This supplement to CNS Spectrums focuses on exciting emerging data on therapeutic approaches that can help the clinician with difficult-to-treat patients. Over the last decade, there have been tremendous advances in our conceptualization of difficult-to-treat patients, including diagnostic, psychotherapeutic, pharmacotherapeutic, and somatic approaches. A series of articles addressing these advances in the field are presented in this supplement.

Edna B. Foa, PhD, has been a leading expert in cognitive-behavioral therapy (CBT) for anxiety disorders for many years. Foa and colleagues provide a thoughtful analysis of the particular components of CBT that may be responsible for its efficacy in anxiety disorders. This article goes beyond simple trials looking at the efficacy of CBT or combined treatment with pharmacotherapy and CBT. Foa and colleagues identify individual treatment and patient factors as well as the interaction between the two, that may influence treatment response. Treatment of posttraumatic stress disorder is used as a model for helping us understand this exciting work.

Next, Waguih William IsHak, MD, presents important data about the use of practical and pragmatic treatment paradigms in patients with mood and anxiety disorders. Dr. IsHak emphasizes the importance of standardized structured approaches to facilitate understanding of the breadth of psychopathology present in the patient. The model Dr. IsHak proposes for the evaluation and conceptualization of the patient facilitates the integration of biological factors, psychological factors, and psychosocial variables. His algorithms go beyond merely a technique for assessment and present a rational approach to therapy for patients. These algorithms are limited by existing data, but the steps elaborated within the algorithm are powerful and useful for the clinician. This article serves as a useful guide for both trainees and clinicians with many years in practice.

Effective cognitive-behavioral therapy (CBT) programs have been developed for aU of the anxiety disorders. Common elements of CBT for these disorders include exposure to feared objects, situations, activities, thoughts, memories, and sensations; cognitive restructuring of dysfunctional beliefs; and training in anxiety management skills, such as controlled breathing and relaxation. This article describes CBT procedures for anxiety disorders and summarizes the research documenting its efficacy. Next, the article discusses the factors that influence the efficacy of these treatment program. Finally, emotional-processing theory is discussed to explain the efficacy of CBT for anxiety and how this theory can assist in selecting optimal treatment brocedures.

Clinical pathways generally recommend potential steps in the diagnosis and treatment of a condition or procedure for individual patients. Their usefulness in guiding clinicians through the steps of nonresponse or partial response to interventions has been documented. They are predominantly management tools based on clinical information developed from evidence-based psychiatry, practice guidelines, or expert consensus statements. Pathways may not be appropriate for use in all circumstances, nor are they a substitute for the practitioner's experience and judgment. Their applicability must be assessed by the responsible practitioner in light of relevant circumstances presented by individual patients in order to optimize treatment.

Management strategies for treatment-resistant depression and anxiety disorders have evolved over the last decade. Our understanding of the factors that impair recovery from an episode of major depression has increased, leading to the development of more precise diagnostic methodology that highlight the presence of comorbid conditions. New medications, creative uses of existing medications, increased empirical data about augmentation strategies, and the development of innovative nonpharmacologic interventions are responsible for a marked expansion in treatment options. Traditionally, augmentations with lithium, thyroid hormones, or electroconvulsive therapy have demonstrated effectiveness in some patients with treatment-resistant mood disorders. Among the promising treatments in both depression and anxiety is augmentation using low-dose antipsychotics medications, combining antidepressants of different classes, and the addition of psychotherapy. Nonpharmacologic interventions that may have potential include transcranial magnetic stimulation, deep-brain stimulation, and vagus-nerve stimulation. This article provides a brief review of the available data summarizing existing and new treatment strategies in depression and anxiety disorders.