20 mg of dl-pindolol. Hence, it is possible for dl-pindolol to suppress a PRL response associated with buspirone challenge, and/or to evoke a PRL response to itself after acute challenge, in some subjects, depending on the dose. Considering all available data, we suggest that the most salient differ¬ ence between the study by Meltzer et al and our study resides in the ad¬ ministration of the different doses of dl-pindolol. Meltzer et al used a sin¬ gle dose of 30 mg of dl-pindolol, while we used doses between 5 mg and 20 mg. As stated in our original article, we observed substantial suppression of the PRL response to buspirone at 10 mg in one subject and 20 mg in the other subject. In fact, if we had to choose one dose for the purpose of suppressing buspirone-induced PRL release, we would select the 10-mg dose (associated with nearly a 70% suppression of the peak buspironePRL release in each of these two sub¬ jects). Since 1-pindolol is known to be a mixed agonist-antagonist at the 5-HT-la receptor1 (d-pindolol is in¬ active in this regard), the difference between our results and those of Melt¬ zer et al probably relate to the lower doses of used in our study. Under the conditions of these exper¬ iments, lower doses of dl-pindolol are

dl-pindolol

expected to compete with buspirone

for 5-HT-la receptor sites in an an¬ tagonistic fashion and display increas¬ ingly fewer antagonistic properties as doses increase. It was because of this factor that we chose to perform a pre¬ liminary dose-response study (we did not know, a priori, which dose of dl-pindolol would exhibit predomi¬ nant 5-HT-la antagonistic effects in man). A review of animal studies2 employing 1-pindolol as a 5-HT-la re¬ ceptor agent discloses that doses of less than 0.1 to 0.03 mg/kg of 1-pin¬ dolol are associated with suppression of 5-HT-la-mediated neuroendocrine responses to 5-HT challenge, while higher doses tend to display 5-HT-la receptor agonist effects. In our pre¬ liminary study, a pindolol dose of 10 mg represents 0.07 mg of 1-pin¬ dolol while the doses in the study by Meltzer et al represent approximately 0.25 mg/kg of 1-pindolol. Hence, the study by Meltzer et al does not disprove the hypothesis that buspirone-induced PRL release is me¬ diated by 5-HT-la receptors. Rather,

it is consistent with our hypothesis that doses of dl-pindolol greater than 20 mg may not block the 5-HT-la re¬ ceptors mediating PRL release as ef¬ fectively as lower doses. The differ¬ ing results reported in our two stud¬ ies point to the difficulty of selecting a single dose for 5-HT-la receptor blockade when the agents in ques¬ tion are mixed agonist-antagonists at this site and illustrate the potential

utility of dose-finding procedures. Emil F. Coccaro, MD

Department of Psychiatry Eastern Pennsylvania Psychiatric Institute Medical College of Pennsylvania 3200 Henry Ave Philadelphia, PA 19129

evi-

Blacks, Schizophrenia,

Neuroleptic

Treatment

To the Editor.\p=m-\The reports by Van Putten et al1 and Levinson et al2 in the August 1990 issue of the Archives extend our knowledge of the appropriate dosages for neuroleptic medications in the treatment of psychotic illnesses. There are some unanswered questions that I hope the authors can address in greater detail. In both reports, the populations studied were largely black. This could provide specific answers to important treatment issues related to black patients diagnosed as schizophrenic. For instance, it has been reported that black patients respond to neuroleptic medications differently than white patients do.3 It has also been suggested that black patients may be misdiagnosed

schizophrenic

at

a

significantly

Downloaded From: by a UNIVERSITY OF ADELAIDE LIBRARY User on 05/05/2018

do.

occurs

nificant racial differences in treatment response within neuroleptic dosage groups? Were there significant racial differences in the dropout rates within dosage groups? Did the higher rate of extrapyramidal insymptoms in the higher dosage groups both reports suggest that black patients are misdiagnosed

schizophrenic when,

in

fact, they

leptic medications.5-6)

dence for a role for central 5-HT-1a receptor function in impulsive aggressive behavior in humans. Psychopharmacol Bull. 1990;29:393-405.

as

patients

may have bipolar disorders with psy¬ chotic characteristics? (A mood disor¬ der has been described as a significant risk factor in patients developing ex¬ trapyramidal symptoms from neuro¬

1. Hjorth S, Carlsson A. Is pindolol a mixed agonist/antagonist at central serotonin (5-HT) receptors? Eur J pharmacol. 1986;129:131-138. 2. Coccaro EF, Gabriel S, Siever LJ.

and

rate than white

primarily in black patients with bipolar disorders who are misdiagnosed as schizophrenic. Given these findings, were there sig-

as

Steven Gabriel, Phd Theresa Mahon Joseph Macaluso, MD Larry J. Siever, MD Bronx, NY

Buspirone challenge: preliminary

higher

Jones and Gray4 say that this

Given the rigorous design of the work done by Van Putten et al and Levinson et al, it would be useful to have answers to these questions of ra¬ cial aspects of treatment response. This may clarify those issues raised in the literature, and passed down in treat¬ ment lore, regarding the treatment of psychotically ill black patients. Stephen A. Mcleod-Bryant, MD

Department of Psychiatry

and Behavioral Sciences Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 1. Van Putten T, Marder SR, Mintz J. A controlled dose comparison of haloperidol in newly admitted schizophrenic patients. Arch Gen Psychiatry. 1990;47:754\x=req-\ 758. 2. Levinson DF, Simpson GM, Singh H, Yadalam K, Jain A, Stephanos MJ, Silver P. Fluphenazine dose, clinical response, and extrapyramidal symptoms

during acute treatment. chiatry. 1990;47:761-768. 3. Raskin

Arch Gen

Psy-

A, Crook TH. Antidepres-

sants in black and white inpatients: differential response to a controlled trial of

chlorpromazine and imipramine. Arch Gen Psychiatry. 1975;32:643-649. 4. Jones BE, Gray BA. Problems in diagnosing schizophrenia and affective disorders among blacks. Hosp Community Psychiatry. 1986;37:61-65. 5. Pearlman CA. Neuroleptic malignant syndrome: a review of the literature. J Clin Psychopharmacol. 1986; 6:257-273. 6. Nasrallah

HA, Churchill CM, Hamdan-Allanon GA. Higher frequency of neuroleptic-induced dystonia in ma-

nia than in

schizophrenia. Am J Psychia-

try. 1988;145:1455-1456.

In Reply. \p=m-\DrMcLeod-Bryant raises interesting and important questions. Of the 53 participants in our study, 26 were

white, 26

were

black, and

one

Oriental (and was omitted from the following analyses) With regard to completers and dropouts, there were fewer dropouts among blacks (nine of 35) than whites (13 of 39); and there were fewer "non-Research Diagnostic Criteria" diagnoses (ie, Research Diagnostic Criteria exclusions for substance abuse or atypical features) among blacks (11 of 33) than whites (23 of 41), a difference that neared significance (x2=3.82, P =.051). Blacks and whites did not significantly differ with regard to schizoaffective diagnoses (seven of 26 whites and six of 26 blacks), dystonic reactions, tardive dyskinesia, need for treatment for parkinsonian side effects, or achievement of 40% or greater improvement in Brief Psychiatric Rating Scale positive symptoms (hallucinatory behavior + unusual thought conwas

tent +

conceptual disorganization).

They did not differ in total dose, dosage in milligrams per kilogram, maxi¬ mum Neurological Rating Scale score

achieved

dystonic

by those who did not have

reactions, percentage of im¬

provement in positive symptoms, or percentage of change in negative symptoms. Analyzed separately, blacks and whites with 40% or greater improvement in positive symptoms

showed a linear relationship between dose and improvement in positive symptoms, as reported in the article. Data revealed that there was a trend to¬ ward black participants who were slightly less likely to develop akathisia, which was a of poor response (14 of 25 whites and seven of 17 blacks with valid ratings; 2 2.92, P= .087). Blacks did have slightly but signifi¬ cantly lower baseline ratings for posi¬ tive symptoms (i=2.275, =.027) and negative symptoms (f 2.089,

predictor

=

=

=.042).

We share Dr McLeod-Bryant's con¬ about the possibility of misdiagnosis of affective psychoses (and overdiagnosis of schizophrenia) in patients who differ greatly from the diagnosti¬ cian in culture or language. Our data do not reveal any difference in neuro¬ leptic responsiveness in black vs white cern

patients diagnosed by an experienced

research team. We agree with Dr McLeod-Bryant's implication that careful diagnostic practices are critical

Downloaded From: by a UNIVERSITY OF ADELAIDE LIBRARY User on 05/05/2018

in the research and clinical setting, and that particular vigilance is called for when racial or other differences exist. Douglas F. Levinson, MD George M. Simpson, MD

Department of Psychiatry College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute 3200 Henry Ave Philadelphia, PA 19129 Medical

Reply. —With regard to the query by Dr McLeod-Bryant about racial dif¬ In

ferences in treatment response with neuroleptics, we reanalyzed our haloperidol data (n 77; 42 blacks and 35 whites) and could not find any dif¬ ference in response between black and white patients. There were no signif¬ icant racial differences in dropout rates. The Extrapyramidal Symptom Rating Scale appeared to be the same in both groups. Theodore Van Putten, MD Stephen R. Marder, MD Jim Mintz, PhD Veterans Affairs Medical Center 11301 Wilshire Blvd Bldg 210C Los Angeles, CA 90073 =