Neurological soft signs as trait markers of a subset of patients with obsessive-compulsive disorder with low insight and altered cognitive abilities.

Neurological soft signs (NSS) are subtle motor control impairments that include involuntary movements and abnormalities of motor coordination, sensory integration and lateralization. They engage different brain networks, including the prefrontal networks that support the higher cognitive functions that are dysfunctional in obsessive-compulsive disorder (OCD). This study investigated the relationships between the presence of NSS and patients' severity of OCD symptoms, insight, and treatment resistance in a sample of 63 patients. Treatment-resistance was assessed considering all the treatments the patients received during the course of their disease. The four dimensions of OCD defined in the dimensional obsessive-compulsive scale were considered. Links between the patients' cognitive abilities and NSS were assessed using tests targeting specifically the core components of executive functions. As expected, OCD patients displayed more NSS than individually matched control participants. In OCD patients, high NSS scores were associated with poor insight and lower cognitive abilities. Multiple regression analysis identified worse visuospatial working memory, attentional control, and verbal fluency as predictive factors of high NSS scores among cognitive functions. Unexpectedly, the patients displaying symptoms in the contamination/washing dimension displayed less NSS than the other patients. In contrast, neither the severity of OCD symptoms nor long-range treatment resistance was significantly related to patients' NSS scores. Altogether, our findings suggest that high NSS scores may be a trait marker of a subset of OCD patients with low insight and particularly altered cognitive abilities who would not express the contamination/washing dimension of the pathology.

Digital Phenotyping: Data-Driven Psychiatry to Redefine Mental Health.

The term "digital phenotype" refers to the digital footprint left by patient-environment interactions. It has potential for both research and clinical applications but challenges our conception of health care by opposing 2 distinct approaches to medicine: one centered on illness with the aim of classifying and curing disease, and the other centered on patients, their personal distress, and their lived experiences. In the context of mental health and psychiatry, the potential benefits of digital phenotyping include creating new avenues for treatment and enabling patients to take control of their own well-being. However, this comes at the cost of sacrificing the fundamental human element of psychotherapy, which is crucial to addressing patients' distress. In this viewpoint paper, we discuss the advances rendered possible by digital phenotyping and highlight the risk that this technology may pose by partially excluding health care professionals from the diagnosis and therapeutic process, thereby foregoing an essential dimension of care. We conclude by setting out concrete recommendations on how to improve current digital phenotyping technology so that it can be harnessed to redefine mental health by empowering patients without alienating them.

Variability in Motor Threshold during Transcranial Magnetic Stimulation Treatment for Depression: Neurophysiological Implications.

The measurement of the motor threshold (MT) is an important element in determining stimulation intensity during Transcranial Magnetic Stimulation treatment (rTMS). The current recommendations propose its realization at least once a week. The variability in this motor threshold is an important factor to consider as it could translate certain neurophysiological specificities. We conducted a retrospective naturalistic study on data from 30 patients treated for treatment-resistant depression in an rTMS-specialized center. For each patient, weekly motor-evoked potential (MEP) was performed and several clinical elements were collected as part of our clinical interviews. Regarding response to treatment (Patient Health Questionnaire-9 (PHQ-9) before and after treatment), there was a mean difference of -8.88 (-21 to 0) in PHQ9 in the Theta Burst group, of -9.00 (-18 to -1) in the High-Frequency (10 Hz) group, and of -4.66 (-10 to +2) in the Low-Frequency (1 Hz) group. The mean improvement in depressive symptoms was 47% (p < 0.001, effect-size: 1.60). The motor threshold changed over the course of the treatment, with a minimum individual range of 1 point and a maximum of 19 points (total subset), and a greater concentration in the remission group (4 to 10) than in the other groups (3 to 10 in the response group, 1 to 8 in the partial response group, 3 to 19 in the stagnation group). We also note that the difference between MT at week 1 and week 6 was statistically significant only in the remission group, with a different evolutionary profile showing an upward trend in MT. Our findings suggest a potential predictive value of MT changes during treatment, particularly an increase in MT in patients who achieve remission and a distinct "break" in MT around the 4th week, which could predict nonresponse.

Repetitive Transcranial Magnetic Stimulation (rTMS) in Post-Traumatic Stress Disorder: Study Protocol of a Nationwide Randomized Controlled Clinical Trial of Neuro-Enhanced Psychotherapy "TraumaStim".

The use of high-frequency Transcranial Magnetic Stimulation (HF-rTMS) of the right dorsolateral prefrontal cortex (DLPFC) in treating Post-traumatic Stress Disorder (PTSD) is currently regarded as a level B intervention (probable effectiveness). HF-rTMS has attracted interest as a neuromodulation therapeutic method for PTSD. Prolonged exposure and reactivation therapy are also regarded as first-line treatments for PTSD. Randomized controlled clinical studies examining the effectiveness of several HF-rTMS sessions coupled with psychotherapy have not yet been completed. In total, 102 patients with refractory PTSD will be randomly assigned (1:1) to reactivation therapy, in addition to either active HF-rTMS (20 Hz) or sham HF-rTMS, for 12 sessions in a nationwide, multicenter, double-blind controlled trial. The impact on PTSD symptoms and neurocognitive functioning will be assessed. The primary outcome is the PTSD severity score measured based on the Clinician-Administered PTSD Scale (CAPS-5) at one month. If this additional therapy is successful, it may strengthen the case for regulatory authorities to approve this additional technique of treating PTSD. Additionally, it expands the field of neurostimulation-assisted psychotherapy.

Transcranial Magnetic Stimulation (rTMS) on the Precuneus in Alzheimer's Disease: A Literature Review.

The current literature review aimed to evaluate the effectiveness of rTMS on the precuneus as a potential treatment for Alzheimer's disease (AD). Although the number of studies specifically targeting the precuneus is limited, the results from this review suggest the potential benefits of this approach. Future studies should focus on exploring the long-term effects of rTMS on the precuneus in Alzheimer's disease patients, as well as determining the optimal stimulation parameters and protocols for this population. Additionally, investigating the effects of rTMS on the precuneus in combination with other brain regions implicated in AD may provide valuable insights into the development of effective treatment for this debilitating neurodegenerative disorder.

High treatment resistance is associated with lower performance in the Stroop test in patients with obsessive-compulsive disorder.

Around 50% of the patients with obsessive-compulsive disorder (OCD) are resistant to treatment, and patients with OCD show alterations in a broad range of cognitive abilities. The present study investigated the links between treatment-resistance, executive and working memory abilities, and the severity of OCD symptoms among 66 patients with OCD. The patients performed seven tests gauging their executive functions and working memory and filled in questionnaires for OCD severity and insight into their pathology. In addition, the executive and working memory abilities of a subset of these patients were compared with those of individually matched control participants. In contrast with previous studies, patients' treatment resistance was evaluated by considering the clinical outcomes of all the treatments that they received during the course of their disease. Higher treatment resistance was associated with lower performance in one particular executive test, the Stroop test, which assessed patients' ability to inhibit prepotent/automatic responses. Older age and more severe OCD symptoms were also associated with higher treatment resistance. Regardless of OCD severity, the patients displayed small to moderate deficits across most components of executive functions compared to control participants. Interestingly, patients with OCD took more time than control participants to perform speeded neuropsychological tests but never made more errors. Altogether, this study shows that the treatment-resistance of patients with OCD may be reliably quantified over the course of years and treatments using Pallanti and Quercioli's (2006) treatment resistance-related scales. The data suggest that the Stroop test could be used clinically to anticipate treatment outcomes in to-be-treated patients.

The priming effect of repetitive transcranial magnetic stimulation on clinical response to electroconvulsive therapy in treatment-resistant depression: a randomized, double-blind, sham-controlled study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD. METHODS: In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment. RESULTS: After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests. CONCLUSIONS: rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

Digital phenotype of mood disorders: A conceptual and critical review.

Background: Mood disorders are commonly diagnosed and staged using clinical features that rely merely on subjective data. The concept of digital phenotyping is based on the idea that collecting real-time markers of human behavior allows us to determine the digital signature of a pathology. This strategy assumes that behaviors are quantifiable from data extracted and analyzed through digital sensors, wearable devices, or smartphones. That concept could bring a shift in the diagnosis of mood disorders, introducing for the first time additional examinations on psychiatric routine care. Objective: The main objective of this review was to propose a conceptual and critical review of the literature regarding the theoretical and technical principles of the digital phenotypes applied to mood disorders. Methods: We conducted a review of the literature by updating a previous article and querying the PubMed database between February 2017 and November 2021 on titles with relevant keywords regarding digital phenotyping, mood disorders and artificial intelligence. Results: Out of 884 articles included for evaluation, 45 articles were taken into account and classified by data source (multimodal, actigraphy, ECG, smartphone use, voice analysis, or body temperature). For depressive episodes, the main finding is a decrease in terms of functional and biological parameters [decrease in activities and walking, decrease in the number of calls and SMS messages, decrease in temperature and heart rate variability (HRV)], while the manic phase produces the reverse phenomenon (increase in activities, number of calls and HRV). Conclusion: The various studies presented support the potential interest in digital phenotyping to computerize the clinical characteristics of mood disorders.

Memory reconsolidation impairment using the ß-adrenergic receptor blocker propranolol reduces nightmare severity in patients with posttraumatic stress disorder: a preliminary study.

STUDY OBJECTIVES: Posttraumatic nightmares may exacerbate and perpetuate the daytime symptoms of posttraumatic stress disorder and might represent a therapeutic target. The therapeutic strategy of memory reconsolidation using the ß-adrenergic receptor blocker propranolol associated with re-exposure psychotherapy is a promising treatment in patients with posttraumatic stress disorder. Previous studies have established this therapy is effective in reducing overall clinician-assessed posttraumatic stress disorder symptoms, but to date no previous study has specifically focused on posttraumatic nightmares in this therapy. This study provides a preliminary assessment of the evolution of nightmare severity during this therapy protocol compared with the decrease of the other posttraumatic stress disorder symptoms. It evaluates the incidence of side effects and examines the relative effects on posttraumatic nightmares. METHODS: Patients were recruited as part of the Paris Mémoire Vive Study. Data were collected using a prospective longitudinal design including 1 baseline visit, 6 therapeutic visits, and 2 follow-up visits. During the 6 therapeutic visits, propranolol was administered orally 60 to 75 minutes prior to the psychotherapeutic session. RESULTS: On average, nightmare severity decreased from "severe" to "mild" during the protocol and remained stable 2 months after the last session. Whereas 85% of patients reported nightmares at baseline, only 50% still had them after the protocol. The protocol was generally well tolerated and did not increase nightmare severity for any patient in the study. CONCLUSIONS: Memory reconsolidation therapy with propranolol seems promising in reducing nightmare severity, up to and including remission. However, research using a randomized controlled design and assessing maintenance of nightmare extinction is warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Using Reconsolidation Blockade to Treat Trauma Related Disorders After Paris Attacks: An Effectiveness Study (PARIS-MEM); Identifier: NCT02789982; URL: https://www.clinicaltrials.gov/ct2/show/NCT02789982. CITATION: Mallet C, Chick CF, Maatoug R, Fossati P, Brunet A, Millet B. Memory reconsolidation impairment using the ß-adrenergic receptor blocker propranolol reduces nightmare severity in patients with posttraumatic stress disorder: a preliminary study. J Clin Sleep Med. 2022;18(7):1847-1855.

Impact of brain-derived neurotrophic factor Val66Met polymorphism and response to escitalopram or paroxetine in obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a severe psychiatric disorder characterized by its heterogeneous nature and by different dimensions of obsessive-compulsive (OC) symptoms. Serotonin reuptake inhibitors (SRIs) are used to treat OCD, but up to 40% to 60% of patients do not show a significant improvement with these medications. In this study, we aimed to test the impact of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on the efficacy of antidepressants in OCD overall, and in relation to the different OC dimensions. METHODS: In a 6-month prospective treatment study, 69 Caucasian OCD patients were treated with escitalopram for 24 weeks or with escitalopram for 12 weeks followed by paroxetine for an additional 12-week period. Patients were genotyped and assessed for treatment response. The main clinical outcomes were improvement of the Yale-Brown Obsessive-Compulsive Scale score and in different OC symptom dimension scores. RESULTS: The Val/Val group comprised 43 (62%) patients, the Val/Met and Met/Met group comprised 26 (38%) patients. Forty-two patients were classified as responders at 12 weeks and 38 at 24 weeks; no significant association was found between BDNF Val66Met and SRIs response at 12 and 24 weeks. In analyses of the different OC symptom dimensions, the Met allele was associated with a slightly reduced score in the aggressive/checking dimension at 6 months (P = .048). CONCLUSIONS: Our findings do not support the usefulness of BDNF Val66Met genotyping to predict overall response to treatment with SRIs in OCD; they did however suggest a better outcome at 6 months for the aggressive/checking symptom dimension for patients carrying the Met allele.

In Search of Digital Dopamine: How Apps Can Motivate Depressed Patients, a Review and Conceptual Analysis.

INTRODUCTION: Depression is highly prevalent and causes considerable suffering and disease burden despite the existence of wide-ranging treatment options. Momentary assessment is a promising tool in the management of psychiatric disorders, and particularly depression. It allows for a real-time evaluation of symptoms and an earlier detection of relapse or treatment efficacy. Treating the motivational and hedonic aspects of depression is a key target reported in the literature, but it is time-consuming in terms of human resources. Digital Applications offer a major opportunity to indirectly regulate impaired motivational circuits through dopaminergic pathways. OBJECTIVE: The main objective of this review was twofold: (1) propose a conceptual and critical review of the literature regarding the theoretical and technical principles of digital applications focused on motivation in depression, activating dopamine, and (2) suggest recommendations on the relevance of using these tools and their potential place in the treatment of depression. MATERIAL AND METHODS: A search for words related to "dopamine", "depression", "smartphone apps", "digital phenotype" has been conducted on PubMed. RESULTS: Ecological momentary interventions (EMIs) differ from traditional treatments by providing relevant, useful intervention strategies in the context of people's daily lives. EMIs triggered by ecological momentary assessment (EMA) are called "Smart-EMI". Smart-EMIs can mimic the "dopamine reward system" if the intervention is tailored for motivation or hedonic enhancement, and it has been shown that a simple reward (such as a digital badge) can increase motivation. DISCUSSION: The various studies presented support the potential interest of digital health in effectively motivating depressed patients to adopt therapeutic activation behaviors. Finding effective ways to integrate EMIs with human-provided therapeutic support may ultimately yield the most efficient and effective intervention method. This approach could be a helpful tool to increase adherence and motivation. CONCLUSION: Smartphone apps can motivate depressed patients by enhancing dopamine, offering the opportunity to enhance motivation and behavioral changes, although longer term studies are still needed.

The wide spectrum of COVID-19 neuropsychiatric complications within a multidisciplinary centre.

A variety of neuropsychiatric complications has been described in association with COVID-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with COVID-19 seen in a multidisciplinary hospital centre over 6 months. We conducted a retrospective, observational study of all patients showing neurological or psychiatric symptoms in the context of COVID-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris-Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of COVID-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 COVID-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%) and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders.

Ecological Momentary Assessment Using Smartphones in Patients With Depression: Feasibility Study.

BACKGROUND: Ecological momentary assessment (EMA) is a promising tool in the management of psychiatric disorders and particularly depression. It allows for a real-time evaluation of symptoms and an earlier detection of relapse or treatment efficacy. The generalization of the smartphone in the modern world offers a new, large-scale support for EMA. OBJECTIVE: The main objective of this study was twofold: (1) to assess patients' compliance with an EMA smartphone app defined by the number of EMAs completed, and (2) to estimate the external validity of the EMA using a correlation between self-esteem/guilt/mood variables and Hamilton Depression Rating Scale (HDRS) score. METHODS: Eleven patients at the Pitié-Salpêtrière Hospital, Paris, France, were monitored for 28 days by means of a smartphone app. Every patient enrolled in the study had two types of assessment: (1) three outpatient consultations with a psychiatrist at three different time points (days 1, 15, and 28), and (2) real-time data collection using an EMA smartphone app with a single, fixed notification per day at 3 pm for 28 days. The results of the real-time data collected were reviewed during the three outpatient consultations by a psychiatrist using a dashboard that aggregated all of the patients' data into a user-friendly format. RESULTS: Of the 11 patients in the study, 6 patients attended the 3 outpatient consultations with the psychiatrist and completed the HDRS at each consultation. We found a positive correlation between the HDRS score and the variables of self-esteem, guilt, and mood (Spearman correlation coefficient 0.57). Seven patients completed the daily EMAs for 28 days or longer, with an average response rate to the EMAs of 62.5% (175/280). Furthermore, we observed a positive correlation between the number of responses to EMAs and the duration of follow-up (Spearman correlation coefficient 0.63). CONCLUSIONS: This preliminary study with a prolonged follow-up demonstrates significant patient compliance with the smartphone app. In addition, the self-assessments performed by patients seemed faithful to the standardized measurements performed by the psychiatrist. The results also suggest that for some patients it is more convenient to use the smartphone app than to attend outpatient consultations.

Improving clinical decision-making in psychiatry: implementation of digital phenotyping could mitigate the influence of patient's and practitioner's individual cognitive biases.

High stake clinical choices in psychiatry can be impacted by external irrelevant factors. A strong understanding of the cognitive and behavioural mechanisms involved in clinical reasoning and decision-making is fundamental in improving healthcare quality. Indeed, the decision in clinical practice can be influenced by errors or approximations which can affect the diagnosis and, by extension, the prognosis: human factors are responsible for a significant proportion of medical errors, often of cognitive origin. Both patient's and clinician's cognitive biases can affect decision-making procedures at different time points. From the patient's point of view, the quality of explicit symptoms and data reported to the psychiatrist might be affected by cognitive biases affecting attention, perception or memory. From the clinician's point of view, a variety of reasoning and decision-making pitfalls might affect the interpretation of information provided by the patient. As personal technology becomes increasingly embedded in human lives, a new concept called digital phenotyping is based on the idea of collecting real-time markers of human behaviour in order to determine the 'digital signature of a pathology'. Indeed, this strategy relies on the assumption that behaviours are 'quantifiable' from data extracted and analysed through connected tools (smartphone, digital sensors and wearable devices) to deduce an 'e-semiology'. In this article, we postulate that implementing digital phenotyping could improve clinical reasoning and decision-making outcomes by mitigating the influence of patient's and practitioner's individual cognitive biases.

Sustained Recovery in a Treatment-Refractory Obsessive-Compulsive Disorder Patient After Deep Brain Stimulation Battery Failure.

Obsessive-compulsive disorder (OCD) is a widespread chronic neuropsychiatric disorder characterized by recurrent intrusive thoughts, images, or urges (obsessions) that typically cause anxiety or distress. Even when optimal treatment is provided, 10% of patients remain severely affected chronically. In some countries, deep brain stimulation (DBS) is an approved and effective therapy for patients suffering from treatment-resistant OCD. Hereafter, we report the case of a middle-aged man with a long history of treatment-resistant OCD spanning nearly a decade with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores oscillating between 21 and 28. The patient underwent bilateral implantation of ventral striatum/ventral capsule DBS leads attached to a battery-operated implanted pulse generator. After a 3-month postimplantation period, the DBS protocol started. Three months after the onset of DBS treatment, the patient's Y-BOCS score had dropped to 3, and he became steadily asymptomatic. However, inadvertently, at this time, it was found out that the implanted pulse generator battery had discharged completely, interrupting brain stimulation. The medical team carried on with the original therapeutic and evaluation plan in the absence of active DBS current. After 12 additional months under off-DBS, the patient remained at a Y-BOCS score of 7 and asymptomatic. To our knowledge, this is the first report that provides an opportunity to discuss four different hypotheses of long-term recovery induced by DBS in a treatment-refractory OCD patient, notably: (1) A placebo effect; (2) Paradoxical improvements induced by micro-lesions generated by DBS probe implantation procedures; (3) Unexpected late spontaneous improvements; (4) Recovery driven by a combination of active DBS-induction, the effects of medication, and DBS-placebo effects.

Late-Onset OCD as a Potential Harbinger of Dementia With Lewy Bodies: A Report of Two Cases.

OBJECTIVES: Obsessive-compulsive disorder usually begins in adolescence or young adulthood. OCD cases appearing after the age of 50 years are rare, most often associated with inflammatory, brain lesions, or neurodegenerative comorbidities. We describe two cases of late-onset obsessive compulsive disorder followed by the development of Dementia with Lewy Bodies and review the links between these two disorders. METHODS AND RESULTS: We describe the clinical history of two patients that first showed OCD symptoms at an atypical age (>60 years). After several failed treatment attempts, they were hospitalized in our unit. Both presented severe sensitivity to antipsychotic agents that led to a diagnosis of Dementia with Lewy Bodies. Administration of cholinesterase inhibitors was associated with decrease of psychiatric symptoms in both cases. In addition to those clinical observations, a systematic review of the literature suggests that, beyond prefrontal cortex, temporal lobe and putamen have important roles in OCD pathophysiology. Based on these findings, we discuss four hypotheses to explain the sequential appearance of OCD and DLB symptoms. First, we considered the possibility that comorbidity of OCD with DLB was coincidental. Second, we propose to interpret OCD symptoms as motor stereotypies. Third, we hypothesize that late-onset OCD might be a symptom of late-onset depression. Four, we hypothesize that through early deterioration of basal ganglia, DLB caused the onset of OCD. CONCLUSION: In conclusion, we recommend that cases of late-onset treatment-resistant OCD should be carefully tested for possible organic etiologies, and for DLB in particular.

Correction: Performance in delayed non-matching to sample task predicts the diagnosis of obsessive-compulsive disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Psychiatric Advance Directives and Artificial Intelligence: A Conceptual Framework for Theoretical and Ethical Principles.

The patient's decision-making abilities are often altered in psychiatric disorders. The legal framework of psychiatric advance directives (PADs) has been made to provide care to patients in these situations while respecting their free and informed consent. The implementation of artificial intelligence (AI) within Clinical Decision Support Systems (CDSS) may result in improvements for complex decisions that are often made in situations covered by PADs. Still, it raises theoretical and ethical issues this paper aims to address. First, it goes through every level of possible intervention of AI in the PAD drafting process, beginning with what data sources it could access and if its data processing competencies should be limited, then treating of the opportune moments it should be used and its place in the contractual relationship between each party (patient, caregivers, and trusted person). Second, it focuses on ethical principles and how these principles, whether they are medical principles (autonomy, beneficence, non-maleficence, justice) applied to AI or AI principles (loyalty and vigilance) applied to medicine, should be taken into account in the future of the PAD drafting process. Some general guidelines are proposed in conclusion: AI must remain a decision support system as a partner of each party of the PAD contract; patients should be able to choose a personalized type of AI intervention or no AI intervention at all; they should stay informed, i.e., understand the functioning and relevance of AI thanks to educational programs; finally, a committee should be created for ensuring the principle of vigilance by auditing these new tools in terms of successes, failures, security, and relevance.