Delayed- Maturation Theory of Obsessive Compulsive Disorder
Drug treatment of OCD may be assumed to affect a proposed functional imbalance between the frontal lobes and other parts of the brain. Serotonin reuptake inhibitors, SRI, especially potent ones given at high doses over long periods of time, are often effective in the treatment of obsessive-compulsive disorder. However, a large percentage of patients do not respond to treatment with the SRI, and those who do respond often do not fully remit, which should be the standard goal of treatment in OCD. If a patient has been treated for several months and has not yet responded to treatment with several types of SRI medication, the physician should perform a careful assessment of resistant and/or residual clinical symptoms. Any comorbid conditions to determine which next-step treatment would be the most appropriate. One strategy for patients who have not responded to treatment with a SRI is to switch them to aserotonin-norepinephrine reuptake inhibitors.
Clomipramine
Relatively high doses of SRIs are needed for effectiveness in the treatment of OCD. Studies have found that high dosages of SSRIs above the normally recommended maximums are significantly more effective in OCD treatment than lower dosages (e.g., 250 to 400 mg/day sertraline versus 200 mg/day sertraline). In addition, the combination of clomipramine and SSRIs has also been found to be significantly more effective in alleviating OCD symptoms, and clomipramine is commonly used to augment SSRIs for this reason. Studies have found that intravenous clomipramine, which is associated with very high circulating concentrations of the drug and a much higher ratio of clomipramine to its metabolite desmethylclomipramine, is more effective than oral clomipramine in the treatment of OCD. There is a case report of complete remission from OCD for approximately one month following a massive overdose of fluoxetine, an SSRI with a uniquely long duration of action. Taken together, stronger serotonin reuptake inhibition has consistently been associated with greater alleviation of OCD symptoms, and since clomipramine, at the clinical dosages in which it is employed, is effectively the strongest SRI used medically (see table above), this may underlie its unique effectiveness in the treatment of OCD.