Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00206765
Status:
TERMINATED
Last Update Posted:
2012-10-22
First Post:
2005-09-13
Brief Title:
Risperidone vs Paroxetine for Panic Attacks
Sponsor:
Beth Israel Medical Center
Organization:
Beth Israel Medical Center
Study Overview
Official Title:
A Single-blind Trial of Risperidone vs Paroxetine for Treatment of Panic Attacks
Status:
TERMINATED
Status Verified Date:
2012-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
We are comparing the efficacy of Risperidone versus Paroxetine in the treatment of panic symptoms The study hypothesis is that Risperidone will be a superior medicine for treating panic
Detailed Description:
Rationale
Risperidone is an atypical antipsychotic drug that acts as an antagonist at 5-HT2A2C and D2 receptors Chouignard et al 1993 Marder Meibach 1994 In its serotonergic activity risperidone resembles both the atypical antidepressant and 5HT2-antagonist nefazodone Bakish et al 1993 and a 5HT2-antagonist ritanserine Lima Moncrieff 2000 Preskorn 1995 Nefazodone treats anxiety symptoms and induces less agitation than other reuptake blockers Fawcett et al 1995 while ritanserin shows effectiveness in treatment of dysthymia in clinical trials Moreover risperidone increases release of dopamine and norepinephrine in the prefrontal cortex Zhang et al 2000 an activity that in other pharmacological agents is associated with their antidepressant anxiolytic and antipanic properties Thase 2002
Therefore risperidone has a potential to be effective for treatment of either Generalized Anxiety Disorder or Panic Disorder or Major Depressive Disorder with Panic Attacks DSM-IV 1994 as a single agent Moreover due to its D2 and 5-HT2A2C antagonism and proven antipsychotic efficacy the drug could be uniquely effective for severe panic attacks with psychotic features or para-psychotic features Galynker et al 1996 Consistent with this supposition Marder et al 1997 reported that in patients with schizophrenia risperidone produced significantly greater improvements than haloperidol in PANSS scores measuring anxiety and depression
Our clinical experience with over 50 patients with panic attacks showed that low dose risperidone similar to lorazepam reduced or eliminated anxiety and panic often after the first dose Risperidone was most effective for patients experiencing obsessive intrusive anxiety-inducing thoughts In contrast to lorazepam risperidone treatment did not result in building of tolerance to the drug or disinhibition We did not observe extrapyramidal side effects in patients treated with risperidone for panic attacks Thus our preliminary clinical data indicate that due to its efficacy quick onset of action absence of addictive potential and lack of side effects risperidone could be superior to both benzodiazepines and SSRIs for treatment of panic attacks particularly for severe panic attacks Moreover risperidone has a potential to be the first line drug for treatment of these symptoms
Consequently at present a clinical study of risperidone for treatment of panic attacks is indicated and is of great potential value We are therefore proposing an exploratory open label single-blind trial of risperidone in vs paroxetine for treatment of panic attacks
HypothesisObjectives
Objective One To compare the efficacy of risperidone to that of paroxetine in treatment of panic attacks in patients with Panic Disorder and with Major Depressive Disorder with Panic attacks
Hypothesis One Risperidone and will be more efficacious in treatment of panic symptoms in both patient groups Some patients will improve within 24 hrs
Objective Two To compare the side effect profile of risperidone vs paroxetine in treatment of panic attacks
Hypothesis Two Risperidone compared to paroxetine will cause less sexual side effects anxiety and restlessness There will be no difference in extrapyramidal side effects between the paroxetine and the risperidone groups
Objective Three To compare response rates of risperidone vs paroxetine in treatment of panic attacks
Hypothesis Three Patients with panic attacks will respond significantly faster to risperidone that to paroxetine
Objective Four To examine demographic and clinical predictors of robust response to risperidone treatment using appropriate statistical analysis of individual scales items and treatment response rates
Hypothesis Four The subgroup patients with panic attacks who will have high scores on items reflecting somatic anxiety and ruminative intrusive thinking and those with nocturnal panic attacks will show better response to risperidone therapy than patients with low scores on those items
If study hypotheses are confirmed future research could include a randomized double blind fixed dose study of risperidone as the sole agent for treatment of panic disorder and Phase IV trials aimed to determine the effectiveness of 0125 mg and 00675 mg dose of risperidone for treatment of anxiety and panic attacks
Study Population
The patient population will consist of psychiatric outpatients who meet criteria for the DSM-IV diagnosis of Major Depressive Disorder with Panic Attacks or Panic Disorder The subjects will be recruited from the Center for Treatment of Affective Disorders and from the Anxiety and Trauma Center in the Department of Psychiatry at the Beth Israel Medical center that provide care to 900 patients At present the patient ethnic and racial mix is 50 Hispanic 15 African American 325 Caucasian and 25 Asian The gender distribution is approximately 33 male and 67 female The outpatient payer mix is 20 Medicare 74 Medicaid and 6 combined Of those patients approximately 40 360 manifest panic attacks Based on our previous experience with recruitment for research studies we expect that 10-12 of patients 36-42 meeting diagnostic criteria will also meet the inclusion and exclusion criteria will sign the inform consent and will participate in the study We expect to recruit 40 patients per year and to complete the study in 3 years
Inclusion Criteria
1 Males and females ages 21-55
2 Ability to sign an informed consent
3 Diagnosis of Panic Disorder or MDD with Panic attacks single episode recurrent or chronic
4 HAM-A score 17
Exclusion Criteria
1 Alcohol or substance abuse within the last 6 months
2 Current diagnosis of Obsessive-Compulsive Disorder
3 Current diagnosis of Schizophrenia Schizoaffective Disorder or Bipolar Mood Disorder
4 Use of antipsychotic medications over the two months preceding enrollment in the study
5 Changes in antidepressant or mood stabilizer dosing over the two months preceding enrollment in the study
6 Previous adverse reaction to risperidone or paroxetine
Study Design and Drug Regimens
The study will be an 8-week parallel comparison with a blinded rater of risperidone and paroxetine for treatment of three groups of patients with panic attacks Each group will consist of 30 subjects
After signing an informed consent the subjects will be randomly assigned in the open manner to treatment with risperidone or paroxetine alone
Arm 1 Treatment with risperidone will be flexible-dose and will be initiated at 025 mg po qhs For the subjects who did not achieve a remission of panic symptoms the dose will be increased to 05 mg po qhs on day 3 For subjects who experienced morning sedation the dose will be decreased to 0125-mg po qhs on day 3
Arm 2 Treatment with Paroxetine will be flexible-dose and will be initiated at 10-mg po qhs For subjects who experienced morning sedation the dose will be decreased to 5-mg po qhs on day 3 For the subjects who did not achieve a remission of panic symptoms the dose will be increased to 20-mg po qhs For the subjects who did not achieve a remission of panic symptoms the dose will be increased to 40-mg po qhs as needed
Arm 3 Treatment with Paroxetine on a fixed dose schedule will be initiated at 10 mg po qhs on day 1 On day 3 it will be increased to 20 mg po qhs On day 7 it will be increased to 30 mg po qhs Most patients respond to an average therapeutic dose of 30 mg of paroxetine This will ensure that a subgroup of subjects will receive optimum therapeutic dose of Paroxetine and also aid to titrate Paroxetine equivalent dose of Risperidone
Patients randomized on any of the above arms and not responding or having side effects will be taken off the study and referred for regular psychiatric treatment
The subjects receiving fixed dose antidepressants or mood stabilizers prior to their enrollment in the study will be continued on these medications throughout the study No dose adjustment of antidepressants or mood stabilizers will be allowed At the end of study participants can choose to continue their study medications under the care of one of study physicians or one of the other psychiatrists at Psychiatric outpatients service for adults Beth Israel Medical Center 16 Street at First Avenue 2 Bernstein Those wishing to stop the study medications at the end of the study will be able to do so under the supervision of one of the study physicians Paroxetine will be tapered over a two-week period to avoid SSRI withdrawal Risperidone will be stopped abruptly since no withdrawal symptoms have been reported in the literature making risperidone taper unnecessary
Assessments to evaluate mood improvement will be performed by a rater blinded to medication status on a daily basis for the first three days and every other day for the first two weeks The assessments please see Appendix 1 for the assessment battery will continue weekly for the rest of the study
All study participants will provided with psychiatric treatment free of charge at our clinic for one month following the end of the study At the end of one-month period we will assist you in finding further psychiatric care Travel expenses will be reimbursed for the subjects participating in the study
Data Analysis
We will calculate Pearson Product Moment correlation coefficients r for each of the treatment outcome variable groups This will enable us to determine the degree of association between treatment and outcome More importantly we can interpret r with the Binomial Effect Size Display BESD Rosenthal 1991 The BESD will enable us to estimate a clinically meaningful improvement rate and to estimate the number of people that would improve as a result of treatment
Power Analysis and Precision Analysis
As stated above our measure of effect size will be the Pearson Product Moment correlation coefficient r For this study we chose an effect size of r 50 as the smallest effect size that would be clinically meaningful and then calculated that we would need a sample size of 26 to obtain power of 81 and a 950 confidence interval r 13 to r 75 that would not include zero Rosenthal 1991
Risperidone is an atypical antipsychotic drug that acts as an antagonist at 5-HT2A2C and D2 receptors Chouignard et al 1993 Marder Meibach 1994 In its serotonergic activity risperidone resembles both the atypical antidepressant and 5HT2-antagonist nefazodone Bakish et al 1993 and a 5HT2-antagonist ritanserine Lima Moncrieff 2000 Preskorn 1995 Nefazodone treats anxiety symptoms and induces less agitation than other reuptake blockers Fawcett et al 1995 while ritanserin shows effectiveness in treatment of dysthymia in clinical trials Moreover risperidone increases release of dopamine and norepinephrine in the prefrontal cortex Zhang et al 2000 an activity that in other pharmacological agents is associated with their antidepressant anxiolytic and antipanic properties Thase 2002
Therefore risperidone has a potential to be effective for treatment of either Generalized Anxiety Disorder or Panic Disorder or Major Depressive Disorder with Panic Attacks DSM-IV 1994 as a single agent Moreover due to its D2 and 5-HT2A2C antagonism and proven antipsychotic efficacy the drug could be uniquely effective for severe panic attacks with psychotic features or para-psychotic features Galynker et al 1996 Consistent with this supposition Marder et al 1997 reported that in patients with schizophrenia risperidone produced significantly greater improvements than haloperidol in PANSS scores measuring anxiety and depression
Our clinical experience with over 50 patients with panic attacks showed that low dose risperidone similar to lorazepam reduced or eliminated anxiety and panic often after the first dose Risperidone was most effective for patients experiencing obsessive intrusive anxiety-inducing thoughts In contrast to lorazepam risperidone treatment did not result in building of tolerance to the drug or disinhibition We did not observe extrapyramidal side effects in patients treated with risperidone for panic attacks Thus our preliminary clinical data indicate that due to its efficacy quick onset of action absence of addictive potential and lack of side effects risperidone could be superior to both benzodiazepines and SSRIs for treatment of panic attacks particularly for severe panic attacks Moreover risperidone has a potential to be the first line drug for treatment of these symptoms
Consequently at present a clinical study of risperidone for treatment of panic attacks is indicated and is of great potential value We are therefore proposing an exploratory open label single-blind trial of risperidone in vs paroxetine for treatment of panic attacks
HypothesisObjectives
Objective One To compare the efficacy of risperidone to that of paroxetine in treatment of panic attacks in patients with Panic Disorder and with Major Depressive Disorder with Panic attacks
Hypothesis One Risperidone and will be more efficacious in treatment of panic symptoms in both patient groups Some patients will improve within 24 hrs
Objective Two To compare the side effect profile of risperidone vs paroxetine in treatment of panic attacks
Hypothesis Two Risperidone compared to paroxetine will cause less sexual side effects anxiety and restlessness There will be no difference in extrapyramidal side effects between the paroxetine and the risperidone groups
Objective Three To compare response rates of risperidone vs paroxetine in treatment of panic attacks
Hypothesis Three Patients with panic attacks will respond significantly faster to risperidone that to paroxetine
Objective Four To examine demographic and clinical predictors of robust response to risperidone treatment using appropriate statistical analysis of individual scales items and treatment response rates
Hypothesis Four The subgroup patients with panic attacks who will have high scores on items reflecting somatic anxiety and ruminative intrusive thinking and those with nocturnal panic attacks will show better response to risperidone therapy than patients with low scores on those items
If study hypotheses are confirmed future research could include a randomized double blind fixed dose study of risperidone as the sole agent for treatment of panic disorder and Phase IV trials aimed to determine the effectiveness of 0125 mg and 00675 mg dose of risperidone for treatment of anxiety and panic attacks
Study Population
The patient population will consist of psychiatric outpatients who meet criteria for the DSM-IV diagnosis of Major Depressive Disorder with Panic Attacks or Panic Disorder The subjects will be recruited from the Center for Treatment of Affective Disorders and from the Anxiety and Trauma Center in the Department of Psychiatry at the Beth Israel Medical center that provide care to 900 patients At present the patient ethnic and racial mix is 50 Hispanic 15 African American 325 Caucasian and 25 Asian The gender distribution is approximately 33 male and 67 female The outpatient payer mix is 20 Medicare 74 Medicaid and 6 combined Of those patients approximately 40 360 manifest panic attacks Based on our previous experience with recruitment for research studies we expect that 10-12 of patients 36-42 meeting diagnostic criteria will also meet the inclusion and exclusion criteria will sign the inform consent and will participate in the study We expect to recruit 40 patients per year and to complete the study in 3 years
Inclusion Criteria
1 Males and females ages 21-55
2 Ability to sign an informed consent
3 Diagnosis of Panic Disorder or MDD with Panic attacks single episode recurrent or chronic
4 HAM-A score 17
Exclusion Criteria
1 Alcohol or substance abuse within the last 6 months
2 Current diagnosis of Obsessive-Compulsive Disorder
3 Current diagnosis of Schizophrenia Schizoaffective Disorder or Bipolar Mood Disorder
4 Use of antipsychotic medications over the two months preceding enrollment in the study
5 Changes in antidepressant or mood stabilizer dosing over the two months preceding enrollment in the study
6 Previous adverse reaction to risperidone or paroxetine
Study Design and Drug Regimens
The study will be an 8-week parallel comparison with a blinded rater of risperidone and paroxetine for treatment of three groups of patients with panic attacks Each group will consist of 30 subjects
After signing an informed consent the subjects will be randomly assigned in the open manner to treatment with risperidone or paroxetine alone
Arm 1 Treatment with risperidone will be flexible-dose and will be initiated at 025 mg po qhs For the subjects who did not achieve a remission of panic symptoms the dose will be increased to 05 mg po qhs on day 3 For subjects who experienced morning sedation the dose will be decreased to 0125-mg po qhs on day 3
Arm 2 Treatment with Paroxetine will be flexible-dose and will be initiated at 10-mg po qhs For subjects who experienced morning sedation the dose will be decreased to 5-mg po qhs on day 3 For the subjects who did not achieve a remission of panic symptoms the dose will be increased to 20-mg po qhs For the subjects who did not achieve a remission of panic symptoms the dose will be increased to 40-mg po qhs as needed
Arm 3 Treatment with Paroxetine on a fixed dose schedule will be initiated at 10 mg po qhs on day 1 On day 3 it will be increased to 20 mg po qhs On day 7 it will be increased to 30 mg po qhs Most patients respond to an average therapeutic dose of 30 mg of paroxetine This will ensure that a subgroup of subjects will receive optimum therapeutic dose of Paroxetine and also aid to titrate Paroxetine equivalent dose of Risperidone
Patients randomized on any of the above arms and not responding or having side effects will be taken off the study and referred for regular psychiatric treatment
The subjects receiving fixed dose antidepressants or mood stabilizers prior to their enrollment in the study will be continued on these medications throughout the study No dose adjustment of antidepressants or mood stabilizers will be allowed At the end of study participants can choose to continue their study medications under the care of one of study physicians or one of the other psychiatrists at Psychiatric outpatients service for adults Beth Israel Medical Center 16 Street at First Avenue 2 Bernstein Those wishing to stop the study medications at the end of the study will be able to do so under the supervision of one of the study physicians Paroxetine will be tapered over a two-week period to avoid SSRI withdrawal Risperidone will be stopped abruptly since no withdrawal symptoms have been reported in the literature making risperidone taper unnecessary
Assessments to evaluate mood improvement will be performed by a rater blinded to medication status on a daily basis for the first three days and every other day for the first two weeks The assessments please see Appendix 1 for the assessment battery will continue weekly for the rest of the study
All study participants will provided with psychiatric treatment free of charge at our clinic for one month following the end of the study At the end of one-month period we will assist you in finding further psychiatric care Travel expenses will be reimbursed for the subjects participating in the study
Data Analysis
We will calculate Pearson Product Moment correlation coefficients r for each of the treatment outcome variable groups This will enable us to determine the degree of association between treatment and outcome More importantly we can interpret r with the Binomial Effect Size Display BESD Rosenthal 1991 The BESD will enable us to estimate a clinically meaningful improvement rate and to estimate the number of people that would improve as a result of treatment
Power Analysis and Precision Analysis
As stated above our measure of effect size will be the Pearson Product Moment correlation coefficient r For this study we chose an effect size of r 50 as the smallest effect size that would be clinically meaningful and then calculated that we would need a sample size of 26 to obtain power of 81 and a 950 confidence interval r 13 to r 75 that would not include zero Rosenthal 1991
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None