A 15-year follow-up study of patients with panic disorder. A prospective naturalistic study of 326 panic-agoraphobic patients treated with antidepressants. A randomized, double-blind, placebo-controlled study of ziprasidone monotherapy in bipolar disorder with co-occurring lifetime panic or generalized anxiety disorder. Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia. Pre-treatment predictors of treatment outcome in panic disorder and agoraphobia treated with alprazolam and exposure. Treatment of Panic Disorder with Agoraphobia: Randomized Placebo‐Controlled Trial of Four Psychosocial Treatments Combined with Imipramine or Placebo Long‐term outcome of pharmacological and psychological treatment for panic disorder with agoraphobia: a 2‐year naturalistic follow‐up Avoidance behaviour: A predictor of the efficacy of pharmacotherapy in panic disorder? Relationship of panic, anticipatory anxiety, agoraphobia and global improvement in panic disorder with agoraphobia treated with alprazolam and exposure. Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone. Alprazolam, imipramine and placebo treatment of panic disorder: predicting therapeutic response Alprazolam, Propranolol, and Placebo in the Treatment of Panic Disorder and Agoraphobia with Panic Attacks Global measures of outcome in a controlled comparison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary care. Alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia. Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. A double-blind placebo-controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa.
BACKGROUND Panic disorder ( PD ) is generally regarded as a chronic condition with considerable variation in severity of symptoms . AIMS To describe the long-term outcome of naturalistically treated PD . METHODS Fifty-five out patients with PD , who participated in a placebo-controlled drug trial of the efficacy of alprazolam and imipramine 15 years ago were reassessed with the same instruments used in the original study . RESULTS Complete recovery ( no panic attacks and no longer on medication during the last 10 years ) was seen in 18 % of patients , and an additional 13 % recovered but were still on medication . Fifty-one percent experienced recurrent anxiety attacks whereas 18 % still met diagnostic criteria for PD . The incidence of agoraphobia decreased from 69 % to 20 % . Patients with agoraphobia at admission tended to have a poorer long-term outcome according to daily functioning compared with patients without agoraphobia at admission , although both groups reported improved daily functioning at follow-up . Maintenance medication was common . No benzodiazepine abuse was reported . CONCLUSION PD has a favourable outcome in a substantial proportion of patients . However , the illness is chronic and needs treatment . The short-term treatment given in the drug trial had no influence on the long-term outcome OBJECTIVE How far the results of r and omized controlled studies apply to everyday care can not be judged without regular measurements of outcomes in daily practice . We report on systematic data from a 3-year naturalistic prospect i ve study on panic disorder-agoraphobic ( PDA ) patients treated with antidepressants in a setting of routine clinical practice . Our aim is to describe the evolution of PDA in relation to the treatments employed , and to explore demographic and clinical characteristics that might be predictive of outcome . METHODS 326 DSM-III-R PDA patients treated with antidepressants in a setting of routine clinical practice were included in a 3-year naturalistic prospect i ve study . We utilized structured and semi-structures instruments , including the Structured Clinical Interview for Diagnosis and the Longitudinal Interview Follow-up Examination . The main antidepressants used were imipramine ( 39 % ) , clomipramine ( 28.5 % ) and paroxetine ( 23.3 % ) ; only 9 % of patients received other antidepressants . RESULTS 147 patients ( 45.1 % ) stayed on medication throughout the entire period of the follow-up . Of those who interrupted the treatment , 38 % stayed in remission . The probability of achieving at least one remission during the 3-year follow-up period was 96.5 % for PD and 95.9 % for Agoraphobia . Relapses after a period of at least 2 months of complete remission were also common , and the probability of presenting at least one relapse during the 3-years follow-up period was 67.1 % for PD and 39 % for Agoraphobia . The longest period of remission of PD is associated with low severity , medium-lasting course in patients with an onset of the illness in young adulthood . Less severe agoraphobia associated with moderately severe panic attacks appears to confer a better control of phobic behavior . All three major drugs were reasonably well tolerated ( only 9 % dropped out because of side effects ) , with sexual dysfunction and increased appetite being the most common side effects at the last evaluation ; in the first phase of the treatment anticholinergic effects and jitteriness were more common with TCAs . CONCLUSION Both classical antidepressants and paroxetine emerge as a useful treatment in the long-term management of PDA ; paroxetine appears particularly useful in PDA patients because it was significantly less likely to induce jitteriness , thereby reducing barriers to compliance OBJECTIVE Bipolar disorder often co-occurs with anxiety disorders . Evidence suggests that second-generation antipsychotics ( SGAs ) may be useful in treating both conditions . This study examined the efficacy of ziprasidone in the treatment of these disorders . METHOD This 3-site , r and omized , double-blind , placebo-controlled , parallel group , 8-week trial of ziprasidone monotherapy examined 49 subjects with bipolar disorder and lifetime panic disorder ( with or without agoraphobia ) or generalized anxiety disorder ( GAD ) experiencing moderately severe anxiety symptoms at entrance into the study . Both bipolar disorder and anxiety diagnoses were based on DSM-IV-TR criteria . Patients were screened and r and omized from June 25 , 2010 , through August 23 , 2011 . Primary outcome measures were the Clinical Global Impressions-21 Anxiety Scale ( CGI-21 Anxiety ) and the Sheehan Disability Scale ( SDS ) , with secondary measures monitoring anxiety and mood symptoms . RESULTS Last-observation-carried-forward analyses demonstrated that patients in the ziprasidone group did not improve significantly more than those in the placebo group on the CGI-21 Anxiety ( F1 = 0.34 ; P = .564 ) or SDS ( F1 = 0.26 ; P = .611 ) . Secondary analysis using hierarchical linear modeling found similar results ( CGI-21 Anxiety : F1 = 1.82 ; P = .178 ; and SDS : F1 = 0.70 ; P = .408 ) . Regardless of group , time in the study was associated with significant decrease in anxiety ( F1 = 11.08 ; P = .001 ) and total disability ( F1 = 26.16 ; P < .001 ) . Patients in the ziprasidone group showed a greater increase in abnormal involuntary movement , and 81.8 % ( n = 9 ) of the subjects who withdrew from the study due to adverse events , serious adverse events , or side effects were in the ziprasidone group . CONCLUSIONS Results suggest that ziprasidone monotherapy was not associated with a clinical ly significant improvement in anxiety symptoms or improved function for patients with bipolar disorder , lifetime panic disorder or GAD , and concurrent moderately severe anxiety symptoms , and it was associated with a more negative side-effect profile relative to placebo . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01172652 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 Pre-treatment predictors of treatment outcome were examined in a group of 144 patients with panic disorder and agoraphobia r and omly allocated to alprazolam+exposure ( AE ) , placebo+exposure ( PE ) , alprazolam+relaxation ( AR ) , and placebo+relaxation ( PR ) . First-time psychotropic medication use , severity of agoraphobic disability , and longer duration of illness predicted less global improvement at post-treatment . Pre-treatment severity of agoraphobia predicted less improvement both in the short- and the long-term . Predictors of poorer outcome at 6-month follow-up were older age , past history of depression , severity of phobia targets , and longer duration of illness . Sex , source of referral , pre-treatment depression-anxiety-panic , and expectancy from treatment did not relate to outcome 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 Two years after completion of a controlled outcome study of treatments for panic disorder with agoraphobia , patients were revisited and interviewed about their complaints . In the initial study , four treatments had been compared : ( i ) fluvoxamine combined with exposure ; ( ii ) placebo medication plus exposure ; ( iii ) psychological panic management plus exposure : and ( iv ) exposure alone . Comparison of the results at post‐test had revealed superior efficacy of fluvoxamine combined with exposure over the other three treatments in reducing agoraphobic avoidance . The current naturalistic follow‐up study investigated the long‐term efficacy of the treatments with regard to abatement of complaints and reduced dem and for further treatment . In addition , we examined whether patients were able to taper off the study medication without a recurrence of complaints . In total , 71 of the 76 patients of the original trial ( 93 % ) were interviewed . Comparison of the mean level of psychopathology at follow‐up revealed no difference between the original treatment groups . The effect in the fluvoxamine plus exposure group was maintained , but was no longer superior , due to further improvements in the other treatment groups . Most patients received additional treatment during the follow‐up period , usually because the 12 treatment sessions in the controlled study had yielded insufficient improvement . There was a trend for patients who received the fluvoxamine plus exposure treatment to require less aftercare than those who received the other treatments . Finally , almost 50 % of the patients who had received medication in the original trial were able to taper off the use of fluvoxamine without a recurrence of complaints 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 In a controlled trial of alprazolam and exposure in 154 patients with panic disorder with agoraphobia , relations between panic , anticipatory anxiety , and phobic avoidance were examined . The three symptoms were independent of one another at baseline and improved largely independently during treatment ; only early improvement in avoidance predicted global improvement after treatment . Global improvement was more related to reduction of avoidance than a decrease in panics . Panic was not a valuable outcome measure in panic disorder with agoraphobia OBJECTIVE The purpose of this comparative outcome study was to investigate whether the effects of exposure in vivo treatment for panic disorder with agoraphobia could be enhanced by adding interventions specifically for panic attacks before the start of exposure treatment . The additional effect of two types of treatment for panic attacks -- pharmacological ( fluvoxamine ) and psychological ( repeated hyperventilation provocations and respiratory training)--was examined . Thus , the combined treatment of panic interventions with exposure in vivo could be compared to exposure in vivo alone . METHOD Ninety-six patients were r and omly assigned to four treatment conditions : double-blind , placebo-controlled fluvoxamine followed by exposure in vivo , psychological panic management followed by exposure , and exposure in vivo alone . Outcome was assessed by self-report measures , a st and ardized multitask behavioral avoidance test , and continuous monitoring of panic attacks .  Seventy-six patients completed the study . RESULTS All four treatments were effective and result ed in a significant decrease of agoraphobic avoidance . Moreover , the combination of fluvoxamine and exposure in vivo demonstrated efficacy superior to that of the other treatments and had twice as large an effect size ( difference between pre- and posttreatment scores ) on self-reported agoraphobic avoidance . The other treatments did not differ among each other in effectiveness . CONCLUSIONS Results of the study indicate that the short-term outcome of exposure in vivo treatment can be enhanced by adding fluvoxamine treatment . Psychological panic management combined with exposure was not superior to exposure alone of equal duration Factors that predicted the outcome of drug treatment ( alprazolam or imipramine ) of panic disorder were studied in a sample of 123 Sc and inavian patients participating in a multicenter placebo‐controlled 8‐week trial . The attrition rate was 95 % for alprazolam , 73 % for imipramine and 46 % for placebo . For the intention‐to‐treat and 3‐week‐completer sample s , drugs and anxiety symptoms at baseline were the best predictors of improvement on the Global Improvement Scale and on symptom scales focusing on panic attacks , phobic behavior and anticipatory anxiety . For completers of the 8‐week trial , only baseline scores predicted outcome . Generally , more severe symptoms at baseline predicted a worse outcome . A sub sample of patients had a marked placebo response . Avoidance , sex , age , childhood psychopathology and previous treatment experience had no or only a weak impact on the outcome . The relationship between panic disorder and mood disorder is presented elsewhere 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 BACKGROUND Panic disorder , with and without agoraphobia , is a prevalent condition which presents primarily in general practice . Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital setting s , and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care . AIM To evaluate the outcome , in a primary care setting , of fluvoxamine versus cognitive behaviour therapy , each used alone and in combination in a double-blind placebo-controlled framework , balanced for therapist contact . METHOD A total of 149 patients satisfying DSMIII-R criteria for panic disorder were r and omly allocated to receive one of the following : fluvoxamine , placebo , fluvoxamine plus cognitive behaviour therapy , placebo plus cognitive behaviour therapy , and cognitive behaviour therapy alone . These five treatment groups represent the minimum number acceptable for such a comparison to be made . All patients received an identical schedule of contact over 13 weeks . Measures of symptom severity , general health and social disruption were taken at entry point and end point ; measures of change in symptoms were taken at end point only . Outcome was reported in terms of brief global ratings of severity of illness and change in symptoms , and of ratings of general health and social disruption that are suitable for use in general practice . RESULTS All active treatment groups showed statistically significant advantages over placebo over a range of outcome ratings . The groups employing cognitive behaviour therapy showed the most robust and consistent response . CONCLUSION The brief global measures reported here proved adequate to the task of assessing treatment outcome . Results indicate that treatments including cognitive behaviour therapy can be effective in the treatment of panic disorder and agoraphobia in primary care 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 Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment . The safety , side effects and patients ' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study . Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation , fatigue/weakness , memory problems , ataxia and slurred speech . In the imipramine group blurred vision , tachycardia/palpitations , insomnia , sleep disturbance , excitement/nervousness , malaise , dizziness/faintness , headache , nausea/vomiting and decrease in appetite were worse than in the other groups . In the placebo group the anxious symptoms were most prominent . The highest level of compliance was shown in the alprazolam-treated group and the lowest in the placebo-treated group . Strong predictors of side effects were not observed . If a side effect profile is known , it will be easier for a clinician to choose the right drug and the appropriate management by taking into account compliance , safety and efficacy in each patient under treatment . Further information about side effects in long-term maintenance treatment would be of great clinical pertinence in ensuring safety and enhancing patients ' quality of life 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 Social phobia , also known as social anxiety disorder , is a highly prevalent disorder with significant morbidity . Patients with social phobia frequently develop co-morbid psychiatric disorders such as depression and substance abuse , and the disorder impacts significantly on social and occupational functioning . It has been suggested that the selective serotonin reuptake inhibitors ( SSRIs ) are useful in the management of this disorder , but few controlled trials have been undertaken in this regard . There are also few data on the pharmacotherapy of social phobia in South Africa . METHODS A double-blind r and omised placebo-controlled multi-site flexible-dose trial of paroxetine was undertaken over 12 weeks among patients with a primary diagnosis of social phobia . Primary response measures were the Global Improvement item on the Clinical Global Impression scale ( CGI ) and mean change from baseline in the patient-rated Liebowitz Social Anxiety Scale ( LSAS ) total score .  Ninety-three patients participated at 9 South African sites ; their data are reported here . RESULTS There was a significant drug effect on both the CGI Global Improvement score and the LSAS at 12 weeks . In addition , there was no significant difference in overall rate of adverse experiences between those on paroxetine and those on placebo . CONCLUSIONS Paroxetine is both effective and safe in the acute treatment of social phobia . The findings here are consistent with those of previous controlled studies of the SSRIs as well as with previous work done in the USA on the use of paroxetine in the treatment of this disorder . Early diagnosis and treatment of social phobia should be encouraged . However , further research on long-term pharmacotherapy of social phobia is needed
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 .