Psychopharmacology 65, 73
Psychopharmacology
77 (1979)
9 by Springer-Verlag 1979
Amphetamine Psychosis and Psychotic Symptoms David S. Janowsky* and Craig Risch Department of Psychiatry, University of California at San Diego Medical School, La Jo!la, Ca. 92093, U.S.A.
Abstract. Amphetamine psychosis has been considered to be a pharmacologic model of schizophrenia. Fifteen previously reported cases were reviewed in which experimental induction of amphetamine psychosis occurred in nonschizophrenic drug abusers. Seven (possibly ten) cases manifested Schneider's first rank symptoms and all had World Health Organization Present-State Exam symptoms which discriminated schizophrenia. This observation draws further parallels between the phenomeno!ogy of amphetamine psychosis and schizophrenic symptoms.
Key
words: Amphetamine Psychosis Schizophrenia - Schneiderian first rank symptoms Present-state exam
Administration of high doses of amphetamine-like psychostimulants may cause a psychosis which closely resembles paranoid schizophrenia (Connell, 1958; Weiner, 1964; Ellinwood, 1967). However, some investigators (S!ater, 1959; Bell, i965) have questioned whether such reported cases of amphetamine psychosis may have been latently or actively schizophrenic prior to ingestion of the psychostimulant, and also whether the amphetamine-induced psychoses were actually qualitatively similar to schizophrenia. To answer the question of whether or not individuals who develop amphetamine psychosis have preexisting or latent schizophrenia, there have been several prospective, controlled studies in which amphetamine psychosis was induced in nonschizophrenic drug abusers (e.g., in patients carefully screened not to be iatently or actively psychotic prior to the ingestion of Correspondence and reprint requests to: David S. Janowsky, M.D., Department of Psychiatry, University of California at San Diego, P.O. Box 109, La Jolla, Ca. 92037, U.S.A.
the amphetamine). These studies indicate that amphetamine psychosis can indeed occur in nonschizophrenic subjects (Bell, 1973; Angrist and Gershon, 1970; Angrist et al., 1972; Griffith et ai., 1970a, b, 1972). With respect to the question of whether amphetamine psychosis actua!ly is phenomenologically similar to acute schizophrenia, investigators have used a variety of criteria to evaluate this issue. Authors have used relative preva!ence of "thought disorder" (Bell, i965; Angrist and Gershon, 1970), the degree of afl~ctive drive, lability, and blunting (Beil, 1965; Angrist and Gershon, 1970; Griffith et al., 1970a, b), and the type of hallucinations experienced (Griffith et al., 1970a, b, 1972; Bell, 1973; Angrist and Gershon, 1970) to argue both in support of and against the presumption that many similarities exist between amphetamine psychosis and schizophrenia. In recent years, several reliable methods (Schneider, 1959; Mellor, 1970; Carpenter and Strauss, 1974; Carpenter et al., t973a, b, 1974; Taylor, 1972) have been developed for diagnosing schizophrenia which reIy less extensively on criteria previously used (Bleu!er, 1911; DSM II, 1968) to compare amphetamine psychosis and schizophrenia. Two of these methods are based, respectively, on (1) the presence or absence of one or more of Schneider's first rank symptoms of schizophrenia, thought by Schneider (Schneider, 1959) and others (Mellor, 1970) to be pathonomonic of schizophrenia and (2) the presence or absence of those symptoms found to discriminate schizophrenia in the analysis of the 1973 World Health Organization International Pilot Study of Schizophrenia (Carpenter et al., 1973b, ~974). To our knowledge no one has reviewed the literature on experimentally produced '~ psychosis" in nonschizophrenic subjects (Bell, 1973; Angrist and Gershon, 1970, Angrist et al., 1972; Griffith et al., 1970a, 1972) to determine whether or not Schneider's first rank symptoms actually do occur in these cases.
oo37-315s/79/oo6s/oo73/sol.oo
74
Psychopharmacology 65 (1979)
Table 1. Schneiderian first rank symptoms in 15 subjects developing experimentally-inducedamphetamine psychosis
(%) Voices arguing
Bell (1973)
Angrist (]970)
Angrist (1972)
Griffith (1970a, b, 1972)
Patient
Subject
Patient
Various subjects
1
20
Audible thoughts
0
Voices commenting on one's action
0
Somatic passivity
13
Thought insertion
13
Thought withdrawal
0
Thought broadcast
7
Made feelings and/or made impulse (drives)
0
Made volutional acts
0
Delusional perception
40
2
3
6
x
7
x?
A
B
D
2
3
4
x
x
x x
x
x?
x
•
x?
x
x
x
" Derived and modified from Carpenter et al. (1973a); Carpenter and Strauss (1974), Mellor (1970)
Also, the presence or absence of the 43 W o r l d Health O r g a n i z a t i o n Present-State E x a m (PSE) s y m p t o m s (questions) reported to be highly discriminating for schizophrenia (Carpenter et al., 1974) has n o t been formally evaluated in such cases of a m p h e t a m i n e psychosis.
M a t e r i a l s and M e t h o d s
In this report we reviewed available studies in which experimentally induced amphetamine psychosis in nonschizophrenic subjects is described in enough detail to suggest presence or absence of Schneider's first rank symptoms and PSE symptoms discriminating schizophrenia. Criteria for inclusion of a specific case included: (1) Sufficient narrative detail to determine the presence of target symptoms; (2) a clear statement by the author that the subject was not schizophrenic; (3) the prospective administration of a form of amphetamine or a retated psychostimulant under controlled conditions; and (4)the development of psychotic symptoms during psychostimulant administration. Using these criteria, the prospective studies ofGriffith et ah (1970a, b, 1972), Angrist and Gershon (1970), Angrist et al. (1972), and Bell (1973) were reviewed in detail. In the study Bell (1973), five of the eleven reported cases who developed psychoses were presented in enough narrative detail to be analyzed for Schneider's first rank symptoms and schizophrenicPSE symptoms. Similarly,in the study by Angrist and Gershon (1970), all three subjects developingpsychoses were analyzable, as were all three subjects in the study of Angrist et al. (1972). In Griffith et al. (1970a, b, 1972) four of the five qualifying subjects were presented in enough narrative detail to allow analysis. Each of the above 15 analyzable cases was scrutinized for the present or absence of one or more of Schneider's first rank symptoms (Carpenter et al., 1973a; Carpenter and Strauss, 1974; Mellor, 1970) and each was reviewed
for the presence or absence of PSE symptoms discriminating schizophrenia (Carpenter et ah, 1974).
Results
As s h o w n in Table 1, Schneider's first r a n k s y m p t o m s were f o u n d in experimentally induced a m p h e t a m i n e psychosis in a n u m b e r of subjects. T a b l e 1 outlines Schneider's first r a n k s y m p t o m s (Schneider, 1959) n o t e d in the 15 subjects. I n Bell's study (1973) one or more of Schneider's first r a n k s y m p t o m s were f o u n d in two (possibly four) of the five cases evaluated. O f three subjects evaluated in A n g r i s t a n d G e r s h o n ' s study (1970), Schneider's first r a n k s y m p t o m s were f o u n d in one. In their second study (Angrist et al., 1972) one (or two) of three subjects had Schneider's first r a n k symptoms. O f the four subjects evaluated in Griffith et al. (1970a, b, 1972) Schneider's first r a n k s y m p t o m s were f o u n d in three. Therefore, 15 individual cases of obvious a m p h e t a m i n e psychosis in n o n s c h i z o p h r e n i c subjects from four separate prospective studies were presented in e n o u g h narrative detail so that each case was capable o f being analyzed for Schneider's first r a n k symptoms. Schneider's first r a n k s y m p t o m s were f o u n d in at least seven, or possibly ten of these 15 cases (e.g., in 4 6 - 66 % of the subjects). In addition, at least one schizophreniadiscriminating PSE s y m p t o m was f o u n d in each of the 15 subjects. Table 2 outlines the 17 (out of 43) PSE
D. S. Janowsky and Craig Risch: Amphetamine Psychosis and Psychotic Symptoms
75
'fable 2. Present state exam symptoms discriminating for schizophrenia in 15 subjects developing experimentally-induced amphetamine psychosis ~ Bell (1973)
Angrist (I970)
Angrist (1972)
Griffith (1970a, b, 1972)
Patient
Subject
Patient
Various subjects
(%)
! x
Persecntory ideas
40
Suspiciousness
67
Voices speak to patient
13
Voices arguing
20
Auditory hallucinations
33
Nonverbal auditory hallucinations
13
Hallucinated voices speak sentences
13
Thoughts broadcast
13
Thought intrusions
i3
2
3
6
7
A
B
D
x
x
x x
x
x
2
3 x
x
x
x
x
x
4 x x
x
x
• x
x?
x
• •
•
x
•
•
• x
• ?
x
x? •
x
Apophany
13
Poor insight
20
x
Vagueness
20
Idiosyncratic speech
13
x
Incomprehensibility
7
x
x
x
x
x
•
x
x x x
Restricted affect
40
irrelevance
13
• x
x
Preoccupied with delusions
13
x
x
•
x
x x
From Carpenter et el. (I974)
s y m p t o m s d i s c r i m i n a t i n g for s c h i z o p h r e n i a ( C a r p e n t e r et el., 1974) n o t e d in the ~5 subjects.
Discussion O u r review was h a m p e r e d by the fact that in the p r o s p e c t i v e studies e x a m i n e d (Griffith et al., 1970a, b, 1972; A n g r i s t a n d G e r s h o n , 1970; A n g r i s t et al., 1972; Be!l, 1973) case r e p o r t descriptions o f i n d i v i d u a l psychotic s y m p t o m s were usually sketchy, incomplete, or c o m p l e t e l y absent. Thus, an overall accurate estimate o f the prevalence o f Schneider's first r a n k s y m p t o m s and d i s c r i m i n a t i n g P S E s y m p t o m s in e x p e r i m e n t a l l y i n d a c e d a m p h e t a m i n e psychosis in these nonschizop h r e n i c subjects c a n n o t easily be made. Since the studies reviewed were n o t specifically designed to determine the prevaience o f Schneider's first r a n k s y m p t o m s a n d s c h i z o p h r e n i a - d i s c r i m i n a t i n g PSE s y m p t o m s , it might r e a s o n a b l y be expected that these s y m p t o m s w o u l d be u n d e r r e p o r t e d .
O u r results indicate that Schneider's first r a n k s y m p t o m s can a n d do develop in n o n s c h i z o p h r e n i c subjects given high doses o f a m p h e t a m i n e - l i k e p s y c h o stimulants. This finding is consistent with Schneider's s y m p t o m s i n f o r m a l l y described in other case r e p o r t s o f patients with a m p h e t a m i n e psychosis w h o m a y or m a y n o t have been schizophrenic or w h o obviously were s c h i z o p h r e n i c before receiving a m p h e t a m i n e (Conneil, 1958; A n g r i s t a n d G e r s h o n , 1969; Bell, 1965, 1973) and with the r e p o r t o f Bowers a n d F r e e d m a n (1966) showing t h a t Schneider's first r a n k s y m p t o m s do occur in n o n s c h i z o p h r e n i c cases o f d r u g - i n d u c e d psychosis. Schneider considered his first r a n k s y m p t o m s to be p a t h o g n o m o n i c o f schizophrenia. H e stated, " W h e n any o f these m o d e s o f experience is u n d e n i a b l y present, and no basis for s o m a t i c illness can be found, we m a y m a k e the decisive ctinical diagnosis of s c h i z o p h r e n i a " (Schneider, 1959). F u r t h e r m o r e , M e l l o r (1970) rep o r t e d Schneider's first r a n k s y m p t o m s in ~ 19 (72 ~ ) o f i66 inpatients d i a g n o s e d by an i n d e p e n d e n t investig a t o r as suffering f r o m schizophrenia. M e l l o r corn-
76
mented, "These symptoms offer an operational definition of schizophrenia, which may be suitable for research purposes, particularly where a prior and exclusive selection of schizophrenic subjects must be made. It is extremely unlikely that nonschizophrenics would be included in such a study if organic psychosyndromes were excluded" (Mellor, 1970). However, other researchers (McCabe, 1976; Carpenter and Strauss, 1974; Carpenter et al., 1973 a) have recently challenged the assertion that Schneider's symptoms are pathognomonic of schizophrenia, finding Schneider's first rank symptoms present in a variety of other nonorganic psychotic psychiatric disorders. Furthermore, many students of schizophrenia include, in addition to acute symptoms, such factors as long-term outcome, course, and progression when defining schizophrenia. Nevertheless, most investigators (Carpenter and Strauss, 1974; Carpenter et al., 1973a, b, 1974; Taylor, 1972) agree that Schneider's first rank symptoms occur very frequently in schizophrenia. Furthermore, the International Pilot Study of Schizophrenia (Carpenter et al., 1973a), using data from nine participating countries, reported that most of Schneider's first rank symptoms were highly discriminating of either "schizophrenia or paranoid psychosis" with patients with special auditory hallucinations, thought broadcast, thought insertion or withdrawal, or delusions of control having a probability between 0.93 and 0.97 of being diagnosed as having schizophrenia or a paranoid psychosis. Additionally, several investigators (Carpenter and Strauss, 1974; Carpenter et al., 1973a) have reported that Schneider's first rank symptoms occur most frequently in the paranoid variety of schizophrenia, which is the type of schizophrenia most closely simulated by amphetamine psychosis. The observation that Schneider's symptoms develop following high-dose amphetamine ingestion is not incompatible with the possibility that these symptoms develop secondarily to an organic cause. However, no concrete evidence of amphetamineinduced confusion or disorientation chraracteristic of an organic brain syndrome was found in the prospective studies reviewed. As with Schneider's first rank symptoms, a variety of PSE symptoms discriminating schizophrenia were noted in all fifteen cases of amphetamine psychosis reviewed. Such symptoms have been noted previously in earlier reports, although they were not at the time formally identified as highly discriminating of schizophrenia, and the cases presented were not necessarily diagnosed as nonschizophrenic. For example, Ellinwood (1967) noted more than a decade ago, that the following symptoms, later found by the WHO study (Carpenter et al., 1973b, 1974) to discriminate schizophrenia, occurred frequently in amphetamine psy-
Psychopharmacology 65 (1979)
chosis: (1)Suspicious and aware of being watched; (2) organized paranoid behavior; (3) ideas of reference; (4) gross all-prevailing paranoia; (5) auditory hallucinations (noises, voices speaking to patient, conversations with voices); (6)felt bizarre experiences were normal; (7) false recognition of faces (apophany); and (8) increased d6jA vu. Similarly, Jonsson and Sjostron (1970) noted that hallucinatory behavior, disorganization of thoughts, delusions of persecution, suspiciousness, and lack of insight are frequent in amphetamine psychosis. Consistent with previous reports, such symptoms as blunted affect, persecutory ideas, suspiciousness, and auditory hallucinations were prominent in the cases of amphetamine psychosis which we reviewed, and these were among the most schizophrenia-discriminating symptoms noted by Carpenter et al. (1974) using an ANOVA analysis. Also, of considerable interest is the fact that a number of variables (defined by the ratio of means analysis as relatively rare, but highly discriminating of schizophrenia) were noted in the reviewed cases of amphetamine psychosis. Thus, we believe that the frequent occurrence of Schneider's first rank symptoms and schizophreniadiscriminating PSE symptoms in cases of experimentally induced amphetamine psychosis in nonschizophrenic subjects lends credence to the possibility that amphetamine-induced psychosis is a pharmacologic parallel of the schizophrenic state. Acknowledgements. This research was supported by the San Diego Veterans Administration Hospital, Medical Research Service (MRIS 4576), and NIMH Grant 1 P50 MH 309t4-01.
References Angrist, B. M., Gershon, S. : Amphetamine abuse in New York City, 1966-1968. Semin. Psychiatry 1, 195-207 (1969) Angrist, B. M., Gershon, S. : The phenomenology of experimentally induced amphetamine psychosis: Preliminary observations. Biol. Psychiatry 2, 9 5 - 1 0 7 (1970) Angrist, B. M., Shopsin, B., Gershon, S. : Metabolites ofmonoamines in urine and cerebrospinal fluid after large dose amphetamine administration. Psychopharmacologia 26, 1 - 9 (1972) Bell, D. S. : A comparison of amphetamine psychosis and schizophrenia. Br. J. Psychiatry 3, 7 0 1 - 707 (i965) Bell, D. S.: The experimental reproduction of amphetamine psychosis. Arch. Gen. Psychiatry 29, 3 5 - 4 0 (1973) Bleuler, E.: Dementia praecox of the group of schizophrenics. J. Zinkm (trans.). New York: International University Press 14 94 (1911) Bowers, M. J., Freedman, D. X. : 'Psychedelic' experiences in acute psychoses. Arch. Gen. Psychia'~ry 15, 240-248 (1966) Carpenter, W. T., Strauss, J. S.: Cross-cultural evaluation of Schneider's first rank symptoms of schizophrenia: A report from the international pilot study of schizophrenia. Am. J. Psychiatry 131, 682-687 (1974) Carpenter, W. T., Strauss, J. S., Mulch, S. : Are there pathognomonic symptoms in schizophrenia? An empiric investigation of
D. S. Janowsky and Craig Risch: Amphetamine Psychosis and Psychotic Symptoms Schneider's first rank symptoms. Arch. Gen. Psychiatry 28, 847-852 (1973a) Carpenter, W. T., Jr., Strauss, J. S., Bartko, J. J. : Flexible system for the diagnosis of schizophrenia: Report t>om the WHO international pilot study of schizophrenia. Science t82, 12751277 (1973b) Carpenter, W. T., Jr., Strauss, J. S., Bartko, J. J. : Use of signs and symptoms for the identification of schizophrenic patients. Schizophr. Bull. 37-49, 7 6 - 8 i (1974) Connell, P. H. : Amphetamine psychosis. Maudsley Monograph 5. p. 75. London: Oxford University Press 1958 DSM II: Diagnostic and statistical manual of metal disorders, pp. 3 3 - 36. Washington, D.C. : American Psychiatric Association ~968 Eiiinwood, E. H., Jr.: Amphetamine psychosis: Description of the individuals and process. J. Nerv. Ment. Dis. 144, 273-283 (1967) Griffith, J, D., Cavanaugh, J., Held, J.: De• Evaluation of psychomimetic properties in man. Arch. Gen. Psychiatry 26, 9 7 - 1 0 0 (I972) Griffith, J. D., Cavanaugh, J. H., Held, J.: Experimental psychosis induced by the administration of d-amphetamine. In: Amphetamines and related compounds, D. Costa and S. Garattini, eds., pp. 897 904. New York: Raven 1970a
77
Griffith, J. D., Cavanaugh, J. H., Oates, J. A. : Psychosis induced by the administration of d-amphetamine to human volunteers. In : Psychotomimetic drugs, (D. H. Efron, ed.), pp. 287-294. New York: Raven 1970b Jonsson, L. E., Sjostron, K. : A rating scale for the evaluation of the clinical course and symptomology in amphetamine psychosis. Br. J. Psychiatry I17, 661-665 (1970) McCabe, M. S.: Reactive psychosis and schizophrenia with good prognosis. Arch. Gen. Psychiatry 33, 571 576 (1976) Mellor, D. S. : First rank symptoms of schizophrenia: The frequency of schizophrenics on admission to hospital. Differences between individual first rank symptoms. Br. J. Psychiatry 117, 1 5 - 2 3 (!970) Schneider, K. : Clinical Psychopathology, M. W. Hamilton (trans.), pp. 8 8 - i 4 4 . New York: Grune and Stratton 1959 Slater, E.: Book review of 'Amphetamine Psychosis' by P. H. Connell. Br. Med. J. 1, 488 (1959) Taylor, M. A.: Schneiderian first rank symptoms and ctinical prognostic features in schizophrenia. Arch. Gen. Psychiatry 26, 6 4 - 6 7 (1972) Weiner, !. B.: Differential diagnosis in amphetamine poisoning. Psychiatr. Q. 38, 707-716 (1964) Received September 1, 1978; Final Version February 6, 1979
Psychopharmacology
77 (1979)
9 by Springer-Verlag 1979
Amphetamine Psychosis and Psychotic Symptoms David S. Janowsky* and Craig Risch Department of Psychiatry, University of California at San Diego Medical School, La Jo!la, Ca. 92093, U.S.A.
Abstract. Amphetamine psychosis has been considered to be a pharmacologic model of schizophrenia. Fifteen previously reported cases were reviewed in which experimental induction of amphetamine psychosis occurred in nonschizophrenic drug abusers. Seven (possibly ten) cases manifested Schneider's first rank symptoms and all had World Health Organization Present-State Exam symptoms which discriminated schizophrenia. This observation draws further parallels between the phenomeno!ogy of amphetamine psychosis and schizophrenic symptoms.
Key
words: Amphetamine Psychosis Schizophrenia - Schneiderian first rank symptoms Present-state exam
Administration of high doses of amphetamine-like psychostimulants may cause a psychosis which closely resembles paranoid schizophrenia (Connell, 1958; Weiner, 1964; Ellinwood, 1967). However, some investigators (S!ater, 1959; Bell, i965) have questioned whether such reported cases of amphetamine psychosis may have been latently or actively schizophrenic prior to ingestion of the psychostimulant, and also whether the amphetamine-induced psychoses were actually qualitatively similar to schizophrenia. To answer the question of whether or not individuals who develop amphetamine psychosis have preexisting or latent schizophrenia, there have been several prospective, controlled studies in which amphetamine psychosis was induced in nonschizophrenic drug abusers (e.g., in patients carefully screened not to be iatently or actively psychotic prior to the ingestion of Correspondence and reprint requests to: David S. Janowsky, M.D., Department of Psychiatry, University of California at San Diego, P.O. Box 109, La Jolla, Ca. 92037, U.S.A.
the amphetamine). These studies indicate that amphetamine psychosis can indeed occur in nonschizophrenic subjects (Bell, 1973; Angrist and Gershon, 1970; Angrist et al., 1972; Griffith et ai., 1970a, b, 1972). With respect to the question of whether amphetamine psychosis actua!ly is phenomenologically similar to acute schizophrenia, investigators have used a variety of criteria to evaluate this issue. Authors have used relative preva!ence of "thought disorder" (Bell, i965; Angrist and Gershon, 1970), the degree of afl~ctive drive, lability, and blunting (Beil, 1965; Angrist and Gershon, 1970; Griffith et al., 1970a, b), and the type of hallucinations experienced (Griffith et al., 1970a, b, 1972; Bell, 1973; Angrist and Gershon, 1970) to argue both in support of and against the presumption that many similarities exist between amphetamine psychosis and schizophrenia. In recent years, several reliable methods (Schneider, 1959; Mellor, 1970; Carpenter and Strauss, 1974; Carpenter et al., t973a, b, 1974; Taylor, 1972) have been developed for diagnosing schizophrenia which reIy less extensively on criteria previously used (Bleu!er, 1911; DSM II, 1968) to compare amphetamine psychosis and schizophrenia. Two of these methods are based, respectively, on (1) the presence or absence of one or more of Schneider's first rank symptoms of schizophrenia, thought by Schneider (Schneider, 1959) and others (Mellor, 1970) to be pathonomonic of schizophrenia and (2) the presence or absence of those symptoms found to discriminate schizophrenia in the analysis of the 1973 World Health Organization International Pilot Study of Schizophrenia (Carpenter et al., 1973b, ~974). To our knowledge no one has reviewed the literature on experimentally produced '~ psychosis" in nonschizophrenic subjects (Bell, 1973; Angrist and Gershon, 1970, Angrist et al., 1972; Griffith et al., 1970a, 1972) to determine whether or not Schneider's first rank symptoms actually do occur in these cases.
oo37-315s/79/oo6s/oo73/sol.oo
74
Psychopharmacology 65 (1979)
Table 1. Schneiderian first rank symptoms in 15 subjects developing experimentally-inducedamphetamine psychosis
(%) Voices arguing
Bell (1973)
Angrist (]970)
Angrist (1972)
Griffith (1970a, b, 1972)
Patient
Subject
Patient
Various subjects
1
20
Audible thoughts
0
Voices commenting on one's action
0
Somatic passivity
13
Thought insertion
13
Thought withdrawal
0
Thought broadcast
7
Made feelings and/or made impulse (drives)
0
Made volutional acts
0
Delusional perception
40
2
3
6
x
7
x?
A
B
D
2
3
4
x
x
x x
x
x?
x
•
x?
x
x
x
" Derived and modified from Carpenter et al. (1973a); Carpenter and Strauss (1974), Mellor (1970)
Also, the presence or absence of the 43 W o r l d Health O r g a n i z a t i o n Present-State E x a m (PSE) s y m p t o m s (questions) reported to be highly discriminating for schizophrenia (Carpenter et al., 1974) has n o t been formally evaluated in such cases of a m p h e t a m i n e psychosis.
M a t e r i a l s and M e t h o d s
In this report we reviewed available studies in which experimentally induced amphetamine psychosis in nonschizophrenic subjects is described in enough detail to suggest presence or absence of Schneider's first rank symptoms and PSE symptoms discriminating schizophrenia. Criteria for inclusion of a specific case included: (1) Sufficient narrative detail to determine the presence of target symptoms; (2) a clear statement by the author that the subject was not schizophrenic; (3) the prospective administration of a form of amphetamine or a retated psychostimulant under controlled conditions; and (4)the development of psychotic symptoms during psychostimulant administration. Using these criteria, the prospective studies ofGriffith et ah (1970a, b, 1972), Angrist and Gershon (1970), Angrist et al. (1972), and Bell (1973) were reviewed in detail. In the study Bell (1973), five of the eleven reported cases who developed psychoses were presented in enough narrative detail to be analyzed for Schneider's first rank symptoms and schizophrenicPSE symptoms. Similarly,in the study by Angrist and Gershon (1970), all three subjects developingpsychoses were analyzable, as were all three subjects in the study of Angrist et al. (1972). In Griffith et al. (1970a, b, 1972) four of the five qualifying subjects were presented in enough narrative detail to allow analysis. Each of the above 15 analyzable cases was scrutinized for the present or absence of one or more of Schneider's first rank symptoms (Carpenter et al., 1973a; Carpenter and Strauss, 1974; Mellor, 1970) and each was reviewed
for the presence or absence of PSE symptoms discriminating schizophrenia (Carpenter et ah, 1974).
Results
As s h o w n in Table 1, Schneider's first r a n k s y m p t o m s were f o u n d in experimentally induced a m p h e t a m i n e psychosis in a n u m b e r of subjects. T a b l e 1 outlines Schneider's first r a n k s y m p t o m s (Schneider, 1959) n o t e d in the 15 subjects. I n Bell's study (1973) one or more of Schneider's first r a n k s y m p t o m s were f o u n d in two (possibly four) of the five cases evaluated. O f three subjects evaluated in A n g r i s t a n d G e r s h o n ' s study (1970), Schneider's first r a n k s y m p t o m s were f o u n d in one. In their second study (Angrist et al., 1972) one (or two) of three subjects had Schneider's first r a n k symptoms. O f the four subjects evaluated in Griffith et al. (1970a, b, 1972) Schneider's first r a n k s y m p t o m s were f o u n d in three. Therefore, 15 individual cases of obvious a m p h e t a m i n e psychosis in n o n s c h i z o p h r e n i c subjects from four separate prospective studies were presented in e n o u g h narrative detail so that each case was capable o f being analyzed for Schneider's first r a n k symptoms. Schneider's first r a n k s y m p t o m s were f o u n d in at least seven, or possibly ten of these 15 cases (e.g., in 4 6 - 66 % of the subjects). In addition, at least one schizophreniadiscriminating PSE s y m p t o m was f o u n d in each of the 15 subjects. Table 2 outlines the 17 (out of 43) PSE
D. S. Janowsky and Craig Risch: Amphetamine Psychosis and Psychotic Symptoms
75
'fable 2. Present state exam symptoms discriminating for schizophrenia in 15 subjects developing experimentally-induced amphetamine psychosis ~ Bell (1973)
Angrist (I970)
Angrist (1972)
Griffith (1970a, b, 1972)
Patient
Subject
Patient
Various subjects
(%)
! x
Persecntory ideas
40
Suspiciousness
67
Voices speak to patient
13
Voices arguing
20
Auditory hallucinations
33
Nonverbal auditory hallucinations
13
Hallucinated voices speak sentences
13
Thoughts broadcast
13
Thought intrusions
i3
2
3
6
7
A
B
D
x
x
x x
x
x
2
3 x
x
x
x
x
x
4 x x
x
x
• x
x?
x
• •
•
x
•
•
• x
• ?
x
x? •
x
Apophany
13
Poor insight
20
x
Vagueness
20
Idiosyncratic speech
13
x
Incomprehensibility
7
x
x
x
x
x
•
x
x x x
Restricted affect
40
irrelevance
13
• x
x
Preoccupied with delusions
13
x
x
•
x
x x
From Carpenter et el. (I974)
s y m p t o m s d i s c r i m i n a t i n g for s c h i z o p h r e n i a ( C a r p e n t e r et el., 1974) n o t e d in the ~5 subjects.
Discussion O u r review was h a m p e r e d by the fact that in the p r o s p e c t i v e studies e x a m i n e d (Griffith et al., 1970a, b, 1972; A n g r i s t a n d G e r s h o n , 1970; A n g r i s t et al., 1972; Be!l, 1973) case r e p o r t descriptions o f i n d i v i d u a l psychotic s y m p t o m s were usually sketchy, incomplete, or c o m p l e t e l y absent. Thus, an overall accurate estimate o f the prevalence o f Schneider's first r a n k s y m p t o m s and d i s c r i m i n a t i n g P S E s y m p t o m s in e x p e r i m e n t a l l y i n d a c e d a m p h e t a m i n e psychosis in these nonschizop h r e n i c subjects c a n n o t easily be made. Since the studies reviewed were n o t specifically designed to determine the prevaience o f Schneider's first r a n k s y m p t o m s a n d s c h i z o p h r e n i a - d i s c r i m i n a t i n g PSE s y m p t o m s , it might r e a s o n a b l y be expected that these s y m p t o m s w o u l d be u n d e r r e p o r t e d .
O u r results indicate that Schneider's first r a n k s y m p t o m s can a n d do develop in n o n s c h i z o p h r e n i c subjects given high doses o f a m p h e t a m i n e - l i k e p s y c h o stimulants. This finding is consistent with Schneider's s y m p t o m s i n f o r m a l l y described in other case r e p o r t s o f patients with a m p h e t a m i n e psychosis w h o m a y or m a y n o t have been schizophrenic or w h o obviously were s c h i z o p h r e n i c before receiving a m p h e t a m i n e (Conneil, 1958; A n g r i s t a n d G e r s h o n , 1969; Bell, 1965, 1973) and with the r e p o r t o f Bowers a n d F r e e d m a n (1966) showing t h a t Schneider's first r a n k s y m p t o m s do occur in n o n s c h i z o p h r e n i c cases o f d r u g - i n d u c e d psychosis. Schneider considered his first r a n k s y m p t o m s to be p a t h o g n o m o n i c o f schizophrenia. H e stated, " W h e n any o f these m o d e s o f experience is u n d e n i a b l y present, and no basis for s o m a t i c illness can be found, we m a y m a k e the decisive ctinical diagnosis of s c h i z o p h r e n i a " (Schneider, 1959). F u r t h e r m o r e , M e l l o r (1970) rep o r t e d Schneider's first r a n k s y m p t o m s in ~ 19 (72 ~ ) o f i66 inpatients d i a g n o s e d by an i n d e p e n d e n t investig a t o r as suffering f r o m schizophrenia. M e l l o r corn-
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mented, "These symptoms offer an operational definition of schizophrenia, which may be suitable for research purposes, particularly where a prior and exclusive selection of schizophrenic subjects must be made. It is extremely unlikely that nonschizophrenics would be included in such a study if organic psychosyndromes were excluded" (Mellor, 1970). However, other researchers (McCabe, 1976; Carpenter and Strauss, 1974; Carpenter et al., 1973 a) have recently challenged the assertion that Schneider's symptoms are pathognomonic of schizophrenia, finding Schneider's first rank symptoms present in a variety of other nonorganic psychotic psychiatric disorders. Furthermore, many students of schizophrenia include, in addition to acute symptoms, such factors as long-term outcome, course, and progression when defining schizophrenia. Nevertheless, most investigators (Carpenter and Strauss, 1974; Carpenter et al., 1973a, b, 1974; Taylor, 1972) agree that Schneider's first rank symptoms occur very frequently in schizophrenia. Furthermore, the International Pilot Study of Schizophrenia (Carpenter et al., 1973a), using data from nine participating countries, reported that most of Schneider's first rank symptoms were highly discriminating of either "schizophrenia or paranoid psychosis" with patients with special auditory hallucinations, thought broadcast, thought insertion or withdrawal, or delusions of control having a probability between 0.93 and 0.97 of being diagnosed as having schizophrenia or a paranoid psychosis. Additionally, several investigators (Carpenter and Strauss, 1974; Carpenter et al., 1973a) have reported that Schneider's first rank symptoms occur most frequently in the paranoid variety of schizophrenia, which is the type of schizophrenia most closely simulated by amphetamine psychosis. The observation that Schneider's symptoms develop following high-dose amphetamine ingestion is not incompatible with the possibility that these symptoms develop secondarily to an organic cause. However, no concrete evidence of amphetamineinduced confusion or disorientation chraracteristic of an organic brain syndrome was found in the prospective studies reviewed. As with Schneider's first rank symptoms, a variety of PSE symptoms discriminating schizophrenia were noted in all fifteen cases of amphetamine psychosis reviewed. Such symptoms have been noted previously in earlier reports, although they were not at the time formally identified as highly discriminating of schizophrenia, and the cases presented were not necessarily diagnosed as nonschizophrenic. For example, Ellinwood (1967) noted more than a decade ago, that the following symptoms, later found by the WHO study (Carpenter et al., 1973b, 1974) to discriminate schizophrenia, occurred frequently in amphetamine psy-
Psychopharmacology 65 (1979)
chosis: (1)Suspicious and aware of being watched; (2) organized paranoid behavior; (3) ideas of reference; (4) gross all-prevailing paranoia; (5) auditory hallucinations (noises, voices speaking to patient, conversations with voices); (6)felt bizarre experiences were normal; (7) false recognition of faces (apophany); and (8) increased d6jA vu. Similarly, Jonsson and Sjostron (1970) noted that hallucinatory behavior, disorganization of thoughts, delusions of persecution, suspiciousness, and lack of insight are frequent in amphetamine psychosis. Consistent with previous reports, such symptoms as blunted affect, persecutory ideas, suspiciousness, and auditory hallucinations were prominent in the cases of amphetamine psychosis which we reviewed, and these were among the most schizophrenia-discriminating symptoms noted by Carpenter et al. (1974) using an ANOVA analysis. Also, of considerable interest is the fact that a number of variables (defined by the ratio of means analysis as relatively rare, but highly discriminating of schizophrenia) were noted in the reviewed cases of amphetamine psychosis. Thus, we believe that the frequent occurrence of Schneider's first rank symptoms and schizophreniadiscriminating PSE symptoms in cases of experimentally induced amphetamine psychosis in nonschizophrenic subjects lends credence to the possibility that amphetamine-induced psychosis is a pharmacologic parallel of the schizophrenic state. Acknowledgements. This research was supported by the San Diego Veterans Administration Hospital, Medical Research Service (MRIS 4576), and NIMH Grant 1 P50 MH 309t4-01.
References Angrist, B. M., Gershon, S. : Amphetamine abuse in New York City, 1966-1968. Semin. Psychiatry 1, 195-207 (1969) Angrist, B. M., Gershon, S. : The phenomenology of experimentally induced amphetamine psychosis: Preliminary observations. Biol. Psychiatry 2, 9 5 - 1 0 7 (1970) Angrist, B. M., Shopsin, B., Gershon, S. : Metabolites ofmonoamines in urine and cerebrospinal fluid after large dose amphetamine administration. Psychopharmacologia 26, 1 - 9 (1972) Bell, D. S. : A comparison of amphetamine psychosis and schizophrenia. Br. J. Psychiatry 3, 7 0 1 - 707 (i965) Bell, D. S.: The experimental reproduction of amphetamine psychosis. Arch. Gen. Psychiatry 29, 3 5 - 4 0 (1973) Bleuler, E.: Dementia praecox of the group of schizophrenics. J. Zinkm (trans.). New York: International University Press 14 94 (1911) Bowers, M. J., Freedman, D. X. : 'Psychedelic' experiences in acute psychoses. Arch. Gen. Psychia'~ry 15, 240-248 (1966) Carpenter, W. T., Strauss, J. S.: Cross-cultural evaluation of Schneider's first rank symptoms of schizophrenia: A report from the international pilot study of schizophrenia. Am. J. Psychiatry 131, 682-687 (1974) Carpenter, W. T., Strauss, J. S., Mulch, S. : Are there pathognomonic symptoms in schizophrenia? An empiric investigation of
D. S. Janowsky and Craig Risch: Amphetamine Psychosis and Psychotic Symptoms Schneider's first rank symptoms. Arch. Gen. Psychiatry 28, 847-852 (1973a) Carpenter, W. T., Jr., Strauss, J. S., Bartko, J. J. : Flexible system for the diagnosis of schizophrenia: Report t>om the WHO international pilot study of schizophrenia. Science t82, 12751277 (1973b) Carpenter, W. T., Jr., Strauss, J. S., Bartko, J. J. : Use of signs and symptoms for the identification of schizophrenic patients. Schizophr. Bull. 37-49, 7 6 - 8 i (1974) Connell, P. H. : Amphetamine psychosis. Maudsley Monograph 5. p. 75. London: Oxford University Press 1958 DSM II: Diagnostic and statistical manual of metal disorders, pp. 3 3 - 36. Washington, D.C. : American Psychiatric Association ~968 Eiiinwood, E. H., Jr.: Amphetamine psychosis: Description of the individuals and process. J. Nerv. Ment. Dis. 144, 273-283 (1967) Griffith, J, D., Cavanaugh, J., Held, J.: De• Evaluation of psychomimetic properties in man. Arch. Gen. Psychiatry 26, 9 7 - 1 0 0 (I972) Griffith, J. D., Cavanaugh, J. H., Held, J.: Experimental psychosis induced by the administration of d-amphetamine. In: Amphetamines and related compounds, D. Costa and S. Garattini, eds., pp. 897 904. New York: Raven 1970a
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Griffith, J. D., Cavanaugh, J. H., Oates, J. A. : Psychosis induced by the administration of d-amphetamine to human volunteers. In : Psychotomimetic drugs, (D. H. Efron, ed.), pp. 287-294. New York: Raven 1970b Jonsson, L. E., Sjostron, K. : A rating scale for the evaluation of the clinical course and symptomology in amphetamine psychosis. Br. J. Psychiatry I17, 661-665 (1970) McCabe, M. S.: Reactive psychosis and schizophrenia with good prognosis. Arch. Gen. Psychiatry 33, 571 576 (1976) Mellor, D. S. : First rank symptoms of schizophrenia: The frequency of schizophrenics on admission to hospital. Differences between individual first rank symptoms. Br. J. Psychiatry 117, 1 5 - 2 3 (!970) Schneider, K. : Clinical Psychopathology, M. W. Hamilton (trans.), pp. 8 8 - i 4 4 . New York: Grune and Stratton 1959 Slater, E.: Book review of 'Amphetamine Psychosis' by P. H. Connell. Br. Med. J. 1, 488 (1959) Taylor, M. A.: Schneiderian first rank symptoms and ctinical prognostic features in schizophrenia. Arch. Gen. Psychiatry 26, 6 4 - 6 7 (1972) Weiner, !. B.: Differential diagnosis in amphetamine poisoning. Psychiatr. Q. 38, 707-716 (1964) Received September 1, 1978; Final Version February 6, 1979
