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Meta-Analysis
. 2018 Apr 5;4(4):CD010676.
doi: 10.1002/14651858.CD010676.pub2.

Antidepressants versus placebo for panic disorder in adults

Irene Bighelli  1 , Mariasole Castellazzi, Andrea Cipriani, Francesca Girlanda, Giuseppe Guaiana, Markus Koesters, Giulia Turrini, Toshi A Furukawa, Corrado Barbui
Affiliations
Meta-Analysis

Antidepressants versus placebo for panic disorder in adults

Irene Bighelli et al. Cochrane Database Syst Rev. .

Abstract

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; and3. to investigate the adverse effects of antidepressants in panic disorder, with or without agoraphobia, including the general prevalence of adverse effects, compared to placebo.

Search methods: We searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference lists of relevant papers and previous systematic reviews.

Selection criteria: All double-blind, randomised, controlled trials (RCTs) allocating adults with panic disorder to antidepressants or placebo.

Data collection and analysis: Two review authors independently checked eligibility and extracted data using a standard form. We entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details and settings. Primary outcomes included failure to respond, measured by a range of response scales, and treatment acceptability, measured by total number of dropouts for any reason. Secondary outcomes included failure to remit, panic symptom scales, frequency of panic attacks, agoraphobia, general anxiety, depression, social functioning, quality of life and patient satisfaction, measured by various scales as defined in individual studies. We used GRADE to assess the quality of the evidence for each outcome MAIN RESULTS: Forty-one unique RCTs including 9377 participants overall, of whom we included 8252 in the 49 placebo-controlled arms of interest (antidepressant as monotherapy and placebo alone) in this review. The majority of studies were of moderate to low quality due to inconsistency, imprecision and unclear risk of selection and performance bias.We found low-quality evidence that revealed a benefit for antidepressants as a group in comparison with placebo in terms of efficacy measured as failure to respond (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.66 to 0.79; participants = 6500; studies = 30). The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 7 (95% CI 6 to 9): that means seven people would need to be treated with antidepressants in order for one to benefit. We observed the same finding when classes of antidepressants were compared with placebo.Moderate-quality evidence suggested a benefit for antidepressants compared to placebo when looking at number of dropouts due to any cause (RR 0.88, 95% CI 0.81 to 0.97; participants = 7850; studies = 30). The magnitude of effect corresponds to a NNTB of 27 (95% CI 17 to 105); treating 27 people will result in one person fewer dropping out. Considering antidepressant classes, TCAs showed a benefit over placebo, while for SSRIs and serotonin-norepinephrine reuptake inhibitor (SNRIs) we observed no difference.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. In particular, TCAs and SSRIs produced more dropouts due to adverse effects in comparison with placebo, while the confidence interval for SNRI, noradrenergic reuptake inhibitors (NRI) and other antidepressants were wide and included the possibility of no difference.

Authors' conclusions: 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. Efficacy can be quantified as a NNTB of 7, implying that seven people need to be treated with antidepressants in order for one to benefit. 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.The choice of whether antidepressants should be prescribed in clinical practice cannot be made on the basis of this review.Limitations in results include funding of some studies by pharmaceutical companies, and only assessing short-term outcomes.Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.

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Conflict of interest statement

IB: none MC: none AC is supported by the NIHR Oxford Cognitive Health Clinical Research Facility and was expert witness for Accord Healthcare for a patent issue about quetiapine extended release. FG: none GG: none MK: none GT: none TAF has received lecture fees from Eli Lilly, Janssen, Meiji, MSD, Otsuka, Pfizer and Tanabe‐Mitsubishi, and consultancy fees from Sekisui Chemicals and Takeda Science Foundation. He has received royalties from Igaku‐Shoin and Nihon Bunka Kagaku‐sha publishers. He has received grant or research support from the Japanese Ministry of Education, Science, and Technology, the Japanese Ministry of Health, Labour and Welfare, the Japan Society for the Promotion of Science, the Japan Foundation for Neuroscience and Mental Health, Mochida and Tanabe‐Mitsubishi. He is diplomate of the Academy of Cognitive Therapy. CB: none

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
4
4
Forest plot of comparison 1. Antidepressants versus placebo, outcome 1.1, failure to respond
5
5
Forest plot of comparison 1. Antidepressants versus placebo, outcome 1.2, total number of dropouts
1.1
1.1. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 1 Failure to respond.
1.2
1.2. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 2 Total number of dropouts.
1.3
1.3. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 3 Failure to remit.
1.4
1.4. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 4 Panic symptoms ‐ endpoint score.
1.5
1.5. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 5 Panic symptoms ‐ mean change.
1.6
1.6. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 6 Frequency of panic attacks ‐ endpoint score.
1.7
1.7. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 7 Frequency of panic attacks ‐ mean change.
1.8
1.8. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 8 Agoraphobia ‐ endpoint score.
1.9
1.9. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 9 Agoraphobia ‐ mean change.
1.10
1.10. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 10 General anxiety ‐ endpoint score.
1.11
1.11. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 11 General anxiety ‐ mean change.
1.12
1.12. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 12 Depression ‐ endpoint score.
1.13
1.13. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 13 Depression ‐ mean change.
1.14
1.14. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 14 Social functioning ‐ endpoint score.
1.15
1.15. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 15 Social functioning ‐ mean change.
1.16
1.16. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 16 Quality of life.
1.17
1.17. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 17 Patient satisfaction.
1.19
1.19. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 19 Number of dropouts due to adverse effects.
1.20
1.20. Analysis
Comparison 1 Antidepressants versus placebo, Outcome 20 Number of participants experiencing at least one adverse effect.
2.1
2.1. Analysis
Comparison 2 TCAs versus placebo, Outcome 1 Failure to respond.
2.2
2.2. Analysis
Comparison 2 TCAs versus placebo, Outcome 2 Total number of dropouts.
2.3
2.3. Analysis
Comparison 2 TCAs versus placebo, Outcome 3 Failure to remit.
2.4
2.4. Analysis
Comparison 2 TCAs versus placebo, Outcome 4 Panic symptoms ‐ endpoint score.
2.5
2.5. Analysis
Comparison 2 TCAs versus placebo, Outcome 5 Panic symptoms ‐ mean change.
2.6
2.6. Analysis
Comparison 2 TCAs versus placebo, Outcome 6 Frequency of panic attacks ‐ endpoint score.
2.7
2.7. Analysis
Comparison 2 TCAs versus placebo, Outcome 7 Frequency of panic attacks ‐ mean change.
2.8
2.8. Analysis
Comparison 2 TCAs versus placebo, Outcome 8 Agoraphobia ‐ endpoint score.
2.9
2.9. Analysis
Comparison 2 TCAs versus placebo, Outcome 9 Agoraphobia ‐ mean change.
2.10
2.10. Analysis
Comparison 2 TCAs versus placebo, Outcome 10 General anxiety ‐ endpoint score.
2.11
2.11. Analysis
Comparison 2 TCAs versus placebo, Outcome 11 General anxiety ‐ mean change.
2.12
2.12. Analysis
Comparison 2 TCAs versus placebo, Outcome 12 Depression ‐ endpoint score.
2.13
2.13. Analysis
Comparison 2 TCAs versus placebo, Outcome 13 Depression ‐ mean change.
2.14
2.14. Analysis
Comparison 2 TCAs versus placebo, Outcome 14 Social functioning ‐ endpoint score.
2.15
2.15. Analysis
Comparison 2 TCAs versus placebo, Outcome 15 Social functioning ‐ mean change.
2.16
2.16. Analysis
Comparison 2 TCAs versus placebo, Outcome 16 Patient satisfaction.
2.17
2.17. Analysis
Comparison 2 TCAs versus placebo, Outcome 17 Number of dropouts due to adverse effects.
2.18
2.18. Analysis
Comparison 2 TCAs versus placebo, Outcome 18 Number of participants experiencing at least one adverse effect.
3.1
3.1. Analysis
Comparison 3 SSRIs versus placebo, Outcome 1 Failure to respond.
3.2
3.2. Analysis
Comparison 3 SSRIs versus placebo, Outcome 2 Total number of dropouts.
3.3
3.3. Analysis
Comparison 3 SSRIs versus placebo, Outcome 3 Failure to remit.
3.4
3.4. Analysis
Comparison 3 SSRIs versus placebo, Outcome 4 Panic symptoms ‐ endpoint score.
3.5
3.5. Analysis
Comparison 3 SSRIs versus placebo, Outcome 5 Panic symptoms ‐ mean change.
3.6
3.6. Analysis
Comparison 3 SSRIs versus placebo, Outcome 6 Frequency of panic attacks ‐ endpoint score.
3.7
3.7. Analysis
Comparison 3 SSRIs versus placebo, Outcome 7 Frequency of panic attacks ‐ mean change.
3.8
3.8. Analysis
Comparison 3 SSRIs versus placebo, Outcome 8 Agoraphobia ‐ endpoint score.
3.9
3.9. Analysis
Comparison 3 SSRIs versus placebo, Outcome 9 Agoraphobia ‐ mean change.
3.10
3.10. Analysis
Comparison 3 SSRIs versus placebo, Outcome 10 General anxiety ‐ endpoint score.
3.11
3.11. Analysis
Comparison 3 SSRIs versus placebo, Outcome 11 General anxiety ‐ mean change.
3.12
3.12. Analysis
Comparison 3 SSRIs versus placebo, Outcome 12 Depression ‐ endpoint score.
3.13
3.13. Analysis
Comparison 3 SSRIs versus placebo, Outcome 13 Depression ‐ mean change.
3.14
3.14. Analysis
Comparison 3 SSRIs versus placebo, Outcome 14 Social functioning ‐ endpoint score.
3.15
3.15. Analysis
Comparison 3 SSRIs versus placebo, Outcome 15 Social functioning ‐ mean change.
3.16
3.16. Analysis
Comparison 3 SSRIs versus placebo, Outcome 16 Quality of life.
3.17
3.17. Analysis
Comparison 3 SSRIs versus placebo, Outcome 17 Number of dropouts due to adverse effects.
3.18
3.18. Analysis
Comparison 3 SSRIs versus placebo, Outcome 18 Number of participants experiencing at least one adverse effect.
4.1
4.1. Analysis
Comparison 4 MAOIs versus placebo, Outcome 1 Failure to respond.
4.2
4.2. Analysis
Comparison 4 MAOIs versus placebo, Outcome 2 Panic symptoms.
4.3
4.3. Analysis
Comparison 4 MAOIs versus placebo, Outcome 3 Agoraphobia.
4.4
4.4. Analysis
Comparison 4 MAOIs versus placebo, Outcome 4 General anxiety.
4.5
4.5. Analysis
Comparison 4 MAOIs versus placebo, Outcome 5 Depression.
5.1
5.1. Analysis
Comparison 5 SNRIs versus placebo, Outcome 1 Failure to respond.
5.2
5.2. Analysis
Comparison 5 SNRIs versus placebo, Outcome 2 Total number of dropouts.
5.3
5.3. Analysis
Comparison 5 SNRIs versus placebo, Outcome 3 Failure to remit.
5.4
5.4. Analysis
Comparison 5 SNRIs versus placebo, Outcome 4 Panic symptoms ‐ endpoint score.
5.5
5.5. Analysis
Comparison 5 SNRIs versus placebo, Outcome 5 Panic symptoms ‐ mean change.
5.6
5.6. Analysis
Comparison 5 SNRIs versus placebo, Outcome 6 Frequency of panic attacks.
5.7
5.7. Analysis
Comparison 5 SNRIs versus placebo, Outcome 7 Agoraphobia.
5.8
5.8. Analysis
Comparison 5 SNRIs versus placebo, Outcome 8 General anxiety.
5.9
5.9. Analysis
Comparison 5 SNRIs versus placebo, Outcome 9 Social functioning ‐ endpoint score.
5.10
5.10. Analysis
Comparison 5 SNRIs versus placebo, Outcome 10 Social functioning ‐ mean change.
5.11
5.11. Analysis
Comparison 5 SNRIs versus placebo, Outcome 11 Quality of life.
5.12
5.12. Analysis
Comparison 5 SNRIs versus placebo, Outcome 12 Patient satisfaction.
5.13
5.13. Analysis
Comparison 5 SNRIs versus placebo, Outcome 13 Number of dropouts due to adverse effects.
5.14
5.14. Analysis
Comparison 5 SNRIs versus placebo, Outcome 14 Number of participants experiencing at least one adverse effect.
6.1
6.1. Analysis
Comparison 6 NRIs versus placebo, Outcome 1 Failure to respond.
6.2
6.2. Analysis
Comparison 6 NRIs versus placebo, Outcome 2 Total number of dropouts.
6.3
6.3. Analysis
Comparison 6 NRIs versus placebo, Outcome 3 Panic symptoms.
6.4
6.4. Analysis
Comparison 6 NRIs versus placebo, Outcome 4 Frequency of panic attacks.
6.5
6.5. Analysis
Comparison 6 NRIs versus placebo, Outcome 5 Agoraphobia.
6.6
6.6. Analysis
Comparison 6 NRIs versus placebo, Outcome 6 Number of dropouts due to adverse effects.
7.1
7.1. Analysis
Comparison 7 Other antidepressants versus placebo, Outcome 1 Failure to respond.
7.2
7.2. Analysis
Comparison 7 Other antidepressants versus placebo, Outcome 2 Total number of dropouts.
7.3
7.3. Analysis
Comparison 7 Other antidepressants versus placebo, Outcome 3 Agoraphobia.
7.4
7.4. Analysis
Comparison 7 Other antidepressants versus placebo, Outcome 4 General anxiety.
7.5
7.5. Analysis
Comparison 7 Other antidepressants versus placebo, Outcome 5 Depression.
7.6
7.6. Analysis
Comparison 7 Other antidepressants versus placebo, Outcome 6 Number of dropouts due to adverse effects.
8.1
8.1. Analysis
Comparison 8 High risk of bias excluded ‐ antidepressants versus placebo, Outcome 1 Failure to respond.
8.2
8.2. Analysis
Comparison 8 High risk of bias excluded ‐ antidepressants versus placebo, Outcome 2 Total number of dropouts.
9.1
9.1. Analysis
Comparison 9 High risk of bias excluded ‐ TCAs versus placebo, Outcome 1 Failure to respond.
9.2
9.2. Analysis
Comparison 9 High risk of bias excluded ‐ TCAs versus placebo, Outcome 2 Total number of dropouts.
10.1
10.1. Analysis
Comparison 10 High risk of bias excluded ‐ SSRIs versus placebo, Outcome 1 Failure to respond.
10.2
10.2. Analysis
Comparison 10 High risk of bias excluded ‐ SSRIs versus placebo, Outcome 2 Total number of dropouts.
11.1
11.1. Analysis
Comparison 11 High risk of bias excluded ‐ SNRIs versus placebo, Outcome 1 Failure to respond.
11.2
11.2. Analysis
Comparison 11 High risk of bias excluded ‐ SNRIs versus placebo, Outcome 2 Total number of dropouts.
12.1
12.1. Analysis
Comparison 12 High dropout rates excluded ‐ Antidepressants versus placebo, Outcome 1 Failure to respond.
12.2
12.2. Analysis
Comparison 12 High dropout rates excluded ‐ Antidepressants versus placebo, Outcome 2 Total number of dropouts.
13.1
13.1. Analysis
Comparison 13 High dropout rates excluded ‐ TCAs versus placebo, Outcome 1 Failure to respond.
13.2
13.2. Analysis
Comparison 13 High dropout rates excluded ‐ TCAs versus placebo, Outcome 2 Total number of dropouts.
14.1
14.1. Analysis
Comparison 14 High dropout rates excluded ‐ SSRIs versus placebo, Outcome 1 Failure to respond.
14.2
14.2. Analysis
Comparison 14 High dropout rates excluded ‐ SSRIs versus placebo, Outcome 2 Total number of dropouts.
15.1
15.1. Analysis
Comparison 15 Funded excluded ‐ antidepressants versus placebo, Outcome 1 Failure to respond.
15.2
15.2. Analysis
Comparison 15 Funded excluded ‐ antidepressants versus placebo, Outcome 2 Total number of dropouts.
16.1
16.1. Analysis
Comparison 16 Funded excluded ‐ TCAs versus placebo, Outcome 1 Failure to respond.
16.2
16.2. Analysis
Comparison 16 Funded excluded ‐ TCAs versus placebo, Outcome 2 Total number of dropouts.
17.1
17.1. Analysis
Comparison 17 Funded excluded ‐ SSRIs versus placebo, Outcome 1 Failure to respond.
17.2
17.2. Analysis
Comparison 17 Funded excluded ‐ SSRIs versus placebo, Outcome 2 Total number of dropouts.
18.1
18.1. Analysis
Comparison 18 Irregular benzodiazepine use excluded ‐ antidepressants versus placebo, Outcome 1 Failure to respond.
18.2
18.2. Analysis
Comparison 18 Irregular benzodiazepine use excluded ‐ antidepressants versus placebo, Outcome 2 Total number of dropouts.
19.1
19.1. Analysis
Comparison 19 Irregular benzodiazepine use excluded ‐ TCAs versus placebo, Outcome 1 Failure to respond.
19.2
19.2. Analysis
Comparison 19 Irregular benzodiazepine use excluded ‐ TCAs versus placebo, Outcome 2 Total number of dropouts.
20.1
20.1. Analysis
Comparison 20 Irregular benzodiazepine use excluded ‐ SSRIs versus placebo, Outcome 1 Failure to respond.
20.2
20.2. Analysis
Comparison 20 Irregular benzodiazepine use excluded ‐ SSRIs versus placebo, Outcome 2 Total number of dropouts.
21.1
21.1. Analysis
Comparison 21 Irregular benzodiazepine use excluded ‐ SNRIs versus placebo, Outcome 1 Failure to respond.
21.2
21.2. Analysis
Comparison 21 Irregular benzodiazepine use excluded ‐ SNRIs versus placebo, Outcome 2 Total number of dropouts.
22.1
22.1. Analysis
Comparison 22 Psychiatric comorbidities excluded ‐ antidepressants versus placebo, Outcome 1 Failure to respond.
22.2
22.2. Analysis
Comparison 22 Psychiatric comorbidities excluded ‐ antidepressants versus placebo, Outcome 2 Total number of dropouts.
23.1
23.1. Analysis
Comparison 23 Psychiatric comorbidities excluded ‐ TCAs versus placebo, Outcome 1 Failure to respond.
23.2
23.2. Analysis
Comparison 23 Psychiatric comorbidities excluded ‐ TCAs versus placebo, Outcome 2 Total number of dropouts.
24.1
24.1. Analysis
Comparison 24 Psychiatric comorbidities excluded ‐ SSRIs versus placebo, Outcome 1 Failure to respond.
24.2
24.2. Analysis
Comparison 24 Psychiatric comorbidities excluded ‐ SSRIs versus placebo, Outcome 2 Total number of dropouts.
25.1
25.1. Analysis
Comparison 25 Psychiatric comorbidities excluded ‐ SNRIs versus placebo, Outcome 1 Failure to respond.
25.2
25.2. Analysis
Comparison 25 Psychiatric comorbidities excluded ‐ SNRIs versus placebo, Outcome 2 Total number of dropouts.
26.1
26.1. Analysis
Comparison 26 Imputation excluded ‐ antidepressants versus placebo, Outcome 1 Failure to respond.
26.2
26.2. Analysis
Comparison 26 Imputation excluded ‐ antidepressants versus placebo, Outcome 2 Total number of dropouts.
27.1
27.1. Analysis
Comparison 27 Imputation excluded ‐ SSRIs versus placebo, Outcome 1 Failure to respond.
27.2
27.2. Analysis
Comparison 27 Imputation excluded ‐ SSRIs versus placebo, Outcome 2 Total number of dropouts.
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Update of

  • doi: 10.1002/14651858.CD010676

References

References to studies included in this review

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Gentil 1993‐clo {published data only}
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Gentil 1993‐imi {published data only}
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GSK 1994 {unpublished data only}
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Hoehn‐Saric 1993 {published data only}
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Johnston 1995 {published data only}
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Lecrubier 1997 {published data only}
    1. Bakker A, Dyck R, Spinhoven P, Balkom AJLM. Paroxetine, clomipramine and cognitive therapy in the treatment of panic disorder. Journal of Clinical Psychiatry 1999;60:831‐38. - PubMed
    1. GlaxoSmithKline. A double‐blind placebo‐controlled comparative study of paroxetine and clomipramine in the treatment of panic disorder. GSK‐ClinicalStudy Register (www.gsk‐clinicalstudyregister.com) 1993/11/12. [Study No.: MY‐1036/BRL‐029060/1/CPMS‐187 (PAR 187)]
    1. Lecrubier Y, Bakker A, Dunbar G, Judge R, Collaborative Paroxetine Panic Study Investigators. A comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Acta Psychiatrica Scandinavica 1997;95:145‐52. - PubMed
    1. Spinhoven P, Balkom AJLM. Paroxetine, clomipramine and cognitive therapy in the treatment of panic disorder. American Psychiatric Association Annual Meeting. Toronto, Ontario, Canada, 1998.
Liebowitz 2009 {published data only}
    1. Liebowitz MR, Asnis G, Mangano R, Tzanis E. A double‐blind, placebo‐controlled, parallel‐group, flexible‐dose study of venlafaxine extended release capsules in adult outpatients with panic disorder. Journal of Clinical Psychiatry 2009;70(4):550‐61. - PubMed
Londborg 1998 {published data only}
    1. Londborg PD, Wolkow R, Smith WT, DuBoff E, England D, Ferguson J, et al. Sertraline in the treatment of panic disorder. A multi‐site, double‐blind, placebo‐controlled, fixed‐dose investigation. The British Journal of Psychiatry 1998;173:54‐60. - PubMed
Lydiard 1993 {published data only}
    1. Lydiard RB, Morton WA, Emmanuel NP, Zealberg JJ, Laraia MT, Stuart GW, et al. Preliminary report: placebo‐controlled, double‐blind study of the clinical and metabolic effects of desipramine in panic disorder. Psychopharmacology Bulletin 1993;29(2):183‐8. - PubMed
Mavissakalian 1989 {published data only}
    1. Groot CM, Mavissakalian MR. Blood pressure and heart rate response of panic disorder patients receiving imipramine in a dose‐response treatment paradigm. Journal of Clinical Psychopharmacology 1994;14(2):107‐10. - PubMed
    1. Mavissakalian MR, Perel JM. Imipramine dose‐response relationship in panic disorder with agoraphobia. Archives of General Psychiatry 1989;46:127‐31. - PubMed
Michelson 2001 {published data only}
    1. Lydiard RB, Pollack MH, Judge R, Michelson D, Tamura R. Fluoxetine in panic disorder: a placebo‐controlled study. 10th European College of Neuropsychopharmacology Congress, 13th‐17th September 1997. Vienna, Austria, 1997.
    1. Michelson D, Allgulander C, Dantendorfer K, Knezevic A, Maierhofer D, Micev V, et al. Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo‐controlled trial. The British Journal of Psychiatry 2001;179:514‐8. - PubMed
Nair 1996 {published data only}
    1. Bakish D, Hooper CL, Filteau MJ, Charbonneau Y, Fraser G, Lee West D, et al. A double‐blind placebo‐controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobia. Psychopharmacology Bulletin 1996;32(1):135‐41. - PubMed
    1. Nair NPV, Bakish D, Saxena B, Amin M, Schwartz G, West TEG. Comparison of fluvoxamine, imipramine and placebo in the treatment of outpatients with panic disorder. Anxiety 1996;2:192‐8. - PubMed
Pohl 1989 {published data only}
    1. Pohl R, Balon R, Yeragani VK, Gershon S. Serotoninergic anxiolytics in the treatment of panic disorder: a controlled study with buspirone. Psychopathology 1989;22(Suppl 1):60‐7. - PubMed
Pollack 1998 {published data only}
    1. Baumel B, Bielski R, Carman J, Goodman W, Hegel M, Houck C, et al. Double‐blind comparison of sertraline and placebo in patients with panic disorder. Poster Presentations P‐1o‐14.
    1. Pohl R, Wolkow RM, Clary CM. Sertraline in the treatment of panic disorder: a double‐blind multicenter study. American Journal of Psychiatry 1998;155:1189‐95. - PubMed
    1. Pollack MH, Otto MW, Worthington JJ, Gus Manfro G, Wolkow R. Sertraline in the treatment of panic disorder: a flexible‐dose multicenter trial. Archives of General Psychiatry 1998;55:1010‐6. - PubMed
    1. Wolkow R, Apter J, Clayton A, Coryell W, Cunningham L, McEntee W, et al. Double‐blind, flexible dose study of sertraline and placebo in patients with panic disorder. Poster Presentations P‐10‐17.
Pollack 2007‐a {published data only}
    1. Pollack M, Whitaker T, Mangano R, Gao B. A comparison of venlafaxine XR and paroxetine in the treatment of outpatients with panic disorder. ACNP 2004 Annual Meeting S201‐S202.
    1. Pollack MH, Mangano R, Entsuah R, Tzanis E, Simon NM. A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder. Psychopharmacology 2007;194:233‐42. - PubMed
Pollack 2007‐b {published data only}
    1. Pollack MH, Lepola U, Koponen H, Simon NM, Worthington JJ, Emilien G, et al. A double‐blind study of the efficacy of venlafaxine extended‐release, paroxetine and placebo in the treatment of panic disorder. Depression and Anxiety 2007;24:1‐14. - PubMed
Schweizer 1993 {published data only}
    1. Rickels K, Schweizer E. Panic disorder: long‐term pharmacotherapy and discontinuation. Journal of Clinical Psychopharmacology 1998;18(6 Suppl 2):12‐8. - PubMed
    1. Rickels K, Schweizer E, Weiss S, Zavodnick S. Maintenance drug treatment for panic disorder. II. Short‐ and long‐term outcome after drug taper. Archives of General Psychiatry 1993;50:61‐8. - PubMed
    1. Schweizer E, Rickels K, Weiss S, Zavodnick S. Maintenance drug treatment of panic disorder I. Results of a prospective, placebo‐controlled comparison of alprazolam and imipramine. Archives of General Psychiatry 1993;50:51‐60. - PubMed
Sharp 1996 {published data only}
    1. Sharp DM, Power KG, Simpson RJ, Swanson V, Anstee JA. Global measures of outcome in a controlled comparison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary care. British Journal of General Practice 1997;47:150‐5. - PMC - PubMed
    1. Sharp DM, Power KG, Simpson RJ, Swanson V, Moodie E, Anstee JA, et al. Fluvoxamine, placebo and cognitive behaviour therapy used alone and in combination in the treatment of panic disorder and agoraphobia. Journal of Anxiety Disorders 1996;10(4):219‐42.
Sheehan 1990 {published data only}
    1. Sheehan DV, Raj AB, Hartnett Sheehan K, Soto S. Buspirone effective for panic disorder?. Journal of Clinical Psychopharmacology 1990;10(1):3‐11. - PubMed
Sheehan 2005 {published data only}
    1. GlaxoSmithKline. A double‐blind, placebo‐controlled, flexible‐dosing trial to evaluate the efficacy of controlled‐release paroxetine in the treatment of panic disorder. GSK‐Clinical Study Register (www.gsk‐clinicalstudyregister.com) 1997. [Study No.: 29060/497]
    1. GlaxoSmithKline. A double‐blind, placebo‐controlled, flexible‐dosing trial to evaluate the efficacy of controlled‐released paroxetine in the treatment of panic disorder. GSK‐Clinical Study Register (www.gsk‐clinicalstudyregister.com) 1997. [Study No.: 29060/495]
    1. GlaxoSmithKline. A double‐blind, placebo‐controlled, flexible‐dosing trial to evaluate the efficacy of modified‐release paroxetine in the treatment of panic disorder. GSK‐Clinical Study Register (www.gsk‐clinicalstudyregister.com) 1997. [Study No.: 29060‐494]
    1. Sheehan DV, Burnham DB, Iyengar MK, Perera P. Efficacy and tolerability of controlled‐release paroxetine in the treatment of panic disorder. Journal of Clinical Psychiatry 2005;66:34‐40. - PubMed
Sheikh 2000 {published data only}
    1. Sheikh JI, Swales PJ. Treatment of panic disorder in older adults: a pilot study comparison of alprazolam, imipramine and placebo. International Journal of Psychiatry in Medicine 2000;29(1):107‐17. - PubMed
Stahl 2003‐cit {published and unpublished data}
    1. Bandelow B, Stein DJ, Dolberg OT, Andersen HF, Baldwin DS. Improvement of quality of life in panic disorder with escitalopram, citalopram, or placebo. Pharmacopsychiatry 2007;40:152‐6. - PubMed
    1. Stahl S, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double‐blind, placebo‐controlled trial. Journal of Clinical Psychiatry 2003;64:1322‐7. - PubMed
Stahl 2003‐esc {published and unpublished data}
    1. Bandelow B, Stein DJ, Dolberg OT, Andersen HF, Baldwin DS. Improvement of quality of life in panic disorder with escitalopram, citalopram, or placebo. Pharmacopsychiatry 2007;40:152‐6. - PubMed
    1. Stahl S, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double‐blind, placebo‐controlled trial. Journal of Clinical Psychiatry 2003;64:1322‐7. - PubMed
Taylor 1990 {published data only}
    1. Clark DB, Taylor B, Roth WT, Hayward C, Ehlers A, Margraf J, et al. Surreptitious drug use by patients in a panic disorder study. American Journal of Psychiatry 1990;147(4):507‐9. - PubMed
    1. Margraf J, Ehlers A, Roth WT, Clark DB, Sheikh J, Agras WS, et al. How "blind" are double‐blind studies?. Journal of Consulting and Clinical Psychology 1991;59(1):184‐7. - PubMed
    1. Taylor CB, Hayward C, King R, Ehlers A, Margraf J, Maddock R, et al. Cardiovascular and symptomatic reduction effects of alprazolam and imipramine in patients with panic disorder: results of a double blind, placebo‐controlled trial. Journal of Clinical Psychopharmacology 1990;10(2):112‐8. - PubMed
Tsutsui 1997 {published data only}
    1. Tsutsui S, Osada H, Muranaka M, Namiki M, Katsura T, Kamijima K, et al. Clinical evaluation of sertraline hydrochloride, a selective serotonin reuptake inhibitor for panic disorder: a double‐blind, placebo‐controlled trial. Journal of Neuropsychopharmacology 1997;19:639‐57.
Tsutsui 2000a {published data only}
    1. Tsutsui S. Clinical evaluation of paroxetine Hcl, a selective serotonin reuptake inhibitor, in the treatment of panic disorder: late phase II double‐blind, parallel group study. Japanese Pharmacology and Therapeutics 2000;28:S271‐94.
Tsutsui 2000b {published data only}
    1. Tsutsui S. Clinical evaluation of paroxetine Hcl, a selective serotonin reuptake inhibitor, in the treatment of panic disorder: phase III double‐blind, parallel group study. Japanese Pharmacology and Therapeutics 2000;28:S295‐314.
Uhlenhuth 1989 {published data only}
    1. Uhlenhuth EH, Matuzas W, Glass RM, Easton C. Response of panic disorder to fixed doses of alprazolam or imipramine. Journal of Affective Disorders 1989;17:261‐70. - PubMed
Van Vliet 1993 {published data only}
    1. Vliet IM, Westenberg HGM, Boer JA. MAO inhibitors in panic disorder: clinical effects of treatment with brofaromine. Psychopharmacology 1993;112:483‐9. - PubMed
Versiani 2002 {published data only}
    1. Versiani M, Cassano G, Perugi G, Benedetti A, Mastalli L, Nardi A, et al. Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well tolerated treatment for panic disorder. Journal of Clinical Psychiatry 2002;63(1):31‐7. - PubMed
Wade 1997 {published data only}
    1. Leinonen E, Lepola U, Koponen H, Turtonen J, Wade A, Lehto H. Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial. Journal of Psychiatry & Neuroscience 2000;25(1):24‐32. - PMC - PubMed
    1. Lepola U, Wade AG, Leinonen EV, Koponen HJ, Frazer J, Sjoedin I, et al. A controlled, prospective, 1‐year trial of citalopram in the treatment of panic disorder. Journal of Clinical Psychiatry 1998;59:528‐34. - PubMed
    1. Wade A, Overe KF, Lemming O. Weight monitoring during two long‐term trials of citalopram. European Neuropsychopharmacology 1999;9 Suppl 5:S221.
    1. Wade AG, Lepola U, Koponen HJ, Pedersen V, Pedersen T. The effect of citalopram in panic disorder. The British Journal of Psychiatry 1997;170:549‐53. - PubMed

References to studies excluded from this review

Balon 1993 {published data only}
    1. Balon R, Yeragani VK, Pohl R, Merlos B, Sherwood P. Changes in appetite and weight during the pharmacological treatment of patients with panic disorder. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 1993;38:19‐22. - PubMed
Dusseldorp 2007 {published data only}
    1. Dusseldorp E, Spinhoven P, Bakker A, Dyck R, Balkom AJLM. Which panic disorder patients benefit from which treatment: cognitive therapy or antidepressants?. Psychotherapy & Psychosomatics 2007;76(3):154‐61. - PubMed
Evans 1986 {published data only}
    1. Evans L, Kenardy J, Schneider P, Hoey H. Effect of a selective serotonin uptake inhibitor in agoraphobia with panic attacks. A double‐blind comparison ofzimeldine, imipramine and placebo. Acta Psychiatrica Scandinavica 1986;73(1):49‐53. - PubMed
Fahy 1992 {published data only}
    1. Fahy TJ, O'Rourke D, Brophy J, Schazmann W, Sciascia S. Clomipramine and lofepramine in DSM III‐R panic disorder: a placebo controlled trial. Clinical Neuropharmacology 1992;15(1 pt B):94. - PubMed
    1. Fahy TJ, O’Rourke D, Brophy J, Schazmann W, Sciascia S. The Galway Study of Panic Disorder I: clomipramine and lofepramine in DSM‐III‐R panic disorder: a placebo controlled trial. Journal of Affective Disorders 1992;25(1):63‐75. - PubMed
GlaxoSmithKline 2002 {unpublished data only}
    1. GlaxoSmithKline. Clinical comparison of paroxetine and placebo on the symptoms emerging during the taper phase of a chronic benzodiazepine treatment, in patients suffering from a variety of anxiety disorders. GSK‐ Clinical Study Register (www.gsk‐clinicalstudyregister.com) 2002.
Green 1988 {published data only}
    1. Green MA, Curtis GC. Personality disorders in panic patients: response to termination of antipanic medication. Journal of Personality Disorders 1988;2(4):303‐14.
Hoffart 1993 {published data only}
    1. Hoffart A, Due Madsen J, Lande B, Gude T, Bille H, Torgersen S. Clomipramine in the treatment of agoraphobic in patients resistant to behavioral therapy. Journal of Clinical Psychiatry 1993;54(12):481‐7. - PubMed
Ito 1995 {published data only}
    1. Ito LM, Gorenstein C, Gentil V, Miyakawa E. Minnesota multiphasic personality inventory correlates of panic disorder with agoraphobia: changes with treatment. Brazilian Journal of Medical and Biological Research 1995;28(9):961‐5. - PubMed
Kahn 1987 {published data only}
    1. Kahn RS, Westenberg HG, Verhoeven WM, Gispen de Wied CC, Kamerbeak WD. Effect of a serotonin precursor and uptake inhibitor in anxiety disorders: a double‐blind comparison of 5‐hydroxytryptophan, clomipramine and placebo. International Clinical Psychopharmacology 1987;2(1):33‐45. - PubMed
Kamijima 2005 {published data only}
    1. Kamijima K, Kuboki T, Kumano H, Burt T, Cohen G, Arano I, et al. A placebo‐controlled, randomized withdrawal study of sertraline for panic disorder in Japan. International Clinical Psychopharmacology 2005;20(5):265‐73. - PubMed
Kawashima 2012 {published data only}
    1. Kawashima S, Ichiki M, Ono S, Katayama S, Matsuki S, Iimori M. The effectiveness of hypnosis for patients with panic disorder (2): its possibilities for reduction of symptom severity. Journal of Tokyo medical University 2012;70(3):351‐9.
Keller 1993 {published data only}
    1. Keller MB, Lavori PW, Goldenberg IM, Baker LA, Pollack MH, Sachs GS, et al. Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo. Journal of Affective Disorders 1993;28(1):27‐38. - PubMed
Klerman 1990 {published data only}
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Modigh 1992 {published data only}
    1. Modigh K, Westenberg P, Eriksson E. Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo‐controlled trial. Journal of Psychopharmacology 1992;12(4):251‐61. - PubMed
Oehrberg 1995 {published data only}
    1. Oehrberg S, Christiansen PE, Behnke K, Borup AL, Severin B, Soegaard J, et al. Paroxetine in the treatment of panic disorder: a randomised, double‐blind, placebo‐controlled study. British Journal of Psychiatry 1995;167(3):374‐9. - PubMed
Pfizer Sertraline Company Study 2003 {unpublished data only}
    1. Pfizer‐Sertraline‐Company‐Study. A placebo‐controlled, double‐blind, comparative study of sertraline in the treatment of subjects with panic disorder ‐ randomized withdrawal study. Pfizer‐Clinical Study Register (www.clinicalstudyresults.com) 2003.
Saxena 1992 {published data only}
    1. Saxena B, Bakish D, Bowen R, D’Souza J. Brofaromine and clomipramine in panic disorder: a double‐blind study. Clinical Neuropharmacology 1992;15(1 ptB):60.
Versiani 2001 {published data only}
    1. Versiani MV, Montgomery SA, Stahl SM, Schwartz GE. [Effect of the novel selective noradrenaline reuptake inhibitor reboxetine on anxiety]. 154th Annual Meeting of the American Psychiatry Association, 5‐10 May 2001. New Orleans, LA, 2001. [NR635]
Yang 2005 {published data only}
    1. Yang H, Yu C, Gao H. The control study of mirtazapine in treating patients with panic disorder. Medical Journal of Chinese People's Health 2005;17(3):133‐5.
Yang 2006 {published data only}
    1. Yang H, Gao H, Yu C. Effect of citalopram in the treatment of panic disorder. Shandong Archives of Psychiatry 2006;19(2):186‐7.
Yeragani 1992 {published data only}
    1. Yeragani VK, Pohl R, Balon R, Ramesh C, Weinberg P. Imipramine‐induced jitteriness and decreased serum iron levels. Neuropsychobiology 1992;25:8‐10. - PubMed
Zhao 2003 {published data only}
    1. Zhao C, Wang Y, Shen X. Venlafaxine plus cognitive behavior therapy in treatment of panic disorder. Shandong Archives of Psychiatry 2003;16(1):12.
Zitrin 1983 {published data only}
    1. Zitrin CM, Klein DF, Woerner MG, Ross DC. Treatment of phobias. Comparison of imipramine hydrochloride and placebo. Archives of General Psychiatry 1983;40(2):125‐38. - PubMed

References to studies awaiting assessment

Anon 1994 {published data only}
    1. Anon. Placebo‐controlled study of efficacy of imipramine, diazepam, baclofen and propranolol in patients with panic disorder. Obozrenie Psikhiatrii Med Psikhologii Im V M Bekhtereva 1994:43‐50.
Diukova 1991 {published data only}
    1. Diukova GM, Shepeleva IP, Vorob’eva OV. Treatment of autonomic crises (attacks of panic). Zhurnal Nevropatologii i Psikhiatrii Imeni S. S. Korsakova 1991;91(5):3‐5. - PubMed
    1. Diukova GM, Shepeleva IP, Vorov’eva OV. Treatment of autonomic attacks (panic attacks). Journal of Russian and East European Psychiatry 1993;26(1):22‐7.
Mallick 2003 {published data only}
    1. Mallick R, Gao B. Quality of life and functionality in panic disorder improve with treatment. 156th Annual Meeting of the American Psychiatric Association, 17‐22 May 2003. San Francisco, CA, 2003. [NR798]
Musgnung 2005 {published data only}
    1. Musgnung J, Pollack M, Whitaker T, Mangano R, Gao B. Short‐term treatment of panic disorder with venlafaxine XR or paroxetine: a placebo‐controlled trial. Psychiatriki 2005;16(Suppl 1):223.
Papp 1996 {published data only}
    1. Papp LA. Pharmacotherapy. Xth World Congress of Psychiatry, 23‐28 August, 1996. Madrid, Spain, 1996.
Pfizer NCT00044772 {unpublished data only}
    1. Pfizer. Study evaluating venlafaxine ER in patients with panic disorder. clinicaltrials.gov/ct2/show/record/NCT00044772?term=NCT00044772&rank=1 2009.
Sandmann 1995 {published data only}
    1. Sandmann J, Lorch B, Bandelow B, Benkert O. Effect of fluvoxamine in panic disorder. A double‐blind placebo‐controlled study. Pharmacopsychiatry 1995;28:209.
Schneier 1998 {published data only}
    1. Schneier FR, Fallon BA, Lin S‐H, Marshall RD, Vermes D, Sanchez‐Lacay JA, et al. Pattern analysis of a clinical trial of fluoxetine in panic disorder. 151st Annual Meeting of the American Psychiatry Association, 30 May‐4 June 1998. Toronto, Ontario, Canada, 1998.
Tsutsui 2000 {published data only}
    1. Tsutsui S. Early phase II study of paroxetine Hcl, a selective serotonin reuptake inhibitor, in the treatment of panic disorder. Japanese Pharmacology and Therapeutics 2000;28(Suppl 1):S253‐69.
Uhlenhuth 2002 {published data only}
    1. Uhlenhuth EH, Warner TD, Matuzas W. Interactive model of therapeutic response in panic disorder: moclobemide, a case in point. Journal of Clinical Psychopharmacology 2002;22(3):275‐84. - PubMed
Wolkow 1996 {published data only}
    1. Wolkow R. A double‐blind, parallel, 12‐week comparison of sertraline and placebo in patients with panic disorder. Xth World Congress of Psychiatry. Madrid, Spain, 1996.

References to ongoing studies

Kruimel 2015 {unpublished data only}
    1. Kruimel J, Leue C. Escitalopram trial for Irritable Bowel Syndrome (IBS) patients with panic disorder. clinicaltrials.gov May 2015. [NCT01551225]

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References to other published versions of this review

Guaiana 2013b
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