Because phenobarbital has been used for so many years, doctors have been able to study and observe its long-term side effects extensively—an advantage, in some respects, over the new medicines. During the past several decades, however, most doctors have recommended phenobarbital only after trying several other seizure medicines because its side effects often outweigh its benefits (except for certain groups such as very young children). Because of its low cost, however, it may be used more frequently in situations where cost is a critical issue, such as in developing countries.

Because phenobarbital is a barbiturate, it depresses brain function, reduces the breathing and heart rate, and decreases blood pressure and body temperature. As a result, the most common side effect of phenobarbital is sleepiness or fatigue. Be careful with driving, operating machinery, or any other dangerous activity until you know how you react to this medication.

Other side effects include:

• depression
• hyperactivity (in children)
• impaired attention (in children and adults)
• dizziness
• memory problems
• decreased sexual interest (libido)
• impotence
• slurred speech
• nausea
• anemia
• folate deficiency
• rash
• fever
• low calcium levels, bone loss

If you notice problems like any of these while you are taking phenobarbital, it's probably a good idea to discuss them with your doctor or nurse. You shouldn't stop taking phenobarbital or any other seizure medication without your doctor's advice.

Phenobarbital also has been found to reduce the effectiveness of oral contraceptives (birth control pills), so women who could become pregnant may want to consider another form of birth control.

Some studies have found greater problems with behavior and thinking in children taking phenobarbital than in children taking other seizure medicines. Some studies have found that phenobarbital worsens pre-existing hyperactivity and aggressive tendencies. Many physicians believe that phenobarbital sedates children, with a greater effect at higher doses. A number of studies have not found any sedation, however, perhaps because some children become extra alert and their scores cancel out those of sedated children. Nevertheless, the problems with phenobarbital should not be overestimated.

Taking supplements of both calcium and vitamin D may help to prevent bone loss. If you have been taking phenobarbital for more than 5 years, it might be a good idea to have a bone density test. If this easy, painless test shows significant thinning of your bones, your doctor may want you to see a bone metabolism specialist.

Long-term effects
Long-term use of phenobarbital can lead to changes in the soft tissues, including:

• joint pains mimicking rheumatism
• heel and knuckle pads
• frozen shoulder
• Dupuytren's contractures (shortening and thickening of tissue underlying the skin of the palm; corrective surgery may be needed)
• fibromas (fibrous tumors) of the bottom of the foot
• Peyronie's disease (hardening of a portion of the penis)

Be sure to read about the more serious side effects of phenobarbital. Serious problems are very rare but everyone who takes this medicine should be aware of them.

Reviewed February 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.