320 CHANGES IN MANIC SYMPTOMS AND SERUM-G.H. IN TWELVE
vious occasion. The period between X-ray examinations was 28-265 months (mean 101 months). Changes in magnification were corrected by measuring anterior-posterior skull size and adjusting sellar area accordingly. There was no significant increase in sellar size as determined by Student’s t test (see table). The correlation between serum-prolactin and phenothiazine dose (expressed as chlorpromazine units) was also insignificant. Although chronic phenothiazine therapy theoretically may produce pituitary enlargement, sellar remodelling, and hypopituitarism through lactotroph hyperplasia, we found no evidence for this in our patients. Department of Endocrinology, Wadsworth V.A. Hospital, Los Angeles, California 90073, U.S.A.
Department of Psychiatry, Brentwood V.A. Hospital,
PATIENTS FOLLOWING PLACEBO
(P) OR NALOXONE (N)
SIDNEY ROSENBLATT
JEROME M. HERSHMAN STEPHEN MARDER THOMAS GARAI
Los Angeles
NALOXONE EFFECTS ON MANIC SYMPTOMS AND GROWTH-HORMONE LEVELS
SIR,-Considerable attention has focused on the possibility that endogenous peptides with opioid-like activity (endorphins) may influence human behaviour. Byck’ and Belluzzi and Stein2 suggested that an excess of endorphins may underlie euphoria and mania and that the relatively specific narcotic antagonist, naloxone, might have antimanic and anti-euphoric properties. Furthermore, naloxone antagonises psychostimulant-induced hyperactivity in rats.3 We have investigated the link between endorphins and manic symptoms by administering naloxone (’Narcan’, Endo Laboratories) to twelve patients (eleven males, one female) with manic or hypomanic symptoms. One patient was diagnosed as having schizophrenia, schizoaffective type, excited type; one had a cyclothymic personality; and the rest had manic-depressive illness, circular type, manic. Nine patients were on antipsychotic drugs, and several were also taking lithium carbonate and/or flurazepam. Because animal experiments had shown that naloxone decreases serum-growth-hormone (G.H.) levels,4 we measured naloxone’s influence on this neurohormone in the hope that it might be a marker of naloxone’s central effects. In a counterbalanced, double-blind, cross-over trial design every patient received a 20 min intravenous infusion of naloxone 20 mg on one day and a saline (placebo) infusion on the preceding or following day. As part of a more complete data-collection effort,s each infusion was in. part preceded and followed by non-structured interviews and behavioural ratings by a research psychiatrist. The psychiatrist rated the subjects’ manic symptoms on a 0-5 point continuum just before and 30 min after infusion, using a modification of the Beigel-Murphy manic rating scale.6 Six of the eleven items found by Beigel and Murphy to be most representative of manic intensity (is talking, moves from one place to another, is distract able, is active, demands contact with others, jumps from one subject to another) were combined in an "arousal-activation" subscale, which we consider to represent the motor components of mania. A total euphoria-grandiosity/arousalactivation score was then generated by summing the two subscale scores. Blood-samples, obtained from an indwelling catheter just before and 30 min after infusion, were assayed for G.H.’ Data were analysed by analyses of variance. Pearson product-moment correlations were used to assess the relationship between net changes in manic symptoms and serum-G.H.levels.
When
compared
with
placebo,
naloxone caused small but
*P
vious occasion. The period between X-ray examinations was 28-265 months (mean 101 months). Changes in magnification were corrected by measuring anterior-posterior skull size and adjusting sellar area accordingly. There was no significant increase in sellar size as determined by Student’s t test (see table). The correlation between serum-prolactin and phenothiazine dose (expressed as chlorpromazine units) was also insignificant. Although chronic phenothiazine therapy theoretically may produce pituitary enlargement, sellar remodelling, and hypopituitarism through lactotroph hyperplasia, we found no evidence for this in our patients. Department of Endocrinology, Wadsworth V.A. Hospital, Los Angeles, California 90073, U.S.A.
Department of Psychiatry, Brentwood V.A. Hospital,
PATIENTS FOLLOWING PLACEBO
(P) OR NALOXONE (N)
SIDNEY ROSENBLATT
JEROME M. HERSHMAN STEPHEN MARDER THOMAS GARAI
Los Angeles
NALOXONE EFFECTS ON MANIC SYMPTOMS AND GROWTH-HORMONE LEVELS
SIR,-Considerable attention has focused on the possibility that endogenous peptides with opioid-like activity (endorphins) may influence human behaviour. Byck’ and Belluzzi and Stein2 suggested that an excess of endorphins may underlie euphoria and mania and that the relatively specific narcotic antagonist, naloxone, might have antimanic and anti-euphoric properties. Furthermore, naloxone antagonises psychostimulant-induced hyperactivity in rats.3 We have investigated the link between endorphins and manic symptoms by administering naloxone (’Narcan’, Endo Laboratories) to twelve patients (eleven males, one female) with manic or hypomanic symptoms. One patient was diagnosed as having schizophrenia, schizoaffective type, excited type; one had a cyclothymic personality; and the rest had manic-depressive illness, circular type, manic. Nine patients were on antipsychotic drugs, and several were also taking lithium carbonate and/or flurazepam. Because animal experiments had shown that naloxone decreases serum-growth-hormone (G.H.) levels,4 we measured naloxone’s influence on this neurohormone in the hope that it might be a marker of naloxone’s central effects. In a counterbalanced, double-blind, cross-over trial design every patient received a 20 min intravenous infusion of naloxone 20 mg on one day and a saline (placebo) infusion on the preceding or following day. As part of a more complete data-collection effort,s each infusion was in. part preceded and followed by non-structured interviews and behavioural ratings by a research psychiatrist. The psychiatrist rated the subjects’ manic symptoms on a 0-5 point continuum just before and 30 min after infusion, using a modification of the Beigel-Murphy manic rating scale.6 Six of the eleven items found by Beigel and Murphy to be most representative of manic intensity (is talking, moves from one place to another, is distract able, is active, demands contact with others, jumps from one subject to another) were combined in an "arousal-activation" subscale, which we consider to represent the motor components of mania. A total euphoria-grandiosity/arousalactivation score was then generated by summing the two subscale scores. Blood-samples, obtained from an indwelling catheter just before and 30 min after infusion, were assayed for G.H.’ Data were analysed by analyses of variance. Pearson product-moment correlations were used to assess the relationship between net changes in manic symptoms and serum-G.H.levels.
When
compared
with
placebo,
naloxone caused small but
*P
