Phenobarbital: Long-Term Side Effects

Phenobarbital, known by the brand names Nembutal, Luminal, and others, is a barbiturate drug.
 
Barbiturates are central nervous system depressants that were originally designed to treat anxiety, anxiety disorders, and seizures. Their list of potential medicinal uses also includes assisting with the treatment of insomnia, acting as a preanesthetic drug to relax individuals before anesthesia is administered, and assisting in withdrawal from alcohol and even other benzodiazepines. They are also used as muscle relaxants and as lethal injection drugs in prisons.

The United States Drug Enforcement Administration classifies phenobarbital as a Schedule IV controlled substance. Drugs in this class have a moderate potential for abuse and can result in the development of physical dependence if taken for lengthy periods of time.
pill drugExcept for the control of seizures, phenobarbital is not typically prescribed for long periods of time. Its use as an anti-anxiety medication has declined significantly since the development of benzodiazepines. Even when phenobarbital is used as an anti-anxiety medication, it is considered to be a short-term solution that can help an individual while behavioral interventions are delivered.

Using phenobarbital as a withdrawal management medication or sleep aid would also be considered a short-term process due to individuals developing tolerance to phenobarbital rapidly; its initial medicinal effects also wear off rapidly.

According to the Substance Abuse and Mental Health Services Administration (SAMHSA), barbiturates like phenobarbital are not as commonly used as they once were. They are more likely to be prescribed to elderly individuals as sleep aids or to treat anxiety. Phenobarbital is still useful in the control of seizures, and individuals who use phenobarbital for this purpose often use it for lengthy periods of time. Much of the data describing the long-term effects of phenobarbital use come from animal research studies and observational studies in individuals with epilepsy or other seizure disorders who took the drug for lengthy periods.

Effects of Phenobarbital

Research regarding the effects of phenobarbital is extensive. The majority of the information in this article comes from the books Handbook of Epilepsy Treatment, The Oxford Textbook of Epilepsy and Epileptic Seizures, and Contemporary Neurology Series: Seizures and Epilepsy. Some of the known long-term effects of using phenobarbital are outlined below:

  • The development of physical dependence and/or a substance use disorder: It is well established that individuals who use phenobarbital for a significant length of time may develop physical dependence on the drug. In addition, chronic use or abuse of phenobarbital can result in the development of a substance use disorder that would be classified as a sedative, hypnotic, or anxiolytic use disorder.
  • Birth defects: The use of phenobarbital by pregnant women is associated with an increased risk for birth defects in their children.
  • Cognitive deficits in children: Phenobarbital use in children is associated with a number of different cognitive effects, most often including issues with learning and memory, attention and concentration, cognitive flexibility, problem-solving, and judgment.
  • Cognitive deficits in adults: Long-term use of phenobarbital is associated with a number of cognitive deficits in adults that can include similar issues with learning and memory, attention and concentration, complex attention, expressive and receptive speech, and problem-solving. Individuals who use phenobarbital for lengthy periods are also often noted to have slower rates of thinking/cognition compared to individuals who do not use the drug.
  • Cancer: Both animal studies and observational studies in humans indicate that long-term use of phenobarbital is associated with an increased risk of liver cancer. Phenobarbital use in pregnant woman is also associated with increased risk for brain tumors in their children. Increased risk for other forms of cancers is reported, such as renal cancer.
  • Acquired hypersensitivity: Long-term use of phenobarbital is associated with an acquired allergic reaction to the drug in some individuals. Often, these individuals have pre-existing conditions, such as asthma or other allergies.
  • Musculoskeletal effects: Chronic phenobarbital use is associated with an increased potential to develop osteoporosis, decreased bone mineral density, increased bone fractures, and palmar fibromatosis, which is a thickening and tightening of the tissue under the skin in the hands.
  • Skin: Several different studies have indicated that individuals who use phenobarbital may have an increased risk for many different types of dermatological issues.
  • Metabolic issues: Numerous reports have documented many different types of metabolic issues in individuals who chronically used phenobarbital. Many of these issues include difficulties with absorbing certain nutrients, like calcium, B vitamins, vitamin D, vitamin K, and hypophosphatemia (an electrolyte imbalance where there are low levels of phosphate in the blood).
  • Endocrine issues: Some reports have suggested that long-term use of phenobarbital may be associated with reduced serum concentrations of thyroid hormones.
  • Cardiovascular effects: Long-term use of phenobarbital is associated with a reduction in blood pressure (hypotension) and reduced heart rate in some individuals. This can produce a number of chronic issues associated with decreased oxygen flow to important organs, including the brain. Chronic use of phenobarbital is also associated with the development of several types of anemia.
  • Respiratory effects: Using phenobarbital for lengthy periods of time is also associated with respiratory suppression (decreased breathing rates). Like the potential cardiovascular effects mentioned above, this can result in a number of long-term issues in numerous organ systems due to chronic hypoxia (decreased oxygen supply). A number of the cognitive issues associated with long-term use of phenobarbital are at least in part affected by the cardiovascular and respiratory effects of the drug.
  • Psychiatric effects: Numerous reports have documented multiple psychological disturbances in individuals who have used phenobarbital for lengthy periods of time. The association between mental health symptoms or disorders and use of phenobarbital may not always represent a cause-and-effect relationship because many individuals who have had chronic histories of epilepsy may have alterations to the brain that make them more vulnerable to the development of these disorders. Some of the disorders mentioned in the literature include agitation, confusion, depression, mood swings, and paradoxical reactions (e.g., becoming excited when one is really sad), attenuated emotions (displaying little emotion), thought disorders, nightmares, panic attacks, phobias, aggressive behaviors, and hallucinations and delusions.
  • Early death: Based on the above list of potential long-term effects associated with chronic phenobarbital use, it should be no surprise that phenobarbital use is also associated with increased mortality rates in individuals who use the drug either medicinally for extended periods of time to manage seizures or who may abuse the drug chronically.
Despite this rather long list of documented long-term effects associated with chronic use of phenobarbital either as a medicinal drug or a drug of abuse, the sources also suggest that there may be long-term side effects associated with phenobarbital use that have not been reported. In some cases, such as for the control of seizures, there is often a cost-benefit analysis to using phenobarbital that must be considered. Individuals who suffer from severe seizures and find that phenobarbital is most effective in controlling them will improve the quality of their life by using the drug, even though there may be some long-term untoward side effects associated with its use.
Individuals who choose to abuse barbiturates like phenobarbital are a different story. Any cost-benefit analysis associated with drug abuse or the development of a substance use disorder will inevitably lead to the conclusion that the costs or risks involved with abusing drugs far outweigh any benefits one may think they are getting. Any person who thinks they, or someone they know, are abusing barbiturates like phenobarbital should consult with a licensed mental health professional to learn about treatment options and begin a program of recovery.

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