- Email: [email protected]
Treatment of steroid psychoses
Treatment of Schizophrenia
44
BIOL PSYCHIATRY 1992;3! :6.~A-252A
81A
COVARIANCE OF POSITIVE AND NEGATIVE SYMPTOMS DURING INITIAL NEUROLEPTIC TREATMENT IN SCHIZOPHRENIA Saulo C.M. Ribeiro, Rajiv Tandon, Robert S. Goldman, JoAnn Goodson, John F. Greden The University of Michigan, Ann Arbor Nil 48109-0120. Negative symptoms in schizophrenia are stereotypically seen as treatment refractory, whereas positive symptoms are thought to respond to treatment. To assess this question, and to evaluate the covariance of positive and negative symptoms during neuroleptic treatment in the acute pkase, we studied 120 RDC/DSMIII-R schizophrenic inpatients at 2-week drug-free baseline and after 3-4 weeks of neuroleptic medication. Patients were typically male (2:1 M/F), 29 __ 8 years old, and had been ill for 8 _+ 7 yeats. Neuroleptic treatment was clinically determined. Positive and negative symptoms were assessed respectively by the BPRS "thot" factor (conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content) and by the SANS sum of global scores. Total symptomatology was assessed by the BPRS total. There was significant improvement in positive symptoms (15.6 - 2.9-10.2 _ 3.2), negative symptoms (12.5 +_ 4.2-8.6 _+ 3.4), and total symptoms (50.2 -+ 8.6-36.6 _ 7.9). The change in posbive symptoms was highly correlated with the change in negative symptoms (r = 0.60, p < 0.001). These findings confirm recent studies suggesting that negative symptoms in schizophrenia respond to neuroleptics during the acute phase of treatment. Positive and negative symptoms do covary during initial treatment, suggesting that common mechanisms may underlie both positive and negative symptomatology during the acute phase of schizophrenia.
45
EFFECT OF MIANSERIN ON NEGATIVE SYMPTOMS IN SCHIZOPHRENIA Ariane Rogue, Patrick Rogue C.H.S., 67720 Hoerdt, France. A subset of schizophrenic patients present hypersensitive 5-HT2 postsynaptic receptors, which could contribute to the pathogenesis of negative symptoms (Bleich, A [1988] SchizophreniaBull. 14:297). Clinical trials with 5-HT2 antagonists such as setopemne (Ceulemans, D [1985] Psychopharmacol. 85: 329) or ritanserine nave confirmed that they have therapeutic potential. We decided to replicate these findings with the 5-HT2 antagonist mianserin using an open add-on design. Chronic schizophrenic inpatients (DSM-IIIR) were equilibrated on a similar depot neumleptic regimen. Mianserin 30-60 mg was then given during 8 weeks. The BPRS, SANS, SAPS, and BQLS (Brief Quality-of-Life Rating Scale, Rogue [1991] Inst. on H&CP Abstr 43:215) were monitored weekly. Preliminary analysis of the data (n = 1I) reveals a nonsignificative trend towards a decrease in the negative and global symptom ratings, with a clear effect in several cases. The results from an amplified sample will be discussed.
46
TREATMENT OF STEROID PSYCHOSES John M. Davis, Philip G. Janicak, Bradley Merk Illinois State Psychiatric Institute, Chicago, IL 60651. This paper evaluates acute or prophylactic treatment for steroid-induced psychiatric symptoms. To this end, a comprehensive computer-guided literature search was undertaken to find all pertinent articles. We found studies of 86 cases of acute or prophylactic treatment. We also received a number of articles in which the clinician offers a clinical recommendation. These data are presented in the context of what we know about steroid discontinuance or spontaneous remission. As steroid psychosis is uncommon, it is difficult to do random-assignment controlled studies, and in their absence, we must rely on the analysis of the clinical literature. These data were condensed into a master table consisting of a number of pertinent variables.
BIOL PSYCHIATRY 1992;31:61A-252A
82A
Treatment of Schizophrenia
Low-dose neuroleptics and electroconvulsive therapy (ECT) have been documented to be effective. Though acute lithium treatment has not been sufficiently studied, data supports the effectiveness of lithium as a prophylactic measure prior to steroid therapy. Two case reports have suggested the effectiveness of carbamazepine, and one of clonazepam, as treatments. Tricyclic medicaticas appear to have either no effect or an exacerbating effect on steroid-induced psychiatric symptoms and are contraindicated.
47
ANTIPSYCHOTIC EFFICACY OF SIGMA ANTAGONISTS Richard L. Borison, Ananda P. Pathiraja, Bruce I. Diamond Medical College of Georgia and Augusta VAMC, Augusta, GA 30912. The sigma receptor was initially characterized by the psychotomimetic actions of pentazocine, and it was later found that haloperidol is the most potent sigma antagonist. A new group of specific sigma antagonists has been developed that do not possess the neurologic or autonomic side effects associated with classical antipsychotic agents. These agents include rimcazole, tiospirone, gevetroline, and BMY-14802, and we now report on their therapeutic activity in schizophrenic patients. For rimcazole, open trials indicated therapeutic efficacy, but controlled studies versus placebo or chlorpromazine failed to show efficacy; rimcazole is a specific but weak sigma antagonist. In contrast, tiospirone is a potent inhibitor of D-2, 5-HT2, and sigma receptors. In early trials with tiospirone, despite high early termination rates, patients showed improvement. In subsequent studies where early termination was minimized, tiospirone was inferior to haloperidol and could not be differentiated from placebo. In preliminary studies, gevetroline showed possible antipsycho'Ac actions, but also produced pancreatitis. In an open trial with BMY-14802, the most selective and potent sigma antagonists, four of six patients showed a marked worsening of psychosis, and the other two showed no change, In summary, sigma antagonism appears to be unrelated to antipsychotic actions, with the functional role of sigma receptors remaining enigmatic.
48
ACUTE EFFECTS OF SCOPOLAMINE CHALLENGE IN CHRONIC SCHIZOPHRENIC PATIENTS Elzbieta Wirkowski, Malcolm McCullough, Sukdeb Mukherjee Medical College of Georgia, Augusta, GA 30912. Central cholinergic dysfunction is known to be associated with impaired cognitive functioning. Scopolamine, a muscarinic receptor antagonist, at a single dose of 0.25 mg, which has no appreciable effect in normals, worsens cognitive functioning in patients with Alzheimer's and Parkinson's disease, but not in cognitively impaired elderly depressed patients, thus showing the discriminating utility of a challenge paradigm for investigating central cholinergic status. We examined in a pilot study the acute effects of a single dose of scopolamine (0.25 mg s.c.) in six DSM-III-R chronic schizophrenic patients (mean __ SD age 39.5 _-x-5.2 years; duration of illness 22.7 +_ 7.2 years; education ! 1.3 "+- 1.2 years). All patients were assessed for psychopathology (BPRS), involuntary movements (Rockland TD Scale), and cognitive performance (MMSE and Buschke SRT) at baseline, and again 9[, rain after scopolamine challenge. All patients tolerated the procedure well. Scopolamine challenge was associated with a significant decrement in the BSRT measures of total recall and long-term recall (paired t-tests, p = 0.006 and 0.01, respectively), with all six patients showing decreased performance on these measures. There was also a slight but statistically nonsignificant decline in total MMSE score (p = 0.20), but aa change in psychopathology or movement disorder ratings. These consistent and robust acute effects of scopolamine on memory function imply decreased central eholinergic reserve in schizophrenia, as has been shown previously for known dementing disorders, and suggest that the basis of cognitive impairment in schizophrenia may differ from that of major mood disorders. Considering the recent evidence of high rates of dementia in elderly schizophrenic patients, the contribution of central cholinergic pathology to the progressive cognitive impairment of chronic schizophrenia merits systematic investigation.
44
BIOL PSYCHIATRY 1992;3! :6.~A-252A
81A
COVARIANCE OF POSITIVE AND NEGATIVE SYMPTOMS DURING INITIAL NEUROLEPTIC TREATMENT IN SCHIZOPHRENIA Saulo C.M. Ribeiro, Rajiv Tandon, Robert S. Goldman, JoAnn Goodson, John F. Greden The University of Michigan, Ann Arbor Nil 48109-0120. Negative symptoms in schizophrenia are stereotypically seen as treatment refractory, whereas positive symptoms are thought to respond to treatment. To assess this question, and to evaluate the covariance of positive and negative symptoms during neuroleptic treatment in the acute pkase, we studied 120 RDC/DSMIII-R schizophrenic inpatients at 2-week drug-free baseline and after 3-4 weeks of neuroleptic medication. Patients were typically male (2:1 M/F), 29 __ 8 years old, and had been ill for 8 _+ 7 yeats. Neuroleptic treatment was clinically determined. Positive and negative symptoms were assessed respectively by the BPRS "thot" factor (conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content) and by the SANS sum of global scores. Total symptomatology was assessed by the BPRS total. There was significant improvement in positive symptoms (15.6 - 2.9-10.2 _ 3.2), negative symptoms (12.5 +_ 4.2-8.6 _+ 3.4), and total symptoms (50.2 -+ 8.6-36.6 _ 7.9). The change in posbive symptoms was highly correlated with the change in negative symptoms (r = 0.60, p < 0.001). These findings confirm recent studies suggesting that negative symptoms in schizophrenia respond to neuroleptics during the acute phase of treatment. Positive and negative symptoms do covary during initial treatment, suggesting that common mechanisms may underlie both positive and negative symptomatology during the acute phase of schizophrenia.
45
EFFECT OF MIANSERIN ON NEGATIVE SYMPTOMS IN SCHIZOPHRENIA Ariane Rogue, Patrick Rogue C.H.S., 67720 Hoerdt, France. A subset of schizophrenic patients present hypersensitive 5-HT2 postsynaptic receptors, which could contribute to the pathogenesis of negative symptoms (Bleich, A [1988] SchizophreniaBull. 14:297). Clinical trials with 5-HT2 antagonists such as setopemne (Ceulemans, D [1985] Psychopharmacol. 85: 329) or ritanserine nave confirmed that they have therapeutic potential. We decided to replicate these findings with the 5-HT2 antagonist mianserin using an open add-on design. Chronic schizophrenic inpatients (DSM-IIIR) were equilibrated on a similar depot neumleptic regimen. Mianserin 30-60 mg was then given during 8 weeks. The BPRS, SANS, SAPS, and BQLS (Brief Quality-of-Life Rating Scale, Rogue [1991] Inst. on H&CP Abstr 43:215) were monitored weekly. Preliminary analysis of the data (n = 1I) reveals a nonsignificative trend towards a decrease in the negative and global symptom ratings, with a clear effect in several cases. The results from an amplified sample will be discussed.
46
TREATMENT OF STEROID PSYCHOSES John M. Davis, Philip G. Janicak, Bradley Merk Illinois State Psychiatric Institute, Chicago, IL 60651. This paper evaluates acute or prophylactic treatment for steroid-induced psychiatric symptoms. To this end, a comprehensive computer-guided literature search was undertaken to find all pertinent articles. We found studies of 86 cases of acute or prophylactic treatment. We also received a number of articles in which the clinician offers a clinical recommendation. These data are presented in the context of what we know about steroid discontinuance or spontaneous remission. As steroid psychosis is uncommon, it is difficult to do random-assignment controlled studies, and in their absence, we must rely on the analysis of the clinical literature. These data were condensed into a master table consisting of a number of pertinent variables.
BIOL PSYCHIATRY 1992;31:61A-252A
82A
Treatment of Schizophrenia
Low-dose neuroleptics and electroconvulsive therapy (ECT) have been documented to be effective. Though acute lithium treatment has not been sufficiently studied, data supports the effectiveness of lithium as a prophylactic measure prior to steroid therapy. Two case reports have suggested the effectiveness of carbamazepine, and one of clonazepam, as treatments. Tricyclic medicaticas appear to have either no effect or an exacerbating effect on steroid-induced psychiatric symptoms and are contraindicated.
47
ANTIPSYCHOTIC EFFICACY OF SIGMA ANTAGONISTS Richard L. Borison, Ananda P. Pathiraja, Bruce I. Diamond Medical College of Georgia and Augusta VAMC, Augusta, GA 30912. The sigma receptor was initially characterized by the psychotomimetic actions of pentazocine, and it was later found that haloperidol is the most potent sigma antagonist. A new group of specific sigma antagonists has been developed that do not possess the neurologic or autonomic side effects associated with classical antipsychotic agents. These agents include rimcazole, tiospirone, gevetroline, and BMY-14802, and we now report on their therapeutic activity in schizophrenic patients. For rimcazole, open trials indicated therapeutic efficacy, but controlled studies versus placebo or chlorpromazine failed to show efficacy; rimcazole is a specific but weak sigma antagonist. In contrast, tiospirone is a potent inhibitor of D-2, 5-HT2, and sigma receptors. In early trials with tiospirone, despite high early termination rates, patients showed improvement. In subsequent studies where early termination was minimized, tiospirone was inferior to haloperidol and could not be differentiated from placebo. In preliminary studies, gevetroline showed possible antipsycho'Ac actions, but also produced pancreatitis. In an open trial with BMY-14802, the most selective and potent sigma antagonists, four of six patients showed a marked worsening of psychosis, and the other two showed no change, In summary, sigma antagonism appears to be unrelated to antipsychotic actions, with the functional role of sigma receptors remaining enigmatic.
48
ACUTE EFFECTS OF SCOPOLAMINE CHALLENGE IN CHRONIC SCHIZOPHRENIC PATIENTS Elzbieta Wirkowski, Malcolm McCullough, Sukdeb Mukherjee Medical College of Georgia, Augusta, GA 30912. Central cholinergic dysfunction is known to be associated with impaired cognitive functioning. Scopolamine, a muscarinic receptor antagonist, at a single dose of 0.25 mg, which has no appreciable effect in normals, worsens cognitive functioning in patients with Alzheimer's and Parkinson's disease, but not in cognitively impaired elderly depressed patients, thus showing the discriminating utility of a challenge paradigm for investigating central cholinergic status. We examined in a pilot study the acute effects of a single dose of scopolamine (0.25 mg s.c.) in six DSM-III-R chronic schizophrenic patients (mean __ SD age 39.5 _-x-5.2 years; duration of illness 22.7 +_ 7.2 years; education ! 1.3 "+- 1.2 years). All patients were assessed for psychopathology (BPRS), involuntary movements (Rockland TD Scale), and cognitive performance (MMSE and Buschke SRT) at baseline, and again 9[, rain after scopolamine challenge. All patients tolerated the procedure well. Scopolamine challenge was associated with a significant decrement in the BSRT measures of total recall and long-term recall (paired t-tests, p = 0.006 and 0.01, respectively), with all six patients showing decreased performance on these measures. There was also a slight but statistically nonsignificant decline in total MMSE score (p = 0.20), but aa change in psychopathology or movement disorder ratings. These consistent and robust acute effects of scopolamine on memory function imply decreased central eholinergic reserve in schizophrenia, as has been shown previously for known dementing disorders, and suggest that the basis of cognitive impairment in schizophrenia may differ from that of major mood disorders. Considering the recent evidence of high rates of dementia in elderly schizophrenic patients, the contribution of central cholinergic pathology to the progressive cognitive impairment of chronic schizophrenia merits systematic investigation.