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Tryptophan depletion and 35% CO2 challenge in panic patients: Preliminary results
Panic and anxiety disorders
SIOL PSYCHIATRY 1997;42:15-2975
111-21 Long-term course of panic disorder-agoraphobia G. PeNgI, A. Benedetti, B. Simonetti, M. Simoneinl, C. Tilll, A. BartJanera, C. TonI. Institute of Psychiatry, University of Piss, Piss, Italy This study has been conducted In order to collect Informatlon about the evolution of Panic Disorder/Agoraphobia (PDA) In relation to the treatment employed; clinical characteristlcs eventually predictive of outcome were also explored. 184 PDA patients naturalistically treated have been observed In a prospective follow-up started in 1991 and still ongoing at the Psychiatric InstiMe, University of Pisa. At baseline patients were evaluated by means of the Structured Clinical In• terview for Diagnosis (SCID), the Panic Disorder/Agoraphobia Questionnaire (pDQ), Longitudinal Interview Follow up Examination (LIIe-up). Successively, Ufe-up was administered every 4 months. After the baseline assessment, patients were assigned to Imipramine, clomipramine or SSRI treatment on the basis of the clinical judgement Our results confirm previous observations that PDA tend to assume a chronic course. In fact, we found both high rates of remissions (percentage of survivals 18.6%) and of relapses (percentage of survivals 41.3%) for panic attacks. Agoraphobia shows fewer number of relapses (percentage of survivals 69%), confirming the report of a constant and progressive Improvement of avoidant behavior. Demographic, clinical and comorbidlty characteristics do not seem to influence the course of PDA in our sample. We did not find any significant difference as far as the treatment was concemed, but we observed that the patients who were administered SSRI had higher rates of remissions. The observation of the chronicity of PDA suggests the need of a long·term maintenance therapy.
111-31 with selective neuropsychological dysfunction In patients panic disorder-agoraphobia C. Toni, S. Cappa', M. Boldrinl, F. Frare, S. Pedr!, P. Medds, G. Perugl. Institute of psychiatry, University of Piss, Piss, Italy. , Institute of Neurology. University of Brescia, Brescia, Italy The aim of the present investigation was to explore the brain: behaviour relationship in a selected sample of unmedieated patients with PO, using a battery of neuropsychological tests. 19 patients and 16 healthy controls were evaluated by means of: 1. Raven Coloured Progressive Matrices (RCPM); 2. Digit Span: 3. Corsi block span; 4. Benton Facial Recognition Test; 5. Copy and recall of the Rey-Dsterreith complex figure; 6. Bushke-Fuld selective reminding test; 7. Corsi supra span leaming task; 8. Controlled associations; 9. The Wisconsin Card Sorting Test (WCSn. Present anxiety level was evaluated by means of the State Trait Anxiety Inventory (STAI). Clinical features of PO were evaluated by means of the Panic Disorder-Agoraphobia Questionnaire (PeNgi et al., 1992). Patients scored significantly lower than controls on both the Copy and the Recall subtest of the Rey-Osterreith Complex Figure. Moreover, they did evidence impaired performance with Controlled Associations and trends approaching significance were found for both measures of the Wisconsin Card Sorting test (category number and perseverative errors). At the moment of the evaluation, anxiety levels were higher in patients than in controls. Our finding confirms previous reports of impaired visuo-spatial abilities in PO and indicates a pattem of neuropsychological dyslunctlon suggestive of an Involvement of the right frontal and tempore-parietal areas.
111-41 toHeart rate and MHPG as predictors of nonresponse drug therapy In panic disorder Vliet 2 ,
B.A. Slaap 1, I.M. van H.G.M. Westenberg 2, J.A. den Boer'. , Groningen graduate school for behavioural and cognitive neurosciences, Department of Psychiatry, Academic Hospital, Groningen, the Netherlands, 2Department of Psychiatry, Academic Hospital Utrecht, the Netherlands The aim of this study was to Investigate whether heart rate, blood pressure, plasma cortisol and plasma MHPG could predict nonresponse to drug therapy In Panic Disorder (PO). Methods: For the present study the data of two previously pUblished, double blind studies were pooled. The 44 PO patients, who were treated lor 12 weeks with brofaromine or f1uvoxamlne, were the subject of this study. A striet definition of nonresponse was used to find patlents who did not respond at all. The variables that differed significantly between the groups were used to predict nonresponse to drug therapy. Results: Using this definition of nonresponse 15 patients (32.6%) were considered nonresponders. These patients were characterized by a higher
17S
plasma MHPG concentration and a higher heart rate. Both variables could predict nonresponse. Conclusions: A higher heart rate and a higher plasma MHPG c0ncen• tration were both predictors of nonresponse to dNg therapy In PD. Further research Is needed to substantiate these findings.
111-51 Floxetlne Panic disorder. A long term treatment study: vs Imipramine K. Magnani, M. Amore. Institute of Psychiatry "P. Ottonello· University of Bologna V. Ie Pepoll rf 5 4() 123, Italy The Authors report a double-blind trial that compares efficacy of f1uoxetine vs Imipramine In the treatment of patients with panic disorder with or without agoraphobia. Methods: Thirty patients with moderate to severe panic disorder were randomly assigned to receive 12 months of f1uoxetine or imipramine. Fifteen patients were assigned to fluoxetine treatment and fifteen patients were assigned to imipramine treatment. Only patients admitted for Panic Disorder, diagnosed according to DSM·IV criteria, entered the study. A starting dose of 10 mg of f1uoxetine was raised In 1o-mg Increments weekly to a maximum of 40 mglday on the basis of clinical improvement and side effects. A starting dose of 10 mg of imipramine was Increased at a rate of 10 mg every 1-2 days so that the patient reached 50 mglday by the end of the first week. Afterwards imipramine was raised in 25 mg increments every 2-4 days up to 2~ mglday on the basis of cllnlcallmprovernent and side effects. All subject were first administered the PASS, SCRAS, HAM-D, CGI and a side effects scales. All of these forms were repeated weekly for the first 6 weeks of the study and then every other week for an additional 10 months. Results: Both treatments tumed out to be eqUally effective and resulted In a significant reduction of panic attacks and agoraphobic avoidance level. Therapeutic action were observed during the third week of treatment and Ieasted for the entire period of observation.
111-61 Tryptophan depletion and 35% C02 challenge In panic patients: Preliminary results K. SchNers, H. Pols, T. Klaassen, H. BOchold, E.J.L Griez. University of Maastricht, Maastricht TIle Netherlands 5erotonerglc mechanisms, as Investigated with the tryptophan depletion method (Young, '85), are suggested to be Important in panic disorder (Goddard, '94). The 35% Carbon dioxide (C~) challenge is a well studied challenge method for panic disorder (Griez, '87). By combining the tryptophan depletion method with the 35% C02 challenge we intended to Investigate a possible common mechanism of action. Methods: 14 Patients meeting DSM·IV criteria for panic disorder with or without agoraphobia, were randomly allocated to a tryptophan depletlon condition or ingestion of a balanced amino acid mixture. Five hours following this mixture, patients underwent a 35% C~ challenge. Outcome measures of the challenge were the visual analogue scale of anxiety (VAAS) and the panic symptom list (PSL-IV). Resulla: Statisticany significant differences between the two separate groups were found. Conclusion: Carbondioxide sensitlvity In panic disorder may be associ· ated with deficient serotonin neurotransmission.
111-71 the A quantitative C·f1umazenll e-flu) PET study of central benzodlazeplne receptors (cBZr) In 11
(11
anxiety disorders (AD) P. Abadie, J.P. Boulenger, K. Benali, L Barre, E. zarifian, J.C. Baron. INSERM U 320, centre Cyceron, CEA, Centre Esqulrol, CHU, Csen,
France
The cBZr have been implicated In MJ on the basis of: I) the sensitivity to benzodiazepine (BZ) In AD; Ii) results of pharmacological challenges in AD, suggesting an endogenous ligand and/or a GABA shift. There Is no report of the cBZr density (Bmax) and affinity (Kd) status in AD. We aimed to I) estimate cBZr Bmax and Kd values in unmedicated MJ patlents; and ii) look for correlations between cBZr parameters and State or Trait Anxiety Inventors, (STAI Spielberger) scores. Methods: 1) Ten patients (sex ratio 1:1; mean age: 39 yrs), unmedicated with BZ were prospectively recNited based on DSM III·R criteria; 2) Ten age· and gender-matched healthy unmedicated volunteers; 3) we used the
SIOL PSYCHIATRY 1997;42:15-2975
111-21 Long-term course of panic disorder-agoraphobia G. PeNgI, A. Benedetti, B. Simonetti, M. Simoneinl, C. Tilll, A. BartJanera, C. TonI. Institute of Psychiatry, University of Piss, Piss, Italy This study has been conducted In order to collect Informatlon about the evolution of Panic Disorder/Agoraphobia (PDA) In relation to the treatment employed; clinical characteristlcs eventually predictive of outcome were also explored. 184 PDA patients naturalistically treated have been observed In a prospective follow-up started in 1991 and still ongoing at the Psychiatric InstiMe, University of Pisa. At baseline patients were evaluated by means of the Structured Clinical In• terview for Diagnosis (SCID), the Panic Disorder/Agoraphobia Questionnaire (pDQ), Longitudinal Interview Follow up Examination (LIIe-up). Successively, Ufe-up was administered every 4 months. After the baseline assessment, patients were assigned to Imipramine, clomipramine or SSRI treatment on the basis of the clinical judgement Our results confirm previous observations that PDA tend to assume a chronic course. In fact, we found both high rates of remissions (percentage of survivals 18.6%) and of relapses (percentage of survivals 41.3%) for panic attacks. Agoraphobia shows fewer number of relapses (percentage of survivals 69%), confirming the report of a constant and progressive Improvement of avoidant behavior. Demographic, clinical and comorbidlty characteristics do not seem to influence the course of PDA in our sample. We did not find any significant difference as far as the treatment was concemed, but we observed that the patients who were administered SSRI had higher rates of remissions. The observation of the chronicity of PDA suggests the need of a long·term maintenance therapy.
111-31 with selective neuropsychological dysfunction In patients panic disorder-agoraphobia C. Toni, S. Cappa', M. Boldrinl, F. Frare, S. Pedr!, P. Medds, G. Perugl. Institute of psychiatry, University of Piss, Piss, Italy. , Institute of Neurology. University of Brescia, Brescia, Italy The aim of the present investigation was to explore the brain: behaviour relationship in a selected sample of unmedieated patients with PO, using a battery of neuropsychological tests. 19 patients and 16 healthy controls were evaluated by means of: 1. Raven Coloured Progressive Matrices (RCPM); 2. Digit Span: 3. Corsi block span; 4. Benton Facial Recognition Test; 5. Copy and recall of the Rey-Dsterreith complex figure; 6. Bushke-Fuld selective reminding test; 7. Corsi supra span leaming task; 8. Controlled associations; 9. The Wisconsin Card Sorting Test (WCSn. Present anxiety level was evaluated by means of the State Trait Anxiety Inventory (STAI). Clinical features of PO were evaluated by means of the Panic Disorder-Agoraphobia Questionnaire (PeNgi et al., 1992). Patients scored significantly lower than controls on both the Copy and the Recall subtest of the Rey-Osterreith Complex Figure. Moreover, they did evidence impaired performance with Controlled Associations and trends approaching significance were found for both measures of the Wisconsin Card Sorting test (category number and perseverative errors). At the moment of the evaluation, anxiety levels were higher in patients than in controls. Our finding confirms previous reports of impaired visuo-spatial abilities in PO and indicates a pattem of neuropsychological dyslunctlon suggestive of an Involvement of the right frontal and tempore-parietal areas.
111-41 toHeart rate and MHPG as predictors of nonresponse drug therapy In panic disorder Vliet 2 ,
B.A. Slaap 1, I.M. van H.G.M. Westenberg 2, J.A. den Boer'. , Groningen graduate school for behavioural and cognitive neurosciences, Department of Psychiatry, Academic Hospital, Groningen, the Netherlands, 2Department of Psychiatry, Academic Hospital Utrecht, the Netherlands The aim of this study was to Investigate whether heart rate, blood pressure, plasma cortisol and plasma MHPG could predict nonresponse to drug therapy In Panic Disorder (PO). Methods: For the present study the data of two previously pUblished, double blind studies were pooled. The 44 PO patients, who were treated lor 12 weeks with brofaromine or f1uvoxamlne, were the subject of this study. A striet definition of nonresponse was used to find patlents who did not respond at all. The variables that differed significantly between the groups were used to predict nonresponse to drug therapy. Results: Using this definition of nonresponse 15 patients (32.6%) were considered nonresponders. These patients were characterized by a higher
17S
plasma MHPG concentration and a higher heart rate. Both variables could predict nonresponse. Conclusions: A higher heart rate and a higher plasma MHPG c0ncen• tration were both predictors of nonresponse to dNg therapy In PD. Further research Is needed to substantiate these findings.
111-51 Floxetlne Panic disorder. A long term treatment study: vs Imipramine K. Magnani, M. Amore. Institute of Psychiatry "P. Ottonello· University of Bologna V. Ie Pepoll rf 5 4() 123, Italy The Authors report a double-blind trial that compares efficacy of f1uoxetine vs Imipramine In the treatment of patients with panic disorder with or without agoraphobia. Methods: Thirty patients with moderate to severe panic disorder were randomly assigned to receive 12 months of f1uoxetine or imipramine. Fifteen patients were assigned to fluoxetine treatment and fifteen patients were assigned to imipramine treatment. Only patients admitted for Panic Disorder, diagnosed according to DSM·IV criteria, entered the study. A starting dose of 10 mg of f1uoxetine was raised In 1o-mg Increments weekly to a maximum of 40 mglday on the basis of clinical improvement and side effects. A starting dose of 10 mg of imipramine was Increased at a rate of 10 mg every 1-2 days so that the patient reached 50 mglday by the end of the first week. Afterwards imipramine was raised in 25 mg increments every 2-4 days up to 2~ mglday on the basis of cllnlcallmprovernent and side effects. All subject were first administered the PASS, SCRAS, HAM-D, CGI and a side effects scales. All of these forms were repeated weekly for the first 6 weeks of the study and then every other week for an additional 10 months. Results: Both treatments tumed out to be eqUally effective and resulted In a significant reduction of panic attacks and agoraphobic avoidance level. Therapeutic action were observed during the third week of treatment and Ieasted for the entire period of observation.
111-61 Tryptophan depletion and 35% C02 challenge In panic patients: Preliminary results K. SchNers, H. Pols, T. Klaassen, H. BOchold, E.J.L Griez. University of Maastricht, Maastricht TIle Netherlands 5erotonerglc mechanisms, as Investigated with the tryptophan depletion method (Young, '85), are suggested to be Important in panic disorder (Goddard, '94). The 35% Carbon dioxide (C~) challenge is a well studied challenge method for panic disorder (Griez, '87). By combining the tryptophan depletion method with the 35% C02 challenge we intended to Investigate a possible common mechanism of action. Methods: 14 Patients meeting DSM·IV criteria for panic disorder with or without agoraphobia, were randomly allocated to a tryptophan depletlon condition or ingestion of a balanced amino acid mixture. Five hours following this mixture, patients underwent a 35% C~ challenge. Outcome measures of the challenge were the visual analogue scale of anxiety (VAAS) and the panic symptom list (PSL-IV). Resulla: Statisticany significant differences between the two separate groups were found. Conclusion: Carbondioxide sensitlvity In panic disorder may be associ· ated with deficient serotonin neurotransmission.
111-71 the A quantitative C·f1umazenll e-flu) PET study of central benzodlazeplne receptors (cBZr) In 11
(11
anxiety disorders (AD) P. Abadie, J.P. Boulenger, K. Benali, L Barre, E. zarifian, J.C. Baron. INSERM U 320, centre Cyceron, CEA, Centre Esqulrol, CHU, Csen,
France
The cBZr have been implicated In MJ on the basis of: I) the sensitivity to benzodiazepine (BZ) In AD; Ii) results of pharmacological challenges in AD, suggesting an endogenous ligand and/or a GABA shift. There Is no report of the cBZr density (Bmax) and affinity (Kd) status in AD. We aimed to I) estimate cBZr Bmax and Kd values in unmedicated MJ patlents; and ii) look for correlations between cBZr parameters and State or Trait Anxiety Inventors, (STAI Spielberger) scores. Methods: 1) Ten patients (sex ratio 1:1; mean age: 39 yrs), unmedicated with BZ were prospectively recNited based on DSM III·R criteria; 2) Ten age· and gender-matched healthy unmedicated volunteers; 3) we used the