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Oral morphine in treatment resistant obsessive-compulsive disorder (OCD)
i?3. Anxiety disorders and anxiolytics anxiolytic effects. To test our hypothesis that ANH displays an anxiolytic action also in man, we used cholecystokinin tetrapeptide (CCK-4) as an experimental panicogen (that also activates HPA axis) and administered ANH as a pretreatment. Methods: A double-blind placebo-controlled study was conducted in nine patients with panic disorder (DSM-III-R) and in nine healthy matched control subjects. Participants were pretreated with a 30-minute intravenous infusion of 150 yg ANH or placebo (in random order on different study days) and they were subsequently given 50 ug CCK-4 as a bolus injection. Anxiety was assessed using the Acute Panic Inventory and a checklist for DSM-III-R panic items. Adenocorticotropic Hormone (ACTH) was measured in plasma using a radioimmunoassay. Results: Pretreatment with ANH decreased the number of induced panic attacks from 8 to 6 in patients and from 5 to 2 in controls. After ANH pretreatment, Acute Panic Inventory ratings after CCK-4 were significantly lowered compared to placebo pretreatment in patients (24.2 f 3.4 vs. 30.1 f 3.7), but not in controls (14.2 f 2.7 vs. 15.4 f 2.7). The release of ACTH after CCK-4 was significantly reduced in both patients and controls by ANH vs. placebo pretreatment. Conclusion: ANH has anxiolytic effects on CCK4-induced panic in patients and reduces the concomittant HPA axis activation. Given lowered basal ANH levels in panic patients and a release of ANH during provoked panic (Kellner et al., 1995) this peptide might be the endogenous behavioural feedback signal for the termination of such anxiety paroxysms. Long-acting ANH analogues should be tested for their potential therapeutic effects on spontaneous panic attacks in patients with panic disorder. References [l] Kellner, M., Herzog, L., Yassouridis, A., Holsboer, F., 1995. Possible role of atria1 natriuretic hormone in pituitary-adrenocortical umesponsiveness in lactate-induced panic. American Journal of Psychiatry 152, 1365-1367. [2] Kellner, M., Wiedemann, K., Holsboer, F., 1992. Atria1 natriurctic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man. Life Sciences 50, 1835-1842. [3] Kellner, M., Wiedemann, K., 1998. Nonresponse of adrenocorticotropic hormone in first-ever lactate-induced attacks in healthy volunteers. Archives of General Psychiatry 55, 85-86.
Ip.3.002)
Oral morphine in treatment resistant obsessive-compulsive disorder (OCD)
S299
beruodiazepineor alcohol abuse, or a medical condition in which narcotics were contraindicated. Patients were randomized to double-blind, two-week, blocks of morphine sulfate starting at 30 mg, lorazepam starting at 1 mg, or placebo in a random block, crossover design. The medication was administered in the clinic. One week after the first administration of each drug, a Y-BOCS rating was done, side effects were assessed, and a decision made to increase, decrease, or maintain the medication dosage for week tSV0.
Results: We report results for the first eight patients, seven men and one woman, mean age (&SD) = 40.0 (*9.1) years. The mean (&SD) baseline Y-BOCS score was 28.3 (f5.9). The mean YBOCS score after the highest morphine dose (mean = 37.5 f 8.0 mg) was 2 1.O (f6. l), and the mean decrease was 26.2% (fl4.5%). Three patients had a 240% decrease in Y-BOCS score and one a 29% decrease. No patient’s Y-BOCS score increased. Several patients had mild, transient drowsiness. In contrast, the mean Y-BOCS score after the highest lorazepam dose (mean = 1.6 * 0.5 mg), was 24.8 (&5.3), and the mean score decrease was 11.3% (5 14.4%). One patient’s Y-BOCS score decreased by 27% and one by 29%; two patients had a small increase in YBOCS scores. In the placebo condition, the mean Y-BOCS score after the highest dose was 25.3 (~t4.9), and the mean decrease was 10.1% (f 11.4%). No placebo patient achieved a Y-BOCS decrease of 225%; one patient’s score increased (12%). The percent decrease in Y-BOCS score following double-blind morphine was statistically significant compared to placebo (Student’s t test, p = 0.006); the percent decrease following lorazepam was not (Student’s t test, p = 0.71). All four morphine responders have continued over periods of 4 to 6 months to experience modest to marked reduction in OCD symptoms with stable, once to twice weekly, oral morphine doses added to their treatment regimens, without experiencing tolerance, euphoria or drug seeking. Conclusion: A stable, once-weekly dose of oral morphine is well tolerated and can substantially ameliorate OCD symptoms in some treatment-resistant patients. Further research is indicated. References [I ] Warneke L., 1997. A possible new treatment approach to obsessive-
compulsive disorder. Can J Psychiatry 42, 667-668. [2] Shapira, N.A., Keck, PE., Jr., Goldsmith T.D., McConville, B.J., Eis, M., McElroy, S.L., 1997. An open-label pilot study of tramadol .-‘+ hydrochloride in treatment-refractory obsessive-compulsive disorder. Depress Anxiety 6, 170-I 73.
L.M. Koran, B. Franz, K.D. Bullock, M.A. Elliot. Stanford University Medical Center; Department of Psychiatry and Behavioml Sciences, Stanford, CA, USA Background: About 3040% of OCD patients experience little improvement despite adequate trials of multiple medications. Case series and open-label trials in treatment resistant OCD patients report a response to oral morphine (Warneke, 1997) and tramadol (Shapira et al., 1997), a mu-opioid receptor mixed agonist/antagonist with modest serotonin and norepinephrine reuptake activity. We are conducting a placebo-controlled, double-blind trial to test the hypothesis that once-weekly oral morphine is effective in treatment-resistant OCD. Method: We recruited patients from our OCD Clinic who had OCD for >3 years, had failed adequate trials of at least two serotonin reuptake inhibitors, and had a Yale-Brown ObsessiveCompulsive Scale (Y-BOCS) score > 21. Patients continued current medications, but these had to be stable for two months before starting the trial. Exclusion criteria were a history of narcotic-,
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No rCBF differences between pentagastrininduced panic and spontaneous panic attacks in panic disorder patients
M.L. Boshuisen, G.J. Ter Horst, J.A. Den Boer. Groningen University Hospital, Department of Psychiatry, Groningen, The Netherlands We studied differences in regional cerebral blood flow (rCBF) between pentagastrin-induced panic attacks and spontaneous panic attacks by means of PET scan in panic disorder (PD) patients. Seventeen drug-free PD patients were scanned to study the rCBF in rest and during a pentagastrin-induced panic attack. Pentagastrin is an accepted panic provocation method in PD patients (Bradwejn et al., 1993; van Megen et al., 1994). It induces a panic attack in about 60% of the patients. It is easily administered aa an intravenous bolus injection, the induction of panic is very fast (within 10 seconds) and disappears within 2
Ip.3.002)
Oral morphine in treatment resistant obsessive-compulsive disorder (OCD)
S299
beruodiazepineor alcohol abuse, or a medical condition in which narcotics were contraindicated. Patients were randomized to double-blind, two-week, blocks of morphine sulfate starting at 30 mg, lorazepam starting at 1 mg, or placebo in a random block, crossover design. The medication was administered in the clinic. One week after the first administration of each drug, a Y-BOCS rating was done, side effects were assessed, and a decision made to increase, decrease, or maintain the medication dosage for week tSV0.
Results: We report results for the first eight patients, seven men and one woman, mean age (&SD) = 40.0 (*9.1) years. The mean (&SD) baseline Y-BOCS score was 28.3 (f5.9). The mean YBOCS score after the highest morphine dose (mean = 37.5 f 8.0 mg) was 2 1.O (f6. l), and the mean decrease was 26.2% (fl4.5%). Three patients had a 240% decrease in Y-BOCS score and one a 29% decrease. No patient’s Y-BOCS score increased. Several patients had mild, transient drowsiness. In contrast, the mean Y-BOCS score after the highest lorazepam dose (mean = 1.6 * 0.5 mg), was 24.8 (&5.3), and the mean score decrease was 11.3% (5 14.4%). One patient’s Y-BOCS score decreased by 27% and one by 29%; two patients had a small increase in YBOCS scores. In the placebo condition, the mean Y-BOCS score after the highest dose was 25.3 (~t4.9), and the mean decrease was 10.1% (f 11.4%). No placebo patient achieved a Y-BOCS decrease of 225%; one patient’s score increased (12%). The percent decrease in Y-BOCS score following double-blind morphine was statistically significant compared to placebo (Student’s t test, p = 0.006); the percent decrease following lorazepam was not (Student’s t test, p = 0.71). All four morphine responders have continued over periods of 4 to 6 months to experience modest to marked reduction in OCD symptoms with stable, once to twice weekly, oral morphine doses added to their treatment regimens, without experiencing tolerance, euphoria or drug seeking. Conclusion: A stable, once-weekly dose of oral morphine is well tolerated and can substantially ameliorate OCD symptoms in some treatment-resistant patients. Further research is indicated. References [I ] Warneke L., 1997. A possible new treatment approach to obsessive-
compulsive disorder. Can J Psychiatry 42, 667-668. [2] Shapira, N.A., Keck, PE., Jr., Goldsmith T.D., McConville, B.J., Eis, M., McElroy, S.L., 1997. An open-label pilot study of tramadol .-‘+ hydrochloride in treatment-refractory obsessive-compulsive disorder. Depress Anxiety 6, 170-I 73.
L.M. Koran, B. Franz, K.D. Bullock, M.A. Elliot. Stanford University Medical Center; Department of Psychiatry and Behavioml Sciences, Stanford, CA, USA Background: About 3040% of OCD patients experience little improvement despite adequate trials of multiple medications. Case series and open-label trials in treatment resistant OCD patients report a response to oral morphine (Warneke, 1997) and tramadol (Shapira et al., 1997), a mu-opioid receptor mixed agonist/antagonist with modest serotonin and norepinephrine reuptake activity. We are conducting a placebo-controlled, double-blind trial to test the hypothesis that once-weekly oral morphine is effective in treatment-resistant OCD. Method: We recruited patients from our OCD Clinic who had OCD for >3 years, had failed adequate trials of at least two serotonin reuptake inhibitors, and had a Yale-Brown ObsessiveCompulsive Scale (Y-BOCS) score > 21. Patients continued current medications, but these had to be stable for two months before starting the trial. Exclusion criteria were a history of narcotic-,
-1
No rCBF differences between pentagastrininduced panic and spontaneous panic attacks in panic disorder patients
M.L. Boshuisen, G.J. Ter Horst, J.A. Den Boer. Groningen University Hospital, Department of Psychiatry, Groningen, The Netherlands We studied differences in regional cerebral blood flow (rCBF) between pentagastrin-induced panic attacks and spontaneous panic attacks by means of PET scan in panic disorder (PD) patients. Seventeen drug-free PD patients were scanned to study the rCBF in rest and during a pentagastrin-induced panic attack. Pentagastrin is an accepted panic provocation method in PD patients (Bradwejn et al., 1993; van Megen et al., 1994). It induces a panic attack in about 60% of the patients. It is easily administered aa an intravenous bolus injection, the induction of panic is very fast (within 10 seconds) and disappears within 2