The knowns and unknowns of SSRI treatment in young people with depression and anxiety: efficacy, predictors, and mechanisms of action

Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.

Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.) 2008 Massachusetts Medical Society

Evidence-based practice involves the consideration of efficacy and effectiveness, clinical expertise, and patient preference in treatment selection. However, patient preference for psychiatric treatment has been understudied. The aim of this meta-analytic review was to provide an estimate of the proportion of patients preferring psychological treatment relative to medication for psychiatric disorders. A literature search was conducted using PubMed, PsycINFO, and the Cochrane Collaboration library through August 2011 for studies written in English that assessed adult patient preferences for the treatment of psychiatric disorders. The following search terms and subject headings were used in combination: patient preference, consumer preference, therapeutics, psychotherapy, drug therapy, mental disorders, depression, anxiety, insomnia, bipolar disorder, schizophrenia, substance-related disorder, eating disorder, and personality disorder. In addition, the reference sections of identified articles were examined to locate any additional articles not captured by this search. Studies that assessed preferred type of treatment and included at least 1 psychological treatment and 1 pharmacologic treatment were included. Of the 644 articles identified, 34 met criteria for inclusion. Authors extracted relevant data including the proportion of participants reporting preference for psychological or pharmacologic treatment. The proportion of adult patients preferring psychological treatment was 0.75 (95% CI, 0.69-0.80), which was significantly higher than equivalent preference (ie, higher than 0.50; P < .001). Sensitivity analyses suggested that younger patients (P = .05) and women (P < .01) were significantly more likely to choose psychological treatment. A preference for psychological treatment was consistently evident in both treatment-seeking and unselected (ie, non-treatment-seeking) samples (P < .001 for both) but was somewhat stronger for unselected samples. Aggregation of patient preferences across diverse settings yielded a significant 3-fold preference for psychological treatment. Given evidence for enhanced outcomes among those receiving their preferred psychiatric treatment and the trends for decreasing utilization of psychotherapy, strategies to maximize the linkage of patients to preferred care are needed. © Copyright 2013 Physicians Postgraduate Press, Inc.