![]() ![]() ![]() 15-18 One such agent is N-acetylcysteine (NAC), which effects the cystine-glutamate antiporter and can modulate glutamatergic neurotransmission. Glutamatergic dysfunction has been gaining evidence as playing a role in OCD, and numerous agents that modulate glutamatergic signaling are under investigation. As a result, several novel options for treatment-resistant OCD are under investigation. ![]() Our understanding of the biological underpinnings of OCD continues to evolve, and molecular changes in glutamatergic signaling, immunological factors, as well as circuit-level dysfunction in the cortico-striato-thalamic-cortical (CSTC) tracts have been implicated in OCD. 11,12 Haloperidol also has limited supportive evidence in OCD, although it is associated with poor tolerability. 9,10 Olanzapine and quetiapine have also been used as augmenting agents, although evidence is limited and mixed. 8 The atypical antipsychotics risperidone and aripiprazole have shown the greatest efficacy, and low doses (up to 3 mg a day of risperidone and up to 15 mg a day of aripiprazole) are typically recommended. With a partial treatment response, augmenting with an antipsychotic is a common and evidence supported strategy, although only about a third of patients will respond. Interestingly, data suggest that a lower demethylation rate of clomipramine may be associated with greater clinical outcomes, which may warrant consideration and potential augmenting with an enzyme inhibitor if a patient fails to respond to clomipramine. 6 Clinical guidelines suggest that certain cases may warrant consideration of greater than FDA max doses of medications. A meta-analysis of dose-response also suggested that higher doses are associated with greater efficacy compared to low or moderate doses although this can also be associated with greater adverse side effects. 5 An important note about SSRI trials, is that prolonged trials (8 to 12 weeks) may be needed for optimal efficacy. Transcranial magnetic stimulation (TMS), which was recently approved by the Food and Drug Administration (FDA) as an adjunct to OCD, may be considered in Melissa’s case.Īn inadequate treatment response with monotherapy of SSRIs or CBT may warrant combining these modalities if available and tolerable. She did not tolerate clomipramine or augmenting trials of risperidone or aripiprazole and is reluctant to trial any additional medications or surgery. Melissa continues to endorse OCD symptoms, recounting how she spends several hours “checking the locks on my doors,” which frequently makes her late to work and appointments. She was also encouraged to begin CBT with ERP and has been consistent with treatment. She was switched to fluvoxamine, which was titrated to the maximum tolerated dose of 300 mg a day with partial response. When she first presented to clinic, she was prescribed sertraline, to which the OCD did not respond. “Melissa” is a 40-year-old female in an outpatient clinic with a history of OCD. Pharmacological Management of Treatment-Resistant Anorexia Nervosa Reducing Heterogeneity in Treatment-Resistant and Non–Treatment-Resistant Schizophreniaįrederick Charles Nucifora Jr, PhD, DO, MHS The Current State of the Art and the Not Too Distant Future While monotherapy with an SSRI is often recommended in patients with more severe OCD, or in history of treatment response to SSRIs or comorbid depression. Monotherapy with CBT with ERP may be recommended in patients with mild or moderate OCD. It is important to take consideration of clinical features, access, and tolerability when choosing between these options. 2 However, many patients do not achieve a full response, often defined as a more than 35% reduction on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with these treatment options. Specifically, selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), particularly exposure response therapy (ERP), have been shown to be effective in the treatment of OCD. First-line treatment options for OCD may include psychotherapeutic or pharmacological strategies. 1 OCD is highly comorbid with other psychiatric disorders, which warrants consideration particularly in difficult to treat cases. OCD is thought to have a lifetime prevalence of between 1% to 3% and is a significant cause of disability worldwide. Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts, urges, and images (obsessions) and/or repetitive behaviors or mental acts aimed at reducing anxiety or distress (compulsions). ![]()
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