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Biphasic effects of metergoline in fluoxetine-treated OCD patients
738
BIOLPSYCHIATRY 1994;35:615-747
SATURDA]~, MAY 21
tional cardiac responsiveness in PD patients that has not been observed in laboratory studies.
444. PANIC DISORDER: GROWTH HORMONE AND IGF RESPONSES TO EXERCISE
with successful outcome in fourteen previous cases.
446. BIPHASIC EFFECTS OF METERGOLINE IN FLUOXETINE-TREATED OCD PATIENTS B.D. Greenberg, J. Benjamin, & D.L.
Murphy
K.M. Gadde & T.W. Uhde National Institute of Mental Health, Bethesda, MD 20892 Patients with panic disorder have been reported to show attenuated growth hormone (GH) responses to clonidiue, growth hormone-releasing hormone (GHRH), caffeine, glucose, and yohimbine. Since insulin.like growth factors (IGFs), IGF-I in particular, play an important role in the regulation of GH, we measured OH, IGF-I and IGF-ll responses to exercise in an effort to examine the GH-IGF axis in patients with panic disorder (PD). Patients with a DSM-IlIR diagnosis of panic disorder (n-I 3) and normal controls (NCs) (n-18)exercised on a treadmill until exhans. tion. There was a significantly positive conelation between peak changes in GH levels and duration of exercise for all subjects (r-0.74). Because the duration of exercise was significantly less in PD patients compared with NCs, an analysis of covariance (ANCOVA) with repeated measures was performed to evaluate GH responses to exercise. ANCOVA of absolute values, with exercise duration as the covariate, indicated that PD patients tended to have higher GH responses compared with NCs (p<0.08). There were no differences in mean baseline levels of IGF.! and IGF-I! in the PD patients compared with NCs. IGF-I levels increased significantly24 hours post-exercise for all subjects; however, there was no significant difference in the degree of increase between the patients and NC subjects. There was no significant increase in the serum IGF-ll levels 24 hours postexercise in either group. There was no significant correlation between peak GH change with exercise and change in IGF-! 24 hours post-exercise. The results suggest a probably relatively preserved GH-IGF axis in patients with panic disorder. The results also suggest that the somatostatin-GH axis, which seems to mediate exercise-augmented GH release under the probable control of the cholinergic neurons, may be hypersensitive in patients with panic disorder.
Section on Clinical Neuropharmacology, Laboratory of Clinical Science, NIMH, NIH, Bethesda, MD 20892
While the effectiveness of serotonin (5-HT) transport inhibitors in obsessive-compulsive disorder (OCD) is well established, their mechanism of therapeutic action, thought to involve adaptive changes in $-HT neurotransmission, remains unclear, in a prior study, OCD patients who had improved on clomipramine were given the mixed $-HTva antagonist metergoline (4 mg p.o.May x 4 days) or placebo in a crossover design. Patients had more OCD symptoms and anxiety after metergoline (Benkelfat et al. 1989). We extended this work by administering a range of single metergnline doses (4-12 tag p.o.) to DSM-m-R diagnosed OCD patients who had stable imwovement on fluoxetine (40-80 mr/d). Symptoms were rated every 30 minutes for 4 hours and then daily for ! week. Four of 6 patients had initial improvement in OCD symptoms lasting hours to days after the single metergoline dose. Clinically significant to severe worsening of OCD symptoms and anxiety from days 2 to 5 after metergoline was seen in the same proportion of patients in this pilot study, in an ongoing plncebo-controlled study of metergoline (8 mg p.o.) in similar patients, 5 of $ displayed initial improvement, and 3 of these developed subsequent worsening.
447. ON THE POSSIBILITIES OF NONMEDICAMENTOUS TREATMENT OF ANXIETY DISORDERS
R. Suija 445. OBSESSIVE-COMPULSIVE AND BIPOLAR DISORDER: PRELIMINARY OUTCOME DATA D.R. McKay, J.A. Yaryura-Tobias, & F.A.
Neziroglu
Institute for Bio-Behaviorai Therapy and Research Obsessive compulsive disorder (OCD) has been observed with comorbid conditions such as depression, panic disorder, substance abuse, and eating disorders. Bipolar conditions have been less fTequentlyobserved. The present data present a case of OCD with bipolar.mania. The patient was fifty yeara old, with a lifelong history of OCD. He was txe.atedwith clomipramine for OCD, and lithium for the bipolar condition. Additionally, he was treated with behavior therapy (specifically, exposure with response pre. venti~t) for OCD. Weekly assessments with the Yale-Brown Obsessive Compulsive Scale indicated significant improventents (time series autocorrelation=0.785). Biweekly assessment with the Beck Depression inventory indicated significantalleviation of mood dysfunction (time series autocorrelation=0.647). Sleep disturbance was improved, and the patient regained normal sleep patt~.'ms.Treatment gains were maintained at eighteen month follow-up, with no significant medication modifications. This case study represents the only systematic single case data available for comorbid OCD and bipolar. It suggests that a combined approach to treatmerit for these conditions is possible, when pre~nted together. Although no controlled outcome data are available, this combination was applied
Psychiatry Clinic of University of Tartu, Tartu, Estonia Patients suffering from a variety of neurotic disorders, anxiety, panic attacks and fear often turn to both general practitioners and specialists in different fields, in particular cardiologists. The reason for this is heart complaints which occur rather often. In the 141 patients studied at the Psychiatry Clinic of the University of Tartu we could find the following complaints: pain in heart region - 89%, episodes of tachycardia (heart rate over 100 per rain) with different duration, extrasystolic arrhythmias 75%, periodical rise of systolic (>!65 nun Hg ) and diastolic (>95 nun Hg ) blood pressure - 73%, syndrome of hyperventilation - 66%. Of the general complaints, emotional lability was observed in 92%, remarkable asthenization with sleep disorders in 72%, sweating combined with some other signs of lability of the autonomous nervous system in 66% of the patients. Treatment with drugs is not always effective enough, especially in fighting neurotic disorders and dysfunction of the autonomous nervous system. Some methods of physical therapy are very effective here (ther. motherapy, sauna therapy, mineral water baths, manual massage, remedial gymnastics), which have a nonspecific influence on an organism, mobilizing its compensatory reactions. The physical therapy included sauna therapy and various methods of electrotherapy. As a result of the therapy, we observed the disappearance of pains in the cardiac region and abatement of tnchycardia and extra systoles; also, arterial blood pressure as well as rate of breathing were normalized. After sauna procedures (10 rain in 9 steam with temperature 70 C, relative moisture 30-40%), the spirits of 93% of those in the study showed a rise; sleep disorders improved 8 ! %
BIOLPSYCHIATRY 1994;35:615-747
SATURDA]~, MAY 21
tional cardiac responsiveness in PD patients that has not been observed in laboratory studies.
444. PANIC DISORDER: GROWTH HORMONE AND IGF RESPONSES TO EXERCISE
with successful outcome in fourteen previous cases.
446. BIPHASIC EFFECTS OF METERGOLINE IN FLUOXETINE-TREATED OCD PATIENTS B.D. Greenberg, J. Benjamin, & D.L.
Murphy
K.M. Gadde & T.W. Uhde National Institute of Mental Health, Bethesda, MD 20892 Patients with panic disorder have been reported to show attenuated growth hormone (GH) responses to clonidiue, growth hormone-releasing hormone (GHRH), caffeine, glucose, and yohimbine. Since insulin.like growth factors (IGFs), IGF-I in particular, play an important role in the regulation of GH, we measured OH, IGF-I and IGF-ll responses to exercise in an effort to examine the GH-IGF axis in patients with panic disorder (PD). Patients with a DSM-IlIR diagnosis of panic disorder (n-I 3) and normal controls (NCs) (n-18)exercised on a treadmill until exhans. tion. There was a significantly positive conelation between peak changes in GH levels and duration of exercise for all subjects (r-0.74). Because the duration of exercise was significantly less in PD patients compared with NCs, an analysis of covariance (ANCOVA) with repeated measures was performed to evaluate GH responses to exercise. ANCOVA of absolute values, with exercise duration as the covariate, indicated that PD patients tended to have higher GH responses compared with NCs (p<0.08). There were no differences in mean baseline levels of IGF.! and IGF-I! in the PD patients compared with NCs. IGF-I levels increased significantly24 hours post-exercise for all subjects; however, there was no significant difference in the degree of increase between the patients and NC subjects. There was no significant increase in the serum IGF-ll levels 24 hours postexercise in either group. There was no significant correlation between peak GH change with exercise and change in IGF-! 24 hours post-exercise. The results suggest a probably relatively preserved GH-IGF axis in patients with panic disorder. The results also suggest that the somatostatin-GH axis, which seems to mediate exercise-augmented GH release under the probable control of the cholinergic neurons, may be hypersensitive in patients with panic disorder.
Section on Clinical Neuropharmacology, Laboratory of Clinical Science, NIMH, NIH, Bethesda, MD 20892
While the effectiveness of serotonin (5-HT) transport inhibitors in obsessive-compulsive disorder (OCD) is well established, their mechanism of therapeutic action, thought to involve adaptive changes in $-HT neurotransmission, remains unclear, in a prior study, OCD patients who had improved on clomipramine were given the mixed $-HTva antagonist metergoline (4 mg p.o.May x 4 days) or placebo in a crossover design. Patients had more OCD symptoms and anxiety after metergoline (Benkelfat et al. 1989). We extended this work by administering a range of single metergnline doses (4-12 tag p.o.) to DSM-m-R diagnosed OCD patients who had stable imwovement on fluoxetine (40-80 mr/d). Symptoms were rated every 30 minutes for 4 hours and then daily for ! week. Four of 6 patients had initial improvement in OCD symptoms lasting hours to days after the single metergoline dose. Clinically significant to severe worsening of OCD symptoms and anxiety from days 2 to 5 after metergoline was seen in the same proportion of patients in this pilot study, in an ongoing plncebo-controlled study of metergoline (8 mg p.o.) in similar patients, 5 of $ displayed initial improvement, and 3 of these developed subsequent worsening.
447. ON THE POSSIBILITIES OF NONMEDICAMENTOUS TREATMENT OF ANXIETY DISORDERS
R. Suija 445. OBSESSIVE-COMPULSIVE AND BIPOLAR DISORDER: PRELIMINARY OUTCOME DATA D.R. McKay, J.A. Yaryura-Tobias, & F.A.
Neziroglu
Institute for Bio-Behaviorai Therapy and Research Obsessive compulsive disorder (OCD) has been observed with comorbid conditions such as depression, panic disorder, substance abuse, and eating disorders. Bipolar conditions have been less fTequentlyobserved. The present data present a case of OCD with bipolar.mania. The patient was fifty yeara old, with a lifelong history of OCD. He was txe.atedwith clomipramine for OCD, and lithium for the bipolar condition. Additionally, he was treated with behavior therapy (specifically, exposure with response pre. venti~t) for OCD. Weekly assessments with the Yale-Brown Obsessive Compulsive Scale indicated significant improventents (time series autocorrelation=0.785). Biweekly assessment with the Beck Depression inventory indicated significantalleviation of mood dysfunction (time series autocorrelation=0.647). Sleep disturbance was improved, and the patient regained normal sleep patt~.'ms.Treatment gains were maintained at eighteen month follow-up, with no significant medication modifications. This case study represents the only systematic single case data available for comorbid OCD and bipolar. It suggests that a combined approach to treatmerit for these conditions is possible, when pre~nted together. Although no controlled outcome data are available, this combination was applied
Psychiatry Clinic of University of Tartu, Tartu, Estonia Patients suffering from a variety of neurotic disorders, anxiety, panic attacks and fear often turn to both general practitioners and specialists in different fields, in particular cardiologists. The reason for this is heart complaints which occur rather often. In the 141 patients studied at the Psychiatry Clinic of the University of Tartu we could find the following complaints: pain in heart region - 89%, episodes of tachycardia (heart rate over 100 per rain) with different duration, extrasystolic arrhythmias 75%, periodical rise of systolic (>!65 nun Hg ) and diastolic (>95 nun Hg ) blood pressure - 73%, syndrome of hyperventilation - 66%. Of the general complaints, emotional lability was observed in 92%, remarkable asthenization with sleep disorders in 72%, sweating combined with some other signs of lability of the autonomous nervous system in 66% of the patients. Treatment with drugs is not always effective enough, especially in fighting neurotic disorders and dysfunction of the autonomous nervous system. Some methods of physical therapy are very effective here (ther. motherapy, sauna therapy, mineral water baths, manual massage, remedial gymnastics), which have a nonspecific influence on an organism, mobilizing its compensatory reactions. The physical therapy included sauna therapy and various methods of electrotherapy. As a result of the therapy, we observed the disappearance of pains in the cardiac region and abatement of tnchycardia and extra systoles; also, arterial blood pressure as well as rate of breathing were normalized. After sauna procedures (10 rain in 9 steam with temperature 70 C, relative moisture 30-40%), the spirits of 93% of those in the study showed a rise; sleep disorders improved 8 ! %