Protocol of a monocentric, double-blind, randomized, superiority, controlled trial evaluating the effect of in-prison OROS-methylphenidate vs. placebo treatment in detained people with attention-deficit hyperactivity disorder (BATIR).

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes. METHODS: This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis). DISCUSSION: We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release. TRIAL REGISTRATION: ClinicalTrials.gov NCT05842330 . Registered on June 5, 2023. Kofam.ch SNCTP000005388. Registered on July 17, 2023.

Case reports: Using Good Psychiatric Management (GPM) conceptualizations in the dimensional assessment and treatment of personality disorders.

Good Psychiatric Management (GPM) is a generalist clinical management approach for borderline personality disorder that incorporates common ingredients of good standard care for any psychiatric diagnosis with what works from prevailing specialist psychotherapies. Similar to all validated therapies for BPD, it relies on a specified formulation of the disorder' symptoms as arising from interpersonal hypersensitivity, to dynamically describe typical patterns of daily self- and interpersonal issues that drive the instability that defines the general personality dysfunction characteristic of the disorder. Recent adaptations of GPM have been proposed for narcissistic personality disorder and obsessive-compulsive personality disorder, with development of similar dynamic models for both (intrapsychic coherence model and model of overcontrol). New dimensional models of personality disorder diagnosis have been developed to address limitations of categorical approach, but the incorporation of these models into usage in the delivery of clinical services (where categorical approach remains the most used) is limited. This paper describes an adaptation of GPM to two cases of personality disorder that illustrate the usefulness of GPM models for dynamic representation of complex daily fluctuations in internal psychic coherence and interpersonal functioning. Specialist psychotherapies will never meet the demands of public health needs to treat personality dysfunction, and incorporation of new dimensional models of diagnosis are needed for treatments that can provide a minimal standard of care for providers and patients.

Phenotypic Assessment of Drug Metabolic Pathways and P-Glycoprotein in Patients Treated With Antidepressants in an Ambulatory Setting.

OBJECTIVE: Drug-metabolizing enzymes (DMEs), such as cytochrome P450 (CYP) enzymes, and transporters have emerged as major determinants of variability in drug metabolism and response. This study investigated the association between CYP and P-glycoprotein activities and plasma antidepressant concentration in an outpatient clinical setting. Secondary outcomes were antidepressant efficacy and tolerance. We also describe phenotypes in patients treated with antidepressants and evaluate the tolerance of a minimally invasive phenotyping approach. METHODS: From January 2015 to August 2015, 64 patients on a stable antidepressant regimen underwent a simultaneous assessment of steady-state antidepressant concentration and DME (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A) and P-glycoprotein transporter activity using a cocktail phenotyping approach. Psychiatric diagnoses were in accordance with DSM-5. RESULTS: We observed a high proportion of subjects (> 20%) with reduced activity of CYP2C19, CYP2D6, CYP3A4, and P-glycoprotein. As expected, higher CYP activity for major metabolic pathways was associated with lower concentration of the parent compound (CYP2C19 and escitalopram, P = .025; CYP2D6 and fluoxetine, P < .001; CYP2C19 and sertraline, P = .001), higher concentration of the metabolite (CYP2D6 and O-desmethylvenlafaxine, P = .007), and higher metabolite-to-parent drug ratio (CYP2C19 and escitalopram, P = .03; CYP2D6 and fluoxetine, P < .001; CYP2C19 and sertraline, P = .048; CYP2B6 and sertraline, P = .006). Phenotyping also highlighted the relevance of a minor metabolic pathway for venlafaxine (CYP3A4). Insufficient response and adverse reactions to antidepressants were not significantly associated with plasma antidepressant concentration, DME, or P-glycoprotein activity. Tolerance of the phenotypic test in ambulatory settings was found to be excellent. CONCLUSIONS: The phenotypic assessment of DMEs and a transporter is a valuable, well-tolerated method to explore the interindividual variability in drug disposition in clinical settings. The method is able to account for the inhibitory activity of antidepressants themselves and for polymedication, which is frequent in this population of refractory depressed patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02438072.

Do suicidal thoughts or behaviors recur during a second antidepressant treatment trial?

OBJECTIVE: A subset of patients undergoing initial antidepressant treatment experience worsening of symptoms, including thoughts of suicide or suicidal behavior. The present study explores whether this subset of patients is also more likely to experience recurrence or worsening of these symptoms during a second treatment trial with a different antidepressant. METHOD: We examined data collected between July 2001 and September 2006 from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter effectiveness study of outpatients with major depressive disorder diagnosed by a DSM-IV checklist. In that study, subjects who did not remit with citalopram treatment were randomized among next-step treatment options. The main outcome measure for this post hoc analysis, presence of suicidal thoughts and behaviors, was assessed using the suicide item on the 16-item Quick Inventory of Depressive Symptomatology--Self-Rated. Logistic regression was used to examine association between emergence or worsening of these symptoms with the first-step (level 1) citalopram treatment and emergence or worsening with next-step (level 2) pharmacologic or psychosocial treatment, including augmentation with bupropion or buspirone; switch to sertraline, venlafaxine, or bupropion; or addition of or switch to cognitive therapy. RESULTS: Of 1,240 subjects entering level 2 with a score less than 3 on the suicide item, 102 (8.2%) experienced emergence or worsening of suicidal thoughts or behaviors. Emergence or worsening at level 1 was strongly associated with reemergence or worsening at level 2 (crude OR = 4.00 [95% CI, 2.45-6.51], adjusted OR = 2.95 [95% CI, 1.76-4.96]). Overall magnitude of risk was similar among next-step pharmacologic augmentation versus switching. CONCLUSIONS: These results suggest that individuals who experience emergence or worsening of suicidal thoughts or behaviors with one antidepressant treatment may warrant closer follow-up during the next-step treatment, as these symptoms may recur regardless of which modality is selected.

Effects of an assertive community program in patients with severe mental disorders and impact on their families.

AIMS: Assertive community treatment (ACT) is known to have a positive impact on the number and length of inpatient stays. However, recent studies have shown little or no effect of such programs in European settings. This paper aims to describe the impact of a newly implemented ACT program on patients and their families' burden. Predictive factors have also been examined. METHOD: Fifty-five patients characterized by heavy use of psychiatric care, numerous hospitalizations, or failure to link with outpatient psychiatric care and their relatives were followed. Data were gathered on patients before and after follow up as well as on relatives' burden and costs. The number and domains of clinician interventions have been detailed. RESULTS: The ACT program had a positive effect on symptoms, psychosocial adaptation and quality of life. Age was the most significant predictor of changes. Older patients, most of them suffering from delusional disorders, showed no improvement or even some impairment. Finally, the program appeared to have a marked effect on easing families' burden in domains such as assistance in daily life activities and costs. CONCLUSIONS: ACT appears to be recommended for patients with poor outcome when treated in other settings. Early intervention seems to be justified as highlighted by younger age being the best predictor of positive changes. Families can be helped considerably, particularly those confronted with patients with persistent disturbing symptoms which do not, however, warrant hospitalization. Finally, the fact that patients with delusional disorder do not seem to improve warrants further research.

[Treating depression: decision analysis for the general practitioner]. / Dépression: analyse décisionnelle pour la prise en charge par le médecin de premier recours.

Unipolar depression is among the leading causes of invalidity and disability-adjusted life-years. General practitioners frequently encounter patients suffering from depressive syndromes and very often, it's they, who make the initial diagnosis, take care of these patients, eventually prescribe an antidepressant treatment, identify difficult cases and address them to the specialists of mental health. In this article, we present concepts of diagnosis and differential diagnoses of depression, its therapy and the collaboration between the general practitioner and the psychiatrist/psychotherapist.

A randomized trial of spiritual assessment of outpatients with schizophrenia: patients' and clinicians' experience.

OBJECTIVE: Recovery-oriented care for patients with schizophrenia involves consideration of cultural issues, such as religion and spirituality. However, there is evidence that psychiatrists rarely address such topics. This study examined acceptance of a spiritual assessment by patients and clinicians, suggestions for treatment that arose from the assessment, and patient outcomes--in terms of treatment compliance and satisfaction with care (as measured by treatment alliance). METHODS: Outpatients with psychosis were randomly assigned to two groups: an intervention group that received traditional treatment and a religious and spiritual assessment (N=40) and a control group that received only traditional treatment (N=38). Eight psychiatrists were trained to administer the assessment to their established and stable patients. After each administration, the psychiatrist attended a supervision session with a psychiatrist and a psychologist of religion. Baseline and three-month data were collected. RESULTS: The spiritual assessment was well accepted by patients. During supervision, psychiatrists reported potential clinical uses for the assessment information for 67% of patients. No between-group differences in medication adherence and satisfaction with care were found at three months, although patients in the intervention group had significantly better appointment attendance during the follow-up period. Their interest in discussing religion and spirituality with their psychiatrists remained high. The process was not as well accepted by psychiatrists. CONCLUSIONS: Spiritual assessment can raise important clinical issues in the treatment of patients with chronic schizophrenia. Cultural factors, such as religion and spirituality, should be considered early in clinical training, because many clinicians are not at ease addressing such topics with patients.