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Amineptine dependence and schizophrenia
CASE REPORTS
Amineptine Dependenceand Schizophrenia Jesus M. Pr[eto,Aria Gost, Joan Obiols, and Natalia Caycedo Key Words: Aminepfine, amphetamine, dependence, abuse, dopamine, schizophrenia
Introduction Amineptine differs from other tricyclic antidepressants because of its 7-aminoheptanoic acid side chain. In vitro studies have estabfished that amineptine inhibits uptake of dopamine and, to a lesser extent, that of noradrenaline without affecting the uptake of serotonin (Ceci et al 1986). The increase in locomotor activity induced by amincptine is significantly reduced by a pretreatment with reserpine. In contrast dexamphetamine-induced locomotor activity is not modified (Chagraoui et al 1989), The mechanism of action differs from that of (+) amphetamine in that amineptine inhibits dopamine intake and is virtually devoid of dopamine releasing effects, displaying a relatively low affinity for the norepinephrine uptake system (Bonnet et al 1986), Amineptine is an indirect dopaminergic agonist that, when given chronically, induces a downreguladon of dopaminergic and adrenergic (beta and alpha 2 subtypes) receptors. These modifications may be relevant for the drug antidepressant activity (Garafini and Mennini 1989). At a dosage of about 200 mg/day the auriclepress,ant effect has been reported to be similar to that of the major reference tryciclics (Vauterin and Bazot 1979; Lemoine et al 1980; O ~ ~ d Bosch-don i983), with a characteristic disinhibiting effect, a better tolerability, and an earlier onset of the therapheutic action. Several cases of amineptine dependence have been documented (Tremine et al 1983; Ginestet et al 1984; Biondi et al 1990; Bertschy et al 1990, Perez De Los Cobos et al 1990; Castot et al 1990) since this drug was introduced in the market. Amineptine can be considered a substance that presents a potential risk for abuse because of its dopaminergic activity (Bozhart 1987) and pharmacokinetic properties (Busto and Sellers 1986). Amineptine is rapidly absorbed, reaches its blood concentration after I hr, its half-life is about 1.5 hr and it has a high plasma clearance. From the Department of Psychiatry and Clinical Psychology, Hospital Clfnie i Provhlcial, l~n~elon~ Spain. Address reprint requests to Jesus Prieto, Department of Psychiatry and Clinical Psychology, Hospital Clfnic i Provincial, Caner Villarroel 170. 08036. Barcelona. Spain. Reccived April 22,1993; revised January 10, 1994.
© 1994 Society of Biological Psychian'y
We report a case of a schizophrenic patiem dependent on amineptine who has been followed in our hospital during the last 8 years.
Case Report In November 1993, Ms 'M, a 38-year-old unemployed single woman, was again hospitalized for an acute psychotic exacerbation after a high-dose consumption of amineptine. Over the preceding 5 days, the patient consumed amineptine in progressively higher doses until she reached 30 tablets/day (3 g/day). The clinical picture was characterized by extreme psychomotor agitation, aggressiveness, persecutory delusions, auditory hallucinations, rapid speech, and labile affect. This symptomatologyabated in less than 1 week with the suppression of the drug and neuroleptic treatment. During this treatment she did not present signs of withdrawal. Afterward a moderate residual psychotic symptomatology could he observed. Ms M began amphetamine use at age 16, initially she used the substance on a daily basis to reduce appetite (2 tablets/day) but after 2 years she began to increase the daily dose (4-5 tablets) intermittently (approximately once a month). Tlae patient had her first psychotic episode at age 19, following the break-up of a romantic relationship. She presented perplexity, fearful, and suspicious mood, no psychomotor agitation, persecutory delusions, experiences of thought control and broadcasting, depersonalization, auditory hallucinations, looseness of associations, and illogical thinking. This episode was reported not to he related to drug abuse. After a 4-month stay with a neuroleptic treatment and a course of electroconvulsive therapy, she was discharged with a moderate improvement. The diagnostic impression at that time was paranoid schizophrenia. There was no family history of psychiatric disorder The patient's early development and schooling were uneventful. Her academic performance was fair, her social development appeared normal, and there was no evidence of premorbid personality abnormalities. From age 19 to 23, and while being amphetamine abstinent Ms M had four psychotic episodes that required long hospital stays 0006-3223/94/$07.00
CaseRepom
mec~sYcmA~v
267
1~4:36:~f~2~t
(mean 6.9 months). The phenomenology was very similar to the first psychotic episode. Between hospitalizations a residual psychotic symptomatology and a lack of returning to base,he functioning could be appreciated. The patient was isolated, had trouble socializing, was unable to live alone, and was clearly impaired in work functioning. She was likely to take the medication inegularly or not at all. In this period, a high daily consumption of caffeine (7 cups of instant coffee, 3 cups of tea, and ! liter of Coke) was reported. At age 24, the patient resumed the amphetamine abuse episodically. Over the next 7 years, she needed five brief hospitalizations (mean 10.1 days) for symptom exacerbations that were clearly related to a high-dose administration of amphetamine. A few days before admission, she began using amphetamine at 10-15 tablets/day. The symptomatology and course of these episodes were strikingly similar to the amineptine-induced psychotic exacerbations. At age 3 !, she began therapy with amineptine to treat a state of mild "depressive" symptomatology. The patient was reportedly depressed with regard relation to her impairment in social and interpersonal relationships, and work functioning. In her past psychiatric history, a period of manic or depressive symptoms sufficient to qualify for a probable mood or schizoaffective disorder was not reported. She took a dose of 200 mg/day for I year and then she began to progressively increase her dosage of amphetamines. During the ensuing 9 years the patient had 14 rehospitedizations for amineptine-induced psychotic exacerbation. Ms M's pattern of amineptine use met the DSM-III-R diagnostic criteria for substance dependence. The patient had a compulsive need to use the drug on a continuing basis. The patient's self-reported reasons to resume amineptine consumption were to gain energy, to increase her socialization level, and to relieve her distressing beliefs. She believed that perhaps she really did have a psychiatric disorder, nobody wanted to many her, people were not good, her brother-in-law wanted to hurt her, and her sister was jealous of her. This symptomatology was not accompanied by irritable or depressed mood, sleep or eating disorders. The affect was mildly reduced, sometimes inappropriate, and thought content and thought processes were moderately pathological. The little insight into her illness and the low treatment compliance made the outpatient treatment very difficult, so in the last 3 years Ms M has been admitted for long hospital stays in order to receive a more suitable treatment.
Discussion a n d Conclusion We report here the first case of which we are aware of a schizophrenic patient who developed frequent amineptine-iaduced psychotic exacerbations. Some nonschizophrenic patients have been reported to develop amineptine-related psychotic symptomatology (Tremine et a11983; Castor et al 1990). The main characteristics of amineptine dependence are the constant search of a psychostimulant effect, strong psychological depeadence, and the existence of what can be considered risk factors. In the patient's past history and in agreement with other reported cases (Tremine et al 1983; Bertschy et al 1990; Biondi et al 1990; Castor et al 1990; Perez de los Cobos et al 1990 et al), we find an addiction disposition and the presence of a mild eating disorder.
These should be comideml risk factors f ~ a ~ ~ abuse. The idea that a functional excess of ~ activity is rel~_t~ to the development of ~ has been the promising and widely accepted hypothesis in the pathogenes~ of this disouler. A human model for ~ is amphemmt~e-
imi-__~_~pmanoidpsydmsi~ end b i e c l ~ y more ~ m ~ v ~ m~ me ~ ~ o ~ of dopami~ ~ su~ as ~ n e (direct) or amineptine (indirect), producing psychosis. This hypothesis is consistent with the godactive symptoms of the disorder, but cannot explain the deficit symptoms of s c ~ - _ ~ a , The pathophysiological he~nogeneity of ~ is reflected in some experimental studies, where we can find that the use of psychostimulants in schizophrenic patients is net followed by a uniform effect. Amphetamines are known to induce psychosis and to worsen symptoms (Ianowsky and Davis 1976: A n g s t et al 1980), and some authors have found that a m ~ q e caused no effects or even improvements in negative symptoms (Kometsky 1977; Angrist et al 1982; Van Kammen et al 1982, Van Kammen and Boronow 1988; Cesarec and Nyman i985). Stimulant drugs can cause or increase psychotic symptoms in s c e n i c patients in low doses that are suhpsychotogenic in r ~ n s c ~ i c subjects 0Aeberman et al 1987). Psychotogenic vulnerability to low-dose stimulants is befieved to reflect an ~ sensitivity to DA stimulation in patients with schizophrenia (Lieberman et at 1987). Our case presented acute productive symptomatologyafter amineptine abuse. Only a very few nonschizophrenic patients develop a psychotic syndrome in a similar dose of aminepti~. The prevalence of substance abuse in schizophrenia seems to be comparable to that in the general population, with the probable exception of stimulant and hallucinogen abuse, which may be greater in patients with schizophrenia (Mueser et al 1990). 1t has been argued that schizophrenics tend to self-medicate their symptoms by preferentially abusing these types of substances (Sclmeier and Sit'is 1987). The patient's explanations for drug abuse were consistent with her desire to refieve her negative and mild positive symptoms. Deniker et al (1981), in an open study with amineptine in hebephrenic patients, described an improvement in intellectual performance, social behavior, and psychomotor activity without reactivation of previous delusional ideas. Guerard des Lauriers ~ut,u ,__1 communication) reported, however, the tread to increase amineptine dose in defectual schizophrenia. Dixon et al (I990) reported that a schizophrenic patient with a family history of drug abuse, who was exposed to drugs, and had little impairment of affect and only mild negative symptoms may be at highest risk for substance abuse (Dixon et al 1990). The same group (Dixon et al 1991) found that schizophrenic patients who abused drugs may represent a subgroup of patients with better prognoses and less severe clinical characteristics of schizophrenia, but their drug abuse may adversely affect global outcome. In conclusion, we believe that amineptine dependence can clearly complicate the course of schizophrenia- We consider that patients on the drug should be carefully supervised, and it should not be prescribed to those with a previous evidence of amphetamine, caffeine, alcohol, or other drug abuse, or those with a history of eating disorder.
mo~ psYctuA~tY 1994'.36~266~
Case Repom
References Angrist B, Rotrosen J, Gershon S (1980): Differential effects of amphetamine and neuroleptics on negative and positive symtoms in schizophrenia. Psychopharmacology 72:17-19. Angrist B, Peselow E, Rubinstein M, Corwin J. Rotrosen J (1982): Partial improvement in negative schizophrenic symptoms after amphetamine, Psychopharmacology 78:128-130. Bertschy G, Luxembourger I, Bizourd P. Vandel S. Allers R. Volmat R (1990): Dependence ~ I' amineptine. D~tection de sujets ~trisques. A propos de huit cas. Encephale 16:405-409, Biondi F, Di Rubbo R, FaraveUi C, Mannaioni P.F ( 1990): Chronic amineptine abuse, Biol Psychiat~.28:1004-1006. Bonnet JJ, Chagraoui A, Protais P, Costentin J (1986): Interactions of amineptine with the neuronal dopamine uptake system: Neurochemical in vitro and in vivo studies. J Neural Transm 69"211-220. Bozhan MA (1987): Ventral tegmental reward system, In Engel J, Orelandd L, Ingvar DH, Penow B, Rtsner S, Pellbom LA (eds), Brain Reward System and Abuse. New York: Raven Press, pp 1-17. Busto U, Sellers E (1986): Pharmacokinetic determinants of drug abuse and dependence~Clin Pharmacokinet 11:144-153. Castor A, Benzaken C, Wagniart F, Efthymiou M. L (1990): Surconsommation d'amineptine. Th~rapie45:399--405. Ceci A, Garatini S, Gobbi M, Mennini T (1986): Effect of longterm amineptine treatment on pre- and postsynaptic mechanisms in rat brain. BrJ Pharmaco188:269-275. Cesarec Z, Nyman A (1985): Differential response to amphetamine in schizophrenia. Acta Po'chiatrScald 71:523-528. Chagraoui A, Vasse M, Protais P (1989): Interaction of amineptine with agents modifying dopaminergic transmission. ClinNeuropharmacol 12(2,suppl)2:19-3 !. Deniker P, Loo H, Zarifian E, et al (1981): Etude preliminaire en ouvert de 1' amineptine sur le syndrome ddficitaire des hebtphr~nes et des toxicomanes au decours du sevrage. Encephale 7:59--64. Dixon L, Haas G, Weiden P, Sweeney J, Frances A (1990): Acute effects of drug abuse'~in schizophrenic patients: clinical observ~ior~ and patients" self-reports. Schizophr Bull ! 6:69-79. Dixon L, Haas G, Weiden P, Sweeney J, Frances A (1991): Drug abuse in schizophrenic patients: clinical correlates and reasons
for use. Am J Psychiatry 148:224-230. Garattini S, Mennini T (1989): Pharmacology ofamineptine: Synthesis and updating. Clin Neuropharmaco112(2,suppl): 13-18. Ginestet D, Cazas, Branciard M (1984): Deux cas de dependence t !' amineptine. Encephale 10"189-191. Janowsky and Davis (1976): MethyIphenidate, dexlroamphetamine, and levamphetamine: Effects on schizophrenic symptoms. Arch Gen Psychiatry33:304-308, Kometsky C (1977): Hyporespousivity of chronic schizophrenic patients todextroamphetamine.Arch Gen Psyckiatry 33:14251428. Lemoine P, Achaintre A, Balvay (3, et al (1980): Appfication de la technique d'analyse de variance ~t I'~valuation du spectre de 1' activit6 d' un nouvel agent dopaminergique: L' amineptine. Etude intercentre ~ double insu versus clomipramine, infPsychiatr 56:1045-105 I. Lieberman J. A, Kane J.M, AIvir J (1987): Provocative tests with psychostimulants drugs in schizophrenia. Psychopharmaco1ogy91:415--433. Mueser K, Yamoid P, Levinson F, et al (1990): Prevalence of substance abuse in schizophrenia: demographic and clinical correlates. Schizophr Bull 16:31-54. Oules J, Boscredon J (1983): Amineptine versus imipramine. Etude control~e a double insu. La PresseMed ! 2:2243-2246. Perez de los Cobos J.C, Jorda L.L, Pelegrin C (1990): Un cas de d~pendence ~t!' amineptine. Encephale 16:41--42. Schneier FR, Sifts SG (1987): A review of psychoactive substance use and abuse in schizophrenia. Patterns of drag choice. JNerv Ment Dis 175:641--652. Tremine T, Lauzel J, Aigrot S, Dubret G, Cousin R (1983): Un cas de toxicomanie ~t1' amineptine, lnfPsychiatr 59:1185-1189. Van Kammen DP, Bunney WE, Docherty JP, et al (1982): Damphetamine-induced heterogeneous changes in psychotic behaviour in schizophrenia. AmJPsychiatry 139:991-997. Van Kammen DP, Boronow JJ (1988): Dextro-amphetamine diminishes negative symptoms in Schizophrenia (1988). Int Clin Psychopharmacol 3: I 11-121. Vauterin C, Bazot M (1979): A double-blind controlled trial of amineptine versus trimipramine in depression. Curr Med Res Opin 6:93-100.
Amineptine Dependenceand Schizophrenia Jesus M. Pr[eto,Aria Gost, Joan Obiols, and Natalia Caycedo Key Words: Aminepfine, amphetamine, dependence, abuse, dopamine, schizophrenia
Introduction Amineptine differs from other tricyclic antidepressants because of its 7-aminoheptanoic acid side chain. In vitro studies have estabfished that amineptine inhibits uptake of dopamine and, to a lesser extent, that of noradrenaline without affecting the uptake of serotonin (Ceci et al 1986). The increase in locomotor activity induced by amincptine is significantly reduced by a pretreatment with reserpine. In contrast dexamphetamine-induced locomotor activity is not modified (Chagraoui et al 1989), The mechanism of action differs from that of (+) amphetamine in that amineptine inhibits dopamine intake and is virtually devoid of dopamine releasing effects, displaying a relatively low affinity for the norepinephrine uptake system (Bonnet et al 1986), Amineptine is an indirect dopaminergic agonist that, when given chronically, induces a downreguladon of dopaminergic and adrenergic (beta and alpha 2 subtypes) receptors. These modifications may be relevant for the drug antidepressant activity (Garafini and Mennini 1989). At a dosage of about 200 mg/day the auriclepress,ant effect has been reported to be similar to that of the major reference tryciclics (Vauterin and Bazot 1979; Lemoine et al 1980; O ~ ~ d Bosch-don i983), with a characteristic disinhibiting effect, a better tolerability, and an earlier onset of the therapheutic action. Several cases of amineptine dependence have been documented (Tremine et al 1983; Ginestet et al 1984; Biondi et al 1990; Bertschy et al 1990, Perez De Los Cobos et al 1990; Castot et al 1990) since this drug was introduced in the market. Amineptine can be considered a substance that presents a potential risk for abuse because of its dopaminergic activity (Bozhart 1987) and pharmacokinetic properties (Busto and Sellers 1986). Amineptine is rapidly absorbed, reaches its blood concentration after I hr, its half-life is about 1.5 hr and it has a high plasma clearance. From the Department of Psychiatry and Clinical Psychology, Hospital Clfnie i Provhlcial, l~n~elon~ Spain. Address reprint requests to Jesus Prieto, Department of Psychiatry and Clinical Psychology, Hospital Clfnic i Provincial, Caner Villarroel 170. 08036. Barcelona. Spain. Reccived April 22,1993; revised January 10, 1994.
© 1994 Society of Biological Psychian'y
We report a case of a schizophrenic patiem dependent on amineptine who has been followed in our hospital during the last 8 years.
Case Report In November 1993, Ms 'M, a 38-year-old unemployed single woman, was again hospitalized for an acute psychotic exacerbation after a high-dose consumption of amineptine. Over the preceding 5 days, the patient consumed amineptine in progressively higher doses until she reached 30 tablets/day (3 g/day). The clinical picture was characterized by extreme psychomotor agitation, aggressiveness, persecutory delusions, auditory hallucinations, rapid speech, and labile affect. This symptomatologyabated in less than 1 week with the suppression of the drug and neuroleptic treatment. During this treatment she did not present signs of withdrawal. Afterward a moderate residual psychotic symptomatology could he observed. Ms M began amphetamine use at age 16, initially she used the substance on a daily basis to reduce appetite (2 tablets/day) but after 2 years she began to increase the daily dose (4-5 tablets) intermittently (approximately once a month). Tlae patient had her first psychotic episode at age 19, following the break-up of a romantic relationship. She presented perplexity, fearful, and suspicious mood, no psychomotor agitation, persecutory delusions, experiences of thought control and broadcasting, depersonalization, auditory hallucinations, looseness of associations, and illogical thinking. This episode was reported not to he related to drug abuse. After a 4-month stay with a neuroleptic treatment and a course of electroconvulsive therapy, she was discharged with a moderate improvement. The diagnostic impression at that time was paranoid schizophrenia. There was no family history of psychiatric disorder The patient's early development and schooling were uneventful. Her academic performance was fair, her social development appeared normal, and there was no evidence of premorbid personality abnormalities. From age 19 to 23, and while being amphetamine abstinent Ms M had four psychotic episodes that required long hospital stays 0006-3223/94/$07.00
CaseRepom
mec~sYcmA~v
267
1~4:36:~f~2~t
(mean 6.9 months). The phenomenology was very similar to the first psychotic episode. Between hospitalizations a residual psychotic symptomatology and a lack of returning to base,he functioning could be appreciated. The patient was isolated, had trouble socializing, was unable to live alone, and was clearly impaired in work functioning. She was likely to take the medication inegularly or not at all. In this period, a high daily consumption of caffeine (7 cups of instant coffee, 3 cups of tea, and ! liter of Coke) was reported. At age 24, the patient resumed the amphetamine abuse episodically. Over the next 7 years, she needed five brief hospitalizations (mean 10.1 days) for symptom exacerbations that were clearly related to a high-dose administration of amphetamine. A few days before admission, she began using amphetamine at 10-15 tablets/day. The symptomatology and course of these episodes were strikingly similar to the amineptine-induced psychotic exacerbations. At age 3 !, she began therapy with amineptine to treat a state of mild "depressive" symptomatology. The patient was reportedly depressed with regard relation to her impairment in social and interpersonal relationships, and work functioning. In her past psychiatric history, a period of manic or depressive symptoms sufficient to qualify for a probable mood or schizoaffective disorder was not reported. She took a dose of 200 mg/day for I year and then she began to progressively increase her dosage of amphetamines. During the ensuing 9 years the patient had 14 rehospitedizations for amineptine-induced psychotic exacerbation. Ms M's pattern of amineptine use met the DSM-III-R diagnostic criteria for substance dependence. The patient had a compulsive need to use the drug on a continuing basis. The patient's self-reported reasons to resume amineptine consumption were to gain energy, to increase her socialization level, and to relieve her distressing beliefs. She believed that perhaps she really did have a psychiatric disorder, nobody wanted to many her, people were not good, her brother-in-law wanted to hurt her, and her sister was jealous of her. This symptomatology was not accompanied by irritable or depressed mood, sleep or eating disorders. The affect was mildly reduced, sometimes inappropriate, and thought content and thought processes were moderately pathological. The little insight into her illness and the low treatment compliance made the outpatient treatment very difficult, so in the last 3 years Ms M has been admitted for long hospital stays in order to receive a more suitable treatment.
Discussion a n d Conclusion We report here the first case of which we are aware of a schizophrenic patient who developed frequent amineptine-iaduced psychotic exacerbations. Some nonschizophrenic patients have been reported to develop amineptine-related psychotic symptomatology (Tremine et a11983; Castor et al 1990). The main characteristics of amineptine dependence are the constant search of a psychostimulant effect, strong psychological depeadence, and the existence of what can be considered risk factors. In the patient's past history and in agreement with other reported cases (Tremine et al 1983; Bertschy et al 1990; Biondi et al 1990; Castor et al 1990; Perez de los Cobos et al 1990 et al), we find an addiction disposition and the presence of a mild eating disorder.
These should be comideml risk factors f ~ a ~ ~ abuse. The idea that a functional excess of ~ activity is rel~_t~ to the development of ~ has been the promising and widely accepted hypothesis in the pathogenes~ of this disouler. A human model for ~ is amphemmt~e-
imi-__~_~pmanoidpsydmsi~ end b i e c l ~ y more ~ m ~ v ~ m~ me ~ ~ o ~ of dopami~ ~ su~ as ~ n e (direct) or amineptine (indirect), producing psychosis. This hypothesis is consistent with the godactive symptoms of the disorder, but cannot explain the deficit symptoms of s c ~ - _ ~ a , The pathophysiological he~nogeneity of ~ is reflected in some experimental studies, where we can find that the use of psychostimulants in schizophrenic patients is net followed by a uniform effect. Amphetamines are known to induce psychosis and to worsen symptoms (Ianowsky and Davis 1976: A n g s t et al 1980), and some authors have found that a m ~ q e caused no effects or even improvements in negative symptoms (Kometsky 1977; Angrist et al 1982; Van Kammen et al 1982, Van Kammen and Boronow 1988; Cesarec and Nyman i985). Stimulant drugs can cause or increase psychotic symptoms in s c e n i c patients in low doses that are suhpsychotogenic in r ~ n s c ~ i c subjects 0Aeberman et al 1987). Psychotogenic vulnerability to low-dose stimulants is befieved to reflect an ~ sensitivity to DA stimulation in patients with schizophrenia (Lieberman et at 1987). Our case presented acute productive symptomatologyafter amineptine abuse. Only a very few nonschizophrenic patients develop a psychotic syndrome in a similar dose of aminepti~. The prevalence of substance abuse in schizophrenia seems to be comparable to that in the general population, with the probable exception of stimulant and hallucinogen abuse, which may be greater in patients with schizophrenia (Mueser et al 1990). 1t has been argued that schizophrenics tend to self-medicate their symptoms by preferentially abusing these types of substances (Sclmeier and Sit'is 1987). The patient's explanations for drug abuse were consistent with her desire to refieve her negative and mild positive symptoms. Deniker et al (1981), in an open study with amineptine in hebephrenic patients, described an improvement in intellectual performance, social behavior, and psychomotor activity without reactivation of previous delusional ideas. Guerard des Lauriers ~ut,u ,__1 communication) reported, however, the tread to increase amineptine dose in defectual schizophrenia. Dixon et al (I990) reported that a schizophrenic patient with a family history of drug abuse, who was exposed to drugs, and had little impairment of affect and only mild negative symptoms may be at highest risk for substance abuse (Dixon et al 1990). The same group (Dixon et al 1991) found that schizophrenic patients who abused drugs may represent a subgroup of patients with better prognoses and less severe clinical characteristics of schizophrenia, but their drug abuse may adversely affect global outcome. In conclusion, we believe that amineptine dependence can clearly complicate the course of schizophrenia- We consider that patients on the drug should be carefully supervised, and it should not be prescribed to those with a previous evidence of amphetamine, caffeine, alcohol, or other drug abuse, or those with a history of eating disorder.
mo~ psYctuA~tY 1994'.36~266~
Case Repom
References Angrist B, Rotrosen J, Gershon S (1980): Differential effects of amphetamine and neuroleptics on negative and positive symtoms in schizophrenia. Psychopharmacology 72:17-19. Angrist B, Peselow E, Rubinstein M, Corwin J. Rotrosen J (1982): Partial improvement in negative schizophrenic symptoms after amphetamine, Psychopharmacology 78:128-130. Bertschy G, Luxembourger I, Bizourd P. Vandel S. Allers R. Volmat R (1990): Dependence ~ I' amineptine. D~tection de sujets ~trisques. A propos de huit cas. Encephale 16:405-409, Biondi F, Di Rubbo R, FaraveUi C, Mannaioni P.F ( 1990): Chronic amineptine abuse, Biol Psychiat~.28:1004-1006. Bonnet JJ, Chagraoui A, Protais P, Costentin J (1986): Interactions of amineptine with the neuronal dopamine uptake system: Neurochemical in vitro and in vivo studies. J Neural Transm 69"211-220. Bozhan MA (1987): Ventral tegmental reward system, In Engel J, Orelandd L, Ingvar DH, Penow B, Rtsner S, Pellbom LA (eds), Brain Reward System and Abuse. New York: Raven Press, pp 1-17. Busto U, Sellers E (1986): Pharmacokinetic determinants of drug abuse and dependence~Clin Pharmacokinet 11:144-153. Castor A, Benzaken C, Wagniart F, Efthymiou M. L (1990): Surconsommation d'amineptine. Th~rapie45:399--405. Ceci A, Garatini S, Gobbi M, Mennini T (1986): Effect of longterm amineptine treatment on pre- and postsynaptic mechanisms in rat brain. BrJ Pharmaco188:269-275. Cesarec Z, Nyman A (1985): Differential response to amphetamine in schizophrenia. Acta Po'chiatrScald 71:523-528. Chagraoui A, Vasse M, Protais P (1989): Interaction of amineptine with agents modifying dopaminergic transmission. ClinNeuropharmacol 12(2,suppl)2:19-3 !. Deniker P, Loo H, Zarifian E, et al (1981): Etude preliminaire en ouvert de 1' amineptine sur le syndrome ddficitaire des hebtphr~nes et des toxicomanes au decours du sevrage. Encephale 7:59--64. Dixon L, Haas G, Weiden P, Sweeney J, Frances A (1990): Acute effects of drug abuse'~in schizophrenic patients: clinical observ~ior~ and patients" self-reports. Schizophr Bull ! 6:69-79. Dixon L, Haas G, Weiden P, Sweeney J, Frances A (1991): Drug abuse in schizophrenic patients: clinical correlates and reasons
for use. Am J Psychiatry 148:224-230. Garattini S, Mennini T (1989): Pharmacology ofamineptine: Synthesis and updating. Clin Neuropharmaco112(2,suppl): 13-18. Ginestet D, Cazas, Branciard M (1984): Deux cas de dependence t !' amineptine. Encephale 10"189-191. Janowsky and Davis (1976): MethyIphenidate, dexlroamphetamine, and levamphetamine: Effects on schizophrenic symptoms. Arch Gen Psychiatry33:304-308, Kometsky C (1977): Hyporespousivity of chronic schizophrenic patients todextroamphetamine.Arch Gen Psyckiatry 33:14251428. Lemoine P, Achaintre A, Balvay (3, et al (1980): Appfication de la technique d'analyse de variance ~t I'~valuation du spectre de 1' activit6 d' un nouvel agent dopaminergique: L' amineptine. Etude intercentre ~ double insu versus clomipramine, infPsychiatr 56:1045-105 I. Lieberman J. A, Kane J.M, AIvir J (1987): Provocative tests with psychostimulants drugs in schizophrenia. Psychopharmaco1ogy91:415--433. Mueser K, Yamoid P, Levinson F, et al (1990): Prevalence of substance abuse in schizophrenia: demographic and clinical correlates. Schizophr Bull 16:31-54. Oules J, Boscredon J (1983): Amineptine versus imipramine. Etude control~e a double insu. La PresseMed ! 2:2243-2246. Perez de los Cobos J.C, Jorda L.L, Pelegrin C (1990): Un cas de d~pendence ~t!' amineptine. Encephale 16:41--42. Schneier FR, Sifts SG (1987): A review of psychoactive substance use and abuse in schizophrenia. Patterns of drag choice. JNerv Ment Dis 175:641--652. Tremine T, Lauzel J, Aigrot S, Dubret G, Cousin R (1983): Un cas de toxicomanie ~t1' amineptine, lnfPsychiatr 59:1185-1189. Van Kammen DP, Bunney WE, Docherty JP, et al (1982): Damphetamine-induced heterogeneous changes in psychotic behaviour in schizophrenia. AmJPsychiatry 139:991-997. Van Kammen DP, Boronow JJ (1988): Dextro-amphetamine diminishes negative symptoms in Schizophrenia (1988). Int Clin Psychopharmacol 3: I 11-121. Vauterin C, Bazot M (1979): A double-blind controlled trial of amineptine versus trimipramine in depression. Curr Med Res Opin 6:93-100.