Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder. Discontinuation of benzodiazepine treatment: efficacy of cognitive-behavioral therapy for patients with panic disorder. Efficacy of CBT for benzodiazepine discontinuation in patients with panic disorder: Further evaluation. Combined Paroxetine and Clonazepam Treatment Strategies Compared to Paroxetine Monotherapy for Panic Disorder Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia? Maintenance drug therapy of panic disorder. Therapeutic response to benzodiazepine in panic disorder subtypes. Diazepam and propranolol in panic disorder and agoraphobia. Diazepam versus alprazolam for the treatment of panic disorder. Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia. Controlled discontinuation of benzodiazepine treatment for patients with panic disorder. Cognitive-behavioral therapy helps prevent relapse and recurrence of panic disorder following alprazolam discontinuation: a long-term follow-up of the Peoria and Dartmouth studies. Does the addition of cognitive behavioral therapy improve panic disorder treatment outcome relative to medication alone in the primary-care setting? Treatment of Panic Disorder with Agoraphobia: Randomized Placebo‐Controlled Trial of Four Psychosocial Treatments Combined with Imipramine or Placebo The 35% CO 2 Hyperreactivity and Clinical Symptomatology in Patients With Panic Disorder After 1 Week of Treatment With Citalopram: An Open Study Effect of alprazolam and diazepam on anxiety and panic attacks in panic disorder: a controlled study. Cognitive behavioral group therapy in panic disorder patients: the efficacy of CBGT versus drug treatment.
BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy OBJECTIVE The primary disadvantage of high-potency benzodiazepine treatment for panic disorder is the difficulty of discontinuing the treatment . During treatment discontinuation , new symptoms may emerge and anxiety may return , preventing many patients from successfully discontinuing their treatment . In this controlled , r and omized trial the authors investigated the efficacy of a cognitive-behavioral program for patients with panic disorder who were attempting to discontinue treatment with high-potency benzodiazepines .  METHOD Out patients treated for panic disorder with alprazolam or clonazepam for a minimum of 6 months and expressing a desire to stop taking the medication ( N = 33 ) were r and omly assigned to one of two taper conditions : a slow taper condition alone or a slow taper condition in conjunction with 10 weeks of group cognitive-behavioral therapy . RESULTS The rate of successful discontinuation of benzodiazepine treatment was significantly higher for the patients receiving the cognitive-behavioral program ( 13 of 17 ; 76 % ) than for the patients receiving the slow taper program alone ( four of 16 ; 25 % ) . There was no difference in the likelihood of discontinuation success between the patients treated with alprazolam and those who received clonazepam . At the 3-month follow-up evaluation , 77 % of the patients in the cognitive-behavioral program who successfully discontinued benzodiazepine treatment remained benzodiazepine free . CONCLUSIONS These findings support the efficacy of cognitive-behavioral interventions in aiding benzodiazepine discontinuation for patients with panic disorder Despite its acute efficacy for the treatment of panic disorder , benzodiazepines ( BZs ) are associated with a withdrawal syndrome that closely mimics anxiety sensations , leading to difficulty with treatment discontinuation and often disorder relapse . An exposure-based cognitive-behavioral treatment for BZ discontinuation , Panic Control Treatment for BZ Discontinuation ( CBT ) targets the fear of these sensations and has demonstrated efficacy in preventing disorder relapse and facilitating successful BZ discontinuation among patients with panic disorder . In this r and omized controlled trial , CBT was compared to taper alone and a taper plus a relaxation condition to control for the effect of therapist contact and support among 47 patients with panic disorder seeking taper from BZs . Based on the primary outcome of successful discontinuation of BZ use , results indicate that adjunctive CBT provided additive benefits above both taper alone and taper plus relaxation , with consistently medium and large effect sizes over time that reached significance at the six month follow-up evaluation . The efficacy of CBT relative to either of the other taper conditions reflected very large and significant effect sizes at that time . These findings suggest that CBT provides specific efficacy for the successful discontinuation from BZs , even when controlling for therapist contact and relaxation training 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 OBJECTIVE Recently , pharmacological treatment guidelines for panic disorder have changed as newer treatment options have become available . The authors examined how the use of psychotropic drugs has shifted over the course of 10 years to determine if prescribing patterns have changed to reflect these revised treatment guidelines . METHOD A total of 443 patients with panic disorder were enrolled in the Harvard/Brown Anxiety Research Project , a prospect i ve longitudinal study of anxiety disorders . These patients were interviewed over the course of 10 years to examine their use of psychotropic medications . RESULTS Despite efforts aim ed at increasing the use of selective serotonin reuptake inhibitors ( SSRIs ) in patients with panic disorder ( e.g. , APA 's practice guideline for panic disorder , Food and Drug Administration approval of particular SSRIs for the treatment of panic disorder ) , only a modest increase in their use was found . Treatment patterns for psychotropic drugs  appear to have remained stable over the past decade , with benzodiazepines being the most commonly used medication for panic disorder . In comparison , SSRI use throughout the follow-up period has remained low . Patients using an SSRI did not have a more favorable clinical course than those using a benzodiazepine , nor were there significantly better rates of remission in patients using SSRIs and benzodiazepines concomitantly . CONCLUSIONS These results highlight a gap between pharmacological treatment guidelines and actual delivery of care in that recommendations to use SSRIs to treat panic disorder are not being followed . Factors potentially associated with promoting and ignoring treatment recommendations are discussed The efficacy of tricyclics and benzodiazepines in the short term ( approximately 2 - 4 months ) treatment of panic disorder is well demonstrated , but efficacy over the longer term is not considered established . The present study provided systematic data from a double blind comparison of maintenance therapy ( up to 8 months ) of panic disorder with or without agoraphobia with alprazolam , imipramine , or placebo in 181 patients who had responded to the same regimen in a r and omized 8-week treatment trial . All three groups had improved during the first 2 months ( active treatments more than placebo and about equal to each other ) , and all maintained or extended their improvement over the next 6 months without any significant change in dose . More than twice as many alprazolam and imipramine than placebo patients ( 15 % ) remained in treatment for the full 8 months and did slightly better on symptom measures than the remaining placebo patients . Both medications were well tolerated during the maintenance period . The data suggest sustained efficacy and safety of imipramine and alprazolam over an extended period . More specifically , they suggest that tolerance does not develop to the therapeutic effects of either drug 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 The response to diazepam and propranolol hydrochloride was compared in 21 patients who ( with one exception ) met DSM-III criteria for panic disorder and agoraphobia . Each drug was administered for two weeks in double-blind fashion according to a crossover design . The response to diazepam was significantly superior on all measures . By observer rating , 18 patients showed at least moderate improvement with diazepam compared with seven receiving propranolol .  Panic attacks and phobic symptoms responded to diazepam , but not to propranolol . The results suggest that benzodiazepines constitute effective short-term treatment for these newly defined disorders BACKGROUND Alprazolam has proven efficacy as a treatment for panic disorder , but the place of other benzodiazepines is less well established . METHOD To compare the efficacy and tolerability of diazepam and alprazolam for the disorder , a placebo-controlled , double-blind trial was undertaken in two sites . Two hundred forty-one subjects with panic disorder or agoraphobia with panic attacks were r and omly assigned to flexible doses of diazepam , alprazolam , or placebo for 8 weeks . RESULTS At the end of the trial , over 60 % of subjects taking either diazepam or alprazolam were at least moderately improved compared with less than 30 % of those taking placebo . On all measures of efficacy , subjects taking diazepam and alprazolam showed an equally favorable response . Despite some sedation early in the trial , both drugs were tolerated well . More severely ill subjects responded less well to either benzodiazepine . CONCLUSION The results indicate that diazepam is an effective alternative to alprazolam for the treatment of panic disorder The past decade has brought major new developments in the psychopharmacologic management of generalized anxiety disorder and social phobia . We examined medication-prescribing patterns for the treatment of these anxiety disorders for 12 years to assess changes in patients ' anti-anxiety psychotropic medication usage during that period of evolving practice guidelines . We examined psychotropic medication use in 305 patients with generalized anxiety disorder and 232 with social phobia enrolled in the Harvard/Brown Anxiety Disorders Research Project ( HARP ) , a prospect i ve , longitudinal study of anxiety disorders .  Psychotropic treatment patterns seem to have remained relatively stable over 12 years with benzodiazepines the medications most commonly used for both generalized anxiety disorder and social phobia . Comparatively , selective serotonin reuptake inhibitor ( SSRI ) and venlafaxine usage as st and -alone medications for these disorders remained low throughout the follow-up period . At the 12-year follow-up , 24 % of patients with generalized anxiety disorder and 30 % of patients with social phobia were utilizing neither an  SSRI/selective norepinephrine reuptake inhibitor ( SNRI ) nor a benzodiazepine . Treatment recommendations for use of SSRIs and venlafaxine in the management of generalized anxiety disorder and social phobia initially promulgated in 1998 had a modest impact on changes in psychopharmacologic practice 4 - 5 years later . Difficulties in the implementation of treatment guidelines are discussed OBJECTIVE The purpose of this study was to compare the effects of discontinuing treatment with intermediate- and long-acting benzodiazepines . METHOD Fifty patients with panic disorder who had taken part in a double-blind treatment study and had responded to alprazolam , diazepam , or placebo for 8 months were asked to stop taking these medications gradually . RESULTS After a relatively rapid dose reduction , the majority of patients relapsed . Rebound anxiety and withdrawal symptoms were identified in a substantial minority of patients . Those who were taking alprazolam showed earlier and more intense rebound anxiety and withdrawal symptoms than did the patients who received diazepam . Both the level of pretreatment anxiety and the drug the patient was taking predicted the level of anxiety when drug treatment was discontinued . CONCLUSIONS The findings indicate that withdrawal phenomena commonly occur after patients stop taking benzodiazepines and that they are more frequent after discontinuation of treatment with shorter-acting drugs The present research evaluated patients from 2 previous studies ( 1 conducted in Peoria , the other at Dartmouth ) during a 2- to 5-year posttreatment period . Results showed that 75 % of the Peoria sample and 76 % of the Dartmouth sample were able to discontinue alprazolam therapy , remain abstinent of any type of treatment for panic disorder , and maintain their acute-treatment clinical gains over this follow-up period . The degree to which patients ' anxiety sensitivity declined during treatment predicted relapse versus survival during the 1st 6 months of follow-up , when most relapses occurred . Implication s of these findings for benzodiazepine discontinuation , combined pharmacotherapy and psychotherapy , and relapse prevention in panic disorder are discussed BACKGROUND R and omized clinical trials indicate a benefit from combining medications with cognitive behavioral therapy ( CBT ) relative to medication alone for panic disorder . Using an as-treated analysis , we evaluated whether the addition of CBT enhanced outcomes for panic disorder relative to medications alone in the primary -care setting . METHOD Primary -care patients with panic disorder reported on their receipt of CBT and medications over the 3 months following baseline assessment . The degree to which outcomes for those who used anti-panic medications were enhanced by the receipt of at least one component of CBT was analyzed using a propensity score model that took into account observable baseline patient characteristics influencing both treatment selection and outcomes . RESULTS The addition of CBT result ed in statistically and clinical ly significant improvements at 3 months on anxiety sensitivity , social avoidance , and disability . Also , patients receiving CBT in the first 3 months of the study were more improved at 12 months than patients who took medications only during the first 3 months of the study . CONCLUSIONS The clinical utility of the findings are discussed in terms of the importance of primary -care physicians encouraging their panic disorder patients to receive CBT as well as medications 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 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 Forty-eight patients currently experiencing panic attacks were r and omly assigned to double-blind treatment with alprazolam , diazepam , or placebo .  Efficacy was assessed using the Hamilton Rating Scale for Anxiety and a panic attack frequency rating scale . Results indicate that the two active treatments appeared equally effective in reducing both the frequency of panic attacks and the severity of generalized anxiety when compared with placebo . Overall , these data support the use of benzodiazepines in the treatment of panic disorder The aim of our study was to evaluate the effectiveness of Cognitive Behavioral Group Therapy ( CBGT ) in the treatment of Panic Disorder ( PD ) and to compare the treatment outcome of CBGT versus Paroxetine pharmacotherapy .  Fifty seven patients referred to our anxiety disorder clinic for the treatment of PD were r and omly allocated to receive either CBGT or Paroxetine . Follow up was done by a masked rater after four and twelve weeks of treatment in order to compare the efficacy of CBGT versus Paroxetine . CBGT and Paroxetine were both effective in the short-term treatment of PD . Assessment s at weeks four and twelve of treatment showed no statistically significant differences between the two groups in terms of treatment outcome . Treatment with CBGT alone for the acute phase of PD appears to be equally efficacious to treatment with Paroxetine alone . Our study shows that CBGT produced beneficial results , for it was associated with a reduction in the number and frequency of panic attacks and with an improved feeling of well-being
The review established the paucity of high quality evidence investigating the efficacy of psychotherapy combined with benzodiazepines for panic disorder .
Currently , there is inadequate evidence to assess the clinical effects of psychotherapy combined with benzodiazepines for patients who are diagnosed with panic disorder
BACKGROUND The efficacy of combining psychotherapy and benzodiazepines for panic disorder is unclear , despite widespread use .
OBJECTIVES To examine the efficacy of the combination compared with either treatment alone .