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Effects of naltrexone on mannerisms and water imbalance in polydipsic schizophrenics: a pilot study
SCHIZOPHRENIA RESEARCH ELSEVIER
SchizophreniaResearch 17 (1995) 279-282
Effects of naltrexone on mannerisms and water imbalance in polydipsic schizophrenics: a pilot study Julia A. Becker a, Morris B. Goldman a,b,,, M o h a m m e d Y. Alam a, Daniel J. Luchins a.b a Lniversity of Chicago Pritzker School of Medicine, 5841 S. Maryland Ave, MC3077 Chicago, IL 60637, USA b Psychiatric Institute of the University of Illinois in Affiliation with the University of Chicago; 1601 West Taylor Street: Chicago, IL 60612, USA
Received 24 October 1994; revision received 23 January 1995; accepted 6 February 1995
Abstract
In an open design, the opiate antagonist, naltrexone (25 mg bid), was added for six weeks to the neuroleptic regimen of seven inpatient polydipsic hyponatremic schizophrenics. Mannerisms and diurnal weight change improved slightly, the latter probably not as a consequence of diminished intake alone. Further studies are needed to clarify if stereotypies and polydipsia are modulated by endogenous opiates, and if opiate antagonists are of therapeutic value in this population. Keywords." Stereotypy; (Schizophrenia)
Naltrexone;
Polydipsia;
Negative
1. Introduction
In addition to positive and negative symptoms, schizophrenics often manifest stereotypic behaviors t i.e. hoarding, mannerisms, pica, bulimia, and pacing) that are repetitive, serve no apparent purpose, can lead to serious morbidity (e.g. asphyxiation, peritonitis), and markedly interfere with efforts at rehabilitation (Arieti, 1974; Luchins et al., 1992). These behaviors appear to be particularly prominent in patients with primary polydipsia (De Leon et al., 1994), and we have proposed that * Corresponding author. Tel: + 1 312-702-1542; fax: + 1 312-702-6454. 0920-9964/95/$09.50 © 1995ElsevierScienceB.V. All rights reserved SSDI 0920-9964(95)00011-9
symptom;
Endogenous
opiate;
Hyponatremia;
stereotypies and polydipsia both arise from hippocampal dysfunction (Luchins et al., 1991). Similar appearing behaviors (e.g. rocking, self-mutilation) in Lesch-Nyhan Syndrome and the mentally retarded diminish with opiate antagonists (Goldstein et al., 1985; Sandman et al., 1990). The association of polydipsia with substance abuse and heavy smoking (De Leon et al., 1994), and the effects of hydration status on opiate binding (Snyder, 1984), support the concept that it too is associated with addictive behaviors. Nishikawa et al. (1994), in fact, report that the injectable opiate antagonist, naloxone, improves polydipsia in at least some schizophrenics, though the extent of the improvement, and specifically its clinical significance, were unclear. We wished
280
J.A. Becker et al./Schizophrenia Research 17 (1995) 279 282
to determine whether an orally administered opiate antagonist was effective in improving stereotypic behaviors and water imbalance in this population.
2. Methods
2.1. Subjects Eight male adults were studied on the University of Chicago inpatient research unit at the Illinois State Psychiatric Institute. All had polyuria based on measured 24 h urine volumes over 3 liters, and multiple 4 pm spot urine creatinines of less than 70 mg/dl (Goldman et al., 1992). All had a documented history of hyponatremia (<130 mEq/1) (which could not be explained by known factors (Goldman, 1991)), and were stabilized on a high potency neuroleptic regimen. All were managed with the target weight procedure throughout the study (Goldman, 1991).
2.2. Design Subjects underwent a 2 week baseline period, following which they received naltrexone hydrochloride, 25 mg PO BID, for 6 weeks, in addition to their other psychotropic medications. This dose of naltrexone was chosen to minimize the risk of hepatotoxicity (Sandman et al., 1990). Behavior change was assessed with the Elgin Behavior Rating Scale. Scores range from zero (not observed) to six (extremely severe)(1-2=mild, 3-4 = moderate, 5-6 = severe), and include defined anchor points (Luchins et al., 1992). Ratings were conducted by two nursing staff members at the end of the 8 am-4 pm shifts on Monday, Wednesday, and Friday of each week. Adequate inter-rater reliability was obtained, however, only with the polydipsia (intraclass correlation coefficient r=0.42), social withdrawal (r=0.48) and mannerisms (r=0.45) items, and thus only these are reported here. Because precise measures of water imbalance are difficult to obtain in this population, we relied on several indices, in addition to the staff ratings. Diurnal weight gain (4 pm minus 8 am body
weight) was determined daily as an index of hydration status (Viewig et al., 1987; Delva and Crammer, 1988). Urine osmolality was obtained three times weekly in the morning and afternoon (Goldman et al., 1992), and plasma osmolality was obtained three times during the baseline period and again during the last week of the study. Side effects were recorded daily by nursing staff, and liver function tests were measured every week during the study. Subjects provided informed witnessed consent.
2.3. Data analysis Urine osmolality was log transformed to normalize the data. We relied on multivariate analysis of variance for repeated measures (MANOVA, SPSS-PC, Chicago, IL) to analyze the data. Analyses were based on averaged data from each of the 4 two week periods in each subject. In order to determine treatment effects we examined the three a priori simple contrasts comparing baseline to (1) weeks 1-2; (2) weeks 3-4; and (3) weeks 5-6 of treatment. We hypothesized that we would find diminished mannerisms and decreased fluid intake (as indicated by decreased severity in the ratings, increased morning and afternoon urine osmolality, and decreased diurnal weight gain) in the last two treatment periods with no change in social withdrawal in any of the periods. Values shown are mean__+standard deviation.
3. Results
One of the subjects was dropped from the study after three weeks on naltrexone because of failure to cooperate and continued aggression. His results are not reported, but did not appear to vary from those of the other subjects. In the remaining seven, mean age (mean+SD) was 42__+10 years, and diagnoses (DSM-IIIR criteria) were chronic undifferentiated schizophrenia (5) and chronic paranoid schizophrenia (2). Mean duration of illness was 20__+7 years, mean total Positive and Negative Symptom Scale score was 86 _ 7, and mean fluphenazine equivalent dose was 17 _ 10 mg. Benztropine mesylate (n = 2) and propranolol (n =
J.A. Becker et al./Schizophrenia Research 17 (1995) 2 79-282
4) were used to treat extrapyramidal side effects. At baseline, three subjects were consistently rated as exhibiting moderate levels of mannerisms (maintaining odd postures or moving hands in a circular motion in front of their face), and none had evidence of tardive dyskinesia or other extrapyramidal signs. While on adjunctive naltrexone, MANOVA demonstrated that mannerisms and diurnal weight change were significantly reduced from baseline during the last treatment period, and that social isolation tended to drop during the second treatment period (Table 1). Ratings of polydipsia nonsignificantly decreased during the last treatment period (p=0.21), and urine osmolality nonsignificantly increased in the morning (p=0.18) and afternoon (p--0.19) during the second treatment period (Table 1). Plasma osmolality was nonsignificantly higher the last week of adjunctive treatment (279 + 10 mOsm/kg) compared to baseline (271 + 14, t = 1.19 df=6, p <0.30). No patient developed water intoxication, or required fluid restriction based on the target weight procedure, during either the baseline or treatment periods. None suffered significant side effects, nor exhibited impaired liver function tests.
4. Discussion
Our data indicate that adjunctive naltrexone may modestly improve mannerisms in chronic,
281
polydipsic hyponatremic schizophrenics (Table 1 ). The possible improvement in social withdrawal was unexpected, given that high doses of naltrexone (250-800 mg administered alone) have generally had no salutary effect on classic symptoms (Nemeroff et al., 1987), and thus suggest that improved social interaction may instead be a consequence of diminished mannerisms. Our data confirm the findings of Nishikawa et al. (1994) of a fall in diurnal weight gain (Table 1); and coupled with a non-significant decrease in ratings of water intake, and increases in morning and afternoon urine osmolality, and morning plasma osmolality, suggest that the drug may modestly improve water imbalance. The rise in urine osmolality, even if it were statistically significant, however, points to a very small decrease in intake, and thus is unlikely to explain the diminished diurnal weight change. Thus this change is more likely attributable to improved diluting capacity (Robertson, 1987), or alternatively completely unrelated to changes in fluid balance. The small sample size and absence of episodes of severe hyponatremia during the baseline period make it impossible to conclude whether naltrexone reduces the incidence of symptomatic hyponatremia, and hence whether it is likely to be of therapeutic benefit. Thus these data provide some, albeit very limited, support for the hypothesis that mannerisms and polydipsia are mediated by endogenous opiates. A larger, placebo-controlled, study with more extensively trained raters, and more subjects,
Table 1. Behaviorsa and indices of water imbalance prior to and following adjunctive naltrexone Measure
Mannerisms Polydipsic behavior Social isolation Diurnal weight change ( lb ) Morning urine osmolality (mOsm/Kg) Afternoon urine osmolality (mOsm/Kg)
Baseline
Adjunctive Naltrexone
Weeks - 1 - 0
Weeks 1-2
Weeks 3-4
Weeks 5-6
1.5 _+0.9 2.2 _+1.6 1.6 + 1.3 5.2 -+4.5 103 ___50 76 -+44
1.4+_0.9 2.0+_1.0 1.0_+ 1.1 5.1 _+4.4 144+_116 82_+32
1.2-t- 1.2 2.0+1.3 0.8 _+0.6** 3.4_+6.3 127_+58 101 +48
0.9+0.6* 1.4+1.2 1.2_+ 1.3 2.5_+4.0* 129+93 82+32
Values are mean +__standard deviation. Mannerisms, social withdrawal and drinking behavior were rated by nursing staff with the Elgin Behavior Rating Scale. * p < 0.05 vs baseline by simple contrast on MANOVA. * p < 0.10 vs baseline by simple contrast on MANOVA.
a
282
J.A. Becker et al./Schizophrenia Research 17 (1995) 279-282
is needed to definitively address these issues. Furthermore, since half of the measures appeared to be improving at the end of the study (Table 1), and no side effects were noted, a longer follow-up with higher doses of naltrexone, might increase the probability of identifying a treatment effect.
Acknowledgements The authors would like to thank Miljana Petkovic, Exermanger Blake, and Rebecca Gibson Hatchett for their assistance in data collection.
References Arieti, S. (1974) Interpretation of Schizophrenia, 2nd. ed. Basic Books, New York pp. 415-522. De Leon, J., Tracy, J.L., McCann, E.M., McGrory, A. and Josiassen, R.C. (1994) Do polydipsia patients display other repetitive behaviors? Biol. Psychiat. 35, 615-747. Delva, N.J. and Crammer, J.L. (1988) Polydipsia in chronic psychiatric patients: body weight and plasma sodium. Br. J. Psychiat. 152, 242-245. Goldman, M.B.(1991) A rational approach to disorders of
water balance in psychaitric patients. Hosp. Commun. Psychiatry 42, 488-494. Goldman, M.B., Marks, R.C., Blake, L., Petkovic, M., Hedeker, D. and Luchins, D.J. (1992) Estimating Daily Urine Volume in Psychiatric Patients: Empiric Confirmation. Biol. Psychiat. 31, 1228-1231. Goldstein, M., Anderson, L.T., Reuben, R. and Dancis, J. (1985) Self-mutilation in Lesch-Nyhan disease is caused by dopaminergic denervation. Lancet I, 338-339. Luchins, D.J. (1990) A possible role of hippocampal dysfunction in schizophrenic symptomatology. Biol. Psychiatry 28, 87-91. Luchins, D.J., Goldman, M.B., Lieb, M. and Hanrahan, P. (1992) Repetitive behaviors in chronically institutionalized schizophrenic patients. Schizophr. Res. 8, 119-123. Nemeroff, C.B., Berger, P.A. and Bissette, G. Peptides in schizophrenia. In: H.Y. Meltzer (Ed). Psychopharmacology, The Third Generation of Progress. Raven Press, New York. pp. 730-743. Nishikawa, T., Tsuda, A., Tanaka, M. and Nishikawa, M. (1994) Naloxone attenuates drinking behavior in psychiatric patients displaying self-induced water intoxication. Prog. Neuro-psychopharmacol. Biol. Psychiat. 18, 149-153. Robertson, G.L. (1987) Physiology of ADH Secretion. Kid. Intl. 32(supp 21),$20-$26. Sandman, C.A., Barron, J.L. and Colman, H. (1990) An orally administered opiate blocker, naltrexone, attenuates selfinjurious behavior. Am. J. Ment. Retard. 95, 93-102. Snyder, S.H.(1984) Drug and neurotransmitter receptors in the brain. Science 224, 22-31. Vieweg, V.W.R., Godleski, L., Yank, G. (1987) Diurnal weight gain as an index of polyuria and hyponatremia among chronically psychotic patients. Neuroendocrinol. Lett. 9, 218.
SchizophreniaResearch 17 (1995) 279-282
Effects of naltrexone on mannerisms and water imbalance in polydipsic schizophrenics: a pilot study Julia A. Becker a, Morris B. Goldman a,b,,, M o h a m m e d Y. Alam a, Daniel J. Luchins a.b a Lniversity of Chicago Pritzker School of Medicine, 5841 S. Maryland Ave, MC3077 Chicago, IL 60637, USA b Psychiatric Institute of the University of Illinois in Affiliation with the University of Chicago; 1601 West Taylor Street: Chicago, IL 60612, USA
Received 24 October 1994; revision received 23 January 1995; accepted 6 February 1995
Abstract
In an open design, the opiate antagonist, naltrexone (25 mg bid), was added for six weeks to the neuroleptic regimen of seven inpatient polydipsic hyponatremic schizophrenics. Mannerisms and diurnal weight change improved slightly, the latter probably not as a consequence of diminished intake alone. Further studies are needed to clarify if stereotypies and polydipsia are modulated by endogenous opiates, and if opiate antagonists are of therapeutic value in this population. Keywords." Stereotypy; (Schizophrenia)
Naltrexone;
Polydipsia;
Negative
1. Introduction
In addition to positive and negative symptoms, schizophrenics often manifest stereotypic behaviors t i.e. hoarding, mannerisms, pica, bulimia, and pacing) that are repetitive, serve no apparent purpose, can lead to serious morbidity (e.g. asphyxiation, peritonitis), and markedly interfere with efforts at rehabilitation (Arieti, 1974; Luchins et al., 1992). These behaviors appear to be particularly prominent in patients with primary polydipsia (De Leon et al., 1994), and we have proposed that * Corresponding author. Tel: + 1 312-702-1542; fax: + 1 312-702-6454. 0920-9964/95/$09.50 © 1995ElsevierScienceB.V. All rights reserved SSDI 0920-9964(95)00011-9
symptom;
Endogenous
opiate;
Hyponatremia;
stereotypies and polydipsia both arise from hippocampal dysfunction (Luchins et al., 1991). Similar appearing behaviors (e.g. rocking, self-mutilation) in Lesch-Nyhan Syndrome and the mentally retarded diminish with opiate antagonists (Goldstein et al., 1985; Sandman et al., 1990). The association of polydipsia with substance abuse and heavy smoking (De Leon et al., 1994), and the effects of hydration status on opiate binding (Snyder, 1984), support the concept that it too is associated with addictive behaviors. Nishikawa et al. (1994), in fact, report that the injectable opiate antagonist, naloxone, improves polydipsia in at least some schizophrenics, though the extent of the improvement, and specifically its clinical significance, were unclear. We wished
280
J.A. Becker et al./Schizophrenia Research 17 (1995) 279 282
to determine whether an orally administered opiate antagonist was effective in improving stereotypic behaviors and water imbalance in this population.
2. Methods
2.1. Subjects Eight male adults were studied on the University of Chicago inpatient research unit at the Illinois State Psychiatric Institute. All had polyuria based on measured 24 h urine volumes over 3 liters, and multiple 4 pm spot urine creatinines of less than 70 mg/dl (Goldman et al., 1992). All had a documented history of hyponatremia (<130 mEq/1) (which could not be explained by known factors (Goldman, 1991)), and were stabilized on a high potency neuroleptic regimen. All were managed with the target weight procedure throughout the study (Goldman, 1991).
2.2. Design Subjects underwent a 2 week baseline period, following which they received naltrexone hydrochloride, 25 mg PO BID, for 6 weeks, in addition to their other psychotropic medications. This dose of naltrexone was chosen to minimize the risk of hepatotoxicity (Sandman et al., 1990). Behavior change was assessed with the Elgin Behavior Rating Scale. Scores range from zero (not observed) to six (extremely severe)(1-2=mild, 3-4 = moderate, 5-6 = severe), and include defined anchor points (Luchins et al., 1992). Ratings were conducted by two nursing staff members at the end of the 8 am-4 pm shifts on Monday, Wednesday, and Friday of each week. Adequate inter-rater reliability was obtained, however, only with the polydipsia (intraclass correlation coefficient r=0.42), social withdrawal (r=0.48) and mannerisms (r=0.45) items, and thus only these are reported here. Because precise measures of water imbalance are difficult to obtain in this population, we relied on several indices, in addition to the staff ratings. Diurnal weight gain (4 pm minus 8 am body
weight) was determined daily as an index of hydration status (Viewig et al., 1987; Delva and Crammer, 1988). Urine osmolality was obtained three times weekly in the morning and afternoon (Goldman et al., 1992), and plasma osmolality was obtained three times during the baseline period and again during the last week of the study. Side effects were recorded daily by nursing staff, and liver function tests were measured every week during the study. Subjects provided informed witnessed consent.
2.3. Data analysis Urine osmolality was log transformed to normalize the data. We relied on multivariate analysis of variance for repeated measures (MANOVA, SPSS-PC, Chicago, IL) to analyze the data. Analyses were based on averaged data from each of the 4 two week periods in each subject. In order to determine treatment effects we examined the three a priori simple contrasts comparing baseline to (1) weeks 1-2; (2) weeks 3-4; and (3) weeks 5-6 of treatment. We hypothesized that we would find diminished mannerisms and decreased fluid intake (as indicated by decreased severity in the ratings, increased morning and afternoon urine osmolality, and decreased diurnal weight gain) in the last two treatment periods with no change in social withdrawal in any of the periods. Values shown are mean__+standard deviation.
3. Results
One of the subjects was dropped from the study after three weeks on naltrexone because of failure to cooperate and continued aggression. His results are not reported, but did not appear to vary from those of the other subjects. In the remaining seven, mean age (mean+SD) was 42__+10 years, and diagnoses (DSM-IIIR criteria) were chronic undifferentiated schizophrenia (5) and chronic paranoid schizophrenia (2). Mean duration of illness was 20__+7 years, mean total Positive and Negative Symptom Scale score was 86 _ 7, and mean fluphenazine equivalent dose was 17 _ 10 mg. Benztropine mesylate (n = 2) and propranolol (n =
J.A. Becker et al./Schizophrenia Research 17 (1995) 2 79-282
4) were used to treat extrapyramidal side effects. At baseline, three subjects were consistently rated as exhibiting moderate levels of mannerisms (maintaining odd postures or moving hands in a circular motion in front of their face), and none had evidence of tardive dyskinesia or other extrapyramidal signs. While on adjunctive naltrexone, MANOVA demonstrated that mannerisms and diurnal weight change were significantly reduced from baseline during the last treatment period, and that social isolation tended to drop during the second treatment period (Table 1). Ratings of polydipsia nonsignificantly decreased during the last treatment period (p=0.21), and urine osmolality nonsignificantly increased in the morning (p=0.18) and afternoon (p--0.19) during the second treatment period (Table 1). Plasma osmolality was nonsignificantly higher the last week of adjunctive treatment (279 + 10 mOsm/kg) compared to baseline (271 + 14, t = 1.19 df=6, p <0.30). No patient developed water intoxication, or required fluid restriction based on the target weight procedure, during either the baseline or treatment periods. None suffered significant side effects, nor exhibited impaired liver function tests.
4. Discussion
Our data indicate that adjunctive naltrexone may modestly improve mannerisms in chronic,
281
polydipsic hyponatremic schizophrenics (Table 1 ). The possible improvement in social withdrawal was unexpected, given that high doses of naltrexone (250-800 mg administered alone) have generally had no salutary effect on classic symptoms (Nemeroff et al., 1987), and thus suggest that improved social interaction may instead be a consequence of diminished mannerisms. Our data confirm the findings of Nishikawa et al. (1994) of a fall in diurnal weight gain (Table 1); and coupled with a non-significant decrease in ratings of water intake, and increases in morning and afternoon urine osmolality, and morning plasma osmolality, suggest that the drug may modestly improve water imbalance. The rise in urine osmolality, even if it were statistically significant, however, points to a very small decrease in intake, and thus is unlikely to explain the diminished diurnal weight change. Thus this change is more likely attributable to improved diluting capacity (Robertson, 1987), or alternatively completely unrelated to changes in fluid balance. The small sample size and absence of episodes of severe hyponatremia during the baseline period make it impossible to conclude whether naltrexone reduces the incidence of symptomatic hyponatremia, and hence whether it is likely to be of therapeutic benefit. Thus these data provide some, albeit very limited, support for the hypothesis that mannerisms and polydipsia are mediated by endogenous opiates. A larger, placebo-controlled, study with more extensively trained raters, and more subjects,
Table 1. Behaviorsa and indices of water imbalance prior to and following adjunctive naltrexone Measure
Mannerisms Polydipsic behavior Social isolation Diurnal weight change ( lb ) Morning urine osmolality (mOsm/Kg) Afternoon urine osmolality (mOsm/Kg)
Baseline
Adjunctive Naltrexone
Weeks - 1 - 0
Weeks 1-2
Weeks 3-4
Weeks 5-6
1.5 _+0.9 2.2 _+1.6 1.6 + 1.3 5.2 -+4.5 103 ___50 76 -+44
1.4+_0.9 2.0+_1.0 1.0_+ 1.1 5.1 _+4.4 144+_116 82_+32
1.2-t- 1.2 2.0+1.3 0.8 _+0.6** 3.4_+6.3 127_+58 101 +48
0.9+0.6* 1.4+1.2 1.2_+ 1.3 2.5_+4.0* 129+93 82+32
Values are mean +__standard deviation. Mannerisms, social withdrawal and drinking behavior were rated by nursing staff with the Elgin Behavior Rating Scale. * p < 0.05 vs baseline by simple contrast on MANOVA. * p < 0.10 vs baseline by simple contrast on MANOVA.
a
282
J.A. Becker et al./Schizophrenia Research 17 (1995) 279-282
is needed to definitively address these issues. Furthermore, since half of the measures appeared to be improving at the end of the study (Table 1), and no side effects were noted, a longer follow-up with higher doses of naltrexone, might increase the probability of identifying a treatment effect.
Acknowledgements The authors would like to thank Miljana Petkovic, Exermanger Blake, and Rebecca Gibson Hatchett for their assistance in data collection.
References Arieti, S. (1974) Interpretation of Schizophrenia, 2nd. ed. Basic Books, New York pp. 415-522. De Leon, J., Tracy, J.L., McCann, E.M., McGrory, A. and Josiassen, R.C. (1994) Do polydipsia patients display other repetitive behaviors? Biol. Psychiat. 35, 615-747. Delva, N.J. and Crammer, J.L. (1988) Polydipsia in chronic psychiatric patients: body weight and plasma sodium. Br. J. Psychiat. 152, 242-245. Goldman, M.B.(1991) A rational approach to disorders of
water balance in psychaitric patients. Hosp. Commun. Psychiatry 42, 488-494. Goldman, M.B., Marks, R.C., Blake, L., Petkovic, M., Hedeker, D. and Luchins, D.J. (1992) Estimating Daily Urine Volume in Psychiatric Patients: Empiric Confirmation. Biol. Psychiat. 31, 1228-1231. Goldstein, M., Anderson, L.T., Reuben, R. and Dancis, J. (1985) Self-mutilation in Lesch-Nyhan disease is caused by dopaminergic denervation. Lancet I, 338-339. Luchins, D.J. (1990) A possible role of hippocampal dysfunction in schizophrenic symptomatology. Biol. Psychiatry 28, 87-91. Luchins, D.J., Goldman, M.B., Lieb, M. and Hanrahan, P. (1992) Repetitive behaviors in chronically institutionalized schizophrenic patients. Schizophr. Res. 8, 119-123. Nemeroff, C.B., Berger, P.A. and Bissette, G. Peptides in schizophrenia. In: H.Y. Meltzer (Ed). Psychopharmacology, The Third Generation of Progress. Raven Press, New York. pp. 730-743. Nishikawa, T., Tsuda, A., Tanaka, M. and Nishikawa, M. (1994) Naloxone attenuates drinking behavior in psychiatric patients displaying self-induced water intoxication. Prog. Neuro-psychopharmacol. Biol. Psychiat. 18, 149-153. Robertson, G.L. (1987) Physiology of ADH Secretion. Kid. Intl. 32(supp 21),$20-$26. Sandman, C.A., Barron, J.L. and Colman, H. (1990) An orally administered opiate blocker, naltrexone, attenuates selfinjurious behavior. Am. J. Ment. Retard. 95, 93-102. Snyder, S.H.(1984) Drug and neurotransmitter receptors in the brain. Science 224, 22-31. Vieweg, V.W.R., Godleski, L., Yank, G. (1987) Diurnal weight gain as an index of polyuria and hyponatremia among chronically psychotic patients. Neuroendocrinol. Lett. 9, 218.