Pharmacotherapies in the Management of Obsessive—Compulsive Disorder

Abstract

T he first reports of the potential for medications to exert an antiobsessional effect in patients without major depression were published about 35 years ago (1-4). The tricyclic antidepressant G-34586, or CMI, was used successfully in these first attempts. The serendipitous finding of its beneficial effect on obsessions in depression patients motivated its use in that disorder. Several case series in the following decade seemed to confirm the usefulness of this medication in treating OCD, then denoted obsessive-compulsive neurosis. The first controlled trials demonstrating a therapeutic action of CMI in OCD were published in 1980 (5,6). These were followed by many positive studies (see 7 for a review). Clinical Implications· OCD is a chronic disorder amenable to pharmacotherapy using a single class of medications: the potent SRIs. · With a good knowledge of the properties of these drugs, optimal response and patient safety and comfort can be achieved. · It is possible to augment the anti-OCD response with various augmentation strategies. · The response to various pharmacotherapies is generally partial, and their administration must be prolonged to avoid the resurgence of symptoms. Limitations· SRIs exert class side effects that are sometimes difficult to minimize. · Few augmentation strategies are supported by double-blind studies.Few medications are effective in treating obsessive-compulsive disorder (OCD). As monotherapy, only potent serotonin (5-HT) reuptake inhibitors (SRIs) consistently exert an intrinsic therapeutic action in OCD. Their use in OCD, however, differs from their use in depression. This paper first reviews the evidence supporting the key role of 5-HT as a pivotal neurotransmitter in the anti-OCD response. Then, we describe the practicalities of SRI use, followed by the steps that can be taken when these medications do not produce an adequate clinical response. We provide specifics for the treatment of children and adolescents with OCD. We include a brief description of the brain circuitry involved in OCD and the mechanisms of action of the pharmacologic agents reported to be effective in this disorder, as well as those that are useful in depression but not in OCD. We present this information to promote better understanding of the research endeavours needed to develop new pharmacotherapeutic approaches. Information on funding and support and author affiliations appears at the end of the article.

Obsessive Compulsive Disorder

“…In contrast, the prefrontal cortex (PFC), thought to be the main target in the treatment of OCD, does not undergo desensitization for up to 8 weeks ( 276 ). In addition, animal studies have indicated that higher concentrations of SSRIs are needed to achieve desensitization in the PFC than in the hypothalamus and hippocampus ( 277 ). These observations are congruent with clinical experience that longer medication trials and higher doses of medications are needed to achieve therapeutic benefi t in the treatment of OCD than those needed in the treatment of depression.…”

Invasive Circuitry-Based Neurotherapeutics: Stereotactic Ablation and Deep Brain Stimulation for OCD

“…Nevertheless, anatomical hypotheses derived from neuroimaging (Dougherty et al, 2004), clinical pharmacology of OCD, and basic neuropharmacology of the implicated circuitry (Blier et al, 2006;Greenberg et al, 1997;Westenberg et al, 2007) provide some key starting points. As already discussed, human neuroimaging data suggest that abnormalities in OFC/ACC-basal ganglia-thalamic circuitry are central to the pathophysiology of OCD and responses to treatment.…”

D-cycloserine does not enhance exposure–response prevention therapy in obsessive–compulsive disorder

“…Yet, E/RP does not help all individuals, and those who benefit, often remain symptomatic upon treatment completion. Alternative interventions, such as serotonergic medications, have modest efficacy and are often accompanied by undesirable side effects (Blier et al, 2006;Denys, 2006). Given this, further investigation into approaches that may enhance the therapeutic efficacy of E/RP is warranted.…”