Posted by jimmygold70 on January 25, 2002, at 1:50:04
This is from Archives of General Psychiatry - July 1982
Levodopa in Borderline Disorders
---------------------------------
To the Editor.—Many people believe
that treatment of the borderline personality disorder is neither cost-effective nor clinically effective. In fact, this disorder usually seems to be refractory to a wide range of drugs, and the patients seem to experience most of the side effects and few of the benefits of the commonly used agents.1 We have dealt with the substance-abusing population in the New York metropolitan area and, true to DSM-III criteria, encountered within it a high proportion of patients with borderline personality.
Observations of how the conditions of patients with borderline disorder respond to neuroleptic and antide-pressant agents, and observations as to abuse substances of choice (along with the patients' reasons for preferring a particular drug) suggest that these patients are self-medicators.' These factors and our clinical observations led us to suspect that many patients with borderline syndrome, especially those who exhibit symptoms of marked boredom, dysphoria, and anhedonia, might select drugs that lessen dysphoria and that increase dopaminergic function in the CNS, eg, phencyclidine hydrochlo-ride.
The close association between the dopamine and opioid-peptide systems has been noted in several central and peripheral loci.2 Lesions of the neo-striatum decrease the number of
dopamine nerve terminals as well as lessen the number of opioid receptors. Further, dopamine seems to be the tonic inhibitory regulator of release of pituitary 0-endorphin from the intermediate lobe.3
In five patients, we measured plasma 0-endorphin levels by radioimmu-noassay and found levels to be three to four times those of age-appropriate controls." We reasoned that persistently high levels of endogenous opioid release would lead to tolerance. Therefore, we speculated that augmenting the available dopamine pools within the CNS might lower the level of /3-endorphin release and possibly initiate a reversal of tolerance.
We devised a schedule of a combination of levodopa and carbidopa (Sine-met), using the experience we gained in working with Friedhoff et al in treating tardive dyskinesia by increasing dopamine availability." Patients were started on a regimen of 25 mg of levodopa with 250 mg of carbidopa once daily, increased in 25- and 250-mg increments, respectively, every three days until an optimal dosage was achieved and maintained.
Very shortly after initiating treatment (as compared with the usual time frame for response to antide-pressants), all our patients exhibited marked reduction in dysphoria and depressive ideation, and virtual disappearance of anhedonia coupled with increased amounts of meaningful socialization. Four patients virtually ceased drug-seeking behavior, and the fifth showed a marked reduction. The following is an exemplary case.
Report of a Case —A 52-year-old man had a 40-year history of feelings of emptiness, boredom, dysphoria, and anhedonia. He had a long history of impulsiveness and a 30-year history of addiction to opiates. While receiving maintenance therapy with methadone, he was able to open a business with assistance, but his feelings of dysphoria, anhedonia, and emptiness deepened to the point of suicidal ideation. Impulsiveness persisted in the areas of sex and illicit drug use, and had impaired social relationships to the point of social "phobia " He had marked shifts in mood, from inappropriate displays of anger and irritability to extreme depression. He could not care for himself or his home properly. Antidepressant medications of several types, eg, amitriptyline hydrochlo-ride (Elavil), imipramine hydrochloride (Tofranil), nortriptyline hydrochloride (Pamelor), doxepin, and maprotiline hydrochloride (Ludiomil), produced only side effects and no improvements. Blood levels of /3-endorphin (determined by radioimmunoassay) were about three times higher than normal. He was then given the combination of levodopa and
carbidopa and, after initial nausea was controlled, the severity of his symptoms decreased. He began to undergo detoxification from methadone, and as this progressed (while continuing treatment with levodopa and carbidopa), there was progressive improvement. His business is now improving. His mood is usually pleasant and he has developed friendships on an appropriate basis. He reports experiencing a level of emotional satisfaction in his sexual relationships and his abuse of drugs has diminished sharply. He can adequately care for himself and his home, and can plan for his business and future social life. His methadone detoxification is uneventful, and at this writing he receives 5 mg/ day of methadone and continues to receive 200 mg/day of levodopa.
Comment—Although this might be construed as a placebo effect, these patients' conditions did not respond to a wide variety of other psychotropic medications (although this finding^ needs to be studied further in a double-blind study).
We cannot be certain that these results are due tcTan increase in the dopamine pools, because levodopa and peripheral decarboxylase can also effect lesser increases in norepi-nephrine and secondarily produce changes in release rates of acetylcho-line and 7-aminobutyric acid.6
The only major side effect encountered to date has been nausea, which persisted in one patient and which we are attempting to counter by altering the ratio of levodopa to carbidopa.
We are now structuring a formal 'J study to differentiate those patients likely to respond, and to characterize the types of responses elicited as well as treatment-emergent effects.
KENNETH A. BONNET, PHD
Department of Psychiatry
New York University Medical Center j
New York, NY 10003
HARVEY R. REDFORD, MD
Department of Psychiatry
Downstate Medical Center
Brooklyn, NY 11203
1 Hartocollis P (ed) Borderline Personality Disorders New York, International Universitie Press, 1979.
2 Iwamoto ET, Way EL' Neurotransmitti and opioid interactions. Adv Biochem Psych pharmacol 1979,20.357-407.
3. Pryzwlocki R, Hollt V, Herz A: Modulation^ of in vitro release of beta-endorphin from the| separate lobes of the rat pituitary. Life 1979,24 1601-1607.
4. Ghazarossian V, Dent R, Otan K, et _ Development and validation of a sensitive radu immunoassay for naturally occurring beti endorphin like peptides in human blood analy cal biochemistry. 1980,102 80-89.
5 Alpert M, Friedhoff AJ, Marcos L, et Paradoxical reaction to L-dopa in schizophrenK patients Am J Psychiatry 1978,135 1329-1332.
6 Meltzer HY, Stahl SM: The dop " hypothesis of sehizophrema A review. Schizo Bull 1976,2 19-76.
poster:jimmygold70
thread:91509
URL: http://www.dr-bob.org/babble/20020124/msgs/91509.html