A prospective naturalistic study of 326 panic-agoraphobic patients treated with antidepressants. Do antidepressants selectively suppress spontaneous (unexpected) panic attacks? A replication. Treatment of Panic Disorder with Agoraphobia: Randomized Placebo‐Controlled Trial of Four Psychosocial Treatments Combined with Imipramine or Placebo A 15-year follow-up study of patients with panic disorder. Long‐term outcome of pharmacological and psychological treatment for panic disorder with agoraphobia: a 2‐year naturalistic follow‐up The 35% CO 2 Hyperreactivity and Clinical Symptomatology in Patients With Panic Disorder After 1 Week of Treatment With Citalopram: An Open Study SECOND-STAGE TREATMENTS FOR RELATIVE NONRESPONDERS TO COGNITIVE BEHAVIORAL THERAPY (CBT) FOR PANIC DISORDER WITH OR WITHOUT AGORAPHOBIA-CONTINUED CBT VERSUS SSRI: A RANDOMIZED CONTROLLED TRIAL. Rate of improvement during and across three treatments for panic disorder with or without agoraphobia: cognitive behavioral therapy, selective serotonin reuptake inhibitor or both combined. Global measures of outcome in a controlled comparison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary care. Interactive Model of Therapeutic Response in Panic Disorder: Moclobemide, a Case in Point Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Clomipramine and fluoxetine effects in the treatment of panic disorder. Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone. MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy Panic disorder, autonomic nervous system and dissociation - changes during therapy. Long-term follow-up after a drug trial for panic disorder. Time to response in panic disorder in a naturalistic setting: combination therapy with alprazolam orally disintegrating tablets and serotonin reuptake inhibitors compared to serotonin reuptake inhibitors alone.
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 The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a small therapeutic study : ( 1 ) the pathogenesis of panic disorder includes at least two identifiable components : a biological component represented by spontaneous ( unexpected ) panic attacks , and a cognitive component represented by situational attacks and especially by phobias ; ( 2 ) these components respond differently to treatment ; ( 3 ) many biological processes respond to an effective intervention in proportion to their deviance from " normal " prior to treatment ( " Law of Initial Value " ) ; and ( 4 ) the response of spontaneous panic attacks to an effective treatment conforms to that model . Previously , the authors reanalyzed an 8-week therapeutic study of panic disorder that included groups treated with  placebo  and with  imipramine ( 225 mg daily ) . The criteria of response were spontaneous panic attacks ( biological component ) , situational panic attacks ( both components ) , and agoraphobia ratings ( cognitive component ) . The analyses compared the regression lines for posttreatment status on pretreatment status in the imipramine and placebo groups . The effect of imipramine on spontaneous panic attacks fitted the hypothesized model : the pre-post slope in the placebo group was approximately 1 ( 45 degrees ) , whereas the slope in the imipramine group was approximately 0 . There was no significant difference in pre-post slopes between the imipramine and placebo groups for situational panic attacks or agoraphobia ratings . For this report , the authors applied the same approach to another larger data set from a study using a similar design , but a different antidepressant . In this multicenter , double-blind study , patients with panic disorder were r and omly assigned to receive 10 weeks of treatment with  placebo ( N = 78 ) or fluoxetine 10 mg ( N = 84 ) or 20 mg ( N = 81 ) daily . Spontaneous and situational panic attacks were registered in a daily diary , and agoraphobia was rated at each visit . Using baseline and endpoint data , fluoxetine had a statistically significant , dose-dependent , suppressive effect on spontaneous panic attacks , as measured by the pre-post slopes in the three treatment groups . The placebo group showed some response ( slope = 0.69 ) . There were no significant drug effects on situational panic attacks . On ratings of agoraphobia , the slopes in the placebo and the fluoxetine 20 mg groups did not differ , but the slope in the fluoxetine 10 mg group was significantly less than that in the placebo group , suggesting a therapeutic drug effect on agoraphobia only at the lower dose . These results are consistent with the stated hypotheses . They suggest that the therapeutic effects of antidepressants on panic disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings . Implication s of these results for concepts of pathogenesis , clinical practice , and therapeutic research regarding panic disorder are discussed Few r and omized controlled trials have included panic disorder patients with moderate to severe agoraphobia . Therefore , this population was studied using pharmacotherapy as well as psychotherapy . At the time of the study , imipramine was widely used as a pharmacological treatment . Also , current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy . Therefore , the main objective of this study is to compare four psychosocial treatments — cognitive and grade d in vivo exposure treatments , grade d in vivo exposure , cognitive treatment , and supportive therapy — to evaluate the benefits of combining cognitive therapy with exposure in vivo . These treatments were combined with imipramine or placebo for a total of eight experimental conditions . Participants presented moderate to severe agoraphobia . The method involved a r and omized , double‐blind , placebo‐controlled trial with 137 participants who completed a 14‐session protocol involving the treatments just mentioned . Measures were taken at baseline and posttreatment and at 3‐ , 6‐ , and 12‐month follow‐up . All treatment conditions were statistically and clinical ly effective in reducing self‐reported panic – agoraphobia symptoms over the 1‐year follow‐up . No statistical differences were observed between imipramine and placebo conditions . This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1‐year follow‐up period . These surprising results support the need to document the relations among the various components of an intervention . This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole BACKGROUND 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 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 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 BACKGROUND Cognitive behavioral therapy ( CBT ) and pharmacotherapy are efficacious for the short-term treatment of panic disorder . Less is known about the efficacy of these therapies for individuals who do not respond fully to short-term CBT .  METHOD The current trial is a second-step stratified r and omized design comparing two treatment conditions-selective serotonin reuptake inhibitor ( SSRI ; paroxetine or citalopram ; n = 34 ) and continued CBT  ( n = 24)-in a sample of individuals classified as treatment nonresponders to an initial course of CBT for panic disorder . Participants were r and omized to 3 months of treatment and then followed for an additional 9 months . Only treatment responders after 3 months were maintained on the treatment until 12-month follow-up . Data analysis focused on panic disorder symptoms and achievement of response status across the first 3 months of treatment . Final follow-up data are presented descriptively . RESULTS Participants in the SSRI condition showed significantly lower panic disorder symptoms as compared to continued CBT at 3 months . Results were similar when excluding individuals with comorbid major depression or analyzing the entire intent-to-treat sample . Group differences disappeared during 9-month naturalistic follow-up , although there was significant attrition and use of non study therapies in both arms . CONCLUSIONS These data suggest greater improvement in panic disorder symptoms when switching to SSRI after failure to fully respond to an initial course of CBT . Future studies should further investigate relapse following treatment discontinuation for nonresponders who became responders . Clinical trials.gov Identifier : NCT00000368 ; https:// clinical trials.gov/show/NCT00000368 BACKGROUND Existing literature on panic disorder ( PD ) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy ( CBT ) , Selective Serotonin Reuptake Inhibitor ( SSRI ) or both combined ( CBT+SSRI ) . METHOD Patients were r and omized to CBT , SSRI or CBT+SSRI which each lasted one year including three months of medication taper . Participating patients kept record of the frequency of panic attacks throughout the full year of treatment . Rate of improvement on panic frequency and the relationship between rate of improvement and baseline agoraphobia ( AG ) were examined . RESULTS A significant decline in frequency of panic attacks was observed for each treatment modality . SSRI and CBT+SSRI were associated with a significant faster rate of improvement as compared to CBT . Gains were maintained after tapering medication . For patients with moderate or severe AG , CBT+SSRI was associated with a more rapid improvement on panic frequency as compared to patients receiving either mono-treatment . LIMITATIONS Frequency of panic attacks was not assessed beyond the full year of treatment . Second , only one process variable was used . CONCLUSIONS Patients with PD respond well to each treatment as indicated by a significant decline in panic attacks .  CBT is associated with a slower rate of improvement as compared to SSRI and CBT+SSRI . Discontinuation of SSRI treatment does not result in a revival of frequency of panic attacks . Our data suggest that for patients without or with only mild AG , SSRI-only will suffice . For patients with moderate or severe AG , the combined CBT+SSRI treatment is recommended 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 It was proposed that pre-post regression slopes be used to index treatment response when the effect of baseline scores differed among treatments ( interaction between treatment and baseline score ) . Reanalyses of two studies using imipramine and fluoxetine in panic disorder showed doserelated decreases in pre-post slopes for the frequency of unexpected panic attacks , but not for the frequency of situational panic attacks or measures of agoraphobia . This report presents similar analyses of data from a study using moclobemide .  Patients ( N = 452 ) with panic disorder were r and omized to placebo  or a fixed dose of moclobemide ( 75 , 150 , 300 , 600 , or 900 mg/day ) . They were treated double-blindly and evaluated at baseline and 1 , 2 , 3 , 4 , 6 , and 8 weeks later . The authors analyzed the frequency of unexpected and situational panic attacks compiled from a daily diary , and fear and avoidance ratings based on the patient ’s main phobia using baseline ( pre ) and end-point ( post ) values for all r and omized patients . Adjoining dose groups were combined . Both unexpected and situational panic attacks showed systematic doserelated suppression of pre-post treatment slopes . Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance differed reliably between treatment arms . This study replicates the authors ’ earlier findings , except for situational panic attacks , which probably were not reliably identified . Antidepressants selectively suppress panic attacks , especially unexpected attacks , but not agoraphobia . The findings are consistent with the hypothesis that panic disorder with agoraphobia has clinical ly separable biologic and cognitive components that respond differentially to treatment . Antidepressants benefit primarily patients with many unexpected panic attacks . Investigators should evaluate pre-post treatment slopes before comparing adjusted posttreatment means ( analysis of covariance ) 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 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 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 Panic disorder with agoraphobia ( PD/AG ) is a prevalent mental disorder featuring a substantial complex genetic component . At present , only a few established risk genes exist . Among these , the gene encoding monoamine oxidase A ( MAOA ) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels . Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity . Here , we have thus investigated the impact of MAOA-uVNTR on therapy response , behavioral avoidance and brain activity in fear conditioning in a large controlled and r and omized multicenter study on cognitive behavioral therapy ( CBT ) in PD/AG . The study consisted of 369 PD/AG patients , and genetic information was available for 283 patients . Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale ( 46 % responders vs 67 % , P=0.017 ) . This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation , that is , the behavioral avoidance task . All but one panic attack that happened during this task occurred in risk allele carriers and , furthermore , risk allele carriers did not habituate to the situation during repetitive exposure . Finally , functional neuroimaging during a classical fear conditioning paradigm evidence d that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear . Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes , suggesting differential brain activation patterns upon CBT . Taken together , we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms . These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches OBJECTIVES Alarming somatic symptoms and in particular the cardiovascular symptoms , are the characteristic features of panic attacks . Increased cardiac mortality and morbidity have been proposed in these patients . Power spectral analysis of electrocardiogram R-R intervals is known to be a particularly successful tool in the detection of autonomic instabilities in various clinical disorders . Heart rate variability ( HRV ) has been found to be the outcome of rapidly reacting cardiovascular control systems . The aim of our study is to measure very low frequency b and ( VLF ) , low frequency b and ( LF ) and high frequency b and ( HF ) components of R-R interval during orthostatic experiment in patients with panic disorder before and after treatment and compares it with healthy controls . METHODS We assessed heart rate variability in 19 patients with panic disorder before and after 6-weeks treatment with antidepressants combined with cognitive behavioral therapy ( CBT ) and in 18 healthy controls . Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI ( MINI international neuropsychiatric interview ) . Patients were treated with CBT and psychotropics . They were regularly every week assessed using CGI ( Clinical Global Impression ) , BAI ( Beck Anxiety Inventory ) and BDI ( Beck Depression Inventory ) . Heart rate variability was assessed during 3 positions ( 1st - 5 min supine ; 2nd - 5 min st and ing ; 3rd - 5 min supine ) before and after the treatment . Power spectra were computed for very low frequency - VLF ( 0.0033 - 0.04 Hz ) , low-frequency - LF ( 0.04 - 0.15 Hz ) and high frequency - HF ( 0.15 - 0.40 Hz ) b and s using fast Fourier transformation . RESULTS Nineteen panic disorder patients resistant to pharmacological treatment entered a 6-week open-label treatment study with combination of SSRI and CBT . The combination of CBT and pharmacotherapy proved to be an effective treatment in these patients . The patients significantly improved during the study period in all rating scales . There were highly statistical significant differences between panic patients and control group in all components of power spectral analysis in 2nd ( VLF , LF and H in st and ing ) and in two component of 3rd ( LF and HF in supine ) positions . There was also a statistically significant difference between these two groups in LF/HF ratio in st and ing position ( 2nd ) . During therapy there was a tendency increasing values in all three positions in components of HRV power spectra , but HF in 1st supine position was the only component where the increase reached the level os statistical significance . CONCLUSIONS These findings demonstrate a lower autonomic activity in panic disorder patients measured during the changes of postural position in comparison with healthy controls and tendency to increase this autonomic power during the treatment BACKGROUND This study investigates the naturalistic course of panic disorder over four years and attempts to identify predictors for outcome . METHOD 423 DSM-III-R panic disorder patients who had taken part in an international multicentre drug trial were selected for follow-up ; we were able to re-interview 367 ( 87 % ) . For panic attacks , phobic avoidance and disabilities the same rating scales were administered as had been used for the clinical trials . RESULTS While 61 % of all patients experienced at least occasional panic attacks at follow-up , few suffered from serious phobic avoidance ( 16.7 % ) or serious disabilities ( work 7.9 % ) ; family 8.7 % ; social 13.9 % ) . Panic attack frequency at baseline , original trial medication and continuous use of psychotropic medication during follow-up are not related to outcome , whereas longer duration of illness and more severe phobic avoidance at baseline are unfavourable . CONCLUSION The course of panic disorder is not uniform . Since long duration of illness and severe phobic avoidance at baseline are predictors for an unfavourable outcome , more rigorous efforts should be undertaken to detect and treat panic disorder at an early stage OBJECTIVE This study evaluated time to response in the treatment of panic disorder with a selective serotonin reuptake inhibitor ( SSRI ) or serotonin norepinephrine reuptake inhibitor ( SNRI ) combined with alprazolam orally disintegrating tablets ( ODT ) , or SSRI/SNRI alone . DESIGN Subjects were r and omized to eight weeks open-label treatment with alprazolam ODT ( 4 weeks treatment followed by 3 - 4 week taper ) combined with an SSRI or SNRI , or treatment with SSRI/SNRI alone . SETTING The study was conducted under naturalistic conditions at 62 primary care and 34 psychiatric practice s. PARTICIPANTS Male or female subjects ≥18 years of age diagnosed with panic disorder , with or without agoraphobia . MEASUREMENTS The primary efficacy measure was time to response , defined as ≥50-percent decrease from baseline Hamilton Rating Scale for Anxiety ( HAM-A ) total score . Secondary measures included change from baseline in HAM-A scores and the Clinical Global Impression of Improvement ( CGI-I ) and Patient Global Impression ( PGI ) scales . RESULTS The intent-to-treat ( ITT ) population comprised 245 subjects . There was no statistical difference between treatment groups in time to response in the ITT population ; however , a prospect ively defined per protocol analysis revealed a statistically significant earlier onset of effect in subjects receiving SSRI/SNRI plus alprazolam ODT ( P<0.05 ) . Mean change from baseline in HAM-A total score and clinician and patient measures of global improvement also showed statistically significant early advantages for combination therapy compared with SSRI/SNRI monotherapy . CONCLUSION Combined treatment of panic disorder with alprazolam ODT and an SSRI/SNRI may be associated with more rapid improvement in anxiety symptoms compared with an SSRI/SNRI alone
We observed the same finding when classes of antidepressants were compared with placebo .
When looking at dropouts due to adverse effects , which can be considered as a measure of tolerability , we found moderate- quality evidence showing that antidepressants as a whole are less well tolerated than placebo .
The identified studies comprehensively address the objectives of the present review .Based on these results , antidepressants may be more effective than placebo in treating panic disorder .
Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts , but a less favourable profile in terms of dropout due to adverse effects .
However , the tolerability profile varied between different classes of antidepressants .
BACKGROUND Panic disorder is characterised by repeated , unexpected panic attacks , which represent a discrete period of fear or anxiety that has a rapid onset , reaches a peak within 10 minutes , and in which at least four of 13 characteristic symptoms are experienced , including racing heart , chest pain , sweating , shaking , dizziness , flushing , stomach churning , faintness and breathlessness .
It is common in the general population with a lifetime prevalence of 1 % to 4 % .
The treatment of panic disorder includes psychological and pharmacological interventions .
Amongst pharmacological agents , the National Institute for Health and Care Excellence ( NICE ) and the British Association for Psychopharmacology consider antidepressants , mainly selective serotonin reuptake inhibitors ( SSRIs ) , as the first-line treatment for panic disorder , due to their more favourable adverse effect profile over monoamine oxidase inhibitors ( MAOIs ) and tricyclic antidepressants ( TCAs ) .
Several classes of antidepressants have been studied and compared , but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition .
OBJECTIVES To assess the effects of antidepressants for panic disorder in adults , specifically:1 .
to determine the efficacy of antidepressants in alleviating symptoms of panic disorder , with or without agoraphobia , in comparison to placebo;2 .
to review the acceptability of antidepressants  in panic disorder , with or without agoraphobia , in comparison with placebo ; and 3 .
to investigate the adverse effects of antidepressants  in panic disorder , with or without agoraphobia , including the general prevalence of adverse effects , compared to placebo .