Open Access

Background Signs of an inflammatory process have been described in major depression. Methods In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls. Results KYN levels were significantly lower in patients (p = 0.008), and the QUIN/KYN ratios were significantly higher (p = 0.028). At baseline, the higher KYN/TRP ratio was predictive for remission during celecoxib add-on treatment (p = 0.04) as well as for remission in the overall patient group (p = 0.01). In the placebo group, remitters showed a higher KYNA/QUIN ratio (p = 0.032). In the overall group, remitters showed lower KYNA/KYN (p = 0.035) and QUIN/KYN (p = 0.011) ratios. The lower the formation of downstream metabolites, especially QUIN, the better the treatment outcome. Conclusion The high KYN/TRP ratio predicted remission after treatment with celecoxib in this small sample of depressed patients. Eventually, the KYN/TRP ratio might be a marker for those patients, which benefit from an additional anti-inflammatory treatment.

Background: Controversy surrounds the questions whether co-occurring depression has negative effects on cognitivebehavioral therapy (CBT) outcomes in patients with panic disorder (PD) and agoraphobia (AG) and whether treatment for PD and AG (PD/AG) also reduces depressive symptomatology. Methods: Post-hoc analyses of randomized clinical trial data of 369 outpatients with primary PD/AG (DSM-IV-TR criteria) treated with a 12-session manualized CBT (n = 301) and a waitlist control group (n = 68). Patients with comorbid depression (DSM-IV-TR major depression, dysthymia, or both: 43.2% CBT, 42.7% controls) were compared to patients without depression regarding anxiety and depression outcomes (Clinical Global Impression Scale [CGI], Hamilton Anxiety Rating Scale [HAM-A], number of panic attacks, Mobility Inventory [MI], Panic and Agoraphobia Scale, Beck Depression Inventory) at post-treatment and follow-up (categorical). Further, the role of severity of depressive symptoms on anxiety/depression outcome measures was examined (dimensional). Results: Comorbid depression did not have a significant overall effect on anxiety outcomes at post-treatment and follow-up, except for slightly diminished post-treatment effect sizes for clinician-rated CGI (p = 0.03) and HAM-A (p = 0.008) when adjusting for baseline anxiety severity. In the dimensional model, higher baseline depression scores were associated with lower effect sizes at post-treatment (except for MI), but not at follow-up (except for HAM-A). Depressive symptoms improved irrespective of the presence of depression. Conclusions: Exposure-based CBT for primary PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbid depression or depressive symptomatology.

Abstract Background The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. Methods This multicenter randomized controlled trial compared two variants of prediction error‐based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx‐I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx‐S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6‐months follow‐up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. Results Both treatments resulted in substantial improvements at post (PeEx‐I: dwithin = 1.50, PeEx‐S: dwithin = 1.78) and follow‐up (PeEx‐I: dwithin = 2.34; PeEx‐S: dwithin = 2.03). Both groups showed formally equivalent symptom reduction at post and follow‐up. However, time until response during treatment was 32% shorter in PeEx‐I (median = 68 days) than PeEx‐S (108 days; TRPeEx‐I = 0.68). Interestingly, drop‐out rates were lower during intensified exposure. PeEx‐I was also superior in reducing disability days and improving quality of life at follow‐up without increasing relapse. Conclusions Both treatment variants focusing on the transdiagnostic exposure‐based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop‐out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.