New frontiers in the pharmacological treatment of social anxiety disorder in adults: an up-to-date comprehensive overview.

INTRODUCTION: Social anxiety disorder (SAD) is associated with scarce functioning and poor quality of life. Although selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are currently first-line treatments, side effects are common and affect treatment compliance in approximately 50% of patients. This review aimed to summarize data on the efficacy of unlabeled molecules for SAD treatment. AREAS COVERED: Research in the main psychiatric databases was conducted (PubMed, PsychINFO, and EMBASE-Ovid) to select studies investigating the efficacy of marketed molecules not labeled for SAD treatment. EXPERT OPINION: Pregabalin at high doses (450-600 mg/day) appears to be a reliable alternative strategy for SAD treatment. Among the SSRIs not labeled for SAD, citalopram showed the most promising results. Quetiapine, levetiracetam, and other antidepressants/serotonergic agents, such as fluoxetine, duloxetine, monoamine oxidase inhibitors, tricyclics, mirtazapine, atomoxetine, nefazodone, vilazodone, and buspirone, presented negative, limited, or contrasting results. Data on anticonvulsants, olanzapine, tiagabine, and ketamine were positive, but preliminary. The risk/benefit ratio must be considered in the prescription of unlabeled compounds; treatment with pregabalin may be associated with somnolence and dizziness. Future research may contribute to the identification of targeted molecules for the treatment of this disorder.

Possible Use of Minocycline in Adjunction to Intranasal Esketamine for the Management of Difficult to Treat Depression following Extensive Pharmacogenomic Testing: Two Case Reports.

The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant, promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients-already receiving intranasal ESK but showing an instable course-who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.