeks of the study . Seventy-four percent of the patients were considered responders , according to a decrease of at least 50 % in panic attack frequency . All primary and secondary efficacy measures showed a significant improvement from the second week of active treatment onwards to endpoint . The main side-effects were different from the usual side-effects in selective serotonin reuptake inhibitors ( SSRIs ) ( initial drowsiness , weight gain and pain in the legs ) . The results of this open label study in panic disorder suggest that mirtazapine seems to be a fast and effective treatment alternative for SSRIs in panic disorder OBJECTIVE To compare the long-term efficacy of venlafaxine extended release ( ER ) with placebo in preventing panic disorder relapse in out-patient treatment responders . METHOD Out patients aged > or = 18 years who met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for panic disorder with or without agoraphobia for at least the previous 3 months , with > or = 6 full symptom panic attacks in the 2 weeks prior to screening and > or = 3 in the 2 weeks before baseline and a Clinical Global Impressions-Severity of Illness rating > or = 4 at screen were eligible to participate . Out patients received flexible-dose ( 75 - 225 mg/day ) venla-faxine ER for 12 weeks . Treatment responders were r and omly assigned to venlafaxine ER or placebo for 26 weeks . Criteria for response were < or = 1 panic attack per week during the last 2 weeks of open-label treatment and a Clinical Global Impressions-Improvement score of 1 or 2 . The primary endpoint , time to relapse during double-blind treatment , defined as > or = 2 full symptom panic attacks per week for 2 consecutive weeks or discontinuation due to loss of effectiveness , was evaluated using Kaplan-Meier survival analysis . The study was conducted between December 2001 and August 2003 . RESULTS The intent-to-treat population had 291 patients in the open-label phase and 169 in the double-blind phase  ( placebo , N = 80 ; venlafaxine ER , N = 89 ; mean daily dose 165 - 171 mg ) . Time to relapse was significantly longer with venlafaxine ER than placebo ( p < .001 ) . All secondary measures of panic attack treatment efficacy , quality of life , and disability were significantly better with venlafaxine ER than placebo ( p < or = .005 ) . CONCLUSION Venlafaxine ER was safe , well tolerated , and effective in preventing relapse in out patients with panic disorder INTRODUCTION Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent . More research examining pharmacotherapy augmentation strategies to improve outcomes is needed . METHODS In an 8-week , open-label , prospect i ve augmentation study , we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult out patients with generalized anxiety disorder ( n=13 ) or panic disorder ( n=10 ) who remained symptomatic despite treatment for at least 8 weeks with an adequate ( or maximally tolerated ) dose of typical pharmacotherapy . RESULTS Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores ( paired t=4.41 , df=22 , P<.001 ) in the intent-to-treat sample of 23 individuals . Three subjects ( 13 % ) discontinued due to sedation , chest discomfort , and restlessness , respectively . CONCLUSION These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy INTRODUCTION There is evidence that a decreased GABAergic tone plays a role in the pathophysiology of panic disorder ( PD ) . Selective GABAergic treatment has been suggested as a new therapeutic strategy in PD . In this pilot- study anxiolytic effects of the GABA reuptake inhibitor tiagabine ( TGB ) were investigated in PD . METHODS A total of 19 patients were treated with TGB ( n=10 ) or placebo ( n=9 ) for 4 weeks . PAS , HAM-A , and CGI ratings were administered every week . To further assess specific antipanic activity , panic challenges with CCK-4 were carried out in single subjects . RESULTS Although there was a significant reduction of clinical rating scores over time , no differences were detected between the groups . However , during challenge experiments TGB treated subjects showed decreased sensitivity to CCK-4 . DISCUSSION Whereas tiagabine did not show beneficial effects on clinical symptoms in PD compared to placebo , results of challenge experiments suggest effects of TGB on sensitivity to experimentally induced panic In a recent study , the authors suggested that tachycardia , dry mouth , and sweating continued to burden patients with panic disorder with agoraphobia who have shown marked and stable response to 6 months of imipramine treatment at the fixed , weight-adjusted dose of 2.25 mg/kg/day . Although sexual dysfunction and weight gain were not a significant burden in that study , they are important problems in long-term treatment with antidepressant drugs . In the present study , in the context of a r and omized , double-blind , placebo-controlled , 1-year discontinuation and maintenance study of 53 patients with panic disorder with agoraphobia who respond to imipramine  , the authors examine the extent and the specificity of these five side effects of imipramine maintenance using data at pretreatment , at the end of 24 weeks of open imipramine treatment ( or month 0 of r and omization ) , and at months 2 , 4 , 6 , 8 , 10 , and 12 of r and omized treatment . Hierarchical linear modeling and repeated measures of analyses of variance in sub sample s of completers confirmed that dry mouth , sweating , and increased heart rate constitute a significant and specific enduring burden of imipramine maintenance treatment . The data also revealed that weight gain is a significant and specific side effect of 1-year imipramine maintenance treatment ; however , the likelihood of reporting sexual dysfunction decreased over time , with no difference between the placebo and imipramine maintenance conditions . The results are discussed in the context of previous studies of imipramine  side effects in the management of depression and the available literature of sexual and weight side effects of antidepressant medications in the treatment of anxiety disorders In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines Serotonergic mechanisms have been implicated in panic disorder , and several preliminary studies suggest that fluvoxamine , a selective serotonin reuptake inhibitor ( SSRI ) , is helpful in its treatment . This 8-week double-blind parallel-group study compared fluvoxamine with a placebo in 188 patients with DSM-III-R defined panic disorder with or without agoraphobia . Efficacy assessment s included a Daily Panic Attack Inventory , the Sheehan Disability Scale , the Clinical Anxiety Scale and the Clinical Global Impression Scale . When compared with the placebo , fluvoxamine produced highly significant improvements in most measures of the frequency and severity of panic disorder and in the more global aspects of disability and distress . Significant improvement was evident as early as week 1 for some panic variables . Fluvoxamine is a potent anti-panic agent with a relatively rapid onset of action 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 Fifteen patients with panic disorder participated in a 12-week treatment trial with open-label nefazodone . Nefazodone was well-tolerated with minimal side effects ; none of the patients reported sexual dysfunction , and only one patient experienced weight gain . Although the response rate was lower than that found with most other antipanic medications , given its favorable side effect profile , nefazodone may be a good alternative for patients apprehensive about potential adverse drug reactions 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 The effect of a short treatment ( 7 days ) with citalopram on the reactivity to inhalations of 35 % CO 2 and 65 % oxygen and on clinical symptomatology was investigated in 15 patients with panic disorder who had a positive response to 35 % CO 2 inhalation . An open study design was applied . On day 0 , before starting drug treatment , and after 1 week of treatment , each patient underwent the 35 % CO 2 challenge , and clinical symptomatology was evaluated with psychometric scales . The results showed a significant reduction of CO 2 reactivity and of scores on the anticipatory anxiety subscale of Panic Associated Symptoms Scale . These results confirm that the serotonergic system plays an important role in the modulation of CO 2 hyperreactivity and suggest an early anxiolytic effect of citalopram in patients who have panic disorder and are hyperreactive to CO 2 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 Our objective was to explore the dose-response relationship in patients with panic disorder and social anxiety disorder comorbidity ( DSM-IV ) . After 1 week of no-drug washout , 36 such patients were assigned to a double-blind controlled comparison of the effects of 30 mg and 60 mg of tranylcypromine , and were followed up for 12 weeks . The main instrument used to measure the number of panic attacks was the Sheehan Panic and Anticipatory Anxiety Scale . The primary outcome measure for social anxiety disorder symptoms was the mean change from baseline in the Liebowitz Social Anxiety Scale ( LSAS ) . After 12 weeks of treatment , panic attacks were reduced 69.6 % from baseline in the 30-mg group ( n=19 ) compared with a 74.8 % reduction in the 60-mg group ( n=17 ) . Twelve patients ( 70.6 % ) of the higher dose group and 14 patients ( 68.4 % ) of the lower dose were completely free of panic attacks . There was no difference in efficacy between the tranylcypromine groups in the panic disorder symptoms . The 60-mg dose was more efficacious as measured by the LSAS scores , showing a significant difference in relation to the lower group . Mean change from baseline in LSAS total score ( mean+/-SD ) for 30-mg group was 17.9+/-14.7 and for the 60-mg group was 35.0+/-14.8 . The social anxiety symptom scale showed a two-fold greater change with the 60-mg dose , and the 30-mg dose group could be considered the equivalent of a placebo control group . Tranylcypromine--60 mg daily -- was found effective in the treatment of panic disorder and social anxiety disorder comorbidity
target: These drugs were better tolerated than tricyclics and benzodiazepines as they had a low risk of dependence and overdosing complications .
  The serotonergic , noradrenergic and GABAergic pathways play a major role in the fear network and in the physiopathology of PD .
background: INTRODUCTION Panic disorder ( PD ) is a prevalent psychiatric disorder characterized by unexpected and recurrent panic attacks .
  PD patients present significant psychosocial impairment and a high risk of psychiatric comorbidities and suicide .
  PD should be treated effectively as soon as the symptoms emerge because the longer these patients remain without treatment , the worse the prognosis will be .
  SSRIs and SNRIs are the first-line compounds in the treatment of PD .