Does a lack of emotions make chatbots unfit to be psychotherapists?

Mental health chatbots (MHCBs) designed to support individuals in coping with mental health issues are rapidly advancing. Currently, these MHCBs are predominantly used in commercial rather than clinical contexts, but this might change soon. The question is whether this use is ethically desirable. This paper addresses a critical yet understudied concern: assuming that MHCBs cannot have genuine emotions, how this assumption may affect psychotherapy, and consequently the quality of treatment outcomes. We argue that if MHCBs lack emotions, they cannot have genuine (affective) empathy or utilise countertransference. Consequently, this gives reason to worry that MHCBs are (a) more liable to harm and (b) less likely to benefit patients than human therapists. We discuss some responses to this worry and conclude that further empirical research is necessary to determine whether these worries are valid. We conclude that, even if these worries are valid, it does not mean that we should never use MHCBs. By discussing the broader ethical debate on the clinical use of chatbots, we point towards how further research can help us establish ethical boundaries for how we should use mental health chatbots.

The Effects of Patient Preference on Clinical Outcome, Satisfaction and Adherence Within the Treatment of Anxiety and Depression: A Meta-Analysis.

BACKGROUND: Taking patient preference into consideration has received increased attention in the last decades. We conducted a meta-analysis to estimate the effects of patient preference on clinical outcome, satisfaction and adherence regarding treatment of depression and anxiety. METHODS: Pubmed, Embase, PsycINFO and Scopus were searched for (cluster) randomized controlled trials. Twenty-six randomized controlled clinical trials were included, comprising 3670 participants, examining the effect of patient preference regarding treatment of anxiety and depression on clinical outcome, satisfaction and/or adherence. RESULTS: No effect of patient preference was found on clinical outcome [d = 0.06, 95% CI = (-0.03, 0.15), p = 0.16, n = 23 studies]. A small effect of patient preference was found on treatment satisfaction [d = 0.33, 95% CI = (0.08, 0.59), p = 0.01, n = 6 studies] and on treatment adherence [OR = 1.55, 95% CI = (1.28, 1.87), p < 0.001, n = 22 studies]. LIMITATIONS: Patient preference is a heterogeneous concept, future studies should strive to equalize operationalization of preference. Subgroup analyses within this study should be interpreted with caution because the amount of studies per analysed subgroup was generally low. Most studies included in this meta-analysis focused on patients with depression. The small number of studies (n = 6) on satisfaction, prevents us from drawing firm conclusions. CONCLUSIONS: While this meta-analysis did not find a positive effect of considering patient preference on clinical outcome, it was associated with slightly better treatment satisfaction and adherence. Accommodating preference of patients with anxiety and depression can improve treatment. TRIAL REGISTRATION: PROSPERO: CRD42020172556.

The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

Insomnia and the incidence, recurrence and persistence of common mental disorders: Sex-differences in the general population.

Insomnia is common throughout the population and thought to be a risk factor for mental disorders. We assessed the association of insomnia symptoms with incidence, recurrence and persistence of mood, anxiety and substance use disorders. In 4007 participants (55 % women, mean age 51.0 ± 12.3) of the population-based Netherlands Mental Health Survey and Incidence Study (NEMESIS), having insomnia symptoms increased the odds of developing, recurring and persisting mood disorders, mostly in men. Insomnia only associated with recurring anxiety disorders, particularly in women, and not with substance use disorders. Treating insomnia may aid recovery and prevention of mental disorders, particularly mood disorders.

Treatment Preferences of Adolescents and Young Adults with Depressive Symptoms: A Discrete Choice Experiment.

BACKGROUND: Depression in adolescents and young adults is common and causes considerable disease burden while hampering their development, leading to adverse consequences in later life. Although treatment is available, young people are a vulnerable group regarding uptake and completion of treatment. To improve this, insight into youth's preferences for treatment is essential. OBJECTIVE: The aim of this study was to investigate patient preferences for depression treatment in a Dutch sample aged 16-24 years using a discrete choice experiment (DCE). METHODS: The study was conducted in The Netherlands between October 2018 and June 2019, and included 236 adolescents and young adults with current depressive symptoms or previous treatment. The DCE included five attributes (treatment type, frequency of appointment, waiting time, effectiveness, evaluation of therapeutic alliance) with corresponding levels. Results were analysed using latent class analysis. RESULTS: Results show a general preference for individual psychotherapy, treatment with high frequency, high effectiveness, short waiting time and a standard evaluation of the therapeutic alliance ('click' with the therapist) early in treatment. Latent class analysis revealed three different patterns of preferences regarding treatment type and willingness to engage in therapy. The first class showed a strong preference for individual therapy. The second class, including relatively older, higher educated and treatment-experienced participants, preferred high frequency treatment and was more open to different forms of therapy. The third class, including lower educated, younger and treatment-naïve adolescents showed reluctance to engage in therapy overall and in group therapy specifically. CONCLUSION: In this DCE, three classes could be identified that share similar preferences regarding treatment effectiveness, waiting time and evaluation of the therapeutic alliance, but varied considerably in their preference for treatment type (individual, group, or combined psychotherapy) and their willingness to engage. The results from this study may inform mental health care providers and institutions and help optimize professional care for adolescents and young adults with depressive symptoms, improving engagement in this vulnerable group.

Understanding and preventing nonadherence and treatment dropout in adolescents and young adults with anxiety and depressive disorders.

Dropout from psychological or pharmacological treatment for anxiety and depressive disorders is common. It is especially problematic in adolescents and young adults because of the adverse consequences for their development. Reasons for treatment dropout can be divided into therapy-process related factors, attitudinal aspects, and practical issues. Adjusting treatment to patient preferences and shared decision making, improving the therapeutic alliance, and interventions such as (family) psychoeducation, motivational interviewing, and help with practical issues are promising strategies to optimize engagement and adherence.

TMS-induced plasticity improving cognitive control in OCD I: Clinical and neuroimaging outcomes from a randomised trial of rTMS for OCD.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment option for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have, however, been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following three different rTMS stimulation protocols, all combined with exposure and response prevention (ERP). Methods: In this three-arm proof-of-concept randomized controlled clinical trial, 61 treatment-refractory adult OCD patients received 16 sessions of rTMS immediately prior to ERP over 8 weeks, with task-based functional MRI (tb-fMRI) scans and clinical assessments pre- and post-treatment. Patients received either: high frequency (HF) rTMS to the left dorsolateral prefrontal cortex (DLPFC) (n=19 (6M/13F)); HF rTMS to the left pre-supplementary motor area (preSMA) (n=23 (10M/13F)); or control rTMS to the vertex (n=19 (6M/13F)). Changes in tb-fMRI activation pre-post treatment were compared using both a Bayesian region-of-interest and a general linear model whole-brain approach. Results: Mean OCD symptom severity decreased significantly in all treatment groups (delta=- 10.836, p<0.001, 95% CI [-12.504, -9.168]), with no differences between groups. Response rate in the entire sample was 57.4%. Groups receiving DLPFC or preSMA rTMS showed, respectively, a decrease in planning and error processing task-related activation after treatment that was associated with symptom improvement, while individuals in the vertex rTMS group with greater symptom improvement showed an increase in inhibition-related activation. Conclusions: PreSMA and DLPFC rTMS combined with ERP led to significant symptom improvement related to activation decreases in targeted task networks, although we observed no differences in symptom reduction between groups. This trial was registered at clinicaltrials.gov ( NCT03667807 ).

Risk factors of chronic course of anxiety and depressive disorders: a 3-year longitudinal study in the general population.

BACKGROUND: Risk factors of a chronic course of anxiety and depressive disorders were previously studied using a limited definition of recovery, i.e. remission of the index disorder. However, frequently, other mental disorders are present at follow-up. Thus, the course of anxiety and depressive disorders was represented too rosy and the identified determinants may not apply when using a broader, more realistic definition. Additionally, physical health risk factors have often been ignored. METHODS: Data were used from two waves of the Netherlands Mental Health Survey and Incidence Study-2 including 509 respondents with 12-month anxiety disorder (panic disorder, social phobia, agoraphobia or generalized anxiety disorder) or/and major depressive disorder at baseline. Chronic course was defined as (1) presence of index disorder; and (2) presence of any anxiety, mood or substance use disorder (overall course) during the subsequent three years. Regression models were built with sociodemographic, clinical, and lifestyle/physical health indicators. Predictive accuracy was evaluated with area under the curve (AUC). RESULTS: Chronic course of the index disorder was present among 24.8% of cases, whereas 38.7% had a chronic overall course. The accuracy of prediction of chronic course of the index disorder was suboptimal (AUC = 0.68) compared to prediction of overall course (AUC = 0.75). The main risk factors were baseline number of mental disorders, neuroticism, childhood abuse, parental psychopathology and alcohol use. Lifestyle and physical health indicators were marginally relevant. CONCLUSION: Transdiagnostic risk factors are important in predicting overall course of anxiety and depressive disorders but cannot accurately predict chronic course of the index disorder.

Baseline Severity as a Moderator of the Waiting List-Controlled Association of Cognitive Behavioral Therapy With Symptom Change in Social Anxiety Disorder: A Systematic Review and Individual Patient Data Meta-analysis.

Importance: Social anxiety disorder (SAD) can be adequately treated with cognitive behavioral therapy (CBT). However, there is a large gap in knowledge on factors associated with prognosis, and it is unclear whether symptom severity predicts response to CBT for SAD. Objective: To examine baseline SAD symptom severity as a moderator of the association between CBT and symptom change in patients with SAD. Data Sources: For this systematic review and individual patient data meta-analysis (IPDMA), PubMed, PsycInfo, Embase, and the Cochrane Library were searched from January 1, 1990, to January 13, 2023. Primary search topics were social anxiety disorder, cognitive behavior therapy, and randomized controlled trial. Study Selection: Inclusion criteria were randomized clinical trials comparing CBT with being on a waiting list and using the Liebowitz Social Anxiety Scale (LSAS) in adults with a primary clinical diagnosis of SAD. Data Extraction and Synthesis: Authors of included studies were approached to provide individual-level data. Data were extracted by pairs of authors following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline, and risk of bias was assessed using the Cochrane tool. An IPDMA was conducted using a 2-stage approach for the association of CBT with change in LSAS scores from baseline to posttreatment and for the interaction effect of baseline LSAS score by condition using random-effects models. Main Outcomes and Measures: The main outcome was the baseline to posttreatment change in symptom severity measured by the LSAS. Results: A total of 12 studies including 1246 patients with SAD (mean [SD] age, 35.3 [10.9] years; 738 [59.2%] female) were included in the meta-analysis. A waiting list-controlled association between CBT and pretreatment to posttreatment LSAS change was found (b = -20.3; 95% CI, -24.9 to -15.6; P < .001; Cohen d = -0.95; 95% CI, -1.16 to -0.73). Baseline LSAS scores moderated the differences between CBT and waiting list with respect to pretreatment to posttreatment symptom reductions (b = -0.22; 95% CI, -0.39 to -0.06; P = .009), indicating that individuals with severe symptoms had larger waiting list-controlled symptom reductions after CBT (Cohen d = -1.13 [95% CI, -1.39 to -0.88] for patients with very severe SAD; Cohen d = -0.54 [95% CI, -0.80 to -0.29] for patients with mild SAD). Conclusions and Relevance: In this systematic review and IPDMA, higher baseline SAD symptom severity was associated with greater (absolute but not relative) symptom reductions after CBT in patients with SAD. The findings contribute to personalized care by suggesting that clinicians can confidently offer CBT to individuals with severe SAD symptoms.

Antidepressants or running therapy: Comparing effects on mental and physical health in patients with depression and anxiety disorders.

BACKGROUND: Antidepressant medication and running therapy are both effective treatments for patients with depressive and anxiety disorders. However, they may work through different pathophysiological mechanisms and could differ in their impact on physical health. This study examined effects of antidepressants versus running therapy on both mental and physical health. METHODS: According to a partially randomized patient preference design, 141 patients with depression and/or anxiety disorder were randomized or offered preferred 16-week treatment: antidepressant medication (escitalopram or sertraline) or group-based running therapy ≥2 per week. Baseline (T0) and post-treatment assessment at week 16 (T16) included mental (diagnosis status and symptom severity) and physical health indicators (metabolic and immune indicators, heart rate (variability), weight, lung function, hand grip strength, fitness). RESULTS: Of the 141 participants (mean age 38.2 years; 58.2 % female), 45 participants received antidepressant medication and 96 underwent running therapy. Intention-to-treat analyses showed that remission rates at T16 were comparable (antidepressants: 44.8 %; running: 43.3 %; p = .881). However, the groups differed significantly on various changes in physical health: weight (d = 0.57; p = .001), waist circumference (d = 0.44; p = .011), systolic (d = 0.45; p = .011) and diastolic (d = 0.53; p = .002) blood pressure, heart rate (d = 0.36; p = .033) and heart rate variability (d = 0.48; p = .006). LIMITATIONS: A minority of the participants was willing to be randomized; the running therapy was larger due to greater preference for this intervention. CONCLUSIONS: While the interventions had comparable effects on mental health, running therapy outperformed antidepressants on physical health, due to both larger improvements in the running therapy group as well as larger deterioration in the antidepressant group. TRIAL REGISTRATION: Trialregister.nl Number of identification: NTR3460.

The link between cardiac status and depression and anxiety in implantable cardioverter defibrillator patients: Design and first results of the PSYCHE-ICD study.

OBJECTIVE: Depression and anxiety in patients with an implantable cardioverter-defibrillator (ICD) are associated with adverse outcomes. This study describes the design of the PSYCHE-ICD study and evaluates the correlation between cardiac status and depression and anxiety in ICD patients. METHODS: We included 178 patients. Prior to implantation, patients completed validated psychological questionnaires for depression, anxiety and personality traits. Cardiac status was evaluated by means of left ventricular ejection fraction assessment (LVEF), New York Heart Association (NYHA) functional class, 6-minute walk test (6MWT), and 24-h Holter monitoring for heart rate variability (HRV). A cross-sectional analysis was performed. Follow-up with annual study visits, including repeated full cardiac evaluation, will continue 36 months after ICD implantation. RESULTS: Depressive symptoms were present in 62 (35%) and anxiety in 56 (32%) patients. Values of depression and anxiety significantly increased with higher NYHA class (P < 0.001). Depression symptoms were correlated with a reduced 6MWT (411 ± 128 vs. 488 ± 89, P < 0.001), higher heart rate (74 ± 13 vs. 70 ± 13, P = 0.02), higher thyroid stimulation hormone levels (1.8 [1.3-2.8] vs 1.5 [1.0-2.2], P = 0.03) and multiple HRV parameters. Anxiety symptoms were correlated with higher NYHA class and a reduced 6MWT (433 ± 112 vs 477 ± 102, P = 0.02). CONCLUSION: A substantial part of patients receiving an ICD have symptoms of depression and anxiety at time of ICD implantation. Depression and anxiety were correlated with multiple cardiac parameters, suggesting a possible biological links between psychological distress and cardiac disease in ICD patients.

Schema therapy with cognitive behaviour day-treatment in patients with treatment-resistant anxiety disorders and obsessive-compulsive disorder: an uncontrolled pilot study.

BACKGROUND: Treatment resistance in patients with anxiety disorders and obsessive-compulsive disorder (OCD) might be caused by dysfunctional personality traits or, more specifically, early maladaptive schemas (EMSs) and schema modes, that can be treated with schema therapy (ST). AIM: To explore possible effectiveness of ST-CBT day-treatment in patients with treatment-resistant anxiety disorders and OCD in an uncontrolled pilot study. METHOD: Treatment-resistant patients with anxiety disorders or OCD (n = 27) were treated with ST-CBT day-treatment for 37 weeks on average including 11.5 therapy hours per week. The Symptom Questionnaire-48, Young Schema Questionnaire-2 and Schema Mode Inventory were completed before and after treatment. RESULTS: General psychopathology, EMSs and schema modes significantly improved after treatment. Spearman's correlations between pre- to post-treatment difference scores of general psychopathology, EMSs and schema modes were significant and high. The level of pre-treatment EMSs and schema modes did not predict post-treatment general psychopathology. CONCLUSIONS: Symptom reduction was strongly correlated with improvement of EMSs and schema modes. Stronger pre-treatment EMSs and schema modes did not hinder improvement of symptoms. ST-CBT day-treatment is promising for patients with treatment-resistant anxiety disorders and OCD. Further controlled research is needed to substantiate evidence for schema therapy in patients with treatment-resistant anxiety disorders and OCD.

Recurrence of anxiety disorders and its predictors in the general population.

BACKGROUND: Anxiety disorders frequently recur in clinical populations, but the risk of recurrence of anxiety disorders is largely unknown in the general population. In this study, recurrence of anxiety and its predictors were studied in a large cohort of the adult general population. METHODS: Baseline, 3-year and 6-year follow-up data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Respondents (N = 468) who had been in remission for at least a year prior to baseline were included. Recurrence was assessed at 3 and 6 years after baseline, using the Composite International Diagnostic Interview version 3.0. Cumulative recurrence rates were estimated using the number of years since remission of the last anxiety disorder. Furthermore, Cox regression analyses were conducted to investigate predictors of recurrence, using a broad range of putative predictors. RESULTS: The estimated cumulative recurrence rate was 2.1% at 1 year, 6.6% at 5 years, 10.6% at 10 years, and 16.2% at 20 years. Univariate regression analyses predicted a shorter time to recurrence for several variables, of which younger age at interview, parental psychopathology, neuroticism and a current depressive disorder remained significant in the, age and gender-adjusted, multivariable regression analysis. CONCLUSIONS: Recurrence of anxiety disorders in the general population is common and the risk of recurrence extends over a lengthy period of time. In clinical practice, alertness to recurrence, monitoring of symptoms, and quick access to health care in case of recurrence are needed.

The impact of borderline personality disorder symptoms on onset and course of anxiety disorders: Results of a general population study.

Borderline personality disorder (BPD) has a negative impact on the onset and course of anxiety disorders. However, even though many people with anxiety disorders only have some BPD symptoms, little is known about the impact of BPD symptoms on anxiety disorders. This study examines the impact of BPD symptoms on the onset and persistence of anxiety disorders over a 3-year follow-up in the general population. Longitudinal data from the Netherlands Mental Health Survey and Incidence study were used (N = 4,618). BPD symptoms were assessed using the International Personality Examination, and anxiety disorders and other mental disorders were assessed with the Composite International Diagnostic Interview. Logistic regression analyses were performed, adjusting for a wide range of potential confounders such as childhood abuse and mood disorders. In all, 72.1% of the participants reported no BPD symptoms, 24.0% reported one to two symptoms, 3.1% reported three to four symptoms, and 0.8% reported ≥ 5 symptoms. There was a clear dose-response relation, with more BPD symptoms being associated with a higher risk for onset and persistence of anxiety disorders (both p for trend < .001). Even one to two BPD symptoms significantly impacted the onset (odds ratio = 3.32, 95% confidence interval [1.68, 6.54]) and persistence (odds ratio = 3.12, 95% confidence interval [1.01, 9.64]). Results appeared to be independent of multiple potential confounders. Even a low number of BPD symptoms impact the onset and persistence of anxiety disorders. Targeting these symptoms may improve the outcome of anxiety disorders. Future research should study the effect of various interventions for people with anxiety disorders and BPD symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

How chronic are depressive and anxiety disorders? 9-year general population study using narrow and broad course outcomes.

BACKGROUND: Existing studies on disease course usually apply relatively short follow-up periods and narrow definitions of disease course resulting in too optimistic views on disease prognosis. This study explores the relevance of using a longer and broader (cross-disorder) perspective. METHODS: Respondents with a 12-month disorder at baseline and available at 3-, 6- and 9-year follow-up were selected (major depressive disorder, MDD: n = 208; anxiety disorder: n = 220) from a general population study (N = 6646). DSM-IV disorders were assessed with the Composite International Diagnostic Interview. Disease course was described using a short and narrow perspective (i.e., 3-year follow-up, and considering presence of the index disorder only) and a long and broad perspective (9-year follow-up, and considering presence of any mood, anxiety or substance use disorder as outcome). RESULTS: The recovery rates of both MDD and anxiety disorder reduced by half when the perspective switched from short and narrow (MDD: 74.0 %; anxiety disorder: 79.5 %) to long and broad (35.6 % and 40.0 % respectively). At 9-year follow-up, the rates of a persistent disorder (a disorder at each follow-up assessment) tripled when the perspective switched from narrow to broad (MDD: from 4.8 % to 13.9 %; anxiety disorder: from 4.5 % to 15.5 %). LIMITATIONS: The findings are not generalizable to the most severe depressed and anxious patients. CONCLUSIONS: Most people with MDD or anxiety disorder in the general population have a rather favourable prognosis when a narrow perspective is applied, but an unfavourable prognosis when a long-term and broad perspective is applied. Consequently, MDD and anxiety disorder should not merely be perceived as episodic disorders, and require longer-term disease monitoring and management.

Psychological interventions to prevent relapse in anxiety and depression: A systematic review and meta-analysis.

OBJECTIVES: The aim of this review is to establish the effectiveness of psychological relapse prevention interventions, as stand-alone interventions and in combination with maintenance antidepressant treatment (M-ADM) or antidepressant medication (ADM) discontinuation for patients with remitted anxiety disorders or major depressive disorders (MDD). METHODS: A systematic review and a meta-analysis were conducted. A literature search was conducted in PubMed, PsycINFO and Embase for randomised controlled trials (RCTs) comparing psychological relapse prevention interventions to treatment as usual (TAU), with the proportion of relapse/recurrence and/or time to relapse/recurrence as outcome measure. RESULTS: Thirty-six RCTs were included. During a 24-month period, psychological interventions significantly reduced risk of relapse/recurrence for patients with remitted MDD (RR 0.76, 95% CI: 0.68-0.86, p<0.001). This effect persisted with longer follow-up periods, although these results were less robust. Also, psychological interventions combined with M-ADM significantly reduced relapse during a 24-month period (RR 0.76, 95% CI: 0.62-0.94, p = 0.010), but this effect was not significant for longer follow-up periods. No meta-analysis could be performed on relapse prevention in anxiety disorders, as only two studies focused on relapse prevention in anxiety disorders. CONCLUSIONS: In patients with remitted MDD, psychological relapse prevention interventions substantially reduce risk of relapse/recurrence. It is recommended to offer these interventions to remitted MDD patients. Studies on anxiety disorders are needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2018: CRD42018103142.

The bidirectional relationship between anxiety disorders and alcohol use disorders in adults: Findings from a longitudinal population-based study.

BACKGROUND: Anxiety disorders (AD) and alcohol use disorder (AUD) frequently co-occur, but the temporal order of the association is unclear. We have determined the association between AD and the presence and first-onset of AUD, and vice versa. METHODS: Data were used from n = 6.646 participants and four measurement waves (baseline, 3-, 6- and 9-years) of the Netherlands Mental Health Survey and Incidence Study 2 (NEMESIS-2), a cohort study of the Dutch general population aged 18-64 years. AD and AUD were assessed with the Composite International Diagnostic Interview 3.0. Multilevel logistic autoregressive models were controlled for previous-wave AD or AUD, sociodemographics (Model 1), smoking and clinical factors (Model 2). RESULTS: People with AUD had a higher risk of present (OR = 1.65, 95 % CI 1.11-2.43; Model 2) and first-onset (OR = 2.03, 95 % CI 1.17-3.51; Model 2) AD in 3-years follow-up intervals than people without AUD. Vice versa, people with AD also had a higher sociodemographics-adjusted risk of present and first-onset AUD over 3-years follow-up intervals, but these associations attenuated into insignificance after adjustment for smoking and clinical variables. Limitations For statistical power reasons we were not able to analyze 9-year follow-up data or distinguish between AD and AUD types. CONCLUSIONS: Our results indicate a bidirectional relationship between AD and AUD; especially those with severe AD (medication use, comorbid depression) are at risk of developing AUD. Health care professionals should focus on prevention of AD in AUD patients and prevention of AUD in patients with (more severe) AD. Further research should investigate the mechanisms underlying the observed associations.