CoChat
Sign Up
Cited by 32Anxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesDigital Mental Health InterventionsCardiac Health and Mental Health

Pharmacotherapy of panic disorder

Open access
Pull, Charles·2008·Neuropsychiatric Disease and Treatment
DOI 10.2147/ndt.s1224PMC PMC2536545
Open this paper in CoChat — free accountOpen PDF

Abstract

Panic disorder (PD) is a common, persistent and disabling mental disorder. It is often associated with agoraphobia. The present article reviews the current status of pharmacotherapy for PD with or without agoraphobia as well as the current status of treatments combing pharmacotherapy with cognitive behavior therapy (CBT). The review has been written with a focus on randomized controlled trials, meta-analyses, and reviews that have been published over the past few years. Effective pharmacological treatments include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and various benzodiazepines. Treatment results obtained with CBT compare well with pharmacotherapy, with evidence that CBT is at least as effective as pharmacotherapy. Combining pharmacotherapy with CBT has been found to be superior to antidepressant pharmacotherapy or CBT alone, but only in the acute-phase treatment. Long term studies on treatments combining pharmacotherapy and CBT for PD with or without agoraphobia have found little benefit, however, for combination therapies versus monotherapies. New investigations explore the potential additional value of sequential versus concomitant treatments, of cognitive enhancers and virtual reality exposure therapy, and of education, self management and Internet-based interventions.

Integrity signals

Registry

Crossref · 10.2147/ndt.s1224

Cites

67 of 67 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 120 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    In the pooled analysis, 63% of paroxetine CR-treated patients and 53% of placebo-treated patients were panic-free during the final 2 weeks.

    “Of the total population that completed or prematurely terminated treatment, 63% and 53% of paroxetine CR- and placebo-treated patients, respectively, were panic-free during the final 2 weeks.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sheehan et al (2005)

      Not checked in the free run.

  • Findingcitation

    Fluoxetine, particularly the 20 mg/day dose, is associated with more improvement than placebo in patients with panic disorder across multiple symptom measures, including global improvement, total panic attack frequency, phobic symptoms, and functional impairment.

    “Fluoxetine, particularly the 20 mg/day dose, was associated with more improvement than was placebo in patients with PD across multiple symptom measures, including global improvement, total panic attack frequency, phobic symptoms, and functional impairment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Michelson et al 1998

      Not checked in the free run.

  • Findingcitation

    Sertraline and paroxetine have equivalent efficacy in panic disorder.

    “Sertraline and paroxetine had equivalent efficacy in PD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bandelow et al 2004

      Not checked in the free run.

  • Findingcitation

    Sertraline is significantly more effective than placebo in decreasing the number of full and limited-symptom panic attacks.

    “In a randomized, double-blind, parallel-group, flexible-dose comparison of sertraline and placebo in outpatients with a DSM-III-R diagnosis of PD with or without agoraphobia (Pohl et al 1998), sertraline was significantly more effective than placebo in decreasing the number of full and limited-symptom panic attacks.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pohl et al 1998

      Not checked in the free run.

  • Findingcitation

    For week 10 completers, 73% of paroxetine CR-treated patients and 60% of placebo-treated patients were panic-free at week 10.

    “For week 10 completers (72% of total), 73% and 60% of paroxetine CR- and placebo-treated patients, respectively, were panic-free at week 10.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sheehan et al (2005)

      Not checked in the free run.

  • May combine two claims. 64
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 8

  • May combine two claims.

    Findingcitation

    Sertraline is superior to placebo in reducing the number of panic attacks, situational attacks, unexpected attacks, limited symptom attacks, and time spent worrying.

    “Sertraline was superior to placebo in reducing the number of panic attacks, situational attacks, unexpected attacks, limited symptom attacks, and time spent worrying.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Londborg et al 1998

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Moclobemide is as efficacious as fluoxetine or clomipramine in the treatment of panic disorder with or without agoraphobia and has no serious side effects.

    “In 2 comparative trials (Kruger and Dahl 1999; Tiller et al 1999), moclobemide was found to be as efficacious as fluoxetine or clomipramine in the treatment of PD with or without agoraphobia and to have no serious side effects.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kruger and Dahl 1999

      Not checked in the free run.

    • cites Tiller et al 1999

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Paroxetine produces significant improvements compared with placebo in various measurements of panic attack frequency and is as effective as clomipramine.

    “Paroxetine produced significant improvements compared with placebo in various measurements of panic attack frequency, and was as effective as clomipramine.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lecrubier et al (1997)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Imipramine acts more rapidly than sertraline, but there is no difference in efficacy between the two drugs at week 8.

    “In a study by Mavissakalian (2003), imipramine was found to act more rapidly than sertraline, but there was no difference in efficacy between the two drugs at week 8.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mavissakalian (2003)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    All three sertraline doses (50 mg, 100 mg, or 200 mg) produce significant efficacy compared with placebo, with no consistent evidence of a dose-response effect.

    “All three sertraline doses produced significant efficacy compared with placebo, with no consistent evidence of a dose-response effect.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sheikh and colleagues (2000)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Fluvoxamine is more effective than placebo and as effective as imipramine in reducing spontaneous panic attacks in moderate to severe panic disorder.

    “Fluvoxamine was more effective than placebo and as effective as imipramine in reducing spontaneous panic attacks in moderate to severe PD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bakish et al 1996

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Paroxetine is more effective than placebo in achieving a 50% reduction in total number of panic attacks and reducing panic attacks to one or zero.

    “Analysis of the results showed statistically significant differences in favor of paroxetine between the two treatment groups in 2 primary measures of outcome, ie, 50% reduction in total number of panic attacks and number of panic attacks reduced to one or zero over the study period.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Oehrberg et al 1995

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Fluvoxamine is more effective than placebo and cognitive therapy in treating moderate to severe panic disorder, as measured by the proportion of patients rated moderately improved or better.

    “In a study by Black and colleagues (1993), patients with moderate to severe PD were randomly assigned to receive 8 weeks of fluvoxamine, cognitive therapy, or placebo. At the main comparison point, 57% of patients receiving fluvoxamine were rated moderately improved or better vs 40% of the group given cognitive therapy and 22% of the placebo-treated group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Black and colleagues (1993)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Brofaromine is as efficacious as clomipramine or fluvoxamine and has no serious side effects.

    “In 2 comparative trials (Bakish and al 1993; Van Vliet et al 1996), brofaromine was found to be as efficacious as clomipramine or fluvoxamine and to have no serious side effects.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Bakish and al 1993

      Not checked in the free run.

    • cites Van Vliet et al 1996

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Selective serotonin reuptake inhibitors and tricyclic antidepressants do not differ in efficacy on effect sizes for panic, agoraphobia, depression, or general anxiety, nor in the percentage of patients free of panic attacks at post-test.

    “There were no differences between SSRIs and TCAs on any of the effect sizes, indicating that both groups of antidepressants are equally effective in reducing panic symptoms, agoraphobic avoidance, depressive symptomatology and general anxiety.”
    • Also stated in: § Tricyclic antidepressants · plain
      “In addition, the percentage of patients free of panic attacks at post-test did not differ.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bakker et al 2002

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Fluvoxamine is more effective than placebo and cognitive therapy in producing freedom from panic attacks.

    “At that point, 43% of the fluvoxamine recipients vs 25% of cognitive therapy and 4% of placebo recipients were free of panic attacks.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Black and colleagues (1993)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    At week 10, 86% of patients taking paroxetine 40 mg/day, 65.2% of those taking 20 mg, 67.4% of those taking 10 mg, and 50.0% of placebo-treated patients were free of full panic attacks.

    “At week 10, 86% of the patients taking 40 mg/day, 65.2% of those taking 20 mg, 67.4% of those taking 10 mg, and 50.0% of the placebo-treated patients were free of full panic attacks.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ballenger et al 1998

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Venlafaxine-treated patients experience significantly greater global improvement than placebo-treated patients and exhibit trends toward greater improvement on anxiety and depression symptoms.

    “Patients treated with venlafaxine experienced significantly greater global improvement than those on placebo and exhibited trends toward greater improvement on anxiety and depression symptoms as assessed by the Hamilton rating scales.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pollack et al 1996

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The probability of response during the 12 months was significantly greater with all treatment regimens than with placebo, with citalopram 20 or 30 mg/day demonstrating the best response.

    “As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo, with citalopram 20 or 30 mg/day demonstrating the best response.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lepola et al 1998

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The rate of discontinuation for adverse events is 6.3% for escitalopram, 8.4% for citalopram, and 7.6% for placebo.

    “The rate of discontinuation for adverse events was 6.3% for escitalopram, 8.4% for citalopram, and 7.6% for placebo.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Stahl et al (2003)

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    No significant differences are observed between venlafaxine ER (75 or 150 mg/day), paroxetine (40 mg/day), and placebo in adult outpatients with panic disorder with or without agoraphobia.

    “No significant differences were observed between active treatment groups.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pollack et al (2007)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Escitalopram is efficacious, safe, and well tolerated in the treatment of panic disorder.

    “A randomized, double-blind, placebo-controlled trial of 366 subjects (128 escitalopram patients, 119 citalopram patients, and 119 placebo patients) conducted by Stahl et al (2003) showed that escitalopram is efficacious, safe, and well tolerated in the treatment of PD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Stahl et al (2003)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    There was a significant advantage for the combined treatment groups early in treatment, but subsequently outcome in all three groups was similar.

    “There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pollack et al (2003)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Citalopram at 20 or 30 mg, 40 or 60 mg, and clomipramine are significantly superior to placebo, judged by the number of patients free of panic attacks in the week prior to the final assessment.

    “Treatment with citalopram at 20 or 30 mg, 40 or 60 mg and clomipramine were significantly superior to placebo, judged by the number of patients free of panic attacks in the week prior to the final assessment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wade et al 2000

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Treatment patterns for psychotropic drugs in patients with panic disorder have remained stable over the past decade, with benzodiazepines being the most commonly used medication for panic disorder.

    “Treatment patterns for psychotropic drugs appeared to have remained stable over the past decade, with benzodiazepines being the most commonly used medication for PD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bruce et al (2003)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Venlafaxine ER is not associated with a greater proportion of patients free from full-symptom panic attacks at the final on-therapy evaluation, but is associated with lower mean panic attack frequency, a higher proportion free from limited-symptom panic attacks, higher response and remission rates, and improvements in anticipatory anxiety, fear and avoidance.

    “Venlafaxine ER was not associated with a greater proportion of patients free from full-symptom panic attacks at the final on-therapy evaluation, but was associated with lower mean panic attack frequency and a higher proportion free from limited-symptom panic attacks, higher response and remission rates, and improvements in anticipatory anxiety, fear and avoidance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bradwejn et al 2005

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Fluoxetine responders randomized to continue on their acute-phase fluoxetine dose experience statistically significant improvement in panic attack frequency and phobia rating scale score over 24 weeks of therapy, while those switched to placebo experience statistically significant worsening in Hamilton Anxiety (HAM-A), Hamilton Depression (HAM-D), and SCL-90-R rating scores.

    “Fluoxetine responders randomized to continue on their acute-phase fluoxetine dose experienced statistically significant improvement in panic attack frequency and phobia rating scale score over 24 weeks of therapy, while those switched to placebo experienced statistically significant worsening in Hamilton Anxiety (HAM-A), Hamilton Depression (HAM-D), and SCL-90-R rating scores.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Michelson et al (1999)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Combined treatment with paroxetine and clonazepam results in more rapid response than with the selective serotonin reuptake inhibitor alone, but there is no differential benefit beyond the initial few weeks of therapy.

    “The combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pollack et al (2003)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Paroxetine and clomipramine are significantly more effective than placebo throughout a long-term study in reduction from baseline of full panic attacks, and at the end of treatment in the proportion of patients who eventually experienced no panic attacks.

    “Paroxetine and clomipramine were significantly more effective than placebo throughout the long-term study in reduction from baseline of full panic attacks, and at the end of treatment in the proportion of patients who eventually experienced no panic attacks.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lecrubier and Judge (1997)

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Approximately 75% of patients given active treatment are responders, and nearly 45% achieve remission.

    “Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pollack et al (2007)

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Several tricyclic antidepressants are effective treatments for panic disorder with or without agoraphobia, but their use is limited by side effects.

    “While several tricyclic antidepressants are effective treatments for PD with or without agoraphobia, their use is limited by their side effects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Roy-Byrne and Cowley (2002)

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Selective and reversible monoamine oxidase-A inhibitors such as moclobemide and brofaromine do not require dietary restrictions, have fewer drug interactions than irreversible monoamine oxidase inhibitors, and are better tolerated.

    “Selective and reversible MAO-A inhibitors (RIMAs) exemplified by moclobemide and brofaromine do not require dietary restrictions, have fewer drug interactions than irreversible MAO inhibitors, and are better tolerated.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Riederer et al 2004

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Selective serotonin reuptake inhibitors and tricyclic antidepressants are equal in efficacy for panic disorder, but selective serotonin reuptake inhibitors are tolerated better.

    “The authors conclude that SSRIs and TCAs are equal in efficacy in the treatment of PD, but SSRIs are tolerated better.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bakker et al 2002

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Irreversible monoamine oxidase inhibitors are effective treatments for panic disorder with or without agoraphobia, but their use is limited by side effects and interactions with other drugs and food components.

    “While several irreversible MAO inhibitors are effective treatments for PD with or without agoraphobia, their use is limited by their side effects and by their interactions with other drugs and food components.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Riederer et al 2004

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The efficacy of various psychotropic medications (mainly antidepressants and benzodiazepines) and cognitive behavior therapy for treating panic disorder has been established in numerous randomized controlled trials.

    “The efficacy of various psychotropic medications (mainly antidepressants and benzodiazepines) as well as the efficacy of cognitive behavior therapy (CBT) for treating the disorder has been established in numerous randomized controlled trials.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Although benzodiazepines as a class act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome.

    “Although as a class benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chouinard (2004)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that same study, the likelihood of experiencing at least one relapse over three years was 67.1% for panic disorder and 39% for agoraphobia.

    “the probability of presenting at least 1 relapse during the 3-year follow-up period was 67.1% for PD and 39% for agoraphobia.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Toni et al (2000)

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    Combining benzodiazepine and antidepressant agents early in treatment offers the potential of accelerating response compared with antidepressant monotherapy and the possibility of additive or synergistic effects, but there has been relatively little systematic assessment of the safety and efficacy of this strategy.

    “As noted by Pollack et al (2003), combining benzodiazepine and antidepressant agents early in treatment offers the potential of accelerating response compared with antidepressant monotherapy and the possibility of additive or synergistic effects from the two classes of agents, but there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pollack et al (2003)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    There has been little systematic work regarding the long-term treatment of panic disorder with or without agoraphobia, and data on the prophylactic effectiveness of maintenance treatment are still limited, as well as information on the risk of relapse due to discontinuation of pharmacological treatment after an initial response to acute therapy.

    “There has been little systematic work done regarding the long-term treatment of PD with or without agoraphobia, and data on the prophylactic effectiveness of maintenance treatment are still limited, as well as information on the risk of relapse due to discontinuation of pharmacological treatment after an initial response to acute therapy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Benzodiazepines such as lorazepam, alprazolam, and clonazepam are effective treatments for panic disorder with or without agoraphobia, alone or in combination with one of the selective serotonin reuptake inhibitors.

    “Benzodiazepines such as lorazepam (Schweitzer et al 1990), alprazolam (Verster and Volkerts 2004),) and clonazepam (Rosenbaum 2004) are effective treatments for PD with or without agoraphobia, alone or in combination with one of the SSRIs.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Schweitzer et al 1990

      Not checked in the free run.

    • cites Verster and Volkerts 2004

      Not checked in the free run.

    • cites Rosenbaum 2004

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    High-potency benzodiazepines are effective in treating panic disorder and panic attacks with or without agoraphobia, alone or as add-on therapy to selective serotonin reuptake inhibitors.

    “High-potency benzodiazepines are effective in treating PD and panic attacks with or without agoraphobia, alone or as add-on therapy to selective serotonin reuptake inhibitors.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Chouinard (2004)

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients.

    “The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted PD with agoraphobia patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mavissakalian and Perel (2002)

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Continued improvement is seen with long-term paroxetine or clomipramine treatment, indicating the importance of long-term treatment in patients with panic disorder.

    “Not only was efficacy maintained, but continued improvement was also seen, indicating the importance of long-term treatment in patients with PD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lecrubier and Judge (1997)

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The results confirm the very high degree of prophylactic effectiveness of maintenance imipramine treatment and confirm that relapse is substantial after discontinuation of treatment.

    “The results confirm the very high degree of prophylactic effectiveness of maintenance imipramine treatment and confirm that relapse is substantial after discontinuation of treatment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mavissakalian and Perel (1999)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The improvement appeared early in treatment and persisted at three months.

    “The improvement was evident early in treatment and was maintained at 3 months.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ressler et al (2004)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Two meta-analyses by Westen et al. (2005) and Mitte et al. (2005) indicated that CBT is at least as effective as pharmacotherapy and has good tolerability, sustained benefits, cost-effectiveness, and positive effects on comorbid conditions and quality of life.

    “rates of patients who are panic-free or meet criteria for recovery and high end-state functioning after treatment with CBT compare well with pharmacotherapy, with evidence that CBT is at least as effective as pharmacotherapy, with strong tolerability, maintenance of treatment gains, cost efficacy, improvements in comorbid conditions, and quality of life.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Westen et al (2005)

      Not checked in the free run.

    • cites Mitte et al (2005)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Heldt et al. (2006) reported significant reductions on all outcome measures-panic attack frequency, agoraphobia, and anticipatory anxiety-with gains maintained at one-year follow-up.

    “Significant reductions in symptoms were evident for all outcome measures (frequency of panic attacks, agoraphobia and anticipatory anxiety) with maintenance of these gains at 1-year follow-up.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Heldt et al (2006)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Initial results from an ongoing randomized controlled trial by Botella et al. (2004a, 2004b) indicate that VRET and CBT produce significantly greater improvement than waiting-list control, and that VRET and in vivo exposure do not differ significantly.

    “Initial results of the study indicate that patients in the VRET and in the CBT groups improve significantly more than patients in the waiting list control group, and that there are no significant differences in outcome measures between patients treated by VRET and patients treated by exposure in vivo.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Botella et al (2004a, 2004b)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The efficacy of CBT for PD and for agoraphobia has been established in a number of randomized controlled trials.

    “The efficacy of CBT for the treatment of PD as well as for agoraphobia has been established in a number of randomized controlled trials.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Butler et al. (2006) reported that the outcome findings for CBT in PD are supportive and robust.

    “the outcome findings on CBT for PD are supportive and robust.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Butler et al (2006)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The same authors attributed low CBT use to public unfamiliarity with CBT relative to medication, limited access to professionals familiar with CBT, and insufficient training among mental-health professionals treating PD.

    “low rates of use are probably due to public unfamiliarity with the nature and efficacy of CBT relative to medication, to restricted access to professionals who are familiar with its efficacy and delivery, and to little training and familiarity with CBT for many mental-health professionals who currently treat patients with PD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Roy-Byrne et al (2006)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Two recent randomized, double-blind, placebo-controlled studies suggest that patients with PD who do not respond to initial CBT may benefit from adding an SSRI as a second treatment, and vice versa.

    “2 recent randomized, double-blind, placebo-controlled study do suggest that patients with PD who are unsuccessfully treated with initial CBT may in fact benefit from the addition of an SSRI as a second treatment modality and vice versa.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kampman et al (2002)

      Not checked in the free run.

    • cites Heldt et al (2006)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The same authors stated that meta-analytic evidence indicates CBT has much better long-term persistence of effects, with relapse rates half those of pharmacotherapy.

    “there appears to be robust and convergent metaanalytic evidence that CBT produces vastly superior long-term persistence of effects, with relapse rates half those of pharmacotherapy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Butler et al (2006)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Roy-Byrne et al. (2006) concluded that while evidence for CBT's efficacy is strong, CBT is underused in most countries relative to medication.

    “Roy-Byrne et al (2006) concluded that the nature of the evidence concerning the efficacy of CBT is robust, but that CBT approaches are underused in most countries, compared with drug treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Roy-Byrne et al (2006)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Kampman et al. (2002) found that patients receiving continued CBT plus paroxetine improved significantly on agoraphobic behavior and anxiety discomfort, while those receiving continued CBT plus placebo did not.

    “Overall, patients in the CBT plus paroxetine condition improved significantly on agoraphobic behavior and anxiety discomfort, whereas patients in the CBT plus placebo condition did not.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kampman et al (2002)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    That meta-analysis also showed that CBT's effect size remained nearly unchanged at one-year follow-up, while pharmacological treatment's effect size dropped considerably.

    “The CBT treatment showed virtually no slippage in effect size by 1-year follow-up compared with sizable slippage for pharmacological treatment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gould et al (1995)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After the acute phase, that meta-analysis found combined therapy still outperformed pharmacotherapy alone but no longer outperformed psychotherapy alone.

    “After termination of the acute phase treatment, the combined therapy was still more effective than pharmacotherapy alone but no longer more effective than psychotherapy alone.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Furukava et al (2006)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For the comparison with psychotherapy, there was no evidence that combination therapy provided long-term benefit over psychotherapy alone; combination treatments were not more effective than CBT alone.

    “For the comparison between combination therapy and psychotherapy, there was no evidence of long-term benefit of the former with the latter, ie, combination treatments were not more effective than CBT alone.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Furukava et al (2006)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Only a limited number of studies have examined the efficacy of self-management interventions, and many of those studies have methodological shortcomings.

    “The efficacy of self-management interventions has been investigated in only a limited number of studies, and the methodology in many of those studies is far from perfect.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pull 2005

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Tricyclic antidepressants, MAO inhibitors, and benzodiazepines also have proven efficacy in panic disorder.

    “Other medications with proven efficacy in PD include tricyclic antidepressants, MAO inhibitors, and benzodiazepines.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Benzodiazepines act rapidly and are generally well tolerated, but they carry clinical risks including rebound anxiety, memory impairment, discontinuation syndrome, and potential for abuse and dependence.

    “Although, as a class, benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as rebound anxiety, memory impairment, discontinuation syndrome, and a potential for abuse and dependence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Irreversible MAO inhibitors are effective for panic disorder with or without agoraphobia, but their side effects and interactions with other drugs and foods restrict their use.

    “While irreversible MAO inhibitors are effective treatments for PD with or without agoraphobia, their use is limited by their side effects and by their interactions with other drugs and food components.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    CBT is highly effective for panic disorder with or without agoraphobia, compares favorably with pharmacological treatments in the acute phase, and may be more effective in the long run.

    “CBT is a highly effective treatment for PD with or without agoraphobia that compares favorably with any of the pharmacological treatments in the acute phase of the treatment and may in fact be more effective in the long run.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Both pharmacological treatments and CBT are effective for acute and long-term treatment of panic disorder with or without agoraphobia.

    “Different pharmacological treatments as well as CBT are effective in the acute as well as in the long term treatment of PD with or without agoraphobia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Collaborative care strategies tailored for primary care and self-management interventions are more effective than usual care and should be further developed.

    “Finally, collaborative care strategies tailored for use in primary care as well as self-management interventions are more effective than usual care and should be further developed and refined.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Panic disorder, with or without agoraphobia, is common in primary care settings.
    • Rests on an assumption: Even though panic disorder with or without agoraphobia often responds well to available treatments, many sufferers do not benefit because they cannot locate a specialist or are unaware that such treatments exist.

  • May combine two claims.

    Interpretationnone given

    Several tricyclic antidepressants are effective for panic disorder with or without agoraphobia, but their side effects limit their use.

    “While several tricyclic antidepressants are effective treatments for PD with or without agoraphobia, their use is limited by their side effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    With several medications, long-term treatment maintained or further increased efficacy, which indicates the importance of long-term pharmacological treatment.

    “In long-term treatments with several medications, efficacy was maintained or further increased in the long run, indicating the importance of long-term pharmacological treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Rollman et al. (2003) found that at 12-month follow-up, patients receiving the telephone-based care management intervention had reduced anxiety and depressive symptoms, better mental health-related quality of life, greater increases in hours worked per week, and fewer missed work days than usual care patients.

    “At 12-month follow-up, intervention patients reported reduced anxiety and depressive symptoms, improved mental health-related quality of life, larger improvements relative to baseline in hours worked per week, and fewer work days absent in the past month than usual care patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rollman et al (2003)

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Selective and RIMA agents such as moclobemide and brofaromine require no dietary restrictions, have fewer drug interactions than irreversible MAO inhibitors, and are better tolerated.

    “Selective and RIMAs exemplified by moclobemide and brofaromine, do not require dietary restrictions, have fewer drug interactions than irreversible MAO inhibitors, and are better tolerated.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    For long-term treatment of panic disorder with or without agoraphobia, combination treatments may outperform pharmacotherapy alone but not CBT alone.

    “In the long-term treatment of PD with or without agoraphobia, combination treatments may be more effective than pharmacotherapy alone, but not more effective than CBT alone.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Many patients fail to respond fully, or respond poorly, to either pharmacotherapy or CBT when used alone.

  • May combine two claims.

    Interpretationnone given

    High-potency benzodiazepines (lorazepam, alprazolam, clonazepam) are effective for panic disorder and panic attacks with or without agoraphobia, either alone or as add-on therapy to SSRIs.

    “High-potency benzodiazepines such as lorazepam, alprazolam, and clonazepam are effective in treating PD and panic attacks with or without agoraphobia, alone or as add-on therapy to SSRIs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A blind telephone interview after treatment showed that 77% of treated patients no longer met criteria for PD, while all waitlisted participants still did.

    “A blind telephone interview after the end of treatment revealed that 77% of the treated patients no longer fulfilled the criteria for PD, whereas all of the waitlisted subjects still suffered from it.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Calbring et al (2007)

      Not checked in the free run.

67 of 67

  • The paper relies on this without support.

    Many patients fail to respond fully, or respond poorly, to either pharmacotherapy or CBT when used alone.

    “A substantial proportion of patients does not fully respond or responds poorly to either pharmacotherapy or CBT alone.”

  • The paper relies on this without support.

    Panic disorder, with or without agoraphobia, is common in primary care settings.

    “PD with or without agoraphobia is highly prevalent in primary care.”

  • The paper relies on this without support.

    The reduction of fear during exposure therapy resembles extinction learning.

    “As fear reduction in exposure therapy is similar to extinction learning”

  • The paper relies on this without support.

    D-cycloserine was previously reported to enhance fear extinction in rodents.

    “a partial agonist at the N-methyl-d-aspartate receptor that has previously been shown to improve extinction of fear in rodents.”

  • The paper relies on this without support.

    Even though panic disorder with or without agoraphobia often responds well to available treatments, many sufferers do not benefit because they cannot locate a specialist or are unaware that such treatments exist.

    “Although PD with or without agoraphobia is often highly amenable to currently available treatments, either pharmacotherapy or CBT, or a combination of both, a considerable proportion of sufferers do not benefit from those treatments, either because they cannot find a specialist to provide them, or because they do not know that such treatments exist.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract rules out a post-acute combination benefit reported later

    Minor

    The abstract limits the advantage of combined treatment over pharmacotherapy to the acute phase. The later review says combined treatment remained more effective than pharmacotherapy after that phase ended.

  • Reported relapse percentage does not match the patient count

    Minor

    Twenty-one of 143 patients is approximately 14.7%, which rounds to 15% rather than the reported 14%.

    Reported 14 · recomputed 14.685315

  • A study described as controlled is later identified as open

    Minor

    The sequential-treatment section describes two recent studies as randomized, double-blind, and placebo-controlled. One of the two studies discussed there, Heldt et al (2006), is explicitly described as an open study.

3 of 3

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Pull, C.
Affiliations
Centre Hospitalier de Luxembourg (LU)
Corresponding author
Pull, Charles
Venue
Neuropsychiatric Disease and Treatment
Publisher
Informa UK Limited
Published
2008-09
Volume
4
Issue
4
Pages
779
ISSN
1176-6328 (ISSN-L)
DOI
10.2147/ndt.s1224
PMC
PMC2536545
OpenAlex
W2022665606
Cited by
32
References
67
Citations by year
2026: 1 · 2025: 5 · 2022: 1 · 2021: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 1
FWCI
4.54
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Neuropsychiatric Disease and Treatment (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Social Sciences › Psychology › Applied Psychology › Digital Mental Health Interventions
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
Keywords
panic disorder, agoraphobia, pharmacotherapy, cognitive behavioral therapy, combination therapy, tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, benzodiazepines, virtual reality exposure therapy, nootropic drugs, self-management, online intervention

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review