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YOHIMBINE AND PSYCHOGENIC IMPOTENCE
1088 received naltrexone first showed that, during the naltrexone period, naltrexone reversed the bulimic symptoms; compared to its initial frequency, bingeing was reduced by 80%, which is consistent with the results of Jonas and Gold.’ In our crossover study, when placebo followed naltrexone, bingeing frequency remained low (a decrease of 69% compared with baseline. It could be argued that this decrease is a remnant of the drug effect. When used first, placebo had only a slight effect (reduction of binge frequency by 27 %, not significant) and resulted in a high drop-out rate. While there were no drop-outs among the patients who had naltrexone first, 4 of the 5 patients who had placebo first dropped out (1 after 15 days and 3 after a month). The difference in drop-out frequency was not significant, perhaps because of the small number of patients. Therefore no definite conclusion can be drawn from the study of Jonas and Goldl or from ours, and further long-term crossover double-blind studies are needed. Open studies will not be conclusive, since bulimic symptoms respond to many interventions. Crossover studies must include larger series of patients to control for possible drop-out related bias. Hôpital Bichat, 46 Rue Huchard, 75018 Pans, France 1. 2.
LAURENCE IGOIN-APFELBAUM MARIAN APFELBAUM
Jonas JM, Gold MS. Naltrexone reverses bulimic symptoms. Lancet 1986; i: 807. Jonas JM, Hudson JI, Pope HG. Treatment of bulimia with MAO inhibitors J Clin Pharmacol 1983; 3: 59-60.
Pope HG, Hudson JI, Jonas JM, et al Bulimia treated with imipramine: a placebo controlled double blind study. Am J Psychiatry 1983; 140: 554-58. 4. Pope HG, Herridge PL, Hudson JI, et al. Treatment of bulimia with nomifensive. Am J Psychiatry 1986; 143: 371-73. 5. Fantino M, Hosotte J, Apfelbaum M. An opioid antagonist, naltrexone, reduces preference for sucrose in humans. Am J Physiol 1986; 251: R91-96. 3.
YOHIMBINE AND PSYCHOGENIC IMPOTENCE
SiR,—Having taken the trouble of seeking the opinions of partners on the effect of yohimbine in the treatment of psychogenic impotence (Aug 22, p 421), K. Reid and colleagues do not tell us how the ratings of the partners and the patients were combined. Ideally we need a coefficient of agreement for a nominal or ordinal scale. How were the ratings collated when partner and patient disagreed? Only 21 % of the patients who were switched to yohimbine after a course of placebo responded to treatment, which as Reid and colleagues say, could have been due to negative expectancy. If observers were asked to guess which drug the patients were taking, giving reasons for the guess, the results couldthen be analysed in terms of expectancy. Hesketh Park
Hospital, Southport, Merseyside PR9 0LT
M. L. ROBINSON
SiR,—K. Reid and colleagues propose yohimbine as one of the treatment options for psychogenic impotence. They report a clincially and statistically significant difference in the rate of response between the yohimbine and placebo groups (62 % vs 16 %) at the end of phase i. In phase n patients earlier allocated to the placebo group received yohimbine, but their response rate was poor (21 %) and significantly worse than that to yohimbine in phase I (p<0’01). Since the trial was double-blind this finding suggests inherent differences between the two groups of patients that decisively influence clinical outcome (differences in age, for example). Randomisation does not guarantee comparability and we are not told whether patient variables were homogeneously distributed. Reid et al hypothesise a "negative expectancy effect"
***Kelly Reid’s reply follows.-ED. L. SIR,--Our intention in soliciting the partners’ opinions of the success of treatment was to increase the reliability of our patients’ reports of treatment efficacy. It is very difficult to measure treatment response in this . sort of research.’ Any psychophysiological response that we could measure in the laboratory could be criticised for being artificial; that is, anything less than intercourse with a partner lacks validity as an outcome measure. Furthermore the relation between erections elicited in the laboratory in response to sexual stimuli and erections elicited in a sexual encounter is unknown.2 We believed that patients’ reports, corroborated by the partners, was the most valid approach. Our rating scale was quite broad, and as a result there was complete agreement between patients and their partners on this scale. Department of Psychology, Queen’s University, Kingston, Ontario K7L 3N6, Canada 1. Condra
KELLY REID
M, Morales A, Surridge DH, Owen JA, Marshall P, Fenemore J. The nocturnal penile tumescence recording as an outcome the treatment of organic impotence. J Urol 1986; 136: 280.
unreliablility of measurement in
C, Morales A, Marshall WL. Penile sufficiency: an operational definition. JUrol (in press)
2. Earls
LINKED DNA MARKERS IN CLINICAL DIAGNOSIS OF JUVENILE HUNTINGTON’S DISEASE
SjR,—Establishing the clinical diagnosis of Huntington’s disease at onset, is difficultl and no specific diagnostic technique is available. There are clinical differences between the (HD), especially
symptoms of HD in children and in adults, and differentiation between early juvenile HD and other neurological disorders of childhood can rarely be made with certainty.2 We have used DNA markers to support the clinical suspicion of juvenile HD in a 6-yearold boy (111.1, upper figure) at 50% risk. When the propositus was aged 5, his mother noticed that he had ceased climbing in the playground and riding his bicycle. He was also occasionally aggressive towards other children. Despite normal growth he did not gain weight for 6 months. On examination the boy had involuntary choreatic movements predominantly of his right hand, rigidity of the arms, and delayed speech development with difficulties in articulation. Electroencephalography and magnetic resonance imaging were normal. The findings were considered insufficient for a diagnosis of juvenile HD. His 35-year-old father and two affected aunts showed their first symptoms between the ages of 25 and 30. They all have HD with choreatic movements, progressive dementia, and personality alterations. No case of juvenile HD is known in this family. The earlier onset of HD in affected children of affected fathers compared with affected mothers has been reported.3 Confirmation of the suspected diagnosis is important for prognosis, management, and
first
derived from the previous poor response to placebo. Such an effect of patient’s expectations would have to be strong (62 % vs 21 %) to nullify the pharmacological action of yohimbine. We are not told how many patients who responded to yohimbine in phase 11 had responded to placebo in phase I . Problems in interpretation could have been overcome in a blinded crossover trial design. Clinical
Pharmacology Unit, Hospital de la SS La Paz, 28046 Madrid, Spam
F. B.
J. ABAJO GARIJO
J. FRIAS
Pedigree (upper) and autoradiograph (lower) showing inheritance ofF5’52/MspI alleles in a family with HuntitÌ.gton’s disease. Allele 1=. 5 kb; allele 2 - 28 kb.
LAURENCE IGOIN-APFELBAUM MARIAN APFELBAUM
Jonas JM, Gold MS. Naltrexone reverses bulimic symptoms. Lancet 1986; i: 807. Jonas JM, Hudson JI, Pope HG. Treatment of bulimia with MAO inhibitors J Clin Pharmacol 1983; 3: 59-60.
Pope HG, Hudson JI, Jonas JM, et al Bulimia treated with imipramine: a placebo controlled double blind study. Am J Psychiatry 1983; 140: 554-58. 4. Pope HG, Herridge PL, Hudson JI, et al. Treatment of bulimia with nomifensive. Am J Psychiatry 1986; 143: 371-73. 5. Fantino M, Hosotte J, Apfelbaum M. An opioid antagonist, naltrexone, reduces preference for sucrose in humans. Am J Physiol 1986; 251: R91-96. 3.
YOHIMBINE AND PSYCHOGENIC IMPOTENCE
SiR,—Having taken the trouble of seeking the opinions of partners on the effect of yohimbine in the treatment of psychogenic impotence (Aug 22, p 421), K. Reid and colleagues do not tell us how the ratings of the partners and the patients were combined. Ideally we need a coefficient of agreement for a nominal or ordinal scale. How were the ratings collated when partner and patient disagreed? Only 21 % of the patients who were switched to yohimbine after a course of placebo responded to treatment, which as Reid and colleagues say, could have been due to negative expectancy. If observers were asked to guess which drug the patients were taking, giving reasons for the guess, the results couldthen be analysed in terms of expectancy. Hesketh Park
Hospital, Southport, Merseyside PR9 0LT
M. L. ROBINSON
SiR,—K. Reid and colleagues propose yohimbine as one of the treatment options for psychogenic impotence. They report a clincially and statistically significant difference in the rate of response between the yohimbine and placebo groups (62 % vs 16 %) at the end of phase i. In phase n patients earlier allocated to the placebo group received yohimbine, but their response rate was poor (21 %) and significantly worse than that to yohimbine in phase I (p<0’01). Since the trial was double-blind this finding suggests inherent differences between the two groups of patients that decisively influence clinical outcome (differences in age, for example). Randomisation does not guarantee comparability and we are not told whether patient variables were homogeneously distributed. Reid et al hypothesise a "negative expectancy effect"
***Kelly Reid’s reply follows.-ED. L. SIR,--Our intention in soliciting the partners’ opinions of the success of treatment was to increase the reliability of our patients’ reports of treatment efficacy. It is very difficult to measure treatment response in this . sort of research.’ Any psychophysiological response that we could measure in the laboratory could be criticised for being artificial; that is, anything less than intercourse with a partner lacks validity as an outcome measure. Furthermore the relation between erections elicited in the laboratory in response to sexual stimuli and erections elicited in a sexual encounter is unknown.2 We believed that patients’ reports, corroborated by the partners, was the most valid approach. Our rating scale was quite broad, and as a result there was complete agreement between patients and their partners on this scale. Department of Psychology, Queen’s University, Kingston, Ontario K7L 3N6, Canada 1. Condra
KELLY REID
M, Morales A, Surridge DH, Owen JA, Marshall P, Fenemore J. The nocturnal penile tumescence recording as an outcome the treatment of organic impotence. J Urol 1986; 136: 280.
unreliablility of measurement in
C, Morales A, Marshall WL. Penile sufficiency: an operational definition. JUrol (in press)
2. Earls
LINKED DNA MARKERS IN CLINICAL DIAGNOSIS OF JUVENILE HUNTINGTON’S DISEASE
SjR,—Establishing the clinical diagnosis of Huntington’s disease at onset, is difficultl and no specific diagnostic technique is available. There are clinical differences between the (HD), especially
symptoms of HD in children and in adults, and differentiation between early juvenile HD and other neurological disorders of childhood can rarely be made with certainty.2 We have used DNA markers to support the clinical suspicion of juvenile HD in a 6-yearold boy (111.1, upper figure) at 50% risk. When the propositus was aged 5, his mother noticed that he had ceased climbing in the playground and riding his bicycle. He was also occasionally aggressive towards other children. Despite normal growth he did not gain weight for 6 months. On examination the boy had involuntary choreatic movements predominantly of his right hand, rigidity of the arms, and delayed speech development with difficulties in articulation. Electroencephalography and magnetic resonance imaging were normal. The findings were considered insufficient for a diagnosis of juvenile HD. His 35-year-old father and two affected aunts showed their first symptoms between the ages of 25 and 30. They all have HD with choreatic movements, progressive dementia, and personality alterations. No case of juvenile HD is known in this family. The earlier onset of HD in affected children of affected fathers compared with affected mothers has been reported.3 Confirmation of the suspected diagnosis is important for prognosis, management, and
first
derived from the previous poor response to placebo. Such an effect of patient’s expectations would have to be strong (62 % vs 21 %) to nullify the pharmacological action of yohimbine. We are not told how many patients who responded to yohimbine in phase 11 had responded to placebo in phase I . Problems in interpretation could have been overcome in a blinded crossover trial design. Clinical
Pharmacology Unit, Hospital de la SS La Paz, 28046 Madrid, Spam
F. B.
J. ABAJO GARIJO
J. FRIAS
Pedigree (upper) and autoradiograph (lower) showing inheritance ofF5’52/MspI alleles in a family with HuntitÌ.gton’s disease. Allele 1=. 5 kb; allele 2 - 28 kb.