[Alcohol addiction and old age : state of the art]. / Alcoolodépendance et transition vers l'âge avancé : état des lieux.

The age of retirement until old age are driving on same important changes for physical health, mental health and decreasing social or working environment. The prevalence of alcohol addiction increases in this age group and is often underestimated by caregivers. Retirement is given as a risk factor to develop an alcohol addiction (late onset). It's also a worsening factor, when an alcohol addiction is already present (early onset). The consequences on physical health, mental health and psychosocial problems requires plural skills and coordination between the different stakeholders in the health, social and family sectors in order to find need- adapted solutions and treatments.

La phase de transition entre 55 ans et l'âge avancé amène de nombreux changements pour les personnes concernées, que ce soit au niveau psychique, physique ou socioprofessionnel. Dans le contexte du vieillissement de la population, les prises en charge des personnes souffrant de problèmes d'alcoolodépendance dans cette tranche d'âge prennent plus d'importance et sont souvent sous-estimées. Le passage à la retraite constitue un facteur de risque de développement d'une alcoolodépendance et un facteur d'aggravation quand celle-ci est déjà installée. L'intrication des problèmes (addictologiques, psychiques, somatiques, psychosociaux) exige des compétences plurielles et une coordination entre les différents intervenants des domaines de la santé, du social et de l'entourage familial afin de trouver des solutions adaptées aux besoins de la personne concernée.

[Addiction: what's new in 2022]. / Addictions : ce qui a changé en 2022.

Addictions appear everywhere, mutate, transform with new products and behaviors, playing on our painstaking efforts to try to control them. Drawn into this current, the impression that dominates invites more to understand and to coax rather than to fight. Addictions are our condition, let's deal with it, rather than fight against them. It is therefore a question of knowing the products, that everyone can identify their level of risk, and of giving as many tools as possible, at any age, whatever the behavior or the product. This article shows us that there is a lot to do, from school benches to liver transplantation. There is also a lot to discover, in the recognition of the therapeutic virtues, of cannabinoids for example or even in their prescription, of pharmaceutical heroin for example, sometimes by far the best option.

Les addictions émergent de partout, mutent, se transforment avec des nouveaux produits et comportements, se jouant de nos efforts laborieux pour tenter de les contrôler. Entraînés dans ce courant, l'impression qui domine invite davantage à comprendre et à amadouer plutôt qu'à lutter. Les addictions sont notre condition, faisons avec, plutôt que contre. Il s'agit donc de connaître les produits, que chacun puisse identifier son niveau de risque, et de donner autant d'outils que possible, à tout âge, quel que soit le comportement ou le produit. Cet article nous montre qu'il y a beaucoup à faire, des bancs de l'école à la transplantation hépatique. Il y a aussi beaucoup à découvrir, dans la reconnaissance des vertus thérapeutiques, des cannabinoïdes par exemple, ou encore dans leur prescription, de l'héroïne pharmaceutique, parfois de loin la meilleure option.

[Virtual reality exposure therapy for treating addictions and craving]. / La thérapie par exposition en réalité virtuelle pour traiter les addictions et le craving.

Heroin addiction causes damage to physical and psychological health and can have serious social consequences. For people with addictive disorders, maintaining abstinence is a major difficulty. The stimuli that trigger cravings and urges are present in everyday life. For example, the presence of the substance, its smell, a stressful situation or a negative or positive emotion can trigger a strong urge for substance use. Craving can contribute to relapse episodes. Virtual reality exposure therapy (VET) may train people to cope differently when facing such triggers. This article presents a synthesis of the literature and the clinical steps involved in VET.

La dépendance à l'héroïne provoque des dommages à la santé physique et psychique, et peut avoir des conséquences médicales, sociales et familiales graves. Pour ces patients, le maintien de l'abstinence est une difficulté majeure. Les stimuli déclenchant des envies impérieuses de consommation (craving) sont présents dans le quotidien ; ainsi, la présence de la substance, son odeur, une situation stressante ou encore une émotion négative ou positive peuvent déclencher un important craving qui peut contribuer aux épisodes de rechute. La thérapie par exposition en réalité virtuelle (TERV) pourrait entraîner les personnes à y faire face autrement qu'en consommant. Cet article présente une synthèse des données de la littérature ainsi que les étapes de déroulement d'un programme clinique avec la TERV.

Prison Unhealthy Lifestyle and Poor Mental Health of Older Persons-A Qualitative Study.

Background: Mental healthcare and lifestyle habits in prison, especially for older individuals, has been shown to be suboptimal. Most psychiatric conditions left untreated worsen food choices, physical inactivity, and substance abuse. In turn, bad habits lead to poorer mental health. Methods: To comprehensively illustrate this downward spiraling, we completed a thorough analysis of data obtained through semi-structured qualitative interviews. There were 50 interviews of aging incarcerated people included in this article. They were analyzed following a classical six-stepped thematic analysis. Results: According to our participants, sports are not well-adapted to aging individuals, nor to people with medical conditions. Prison is even more unadapted for those who both are aging and have medical conditions. Also, food served is less than optimal. According to our interviews, the older imprisoned individual often does not have access to food adapted to his or her medical conditions. Sport is maladapted for older incarcerated individuals and mostly tailored for younger ones. Finally, boredom and lack of responsibility hinder change toward a better lifestyle for older adults in prison. Conclusion: Our paper shows why prison environmental modifications are needed to help older adults with their lifestyle habits. It also exposes an original way to see the relationship between mental health and lifestyle habits.

Persistence of Neuronal Alterations in Alcohol-Dependent Patients at Conclusion of the Gold Standard Withdrawal Treatment: Evidence From ERPs.

Background: One of the main challenges for clinicians is to ensure that alcohol withdrawal treatment is the most effective possible after discharge. To address this issue, we designed a pilot study to investigate the efficacy of the rehabilitation treatment on the main stages of information processing, using an electroencephalographic method. This topic is of main importance as relapse rates after alcohol withdrawal treatment remain very high, indicating that established treatment methods are not fully effective in all patients in the long run. Method: We examined in alcohol-dependent patients (ADP) the effects of the benzodiazepine-based standard detoxification program on event-related potential components at incoming (D0) and completion (D15) of the treatment, using tasks of increasing difficulty (with and without workload) during an auditory oddball target paradigm. Untreated non-alcohol-dependent-volunteers were used as matching controls. Results: At D0, ADP displayed significantly lower amplitude for all ERP components in both tasks, as compared to controls. At D15, this difference disappeared for the amplitude of the N1 component during the workload-free task, as well as the amplitude of the P3b for both tasks. Meanwhile, the amplitude of the N2 remained lower in both tasks for ADP. At D0, latencies of N2 and P3b in both task conditions were longer in ADP, as compared to controls, whilst the latency of N1 was unchanged. At D15, the N2 latency remained longer for the workload condition only, whereas the P3b latency remained longer for the workload-free task only. Conclusion: The present pilot results provide evidence for a persistence of impaired parameters of ERP components, especially the N2 component. This suggests that neural networks related to attention processing remain dysfunctional. Longitudinal long-term follow-up of these patients is mandatory for further assessment of a link between ERP alterations and a later risk of relapse.

[Adaptations of an outpatient Dialectical Behavioral Therapy during the COVID-19 pandemic and consequences of the confinement on patients with borderline personality disorder]. / Adaptations de la thérapie comportementale dialectique ambulatoire en période de pandémie COVID-19 et conséquences du confinement sur des patients souffrant d'un état-limite.

BACKGROUND: The COVID-19 pandemic impacted the accessibility of psychotherapy for particularly vulnerable patients during the period of confinement in the French-speaking part of Switzerland. We had to adapt our usual therapeutic programs. We illustrate this approach in an outpatient program of dialectical behavioral therapy for patients with borderline personality disorder. Each week the individual therapies took place by videoconference or phone. The skills training group was held individually by videoconference or phone and was supported by an online skills training program. Patients filled out their diary cards online. Intersession contact with the therapist remained available as usual and we could organize team consultation. The aim of this study is to describe how a sample of our patients experienced the period of confinement. METHOD: We compared the experiences of seven patients suffering from borderline personality disorder during two periods: eight weeks prior to confinement, and during the eight weeks of confinement. We analyzed their daily diary cards (n = 426) and their weekly frequency of problem behaviors (n = 69). We performed multilevel analyses to take into account the hierarchical structure of the data and the autocorrelation of observations. RESULTS: The seven patients were predominantly female (85.7 %) and had an average age of 35.1 (11.5) years. Measurements prior to the start of the pandemic indicated on average severe depression (Beck Depression Inventory, m = 30.9 [10.0]) and marked hopelessness (Beck Hopelessness Scale, m = 15.0 [5.0]). Analysis of the daily diary cards indicated that the confinement period significantly predicted a decrease in feelings of shame or guilt, fear and tension. At the same time, however, there was an increase in distress. Weekly monitoring of problem behaviors showed a decrease in binge-eating behaviors and a trend towards a decrease in alcohol consumption during confinement. CONCLUSIONS: Despite the small number of patients included, two types of repeated measurements indicated convergent results, with some improvements during confinement: a decrease of the feelings of fear, shame or guilt, and tension, and a decrease of the frequency of binge-eating behaviors. The decreased pace of daily social and professional life may explain these improvements. The diminution of the above-mentioned feelings as triggers for addictive and compulsive behaviors may also account for the improvements regarding binge-eating. However, they also experienced an increased distress that may reflect the loneliness experienced during this period. The pre-pandemic development of computerized tools that were already familiar to patients greatly facilitated the necessary adaptations to maintain an intensive therapeutic setting during the confinement. This may partly explain why these patients were able to adjust the challenges of this period.

False memory production in schizophrenia: A neurophysiological investigation.

BACKGROUND: The topic of false memory in schizophrenia has been well documented in earlier research contributions. To date, there is no study exploring the implications of specific neural networks during this phenomenon in patients suffering from schizophrenia. METHODS: We compared 17 patients suffering from psychosis (SCZ) to 33 healthy controls (HC) performing a verbal memory task designed to produce false memories, i.e. the Deese-Roediger-McDermott paradigm (DRM). Electroencephalography was used to specifically analyze the P2 and N400 event-related potentials components. RESULTS: The SCZ patients showed a reduced ability to distinguish between true and false memories as assessed by the A' index which was calculated based on the false and true memory rates. The morphology of the P2 differed in frontal electrode region with a lower amplitude in SCZ. In addition, the amplitude of N400 was more pronounced (more negative) in HC than in SCZ in centro-parietal electrode site. CONCLUSIONS: We suggest that the differences found in P2 amplitude are associated with difficulties of SCZ patients to efficiently compare item-specific features of a mnesic elements to incoming stimuli which impair the subsequent verbal memory information processing reflected by the N400 component amplitude decrease. These results are consistent with the idea that SCZ use a different strategy while they perform the DRM paradigm.

[Addictions]. / Addictions.

This article describes a new form of administration of inhaled prescribed heroin currently under investigation. It underlines the particularity of opioid agonist prescription in jail and presents new perspectives in using psilocybin in addiction medicine treatment. A brief literature review about vaping confirms its interest in quitting cigarette, with a cost of addiction to vaping and recent worrisome reports of chemical pneumonia. Finally, the withdrawal of WHO guidelines on opiates use in pain management, in the context of a suspicion of conflict of interest, underlines the sensible balance between over- and under- prescription of opiates in analgesic treatment.

Cet article montre l'intérêt d'une nouvelle forme d'administration inhalée d'héroïne pharmaceutique actuellement à l'étude. Il sensibilise aux conditions particulières de la prescription d'agonistes opioïdes en milieu carcéral et ressuscite des souvenirs des seventies en reprenant l'exploration scientifique des vertus thérapeutiques de la psilocybine. Même si le vapotage semble être un bon moyen de lâcher la cigarette, les anciens fumeurs ont tendance à s'y accrocher et un risque de pneumonie chimique parfois mortelle vient d'être mis en évidence. Finalement, le retrait de l'OMS de deux directives relatives à l'usage d'opioïdes dans le traitement de la douleur, sur fond de suspicion de conflit d'intérêts, montre l'équilibre délicat entre sur- et sous-prescription des antalgiques opioïdes.

[Adolescents and young adults with substance abuse and comorbid psychiatric disorders : which treatment ?] / Abus de substances et troubles psychiatriques chez les adolescents et jeunes adultes : quels traitements ?

Substance abuse among adolescents and young adults is common. For 5 to 7 % of young people, substance use become problematic, take a function in the psychic equilibrium of the subject and will stop the adolescent process. For some, continuing substances use will be associated with the development of a primary or secondary psychiatric disorder. People with a first psychotic episode (FEP) with cannabis use will stop their use for 50 % of them, with early management of the disorder, without targeted addictive intervention. For the other half, persistent substance uses deteriorate the evolution of psychotic disorders. The treatment aims to avoid such evolution.

L'abus de substances chez les adolescents et jeunes adultes est fréquent. Pour 5 à 7 % des jeunes, la consommation deviendra problématique, prendra une fonction dans l'équilibre psychique du sujet et bloquera de facto le processus d'adolescence. Pour certains, la consommation sera associée au développement d'un trouble psychique primaire ou secondaire. Les personnes souffrant d'un premier épisode psychotique (FEP) avec consommation de cannabis associée stopperont pour 50 % d'entre elles leur consommation avec une prise en charge précoce du trouble, sans intervention addictologique ciblée. Pour l'autre moitié, la consommation persistante de substances est un facteur aggravant de l'évolution du trouble psychique. L'enjeu du traitement est d'éviter de telles évolutions.

Optimism and the Psychological Recovery Process Among Informal Caregivers of Inpatients Suffering From Depressive Disorder: A Descriptive Exploratory Study.

Background: Informal caregivers of people suffering from depressive disorders go through a psychological recovery process. This process is dynamic, deep, catalyzed by hope and optimism and characterized by stages from which specific needs ensue. This study aimed to describe the stages of the psychological recovery process and the level of optimism among informal caregivers of psychiatric inpatients suffering from depressive disorders in order to provide adapted nursing support and psychoeducation and facilitate a patient's own recovery. Methods: A descriptive exploratory study was conducted using a convenience sample of 29 informal caregivers. Participants filled out a sociodemographic questionnaire, a specially adapted Stages of Recovery Instrument (STORI) and the Life Orientation Test-Revised (LOT-R). Results: A mean optimism score of 16.41 showed that informal caregivers are close to the level of the general European population. The sample included all the stages of the recovery process, with 34.5% of participants being in the growth stage. Informal caregivers' stages in the recovery process were negatively associated with the patient's length of illness (Rho = -.683, p = .000) and positively associated with the caregivers' level of optimism (Rho = .564, p = .001). Conclusion: During the inpatient treatment of a close relative suffering from a depressive disorder, informal caregivers go through an individual psychological recovery process involving several stages. In addition to caring for inpatients, nurses are encouraged to meet and support caregivers as soon as possible in their individual recovery process. Furthermore, the development of a suitably adapted clinical tool would facilitate the assessment of the informal caregiver's stage in the recovery process within care units. A multidisciplinary approach is needed in this domain.

[Clinical utility of evoked potentials in the field of addiction medicine]. / Apport des potentiels évoqués à la prise en charge de la dépendance à l'alcool.

Cognitive impairment is a frequent consequence of chronic and excessive alcohol consumption with impact on the daily lives of the concerned persons. Recovery during abstinence phases is often only partial. Improvement of cognitive functions has often a positive and lasting effect on the quality of live and the clinical symptoms of the patients suffering from an alcohol use disorder. This article presents a critical discussion on the utility of evoked potentials as part of adapted clinical protocols aiming an individualized rehabilitation approaches of alcohol use disorder and focusing on a reduction of the risk of relapse. The implementation of this approach requires a valid classification of evoked potentials based on a solid statistical fundament. Our aim is to achieve this goal.

Les déficits cognitifs comme séquelle fréquente de la consommation d'alcool excessive et chronique s'améliorent au moins partiellement avec l'abstinence à l'alcool, mais on observe souvent des symptômes résiduels persistants. L'amélioration des aptitudes cognitives a un impact positif sur la qualité de vie et les symptômes cliniques. Cet article présente une discussion critique de l'utilité des potentiels évoqués comme outil de détection précoce des déficits cognitifs. Ils peuvent être utilisés lors d'un processus de réhabilitation individualisé ciblant la réduction du taux de rechutes. La mise en œuvre d'une telle approche est originale et nécessite une classification par les potentiels évoqués qui soit statistiquement robuste. Nous avançons des pistes qui permettent de remplir ces conditions.

[Addictions]. / Addictions.

This year, the actuality for addictions in this edition addresses four points. The disease model of addiction is criticized by the cognitive neurosciences which need to consider the agentivity of the persons. Regarding the societal actuality, clinical pharmacology review of cannabidiol presents an update on legal cannabis. The suicidality of excessive gamblers may be prevented specifically. Addiction and first psychotic episodes need an integrated care.

Cette année, l'actualité des addictions pour ce numéro concerne quatre points. Le modèle de la maladie de l'addiction est critiqué par les neurosciences cognitives qui demandent de reconnaître l'agentivité des personnes. Au vu de l'actualité sociétale, une revue pharmacologique clinique du cannabidiol vient mettre à jour nos connaissances sur le cannabis légal. La suicidalité des joueurs excessifs peut faire l'objet de prévention spécifique. L'addiction et le premier épisode psychotique nécessitent une prise en charge intégrée.

Impaired social cognition in schizophrenia during the Ultimatum Game: An EEG study.

BACKGROUND: Schizophrenia has a core feature of cognitive dysfunctions. Since these deficits are predictive for patients' functional outcome, understanding their origin is of great importance to improve their daily lives. A specific component of the deficit involves social decision-making, which can be studied using the Ultimatum Game (UG). In this task, a "proposer" proposes a share of money to a "responder", who can either accept or reject this offer. If the responder accepts the proposal, both win money. If the responder refuses, both players end up with nothing. Therefore, the UG evaluates decision-making strategies and social interaction. METHODS: We compared the neuronal bases of schizophrenic patients with healthy controls, while performing the UG. Electroencephalography (EEG) was used to find differences in the event-related potential (ERP) components typical for the UG, namely the P2 and feedback-related negativity (FRN). Source reconstruction was further used to define the origin of these differences. RESULTS: In the proposer condition, no differences were found in amplitude of the P2 and FRN components. In contrast, in the responder condition, significant differences were found for the amplitude of the FRN (p=0.009). Using source reconstruction, a different activation in a border zone of the dorsolateral and the medial prefrontal cortex was revealed in schizophrenic patients to underlie this component. CONCLUSIONS: We suggest that the difference found in the FRN amplitude is associated with difficulties of patients in interpreting another's behavior. Although schizophrenic patients correctly activate neuronal bases in the proposer condition, they were not able to activate the same networks in the responder condition, thereby exposing their difficulties in social interaction.

[Addictions]. / Addictions.

In 2016, the actuality for addictions in this edition addresses four points. Social neurosciences of addiction are of great importance regarding the vulnerabilities for addiction and for the recovery. Deep brain stimulation is emerging in the therapeutic panel coming from the clinical neurosciences for the addictions. Novelties in opioid agonists for the treatment of opiates dependence, with the apparition in the Swiss market of release morphine and of levomethadone. Cannabis and prison, a pilot study for the maintenance of abstinence in prison.

En 2016, l'actualité des addictions pour ce numéro concerne quatre points. Les neurosciences sociales de l'addiction, qui ont une grande importance en termes de vulnérabilité pour l'addiction mais aussi pour le rétablissement. La stimulation cérébrale profonde qui fait son apparition dans l'éventail thérapeutique issu des neurosciences cliniques pour les addictions. Les nouveautés du traitement agoniste opioïde de la dépendance aux opiacés avec l'apparition dans le marché suisse de la morphine retard puis de la lévométhadone. Des algorithmes sont proposés pour orienter le prescripteur. Cannabis et prison, une étude pilote pour le maintien de l'abstinence en prison.

Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment.

BACKGROUND: Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment (MMT). METHODS: We included 238 MMT patients according to their response to treatment and methadone dosing, along with 217 subjects without substance dependence. All were genotyped for polymorphisms of the dopamine D1, D2, micro-opioid and delta-opioid receptor genes. RESULTS: The polymorphisms of the micro-opioid (118A>G), delta-opioid (921T>C), dopamine D1 (DdeI) and D2 (TaqI A) receptor genes were not associated with response to MMT and methadone dosing, whereas an association was found with the dopamine D2 receptor (DRD2) 957C>T polymorphism. The 957CC carriers were more frequently non-responders to treatment (OR=2.4; p=0.02) and presented a fourfold shorter period of negative urine screening (p=0.02). No significant differences in allele frequencies were observed between the MMT patients and the control group, suggesting no association of the analyzed polymorphisms with opioid dependence. CONCLUSIONS: These results suggest that DRD2 genotype may contribute to the understanding of the interindividual variability to the response to MMT.

ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment.

BACKGROUND AND OBJECTIVE: The in vivo implication of various cytochrome P450 (CYP) isoforms and of P-glycoprotein on methadone kinetics is unclear. We aimed to thoroughly examine the genetic factors influencing methadone kinetics and response to treatment. METHODS: Genotyping for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, ABCB1, and UGT2B7 polymorphisms was performed in 245 patients undergoing methadone maintenance treatment. To assess CYP3A activity, the patients were phenotyped with midazolam. RESULTS: The patients with lower CYP3A activity presented higher steady-state trough (R,S)-methadone plasma levels (4.3, 3.0, and 2.3 ng/mL x mg for low, medium, and high activity, respectively; P = .0002). As previously reported, CYP2B6*6/*6 carriers had significantly higher trough (S)-methadone plasma levels (P = .0001) and a trend toward higher (R)-methadone plasma levels (P = .07). CYP2D6 ultrarapid metabolizers presented lower trough (R,S)-methadone plasma levels compared with the extensive or intermediate metabolizers (2.4 and 3.3 ng/mL x mg, respectively; P = .04), whereas CYP2D6 poor metabolizer status showed no influence. ABCB1 3435TT carriers presented lower trough (R,S)-methadone plasma levels (2.7 and 3.4 ng/mL . mg for 3435TT and 3435CC carriers, respectively; P = .01). The CYP1A2, CYP2C9, CYP2C19, CYP3A5, and UGT2B7 genotypes did not influence methadone plasma levels. Only CYP2B6 displayed a stereoselectivity in its activity. CONCLUSION: In vivo, CYP3A4 and CYP2B6 are the major CYP isoforms involved in methadone metabolism, with CYP2D6 contributing to a minor extent. ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics. The genetic polymorphisms of these 4 proteins had no influence on the response to treatment and only a small influence on the dose requirement of methadone.

Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment.

BACKGROUND AND OBJECTIVE: Recent in vitro studies have suggested an important role of cytochrome P450 (CYP) 2B6 and CYP2C19 in methadone metabolism. We aimed to determine the influence of CYP2B6, CYP2C9, and CYP2C19 genetic polymorphism on methadone pharmacokinetics and on the response to treatment. METHODS: We included 209 patients in methadone maintenance treatment on the basis of their response to treatment and their daily methadone dose. Patients were genotyped for CYP2B6, CYP2C9, and CYP2C19. Steady-state trough and peak (R)-, (S)-, and (R,S)-plasma levels and peak-to-trough plasma level ratios were measured. RESULTS: CYP2B6 genotype influences (S)-methadone and, to a lesser extent, (R)-methadone plasma levels, with the median trough (S)-methadone plasma levels being 105, 122, and 209 ng . kg/mL . mg for the noncarriers of allele *6, heterozygous carriers, and homozygous carriers (*6/*6), respectively (P = .0004). CYP2C9 and CYP2C19 genotypes do not influence methadone plasma levels. Lower peak and trough plasma levels of methadone and higher peak-to-trough ratios were measured in patients considered as nonresponders [median (R,S)-methadone trough plasma levels of 183 and 249 ng . kg/mL . mg (P = .0004) and median peak-to-trough ratios of 1.82 and 1.58 for high-dose nonresponders and high-dose responders, respectively (P = .0003)]. CONCLUSION: Although CYP2B6 influences (S)-methadone plasma levels, given that only (R)-methadone contributes to the opioid effect of this drug, a major influence of CYP2B6 genotype on response to treatment is unlikely and has not been shown in this study. Lower plasma levels of methadone in nonresponders, suggesting a higher clearance, and higher peak-to-trough ratios, suggesting a shorter elimination half-life, are in agreement with the usual clinical measures taken for such patients, which are to increase methadone dosages and to split the daily dose into several intakes.