Refer to: Addario D, Oscherwitz M, Zeidman H: Amphetamine psychosis or paranoid schizophrenia?-Psychiatric Grand Rounds, University of California, San Diego, and University Hospital, San Diego. West J Med 122: 394405, May 1975

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:hizophrenia? d on Psychiatric Grand Rounds held at University Hospital, Diego, a teaching facility of the School of Medicine, Unity of California, San Diego, in November 1973; edited by era Blomgren, BA, and Leighton Huey, MD.

DR. ZEIDMAN: * Harold Leonardot is a single 44year-old airplane mechanic who was admitted to the hospital for his first psychiatric treatment nearly 12 weeks ago. He was brought to the emergency room by his aunt and uncle after his release from jail, where he had been booked on a charge of assault with a deadly weapon. Hal has had diabetes since 1970. His general practitioner prescribed chlorpropamide (Diabinase®) for control of glucose, and anorexics and diuretics for control of weight. In January of 1971 Hal started taking mild anorexics such as diethylpropion hydrochloride (Tepanil®), but by October of that year he began using amphetamines. He has been taking dextroamphetamine and methamphetamine steadily since that time, usually in combination with barbiturates. The prescribed amounts were about 15 mg of amphetamine per day; how much he actually used is hard to say. During that period his weight fluctuated widely. After some time on these compounds Hal began to have strange experiences. *Heywood Zeidman, MD, Resident in Psychiatry. tThe patient's name is fictitious. Reprint requtests to: Barbara Blomgren, Editor, Department of Psychiatry, UCSD School of Medicine, La Jolla, CA 92037.

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He describes an incident when he returned to work one evening to pick up a tool. He noticed men going up a staircase that led to the area reserved for stewardesses. As he was leaving the work area he saw two black cars filled with men following him. One of the cars had an airline decal on it, and he believes it followed him because of something he might have seen while getting his tool. He thinks that maybe the stewardesses were involved in a prostitution ring. These cars continued to follow him until he came to San Diego from his home in Los Angeles. About the same time he began calling the young daughter of his foreman a whore. Until then he had been friendly with his foreman and lived in an apartment behind his house. Hal frequently had dinner with his foreman's family. After the name-calling incidents he was placed on medical leave from the airline and told to seek psychiatric help. Soon thereafter he heard voices telling him that his aunt and uncle in San Diego were in danger. He drove here and stayed with them two weeks without incident. One evening he could not sleep and stayed up all night talking to his aunt and preparing to return home. That night he noticed

AMPHETAMINE PSYCHOSIS OR PARANOID SCHIZOPHRENIA?

creeping things on the curtains and coming through the screens. He also felt that the plants could marry people. While driving toward Los Angeles the next day he heard the trees telling him that his aunt and uncle were in danger; the bigger the tree, the louder the voice. He headed back to his relatives' home. He thought that the plants were holding the family hostage. When he arrived he walked around the house and peered through the windows. He took his unloaded gun from the car, and at that point a neighbor came by to see what was happening. He leveled the gun at her, not sure whether she was allied with the plants or not. She in turn ran into her house and called the police, who arrested Hal. Hal has never been married. Both parents, in their seventies, have diabetes. He believes he had a good relationship with them, although his father was very domineering. He lived with his parents in New York until five years ago, when he had difficulty getting along with a younger brother who also lived at home. At that time Hal moved to Los Angeles. His parents later moved to San Diego for two years; just before the recent events began they returned to New York with the younger brother, who could not find work here. Hal is the oldest of five children, and although he is in contact with his siblings he does not describe a close relationship with any of them. There is no evidence of psychiatric disease within the family, although the younger brother does seem to have a violent temper. The patient started school late because of an asthmatic condition. Because of his asthma he lived on Long Island, with the aunt who is now in San Diego, from his fifth to his seventh year. He left school in the tenth grade to join the Air Force. After leaving the service, he completed high school and attended school to become an airplane mechanic. He has been employed with the same major airline for 18 years. Hal thinks of himself as a loner. He describes one close relationship with a girl when he was 17 years old. He thought he loved her and planned to marry her, but she died suddenly of pneumonia. Around that time, his aunt intercepted a letter he wrote to his mother suggesting that they have sexual relations. (The letter was never forwarded to his mother, and Hal is unaware that anyone else knows about it.) At present his only sexual contact is with prostitutes. He collects pornographic material, and while he was recuperating

on the ward he began to post Playmate pictures around his room. Hal denies abusing any drugs, but he explains that the mechanics often drink the liquor found aboard the planes. They keep an unofficial tally as to who drinks how much. He states that when he became the number two man on the shop list of drinkers he decided it was time to stop. While on the ward he was placed on trifluoperazine hydrochloride (StelazineD) and did well on 5 mg twice a day, although he remained superficial and aloof. After two weeks he insisted on leaving the hospital. Close follow-up was arranged, and he kept his first appointment as scheduled two days after discharge. We later discovered that he thought that the medications were poison and stopped taking them. There was also a hint that he had been drinking, but no determination of alcohol level was made at that time, nor had one been made on his first admission. On the fourth day after discharge he was returning to Los Angeles when he felt a strong urge to go to church. There, over the altar, the patient saw himself nailed to the crucifix and apparently rising to heaven. The vision alarmed him, and he returned to his aunt's home, but, instead of visiting her, he approached the neighbor's house and attempted to break in. He was returned to the ward, where he remained paranoid, delusional and hallucinating despite administration of increasing amounts of phenothiazines for two weeks. He then cleared and seemed ready for discharge, but he suffered a relapse of hallucinations and delusions while awaiting placement after one month of continued medication and apparent improvement. He now appears to have no active hallucinations or fresh delusions, but it was thought best to place him in a board-and-care facility, which is where he came from today. At admission, the emergency room resident felt the patient was probably suffering from amphetamine psychosis. During staff rounds the attending psychiatrist felt he was experiencing a true schizophrenic attack. Later a court-appointed psychiatrist felt he had a toxic psychosis. Results of a Minnesota Multiphasic Personality Inventory (MMPi) were interpreted as showing "schizophrenic reaction or schizophreniform psychosis." It was also noted that he had a strong potential for drug or alcohol abuse. He now is receiving fluphenazine hydrochloride (Prolixin®) given intramuscularly, and the difference in his mental status is striking. He is not as buoyant as he was when THE WESTERN JOURNAL OF MEDICINE

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he first came into the hospital, but he continues to believe in the delusion of being followed in Los Angeles. DR. WEINBERG: * I can add some observations about the patient's behavior during his second stay in hospital. That first month was pretty hectic. On oral medication his mental status fluctuated almost daily. One day he would be hostile, belligerent, sarcastic, difficult to get along with and very threatening. The next day he would be mildmannered and meek, a model patient. He demanded to leave the hospital on a number of occasions; the only way we could keep him there was by pointing out that with his legal problems he was safer in the hospital than he would be in jail. After about a month we started him on intramuscularly administered Prolixin because we thought that he probably would stop taking oral medication as he had after the first stay in hospital. We stabilized him on one weekly injection of 25 mg, and he did pretty well until about three weeks before discharge. One day he said he was afraid he was going to be sent to the state hospital and if that happened, he was going to go to New York to take out a contract on my life-because he felt I would be responsible. The next day he came in and said he did not know why he ever said that; it was a very frightening thing for him. It was also very frightening for me! That was the last really hostile outburst we heard from him until we got ready for discharge. At that time he became resistant and was constantly thinking why he should not go one or another place, and changing plans about where he should go, and when, and about who should follow him. He asked to make out a second MMPI, which he did, and Dr. Stormst thought it showed that he was hallucinating and very depressed and anxious, but not as paranoid or delusional as earlier. I confronted Hal with some of the material on the MMPI and he said that he was not able to tell me exactly, but he felt that the voices were coming back. He was feeling very frightened again; in fact he cried, something I had never seen him do before, and he sounded depressed and anxious and did not want to leave the ward. We put off discharge for about a week, and increased the Proxilin dose a little bit, and he seemed to do well. By the time of discharge he was willing to leave the hospital. I think it's interesting how well * Mikel Weinberg, MD, Resident in Psychiatry. tLowell Storms, PhD, Professor of Psychiatry.

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he had adapted to the hospital; he was very attached to many of the staff. It was hard for him to get used to the idea of leaving a place that had become familiar for him. DR. ZEIDMAN: That part about his being afraid of going to the state hospital was not unrealistic; the court wanted to send him to a state hospital. The law of California states that if a person is judged not guilty of a crime by reason of insanity the State is required to send him to a state hospital for 90 days if he still is psychotic at the time of judgment, no matter where else he is receiving treatment.

(The patient was escorted into the room and introduced to Dr. Oscherwitz, who interviewed him before the residents and staff.) DR. OSCHERWITZ: * Hi, Mr. Leonardo. Patient: Hi. DR. OSCHERWITZ: I'm Dr. Oscherwitz. We're going to do a little talking. Would you mind putting this [microphone] on? Patient: I'm a little afraid of it. DR. OSCHERWITZ: Are you? Why don't you have this seat? We're doing a tape recording of our teaching session here. Is that all right? Patient: Okay. DR. OSCHERWITZ: Dr. Zeidman has told us something about your hospitalization and some of the problems you've been having. How are you feeling now? Patient: I'm feeling great, ready to go to work. DR. OSCHERWITZ: Ready to go to work-back to the airline? Patient: Yep. DR. OSCHERWITZ: Where would that be, in Los Angeles? Patient (promptly): Los Angeles. DR. OSCHERWITZ: Things are pretty well back in place? Patient: I think they're pretty well settled, yeah. DR. OSCHERWITZ: Can you give me some idea of what happened, what your understanding is of the event? Patient: I don't know what happened. It just piled up all of a sudden like. I musta went haywire or something. I heard trees and everything talking to me as though they weren't really normal. *Morris Oscherwitz, chiatry.

MD, Assistant Clinical Professor of Psy-

AMPHETAMINE PSYCHOSIS OR PARANOID SCHIZOPHRENIA?

DR. OSCHERWITZ: That must have been very frightening. Patient: Yes, it was. I turned around twice to come back, and I don't know what happened. Then I took a shotgun and I went in this friend's and was picked up by the police. DR. OSCHERWITZ: What were you doing at that time with the shotgun? What was your idea? Patient: Well, I came back because the voices told me that my aunt and uncle and my niece were being held as hostages, so I came back and I had a shotgun in the back of my car and I pulled that out. DR. OSCHERWITZ: To protect your aunt and uncle and niece? Patient: Right. And I asked the woman next door for help. Instead she turned me in as assault with a deadly weapon. DR. OSCHERWITZ: Who were you protecting your aunt and uncle and niece from? Patient: Plants and trees. DR. OSCHERWITZ: How do you understand that now? Patient: I don't know. I don't believe it any more. I just put it out of my mind. It couldn't be possible. DR. OSCHERWITZ: I see. Now I understand that this started around the time that your parents went back to New York. Is that true? Did the difficulties begin around that time? Patient: Around that time, yes. DR. OSCHERWITZ: Can you explain to me the relationship that you have with your parents and that your younger brother has? My understanding is that . . . Patient (interrupting): Well, my younger brother changes with the full moon. DR. OSCHERWITZ: Yeah? Patient: He can be radical, or, you know, rational. DR. OSCHERWITZ: How old is he? Patient: About 30. DR. OSCHERWITZ: He's the youngest and you're the oldest? Patient: I'm the oldest. DR. OSCHERWITZ: Now, you were with your folks in New York City up until you were 39, is that

right? Patient: 38.

DR. OSCHERWITZ: 3 8. And you left because of some disagreements with him? Patient: Yes. I couldn't get along with him so I moved out of the house. DR. OSCHERWITZ: You moved out, and he stayed with your folks. Just him, the other ... Patient: Just him. The others were already out. DR. OSCHERWITZ: The other three were already out. And then what happened? Did you come out here? Patient: I came out here to live. And everything was stable for about two years, and then they moved out. DR. OSCHERWITZ: Your folks moved out. Patient: Yeah, and then it got unstable again. DR. OSCHERWITZ: Why did they move out? Patient: Uh, I don't know. They just sold their house after so many years, and they wanted to make a move.

DR. OSCHERWITZ: And then things got unstable out here then. Did your brother come with them? Patient: Oh, yeah. He became the dominating force. He didn't go to work any more. Whenever he wanted to throw you out of the house he threw you out. In other words, they put him in charge. DR. OSCHERWITZ: They let him take over? Patient: Yeah, their lives. DR. OSCHERWITZ: And that affected you because Patient: Well, that affected me because I didn't like thzat. I wanted my father to be free. DR. OSCHERWITZ: I see. Your brother dominated him. Patient: Yeah. Him and my mother too. DR. OSCHERWITZ: And then they went back to New York City? Patient: They went back in February of this year. DR. OSCHERWITZ: Why did they go? Patient: Well, they thought the doctors were better on the East Coast. DR. OSCHERWITZ: For whom? Patient: For themselves. DR. OSCHERWITZ: Are they sick? Patient: I guess they are. Both of them have heart trouble. THE WESTERN JOURNAL OF MEDICINE

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DR. OSCHERWITZ: Both of them have bad hearts . . . and so they're back there now with your brother. Patient: Yeah, and now they wanta come back out here. DR. OSCHERWITZ: Now they wanta come back. What do you think about that? Patient: Well, that's up to them. I can't control that. DR. OSCHERWITZ: With or without your brother? Patient: I don't know. I might imagine he'd come with them. DR. OSCHERWITZ: So, in other words, things were tough in your life when they came out here, and they got even tougher when they went back? Patient: When they went back. DR. OSCHERWITZ: Was it during the years that they were out here that you started taking the drugs? Patient: No, no. I had taken the reducing tablets about two and a half years ago. DR. OSCHERWITZ: Um hum. Patient: Maybe it was about the same time they decided to come out. DR. OSCHERWITZ: Did those medicines help you feel better around them and around your brother? Patient: Well, they made me reduce a lot. That's about all. DR. OSCHERNWTZ: Didn't do anything to help your feelings? Patient: No, 1 don't think so. DR. OSCHERWITZ: Did you get pretty angry with your brother at times? Patient: Oh, yeah. DR. OSCHERWITZ: But how bad would it get? Patient: Bad enough to throw a hatchet at you. DR. OSCHERWITZ: Who did the throwing? Patient: He did. DR. OSCHERWITZ: He threw a hatchet at you? Patient: Yeah, and missed me about an inch. DR. OSCHERW1TZ: When was that? Patienit: Oh, about maybe a year and a half ago. DR. OSCHERWITZ: Was he this violent with your parents? Patient: 1 don't know. I wasn't there. 398

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DR. OSCHERWITZ: Okay. I just want to clear that up. I thought that was very important in terms of these problems. Do you think it probably is? Patient: It might have. DR. OSCHERWITZ: So, in other words, when you became upset it was around the idea of protecting your aunt and uncle? Patient: Yes. DR. OSCHERWITZ: Is this the same aunt and uncle that you spent some time with early in your life? Patient: Yes. DR. OSCHERWITZ: My understanding is that you had asthma as a child. Patient: Yes. 1 went to my grandmother's every year. I moved from Westchester to Long Island because the air was better. DR. OSCHERWITZ: Starting at what age? Patient: I don't know. I had it from the time I was S years old. DR. OSCHERWITZ: I see. And then it was this aunt and uncle that you actually spent a few years with. Didn't you move in with them? Patient: Not my uncle, just my aunt then, at my grandmother's house. They weren't married at that time. DR. OSCHERWITZ: Now, when did your aunt and uncle come out here in relation to when you did? Did they precede you? Patient: Ten years before me. They've been about 15 years here now. DR. OSCHERWITZ: Is this something you've always had in the back of your mind? To come out on the West Coast, like they did? Patient: Oh, yeah. DR. OSCHERWITZ: Did you enjoy your first few years away from home? Patient: Oh, I enjoyed it a lot. I was having a ball. DR. OSCHERWITZ: What was it like? Patienit: Well, I was going out every night. I was on my own. Had my own responsibilities. DR. OSCHERWITZ: And it seemed to go all right? Patient: Yeah, it wasn't that difficult. DR. OSCHERWITZ: Until your folks came out? Patient: Until my folks came out. DR. OSCHERWITZ: So what do you think's gonna happen if they come back out again now? Patient: (No reply)

AMPHETAMINE PSYCHOSIS OR PARANOID SCHIZOPHRENIA?

DR. OSCHERWITZ: You don't know? Patient: I don't know. DR. OSCHERWITZ: What have the major problems been for you in the last couple of months? You know, what's been worrying you the most? Patient: Well, I'm just worried about going back to work. I wanta get back to work.

DR. OSCHERWITZ: What are your fears about it? Patient: There are no fears about it. DR. OSCHERWITZ: What are the worries? Patient: No worries. DR. OSCHERWITZ: No worries? Patient: I jlust wanta go to work. DR. OSCHERWITZ: Dr. Zeidman was describing a little about a time when you went back to work to get a tool and you thought you saw ... Patient (interrupting): Well, I thought I saw something, but it was probably only my subconscious mind. DR. OSCHERWITZ: What do you think you saw? What do you recall? Patient: I don't know. I went back for a tool. DR. OSCHERWITZ: Yeah. Patient: And what I saw was these fellows and girls going up on the second floor but see, I don't know ... DR. OSCHERWITZ:You don't know ... Patient: I don't know what transpired. I don't know what was going on. DR. OSCHERWITZ: But the thought apparently was that the stewardesses were being prostitutes, is that it? Patient: Sonmething like that. Like I said, it was

imagination. DR. OSCHERWITZ: Was it an uncomfortable imagination? Patient: Well, we got chewed out for being on the second floor in the first place. At least, I did. And I took it as an affront that I was the only one. And I wasn't. I mean, there was other guys going up there, too, but I was going up there for a specific reason. DR. OSCHERWITZ: What was the reason? Patient: I had to go move some stock around.

DR. OSCHERWITZ: What did the other guys go up for? Patient: Why do I know? Ask them.

DR. OSCHERWITZ: What do you think? I'm sure you have a good imagination. Why might they go up? To be with the stewardesses? Patient: I don't know. Could be. DR. OSCHERWITZ: Had you been dating at that time? Patient: Yeah, I was dating. I had a girl. DR. OSCHERWITZ: How was it going with her? Patient: It was fine, why? DR. OSCHERWITZ: Good relationship? Patient: Yes. DR. OSCHERWITZ: Were you getting closer? Patient: I was getting so close that I think I was knocking on that marriage door and I didn't want to knock on that door. DR. OSCHERWITZ: Oh, really? That's pretty close, huh? Patient: Yeah, that was pretty close. DR. OSCHERWITZ: Why didn't you want to knock on that door? Patient: Well, I don't know. DR. OSCHERWITZ: When was that, that it was getting close? Patient: Oh, a couple of years ago, I guess. Oh, you mean now? About six months ago. DR. OSCHERWITZ: You still see her? Patient: No. I'm down here and she's up there [in Los Angeles]. DR. OSCHERWITZ: How long had you known her? Patient: Oh, about a year. DR. OSCHERWITZ: She wanted to settle down? Patient: She wanted to settle down, but I didn't want to.

DR. OSCHERWITZ: She wanted you to take care of her, huh? Patient: Well, naturally. DR. OSCHERWITZ: How old a gal? Patient: Oh, about 33, 34. DR. OSCHERWITZ: You were getting the jitters,

huh? Patient: Yeah, I was getting ready to move. DR. OSCHERWITZ: You were going to move to get away from her? Patient: Well, I always move, move from one apartment to another. I didn't really settle too long in one area. THE WESTERN JOURNAL OF MEDICINE

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DR. OSCHERWITZ: Was she in the same building? Patient: Yeah, she was in my apartment. DR. OSCHERWITZ: So you were gonna move to ... Patient: Greener pastures. DR. OSCHERWITZ: Greener pastures, huh? Patient: I don't know. I mighta, and I mighta not. I don't know. DR. OSCHERWITZ: You mean you considered ... Patient: Before I cracked up. Yeah, I mean, I was thinking very serious about that. DR. OSCHERWITZ: Would she have been a good woman for you? Patient: I think so. DR. OSCHERWITZ: Was your family aware that you were getting closer with a woman? Patient: I don't know. DR. OSCHERWITZ: Had you told your folks? Patient: I told them about it. DR. OSCHERWITZ: Were they happy about it? Patient: Sure. My mother always wanted me to get nmarried. DR. OSCHERWITZ: She has? Patient: Sure. DR. OSCHERWITZ: She wants to cut your list? Patient: Sure.

DR. OSCHERWITZ: Did that cause some nervousness? Patient (with a slightly disinterested sigh): It mn-ight, 1 don't know. DR. OSCHERW1TZ: What else was going on in your life around the time that you've had these nervous troubles? There was the girl, and the folks and brother moving back and forth. Patient: Well, they didn't move back and forth. He just caused a tremendous disturbance down here, and I got kicked out of the house down here and I had to go back to ... DR. OSCHERWITZ: Out of your folks' house? Patient: Yeah. DR. OSCHERW1TZ: What was the disturbance that he caused? Patient: I don't know. I had somethin' to do with something. I don't remember. But we had a big fight, and I left. DR. OSCHERWITZ: Try to remember. What was this about?

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Patient: Uh, I don't know. I told him to go and get a job, and he told me to go to hell, or something. DR. OSCHERWITZ: Yeah, and then what happened? Patient: So, hle was gonna move out but my parenits didn't want him to move out so they took the key away from me. DR. OSCHERW1TZ: They kicked you out? Patient: 1 was kicked out. DR. OSCHERW1TZ: They figure you're able to take care of yourself and he isn't, is that it? Patient: Well, I worked up in L.A; they lived down here. They expected me to come down every weekend. DR. OSCHERWITZ: So they were expecting you down every weekend, and you were up there with the girl, she must have wanted you up there . Patient: Yeah. Well, I stayed up there when I wanted to stay. DR. OSCHERWITZ: Did she ever meet your folks? Patient: No. DR. OSCHERWITZ: Do you have any questions that you want to ask me about this meeting or about these microphones? Patient: I'd like to know what they are all about. DR. OSCHERWITZ: What do you think? Patient (wryly): Looks like a kangaroo court. DR. OSCHERWITZ: Yeah? What do you mean by a kangaroo court? Patienit: Looks like my verdict is already settled. DR. OSCHERWITZ: What do you think it is? Patient: I don't know. Judgment or what. DR. OSCHERWITZ: What would you say? Patient: Myself.

DR. OSCHERWITZ: A judgment of yourself? What do you think the verdict might be? Patient: Guilty. DR. OSCHERWITZ: Of what? Patient: I don't know. (Lightly) But it sure looks like a kangaroo court. DR. OSCHERWITZ: Yeah, it may look that way, but it isn't .. . Listen, we thank you for coming in. What we're trying to do is to understand, you know, what has happened. We're going to

AMPHETAMINE PSYCHOSIS OR PARANOID SCHIZOPHRENIA?

try to understand it, and Dr. Zeidman will get back to you about it. I wish you good luck. Nice meeting you. (The patient was escorted from the room.) DR. ADDARIO:* Forty-three years ago an allergy specialist, Gordon Ailes, rediscovered and synthesized amphetamines, and the race to the drugstore and the local drug cache began. Amphetamine is efficacious in the treatment of narcolepsy and childhood hyperkinesia, and used widely as a diet medication. It is also the drug most sought and abused by people who want central nervous system stimulants. In 1938 Young and Scoville' first reported amphetamine psychosis in three narcoleptic patients. They felt that the psychosis was brought about by a state of increased alertness, and this theme reappears in much of the literature about amphetamine psychosis. Ideas of reference and misinterpretation of the environment apparently precipitated a paranoid psychosis in a patient whom they felt had latent paranoid tendencies but whom they thought would not have become psychotic if he had not used the drug. Arguments persist in attempts to construct a useful model, and we are still asking three basic questions: Can amphetamines precipitate schizophrenia? What neurochemical pathways, physiological mechanisms and personality features do schizophrenics and amphetamine users have in common? Are certain persons more susceptible than others to amphetamine psychosis? I am going to try to integrate what we think we know with the features of Hal's case. The overall use of amphetamines is astonishing. Approximately 8 billion amphetamine tablets are produced in this country each year, half of which go into illegal markets.2 That makes approximately 35 tablets (of 5 mg) for each man, woman and child in the country. The use, as you can imagine, is quite broad. For instance, 35 percent of all medical students use amphetamine at least once during their student careers. The use of drugs in general varies with age: men and women in their thirties are more likely to use stimulants; those in their forties and fifties are more likely to use tranquilizers; those in their sixties, sedatives. One would think it should be the other way around. Physicians play no small part in this, writing 31 million prescriptions for anorexics in 1967 alone. In spite of an intensive national Dominick Addario, MD, Resident in Psychiatry.

campaign, by 1970 that number had been cut by less than 10 percent. The countries that have had the broadest epidemics are Japan (from 1950 to 1956), Sweden (from 1964 to 1968) and the United States (from 1964 to 1969). Overall, about a tenth of the people who develop amphetamine psychosis remain chronically psychotic. Tatetsu3 found, in a series of 500 cases, that 50 percent of the patients were in hospital less than six months, and 14 percent were there longer than five years. He felt that half of those 14 percent were schizophrenic. In Germany, Ladewig4 found 22 cases of psychosis in a group of 64 amphetamine users. Of the 22 patients, 14 were in the hospital a week or less, presumably suffering from classic amphetamine psychosis; three were in the hospital one to six weeks; five for longer than six weeks. There seems to be no relationship between the incidence of amphetamine psychosis and the duration or amount of drug use. People who have used as much as 300 mg daily for 15 years have not necessarily developed amphetamine psychosis. Others using small amounts over a shorter period of time have developed psychosis. Amphetamine psychosis has, therefore, occurred in all types of users, from the one time low-dose user to the chronic high-dose user. There seem to be two types of amphetamine psychosis. The first type parallels the effects of alcohol or bromides or lysergic acid diethylamide (LSD). There's a lot of organicity. The sensorium is clouded. The patient is disoriented, bleary eyed, obviously spaced. The second type, the nontoxic type, which I think the patient today represents, mimics paranoid schizophrenia or a paranoid state, and is unrelated to dose level-whereas the toxic, fulminating type is usually related to extremely high doses in a single freakout. Bell5 has compared 14 cases of amphetamine psychosis with schizophrenia. In the first seven days they are virtually indistinguishable clinically. But then in amphetamine psychosis the paranoid delusions emerge well formed. These people are extremely sensitive to external stimuli; they do not manifest the classic schizophrenic thought disorder. Their associations are not loose or full of neologisms, nor are speech mechanisms with peculiar syntax present. They have a higher incidence of visual hallucinations than you might suspect. When you see a patient with visual hallucinations, consider an organic factor, a toxin of some type. In approximately 80 percent of Bell's THE WESTERN JOURNAL OF MEDICINE

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14 cases of amphetamine psychosis, the patients had problems with visual miscueing, much like Hal has had. In nontoxic amphetamine psychosis the. sensorium is clear. When I saw Hal in the emergency room, and when Dr. Zeidman saw him the next day, he was not loose; he related well, but he had these fixed visual hallucinations and delusional patterns in his cueing. The amphetamine psychotic has a guarded, aloof affect, not the flatness and anergy that you expect with schizophrenia. Amphetamine psychosis and amphetamine abuse usually carry with them heightened sexuality and stereotyped compulsive behavior. Phenothiazines are effective in treating both schizophrenia and amphetamine psychosis. Now I would like to look at a biochemical model and see if we can stretch it far enough to connect it to a psychodynamic model. In 1972 Snyder' wrote a fine review of the biochemical literature dealing with amphetamines, claiming that amphetamine psychosis is perhaps the best experimental model of paranoid schizophrenia or the paranoid state that we have. In their chemical structure the catecholamines (epinephrine, norepinephrine and dopamine) differ little from amphetamines; except for a couple of small molecules they are basically the same. Amphetamines can mimic catecholamines and have been shown to have activity at the receptor site. They can inhibit the degradative enzyme monoamine oxidase. They can impair the reuptake of catecholamines by nerve endings. They also release catecholamines directly at the synapse. Therefore amphetamines increase the amounts of norepinephrine and dopamine at the synapse. Snyder describes how, using fluorescence histochemistry, Ungerstedt found separate neuroanatomical tracks for norepinephrine and dopamine in the brains of rats. The norepinephrine track seemed to be associated with alerting responses and locomotion and the dopamine track with stereotyped behavior. Carrying this reasoning to the human, Snyder speculates that the schizophrenic-like component of amphetamine psychosis may be mediated from the dopamine level, and the paranoid component facilitated from the norepinephrine level. Pharmacological and stereochemical evidence suggests that the clinical efficacy of phenothiazine drugs in schizophrenia is related to a blockade of dopamine receptors. Taken together these findings provoke speculation that amphetamines acting at dopamine and norepinephrine neurons may account for the major symptoms in the amphetamine psychosis. 402

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Now I would like to look at some of the person-

ality features of the amphetamine addict to see if they can be related to the biochemical findings. At Lexington, Ellinwood7,8 found that 60 percent of the amphetamine addicts were of two types. Either they were schizoid or schizophrenic persons, or they were antisocial. He tried to find common features in these two groups, and he noted the process of internalization. Antisocial people seem to fail to internalize experiencethey are constantly seeking out objects. They have very limited ability to form self images because they have not internalized their experience. And, child-like, they perpetually seek out stimuli; they want to move from one high to the next. Ellinwood felt that the amphetamines might produce a paradoxical calming effect in these people, as they do in hyperkinetic children, by stimulating internal arousal mechanisms and thereby reducing the need for environmental stimuli, and he saw the internal makeup of the schizoid personality as similar. He found also that the schizoid personalities had a greater tendency toward psychosis with the use of amphetamines. He found that these persons tended to be passive and described themselves as loners (as Hal did). They seemed to be sensitive. They felt inadequate and lethargic at times and were daydreamers with a lot of visual miscueing. Ellinwood felt these people sought amphetamine for its energizing and organizing effect on the ego, that it gave them an increased sense of internal arousal, internal awareness, a general sense of well being and a greater sense of self. I will preface my remarks about Hal's case with a statement from a conference at the University of California at Los Angeles at which toxic and functional psychoses were compared: "No illness operates outside the psychic state and psychological background of the patient." All unresolved conflicts, guilts, and fears are activated and magnified by illness or stress. When we work with patients we too frequently look upon hallucinations or delusions simply as things we want to get rid of. It is important to realize that the distortions and delusions represent the particular coping mechanisms of that person, and allow him some function in the face of tremendous turmoil and inner chaos. Rather than get rid of these delusions and distortions we need to explore what they may mean symbolically to that person. If we reject them as simply "unreal" we're missing the boat. Hal is 44 years old, and this is his first psychi-

AMPHETAMINg PSYCHOSIS OR PARANOID SCHIZOPHRENIA?

atric illness. He seems a little old for the first onset of schizophrenia. He has a dramatic history of ingesting a toxin that can produce a psychosis we know is initially indistinguishable from schizophrenia. There are a number of schizoid features in his personality. He describes himself as a loner, and in his history and sibling relationships we notice deficits in his psychosexual development and his object relationships. I feel that the foreman is an important figure here. Hal lived behind him, and his initial delusions dealt with the foreman's daughter. The amphetamines may have produced a homosexual panic. Because of the sexual turmoil, Hal may have misinterpreted his need for nurturing from the foreman. He remembers that when he was 19, his girlfriend died. He subsequently wrote what seemed to be an incestuous letter to his mother. I think that the death of that girlfriend is important and that it may represent a screen memory, specifically "recovery" of an experience to mask inner feelings. The death of the girlfriend may be connected to his sibling rivalry and a confusing wish that his brother had died. The incestuous letter strikes me as the attempt of a schizoid to return once again to the object relationship with the mother and gain from her. His return to the family after the hallucinations on the highway may be angry projections toward the family, and his involvement with the anonymous lady and the gun, and his view of the stewardesses as prostitutes, degraded objects, could be attempts to degrade the mother figure and assert his independence. There is evidence of stereotypic behavior in his return to the scene of his arrest. It may be due to the amphetamines, but also it may be a message to us. I think that Hal, when he saw himself on the cross rising to heaven (which I interpret as a death phenomenon), ran back to be rearrested, seeking external controls when he felt he was becoming homicidal or suicidal. Too, we have to understand, in working with him, the issue of what drug taking means. Is it an attempt to become alive again? Is it a search for a new body image, a new sense of self, what? In sum, I think we are dealing with a schizophreniform psychosis due to amphetamines in a person with a premorbid schizoid makeup. I think that Bell's clinical criteria are met: the delusions are paranoid and there is not much of an overt thinking disorder; the visual hallucinations are prominent and continual; his difficulties with ob-

ject relationships are accentuated by the current stress. DR. OSCHERWITZ: When there's a diagnostic problem involving possible psychotic illness I find it useful to take a careful developmental history to try to understand the organization of the coping mechanisms, the defenses the person is using to learn about the anxieties that are being fought against. Many theorists believe that what takes place in approximately the first three years in the development and growth of the infant and child reverberates throughout life, characterizing the kind of personality, the kind of coping mechanisms and the kind of conflicts that will develop in that person. The most careful work on development that I have read has been by Margaret Mahler9 who has distinguished normal sequential periods of separation and individuation in the first 36 months of life. She considers the first month to be normally autistic. Then a normal symbiosis between mothfer and infant lasts until the baby is about four months old. In the differentiation period between four and seven months the infant recognizes that there are other people besides himself; he becomes anxious with strangers and will cry when he sees a new face. Then there is a period of practicing. Mahler's description of practicing is very much like a description of manic or hypomanic behavior. She talks about the infant's love affair with the world. The child will run about on these newly walking legs and explore everything and be euphoric about everything he finds. The next period she calls rapprochement: the child will go out and recognize that he is by himself and then feel an urgent need to get back to his mother and cling to her. That goes on from 16 months until about 25 months. If things continue to go well the child achieves object constancy: the mother exists as an internal representation whether or not she is present. The child exists too, in his own right, in his own mind. This process is usually complete around 36 months. Erik Erikson's work'0 on the development of identity is classic. He writes about the importance of developing trust instead of mistrust in the first year of life. Then he describes the achievement of autonomy instead of living with shame and selfdoubt. Then the child either develops initiative or remains paralyzed by guilt. I am focusing on these early developmental tasks because we are discussing a patient who obviously has difficulties in THE WESTERN JOURNAL OF MEDICINE

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these areas. The psychic reverberations of borderline or psychotic patients usually come from poor personality integration in these early years. The other theoretical concepts that I find particularly helpful here are those of Melanie Klein1" and some of her successors, which deal with object relations. Interactions with parents, usually the mother, during the first 36 months of life have to do with loving and hating and whether the mother is able to maintain the loving relationship with the child. As this process unfolds, certain positions can be described. Klein recognized in infants feelings of disintegration, of fusing, of not even existing, and she described the anxiety these feelings of annihilation and persecution provoke, and the defenses used against them. If distrust develops-if, for instance, he is left unfeda child is overwhelmed with rage, and in order to maintain the loving relationship with his mother he needs to separate the rage from her. So the first position a child assumes in order to cope is a paranoid-sclhizoid position. Klein thought that this happened within the first six months of life, but we know now that infants are not able to differentiate themselves from the people around them until approximately seven months of age, so although Klein's original timetable is probably incorrect, her clinical perception was very good. Then, to deal with the anxiety that accompanies the realization of isolation and dependence on the mother, the child adopts a manic defense (comparable to Mahler's practicing), and this Klein called the depressive position. Third, it is hoped, comes reparation: love overcomes anger, and the child is able to move on from these primary relationships with the mother and father and siblings to relate with other people. What happens if some of these developmental steps go awry? I think we see some of that in Hal. As Dr. Addario described, his delusions, his anxiety, have to do with destruction and persecution. It seems to me the central conflict for him is about dependency on his family. He was moved in and out of the home because of his asthma. We do not know much about the three other siblings, but he has an intense interaction with his younger brother. Moreover, the current question seems to be about his having a life with a woman on his own or going back into the family to go along with the whims of his parents and that controlling brother. I think his chronic underlying conflict is how to deal with his rage, and that is why the object relations theories are relevant here.

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Let us consider a little more the coping mechanisms that people use to deal with their rage. Kernberg' 2 writes about splitting other people into good or bad, because if one person is good anid bad and if your rage is greater than your love, then that person cannot exist for you. Or the split can be between the external environment (and the people in it) and the internal. Hal projected aggression onto the trees; he had to use relatively inanimate objects; he could not find a person whom he was willing to delegate the rage to. That is why 1 asked him who he was trying to protect the aunt and uncle against. His splitting of the rage to an inanimate object is a primitive maneuver; we see that in very young children. Sometimes, when the boundaries of the self are unclear, rage is projected onto the environment and other people, but the lbve is kept to the self. It is just a different kind of split, separating the rage from the love so that other people can exist and so that the person himself can exist. I think that when Hal was having his most intense anxiety he was in the first position, at the level of annihilation and fusion and persecution anxiety. Did he exist as a human being or not? He was not depressed or guilty. To be in the depressive position you have to be aware that you need and want the person (mother) and at times cannot have her, and that you love and hate her at different times. I think Hal regressed to an earlier level than that. This may explain why, with time, there was a higher depressive score on the MMPI. At least I hope that he was moving from the schizoid fears of annihilation to a more clear awareness that there are other people around him, and that he is angry with them, and that his anger does not destroy them. The specific diagnosis is not a problem for me because I assume that several things are operating: a toxic element and the developmental difficulty and a chronic schizoid personality. I do not see any reason to try to determine which one it is; it is usually a matter of which one is in ascendancy, but there is always a combination of factors. DR. NEMIROFF: * The case presentation and discussion have made this patient's problems with separation and individuation very clear for me. Wieder and Kaplan"3 have tried to learn why people use particular drugs, how the effects of certain drugs mesh with individual needs. They *Robert Nemiroff, MD, Assistant Clinical Professor of Psychiatry.

AMPHETAMINE PSYCHOSIS OR PARANOID SCHIZOPHRENIA?

studied people who use LSD or marijuana or heroin or amphetamines as well as people in treatment of various sorts. They suggest that people who choose amphetamines seem to be fixated in this separation-individuation conflict. The drug gives them a sense of alertness and competence. "I don't need anybody; I can do it myself." This patient too struggles with an overwhelming sense of inadequacy and incompetence, the fear that he cannot make it, that he is nothing-zero. The drug must have provided the illusion that he could cope better. DR. ADDARIO: Hal's life is in a shambles right now. He is discredited by his foreman in Los Angeles; he has been admitted to hospital for psychiatric reasons; legal charges hang over his head. Sometimes stress can damage an ego so badly that it does not reconstitute even though a significant precipitating factor (in his case the amphetamines) has been removed. DR. ZEIDMAN: The court ruled him not guilty of the crime by reason of insanity at the time the crime was allegedly committed. But if he were to be insane at the time of the judgment, state law would require that he be sent to a state hospital for 90 days, despite what any psychiatrists say, despite what the judge would like to do, despite what the prosecuting attorney would like to do. Now sentencing has been posponed 90 days. If a court-appointed psychiatrist can say he is no longer insane then, he would be cleared of the charges and would not have to enter a hospital. If that does not happen perhaps he could be admitted to a Veterans Administration hospital in lieu of the state hospital. DR. OSCHERWITZ: There are therapeutic implications in what we have said. Hal seemed to be on

the threshold of being able to make a life on his own with a woman, away from his parents and brother. He felt a great deal of conflict about that, and it turned out that he took a regressive step. This man needs a good deal of buffering from his family and some help in seeking independence. His first comment, "I just want to go to work," gave me the impression that he still uses a good deal of denial. I would guess he behaved this way before his illness. At this point I might describe his personality as schizoid, but it seems like the psychosis is in remission. I hope it is. If I had pressed maybe we would have found that it is not in remission, but I had the feeling that it is. I thought it was a good prognostic sign that he said maybe he should have stayed with that woman. At first his idea was to get away, and then he had some doubt about that. I think that doubt could be worked with. REFERENCES 1. Young D, Scoville WB: Paranoid psychosis in narcolepsy and the possible danger of Benzedrine treatment. Med Clin N Am 22: 637, 1938 2. Ellinwood EH: Amphetamine and stimulant drugs, In Drug Use in America: Problem in Perspective, Vol 1. Washington, Govt Printing Office, 1973 3. Tatetsu S: Methamphetamine psychosis. Folia Psychiat Neurol Jap 7:377-380, 1963 4. Ladewig G: Amphetamine dependence and psychosis. Deutsch Med Wschr 94:101-107, 1969 5. Bell DS: Comparison of amphetamine psychosis and schizophrenia. Br J Psychiatry 111:701-705, 1965 6. Snyder SH: Catecholamines in the brain as mediators of amphetamine psychosis. Arch Gen Psychiatry 27:169-179, 1972 7. Ellinwood EH: Amphetamine psychosis-1. Description of the individuals and process. J Nerv Ment Disord 144:273-283, 1967 8. Ellinwood EH: Amphetamine psychosis-II. Theoretical implications. Int J Neuropsychiat 4:45-54, 1968 9. Mahler MS: On the significance of the normal separationIndividuation phase with reference to research in symbiotic childhood psychoses, In Schur M (Ed): Drives, Affects, Behavior, Vol 2. New York, Int Universities Press, 1965 10. Erikson EH: Identity-Youth and Crisis. New York, W. W.

Norton, 1968 11. Segal H: Introduction to the Work of Melanie Klein. London, The Hogarth Press and The Institute of Psycho-Analysis, 1973 12. Kernberg 0: Structural derivatives of object relations. Int J Psychoanal 47:236-253, 1966 13. Wieder H, Kaplan EH: Drug use in adolescence-Psychodynamic meaning and pharmacologic effect, In The Psychoanalytic Study of the Child 24:399-431, 1969

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