Methylphenidate effective in treating amphetamine abusers with no other psychiatric disorder.
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Biomedical subjects
Publications and source records attributed to X Laqueille.
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OBJECTIVE: Buprenorphine has a partial morphine-agonist pharmacological profile. It is proposed as alternative to methadone in opiate drug addicts with greater safety of use and less cost in terms of public health. The aim of this study was to determine the clinical factors of response to this molecule. METHOD: The study was conducted in 73 patients treated for 3 months with adaptable doses. Mean dose was 8.5 mg/d (range: 3 to 16 mg/d). Response to treatment was defined as: still in the study at 3 months and absence of opiates in 75% of urinary samples over the past month. RESULTS: Forty-eight patients responded and 25 did not. The determinating clinical variables of response were: opiate drug addiction less than 10 years, high score on the Addiction Severity Index (ASI), absence of depression according to the Minnesota Multiphasic Personality Inventory (MMPI) and low rate of disinhibition on Zukerman's sensation seeking scale. Conversely, the dose of buprenorphine within the limits specified in the Marketing Authorisation did not intervene in the response. CONCLUSION: In view of its partial agonist effect, administration of buprenorphine must be reserved for patients addicted to opiates for less than 10 years, non-depressive and with low disinhibition on Zukerman's scale.
OBJECTIVE: The authors compared impulsivity, sensation seeking, and anhedonia in a group of schizophrenic patients with and without lifetime substance abuse or dependence. METHOD: Patients (N=100) with schizophrenia or schizoaffective disorder (per DSM-III-R criteria) were assessed with the Composite International Diagnostic Interview's section on psychoactive substance use disorder, the Positive and Negative Syndrome Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. RESULTS: The mean scores for impulsivity and sensation seeking were higher in the group with substance abuse (N=41) than in the group without substance abuse (N=59). No significant difference between groups was found regarding physical anhedonia. CONCLUSIONS: As in the general population, high levels of impulsivity and sensation seeking are associated with substance abuse in patients with schizophrenia.
The simultaneous determination of methadone (Mtd) enantiomers and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in human urine and serum by enantioselective HPLC using a new Cyclobond 1-2000 RSP column is described. After alkaline extraction from urine or serum with estazolam as an internal standard, Mtd enantiomers and its metabolite (EDDP) are separated on the previous column with reversed-mobile phase and detected at 210 nm. Peak resolutions are about 2.0 for Mtd enantiomers. The relative standard deviations (R.S.D.) of Mtd and EDDP standards are between 0.5 and 4.5%. Most drugs of abuse are shown not to interfere with this technique. The method has been applied to study the levels of each Mtd enantiomer and of its racemic metabolite in urine and serum of patients under maintenance treatment for opiate dependence. In urine, R-(-)-Mtd levels are always higher (about 2+/-0.5-fold) than those of S-(+)-Mtd and in most cases, metabolite concentrations are greater than those of global Mtd enantiomers. However, the R-(-) enantiomer levels of residual drug in serum of some patients were lower than those of its antipode. This method is suitable for pharmacokinetic and toxicological studies of Mtd enantiomers and its major metabolite in biological fluids.
Depressive syndromes are very frequent in drug-addicted patients. Their study is particularly difficult on account of the toxic intake which disturbs the clinical analysis. Methadone has improved our understanding of these pathologies. In fact, methadone permits treatment of some depressive disorders typically linked to addiction, such as a motivational symptoms and depressive mood following intoxication. It brings to the fore the other mood disorders which are often associated with drug intake.
Drug addiction is a serious behavioral disorder. It is a long term evolving process characterized by dependency. It is not only biological and psychological but also social. It should be differentiated from occasional drug use, from drug abuse with minor consequences as well from medical drug dependency in which the individual does not seek a psychological effect. Drug addiction causes are multiple and include psychological, family, social and obviously biological factors (drug addicting potential). In to-day clinical practice, addiction to benzodiazepines or opioids prescribed for maintenance therapy and the newly described secondary addiction of later onset are predominant. Severe social consequences and many psychiatric and medical disorders in particular due to HIV infection also result from drug addiction. Depressive and psychotic disorders cause specific therapeutic problems when patients deny their troubles or when drug use produces special relief. These psychological disorders frequently underlie medical care needs.
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The authors present a review of literature and their personal experience concerning the practice of methadone substitutive therapy for heroin addicts in France. In their experience, the use of methadone, within the frame of a controlled administration and in the perspective of a specific pharmaco-therapeutic profile, is a valuable therapeutical option. Otherwise, methadone could only induce a new and further pharmacological dependence. The use of methadone has often been the subject of controversies overlooking the clinical reality of drug addiction. Therefore, a controlled use of methadone remains a valuable therapeutic tool if its indications are strictly delimited.
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UNLABELLED: Whereas observations of psychotic disorders induced by amphetamines are common, few observations described the impact of chronic amphetamine abuse on schizophrenic patients. We report the case of a schizophrenic patient who presented with amphetamine dependence for several years, without other accompanying addiction. CASE REPORT: During his adolescence, Mr. X. gradually developed delusional beliefs of persecution and telepathy. He believed that the other pupils and teachers spoke about him in malicious terms. At the age of 23, Mr. X began to consume 60-100 mg/week of amphetamines orally. He consumed amphetamines during 7 years. The delusions, in particular the auditory hallucinations worsened after the use of amphetamines. Subsequently, he married and was declared unfit for national service due to the psychotic disorders. Mr. X received neuroleptic treatment with moderate effects on the psychotic symptoms. Between the age of 24 and 30, the patient presented persecutory, megalomanic and physical transformation beliefs, delusions of being controlled as well as auditory, somatic-tactile and visual hallucinations. At the age of 30, while he had stopped his consumption of amphetamines for 9 months, the patient, overwhelmed with the delusions, murdered his wife. He was sent in jail for 13 months, and subsequently hospitalized for one year in a high security psychiatric department and 7 years in our psychiatric department. The neuroleptic treatment was effective, particularly against the hallucinations. Following stabilisation, the symptomatology of the patient was marked by a disorganization syndrome, including prominent thought disorder, disorganized speech, associative loosening, frequent derailments and negative signs of schizophrenia, in particular affective flattening and blunting of emotional expression. When the patient was 43, a trial discharge was authorized owing to improvement of his condition. The neuroleptic treatment was switched with single-drug olanzapine therapy, 10 mg/day which improved the negative symptoms. Mr. X. resumed part-time professional activities and remarried. DISCUSSION: The patient fulfilled the DSM IV criteria for schizophrenia and for amphetamine dependence assessed using the Composite International Diagnostic Interview (CIDI). He presented, in particular, withdrawal syndrome when amphetamines were discontinued. The amphetamine consumption was followed by a marked deterioration in the delusions, particularly the hallucinations. Worsening of the positive symptoms in schizophrenic patients by amphetamines has been established in single dose studies, in particular characterized by persecutory delusions and hallucinations. On the other hand, amphetamines tend to transiently and moderately reduce the negative symptoms. Some stu-dies have shown that amphetamine consumption promoted violent acting out in non-schizophrenic subjects. In our observation, the acting out may be not related to the acute effects of these substances, since it occurred 9 months after stated discontinuation of amphetamine consumption. However, the cerebral toxicity and psycho-behavioural disturbances related to amphetamines might be prolonged after withdrawal. In non-schizophrenic patients, the existence of prolonged neurotoxicity of amphetamines and related psycho-behavioral disturbances has been suggested. The prolonged administration of amphetamines to animals produces neuro-axonal degeneration in the striatum, the frontal cortex, the nucleus accumbens and the amygdala. In human, there are some evidence of persistant deteriorations of the serotoninergic and dopaminergic systems in the caudate nucleus, the putamen and the nucleus accumbens following amphetamine consumption. CONCLUSION: The neurobiological and psycho-behavioural effects of amphetamines may be prolonged following withdrawal in both schizophrenic and non-schizophrenic patients.
In January 2002, the official French methadone legislation prescription was modified. Thus, the number of clinicians authorized to introduce methadone substitution was increased. Knowledge of the pharmacokinetic and pharmacological properties of this compound remains particularly important for its appropriate prescription. Bearing this in mind, we linked methadone pharmacokinetics to its pharmacological use in this article. METHADONE PHARMACOLOGY: Methadone is a synthetic opiate. Its mean bioavailability is around 75%. Cytochrome P450 3A4 and 2D6 are involved in its hepatic metabolism. Its volume of distribution is of around 4 L/kg. The value of half-life elimination is of around 22 hours. These pharmacokinetic properties (long half-life, steady state concentration) are in favour of substitution use of this opiate. In practice, clinicians progressively introduce this substitution therapy to reach 80 mg +/- 20 mg per day, once daily. Therapeutic clinical goals are mainly to reduce craving, withdrawal symptoms, and to manage psychosocial problems and psychiatric co-morbidity. Practitioners should bear the latter in mind once substitution therapy has been appropriately initiated and stabilized. However, wide, interpatient, interindividual variability impacts on pharmacokinetic parameters. Subjects may be either high or poor metabolizers. Thus, bioavibility ranges from 36 to 100%. Induction or inhibition of CYP450 significantly modifies methadone pharmacodynamic properties. Genetic variability and medication can induce non response to substitution, craving, or withdrawal symptoms. PHARMACOLOGICAL INTERACTIONS: We describe here a large number of medications involved in pharmacokinetic or pharmacological interactions. Classical enzymatic inductors, such as antiepileptic molecules (phenobarbital, carbamazepin), antituberculosis compounds (rifampicin), or antiretroviral therapy (efavirenz, nevirapin, ritonavir), could possibly lead to respiratory depression for example. Metabolism inhibitors such as selective serotonin reuptake inhibitors (fluvoxamine, fluoxetine, paroxetine, sertraline) or antifungals of the azol groups could enhance plasma concentration and may sometimes lead to respiratory depression or death. Nevertheless, clinicians should know methadone pharmacokinetic properties and pharmacological interactions for the optimal opiate-dependant patients' management. CLINICAL USE: Clinicians can use plasma concentrations as a useful indicator to reach substitution goals. The methadone plasmatic target value of 400 microg/ml can be recommended for therapeutic drug monitoring. This dosage not only facilitates interaction detection, but also hand encourages communication with the patient.
UNLABELLED: The high prevalence of psychoactive substance abuse or dependence among schizophrenic patients has now been well established. Mueser et al. stressed the need to assess the abuse of specific classes of substances and analyse the data accordingly. The objective of this study was to compare the socio-demographic correlates and the clinical features in a group of schizophrenic patients with a lifetime cannabis abuse or dependence according to the DSM III-R with a group of schizophrenic patients who had never presented any abuse or dependence. SUBJECTS AND METHODS: The study included 124 subjects with diagnoses of schizophrenia or schizoaffective disorders according to the DSM III-R. Inclusion criteria for participation in the study were age 18 years or older and willingness to provide consent to participate in the study. The inpatients were evaluated when their condition was stabilised. Assessment tools were the psychoactive substance use disorder section of the Composite International Diagnostic Interview (CIDI), the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning Scale (GAF). Subjects with cannabis abuse or dependence during their lifetime were compared with subjects without abuse or dependence, using chi(2) test for categorical variables and analyses of covariance (ANCOVA) for quantitative variables. RESULTS: Forty-nine subjects (42,6%) presented lifetime abuse or dependence on one or more substances. Since 19 patients with alcohol, stimulant, sedative or opiate abuse or dependence were excluded, the study finally included 96 subjects including a first group of schizophrenic patients with cannabis abuse (n=6) or dependence (n=24) and a second group without any psychoactive substance abuse (n=66). Thirteen (11.3%) patients presented cannabis abuse or dependence within the 6 months prior to the assessment. The mean SD age of onset of cannabis abuse or dependence was 19.6 +/- 3.0 years. Cannabis abuse/dependence preceded the first psychiatric treatment in 70% of the subjects (n=21). 83.3% of the schizophrenic patients with cannabis abuse or dependence were male (n=25) compared to 62.1% in the group without substance abuse (n=41) (chi(2)=4.32, df=1, p=0.04). Schizophrenic patients with cannabis abuse were significantly younger (mean age: 28.9 +/- 6.3 vs 37.0 +/- 12.7, ANCOVA, F=7.2, df=1,96 p=0.009). There was no significant difference between the two groups for marital status, (chi(2)=5.34, df=2, p=0.07), level of education, (chi(2)=0.93, df=2, p=0.62) professional status, (chi(2)=8.7, df=5, p=0.11), on PANSS total score (ANCOVA, F=0.42, df=1,93, p=0.52), GAF score (ANCOVA, F=0.06, df=1,92, p=0.80), mean number of hospitalizations (ANCOVA, F=3.25, df=1,85, p=0.08), mean age of first psychiatric contact (ANCOVA, F=0.74, df=1,93, p=0.39), and neuroleptic dosages (ANCOVA, F=0.03, df=1,90, p=0.87). In contrast, the total duration of hospitalization was significantly longer for the group with cannabis abuse. Patients with cannabis abuse were more likely to have an history of suicide attempts than subjects without substance abuse (chi(2)=11.52, df=1, p=0.0007). DISCUSSION: The prevalence rates for substance abuse and the socio-demographic characteristics of the population of our study are consistent with findings of previous studies. Male gender and age were significantly related to history of cannabis abuse or dependence. Cannabis abuse frequently preceded the onset of psychiatric treatment. However, both schizophrenia and substance abuse tend to develop gradually, with no clear demarcation for the onset of schizophrenia. The absence of any link between the scores for the subscales of the PANSS and cannabis abuse, both in our study and in some retrospective previous studies, is not suggestive of cannabis abuse as a self-medication of positive or negative symptoms of schizophrenia. Self-medication could concern other symptoms, such as cognitive deficits. In addition, the hypothesis of self-medication has especially been suggested in cocaine abuse or dependence. Some limitations to this study can be discussed. First, although the recruitment was systematic and done in a public mental health service, the patients of our study are not necessarily representative of all schizophrenic patients. Secondly, as in any retrospective study, the prevalence of lifetime substance abuse may have been under-estimated. Urinary toxicology tests may have been able to improve the sensitivity of the diagnosis of recent substance abuse, but structured interviews are more appropriate for the diagnosis of lifetime substance abuse in schizophrenic patients than urinary toxicology tests. CONCLUSION: The socio-demographic characteristics of cannabis abuse or dependence in schizophrenia are similar to those found in general population. Cannabis using schizophrenic patients were more likely to be younger and male than non users. The duration of hospitalization was significantly longer for the group with cannabis abuse. Prevalence of suicide attempts in schizophrenia is closely correlated to cannabis abuse.
Some rituals about a regular consumption of tea, smokeless tobacco (chewing) and milk are described by one of the authors at the time of his anthropological investigation among the Tuaregs of Timbuktu's region (Mali). He carries out some ethnographical and clinical materials which highlight the dependence to these substances and the role of their psychostimulant and anorexigene effects in a society much ritualised. The subject of this article appears original in the literature which approaches more the dependence to coffee than tea, to cigarettes than to chewing tobacco. The observation of daily life of a tuareg encampment shows a ritual consumption of tea at four time a day. The motivations of the Tuaregs are the increase of vigilance and performance with that psychostimulant substance. They describe an intoxication syndrome related to caffeineism, observed among European tourists. The Tuaregs are aware of their addiction to tea and distinguish psychological dependence from physical dependence. The psychological dependence corresponds to a powerful desire to drink tea at ritual moments, while the physical dependence appears at waking-up and when the time of preparing this beverage is too late. The Tuaregs describe also a phenomenon of loss tolerance after an abstinence period. In spite of the maraboutic prohibition to drink tea, which diverts Tuaregs of their religious practice, they defy this ban from the waking-up to take that infusion before the matinal prayer. That addiction appears also in the identity of the Tuaregs who are called "the sons of tea". The consumption of chewing tobacco, mixed with ash, rhythms the daily life. The mean number of chewing is about fifteen by day; every chewing last 30 minutes. The first chewing of the day occurs 15 minutes after waking-up. The Tuaregs use tobacco in order to get relaxation and vigilance. They suggest intoxication symptoms and especially a withdrawal syndrome which appears at the waking-up or after an important interval between chewing. The authors raise the idea about the dependence to this type of tobacco, consistent with the Anglo-Saxon literature of the 80th which tried to implement scales and criteria as to assess the dependence to smokeless tobacco. The Tuaregs could be more addicted than American consumers in regard to american studies: they use more chewing a day and they can't refrain from chewing at the waking-up. Empirical addition of plant ash, made up of hydroxide of calcium, may act a role in pharmacokinetic by alkalinising the pH. It could increase the absorption of nicotine through the mouth mucus membrane. The authors raise the idea about the dependence to the milk, much consumed and ritualised among those nomadic breeders. They rely on the observation of a withdrawal syndrome clearly identified in the tuareg medical nosography. These regular consumptions integrate the daily life within other rituals. Tea and tobacco facilitate certain motor stimulation, a struggle against hunger and some relaxation regarding an hostile environment over climatological, ecological and economical plan. The brutal and unexpected occurring of one of those rituals disrupt, indeed invert, the usual order of social rituals. Those social and religious disruptions materialise the pathological effect of that double dependence to nicotine and caffeine. That one is called by a term which translate its subjective and social appearance, reflecting so the interaction between man, environment and psychoactive substance. This article highlight the importance of cultural factors in the etiopathogeny of poly-dependence among Tuareg subjects. The question about the diagnostic of the dependence in the DSM IV and the CIM-10 is raised. The DSM IV could be completed because it doesn't evoke addiction to caffeine of tea such like it is consumed in West actually. That hermeneutic approach, including anthropological observations and clinical investigations, allow to understand that addiction to psychoactive substances among Tuareg subjects is consistent with their survival in hostile environments.