Agitation is common in the medical and psychiatric emergency department, and appropriate management of agitation is a core competency for emergency clinicians. In this article, the authors review the use of a variety of first-generation antipsychotic drugs, second-generation antipsychotic drugs, and benzodiazepines for treatment of acute agitation, and propose specific guidelines for treatment of agitation associated with a variety of conditions, including acute intoxication, psychiatric illness, delirium, and multiple or idiopathic causes. Pharmacologic treatment of agitation should be based on an assessment of the most likely cause of the agitation. If agitation results from a delirium or other medical condition, clinicians should first attempt to treat the underlying cause instead of simply medicating with antipsychotics or benzodiazepines.

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Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatalthalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study.Methods: At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of $30% in YBOCS score) at the posttreatment assessment and after another month of follow-up.

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Concerns regarding a drought in psychopharmacology have risen from many quarters. From one perspective, the wellspring of bedrock medications for anxiety disorders, depression, and schizophrenia was serendipitously discovered over 30 year ago, the swell of pharmaceutical investment in drug discovery has receded, and the pipeline's flow of medications with unique mechanisms of action (i.e., glutamatergic agents, CRF antagonists) has slowed to a trickle. Might oxytocin (OT)-based therapeutics be an oasis? Though a large basic science literature and a slowly increasing number of studies in human diseases support this hope, the bulk of extant OT studies in humans are single-dose studies on normals, and do not directly relate to improvements in human brain-based diseases. Instead, these studies have left us with a field pregnant with therapeutic possibilities, but barren of definitive treatments. In this clinically oriented review, we discuss the extant OT literature with an eye toward helping OT deliver on its promise as a therapeutic agent. To this end, we identify 10 key questions that we believe future OT research should address. From this overview, several conclusions are clear: (1) the OT system represents an extremely promising target for novel CNS drug development; (2) there is a pressing need for rigorous, randomized controlled clinical trials targeting actual patients; and (3) in order to inform the design and execution of these vital trials, we need further translational studies addressing the questions posed in this review. Looking forward, we extend a cautious hope that the next decade of OT research will birth OT-targeted treatments that can truly deliver on this system's therapeutic potential.

BackgroundThere is a need for a rapid-acting, non-injection, acute treatment for agitation.AimsTo evaluate inhaled loxapine for acute treatment of agitation in schizophrenia.MethodThis phase III, randomised, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov number NCT00628589) enrolled 344 individuals who received one, two or three doses of inhaled loxapine (5 or 10 mg) or a placebo. Lorazepam rescue was permitted after dose two. The primary efficacy end-point was change from baseline in Positive and Negative Syndrome Scale–Excited Component (PANSS–EC) 2 h after dose one. The key secondary end-point was Clinical Global Impression–Improvement scale (CGI–I) score 2 h after dose one.ResultsInhaled loxapine (5 and 10 mg) significantly reduced agitation compared with placebo as assessed by primary and key secondary end-points. Reduced PANSS–EC score was evident 10 min after dose one with both 5 and 10mg doses. Inhaled loxapine was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications.ConclusionsInhaled loxapine provided a rapid, well-tolerated acute treatment for agitation in people with schizophrenia.