Panic Disorder
Conditions
Keywords
Panic Disorder
Brief summary
To evaluate the efficacy and safety of sertraline compared to paroxetine in patients with panic disorder.
Interventions
DRUGsertraline
dosage : 25mg , 50mg , placebo; dosage form : tablet; frequency : once daily after dinner; duration : 14 weeks
DRUGParoxetine
dosage : 10mg, placebo; dosage form : capsule; frequency : once daily after dinner; duration : 14 weeks
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patient who meets diagnosis of Panic Disorder (with or without Agoraphobia) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV). * Patients must have experienced at least 4 panic attacks within 4 weeks before screening. * At baseline patients with Panic Disorder of total score of 18 or higher on the Panic and Agoraphobia scale (clinician rated version).
Exclusion criteria
* Patients who concurrently have bipolar disorder, schizophrenia, delusional disorder, epilepsy, Major Depression Disorder (MDD), Obsessive Compulsive Disorder (OCD), Seasonal Affective Disorder (SAD) or General Anxiety Disorder (GAD) according to the DSM-IV criteria. * Patients who concurrently have depression/depressive state, anxiety disorder and generalized anxiety disorder may be included in the study if the primary diagnosis is identified to be panic disorder * Patients with the total score of at least 18 on the Hamilton Depression Rating Scale (HAM-D) (Items 1 to 17) at the start of Screening (Visit 1) * Patients who require concomitant drug therapy with psychotropic agents (including benzodiazepines) and monoamine oxidase inhibitor during the period of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Panic and Agoraphobia Scale (PAS) Total Score at the End of Treatment Phase | Baseline and 12 weeks | Panic and Agoraphobia Scale has 13 items with a 5-point scale (range: 0 to 4). The total possible score is ranged from 0 to 52. The increasing value are considered worse outcome. The scale is grouped into 5 subscores (not including item U in total score): panic attacks ; agoraphobia/avoidance behavior ; anticipatory anxiety; disability; and health worries. Four point difference in reduction of the PAS total score has been identified as not clinically meaningful in the assessment of Panic Disorder symptomatology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Panic Attack at the End of Treatment Phase | Baseline and 12 weeks | Panic attacks were defined as having four or more of the following Diagnostic and Statistical Manual of Mental Disorders symptoms. Palpitations or increased heart rate, Sweating, Trembling or shaking, Shortness of breath or smothering sensations, Choking, Chest pain or discomfort, Nausea or upset stomach, Dizziness, unsteady feelings or faintness, Feeling unlike yourself, or detached from a situation and/or like things happening around you are strange and unreal, Fear of going crazy or doing something uncontrolled, Fear of dying, Abnormal sense, Hot flashes or chills. |
| Mean Change From Baseline in Hamilton Anxiety Rating Scale Total Score at the End of Treatment Phase | Baseline and 12 weeks | The Hamilton Anxiety Rating Scale provided a 5-point intensity rating (0=None to 4=Very severe) of anxiety symptoms in 14 items. The increasing values are considered worse outcome. The total possible score is ranged from 0 to 52. |
| Percentage of Participants of Responder in Clinical Global Impression (CGI) - Improvement | 12 weeks | The ratings were rated to compare with baseline by 7-point 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. Responder was defined as number of participants who were assessed as very much improved or much improved. |
| Summary of Adverse Events in Tapering Phase | 4 weeks | Number of subjects with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Subjects were counted only once per treatment in each row. |
| Percentage of Participants With Deterioration in Antidepressant Discontinuation Scale During Tapering Phase | 4 weeks | The percentage of participants divided was calcurated as follows: Devide the number of participants who had experienced new symptoms in Week 16, regardless of causal relationship with the study drug, or worsening of the severity in Week 16 compared with Week 12, by total number of participants in each treatment group. |
| Number of Participants With Summary of Adverse Events in Treatment Phase | 1, 2, 4, 6, 8 10 and 12 weeks (or study discontinuation) after administration of study drug | Number of sparticipants with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Participants were counted only once per treatment in each row. |
Countries
Japan
Participant flow
Recruitment details
Participants were screened at 34 centers in Japan.
Pre-assignment details
Subjects who experienced at least one panic attack that met the DSM-IV diagnostic criteria per week between the start of the washout/observation period and the start of the double-blind treatment period and who had a total score of 18 or higher on the Panic and Agoraphobia Scale at the start of the double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day.
At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks. | 157 |
| Paroxetine Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day.
At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks. | 162 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Tapering Phase | Adverse Event | 1 | 5 |
| Tapering Phase | Job transfer | 0 | 1 |
| Tapering Phase | Pregnancy | 0 | 1 |
| Tapering Phase | Withdrawal by Subject | 5 | 3 |
| Treatment Phase | Adverse Event | 14 | 22 |
| Treatment Phase | Lack of Efficacy | 2 | 3 |
| Treatment Phase | Lost to Follow-up | 0 | 1 |
| Treatment Phase | Not treated | 0 | 2 |
| Treatment Phase | Physician Decision | 1 | 0 |
| Treatment Phase | Pregnancy | 0 | 1 |
| Treatment Phase | Protocol Violation | 1 | 1 |
| Treatment Phase | Transference or work related matter | 0 | 5 |
| Treatment Phase | Withdrawal by Subject | 7 | 7 |
Baseline characteristics
| Characteristic | Sertraline | Paroxetine | Total |
|---|---|---|---|
| Age, Customized 18 - 44 years | 119 participants | 126 participants | 245 participants |
| Age, Customized < 18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized 45 -64 years | 38 participants | 36 participants | 74 participants |
| Age, Customized >= 65 years | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 113 Participants | 109 Participants | 222 Participants |
| Sex: Female, Male Male | 44 Participants | 53 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 132 / 157 | 137 / 162 |
| serious Total, serious adverse events | 2 / 157 | 1 / 162 |
Outcome results
Primary
Mean Change From Baseline in Panic and Agoraphobia Scale (PAS) Total Score at the End of Treatment Phase
Panic and Agoraphobia Scale has 13 items with a 5-point scale (range: 0 to 4). The total possible score is ranged from 0 to 52. The increasing value are considered worse outcome. The scale is grouped into 5 subscores (not including item U in total score): panic attacks ; agoraphobia/avoidance behavior ; anticipatory anxiety; disability; and health worries. Four point difference in reduction of the PAS total score has been identified as not clinically meaningful in the assessment of Panic Disorder symptomatology.
Time frame: Baseline and 12 weeks
Population: Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12.~Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sertraline | Mean Change From Baseline in Panic and Agoraphobia Scale (PAS) Total Score at the End of Treatment Phase | -17.4 Scores on scale |
| Paroxetine | Mean Change From Baseline in Panic and Agoraphobia Scale (PAS) Total Score at the End of Treatment Phase | -17.0 Scores on scale |
Comparison: The two-sided 95% confidence interval (CI) of the intergroup difference (sertraline group - paroxetine group) of the mean reduction in the PAS total score at each dose during the treatment phase was calculated using an analysis of covariance (ANCOVA) model with treatment group as a factor and baseline PAS total score as a covariate.95% CI: [-2.5, 1.6]ANCOVA
Secondary
Mean Change From Baseline in Hamilton Anxiety Rating Scale Total Score at the End of Treatment Phase
The Hamilton Anxiety Rating Scale provided a 5-point intensity rating (0=None to 4=Very severe) of anxiety symptoms in 14 items. The increasing values are considered worse outcome. The total possible score is ranged from 0 to 52.
Time frame: Baseline and 12 weeks
Population: Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12.~Last Observation Carried Forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Mean Change From Baseline in Hamilton Anxiety Rating Scale Total Score at the End of Treatment Phase | -11.35 Scores on a scale | Standard Deviation 10.45 |
| Paroxetine | Mean Change From Baseline in Hamilton Anxiety Rating Scale Total Score at the End of Treatment Phase | -10.36 Scores on a scale | Standard Deviation 8.27 |
Secondary
Mean Change From Baseline in Panic Attack at the End of Treatment Phase
Panic attacks were defined as having four or more of the following Diagnostic and Statistical Manual of Mental Disorders symptoms. Palpitations or increased heart rate, Sweating, Trembling or shaking, Shortness of breath or smothering sensations, Choking, Chest pain or discomfort, Nausea or upset stomach, Dizziness, unsteady feelings or faintness, Feeling unlike yourself, or detached from a situation and/or like things happening around you are strange and unreal, Fear of going crazy or doing something uncontrolled, Fear of dying, Abnormal sense, Hot flashes or chills.
Time frame: Baseline and 12 weeks
Population: Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12.~Last Observation Carried Forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Mean Change From Baseline in Panic Attack at the End of Treatment Phase | -4.07 panic attacks per week | Standard Deviation 6.12 |
| Paroxetine | Mean Change From Baseline in Panic Attack at the End of Treatment Phase | -4.59 panic attacks per week | Standard Deviation 7.52 |
Secondary
Number of Participants With Summary of Adverse Events in Treatment Phase
Number of sparticipants with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Participants were counted only once per treatment in each row.
Time frame: 1, 2, 4, 6, 8 10 and 12 weeks (or study discontinuation) after administration of study drug
Population: The safety analysis set : Subset of patients who had taken at least one dose of the study drug and who had visited the study center at least once after taking the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sertraline | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects with serious adverse events | 1 Participants |
| Sertraline | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects discontinued due to adverse events | 14 Participants |
| Sertraline | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects with severe adverse events | 3 Participants |
| Sertraline | Number of Participants With Summary of Adverse Events in Treatment Phase | Dose reduced or temporary discontinuation | 13 Participants |
| Sertraline | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects with adverse events | 127 Participants |
| Paroxetine | Number of Participants With Summary of Adverse Events in Treatment Phase | Dose reduced or temporary discontinuation | 14 Participants |
| Paroxetine | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects with adverse events | 134 Participants |
| Paroxetine | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects with serious adverse events | 1 Participants |
| Paroxetine | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects with severe adverse events | 14 Participants |
| Paroxetine | Number of Participants With Summary of Adverse Events in Treatment Phase | Subjects discontinued due to adverse events | 23 Participants |
Secondary
Percentage of Participants of Responder in Clinical Global Impression (CGI) - Improvement
The ratings were rated to compare with baseline by 7-point 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. Responder was defined as number of participants who were assessed as very much improved or much improved.
Time frame: 12 weeks
Population: Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12.~Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sertraline | Percentage of Participants of Responder in Clinical Global Impression (CGI) - Improvement | 83.5 Percentage of participants |
| Paroxetine | Percentage of Participants of Responder in Clinical Global Impression (CGI) - Improvement | 85.0 Percentage of participants |
Secondary
Percentage of Participants With Deterioration in Antidepressant Discontinuation Scale During Tapering Phase
The percentage of participants divided was calcurated as follows: Devide the number of participants who had experienced new symptoms in Week 16, regardless of causal relationship with the study drug, or worsening of the severity in Week 16 compared with Week 12, by total number of participants in each treatment group.
Time frame: 4 weeks
Population: Completer Set : Subset of patients in the EES who had a PAS rating at Week 16.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sertraline | Percentage of Participants With Deterioration in Antidepressant Discontinuation Scale During Tapering Phase | 59.7 Percentage of participants |
| Paroxetine | Percentage of Participants With Deterioration in Antidepressant Discontinuation Scale During Tapering Phase | 76.3 Percentage of participants |
p-value: 0.0062Fisher Exact
Secondary
Summary of Adverse Events in Tapering Phase
Number of subjects with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Subjects were counted only once per treatment in each row.
Time frame: 4 weeks
Population: The safety analysis set : Subset of patients who had taken at least one dose of the study drug and who had visited the study center at least once after taking the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sertraline | Summary of Adverse Events in Tapering Phase | Subjects with serious adverse events | 1 Participants |
| Sertraline | Summary of Adverse Events in Tapering Phase | Subjects discontinued due to adverse events | 1 Participants |
| Sertraline | Summary of Adverse Events in Tapering Phase | Subjects with severe adverse events | 11 Participants |
| Sertraline | Summary of Adverse Events in Tapering Phase | Dose reduced or temporary discontinuation | 0 Participants |
| Sertraline | Summary of Adverse Events in Tapering Phase | Subjects with adverse events | 73 Participants |
| Paroxetine | Summary of Adverse Events in Tapering Phase | Dose reduced or temporary discontinuation | 0 Participants |
| Paroxetine | Summary of Adverse Events in Tapering Phase | Subjects with adverse events | 87 Participants |
| Paroxetine | Summary of Adverse Events in Tapering Phase | Subjects with serious adverse events | 0 Participants |
| Paroxetine | Summary of Adverse Events in Tapering Phase | Subjects with severe adverse events | 16 Participants |
| Paroxetine | Summary of Adverse Events in Tapering Phase | Subjects discontinued due to adverse events | 4 Participants |