____________________________________________________________________________ Anxiety Disorders
After nine days, all exposure/propranolol subjects touched the tarantula, while the other two groups barely touched its container. By 16 days, all exposure/propranolol subjects fur- ther progressed in approach, while the two other groups did not progress. Approach behavior remained stable for all three groups throughout one year. Most interestingly, significant reduction in self-reported spider fear lagged several months behind the instant behavioral transformation in the exposure/ propranolol group [309]. This study is the first to identify optimal drug and timing for durable remission of phobic anxiety and avoidance. The results challenge the fundamental tenet of CBT that changes in cognition are necessary for behavioral change. Such a novel approach is clearly needed, and similar trials enrolling subjects with agoraphobia and social phobia are expected in the future [309]. TREATMENT OF SEPARATION ANXIETY DISORDER PSYCHOTHERAPY As mentioned, the presence of pathologic separation anxiety has a pervasive negative influence on treatment response in patients with diverse anxiety and mood disorders receiving standard therapies. Patients with SEPAD show poor response to standard CBT and exposure-based therapies. This poorer treatment response may reflect the difficulties these patients experience forming and maintaining attachments, including therapeutic relationships. Growing evidence points to the incompatibility in applying the prevailing fear extinction model of anxiety to patients with SEPAD. This pathophysi- ologic model emphasizes desensitization to threatening stimuli. While theoretically and empirically supported in other anxiety disorders, this model does not consider the role of earlier childhood SEPAD in adult panic disorder and other anxiety disorders [98]. The unmet need for SEPAD-specific treatment has led to psychotherapies that focus on relationships and separation anxiety. These approaches use the therapist-patient relation- ship to recapture and better understand important elements of earlier pathologic parent-child relationships. Panic-focused psychodynamic psychotherapy is an affect-focused therapy that specifically targets separation anxiety as a core component of panic disorder. Preliminary efficacy is shown in patients with prominent separation anxiety symptoms across different anxi- ety and mood disorders. High separation anxiety levels consti- tute a central organizing element in patient self-perception as incompetent and unable to manage developmentally normative tasks without the presence of their central attachment figures. Panic-focused psychodynamic psychotherapy emphasizes free association, centrality of transference, unconscious thoughts that underlie physical sensations of panic, and difficulty with separation and autonomy. The therapist focuses on these
processes as they relate to panic symptoms. Common themes of difficulty with separations and unconscious rage inform interpretive interventions. The pre-determined 24-session, 12-week time limit enhances the opportunity to work with separation anxiety and permits the re-experiencing and better understanding [98]. PHARMACOTHERAPY With adult SEPAD becoming formalized in 2013 as a distinct diagnostic entity and anxiety disorder, little pharmacotherapy research has been performed specifically addressing this con- dition.
EMERGING THERAPIES AND NOVEL TREATMENT APPROACHES
NEUROENHANCING AGENTS TO AUGMENT EXPOSURE THERAPY Some neuroenhancers, especially D-cycloserine (DCS), are promising for treating anxiety disorders because these agents improve extinction learning efficacy, integral in exposure therapy. They facilitate learning new memories through habitu- ation and extinction, and these safe memories will over-ride the previous fear memories. Use of neuroenhancers to aug- ment CBT represents a promising translational effort—taking neuroscience discovery into clinical practice. In contrast, use of anxiolytics and CBT in anxiety disorders did not originate from a theoretical basis for the mechanism of action, and overall effectiveness leaves substantial room for improvement [164]. D-Cycloserine The most extensively studied exposure augmentation agent is DCS, an N -methyl-D-aspartate (NMDA) receptor partial agonist. Findings that extinction learning is modulated, in part, by the glutamatergic NMDA receptor complex prompted interest in the role of glutamatergic transmission in anxiety disorders. Clinical trials began to study the potential efficacy of low-dose DCS for enhancing memory consolidation and thereby improving the effectiveness of exposure therapies for anxiety disorders [165]. DCS studies of patients with specific phobia (e.g., heights, snakes), OCD, panic disorder with agoraphobia, PTSD, or SAD have been published, showing a marginal benefit when combined with exposure therapy. Following promising early findings, more recent studies have reported inconsistent results, including findings that DCS resulted in faster rates of improvement but not higher response or remission rates in SAD and even more symptoms at post- treatment in PTSD. These inconsistent trials have informed the understanding of limitations and indications of DCS augmentation of exposure therapy [310; 311; 312; 313]. Dosing and dose timing of DCS is essential. Most trials report- ing positive results used low-dose DCS (50–250 mg) one to two hours before three to five exposure sessions. Studies with negative results often used higher doses (≥250 mg), chronically
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