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.

Effects of tryptophan depletion on anxiety, a systematic review.

Vulnerability markers for onset of anxiety disorders are scarce. In depression, patients at risk tend to respond with a negative mood to 'acute tryptophan depletion' (ATD), while healthy volunteers and current patients do not. The serotonergic system thus provides indications for vulnerability for depression. It is unknown whether ATD reveals vulnerability in anxiety too. This study systematically reviews the effects of ATD on anxiety and assesses whether challenging anxiety modifies the response. PubMed, Embase and PsychInfo were systematically searched up to April 2019 for studies in which (1) healthy volunteers or patients with a (remitted) anxiety disorder underwent ATD and (2) levels of anxiety were reported. In total, 21 studies were included. Studies conducted in healthy volunteers (n = 13), and patients with a remitted (n = 6) or current (panic, social or generalised) anxiety disorder (n = 4). Studies were mostly of poor quality and heterogeneous regarding population, challenge test used and outcome measures. ATD did not consistently affect anxiety in any of the groups. Moreover, a challenge test after ATD (n = 17 studies) did not consistently provoke anxiety in healthy volunteers or remitted patients. A 35% CO2 challenge did consistently increase anxiety in patients with a current panic disorder (PD). To conclude, this systematic review found no clear indications that ATD provokes anxiety in those at risk for anxiety disorders. Hence, unlike in depression, ATD does not indicate vulnerability to develop an anxiety disorder. Because included studies were heterogeneous and mostly of poor quality, there is an urgent need for high quality research in homogeneous samples.

Prevalence and course of subthreshold anxiety disorder in the general population: A three-year follow-up study.

BACKGROUND: This study examined the prevalence, course and risk indicators of subthreshold anxiety disorder to determine the necessity and possible risk indicators for interventions. METHODS: Data were derived from the 'Netherlands Mental Health Survey and Incidence Study-2' (NEMESIS-2), a psychiatric epidemiological cohort study among the general population (n = 4528). This study assessed prevalence, characteristics, and three-year course of subthreshold anxiety disorder (n = 521) in adults, and compared them to a no anxiety group (n = 3832) and an anxiety disorder group (n = 175). Risk indicators for persistent and progressive subthreshold anxiety disorder were also explored, including socio-demographics, vulnerability factors, psychopathology, physical health and functioning. RESULTS: The three-year prevalence of subthreshold anxiety disorder was 11.4%. At three-year follow-up, 57.3% had improved, 29.0% had persistent subthreshold anxiety disorder and 13.8% had progressed to a full-blown anxiety disorder. Prevalence, characteristics and course of subthreshold anxiety disorder were in between both comparison groups. Risk indicators for persistent course partly overlapped with those for progressive course and included vulnerability and psychopathological factors, and diminished functioning. LIMITATIONS: Course analysis were restricted to the development of anxiety disorders, other mental disorders were not assessed. Moreover, due to the naturalistic design of the study the impact of treatment on course cannot be assessed. CONCLUSIONS: Subthreshold anxiety disorder is relatively prevalent and at three-year follow-up a substantial part of respondents experienced persistent symptoms or had progressed into an anxiety disorder. Risk indicators like reduced functioning may help to identify these persons for (preventative) treatment and hence reduce functional limitations and disease burden.

Failure to Respond after Reinstatement of Antidepressant Medication: A Systematic Review.

BACKGROUND: Following remission of an anxiety disorder or a depressive disorder, antidepressants are frequently discontinued and in the case of symptom occurrence reinstated. Reinstatement of antidepressants seems less effective in some patients, but an overview is lacking. This systematic review aimed to provide insight into the magnitude and risk factors of response failure after reinstatement of antidepressants in patients with anxiety disorders, depressive disorders, obsessive-compulsive disorder (OCD), or posttraumatic stress disorder (PTSD). METHOD: PubMed, Embase, and trial registers were systematically searched for studies in which patients: (1) had an anxiety disorder, a depressive disorder, OCD, or PTSD and (2) experienced failure to respond after reinstatement of a previously effective antidepressant. RESULTS: Ten studies reported failure to respond following antidepressant reinstatement. The phenomenon was observed in 16.5% of patients with a depressive disorder, OCD, and social phobia and occurred in all common classes of antidepressants. The range of response failure was broad, varying between 3.8 and 42.9% across studies. No risk factors for failure to respond were investigated. The overall study quality was limited. CONCLUSION: Research investigating response failure is scarce and the study quality limited. Response failure occurred in a substantial minority of patients. Contributors to the relevance of this phenomenon are the prevalence of the investigated disorders, the number of patients being treated with antidepressants, and the occurrence of response failure for all common classes of antidepressants. This systematic review highlights the need for studies systematically investigating this phenomenon and associated risk factors.

No Menstrual Cyclicity in Mood and Interpersonal Behaviour in Nine Women with Self-Reported Premenstrual Syndrome.

BACKGROUND/AIMS: Before diagnosing premenstrual dysphoric disorder (PMDD), 2 months of prospective assessment are required to confirm menstrual cyclicity in symptoms. For a diagnosis of premenstrual syndrome (PMS), this is not required. Women with PMDD and PMS often report that their symptoms interfere with mood and social functioning, and are said to show cyclical changes in interpersonal behaviour, but this has not been examined using a prospective approach. We sampled cyclicity in mood and interpersonal behaviour for 2 months in women with self- reported PMS. METHODS: Participants met the criteria for PMS on the Premenstrual Symptoms Screening Tool (PSST), a retrospective questionnaire. For 2 menstrual cycles, after each social interaction, they used the online software TEMPEST to record on their smartphones how they felt and behaved. We examined within-person variability in negative affect, positive affect, quarrelsomeness, and agreeableness. RESULTS: Participants evaluated TEMPEST as positive. However, we found no evidence for menstrual cyclicity in mood and interpersonal behaviour in any of the individual women (n = 9). CONCLUSION: Retrospective questionnaires such as the PSST may lead to oversampling of PMS. The diagnosis of PMS, like that of PMDD, might require 2 months of prospective assessment.

Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials.

Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy.Design Systematic review and meta-analyses of relapse prevention trials.Data sources PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016).Study selection Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse.Data extraction Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool.Results The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients' preferences.

Long-term antidepressant use: a qualitative study on perspectives of patients and GPs in primary care.

BACKGROUND: Antidepressant use is often prolonged in patients with anxiety and/or depressive disorder(s) compared with recommendations in treatment guidelines to discontinue after sustained remission. AIM: To unravel the motivations of patients and GPs causing long-term antidepressant use and to gain insight into possibilities to prevent unnecessary long-term use. DESIGN AND SETTING: Qualitative study using semi-structured, in-depth interviews with patients and GPs in the Netherlands. METHOD: Patients with anxiety and/or depressive disorder(s) (n = 38) and GPs (n = 26) were interviewed. Innovatively, the interplay between patients and their GPs was also investigated by means of patient-GP dyads (n = 20). RESULTS: The motives and barriers of patients and GPs to continue or discontinue antidepressants were related to the availability of supportive guidance during discontinuation, the personal circumstances of the patient, and considerations of the patient or GP. Importantly, dyads indicated a large variation in policies of general practices around long-term use and continuation or discontinuation of antidepressants. Dyads further indicated that patients and GPs seemed unaware of each other's (mismatching) expectations regarding responsibility to initiate discussing continuation or discontinuation. CONCLUSION: Although motives and barriers to antidepressant continuation or discontinuation were related to the same themes for patients and GPs, dyads indicated discrepancies between them. Discussion between patients and GPs about antidepressant use and continuation or discontinuation may help clarify mutual expectations and opinions. Agreements between a patient and their GP can be included in a patient-tailored treatment plan.

Optimising Extinction of Conditioned Disgust.

Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS)-only extinction procedures. The relatively strong resistance to extinction might be explained by disgust's adaptive function to motivate avoidance from contamination threats (pathogens) that cannot be readily detected and are invisible to the naked eye. Therefore, the mere visual presentation of unreinforced disgust eliciting stimuli might not be sufficient to correct a previously acquired threat value of the CS+. Following this, the current study tested whether the efficacy of CS-only exposure can be improved by providing additional safety information about the CS+. For the CSs we included two neutral items a pea soup and a sausage roll, whereas for the Unconditioned Stimulus (US) we used one video clip of a woman vomiting and a neutral one about glass blowing. The additional safety information was conveyed by allowing actual contact with the CS+ or by observing an actress eating the food items representing the CS+. When additional safety information was provided via allowing direct contact with the CS+, there was a relatively strong post-extinction increase in participants' willingness-to-eat the CS+. This beneficial effect was still evident at one-week follow up. Also self-reported disgust was lower at one-week follow up when additional safety information was provided. The current findings help explain why disgust is relatively insensitive to CS-only extinction procedures, and provide helpful starting points to improve interventions that are aimed to reduce distress in disgust-related psychopathology.

Daily symptom ratings for studying premenstrual dysphoric disorder: A review.

BACKGROUND: To review how daily symptom ratings have been used in research into premenstrual dysphoric disorder (PMDD), and to discuss opportunities for the future. METHODS: PsycINFO and Medline were systematically searched, resulting in the inclusion of 75 studies in which (1) participants met the diagnostic criteria for late luteal phase dysphoric disorder (LLPDD) or PMDD and (2) diaries were used to study LLPDD/PMDD. RESULTS: To date, diaries have been used to gain insight into the aetiology and phenomenology of PMDD, to examine associated biological factors, and to assess treatment efficacy. We found low consistency among the diaries used, and often only part of the menstrual cycle was analysed instead of the whole menstrual cycle. We also observed that there was substantial variability in diagnostic procedures and criteria. LIMITATIONS: This review excluded diary studies conducted in women with premenstrual syndrome, women seeking help for premenstrual complaints without a clear diagnosis, and women without premenstrual complaints. CONCLUSIONS: Prospective daily ratings of symptoms and related variables provide a valuable and important tool in the study of PMDD. This paper addresses some options for improving the use of diaries and proposes the use of experience sampling and ecological momentary assessment to investigate within-person variability in symptoms in more detail.

Is disgust sensitive to classical conditioning as indexed by facial electromyography and behavioural responses?

Earlier studies provided preliminary support for the role of classical conditioning as a pathway of disgust learning, yet this evidence has been limited to self-report. This study included facial electromyographical (EMG) measurements (corrugator and levator muscles) and a behavioural approach task to assess participants' motivation-to-eat the actual food items (conditioned stimuli, CS). Food items served as CS and film excerpts of a woman vomiting served as unconditioned stimuli (US). Following acquisition the CS+ (neutral CS paired with US disgust) was rated as more disgusting and less positive. Notably, the conditioned response was transferred to the actual food items as evidenced by participants' reported lowered willingness-to-eat. Participants also showed heightened EMG activity in response to the CS+ which seemed driven by the corrugator indexing a global negative affect. These findings suggest that classical conditioning as a pathway of disgust learning can be reliably observed in subjective but not in disgust-specific physiological responding.