Paroxetine

Definition

Paroxetine is an antidepressant of the type known as selective serotonin reuptake inhibitors (SSRI). It is sold in the United States under the brand name Paxil.

Purpose

Paroxetine is approved by the United States Food and Drug Administration (FDA) for treatment of depression and for the following anxiety disorders: obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, post-traumatic stress disorder, and social anxiety disorder.

Description

Paroxetine increases the amount of serotonin (also called 5-HT) available in the brain. Serotonin is a neurotransmitter, or chemical in the brain that carries nerve impulses from a sending neuron (nerve cell) to a receiving neuron. The sending neuron releases serotonin into a little gap between neurons, called the synapse. The receiving neuron picks up the serotonin from the synapse, allowing the nerve impulse to continue on its way.

Researchers think that depression and certain other disorders may be caused, in part, because there is not enough available serotonin in the brain. Normally, once a nerve impulse has crossed the synapse, serotonin is reabsorbed by the sending neuron that released it. Once reabsorbed, this serotonin is no longer available and cannot interact with a receiving neuron. Paroxetine blocks the reabsorption, or re-uptake, of serotonin, leaving it available to stimulate receiving neurons. Therefore, paroxetine facilitates the transmission of nerve impulses by increasing available serotonin in the brain and thus increasing its effectiveness.

Paroxetine is an antidepressant that is virtually completely absorbed via oral administration. Food does not reduce its absorption.

The benefits of paroxetine develop slowly over a period of up to four weeks. Patients should be aware of this and continue to take the drug as directed, even if they feel no immediate improvement.

Recommended dosage

The recommended dosage of paroxetine is 20–50 mg per day. The drug should be taken only once per day. An appropriate initial dosage is 20 mg. Dosage changes should not be made more frequently than once per week.

The recommended dosage for older persons or individuals with liver or kidney disease is 10 mg per day. The total dosage for such persons should not exceed 40 mg per day.

Precautions

Paroxetine should never be taken with monoamine oxidase inhibitors (MAOIs)(see interactions below).

Paroxetine may lower the threshold for a manic episode among people with bipolar (manic-depressive) disorders. For this reason, the drug should be used only with caution and under close supervision in these patients. It may also increase the change of having a seizure in people with a history of seizure disorders.

The possibility of suicide is a component of depression. The minimum number of doses of paroxetine should be dispensed at any one time to minimize the potential for use as a suicide agent.

Hyponatremia (abnormally low concentration of sodium in the blood) has been associated with the use of paroxetine. In all cases, this condition resolved when the drug was discontinued. Most of these instances occurred among older individuals who were also taking diuretics (water pills).

Side effects

Common side effects associated with paroxetine include headache, weakness, chills, malaise, nausea, and sleepiness. Other complaints included dry mouth, dizziness, tremors, constipation, diarrhea, and problems with ejaculation. Adverse reactions to paroxetine have been reported for all organ systems of the body, but all of these side effects are uncommon.

In general, the incidence of side effects increases as the dosage of paroxetine increases.

Interactions

There is the potential for a fatal interaction with another class of antidepressant drugs called monoamine-oxidase (MAO) inhibitors. There have been reports of dangerously elevated body temperature, muscle rigidity, and rapid changes in vital signs such as heart rate and blood pressure. Mental changes ranging from extreme agitation to delirium and coma have also been reported. Because of this, paroxetine should never be taken in combination with MAO inhibitors. Patient taking any MAO inhibitors, for example Nardil (phenelzine sulfate) or Parmate (tranylcypromine sulfate), should stop the MAO inhibitor then wait at least 14 days before starting paroxetine or any other antidepressant. The same holds true when discontinuing paroxetine and starting an MAO inhibitor.

The combination of paroxetine with the antipsychotic drug thioridazine has the potential to cause fatal cardiac arrhythmias (irregular heartbeat). The use of paroxetine in combination with tryptophan may result in unwanted reactions including agitation, restlessness, and gastrointestinal distress. Paroxetine may also increase the change of having a seizure in people with a history of seizure disorders. People taking anticonvulsants to control seizures should be closely monitored and a physician may need to adjust the dosage of their seizure medication.

People with bipolar disorder are commonly treated with lithium. No interactions between paroxetine and lithium have been reported, nor have are there any reported interactions with the common anti-anxiety drug diazepam (Valium).

Phenobarbital at dosages greater than 100 mg per day decreases the bioavailability of paroxetine in some persons. Paroxetine has been reported to increase the systemic bioavailability of procyclidine.

BOOKS

Adams, Michael and Norman Holland. Core Concepts in Pharmacology. Philadelphia: Lippincott-Raven, 1998.

Foreman, John C. and Torben Johansen. Textbook of Receptor Pharmacology. 2nd ed. Boca Raton, FL: CRC Press,2002.

Page, Clive P., and Michael Murphy. Integrated Pharmacology. St. Louis: Mosby-Year Book, 2002.

Von Boxtel, Chris J., Budiono Santoso, and I. Ralph Edwards. Drug Benefits and Risks: International Textbook of Clinical Pharmacology. New York: John Wiley and Sons, 2001.

PERIODICALS

Cherek D. R., S. D. Lane, C. J. Pietras, and J. L. Steinberg. "Effects of chronic paroxetine administration on measures of aggressive and impulsive responses of adult males with a history of conduct disorder." Psychopharmacology (Berlin) 159, no. 3 (2002): 266-274.

Mulsant B. H. and others. "A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients." American Journal of Geriatric Psychiatry 9, no. 4 (2001): 406-414.

Pisani F., G. Oteri, C. Costa, G. Di Raimondo, and R. Di Perri. "Effects of psychotropic drugs on seizure threshold." Drug Safety 25, no. 2 (2002): 91-110.

ORGANIZATIONS

American Academy of Clinical Toxicology. 777 East Park Drive, PO Box 8820, Harrisburg, PA 17105-8820. Telephone: (717) 558-7750. Fax: (717) 558-7845. Web site: <http://www.clintox.org/index.html>.

American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. Telephone:(913) 906-6000. Web site: <http://www.aafp.org/>.

American Medical Association. 515 N. State Street, Chicago, IL 60610. Telephone: (312) 464-5000. Web site: <http://www.ama-assn.org/>.

American Psychiatric Association. 1400 K Street NW, Washington, DC 20005. Telephone: (888) 357-7924. Fax:(202) 682-6850. Web site: <http://www.psych.org/>.

American Society for Clinical Pharmacology and Therapeutics. 528 North Washington Street, Alexandria, VA 22314. Telephone: (703) 836-6981 Fax: (703) 836-5223.

American Society for Pharmacology and Experimental Therapeutics. 9650 Rockville Pike, Bethesda, MD 20814-3995. Telephone: (301) 530-7060. Fax: (301) 530-7061. Web site: <http://www.aspet.org/>.

L. Fleming Fallon, Jr., M.D., Dr.P.H.