Recommendations for treatment of chronic major depressive disorder (cMDD) are mostly based on clinical experiences and on the literature on treatment-resistant depression (TRD) but not on a systematic review of the literature.
We conducted a systematic review of 10 randomized controlled trials (RCTs), with 17 comparisons between antidepressants (ADs), psychotherapy, or the combination of both interventions.
The best evidence is for the combination of psychotherapy and ADs, and especially for the combination of the cognitive behavourial analysis system of psychotherapy and ADs. Evidence is very weak for both ADs alone and psychotherapy alone. Assessment of TRD was mostly absent in the studies.
The best treatment for cMDD is a combination of psychotherapy and ADs. However, there is a lack of well-performed RCTs in both ADs and psychotherapy and their combination for cMDD. Therefore, the conclusions are preliminary.
[Show abstract][Hide abstract] ABSTRACT: Increasing epidemiological and experimental evidence implicates gestational infections as one important factor involved in the pathogenesis of several neuropsychiatric disorders. Corresponding preclinical model systems based upon maternal immune activation (MIA) by treatment of the pregnant female have been developed. These MIA animal model systems have been successfully used in basic and translational research approaches, contributing to the investigation of the underlying pathophysiological mechanisms at the molecular, cellular and behavioural levels. The present article focusses on the application of a specific MIA rodent paradigm, based upon treatment of the gestating dam with the viral mimic polyinosinic-poly cytidilic acid (Poly(I:C)), a synthetic analog of double-stranded RNA (dsRNA) which activates the Toll-like receptor 3 (TLR3) pathway. Important advantages and constraints of this animal model will be discussed, specifically in light of gestational infection as one vulnerability factor contributing to the complex aetiology of mood and psychotic disorders, which are likely the result of intricate multi-level gene x environment interactions. Improving our currently incomplete understanding of the molecular pathomechanistic principles underlying these disorders is a prerequisite for the development of alternative therapeutic approaches which are critically needed in light of the important drawbacks and limitations of currently available pharmacological treatment options regarding efficacy and side effects. The particular relevance of the Poly(I:C) MIA model for the discovery of novel drug targets for symptomatic and preventive therapeutic strategies in mood and psychotic disorders is highlighted in this review article.
[Show abstract][Hide abstract] ABSTRACT: This pragmatic randomized controlled trial tested the effectiveness of long-term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment-as-usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long-standing major depression who had failed at least two different treatments and were considered to have treatment-resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6-monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow-up. The primary outcome measure was the 17-item version of the Hamilton Depression Rating Scale (HDRS-17), with complete remission defined as a HDRS-17 score ≤8, and partial remission defined as a HDRS-17 score ≤12. Secondary outcome measures included self-reported depression as assessed by the Beck Depression Inventory - II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation - Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42-month follow-up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow-up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer-based and self-reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long-term outcome of treatment-resistant depression. End-of-treatment evaluations or short follow-ups may miss the emergence of delayed therapeutic benefit.
World psychiatry: official journal of the World Psychiatric Association (WPA) 09/2015; 14(3):312-21. DOI:10.1002/wps.20267 · 14.23 Impact Factor
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