678
BIOLPSYCHIATRY 1990;27:671--685
Correspondence
nergic neuronal and endocrine systems. Peptides 3:353395. Pique L, Jegou S, Bcrmgna X, Javoy-Agid F, Seurin D, Proeschel MF, Gkm"dF, Agid Y, Vaudry H, Luton JP (1985): Pro-opiomelanocortinpeptides in the human hypothalamus: comparativestudy between normal subjects and Parkinson patients. Neurosci Lett 54:141-146. Reuven Sandyk Pochi PE, Strauss JS (1974): Endocrinologic control of the developmentand activityof the human sebaceous gland. Department of Psychiatry J Invest Dermatol 62:191-197. Albert Einstein College of Medicine Rainem I, Kaye JA, May C, Durso R, Katz DI, Albert ML, Montefiore Medical Center Wolfe N, Pinessi L, FriedlandRP, Rapoport SU (1988): Bronx, NY 10461 Alpha-melanocyte-stimulating hormonelike immunoreactivity is increased in cerebrospinal fluid of patients with Parkinson's disease. Arch Neurol 45:1224-1227. Rainero I, May C, Kaye JA, Friedland RP, Rapoport Sl References (1988): CSF alpha-MSHin dementia of the Alzheimer's type. Neurology 38:1281-1284. Antun-Tay F, Diaz JL, Femandez-GuardiolaA (R~/l): On the effect of melatonin upon human brain. Its possib'~e Sandyk R (1989): Alpha-melanocytestimulating hormone (MSH) in Tourette's syndrome, lnt J Neurosci 44:161therapeutic implications. Life $ci 10:841-850. 164. Carter RJ, Shuster S (1977): Melanocyte-stimula~inghot. Sandyk R (1989): Neuroleptic-inducedakathisia: a role for mone-mimetic action of the phenothiazines. J Pharm MSH peptides. Psychopharmacology 99:134-135. Pharmac Mo130:233-235. Cotzias C, Van Weert MI-I, Schiffer LM (1967): Aromatic Thody AJ (1977): The significance of melanocyte-stimulating hormone(MSH) and the control of its secretion in amino acids and modificationsof parkinsonism.N/~gl the mammal. In Harper NJ, Simmonds AB (eds), Adv J Med 276:374-379. in Drug Research, vol. 1I. London: Academic Press, O'Donohue TL, Dorsa DM (1982): The opiomelanotmphipp. 24-74. pears that further research into the role of pro-opiomelanocortin (POMC)--derived peptides and the effect of neuroleptics on their release and possibly action may prove valuable in further understanding of TD and other drag-induced movement disorders.
Dexamethasone Suppression Test in Brazil To the Editor: The dexamethasone suppression test (DST) has been proposed as a biological aid in the diagnosis of endogenous depressive disorders (Arana et al. 1985; Carroll 1981). However, it lacks specificity (APA 1987; Avery et al. 1985), because numerous other conditions exist that may yield false-positive results (Carroll 1986; Kraus et al. 1988). Carroll (1985), for example, has pointed out that 20% of all inpatients should be excluded due to other possible causes of nonsuppression to DST. A study was undertaken in a psychiatric ward of a public hospital in Sao Paulo City, where 259 consecutively admitted inpatients were diagnosed through the RDC and submitted to the DST 2,~-36 hr after admission and/or at discharge. After obtaining informed consent, the patients re-
ceived 1 mg of dexamethasone at 11 PM and blood was drawn at 4 PM the next day. Nonsuppression was considered to occur when plasma cortisol levels were greater than 4 ttg/di after drag administration (Dratcu and Calil 1989; Frochtengarten et al. 1987). Plasma cortisol was determined in duplicate by radioimmunoassay (Diagnostic Products Corporation, Los Angeles, CA). A total of 93 psychiatric inpatients were submitred ,~ the DST at admission and discharge. Table 1 shows the number and percentage of nonsuppresso|~, ~¢,~ording to the psychiatric diagnosis, indicating the relatively low specificity of DST in identifying endogenous depressive patients. It can also be seen that hospitalization reduced the number of nonsupgessors. However, this reduction was not merely a result of the normalization of the DST from admission, but it was also noted that 10 patients became nonsuppressor$ only at discharge. In only 4 of these patients could the switch to non-
Correspondence
Table 1. RDC
Diagnosis and
BIOL PSYCHIATRY 1990;27:671--685
679
DST Nonsuppression on Admission and at Discharge from Hospital Number (and %) of DST nonsuppression
Number of possible positive nonsuppression
R I ~ diagnoses
N
Admission
DLscUarge
Admission
Discharge
primary endogenous major depressive order agitated retarded Schizophrenia Schizo-affective disorder manic type depressive type Mania bipolar non bipolar Bfiquet's disorder Alcoholism Drug use disorder Others (organic disorders) Total
22
9 (40.9%)
4 (18.2%)
7
2
7 16 5 1 0 1 10 4 6 5 35 2 13 93 (100%)
4 (57.1%) 6 (37.5%) 2 (40.0%) 1
2 (28.6%) 3 (18.7%) 0 1
--0 0
--2 1
--
--
.
.
1 4 (40.0%) 1 (25.0%) 3 (50.0%) 1 (20.0%) I 1 (31.4%) 0 7 (53.8%) 35 (37.3%)
suppression be explained, as they received anticonvulsant therapy during hospitalization. Among 35 nonsuppressors at admission (Table 1), 16 had other conditions associated with false-positive results, such as weight loss and hypertension. Seven out of 9 suppressor depressive patients at admission also had these associated pathologies as confounding variables.
.
1 2 (20.0%) (~ " (33.3%) 1 (20.0%J 9 (25.7%) 0 7 (53.8%) 24 (25.8%)
.
2 --0 a -3 ~6 (45.7%)
2 --1 7 -4 19 (54.3%)
In another group of 166 psychiatric patients evaluated only at admission, 71 (42.7%) had nonsuppression to DST. However, 32 out of the 71 could be attributed to other factors leading to nonsuppression, the most common ones being weight loss and hypertension. Table 2 indicates that among primary major depressive patients, 14 out of 20 (70%) were nonsuppressors, though other conf3unding variables
Table 2. R I ~ Diagnoses and DST Nonsuppression Only at Admission to or Discharge from Hospital Number of patients (N) and number (and %) of DST nonsuppressors at admission only
Number of patients (N) and number (a.~d %) of DST nonsuppressors at discharge only N
Nonsuppressors
14 (70.0%)
7
3 (42.8%)
10 (83.3%) 4 (40.0%) ! (9. I%) 2 (28.6%) I (25.0%) I (33.3%) 6 (33.3%) 3 (42.8%) 3 (27.3%) 6 (35.3%) 22 (46.8%) 10 (52.6%) 11 (40.7%) 71 (42.7%)
1 6 1 ---
I 2 (33.3%) 0
8 2 6 I 16 4 6 43 (100%)
I (12.5%) 0 1 (16.6%) 1 5 (31.2%) 0
RDC diagnosis
N
Nonsuppressors
Primary endogenous major depressive disorder agitated retarded Schizophrenia Schizo-affective disorder manic type depressive type Mania bipolar I non bipolar Bfiquet's disorder Alcoholism Drug ~se disorder Others (organic disorders) Total
20 12 10 11 7 4 3 18 7 11 17 47 19 27 166 (100%)
3 (50.0%)
13 (3O.2%)
680
Correspondence
BIOL PSYCHIATRY 1990;27:671-685
were present in 10 of these cases. As can be seen in Table 2, the percentages of nonsuppression were lower for other psychiatric diagnoses. In summary, in the present study 106 out of 259 (40.9%) consecutive patients admitted in a Brazilian Psychiatric Hospital were nonsuppressors to DST. Depression (54.7%), drug use (47.6%), other medical disorders (43.6%), and alcoholism (41.5%) were the most prevalent diagnoses associated with nonsuppression. However, taking into consideration all factors interfering with DST, 46.2% of nonsuppressors could be false-positives, whereas in 17 out of 23 nonsuppressor depressive patients these variables could also explain test results. In conclusion, in view of the poor living conditions of our population, the deficiencies of the health care system, and widespread use of medications with poor medical supervision, the DST should be used cautiously, if ever, in Brazil and other third world ce~ntries. Florence Kerr t E.A. Carlini t Carol Sonenreich 2
tDepartamento de Psicobiologia Escola Paulista de Medicina Silo Paulo, Brazil 2Hospital do Servidor Ptiblico Federal Silo Paulo, Brazil
References American Psychia~c Association (1987): The dexamethasone suppression test: an overview of its current status in psychiatry. Am J Psychiatry 144:1253-1262. Anma GW, Baldessarini RJ, Omsteen M (I98:~): The ~xamethasone suppressiontest for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 42:1193-1204. Avery DH, Osgood T, Ishiki DM, Wilson I.G, Keuny M, Dunner DL (1985): The DST in psychiatric outpatients with generalized anxiety disorder, panic disorder, or primary affective disorder. Am J Psychiatry 142:844848. Carroll BJ (1985): Dexamethasone suppression test: a reviewof contemporaryconfusion.J ¢lin Psychiatry 46:1324. Carroll BJ (1986): Informed use of the dexamethasone suppression test. J Clin Psychiatry 47 (suppl 1): 10-12. Carroll BJ, Feinberg M, Greden JF, Tarika J, Albala AA, Haskett RF, James NMcl, Kronfol Z, Lohr N, Steiner M, de Vigne JP, Young E (1981): A specific laboratory test for the diagnosis of melancholia. 3tandardization, velidafio~t,and clinicalutility.Arch Gun Psychiatry 38:1522. Dratcu L, Calil HM (1989): The dexa~thasone suppression test: its relationshipto diagnoses, severityof depression, and response to treatment. Prog Neuropsychoplmrmacol Biol Psychiatry 13:99-117. Frochtengarten ML, Villares JCB, Maluf E, Carlini EA (1987): Depressive symptoms and the dexammhasone suppression test in parkinsonian patients. Biol Psychia. try 22:386--389. Kraus RP, Gmf P, Brown GM (1988): Drugs and the DST: need f~r a reappraisal. Am J Psychiatry 145:666-674.
1his work was partially financed by Fundacio de Amparo i Pesquisa de S~o Paqlo (FAPESP) and Associ~AoFundo de Incentivo ~ Psicofarmacologia (AFIP).
Verapamil in Stuttering To the Editor: R has been difficult to find pharmacological treatments of chronic stuttering in adults that are both effective and without intolerable side effects (Ingham 1984). Zach~L~ab (1980) reported promising results with the calcium channel-blocker verapamil. However, this study had major methodological limitations (e.g., a single-blind trial with no objective speech data). We carried out a double-blind, placebo-con-
trolled trial of verapamil in a cross-over experimental design with multiple, objective measures of stuttering severity. As we repoi~ed in this journal (1989), verapamil was found to be significantly more effective than placebo in 2 of 4 speech measures in this brief (l-week) trial. At a 6-month follow-up, only 2 of the original l0 patients were still taking the drag. However, both of these patients reported that their speech continued to be substantially improved. Recently we completed a 2 l/2-year follow-up of these 2 patients. Both are still taking verapamil (180-
BIOLPSYCHIATRY 1990;27:671--685
Correspondence
nergic neuronal and endocrine systems. Peptides 3:353395. Pique L, Jegou S, Bcrmgna X, Javoy-Agid F, Seurin D, Proeschel MF, Gkm"dF, Agid Y, Vaudry H, Luton JP (1985): Pro-opiomelanocortinpeptides in the human hypothalamus: comparativestudy between normal subjects and Parkinson patients. Neurosci Lett 54:141-146. Reuven Sandyk Pochi PE, Strauss JS (1974): Endocrinologic control of the developmentand activityof the human sebaceous gland. Department of Psychiatry J Invest Dermatol 62:191-197. Albert Einstein College of Medicine Rainem I, Kaye JA, May C, Durso R, Katz DI, Albert ML, Montefiore Medical Center Wolfe N, Pinessi L, FriedlandRP, Rapoport SU (1988): Bronx, NY 10461 Alpha-melanocyte-stimulating hormonelike immunoreactivity is increased in cerebrospinal fluid of patients with Parkinson's disease. Arch Neurol 45:1224-1227. Rainero I, May C, Kaye JA, Friedland RP, Rapoport Sl References (1988): CSF alpha-MSHin dementia of the Alzheimer's type. Neurology 38:1281-1284. Antun-Tay F, Diaz JL, Femandez-GuardiolaA (R~/l): On the effect of melatonin upon human brain. Its possib'~e Sandyk R (1989): Alpha-melanocytestimulating hormone (MSH) in Tourette's syndrome, lnt J Neurosci 44:161therapeutic implications. Life $ci 10:841-850. 164. Carter RJ, Shuster S (1977): Melanocyte-stimula~inghot. Sandyk R (1989): Neuroleptic-inducedakathisia: a role for mone-mimetic action of the phenothiazines. J Pharm MSH peptides. Psychopharmacology 99:134-135. Pharmac Mo130:233-235. Cotzias C, Van Weert MI-I, Schiffer LM (1967): Aromatic Thody AJ (1977): The significance of melanocyte-stimulating hormone(MSH) and the control of its secretion in amino acids and modificationsof parkinsonism.N/~gl the mammal. In Harper NJ, Simmonds AB (eds), Adv J Med 276:374-379. in Drug Research, vol. 1I. London: Academic Press, O'Donohue TL, Dorsa DM (1982): The opiomelanotmphipp. 24-74. pears that further research into the role of pro-opiomelanocortin (POMC)--derived peptides and the effect of neuroleptics on their release and possibly action may prove valuable in further understanding of TD and other drag-induced movement disorders.
Dexamethasone Suppression Test in Brazil To the Editor: The dexamethasone suppression test (DST) has been proposed as a biological aid in the diagnosis of endogenous depressive disorders (Arana et al. 1985; Carroll 1981). However, it lacks specificity (APA 1987; Avery et al. 1985), because numerous other conditions exist that may yield false-positive results (Carroll 1986; Kraus et al. 1988). Carroll (1985), for example, has pointed out that 20% of all inpatients should be excluded due to other possible causes of nonsuppression to DST. A study was undertaken in a psychiatric ward of a public hospital in Sao Paulo City, where 259 consecutively admitted inpatients were diagnosed through the RDC and submitted to the DST 2,~-36 hr after admission and/or at discharge. After obtaining informed consent, the patients re-
ceived 1 mg of dexamethasone at 11 PM and blood was drawn at 4 PM the next day. Nonsuppression was considered to occur when plasma cortisol levels were greater than 4 ttg/di after drag administration (Dratcu and Calil 1989; Frochtengarten et al. 1987). Plasma cortisol was determined in duplicate by radioimmunoassay (Diagnostic Products Corporation, Los Angeles, CA). A total of 93 psychiatric inpatients were submitred ,~ the DST at admission and discharge. Table 1 shows the number and percentage of nonsuppresso|~, ~¢,~ording to the psychiatric diagnosis, indicating the relatively low specificity of DST in identifying endogenous depressive patients. It can also be seen that hospitalization reduced the number of nonsupgessors. However, this reduction was not merely a result of the normalization of the DST from admission, but it was also noted that 10 patients became nonsuppressor$ only at discharge. In only 4 of these patients could the switch to non-
Correspondence
Table 1. RDC
Diagnosis and
BIOL PSYCHIATRY 1990;27:671--685
679
DST Nonsuppression on Admission and at Discharge from Hospital Number (and %) of DST nonsuppression
Number of possible positive nonsuppression
R I ~ diagnoses
N
Admission
DLscUarge
Admission
Discharge
primary endogenous major depressive order agitated retarded Schizophrenia Schizo-affective disorder manic type depressive type Mania bipolar non bipolar Bfiquet's disorder Alcoholism Drug use disorder Others (organic disorders) Total
22
9 (40.9%)
4 (18.2%)
7
2
7 16 5 1 0 1 10 4 6 5 35 2 13 93 (100%)
4 (57.1%) 6 (37.5%) 2 (40.0%) 1
2 (28.6%) 3 (18.7%) 0 1
--0 0
--2 1
--
--
.
.
1 4 (40.0%) 1 (25.0%) 3 (50.0%) 1 (20.0%) I 1 (31.4%) 0 7 (53.8%) 35 (37.3%)
suppression be explained, as they received anticonvulsant therapy during hospitalization. Among 35 nonsuppressors at admission (Table 1), 16 had other conditions associated with false-positive results, such as weight loss and hypertension. Seven out of 9 suppressor depressive patients at admission also had these associated pathologies as confounding variables.
.
1 2 (20.0%) (~ " (33.3%) 1 (20.0%J 9 (25.7%) 0 7 (53.8%) 24 (25.8%)
.
2 --0 a -3 ~6 (45.7%)
2 --1 7 -4 19 (54.3%)
In another group of 166 psychiatric patients evaluated only at admission, 71 (42.7%) had nonsuppression to DST. However, 32 out of the 71 could be attributed to other factors leading to nonsuppression, the most common ones being weight loss and hypertension. Table 2 indicates that among primary major depressive patients, 14 out of 20 (70%) were nonsuppressors, though other conf3unding variables
Table 2. R I ~ Diagnoses and DST Nonsuppression Only at Admission to or Discharge from Hospital Number of patients (N) and number (and %) of DST nonsuppressors at admission only
Number of patients (N) and number (a.~d %) of DST nonsuppressors at discharge only N
Nonsuppressors
14 (70.0%)
7
3 (42.8%)
10 (83.3%) 4 (40.0%) ! (9. I%) 2 (28.6%) I (25.0%) I (33.3%) 6 (33.3%) 3 (42.8%) 3 (27.3%) 6 (35.3%) 22 (46.8%) 10 (52.6%) 11 (40.7%) 71 (42.7%)
1 6 1 ---
I 2 (33.3%) 0
8 2 6 I 16 4 6 43 (100%)
I (12.5%) 0 1 (16.6%) 1 5 (31.2%) 0
RDC diagnosis
N
Nonsuppressors
Primary endogenous major depressive disorder agitated retarded Schizophrenia Schizo-affective disorder manic type depressive type Mania bipolar I non bipolar Bfiquet's disorder Alcoholism Drug ~se disorder Others (organic disorders) Total
20 12 10 11 7 4 3 18 7 11 17 47 19 27 166 (100%)
3 (50.0%)
13 (3O.2%)
680
Correspondence
BIOL PSYCHIATRY 1990;27:671-685
were present in 10 of these cases. As can be seen in Table 2, the percentages of nonsuppression were lower for other psychiatric diagnoses. In summary, in the present study 106 out of 259 (40.9%) consecutive patients admitted in a Brazilian Psychiatric Hospital were nonsuppressors to DST. Depression (54.7%), drug use (47.6%), other medical disorders (43.6%), and alcoholism (41.5%) were the most prevalent diagnoses associated with nonsuppression. However, taking into consideration all factors interfering with DST, 46.2% of nonsuppressors could be false-positives, whereas in 17 out of 23 nonsuppressor depressive patients these variables could also explain test results. In conclusion, in view of the poor living conditions of our population, the deficiencies of the health care system, and widespread use of medications with poor medical supervision, the DST should be used cautiously, if ever, in Brazil and other third world ce~ntries. Florence Kerr t E.A. Carlini t Carol Sonenreich 2
tDepartamento de Psicobiologia Escola Paulista de Medicina Silo Paulo, Brazil 2Hospital do Servidor Ptiblico Federal Silo Paulo, Brazil
References American Psychia~c Association (1987): The dexamethasone suppression test: an overview of its current status in psychiatry. Am J Psychiatry 144:1253-1262. Anma GW, Baldessarini RJ, Omsteen M (I98:~): The ~xamethasone suppressiontest for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 42:1193-1204. Avery DH, Osgood T, Ishiki DM, Wilson I.G, Keuny M, Dunner DL (1985): The DST in psychiatric outpatients with generalized anxiety disorder, panic disorder, or primary affective disorder. Am J Psychiatry 142:844848. Carroll BJ (1985): Dexamethasone suppression test: a reviewof contemporaryconfusion.J ¢lin Psychiatry 46:1324. Carroll BJ (1986): Informed use of the dexamethasone suppression test. J Clin Psychiatry 47 (suppl 1): 10-12. Carroll BJ, Feinberg M, Greden JF, Tarika J, Albala AA, Haskett RF, James NMcl, Kronfol Z, Lohr N, Steiner M, de Vigne JP, Young E (1981): A specific laboratory test for the diagnosis of melancholia. 3tandardization, velidafio~t,and clinicalutility.Arch Gun Psychiatry 38:1522. Dratcu L, Calil HM (1989): The dexa~thasone suppression test: its relationshipto diagnoses, severityof depression, and response to treatment. Prog Neuropsychoplmrmacol Biol Psychiatry 13:99-117. Frochtengarten ML, Villares JCB, Maluf E, Carlini EA (1987): Depressive symptoms and the dexammhasone suppression test in parkinsonian patients. Biol Psychia. try 22:386--389. Kraus RP, Gmf P, Brown GM (1988): Drugs and the DST: need f~r a reappraisal. Am J Psychiatry 145:666-674.
1his work was partially financed by Fundacio de Amparo i Pesquisa de S~o Paqlo (FAPESP) and Associ~AoFundo de Incentivo ~ Psicofarmacologia (AFIP).
Verapamil in Stuttering To the Editor: R has been difficult to find pharmacological treatments of chronic stuttering in adults that are both effective and without intolerable side effects (Ingham 1984). Zach~L~ab (1980) reported promising results with the calcium channel-blocker verapamil. However, this study had major methodological limitations (e.g., a single-blind trial with no objective speech data). We carried out a double-blind, placebo-con-
trolled trial of verapamil in a cross-over experimental design with multiple, objective measures of stuttering severity. As we repoi~ed in this journal (1989), verapamil was found to be significantly more effective than placebo in 2 of 4 speech measures in this brief (l-week) trial. At a 6-month follow-up, only 2 of the original l0 patients were still taking the drag. However, both of these patients reported that their speech continued to be substantially improved. Recently we completed a 2 l/2-year follow-up of these 2 patients. Both are still taking verapamil (180-
