The US FDA has recently granted marketing approval for the use of the new antidepressant citalopram. This drug is a new addition to the selective serotonin reuptake inhibitors (SSRI's), which may now be considered the preferred agents for the treatment of this condition. Citalopram is available in two strengths, 20 mg and 40 mg tablets.
Although the drug is new in the United States, it has been used for many years in Europe. Marketed since 1989 in Europe, citalopram is the market leader among SSRI's in several countries and is used by approximately 8 million people worldwide.
How it Works
Citalopram selectively inhibits uptake of serotonin. As with other SSRI's there is a 2 to
3 week delay in the onset of the drug's activity. Citalopram is metabolized primarily to
demethylcitalopram and didemethylcitalopram. These metabolites also inhibit serotonin
reuptake. However, when compared to the effect of the parent drug, their effect is small,
suggesting that they do not contribute significantly to the antidepressant effect of
citalopram.
Clinical Tips
Citalopram has good oral bioavailability. Peak plasma levels are reached within 2 to 4
hours of administration. Citalopram has a half-life of 30 hours and is eliminated
primarily following metabolism by hepatic CYP isoenzymes. Only a small proportion of the
drug is eliminated renally. Some pharmacokinetic results suggest that aging may affect the
drug's AUC and half-life, increasing these parameters by 30% and 50%, respectively.
Citalopram is metabolized by the hepatic cytochrome P450 system and, therefore, should be
used with caution when used with other drugs that affect this system such as ketoconazole,
macrolides, or other inhibitors of the CYP450 system. Some data show that among the
SSRI's, citalopram may be the least likely to cause potential drug interactions. The
efficacy of Celexa has been established in numerous clinical studies, including two
placebo-controlled trials of 4 to 6 weeks' duration. In these studies, no clear effect was
observed for doses of 10 or 20 mg/day, and doses of 60 mg/day were no more effective than
40 mg/day. However, in three other placebo-controlled studies, the drug was no more
effective than placebo; this may have been due to the small study sizes, a high
spontaneous response rate, or in one study, the use of too low a dose.
One of the largest studies to date compared citalopram with the tricyclic antidepressant (TCA) imipramine. From the study, it was concluded that both drugs had similar efficacy. Both drugs reduced scores reflecting the degree of depression similarly after 6 weeks and 22 weeks. The number of patients who responded to both drugs was also similar. Citalopram and maprotiline, a tetracyclic antidepressant, also showed similar efficacy.
However, when compared to the tricyclic agent clomipramine, citalopram was not as effective. By the end of the study period 60% of the patients receiving clomipramine had complete response while only 30% of the patients taking citalopram had complete remission.
A study performed by Bougerol et. al. compared the use of citalopram and fluoxetine in a psychiatric-based setting and in a general practice. The antidepressant efficacy of both drugs was similar when comparing the end results. The two drugs were also similar in tolerability. However, in the general practice setting, citalopram showed a greater incidence of complete recovery after 2 weeks.
The most common adverse effects of citalopram are nausea, dry mouth, increased sweating, somnolence, and insomnia. Six percent of men experienced difficulty with ejaculation, and 3% reported impotence. No serious cardiovascular side effects have been reported with use of the drug during clinical trials. Some patients may experience a slight weight loss during therapy. The incidence of some adverse events increases as the dose of drug increases.
What the Patient Should Know
Concomitant use of citalopram and monoamine oxidase inhibitors (MAOI's) is
contraindicated. MAOI's should be discontinued for at least 2 weeks before using
citalopram and vice-versa.
Patients should be advised to operate hazardous machinery and automobiles with caution. Use of alcohol concomitantly with citalopram is not recommended. Patients should contact their physician before taking any over-the-counter or prescription drugs with Celexa. Patients should also notify their physician if they become pregnant, plan to become pregnant or plan to breast feed. Patients should understand that they may notice a improvement with 1 to 4 weeks of therapy and that they should continue to use citalopram as prescribed.
For further information to ask own physician.
