Anxiety Disorders and Stress Q 1
Chuck is a 20-year-old student diagnosed with obsessive-compulsive behavior. A psychiatrist prescribes clomipramine (Anafranil) to treat his condition. Nurse Nicolette understands the rationale for this treatment is that the clomipramine:
A. Increases dopamine levels
B. Increases serotonin levels
C. Decreases norepinephrine levels
D. Decreases GABA levels
Correct Answer: B. Increases serotonin levels
According to the psychobiological theory, dysregulation of the neurotransmitter serotonin is thought to contribute to obsessive-compulsive behavior. Clomipramine (Anafranil) is used to increase serotonin levels, thereby decreasing the need for obsessive-compulsive behaviors. The only FDA-approved use for clomipramine is for the treatment of the obsessive-compulsive disorder (OCD) in ages 10 and older. Clomipramine was the first FDA-approved medication for OCD in 1989. For the treatment of OCD, a meta-analysis found clomipramine was more effective than sertraline, fluoxetine, and fluvoxamine.
Option A: Clomipramine is a tertiary amine belonging to the class of medications known as tricyclic antidepressants (TCA). It is a dibenzazepine TCA. Clomipramine is a serotonin reuptake inhibitor (S-RI) with a stronger affinity for the serotonin transporter (SERT), compared to other TCAs and S-RIs. The resulting action of clomipramine increases serotonergic and noradrenergic transmission.
Option C: Metabolism of clomipramine is primarily through the liver via oxidation by CYP450 2D6. The half-life of clomipramine is 17 to 28 hours. Clomipramine is then metabolized to the steady-state active metabolite desmethyl clomipramine by CYP450 1A2. Desmethyl clomipramine has more noradrenergic activity than serotonergic.
Option D: Experts often use fluvoxamine, a CYP450 1A2 inhibitor, with clomipramine in treatment-resistant OCD. By adding the CYP450 1A2 inhibitor, the conversion from clomipramine to desmethyl clomipramine is blocked, resulting in increased serotonergic activity. The onset of action of clomipramine is usually between 6 to 12 weeks for OCD; it may treat anxiety or insomnia immediately. If the patient achieves OCD remission with clomipramine, treatment should continue indefinitely.