Cosima Locher

The separation anxiety hypothesis of panic disorder revisited: a meta-analysis.

OBJECTIVE Evidence suggests that childhood separation anxiety disorder may be associated with a heightened risk for the development of other disorders in adulthood. The authors conducted a meta-analysis to examine the relationship between childhood separation anxiety disorder and future psychopathology. METHOD PubMed, PsycINFO, and Embase were searched for studies published through December 2011. Case-control, prospective, and retrospective cohort studies comparing children with and without separation anxiety disorder with regard to future panic disorder, major depressive disorder, any anxiety disorder, and substance use disorders were included in the analysis. Effects were summarized as pooled odds ratios in a random-effects model. RESULTS Twenty-five studies met all inclusion criteria (14,855 participants). A meta-analysis of 20 studies indicated that children with separation anxiety disorder were more likely to develop panic disorder later on (odds ratio=3.45; 95% CI=2.37-5.03). Five studies suggested that a childhood diagnosis of separation anxiety disorder increases the risk of future anxiety (odds ratio=2.19; 95% CI=1.40-3.42). After adjusting for publication bias, the results of 14 studies indicated that childhood separation anxiety disorder does not increase the risk of future depression (odds ratio=1.06; 95% CI=0.78-1.45). Five studies indicated that childhood separation anxiety disorder does not increase the risk of substance use disorders (odds ratio=1.27; 95% CI=0.80-2.03). Of the subgroup analyses performed, differences in comparison groups and sample type significantly affected odds ratio sizes. CONCLUSIONS A childhood diagnosis of separation anxiety disorder significantly increases the risk of panic disorder and any anxiety disorder. These results support a developmental psychopathology conceptualization of anxiety disorders.

Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents: A Systematic Review and Meta-analysis

Importance Depressive disorders (DDs), anxiety disorders (ADs), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents. Objective To examine the relative efficacy and safety of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents. Data Sources PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Database from inception through August 7, 2016. Study Selection Published and unpublished randomized clinical trials of SSRIs or SNRIs in youths with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (eg, tricyclic antidepressants, monoamine oxidase inhibitors) were excluded. Data Extraction and Synthesis Effect sizes, calculated as standardized mean differences (Hedges g) and risk ratios (RRs) for adverse events, were assessed in a random-effects model. Main Outcomes and Measures Primary outcomes, as defined by authors on preintervention and postintervention data, mean change data, and adverse event data, were extracted independently by multiple observers following PRISMA guidelines. Results Thirty-six trials were eligible, including 6778 participants (3484 [51.4%] female; mean [SD] age, 12.9 [5.1] years); 17 studies for DD, 10 for AD, 8 for OCD, and 1 for PTSD. Analysis showed that SSRIs and SNRIs were significantly more beneficial compared with placebo, yielding a small effect size (g = 0.32; 95% CI, 0.25-0.40; P < .001). Anxiety disorder (g = 0.56; 95% CI, 0.40-0.72; P < .001) showed significantly larger between-group effect sizes than DD (g = 0.20; 95% CI, 0.13-0.27; P < .001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g = 1.57; 95% CI, 1.36-1.78; P < .001) compared with those with AD (g = 1.03; 95% CI, 0.84-1.21; P < .001). The SSRIs produced a relatively large effect size for ADs (g = 0.71; 95% CI, 0.45-0.97; P < .001). Compared with participants receiving placebo, patients receiving an antidepressant reported significantly more treatment-emergent adverse events (RR, 1.07; 95% CI, 1.01-1.12; P = .01 or RR, 1.49; 95% CI, 1.22-1.82; P < .001, depending on the reporting method), severe adverse events (RR, 1.76; 95% CI, 1.34-2.32; P < .001), and study discontinuation due to adverse events (RR, 1.79; 95% CI, 1.38-2.32; P < .001). Conclusions and Relevance Compared with placebo, SSRIs and SNRIs are more beneficial than placebo in children and adolescents; however, the benefit is small and disorder specific, yielding a larger drug-placebo difference for AD than for other conditions. Response to placebo is large, especially in DD. Severe adverse events are significantly more common with SSRIs and SNRIs than placebo.

Is the rationale more important than deception? A randomized controlled trial of open-label placebo analgesia

Abstract Research on open-label placebos questions whether deception is a necessary characteristic of placebo effects. Yet, comparisons between open-label and deceptive placebos (DPs) are lacking. We therefore assessed effects of open-label placebos and DPs in comparison with no treatment (NT) with a standardized experimental heat pain paradigm in a randomized controlled trial in healthy participants. Participants (N = 160) were randomly assigned to NT, open-label placebo without rationale (OPR-), open-label placebo with rationale (OPR+), and DP. We conducted baseline and posttreatment measurements of heat pain threshold and tolerance. Apart from the NT, all groups received an application of a placebo cream. Primary outcomes were planned comparisons of heat pain tolerance and the corresponding intensity and unpleasantness ratings. Objective posttreatment pain tolerance did not differ among groups. However, for subjective heat pain ratings at the posttreatment tolerance level, groups with a rationale (OPR+ and DP) reported diminished heat pain intensity (t(146) = −2.15, P = 0.033, d = 0.43) and unpleasantness ratings (t(146) = −2.43, P = 0.016, d = 0.49) compared with the OPR-group. Interestingly, the OPR+ and the DP groups did not significantly differ in heat pain intensity (t(146) = −1.10, P = 0.272) or unpleasantness ratings (t(146) = −0.05, P = 0.961) at the posttreatment tolerance level. Our findings reveal that placebos with a plausible rationale are more effective than without a rationale. Even more, open-label placebos did not significantly differ in their effects from DPs. Therefore, we question the ubiquitously assumed necessity of concealment in placebo administration.

Moderation of antidepressant and placebo outcomes by baseline severity in late-life depression: A systematic review and meta-analysis.

BACKGROUND Baseline severity is a crucial moderator of trial outcomes in adult depression, with the advantage of antidepressants over placebo increasing as severity increases. However, this relationship has not been examined in late-life depression. METHODS PubMed, Embase, Web of Science, PsycINFO, and Cochrane were searched for studies published through September 2014. Randomized, acute phase, and double-blind studies comparing an antidepressant group with a placebo group in depressed elderly patients were included. RESULTS Nineteen studies met all inclusion criteria. Within-group effect sizes revealed significant improvement in antidepressant groups (g=1.35, p<.000), as well as in placebo groups (g=.96, p<.000). Change in depressive symptoms assessed by Hamilton Depression Rating Scale (HDRS) was moderated by baseline severity in antidepressant groups (Z=2.67, p=.008) and placebo groups (Z=4.46, p<.000). However, this would be expected as a result of regression toward the mean, and mean differences between groups did not increase (r=.19, p=.469) as a function of baseline severity. LIMITATIONS Limited to published data and information was only analyzed at the level of treatment groups. CONCLUSION Baseline severity was not associated with an antidepressant-placebo difference and placebo responses are large in the treatment of depressed elderly people. We propose a stepwise approach, i.e., to initially offer elderly depressed patients psychosocial interventions and only consider antidepressants if patients do not respond.

Placebos in der Psychotherapieforschung - eine systematische Analyse am Beispiel der systematischen Desensibilisierung

Hintergrund: Die Voraussetzungen der randomisierten, Placebo-kontrollierten Evaluation - die Ununterscheidbarkeit der Therapiebedingungen für die Patienten und die Verblindung der Therapeuten - sind in der Psychotherapieforschung nicht uneingeschränkt gegeben. Das Ziel dieser qualitativen systematischen Übersichtsarbeit ist es, am Beispiel der systematischen Desensibilisierung (SD) die Vorgehensweisen zur Bestimmung der Behandlungsspezifität zu beschreiben und deren theoretische und praktische Implikationen zu diskutieren. Methodik: Auf der Basis einer systematischen Literaturrecherche in PsycINFO und PubMed für den Zeitraum von 1976-2015 wurden Psychotherapiestudien gesucht, in denen Patienten mit Angstsymptomen einer SD- oder Placebo-Gruppe zugewiesen und verglichen wurden. Nach Extraktion der gewählten Moderator-Variablen konnten 11 Studien eingeschlossen werden. Ergebnisse: Die Ergebnisse zu den spezifischen Effekten der SD waren nicht einheitlich. Eine durchgeführte Moderator-Analyse zeigte, dass der Nachweis spezifischer Effekte von der Glaubwürdigkeit des Placebos und dem dabei erlebten Ausmaß emotionaler Erfahrungen abhängig ist. Schlussfolgerung: Ob ein bestimmtes psychotherapeutisches Verfahren als spezifisch einzustufen ist, hängt von der Operationalisierung der Placebo-Kontrolle ab. Insbesondere bei SD scheint die Einschränkung des zu bearbeitenden Themas und in der Folge die Unterbindung der emotionalen Erfahrung des Patienten innerhalb der Kontrollbedingung eine Voraussetzung dafür zu sein, spezifische Effekte der SD zu finden.

Employing open/hidden administration in psychotherapy research: A randomized-controlled trial of expressive writing

Psychotherapy has been shown to be effective, but efforts to prove specific effects by placebo-controlled trials have been practically and conceptually hampered. We propose that adopting open/hidden designs from placebo research would offer a possible way to establish specificity in psychotherapy. Therefore, we tested the effects of providing opposing treatment rationales in an online expressive writing intervention on affect in healthy subjects. Results indicate that it was possible to conduct the expressive writing intervention both covertly and openly, but that participants in the hidden administration condition did not fully benefit from the otherwise effective expressive writing intervention in the long-run. Effect sizes between open and hidden administration groups were comparable to pre-post effect sizes of the intervention. While this finding is important for the understanding of psychotherapys effects per se, it also proves that alternative research approaches to establish specificity are feasible and informative in psychotherapy research. Trial registration: German Clinical Trials Register DRKS00009428

How to address the placebo response in the prescription SSRIs and SNRIs in children and adolescents

ABSTRACT SSRIs and SNRIs are prescribed as first-line pharmacological treatment for common mental disorders in children and adolescents. Despite their efficacy, they have a high risk for adverse events and exhibit a substantial placebo response. This editorial provides some background on the current evidence on the topic and suggests to carefully weigh the benefits of SSRIs and SNRIs against their potential harms. Therefore, the authors present two different set of conclusions – one for clinical practice, and one for future research designs.