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
The antidepressant effects of clomipramine are thought to be due to reuptake inhibition of serotonin and norepinephrine, while serotonin reuptake inhibition only is thought to be responsible for the effectiveness of clomipramine in the treatment of OCD. Conversely, antagonism of the H, α-adrenergic, and muscarinic acetylcholine receptors is thought to contribute to its side effects. Blockade of the H receptor is specifically responsible for the antihistamine effects of clomipramine and side effects like sedation and somnolence (sleepiness). Antagonism of the α-adrenergic receptor is thought to cause orthostatic hypotension and dizziness. Inhibition of muscarinic acetylcholine receptors is responsible for the anticholinergic side effects of clomipramine like dry mouth, constipation, urinary retention, blurred vision, and cognitive/memory impairment. In overdose, sodium channel blockade in the brain is believed to cause the coma and seizures associated with TCAs while blockade of sodium channels in the heart is considered to cause cardiac arrhythmias, cardiac arrest, and death. On the other hand, sodium channel blockade is also thought to contribute to the analgesic effects of TCAs, for instance in the treatment of neuropathic pain.