63 Basic work on the psychobiology of OCD has suggested that neurotransmitters other than serotonin may be important in its pathogenesis. Indeed, the best studied SSRI-augmenting agents in OCD are low-dose atypical antipsychotics. Early work suggested that these were particularly useful in patients with comorbid tics,64 but subsequent work has indicated that they may be useful in both patients with and without tic disorders.65,66 More recently, evidence for the role of the glutamatergic system in mediating OCD has emerged, and

there has been interest in using Inhibitors,research,lifescience,medical glutamate-modulating drugs in the augmentation of treatment-resistant OCD. The anticonvulsant agent topiramate, which inhibits glutamatergic neurotransmission, may be useful in treatment-refractory OCD.67 Riluzole, which inhibits the release of glutamic acid, thus also blocking Inhibitors,research,lifescience,medical glutamatergic neurotransmission, has been found effective in proof of principle trials. 68,69 Memantine, another glutamatergic agent, may also be useful in treatment-refractory OCD.70 There has also been interest in using the NMDA partial agonist, cycloserine, in combination with CBT in OCD.71 Several other somatic treatment options in OCD are also being explored. First, a range of other mechanisms have been targeted by SSRI-augmentation strategies, including

use of Inhibitors,research,lifescience,medical the 5-HT3 receptor antagonist, STA-9090 order ondansetron.72 Second, given the abundance of literature on autoimmunity in OCD, one strand of work has focused on the use of immunoglobulins and plasmapheresis in patients with pediatric autoimmune neuropsychiatrie disorders associated with streptococcal

infection (PANDAS).73-75 Third, given the work on the neural circuitry of OCD, neurosurgery to remove specific lesions76 or deep brain Inhibitors,research,lifescience,medical stimulation after implantation of electrodes has been investigated.77,78 Such approaches provide promise for the future Inhibitors,research,lifescience,medical management of refractory OCD. Panic disorder Research on the pharmacotherapy of panic disorder (PD) was given significant impetus by the early serendipitous finding that tricyclic antidepressants are effective, and the hypothesis that different pharmacological agents are effective many for different anxiety disorders.79 Subsequent research done in order to register alprazolam and other benzodiazepines for the treatment of panic disorder did not provide a great deal of support for this hypothesis, but was important in contributing to the development of clinical trial methods in this condition. Subsequent rigorous randomized controlled trials of the SSRIs in PD were again an important advance insofar as they provided an effective and relatively well-tolerated treatment option.80-82 As in the case of GAD and OCD, however, much further work is required to optimize the treatment of refractory cases. Fortunately, ongoing studies of the psychobiology of PD have provided several leads which may be helpful in developing more targeted therapies in the future.