Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Sep 12;9(9):CD011567.
doi: 10.1002/14651858.CD011567.pub2.

Antidepressants and Benzodiazepines for Panic Disorder in Adults

Affiliations
Free PMC article
Review

Antidepressants and Benzodiazepines for Panic Disorder in Adults

Irene Bighelli et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: A panic attack is 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. Panic disorder 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, antidepressants and benzodiazepines are the mainstay of treatment for panic disorder. Different classes of antidepressants have been compared; and the British Association for Psychopharmacology, and National Institute for Health and Care Excellence (NICE) 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). In addition to antidepressants, benzodiazepines are widely prescribed for the treatment of panic disorder.

Objectives: To assess the evidence for the effects of antidepressants and benzodiazepines for panic disorder in adults.

Search methods: The Specialised Register of the Cochrane Common Mental Disorders Group (CCMDCTR) to 11 September 2015. This register includes relevant randomised controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-) and PsycINFO (1967-). Reference lists of relevant papers and previous systematic reviews were handsearched. We contacted experts in this field for supplemental data.

Selection criteria: All double-blind randomised controlled trials allocating adult patients with panic disorder to antidepressants or benzodiazepines versus any other active treatment with antidepressants or benzodiazepines.

Data collection and analysis: Two review authors independently checked eligibility and extracted data using a standard form. Data were entered in RevMan 5.3 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings and outcome measures in terms of efficacy, acceptability and tolerability.

Main results: Thirty-five studies, including 6785 participants overall (of which 5365 in the arms of interest (antidepressant and benzodiazepines as monotherapy)) were included in this review; however, since studies addressed many different comparisons, only a few trials provided data for primary outcomes. We found low-quality evidence suggesting no difference between antidepressants and benzodiazepines in terms of response rate (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.67 to 1.47; participants = 215; studies = 2). Very low-quality evidence suggested a benefit for benzodiazepines compared to antidepressants in terms of dropouts due to any cause, even if confidence interval (CI) ranges from almost no difference to benefit with benzodiazepines (RR 1.64, 95% CI 1.03 to 2.63; participants = 1449; studies = 7). We found some evidence suggesting that serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs (when looking at the number of patients experiencing adverse effects). We failed to find clinically significant differences between individual benzodiazepines. The majority of studies did not report details on random sequence generation and allocation concealment; similarly, no details were provided about strategies to ensure blinding. The study protocol was not available for almost all studies so it is difficult to make a judgment on the possibility of outcome reporting bias. Information on adverse effects was very limited.

Authors' conclusions: The identified studies are not sufficient to comprehensively address the objectives of the present review. The majority of studies enrolled a small number of participants and did not provide data for all the outcomes specified in the protocol. For these reasons most of the analyses were underpowered and this limits the overall completeness of evidence. In general, based on the results of the current review, the possible role of antidepressants and benzodiazepines should be assessed by the clinician on an individual basis. The choice of which antidepressant and/or benzodiazepine is prescribed can not be made on the basis of this review only, and should be based on evidence of antidepressants and benzodiazepines efficacy and tolerability, including data from placebo-controlled studies, as a whole. Data on long-term tolerability issues associated with antidepressants and benzodiazepines exposure should also be carefully considered.The present review highlights the need for further higher-quality studies comparing antidepressants with benzodiazepines, which should be conducted with high-methodological standards and including pragmatic outcome measures to provide clinicians with useful and practical data. 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.

Conflict of interest statement

IB: none

CT: 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

TAF has received lecture fees from Eli Lilly, Meiji, Mochida, MSD, Otsuka, Pfizer and Tanabe‐Mitsubishi, and consultancy fees from Sekisui Chemicals and Takeda Science Foundation. He has received royalties from Igaku‐Shoin, Seiwa‐Shoten 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 a diplomate of the Academy of Cognitive Therapy.

GG: none

MK: none

CB: none.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 Antidepressants versus benzodiazepines, outcome: 1.1 Failure to respond.
5
5
Forest plot of comparison: 1 Antidepressants versus benzodiazepines, outcome: 1.2 Total number of dropouts.
1.1
1.1. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 1 Failure to respond.
1.2
1.2. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 2 Total number of dropouts.
1.3
1.3. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 3 Failure to remit.
1.4
1.4. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 4 Panic symptoms ‐ endpoint score.
1.5
1.5. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 5 Panic symptoms ‐ mean change.
1.6
1.6. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 6 Frequency of panic attacks.
1.7
1.7. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 7 Agoraphobia.
1.8
1.8. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 8 General anxiety.
1.9
1.9. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 9 Depression.
1.10
1.10. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 10 Social functioning.
1.14
1.14. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 14 Number of dropouts due to adverse effects.
1.15
1.15. Analysis
Comparison 1 Antidepressants versus benzodiazepines, Outcome 15 Number of patients experiencing at least one adverse effect.
2.1
2.1. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 1 Failure to respond.
2.2
2.2. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 2 Total number of dropouts.
2.3
2.3. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 3 Failure to remit.
2.4
2.4. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 4 Panic symptoms ‐ endpoint score.
2.5
2.5. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 5 Panic symptoms ‐ mean change.
2.6
2.6. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 6 Frequency of panic attacks.
2.7
2.7. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 7 Agoraphobia.
2.8
2.8. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 8 General anxiety.
2.9
2.9. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 9 Depression.
2.10
2.10. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 10 Social functioning.
2.14
2.14. Analysis
Comparison 2 TCAs versus benzodiazepines, Outcome 14 Number of dropouts due to adverse effects.
3.1
3.1. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 1 Failure to respond.
3.2
3.2. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 2 Total number of dropouts.
3.3
3.3. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 3 Failure to remit.
3.4
3.4. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 4 Panic symptoms.
3.5
3.5. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 5 Frequency of panic attacks.
3.6
3.6. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 6 Agoraphobia.
3.7
3.7. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 7 General anxiety.
3.8
3.8. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 8 Depression.
3.9
3.9. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 9 Social functioning.
3.13
3.13. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 13 Number of dropouts due to adverse effects.
3.14
3.14. Analysis
Comparison 3 SSRIs versus benzodiazepines, Outcome 14 Number of patients experiencing at least one adverse effect.
4.1
4.1. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 1 Failure to respond.
4.2
4.2. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 2 Total number of dropouts.
4.3
4.3. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 3 Failure to remit.
4.4
4.4. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 4 Panic symptoms.
4.5
4.5. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 5 Frequency of panic attacks.
4.6
4.6. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 6 Agoraphobia.
4.7
4.7. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 7 General anxiety ‐ endpoint score.
4.8
4.8. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 8 General anxiety ‐ mean change.
4.9
4.9. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 9 Depression ‐ endpoint score.
4.10
4.10. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 10 Depression ‐ mean change.
4.15
4.15. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 15 Number of dropouts due to adverse effects.
4.16
4.16. Analysis
Comparison 4 TCAs versus SSRIs, Outcome 16 Number of patients experiencing at least one adverse effect.
5.1
5.1. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 1 Failure to respond.
5.2
5.2. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 2 Total number of dropouts.
5.4
5.4. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 4 Panic symptoms.
5.5
5.5. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 5 Frequency of panic attacks.
5.7
5.7. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 7 General anxiety.
5.8
5.8. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 8 Depression.
5.13
5.13. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 13 Number of dropouts due to adverse effects.
5.14
5.14. Analysis
Comparison 5 TCAs versus MAOIs, Outcome 14 Number of patients experiencing at least one adverse effect.
6.1
6.1. Analysis
Comparison 6 SSRIs versus MAOIs, Outcome 1 Failure to respond.
6.2
6.2. Analysis
Comparison 6 SSRIs versus MAOIs, Outcome 2 Total number of dropouts.
6.3
6.3. Analysis
Comparison 6 SSRIs versus MAOIs, Outcome 3 Failure to remit.
6.6
6.6. Analysis
Comparison 6 SSRIs versus MAOIs, Outcome 6 Agoraphobia.
6.7
6.7. Analysis
Comparison 6 SSRIs versus MAOIs, Outcome 7 General anxiety.
6.13
6.13. Analysis
Comparison 6 SSRIs versus MAOIs, Outcome 13 Number of dropouts due to adverse effects.
6.14
6.14. Analysis
Comparison 6 SSRIs versus MAOIs, Outcome 14 Number of patients experiencing at least one adverse effect.
7.1
7.1. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 1 Failure to respond.
7.2
7.2. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 2 Total number of dropouts.
7.3
7.3. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 3 Failure to remit.
7.4
7.4. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 4 Panic symptoms.
7.6
7.6. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 6 Agoraphobia.
7.7
7.7. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 7 General anxiety.
7.9
7.9. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 9 Social functioning.
7.10
7.10. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 10 Quality of life.
7.13
7.13. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 13 Number of dropouts due to adverse effects.
7.14
7.14. Analysis
Comparison 7 SSRIs versus SNRIs, Outcome 14 Number of patients experiencing at least one adverse effect.
8.2
8.2. Analysis
Comparison 8 SSRIs versus NaSSAs, Outcome 2 Total number of dropouts.
8.4
8.4. Analysis
Comparison 8 SSRIs versus NaSSAs, Outcome 4 Panic symptoms.
8.7
8.7. Analysis
Comparison 8 SSRIs versus NaSSAs, Outcome 7 General anxiety.
8.13
8.13. Analysis
Comparison 8 SSRIs versus NaSSAs, Outcome 13 Number of dropouts due to adverse effects.
9.1
9.1. Analysis
Comparison 9 SSRIs versus Other Antidepressants, Outcome 1 Failure to respond.
9.2
9.2. Analysis
Comparison 9 SSRIs versus Other Antidepressants, Outcome 2 Total number of dropouts.
9.6
9.6. Analysis
Comparison 9 SSRIs versus Other Antidepressants, Outcome 6 Agoraphobia.
9.7
9.7. Analysis
Comparison 9 SSRIs versus Other Antidepressants, Outcome 7 General anxiety.
9.8
9.8. Analysis
Comparison 9 SSRIs versus Other Antidepressants, Outcome 8 Depression.
9.13
9.13. Analysis
Comparison 9 SSRIs versus Other Antidepressants, Outcome 13 Number of dropouts due to adverse effects.
10.1
10.1. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 1 Failure to respond.
10.2
10.2. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 2 Total number of dropouts.
10.3
10.3. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 3 Failure to remit.
10.4
10.4. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 4 Panic symptoms.
10.5
10.5. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 5 Frequency of panic attacks.
10.6
10.6. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 6 Agoraphobia.
10.7
10.7. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 7 General anxiety.
10.8
10.8. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 8 Depression.
10.10
10.10. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 10 Quality of life.
10.13
10.13. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 13 Number of dropouts due to adverse effects.
10.14
10.14. Analysis
Comparison 10 Individual Antidepressants versus another antidepressant within the same class, Outcome 14 Number of patients experiencing at least one adverse effect.
11.1
11.1. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 1 Failure to respond.
11.2
11.2. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 2 Total number of dropouts.
11.3
11.3. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 3 Failure to remit.
11.4
11.4. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 4 Panic symptoms.
11.5
11.5. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 5 Frequency of panic attacks.
11.7
11.7. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 7 General anxiety.
11.8
11.8. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 8 Depression.
11.9
11.9. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 9 Social functioning.
11.10
11.10. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 10 Quality of life.
11.13
11.13. Analysis
Comparison 11 Individual benzodiazepines versus another benzodiazepine, Outcome 13 Number of dropouts due to adverse effects.
12.1
12.1. Analysis
Comparison 12 High risk of bias excluded ‐ Antidepressants versus benzodiazepines, Outcome 1 Total number of dropouts.
13.1
13.1. Analysis
Comparison 13 High risk of bias excluded ‐ TCAs versus benzodiazepines, Outcome 1 Total number of dropouts.
14.1
14.1. Analysis
Comparison 14 High risk of bias excluded ‐ TCAs versus SSRIs, Outcome 1 Total number of dropouts.
15.1
15.1. Analysis
Comparison 15 High risk of bias excluded ‐ TCAs versus MAOIs, Outcome 1 Total number of dropouts.
16.1
16.1. Analysis
Comparison 16 High risk of bias excluded ‐ SSRIs versus MAOIs, Outcome 1 Failure to respond.
17.1
17.1. Analysis
Comparison 17 High dropout rates excluded ‐ Antidepressants versus benzodiazepines, Outcome 1 Total number of dropouts.
18.1
18.1. Analysis
Comparison 18 High dropout rates excluded ‐ TCAs versus benzodiazepines, Outcome 1 Total number of dropouts.
19.1
19.1. Analysis
Comparison 19 High dropout rates excluded ‐ TCAs versus SSRIs, Outcome 1 Failure to respond.
19.2
19.2. Analysis
Comparison 19 High dropout rates excluded ‐ TCAs versus SSRIs, Outcome 2 Total number of dropouts.
20.1
20.1. Analysis
Comparison 20 Funded excluded ‐ Antidepressants versus benzodiazepines, Outcome 1 Total number of dropouts.
21.1
21.1. Analysis
Comparison 21 Funded excluded ‐ TCAs versus benzodiazepines, Outcome 1 Total number of dropouts.
22.1
22.1. Analysis
Comparison 22 Funded excluded ‐ TCAs versus SSRIs, Outcome 1 Failure to respond.
22.2
22.2. Analysis
Comparison 22 Funded excluded ‐ TCAs versus SSRIs, Outcome 2 Total number of dropouts.
23.1
23.1. Analysis
Comparison 23 Funded excluded ‐ SSRIs versus MAOIs, Outcome 1 Failure to respond.
24.1
24.1. Analysis
Comparison 24 Psychiatric comorbidities excluded ‐ Antidepressants versus benzodiazepines, Outcome 1 Failure to respond.
24.2
24.2. Analysis
Comparison 24 Psychiatric comorbidities excluded ‐ Antidepressants versus benzodiazepines, Outcome 2 Total number of dropouts.
25.1
25.1. Analysis
Comparison 25 Psychiatric comorbidities excluded ‐ TCAs versus benzodiazepines, Outcome 1 Total number of dropouts.
26.1
26.1. Analysis
Comparison 26 Psychiatric comorbidities excluded ‐ TCAs versus SSRIs, Outcome 1 Failure to respond.
26.2
26.2. Analysis
Comparison 26 Psychiatric comorbidities excluded ‐ TCAs versus SSRIs, Outcome 2 Total number of dropouts.
27.1
27.1. Analysis
Comparison 27 Psychiatric comorbidities excluded ‐ Individual antidepressants versus individual antidepressants (within the same class), Outcome 1 Failure to respond.
27.2
27.2. Analysis
Comparison 27 Psychiatric comorbidities excluded ‐ Individual antidepressants versus individual antidepressants (within the same class), Outcome 2 Total number of dropouts.
28.1
28.1. Analysis
Comparison 28 Psychiatric comorbidities excluded ‐ Individual benzodiazepines versus individual benzodiazepines, Outcome 1 Total number of dropouts.
29.1
29.1. Analysis
Comparison 29 Imputation excluded ‐ TCAs versus SSRIs, Outcome 1 Failure to respond.
29.2
29.2. Analysis
Comparison 29 Imputation excluded ‐ TCAs versus SSRIs, Outcome 2 Total number of dropouts.
30.1
30.1. Analysis
Comparison 30 Imputation excluded ‐ Individual antidepressants versus individual antidepressants (within the same class), Outcome 1 Failure to respond.
30.2
30.2. Analysis
Comparison 30 Imputation excluded ‐ Individual antidepressants versus individual antidepressants (within the same class), Outcome 2 Total number of dropouts.
31.1
31.1. Analysis
Comparison 31 Irregular benzodiazepines use excluded ‐ TCAs versus SSRIs, Outcome 1 Failure to respond.
31.2
31.2. Analysis
Comparison 31 Irregular benzodiazepines use excluded ‐ TCAs versus SSRIs, Outcome 2 Total number of dropouts.
32.1
32.1. Analysis
Comparison 32 Irregular benzodiazepines use excluded ‐ SSRIs versus MAOIs, Outcome 1 Failure to respond.
33.1
33.1. Analysis
Comparison 33 Irregular benzodiazepines use excluded ‐ Individual antidepressants versus individual antidepressants (within the same class), Outcome 1 Failure to respond.
33.2
33.2. Analysis
Comparison 33 Irregular benzodiazepines use excluded ‐ Individual antidepressants versus individual antidepressants (within the same class), Outcome 2 Total number of dropouts.

Update of

  • Cochrane Database Syst Rev. doi: 10.1002/14651858.CD011567

Similar articles

See all similar articles

Cited by 8 articles

See all "Cited by" articles

LinkOut - more resources

Feedback