Low-Dose Neuroleptic Regimens in the Treatment of Borderline Patients John R.

Brinkley, MD; Bernard

D.

Beitman, MD; Robert O. Friedel,

\s=b\ The use of pharmacologic agents in treating patients described as borderline generally has been accorded an insignificant, or at best, minor, role. We discuss this observation and review the literature that has dealt with this aspect of treatment. Diagnostic criteria are presented that appear to define a specific population of borderline patients who have been observed to be responsive to low doses of neuroleptic drugs. Five case histories of patients with conditions diagnosed and treated in this manner are presented, followed by a discussion of the implications of this approach in terms of clarifying the nosologic issues that have arisen around the "borderline" concept. (Arch Gen Psychiatry 36:319-326, 1979)

borderline syndrome, both identified as such and under the myriad of other appellations that have been used as synonyms (or near-synonyms), is the focus of increasing attention in the psychiatric literature. A careful examination of this rapidly expanding corpus, however, reveals that only a relatively small portion of it is devoted specifically to treatment of patients whose conditions are diagnosed as borderline. This is illustrated by the fact that Gunderson and Singer, in their timely review of the borderline concept,1 cite only ten of their 87 bibliographic sources as treatment-oriented. This hiatus may well be an indication of a tacitly accepted pessimism regarding the efficacy of treatment in the borderline patient population, an attitude indicated directly, for example, in Dyrud's comment that "if anything is impressive in the literature on the treatment of borderline syndrome, it is that nothing seems to work very well, or for very long."2 The intent of our report is to issue a modest challenge to this pessimism. In doing so, we shall develop three major foci: (1) a review of the literature pertaining to the use of psychotropic medication in treat¬ ing borderline patients (such a review, to our knowledge, has not been done previously); (2) a description and discus¬ sion of explicit diagnostic criteria for defining a particular group of drug-responsive borderline patients; and (3) illus¬ trations of the apparent efficacy of one specific pharmaco¬ logie treatment approach to this group—viz, the use of neuroleptic medication in doses below those commonly used in the pharmacologie maintenance of schizophrenic

The

patients.

REVIEW OF THE LITERATURE

The literature devoted to treatment of borderline patients heavily reflects the fact that the "borderline" Accepted

publication Feb 24, 1978. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle (Drs Brinkley and Beitman) and the Department of Psychiatry, Medical College of Virginia, Richmond (Dr Friedel). Reprint requests to Harborview Community Mental Health Center, 326 Ninth Ave, Seattle, WA 98104 (Dr Brinkley). From the

for

MD

was initially described and discussed in a system¬ atic fashion from a psychoanalytic point of view. Indeed, most of the comprehensive efforts to address this issue have done so largely within the framework of psychoana¬ lytic psychotherapy.'"7 These discussions, either because their appearance in the literature antedated all or most of the modern developments in psychopharmacology, or perhaps, more important, for reasons of ideologic commit¬ ment, generally make no reference to the adjunctive use of medication. The exceptions tend to be nonspecific and cursory, clearly relegating pharmacological intervention to a very minor treatment role. Kernberg," for example, suggests the use of "tranquilizing medication" when a borderline patient's anxiety level reaches the point of interfering with the establishment or maintenance of a meaningful patient-therapist communication, but without making it clear whether he is referring to antianxiety agents per se or to neuroleptics. In widening the focus to include a broader spectrum of treatment and research approaches to the borderline syndrome, one encounters more frequent, but nonetheless sporadic, references to pharmacotherapy. A number of these are simply en passant allusions to the use of medica¬ tion: Schmideberg," in her discussion of treating borderline patients, stated that "sedation, sleeping drafts, and place¬ bos are often useful," and Hoch et al," describing a long-term follow-up study of outcome among a population of pseudoneurotic schizophrenic patients, mention that "many patients received some type of medication (barbitu¬ rate and amphetamine derivatives)...." (This citation is presented for the sake of completeness, in view of the frequent inclusion of pseudoneurotic schizophrenia among the grouping of "borderline disorders," as well as the direct equation, on the part of some authors, of this concept with the term "borderline syndrome." [See, for example, the discussion of such semantic issues in the review by Gunder¬ son and Singer.1 We do this with the realization that it apparently was Hoch's personally held view that the two

concept

not interchangeable.1""]) Interestingly, a number of authors who comment in a general way on the use of medication for borderline patients describe this mode of treatment variously as unnecessary, ineffectual, fraught with potential difficul¬ ties, or even contraindicated. Chessick,12 for instance,

concepts

are

asserts that

"[T]he typical administration of various psychopharmacologic to these patients often complicates the situation in many ways. They abuse the dosage instructions, and the side-effects produced by improper dosage complicate the symptom picture. agents

in

Havens" examines this specific problem and allied ones a thoughtful discussion of drug administration to

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borderline and schizophrenic patients. He notes that resistance to taking medication may stem from the patient's reaction to the drug-induced loss of psychotic symptoms that have some adaptive value, or may result from the failure of subjective benefits from the medication to match the objective improvement noted by the thera¬

pist.

An early discussion of the use of "pharmaceutic agents" in psychotherapy by Ostow14 takes a mildly negative stance in its brief mention of borderline patients: "The adminis¬ tration of an energizer alone will generally only increase the defensiveness and resistance, while the administration of a tranquilizer will accentuate the depletion." An outlook that roughly parallels this position, but followed it by ten years, is that of Dyrud,2 who remarks that

"[E]uphoriants appeal

to them

[borderline patients], though the

response may be unreliable and often paradoxical. Phenothiazines (which should theoretically help with our postulated lack of central inhibition) have in my experience yielded no improved affect; possibly they lengthen the periods of unpleasant affect, and in larger doses result in depressed behavior."

associates,17' Zetzel,1" and Aakrog17 have also expressed varying degrees of reservation with regard to psychopharmacologic intervention. Zetzel minimizes the usefulness of medications simply on the basis of her assertion that borderline patients can manifest improve¬ Last and

ment without

them, but does not elaborate. While acknowl¬

edging the usefulness of neuroleptics during periods of frank psychosis, Aakrog questions their efficacy during psychosis-free periods, based on his experience with a large population of hospitalized borderline adolescents. Last and associates, in describing a population of borderline adults (total number not specified), assert that "they were unre¬ sponsive to the influence of drug therapy,"15 without providing any further data to support this assertion. The first attempts at specifically delineating the responses of borderline patients to psychotropic drugs appeared in reports of experimental administration of various agents. Hoch and his co-workers1"1" published reports of such administration, comparing the response of various patient subpopulations (pseudoneurotic schizo¬ phrenics plus groups of overt schizophrenics representing varying degrees of symptom severity) to mescaline and LSD in

one

case, and to

amobarbital, mescaline, and

methamphetamine hydrochloride in the other. In both studies, normalization, ie, reduction or elimination of one or more base line symptoms, was never observed following mescaline administration and rarely after LSD, but often occurred with amobarbital and somewhat less frequently with methamphetamine. The pseudoneurotic group invari¬ ably showed a greater tendency toward normalization responses, and among all patients manifesting normaliza¬ tion in response to a particular drug, this group's relative degree of normalization tended to be the most pronounced. Parallel findings were described in a later report by Pennes2" describing an experimental study utilizing a similar protocol. Another perspective on borderline patients' drug responses, peripheral to actual clinical trials of pharmacotherapeutic agents, is that shared by authors who have attempted to characterize this population's self-adminis-

tration and/or "abuse" of drugs. A common view is that their nonprescribed usage represents an attempt to ameliorate their symptoms. Schick and Freedman21 aptly present this sentiment: or psychotic individuals often use drugs in extreme amounts to reinstate feelings of closeness through merger and fusion experiences, to narcotize themselves against the psychic pain they feel, and sometimes in an attempt to feel something, even if that means to feel painfully, in order to break through the

"Borderline

depths

The

of

despair and hollow, empty feelings."

same

theme is echoed

by Dyrud:2

"[A] larger

number of them [borderline adults] are self-medicators, not in the sense of recreational use of drugs necessarily, but their irregular and often excessive use of alcohol or other drugs is tied to efforts at adjusting an intolerable feeling state."

Grinker et al,1" Klein and Shader,22 and Kernberg" are among the others who have commented on this issue to varying extents. Moving to the central topic, that of therapeutic drug administration to borderline patients, one finds that avail¬ able reports focus largely on the use of neuroleptics and antidepressants, singly or in combination, with relatively infrequent mention in the literature of other types of agents. Representatives of this latter minority category are the report of Fisher and DiMino2' of using phenytoin in a case of borderline syndrome complicated by heroin addiction; the controlled study by Rifkin et al24 of the response to lithium carbonate among a population having the diagnosis of emotionally unstable character disorder (included by some within the "borderline spectrum," see, for example, Klein27' and Klein and Shader22); and a brief allusion to the usefulness of minor tranquilizers "under conditions of anticipatory anxiety" in the discussion by Klein and Davis2" of pseudoneurotic schizophrenia. Despite the fact that a number of authors have described the use of neuroleptics and/or antidepressants with borderline patients, these accounts have tended to be isolated, not linked to case reports, and at best form an elusive and tenuous thread throughout the aggregate of literature dealing with the syndrome. (Again, for purposes of completeness and perspective, "borderline" is broadly construed.) Klein, both singly and with associates, has published several commentaries within this category. He and Shader,22 for example, have attempted to delineate the drug responses of patients manifesting various syndromes subsumed under the borderline heading. They ascribe efficacy to both the neuroleptics (notably thioridazine) and lithium carbonate among patients with emotional lability, to monoamine oxidase (MAO) inhibitors among "rejectionsensitive dysphorics," and variously, to minor tranquiliz¬ ers, thymoleptics, or neuroleptics among different subtypes of borderline patients experiencing "chronic anxiety-tension states." In an earlier discussion using essentially parallel diag¬ nostic terminology, Klein and Davis2" advocated the use of MAO inhibitors in treating "hysteroid dysphorics," and recommended thioridazine for the emotionally unstable personality-with an allusion to the then-experimental use of lithium for this syndrome. They also recommended

phenothiazines "during supervening agitated depressive

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states" and antidepressants "for periods of fearful with¬ drawal and depressive rumination" in patients whose conditions are diagnosed pseudoneurotic schizophrenia. Klein partially reiterates these treatment concepts in a discussion focusing specifically on psychopharmacologic treatment of the borderline patient.25 Taking a more global view, Winkelman27 espouses the use of neuroleptics (alone or with antidepressants) in treating borderline or pseudoneurotic schizophrenic pa¬ tients for relief of such symptoms as "excessive tendencies to project, that may border on but are not, paranoia, dissociation that is handicapping, anxieties and agitations that are associated with phobia or obsession...." In much the same vein, Detre and Jarecki2* briefly note that such patients, "when given phenothiazines, abandon some of their unusual behavior patterns and become less likely to

decompensate." Our own exploration of the literature has revealed only three double-blind studies examining comparative drug responses in a subject population containing at least a subgroup falling somewhere along the borderline spec¬ trum. The first of these, reported by Vilkin,2" employed a double-blind, flexible-dose protocol in comparing the effi¬ cacy of diazepam (5 mg), trifluoperazine hydrochloride (2 mg), and a fixed-dose meprobamate/benactyzine hydro¬ chloride combination (400 and 2 mg, respectively) in reliev¬ ing symptoms (described as primarily anxiety, depression, and

insomnia)

among

a

group of 45 "chronic borderline"

patients. The drugs were administered two to four times per day, "depending on the severity of the symptoms." Each patient received all three drugs in a randomized serial sequence without an intervening washout period. Each drug was to be given for a two-week period, although in actuality this time span varied (from 2 to 21 days). It was found that diazepam produced significantly "better" symptom relief in this group than did trifluoperazine, and also was more effective than the meprobamate/benacty¬ zine combination, though with only marginal significance. Major difficulties in assessing this report are the wide variability of the actual treatment periods, and the fact that neither are diagnostic criteria and outcome measure¬ ments used in the study described, nor was a placebo group

utilized. The second study was carried out by Klein,30 and compared the effects of placebo, chlorpromazine (begin¬ ning with 300 mg/day and increasing in defined incre¬ ments to a maintenance level of 1,200 mg/day) with procyclidine hydrochloride added in a dose equal to 1.25% of the chlorpromazine dose, up to 15 mg maximum, and imipramine hydrochloride (beginning with 75 mg/day and increasing in defined increments to a maintenance level of 300 mg/day). The drugs were given in liquid form and were administered in a randomized, double-blind fashion for a total period of six weeks, the maximum dosage level being attained at the beginning of the fourth week. The study populations of two separate but essentially equivalent investigations were combined for the statistical analysis, to provide a total of 311 patients who were hospitalized for the duration of the study. Diagnostically, the group repre¬ sented a spectrum including schizophrenic, affective, characterologic, and phobic-anxiety reactive disorders. In-

eluded

was a subgroup of 32 patients whose conditions diagnosed as pseudoneurotic schizophrenia on the basis of criteria that are described in a general fashion in the article (absence of Kraepelinian signs of schizophrenia, but clinical manifestation of "massive anxiety, obsessivecompulsive adaptations, somatic preoccupations, anhedonia, and frequent agitation to the point that they appeared psychotic"). Klein found that imipramine, but not chlorpromazine, produced significant overall improvement among the pseu¬ doneurotic schizophrenic subjects, compared with placebo, as determined by global outcome ratings assigned indepen¬ dently by two or three different raters on a scale of —9 to + 9. However, the chlorpromazine-placebo difference in positive response was significant for the specific symptom of agitated depression within this group. It should be noted that the drug responses of the pseudoneurotic schizophren¬ ic patients constituted one set of data among a number of others generated in the course of Klein's investigation and was not the primary focus of the study. More recently, Hedberg et al" reported a double-blind, crossover study comparing the responses of a group of 96 schizophrenic patients, including 28 diagnosed as "pseu¬ doneurotic" (diagnostic criteria not given), to trifluopera¬ zine, tranylcypromine sulfate, and a combination of the two drugs. Dosages were increased on a fixed incremental schedule, beginning with 8 mg of trifluoperazine hydro¬ chloride per day and adjusted upward until either a dosage of 32 mg/day was achieved or side effects (or improve¬ ment) ensued. In a similar fashion, the dosage of tranylcy¬ promine sulfate ranged between 20 and 30 mg/day. Each drug was given for eight consecutive weeks, with no washout period prior to beginning administration of a new drug. Outcomes were assessed through both observer ratings of global improvement employing the MinnesotaHartford Personality Assay, and subjects' self-ratings (using Minnesota Multiphasic Personality Inventory), with ratings scheduled every four weeks during the study. Contrary to the investigators' expectations, they found that a significantly higher percentage of the pseudoneu¬ rotic group responded best to the tranylcypromine alone, rather than to the other two regimens. This result was in marked contrast to the response pattern for the subjects as a whole, for whom the lowest percentage of positive responses was to tranylcypromine alone. Criticisms of this study include, again, the lack of stated diagnostic criteria, a fixed treatment schedule, and the use of rating scales not specifically designed to evaluate

were

borderline symptoms. The last two of these criticisms also apply to Klein's study. In none of the reports was there specific discussion of subject compliance with the drug regimens or of the occurrence of side effects (although Hedberg et al did note a decreased incidence of side effects when the two agents were given in combination,31 and noncompliance was obviated in Klein's study through the use of liquid-form medication and placebo3"). In terms of our own treatment methods, it also should be noted that the majority of the patients in the three studies were maintained on neurolep¬ tic dosages above what generally would be considered a "low" range.

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appropriate transition to the remaining discus¬ conclude this review with an acknowledgment of sion, Mandell's prevenient comments regarding use of low doses of neuroleptics in treating borderline patients.32 In a reflective discussion of drug treatment initiated within the context of psychoanalytic psychotherapy, he suggests the potential usefulness of "low dosage, high potency fluorinated phenothiazines" as a "stabilizing force" in minimiz¬ ing the potential risks of long-term, intensive therapy with such patients, illustrating this with a brief case report. In a recent (and less formal) article,33 he again alludes to this notion, specifically mentioning the prescribing of low doses of neuroleptics to a borderline patient "to tighten up his associations." As

an

we

SUBJECTS AND METHODS The impetus for these case reports was derived from a number of earlier observations made independently by each of the authors that there were certain patients, whom we labeled as borderline, who showed improvement in a number of areas of symptomatolo¬ gy when given low doses of neuroleptic drugs. Discussion of this shared observation underscored the obvious need for explicit diagnostic criteria if there were to be any kind of meaningful description of these findings, and if a subsequent prospective investigation were to be pursued. The diagnostic criteria that we chose to employ are the following: 1. The occurrence or the history of regressive psychotic symp¬ toms, frequently of a paranoid quality and including some loose¬ ness of associations, thought blocking, impairment of reality testing, and disturbed states of consciousness, all of which are stress-related, reversible, transient, ego alien, and unsystematized. 2. An affective state characterized by the prominence of anger and/or depression, plus varying degrees of prolonged anxiety and anhedonia. 3. Behavior the result of which is self-destructive, although the intent may not be, such as sexual promiscuity, self-mutilation, addiction, job quitting, and repeated suicidal gestures and threats. 4. Interpersonal relationships characterized for the most part by superficiality and transiency, but with a tendency also to form

intense, clinging relationships.

5. A psychiatric illness of at least two years' duration with no preexisting psychiatric conditions such as schizophrenia and affec¬ tive disorders, as defined by rigorous research criteria (eg, those of

Feighner

et

al").

The close resemblance of these criteria to those formulated by Gunderson and Singer1 is by no means coincidental, since we view as essentially tautological the assertion that utilization of a common diagnostic framework is necessary if comparison of subsequent clinical or research data is to have meaning. The differences that do exist reflect alteration of form and emphasis as well as content. The dissociation between performance on structured and unstructured psychological tests noted by Gunder¬ son and Singer has not been found to be consistently useful in defining this patient population in our experience, and therefore has been omitted. In addition, the reported discrepancy between the expected level of social adaptiveness and that actually obtained also was not utilized, because of the difficulty in formu¬ lating this possibly valid criterion in an operational form. Finally, criterion 5 was added to provide what we consider to be a necessary exclusionary "sieve." The case reports that follow were drawn from among our patients who both retrospectively met the above diagnostic crite¬ ria for borderline syndrome, and were observed to consistently

a positive response to the administration of low-dose neuro¬ leptics, prescribed on the basis of a "borderline" diagnosis made prior to our utilization of the criteria presented here. We were unable to identify another group of patients meeting these criteria who experienced a similar therapeutic response to any other class of psychopharmacologic agents. It should be empha¬ sized that the cases presented are illustrative of a consistently observed therapeutic response, rather than merely representing any unique feature limited to the five of them. Also worth noting is the common finding among these patients of other diagnoses given during prior courses of treatment, without a demonstrable basis for such labeling. These would appear to have been "diagnoses of desperation," ie, the outcome of efforts to generate some semblance, albeit incomplete, of an encapsulated clinical perspective on the patients' dysfunction. Unfortunately, it seems to be the case among this population of patients that these frequently rapid shifts in "perspective" gener¬ ally produce negligible enhancement of treatment outcome. Case l.-A 44-year-old woman first came to the attention of one of the authors when she was admitted to the inpatient service of a mental health center after having been ejected from the center's day treatment program for striking one of the counselors. The patient had become increasingly angry with the program, had come to dominate meetings there, and would often become unreasonable as her anger reached a fever pitch. Outbursts of anger were common experiences in her life and seem to have been present since she was an early adolescent, when she would scream uncontrollably at her mother. On one occasion, she beat her mother severely enough for her to require hospitali¬ zation. Her life since then had been characterized by unstable interpersonal relationships that were often distant but sometimes greatly dependent. She had attempted suicide three times, had many episodes of violent speech and behavior, and experienced multiple physical complaints. The patient had not worked for ten years and previously had not been able to hold a job for more than a few months. Her frequent visits to mental health professionals had resulted in at least three hospitalizations for depression and a number of diagnostic labels, including hysterical personality, unstable personality, and depressive neurosis. During the initial interviews, the patient appeared to have some paranoid delusions about her family and other people in her life. When she became angry in the interviews, she demonstrated an obvious thought disorder and consequent loss of reason. Her admission to the ward required that she take an antipsychotic medication. On the second day of therapy with haloperidol, 3 mg orally three times a day, she was remarkably lucid and free of anger; she began to plan a clear and practical future for herself. On the third day, she complained of an inability to think and an inability to feel her anger; she refused to take the medication any more and shortly thereafter left the hospital. Two weeks later, she asked to be readmitted to the unit, complaining that she was lonely and had nothing to do. A regimen of low doses of perphenazine, starting with 2 mg at night and increased slowly to 6 mg at night, was begun. She found herself able to control most of her angry outbursts and was discharged to the medication clinic of the university outpatient department. Here she was seen by a strong but empathie woman psychiatrist who had been appraised of the patient's past history and to whom it was suggested that a higher dose of medication was needed. Under the stern direction of this therapist, the patient reached a dosage of 16 mg of perphenazine each day and maintained that dosage. She continued to protest and complain, but these displays diminished in intensity; she realized that she now had control of herself and could utilize her intelligence in more productive ways. Six months after discharge from the hospital, she had been working three months and had returned to school. When the therapist moved to another setting, the patient quit

show

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her job but continued in school. At present, she remains suscepti¬ ble to fears of rejection, but no longer becomes angry and mildly psychotic as a result. Instead, she complains in an appropriate manner and receives the appropriate help without difficulty. In addition, after years of feeling isolated from and angry toward her immediate family, she attempted to engage them in family therapy with her. While she will probably not be able to make major personality changes because she has for so many years been trapped by uncontrollable episodes of anger, she is moving halt¬ ingly in a constructive direction. Case 2.-This patient is a 37-year-old woman with a ten-year history of brief psychotic episodes during which she heard voices and became terribly frightened, and for which she needed at least ten hospitalizations. She has attempted suicide at least three times during periods of intense depression. She had been in once-a-week psychoanalytically oriented psychotherapy over the past year, during one six-week period of which she was placed on a regimen of 150 mg/day of amitriptyline hydrochloride. She reported some improvement in her feeling state, but her therapist discontinued it, stating, according to the patient, that she would begin to ignore her problems and not come to understand them. She had seen at least six other psychiatrists over the ten-year period; each had tried psychotherapy alone, which did not remove her symptoms nor appear to prevent hospitalizations. Her husband became frustrated with "talking" therapies and took her to the psychopharmacology section of the university outpatient department, asking for medication for his wife. She was clearly quite dependent on him, turning to him for the structure in her life. Otherwise, she had few and superficial contacts with other people outside her family. During the first few interviews, before medication was started, the patient was highly emotional, was easily distracted, rambled from subject to subject, and often apologized for her poor memory. A regimen of thiothixene at low doses, first 5 mg one hour before bedtime, then 10 mg, was begun. After one month of treatment, she was no longer vague and easily distracted. She began to make plans for her future, talked about problems with her children, and began to wonder whether she should not take more medication; she was feeling good and wanted to feel even better. The therapist suggested that she was simply feeling more normal, but that the difference between her old state and her current state represented a substantial change. He cautioned her about future problems with her children and her husband that were subsequently talked about in once-monthly meetings of 30 minutes. After six months, this quiet, distant woman was coming to understand that people sometimes made her angry and that if she expressed that anger when it occurred, she and the other person were often better for it. She began to take classes in preparation for future training in interior decorating. One year later, she decided to discontinue her medication. Three weeks later, her initial symptoms began to return. After resuming

her medication, she resumed her excellent level of functioning. Case 3.-The patient is a 37-year-old married woman who had the recent onset of thoughts that people were scheming to cause her harm, difficulty in "pulling" her thoughts together, marked irritability, and a severe decrease in mood. She had a long history of emotional disturbances dating back to childhood, consisting predominantly of periods of considerable diffuse anger, irritabili¬ ty, depressed mood, and self-destructive acts such as wrist-cutting and drug overdosage requiring hospitalization on at least three different occasions. Each such episode appeared to have been precipitated by some rather modest situational disturbance. Over the years, she had received a number of psychiatric diagnoses including situational adjustment reaction, antisocial personality disorder, affective disorder, and schizophrenia. There was no family history of psychiatric illness. The following therapeutic measures had been tried without significant beneficial effect:

insight-oriented and supportive psychotherapy, electroconvulsive therapy, and all major classes of psychotherapeutic drugs. A regimen of doxepin hydrochloride, 75 mg at bedtime, was begun and after several days, experienced some relief of her symptoms of depression, but not her persecutory delusions or thought "slippage." She then experienced a relapse, with an increase in delusional ideation. The doxepin was discontinued and thiothixene, 2 mg three times a day, was started. Within five days, the delusional material was absent, she was sleeping better and thinking more coherently, was much less depressed, and could return to work. This response continued for several weeks, at which time the patient complained of discomfort in her knees and generalized body restlessness. The thiothixene dose was reduced to 2 mg twice a day, with a subsequent decrease in these side effects. She continues to have occasional episodes of depression, usually triggered by her marital problems, but has not lapsed into a psychotic episode requiring hospitalization. She continues to work and to engage in weekly supportive psychotherapy. Case 4.—A 34-year-old mother of two, separated from her husband of nine years, appeared for an intake evaluation at the outpatient clinic of a university-affiliated psychiatric service. Her chief complaint at that time was anxiety that was almost contin¬ ually present, although with wide variations in intensity, and that frequently was accompanied by episodes of hyperventilation. She also described herself as "often sad" (she had been hospitalized twice in the preceding 14 years for "depression and anxiety," in addition to a hospitalization resulting from "crying, screaming, and breaking things"), and afflicted by a number of other recurring symptoms, including severe headaches, insomnia, and generalized weakness. Her heterosexual relationships had been universally unsatisfying for her; her behavior in these relation¬ ships manifested the conflict between strong dependency needs on

the one hand and considerable ambivalence and anger on the other. Masochistic tendencies were present in her interactions with males from childhood on, and her involvement in ongoing relationships frequently began on a totally impulsive basis, with¬ out apparent integration of her previously self-destructive experi¬ ences in such relationships. She had received outpatient psychiat¬ ric treatment on a number of occasions in the past without much apparent benefit. Various medications in almost every category of psychotropic agents had been prescribed for her at one time or another, with a uniform production of side effects that she found intolerable and a general absence of positive results. The seemingly sole exception to this pattern was diazepam, which she had been taking intermit¬ tently for almost ten years. The diazepam provided some, although not complete, relief of her anxiety and produced no serious side effects. Shortly after her intake, she was seen for a medication evaluation and the diazepam regimen was replaced with oxazepam. This produced essentially the same kind and degree of effect as the diazepam, and she continued taking it. During the next year and a half, she was seen for individual therapy and for periodic renewal of her oxazepam prescription. Her therapist provided emotional support during this period and at the same time attempted to assist the patient in examining her pronounced affective lability, her dependency needs, her maladaptive interpersonal behavior patterns (especially with males), and her anxiety. When a chart review revealed her long-term benzodiazepine regimen, she was referred to one of the authors for réévaluation. During the course of the reassessment interview, the patient did, in fact, manifest some of the behavior that had led in the past to her condition being repeatedly diagnosed as an hysterical person¬ ality disorder. However, more striking was the tangential and loosely associative quality of her verbal style, suggestive of an underlying thought disorder. She acknowledged that others not infrequently told her they had difficulty following her train of

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thought in conversations, and that this was a long-standing phenomenon, antedating any psychiatric treatment. On this basis, the oxazepam (of which she had been taking up to 75 mg/day for even partial relief of her symptoms) was discontinued, and perphenazine, 4 mg twice a day, was substituted. Since then, she has reported considerable, constant attenuation of her anxiety, with complete absence of hyperventilation episodes, gradual alle¬ viation of her insomnia, and absence of headaches. She has reentered a local college and is doing well. In addition to these manifestations of improvement, the verbal signs of thought disorder rapidly diminished and then became absent altogether after initiation of the perphenazine regimen. The seemingly specific reversal of low-grade cognitive dysfunc¬ tion, as in this case, has been a consistent and impressive finding in our experience with low-dose neuroleptics among the borderline patients we have treated. The sensitivity of this dysfunction to neuroleptics is the basis for the low-dose aspect of our approach, even though the improvement in other areas of symptoms (eg, behavioral dyscontrol) may require somewhat higher dosages. In fact, in the clinical setting supervised by one of the authors, a drug commonly used in the successful treatment of such patients is 0.25 mg of fluphenazine hydrochloride given as a single-tablet bedtime dose. Case 5.—A 44-year-old married (four times divorced) woman, on admission to an outpatient clinic, complained of anxiety, amount¬ ing to phobic proportions, when with groups of people, depression and a preoccupation with dying, dissatisfaction with her current marriage, and a uniformly maladaptive style of interacting (alter¬ nating between hostility and overdependence) in the few relation¬ ships she had been able to establish. She also described many vague physical problems, for which she frequently sought medical intervention. Her previous psychiatric outpatient treatment had been limited to a single visit to a therapist in private practice, but she had been hospitalized twice for acute alcohol abuse related to episodes of anxiety. As a substitute for alcohol, she had been taking oxazepam in doses up to 90 mg/day on an intermittent basis the previous two years. The effect of the drug was only partially satisfactory, and had not enabled her to make any significant changes in her behavior pattern. For the next three years, her condition was maintained on a variety of antianxiety medications, including oxazepam, chlordiazepoxide hydrochloride, and hydroxyzine hydrochloride. During this period of time, she was sporadically involved in individual therapy, experienced moderate reduction in her interpersonal symptoms, and was able to make some positive changes in her life situation. She was referred for a medications evaluation because of her chronic use of antianxiety agents. During the interview with the physician supervising the medication clinic, she manifested a high degree of unfocused somatic preoccupation and described an incessant sense of anxiety that was only modestly reduced by the medication. She also displayed a tendency to wander from the topic of discussion, to lose her train of thought, and to reply to questions with an answer not exactly appropriate to what had been asked. The fact that she frequently experienced having her mind "blank out," and found that often people engaged in conversation with her had difficulty understanding what she was trying to express, also was elicited. On the basis of this interview, the decision was made to discontinue her then-current medication (hydroxyzine) and to begin a low dose of a neuroleptic. Thioridazine, 25 mg at bedtime, was prescribed, and she began taking it without experiencing any side effects. Over the next 3Vz months, she reported a considerable improvement in, and stabilization of, her mood, amelioration of her sleep pattern, a vast reduction in her chronic anxiety, and a noticeable improvement in both her concentration and her ability

to "think

clearly."

She continued to take thioridazine for nearly a year, but began expressing concern about a progressive weight gain that she attributed to the drug. This ultimately resulted in her discontinu¬ ing the neuroleptic regimen. In its place, she began taking clorazepate dipotassium, 22.5 mg daily, which she obtained from her primary physician. Although the clorazepate did provide an antianxiety effect comparable to that produced by the thiorida¬ zine, she noticed a gradual return of the deficits in attention, thought, and verbal expression described above. She returned to the medication clinic and fluphenazine hydrochloride, 0.25 mg to be taken at bedtime, was prescribed. After taking the drug for less than a week, she noted a considerable increase in her motivation

However, she also began to experience a degree of postawakening "drug hangover," as she termed it, that was intolerable. Altering the time at which the medication was taken provided no relief. Subsequently, fluphenazine therapy was discontinued and perphenazine, 2 mg daily, was substituted. Her response to the latter was highly satisfactory, with a degree of symptom relief equalling that produced by thioridazine. Eight months later, she discontinued the perphenazine because she questioned the need to take it on a regular basis. Within two weeks, she had begun to experience what she described as and energy.

"continual nervousness," and returned to the medication clinic for réévaluation. Questioning revealed that the "nervousness" consisted of deficits in concentration and cognitive associative functioning, and her clinical presentation paralleled what had been observed during the initial evaluation. She agreed to begin the perphenazine regimen again, and subsequently reported that within a week, her symptoms had remitted completely.

COMMENT

We have found

dosage titration to be a crucial aspect of population, even within the lower range of dosages, since the margin between compli¬

neuroleptic

treatment in this

cation-free amelioration of symptoms and onset of multi¬ ple side effects is frequently small. Because the occurrence of drug-induced sedation seems to be particularly objec¬ tionable to most of these patients, we share the preference of Mandell32 for the higher-potency agents. We have also observed that the neuroleptics that seem to have activating properties, such as thiothixene, trifluoperazine, and fluphenazine, appear to be more useful than those that do not. This is not surprising, since depression is such a common feature of the clinical picture presented by these

patients.

Another aspect of this form of intervention that pharmacological treatment of schizophrenic patients is the utility of permitting selfadministration of medication on an as-needed basis by certain patients. This mode of utilizing the drug can represent considerably more than a mere compromise designed to provide some pharmacologie benefit to a patient who is resistant, for whatever reasons, to the notion of taking "pills": it can provide a basis for the patient's gaining clearer insight into the impact of the external environment on his or her degree of psychologic function, since the ability to stabilize this functioning capacity (ie, through the titrating use of neuroleptics) entails the responsibility for monitoring and anticipating stress-induced changes in function. This is an individual¬ ized issue, since some patients are better able to tolerate and/or benefit from a regular schedule of medication contrasts with the usual

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intake. Nonetheless, it is a feature of treating these patients that deserves mention. It is important to emphasize that we do not view the prescribing of low-dose neuroleptic drugs as an all-inclu¬ sive approach to the treatment of borderline patients. Rather, we ascribe an important supportive role to these agents, since they seem to serve as predictably stabilizing adjuncts to the psychotherapeutic treatment of this patient population, providing an improvement of reality testing and other functions that enables such a patient to utilize psychotherapy more effectively. We are not assuming that these diagnostic criteria include all patients who, under various labels and by various authors, have been consigned to the borderline category. A striking aspect of reviewing the literature concerned with various aspects of the borderline syndrome is the prevalence of a tacit assumption that the term borderline denotes a definable, homogeneous group of individuals. Countering this tendency has been the move¬ ment, rooted in a variety of conceptual frameworks, toward dissecting out of this conglomeration various characterizable subgroups, viewed as representing portions of the overall spectrum. Examples of this approach include the efforts of Grinker and associates,1" Dickes,35 Frosch,3" and Klein and Shader.22 A degree of indirect support for this latter approach is provided by the widely divergent outcomes of the three double-blind drug studies cited above, since a parsimonious explanation of the seemingly conflicting results would be that nosologically distinguish¬ able patient populations were utilized. Our own position is devoid of any implicit null hypothesis that favors either side on this issue, since foreseeable investigations would affect only the constitution of the grouping defined by our criteria. Hence, we avoid one of the criticisms directed by Sidley37 at the criteria of Gunderson and Singer.1 He also argues that application of their criteria is hampered by the dependence on historical data that must be elicited by interview. This is a characteristic shared by our criteria, as is the fact that, as Sidley notes, the criteria intrinsically lend themselves to continuum, rather than to dichotomous judgments regarding their presence in a particular case, ie, some of the proposed characteristics may be present to some degree, rather than simply being present or absent. He further maintains that outcome homogeneity, not homogeneity related to diagnos¬ tic criteria, is the ultimate test of a diagnostic category. Our reaction to these criticisms is reflected in Gunderson's reply.38 While acknowledging the nondichotomous aspect of the criteria and the dependence on historical data, he asserts that the use of such indices may well

provide

"a better

source

for

prognosis than

...

sign

or

symptom data alone." With respect to the third point, he cautions against uncritical acceptance of the superiority of

homogeneity as a validating mechanism, citing etiologic homogeneity as a viable alternative and asserting that, in any event, neither kind of homogeneity can be established unequivocally at present. Blumenthal33 has addressed these issues capably in the context of similar problems encountered in the diagnosis of depression. There is merit, and a degree of common ground, in both views, and we see them as integrable, yielding a synthesis outcome

that is implicit in our own view of how one might proceed in defining borderline patients. A useful analogy is the process of "grinding" a mirror to be used in a reflecting telescope. One begins with two glass "blanks," disks with planar surfaces, introduces abrasive between them, and employing the upper blank as a grinding tool, proceeds to transform the opposing surfaces from planar to elliptical in cross section. What is intrinsic to this phenomenon is the mutuality of the shaping process; at any given time, surface characteristics of each blank are simultaneously transmitted to and modified by the contraposed blank, producing a gradual evolution toward surface con¬ gruence. In similar fashion, the "blanks" of initial criteria (C) and observed treatment response

diagnostic (R) (eg, to low-dose neuroleptics) can be utilized interactively, through drug-response studies, to produce refinement in both, yielding C and R' whose interface defines G', a more narrowly and precisely described diagnostic subcategory than existed previously. It is our contention that for this process to take place, such studies must incorporate at least the following conditions: the use of rigorously defined diagnostic criteria, incorporating inclusion and exclusion criteria; a flexible dosage schedule in order to respond to changing drug needs and the development of side effects; the use of a rating scale or scales specifically developed to measure the wide range of cognitive, emotional, and social symptoms manifested by this patient population; and a treatment period sufficiently long to evaluate drug-place¬

bo differences in chronic symptoms. There is nothing startling about this notion. It repre¬ sents a theme mentioned in a general way by both Sidley and Gunderson, as well as more explicitly and comprehen¬ sively by others, Klein30 being an outstanding example. Its worth lies in underscoring the relationship between a construct (diagnostic criteria) and one observable outcome measure, viz, response to a particular treatment regimen, in producing a more detailed definition of both. It entails a "bootstrap" endeavor, building on the efforts of Gunderson and Singer1 and on case reports such as those presented here, an endeavor directed toward constructing one segment of a more firmly grounded nosologie framework than our current one. The potentially beneficial impact is apparent: we shall be in the position to provide more specific and effective treatment to borderline patients, as well as feeling more certain that when we discuss these patients, we do so with a shared vocabulary. And, not least of all, we shall be able to regard with clearer diagnostic vision a group of individuals who, as one author has aptly suggested,40 "seem to lie on the periphery of psychiatry, on the periphery of society, and on the periphery of penólo-

er." NonproprJetary Names and Trademarks

of

Amitriptyline hydrochloride—Elavil. Benactyzine hydrochloride-P/io&ea:. Chlorpromazine—Chlor-PZ, Cromedazine, Promachel, Clorazepate dipotassium—Transene. Doxepin hydrochloride-^4daptn, Curatin, Sinequan. Thioridazine—Mellaril. Thiothixene—Navane.

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Drugs

Thorazine.

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Basic Books Inc, 1972, pp 159-173. 3. Friedman HJ: Psychotherapy of borderline patients: The influence of theory on technique. Am J Psychiatry 132:1048-1052, 1975. 4. Kernberg O: The treatment of patients with borderline personality organization. Int J Psychoanal 49:600-619, 1968. 5. Weiner IB: Borderline and pseudoneurotic schizophrenia, in Psychodiagnosis in Schizophrenia. New York, John Wiley & Sons Inc, 1966, pp 398-430. 6. Kernberg 0: Borderline Conditions and Pathological Narcissism. New York, Jason Aronson Inc, 1975. 7. Wolberg A: The Borderline Patient. New York, Intercontinental Medical Book Corp, 1973. 8. Schmideberg M: The borderline patient, in Arieti S (ed): American Handbook of Psychiatry. New York, Basic Books Inc, 1959, vol 1, pp 398-416. 9. Hoch PH, Cattell JP, Strahl MO, et al: The course and outcome of pseudoneurotic schizophrenia. Am J Psychiatry 119:106-115, 1962. 10. Grinker RR, Werble B, Drye RC: The Borderline Syndrome: A Behavioral Study of Ego-Functions. New York, Basic Books Inc, 1968. 11. Hoch PH, Cattell JP: The diagnosis of pseudoneurotic schizophrenia. Psychiatr Q 33:17-43, 1959. 12. Chessick RD: The borderline patient, in Arieti S, Brodie E (eds): American Handbook of Psychiatry, ed 2. New York, Basic Books Inc, 1974, vol 3, pp 808-819. 13. Havens LL: Some difficulties in giving schizophrenic and borderline patients medications. Psychiatry 31:44-50, 1968. 14. Ostow M: Drugs in Psychoanalysis and Psychotherapy. New York, Basic Books Inc, 1962. 15. Last U, Lowenthal U, Klein H: Borderline patients in a chronic ward. Arch Gen Psychiatry 28:517-521, 1973. 16. Zetzel ER: A developmental approach to the borderline patient. Am J Psychiatry 127:867-871, 1971. 17. Aakrog T: Conditions in adolescents who were borderline psychotics as children. Acta Psychiatr Scand 49:377-385, 1973. 18. Hoch PH, Cattell JP, Pennes HH: Effects of drugs: Theoretical considerations from a psychological viewpoint. Am J Psychiatry 108:585589, 1952. 19. Hoch PH, Cattell JP, Pennes HH: Effects of mescaline and lysergic acid (d-LSD-25). Am J Psychiatry 108:579-584, 1952. 20. Pennes HH: Clinical reaction of schizophrenics to sodium amytal, pervitin hydrochloride, mescaline sulfate, and d-lysergic acid diethylamide (LSD 25). J Nerv Ment Dis 119:95-112, 1954. 21. Schick JFE, Freedman DX: Research in non-narcotic drug abuse, in Hamburg DA, Brodie HKH (eds): American Handbook of Psychiatry, ed 2.

New York, Basic Books Inc, 1974, vol 6, pp 552-622. 22. Klein DF, Shader RI: The borderline state: Psychopharmacologic treatment approaches to the undiagnosed case, in Shader RI (ed): Manual of Psychiatric Therapeutics: Practical Psychopharmacology and Psychiatry. Boston, Little Brown & Co, 1975, pp 281-293. 23. Fisher D, DiMino J: Case presentation of an alternative therapeutic approach for the borderline psychotic heroin addict: Diphenylhydantoin. Br J Addict 70:51-55, 1975. 24. Rifkin A, Quitkin F, Carrillo C, et al: Lithium carbonate in emotionally unstable character disorders. Arch Gen Psychiatry 27:519-523, 1972. 25. Klein DF: Psychopharmacology and the borderline patient, in Mack JE (ed): Borderline States in Psychiatry. New York, Grune & Stratton Inc, 1973, pp 75-92. 26. Klein DF, Davis JM: Diagnosis and Drug Treatment of Psychiatric Disorders. Baltimore, Williams & Wilkins, 1969. 27. Winkelman NW: The use of neuroleptic drugs in the treatment of nonpsychotic psychiatric patients, in Ayd F (ed): Rational Psychopharmacotherapy and the Right to Treatment. Baltimore, Ayd Medical Communications Ltd, 1975, pp 161-175. 28. Detre T, Jarecki H: Modern Psychiatric Treatment. Philadelphia, JP Lippincott Co, 1971. 29. Vilkin MI: Comparative chemotherapeutic trial in treatment of chronic borderline patients. Am J Psychiatry 120:1004, 1964. 30. Klein DF: Importance of psychiatric diagnosis in prediction of clinical drug effects. Arch Gen Psychiatry 16:118-126, 1967. 31. Hedberg DL, Houck JH, Glueck BC: Tranylcypromine-trifluoperazine combination in the treatment of schizophrenia. Am J Psychiatry 127:11411146, 1971. 32. Mandell AJ: Psychoanalysis and psychopharmacology, in Marmor J (ed): Modern Psychoanalysis. New York, Basic Books Inc, 1968, pp 274290. 33. Mandell AJ: Dr. Hunter S Thompson and the new psychiatry. Psychiatry Dig 37:12-17, 1976. 34. Feighner JP, Robins E, Guze SB, et al: Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 26:57-63, 1972. 35. Dickes R: The concepts of borderline states: An alternative proposal. Int J Psychoanal Psychother 3:1-27, 1974. 36. Frosch J: The psychotic character: Clinical psychiatric considerations. Psychiatr Q 38:81-96, 1964. 37. Sidley NT: What is the real test of a diagnostic category? Am J Psychiatry 132:876, 1975. 38. Gunderson JG: Dr. Gunderson replies. Am J Psychiatry 132:876-877, 1975. 39. Blumenthal MD: Heterogeneity and research on depressive disorders. Arch Gen Psychiatry 24:524-531, 1971. 40. Chessick RD: The borderline patient, in How Psychotherapy Heals. New York, Science House Inc, 1969, pp 144-160.

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