Alprazolam, Propranolol, and Placebo in the Treatment of Panic Disorder and Agoraphobia with Panic Attacks A phase II multicenter dose-finding, efficacy and safety trial of ipsapirone in outpatients with generalized anxiety disorder Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Associations of fearful spells and panic attacks with incident anxiety, depressive, and substance use disorders: a 10-year prospective-longitudinal community study of adolescents and young adults. Quality of life in panic disorder. Two-year course trajectories of anxiety disorders: do DSM classifications matter? Comparative effects of low and high doses of clomipramine and placebo in panic disorder: a double‐blind controlled study Alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia. Quality of life and psychiatric morbidity in panic disorder and generalized anxiety disorder. 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. Psychopharmacological treatment of panic disorder and related states: A Placebo controlled study of alprazolam Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder. Avoidance behaviour: A predictor of the efficacy of pharmacotherapy in panic disorder? Maintenance drug treatment of panic disorder. I. Results of a prospective, placebo-controlled comparison of alprazolam and imipramine. Medical utilisation and costs in panic disorder: a comparison with social phobia. Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Primary anxiety disorders and the development of subsequent alcohol use disorders: a 4-year community study of adolescents and young adults. The use of the Panic and Agoraphobia Scale (P & A) in a controlled clinical trial. Sequence of improvement in agoraphobia with panic attacks. Evidence that decreased function of lymphocyte beta adrenoreceptors reflects regulatory and adaptive processes in panic disorder with agoraphobia. What characteristics of primary anxiety disorders predict subsequent major depressive disorder? Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia?
Fifty-five patients completed a 5-week double-blind study comparing alprazolam , propranolol , and placebo in the treatment of panic disorder and agoraphobia with panic attacks . There was no concomitant behavioral treatment . Patient and therapist rating scales included Sheehan 's Panic and Anxiety Attack Scales , the Marks-Sheehan Phobia Scale , the Hamilton Anxiety Scale , the Hamilton Depression Scale , and the Side Effects Checklist . The results generally support the efficacy of alprazolam , but not propranolol , in the treatment of panic disorder and agoraphobia with panic attacks . The significance of the results are discussed , as well as a number of the unique aspects of our procedures and patient population Benzodiazepines have been prescribed for the treatment of  Generalized Anxiety Disorder ( GAD ) for nearly three decades due to their proven anxiolytic efficacy , despite a considerable side effect and abuse liability profile . A new class of compounds , the azapirones , have been developed as an alternative to benzodiazepine treatment . Ipsapirone is a novel anxiolytic azapirone which has high specificity for the 5-HT1A receptor and which has the potential for offering certain advantages over buspirone . The present 5-week study investigated three doses of ipsapirone ( 2.5 mg , 5.0 mg and 7.5 mg tid ) versus placebo in 267 GAD out patients .  Efficacy was evaluated using the Hamilton Anxiety Rating Scale ( HAM-A ) , Zung Anxiety Scale ( Zung-A ) , and Clinical Global Impression ( CGI ) . The study design consisted of a 1-week placebo run-in , a 4-week double-blind treatment period , and a 1-week placebo washout . The 5.0 mg group demonstrated consistently superior improvement in all efficacy variables during the treatment period , with significant differences ( p < 0.05 ) from placebo and , at times , the 2.5 mg and 7.5 mg groups . Incidence of adverse events , primarily dizziness , nausea , sedation , and asthenia , was found to be dose proportional , with significant increase in the 7.5 mg group , which may account for the diminished effectiveness seen with this dose . Our results suggest that ipsapirone may represent a viable treatment for GAD 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 OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders OBJECTIVE The concept of fearful spells ( FS ) denotes distressing spells of anxiety that might or might not qualify for criteria of panic attacks ( PA ) . Few studies examined prospect ive-longitudinal associations of FS not meeting criteria for PA with the subsequent onset of mental disorders to clarify the role of FS as risk markers of psychopathology . METHOD A representative community sample of adolescents and young adults ( N = 3021 , age 14 - 24 at baseline ) was prospect ively followed up in up to 3 assessment waves over up to 10 years .  FS , PA , anxiety , depressive , and substance use disorders were assessed using the DSM-IV/M-CIDI . Odds Ratios ( OR ) from logistic regressions were used to examine the predictive value of  FS-only ( no PA ) and PA at baseline for incident disorders at follow-up . RESULTS In logistic regressions adjusted for sex and age , FS-only predicted the onset of any subsequent disorder , any anxiety disorder , panic disorder , agoraphobia , GAD , social phobia , any depressive disorder , major depression , and dysthymia ( ORs 1.54 - 4.36 ) ; PA predicted the onset of any anxiety disorder , panic disorder , GAD , social phobia , any depressive disorder , major depression , dysthymia , any substance use disorder , alcohol abuse/dependence , and nicotine dependence ( ORs 2.08 - 8.75 ; reference group : No FS-only and no PA ) . Associations with psychopathology were slightly smaller for FS-only than for PA , however , differences in associations ( PA compared to FS-only ) only reached significance for any anxiety disorder ( OR = 3.26 ) and alcohol abuse/dependence ( OR = 2.26 ) . CONCLUSIONS Findings suggest that compared to PA , FS-only have similar predictive properties regarding subsequent psychopathology and might be useful for an early identification of high-risk individuals Data from the Epidemiologic Catchment Area study showed that a lifetime Diagnostic Interview Schedule/DSM-III diagnosis of panic disorder was associated with pervasive social and health consequences similar to or greater than those associated with major depression . These consequences included subjective feelings of poor physical and emotional health , alcohol and other drug abuse , increased likelihood of suicide attempts , impaired social and marital functioning , financial dependency , and increased use of psychoactive medications , health services , and the hospital emergency department for emotional problems . Comorbidity of panic disorder with major depression , agoraphobia , and alcohol or other drug abuse did not explain these findings . The social and health consequences of panic disorder ( quality of life ) should be considered , as risks and benefits of currently available acute and maintenance treatments are evaluated . Clinical trials of panic disorder , whether of drugs or behavioral treatment , should include quality of life assessment s as outcome measures . Long-term prospect i ve studies based on clinical sample s of patients with panic disorder are indicated to relate the illness more precisely to social morbidity OBJECTIVE Anxiety disorders have been shown to differ in their course , but it is unknown whether DSM-categories represent clinical ly relevant course trajectories . We aim to identify anxiety course trajectories using a data -driven method and to examine whether these course trajectories correspond to DSM-categories or whether other clinical indicators better differentiate them . METHOD 907 patients with panic disorder with agoraphobia , panic disorder without agoraphobia , agoraphobia , social phobia , or generalized anxiety disorder according to DSM-IV criteria were derived from a prospect i ve cohort study ( Netherl and s Study of Depression and Anxiety ) . Baseline data were collected between September 2004 and February 2007 ; follow-up data , between October 2006 and March 2009 . Latent class growth analysis was conducted , based on symptoms of anxiety and avoidance assessed with the Life Chart Interview covering a 2-year time period . Identified course trajectories were compared with DSM-IV diagnoses and a wider set of predictors . RESULTS We identified a class with minimal symptoms over time ( 41.7 % ) , a moderately severe chronic class ( 42.8 % ) , and a severe chronic class ( 15.4 % ) . Panic disorder with agoraphobia ( OR = 2.14 ; 95 % CI , 1.48 - 3.09 ) and social phobia ( OR = 1.97 ; 95 % CI , 1.46 - 2.68 ) predicted moderately severe chronicity ; panic disorder with agoraphobia ( OR = 2.70 ; 95 % CI , 1.66 - 4.40 ) , social phobia ( OR = 2.46 ; 95 % CI , 1.62 - 3.74 ) , and generalized anxiety disorder ( OR = 1.86 ; 95 % CI , 1.23 - 2.82 ) predicted a severe chronic course . However , baseline severity , duration of anxiety , and disability better predicted severe chronic course trajectories than DSM-categories . Additionally , partner status , age at onset , childhood trauma , and comorbid depressive disorder predicted chronic courses . CONCLUSIONS Course of anxiety was pleomorphic with over 40 % having a favorable course , thereby question ing the common notion of chronicity of anxiety disorders . Severity , duration of anxiety , and disability were able to better identify severe chronic course trajectories as compared with DSM-IV categories . These findings facilitate the identification of chronic course trajectories of anxiety disorders in clinical care and support current debates on staging and profiling of mental disorders This study was design ed to explore the dose‐response relationship for clomipramine in patients with panic disorder , with or without agoraphobia . After 1 week of single‐blind placebo pretreatment , 180 such patients were assigned to a multicentre  placebo‐controlled comparison of the effects of high and low doses of clomipramine , and were followed up for 8 weeks . In alleviating anxiety and panic disorder , both clomipramine doses were more efficacious than placebo for panic disorder and , to a lesser degree , for phobia . The lower dose was better tolerated and at least as effective as the higher dose , sometimes more so . These results indicate the clinical ly important possibility that low‐dose clomipramine is effective and well tolerated OBJECTIVE The authors ' goal was to evaluate the relationship between plasma concentrations of alprazolam and both treatment response and side effects in patients with panic disorder and agoraphobia . METHOD Ninety-six patients with panic disorder and agoraphobia were treated at three sites in a 6-week , fixed-dose , double-blind , placebo-controlled , dose-response study of 2 mg/day or 6 mg/day of alprazolam . Assessment s were made of panic attacks , avoidance behavior , generalized anxiety , and global response . Blood sample s were collected throughout the study and analyzed for alprazolam and other benzodiazepines . RESULTS Patient compliance with the protocol was judged to be good on the basis of plasma concentrations . According to logistic regression analysis , the relationships between plasma alprazolam concentration and response , as reflected by number of panic attacks reported , phobia ratings , physicians ' and patients ' ratings of global improvement , and the emergence of side effects , were significant . However , there was no significant relationship between plasma alprazolam concentration and the degree of generalized anxiety symptoms . CONCLUSIONS The authors conclude that plasma concentration of alprazolam  is related to treatment response , particularly in panic attacks . The  alprazolam concentration associated with treatment response or with emergence of a given side effect varied widely among individuals , highlighting the necessity for individualized dose adjustment to obtain optimal treatment response while minimizing side effects OBJECTIVE This report examines the impact of panic disorder and /or generalized anxiety disorder on quality of life and the implication s of these findings on nosological categories . METHOD A total of 357 subjects with a current episode of panic disorder and /or generalized anxiety disorder were diagnosed according to DSM-III-R criteria , using structured clinical interviews , as part of a prospect i ve , naturalistic , longitudinal , multicenter study of a clinical population with anxiety disorders . RESULTS There was a high degree of coexistence of anxiety disorders and major depressive disorder . Subjects with generalized anxiety disorder almost universally had other disorders , were the most likely to have at least one other anxiety disorder or major depressive disorder at intake , had the earliest age at onset , and had the worst emotional health rating . Subjects with panic disorder without agoraphobia had the most likelihood of a history of alcohol abuse . Nine percent of the subjects had a history of suicide attempts or gestures . CONCLUSIONS The subjects showed significant impairment in quality of life . The highly frequent coexistence of other anxiety disorders with generalized anxiety disorder and the overall lack of differences on many quality of life measures raise questions of nosology , particularly for generalized anxiety disorder 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 The paper consists of two parts . A review of the relationship of panic disorder to the phobic states and the treatment of these disorders by means of tricyclic antidepressants , MAOIs , beta blocking drugs and benzodiazepines . A double blind study of alprazolam and placebo in 118 patients with agoraphobia and panic is presented . In an eight week study alprazolam was found to be significantly superior to placebo in the treatment of panic attacks , phobic avoidance , anticipatory anxiety and general anxiety BACKGROUND The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects . The efficacy of alprazolam and placebo in panic disorder with agoraphobia , and the side-effect and adverse effect profiles of both drug groups were measured . METHOD In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were r and omised to alprazolam or placebo .  Subjects in each drug group also received either exposure or relaxation . Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16 . RESULTS Mean alprazolam dose was 5 mg daily . Compared with placebo subjects , alprazolam patients developed more adverse reactions ( 21 % v. 0 % ) of depression , enuresis , disinhibition and aggression ; and more side-effects , particularly sedation , irritability , impaired memory , weight loss and ataxia . Side-effects tended to diminish during treatment but remained significant at week 8 . Despite this , the drop-out rate was low . CONCLUSIONS Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these Summary The impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study ( n=1134 patients ) ; in this double blind r and omized trial alprazolam , imipramine and placebo were compared during an 8-week treatment period . Patients with extensive avoidance behaviour ( agoraphobia ) had the most profit from the active drugs . Counter expectancy these specific drug effects were most pronounced in avoidance behaviour . Active drugs ( in particular imipramine ) were especially more effective than placebo if the patients presented with associated avoidance behaviour . The results suggest that agoraphobia defines more a particular type of anxiety disorder overlapping with panic disorder than merely a severe state of panic disorder One hundred six patients diagnosed according to DSM-III as suffering from agoraphobia with panic disorder , panic disorder with limited phobic avoidance , or uncomplicated panic disorder entered an acute 8-week treatment phase . Patients who improved received an additional 6 months ' maintenance treatment . Significantly more patients treated with alprazolam than with imipramine hydrochloride or placebo remained in therapy and experienced panic attack and phobia relief during the acute treatment phase . During the maintenance phase , neither tolerance nor daily dose increase was observed . All patients who completed the maintenance phase ( 27 in the alprazolam group , 11 in the imipramine group , and 10 in the placebo group ) were panic free at the end of 8 months of study treatment . Alprazolam therapy was effective and well tolerated at a mean daily dose of 5.7 mg . Imipramine hydrochloride ( 175 mg/d ) also produced significant panic relief but was associated with poor patient acceptance There is considerable evidence that people with panic disorder utilise the physical health care system more frequently than people in the general community and so incur for themselves , and impose on the public health care system , considerably greater costs . Although this is probably because of specific characteristics to do with panic disorder , it may also be a function of having any anxiety disorder where panic is prominent . This study represents one of the few comparisons of medical utilisation and costs incurred by people with panic disorder to those incurred by people with another anxiety disorder , in this case , social phobia . Before treatment , 41 people with panic disorder , 15 with social phobia and 43 nonanxious controls  were interviewed about their use of the medical care system over the previous 12 months . As expected , people with panic disorder had significantly higher utilisation rates than either the nonanxious controls or the socially phobic subjects , and incurred substantially higher costs . Adequate screening for panic disorder at the primary medical care level together with appropriate treatment referral therefore have the potential to substantially reduce the personal and community costs incurred by people with panic disorder OBJECTIVE Although panic attacks account for only a portion of the morbidity of panic disorder and panic attack frequency assessment s are unreliable , studies of drug efficacy in panic disorder have generally used reduction in panic attack frequency as the primary measure of improvement . The authors studied the efficacy of fluoxetine treatment in panic disorder and measured the relative contributions of changes in symptoms to overall improvement . METHOD Patients with a diagnosis of panic disorder ( N = 243 ) were r and omly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo . Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impression improvement scores . Other assessment s included a panic attack inventory , clinician-rated and patient-rated versions of the Panic and Phobic Disorder Change Scale , a phobia rating scale , the Hamilton Anxiety Rating Scale , the 21-item Hamilton Depression Rating Scale , and the Sheehan Disability Scale . Correlations were determined between outcomes in individual symptom domains and overall clinical outcome . RESULTS Fluoxetine , particularly the 20-mg/day dose , was associated with more improvement than was placebo in patients with panic disorder across multiple symptom measures , including global improvement , total panic attack frequency , phobic symptoms , and functional impairment . Global improvement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attacks .  Fluoxetine treatment for panic disorder was well tolerated , with a safety profile consistent with that observed for fluoxetine in other disorders . CONCLUSIONS These data provide support for the efficacy and safety of fluoxetine treatment in reducing panic attacks , phobic symptoms , anxiety , and depressive symptoms in patients with panic disorder . Reductions in panic attack frequency in subjects given either fluoxetine or placebo were less closely related to overall clinical improvement than reductions in phobic avoidance , anxiety , depressive symptoms , and functional impairment , suggesting that outcome measures in this disorder should be more broadly based BACKGROUND Cross-sectional findings in community surveys of adults suggest that adolescent anxiety disorders are strong predictors of the subsequent onset of alcohol use , abuse and dependence . However , prospect i ve data that follow a sample of adolescents into adulthood are needed to confirm these associations . METHOD Baseline and 4-year follow-up data from the EDSP- Study , a prospect i ve community survey of 3021 ( 2548 at follow-up ) adolescents and young adults aged 14 to 24 years at baseline carried out in Munich , were used .  DSM-IV anxiety disorders , alcohol use and alcohol use disorders were assessed with the Munich-Composite-International-Diagnostic-Interview ( M-CIDI ) . Multiple logistic regression analysis , controlling for age , gender , other mental disorders , substance use disorders and antisocial behaviour was used to study the associations of baseline anxiety disorders with the subsequent onset and course of alcohol use and alcohol disorders . RESULTS Baseline social phobia significantly predicts the onsets of regular use and hazardous use and the persistence of dependence . Panic attacks significantly predict the onsets of hazardous use and abuse as well as the persistence of combined abuse/dependence . Panic disorder significantly predicts the persistence of combined abuse/dependence . Other anxiety disorders do not significantly predict any of the outcomes . CONCLUSIONS Panic and social phobia are predictors of subsequent alcohol problems among adolescents and young adults . Further studies are needed to investigate the underlying mechanisms and the potential value of targeted early treatment of primary panic and social phobia to prevent secondary alcohol use disorders 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 In a multi-center comparison of alprazolam to placebo in the treatment of agoraphobia with panic attacks , the sequence of sustained remission in both treatment groups , was panic attacks before phobias . This may suggest that phobias are secondary to panic attacks in the pathogenesis of the disorder , although other explanations may account for these data and are discussed OBJECTIVE This study was design ed to clarify the nature of the reduced function of the peripheral beta adrenoceptor system observed in panic disorder with agoraphobia . The authors hypothesized that this phenomenon reflected a regulatory and adaptive process . METHODS Lymphocyte beta adrenoreceptor density and affinity , basal lymphocyte cAMP level , and isoproterenol-stimulated cAMP generation were measured in 27 untreated out patients with panic disorder with agoraphobia and 24 healthy comparison subjects .  Lymphocyte beta receptor attributes were again assessed in patients after 4 weeks of double-blind treatment with adinazolam ( slow-release form ) or placebo .  Panic frequency , agoraphobic symptoms , overall anxiety , and improvement with treatment were assessed with st and ard rating instruments . RESULTS Multivariate statistics revealed significantly lower beta receptor density and isoproterenol-stimulated cAMP generation in patients than in comparison subjects . beta receptor density tended to normalize after adinazolam but not after placebo . Pretreatment beta receptor density was lower in treatment responders than nonresponders . Patients with mild agoraphobia had lower cAMP responsivity than patients with moderate or severe agoraphobia . CONCLUSIONS Decreased function of lymphocyte beta receptors in panic disorder with agoraphobia is expressed as both decreased density and decreased cAMP responsivity . This pattern of changes , and the tendency for receptor density to normalize with treatment , is consistent with an active , regulatory process rather than a structural deficit in the beta receptor system . Preliminary clinical findings suggest that these changes may reflect adaptive processes associated with a favorable clinical course in panic disorder with agoraphobia OBJECTIVE The goal of this study was to examine the associations between specific anxiety disorders and the risk of major depressive disorder  and to explore the role of various clinical characteristics of anxiety disorders in these relationships using a prospect i ve , longitudinal design . METHOD The data are from a 4-year prospect i ve ,  longitudinal community study  , which included both baseline and follow-up survey data on 2548 adolescents and young adults aged 14 to 24 years at baseline . DSM-IV diagnoses were made using the Munich-Composite International Diagnostic Interview . RESULTS The presence at baseline of any anxiety disorder ( odds ratio [ OR ] = 2.2 [ 95 % CI = 1.6 to 3.2 ] ) and each of the anxiety disorders ( specific phobia , OR = 1.9 [ 95 % CI = 1.3 to 2.8 ] ; social phobia , OR = 2.9 [ 95 % CI = 1.7 to 4.8 ] ; agoraphobia , OR = 3.1 [ 95 % CI = 1.4 to 6.7 ] ; panic disorder , OR = 3.4 [ 95 % CI = 1.2 to 9.0 ] ; generalized anxiety disorder , OR = 4.5 [ 95 % CI = 1.9 to 10.3 ] ) was associated with a significantly ( p < .05 ) increased risk of first onset of major depressive disorder . These associations remained significant after we adjusted for mental disorders occurring prior to the onset of the anxiety disorder , with the exception of the panic disorder association . The following clinical characteristics of anxiety disorders were associated with a significantly ( p < .05 ) increased risk of developing major depressive disorder : more than 1 anxiety disorder , severe impairment due to the anxiety disorder , and comorbid panic attacks . In the final model , which included all clinical characteristics , severe impairment remained the only clinical characteristic that was an independent predictor of the development of major depressive disorder ( OR = 2.2 [ 95 % CI = 1.0 to 4.4 ] ) . CONCLUSION Our findings suggest that anxiety disorders are risk factors for the first onset of major depressive disorder . Although a number of clinical characteristics of anxiety disorders appear to play a role in the association between anxiety disorders and depression , severe impairment is the strongest predictor of major depressive disorder 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 azapirones is uncertain due to the lack of meta-analysable data for the primary outcome and low- quality evidence for secondary efficacy outcomes .
A small amount of moderate- quality evidence suggested that the acceptability of azapirones for panic disorder was lower than for placebo .
If further research is to be conducted , studies with larger sample sizes , with different azapirones and with less risk of bias are necessary to draw firm conclusions regarding azapirones for panic disorder
BACKGROUND Panic disorder is common in the general population .
It is often associated with other psychiatric disorders , such as drug dependence , major depression , bipolar disorder , social phobia , specific phobia and generalised anxiety disorder .
Azapirones are a class of drugs used as anxiolytics .
They are associated with less drowsiness , psychomotor impairment , alcohol potentiation and potential for addiction or abuse than benzodiazepines .
However , azapirones are not widely used in the treatment of panic disorder and evidence for their efficacy is unclear .
It is important to find out if azapirones are effective and acceptable in the treatment of panic disorder .
OBJECTIVES To assess the effects of azapirones on panic disorder in adults , specifically:1 .
to determine the efficacy of azapirones in alleviating symptoms of panic disorder , with or without agoraphobia , in comparison with placebo;2 .
to review the acceptability of azapirones in panic disorder , with or without agoraphobia , in comparison with placebo ; and 3 .
to investigate adverse effects of azapirones in panic disorder with or without agoraphobia , including general prevalence of adverse effects , compared with placebo .