The modern era in the pharmacotherapy of obsessive-compulsive disorder (OCD) began in the late 1960s with the observation that clomipramine, not other tricyclic antidepressants such as imipramine (Tofranil), was effective in treating OCD. Clomipramine is the most thoroughly studied drug for OCD and was the first to receive FDA approval for this indication. Like other tricyclic antidepressants, side effects of dry mouth, constipation and urinary retention are common. Like other SRIs, nausea and tremor are also common with clomipramine. Impotence and delayed or failed orgasm occurs with clomipramine. Many patients complain of fatigue and weight gain. Safety concerns with clomipramine include adverse affects on heart conduction and seizures. The risk of seizures increases significantly at doses over 250 mg daily. Intentional overdoses with clomipramine can be lethal.
The only medications that have been consistently shown effective in treating OCD are antidepressants that interact with the brain chemical serotonin. Serotonin is one of the brain’s many chemical messengers or neurotransmitters that allow one nerve cell (called a neuron) to communicate with another neuron. Instead of being joined directly together, most neurons are separated from each other by a narrow fluid-filled gap called the synapse. In order for an electrical signal to pass from one neuron to the next, a neurotransmitter is released into the synapse where it floats freely across to the adjoining neuron. There, it comes in contact with a specialized part of the neuron called the receptor. The receptor is like a lock and the neurotransmitter the key. With the key in the lock, an electrical signal is triggered and passes along the receiving neuron to convey information elsewhere in the brain. In addition to interacting with the adjoining neuron, released serotonin is actively taken back up into the neuron from which it was released. This serotonin reuptake pump acts to recycle serotonin, assisting in reclaiming it for later release. It also may serve to reduce the amount of “noise” that would be generated if too much serotonin lingered in the synapse after each nerve firing.
Clomipramine (Anafranil) has a number of different chemical properties, including the ability to latch on to the serotonin reuptake pump and prevent the movement of serotonin into its home neuron. Medications such as clomipramine which block the serotonin pump are referred to as serotonin reuptake inhibitors or SRIs. In addition to clomipramine, several selective SRIs have been shown effective in treating OCD, including fluvoxamine (Luvox), fluoxetine (Prozac), sertraline (Zoloft) and paroxetine (Paxil). Some evidence suggests the selective SRI citalopram (Celexa) may also be effective for OCD, even though it does not have FDA approval for this indication. In a series of different studies, researchers have shown that SRIs are more effective in treating OCD than other antidepressants that do not interact with the serotonin pump. Thus, all SRIs can treat depression, but not all antidepressants can treat OCD. For example, desipramine, which is not an SRI, is an effective antidepressant but is ineffective in treating obsessive-compulsive symptoms. This specificity of response lends weight to the widely held opinion that OCD might involve some type of a biochemical imbalance.