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
Clomipramine was developed by Geigy. It was first referenced in the literature in 1961 and was patented in 1963. The drug was first approved for medical use in Europe in the treatment of depression in 1970, and was the last of the major TCAs to be marketed. In fact, clomipramine was initially considered to be a "me-too drug" by the FDA, and in relation to this, was declined licensing for depression in the United States. As such, to this day, clomipramine remains the only TCA that is available in the United States that is not approved for the treatment of depression, in spite of the fact that it is a highly effective antidepressant. Clomipramine was eventually approved in the United States for the treatment of OCD in 1989 and became available in 1990. It was the first drug to be investigated and found effective in the treatment of OCD. The first reports of benefits in OCD were in 1967, and the first double-blind, placebo-controlled clinical trial of clomipramine for OCD was conducted in 1976, with more rigorous clinical studies that solidified its effectiveness conducted in the 1980s. It remained the "gold standard" for the treatment of OCD for many years until the introduction of the SSRIs, which have since largely superseded it due to greatly improved tolerability and safety (although notably not effectiveness). Clomipramine is the only TCA that has been shown to be effective in the treatment of OCD and that is approved by the FDA for the treatment of OCD; the other TCAs failed clinical trials for this indication, likely due to insufficient serotonergic activity.