Some Drugs for Psychotic Disorders

The first generation antipsychotics, called "conventional antipsychotics," are effective in controlling hallucinations and delusions, but they also have a number of troubling side effects, including weight gain, sedation, tremors, muscular rigidity, and sometimes repetitive uncontrolled movements known as tardive dyskinesia. They include Haldol (haloperidol), Thorazine (chlorpromazine), Mellaril (thioridazine), Prolixin (fluphenazine), Navane (thiothixene), and Trilafon (perphenazine).

While certain symptoms of schizophrenia and acute psychoses may improve rapidly after treatment with antipsychotic drugs, chronic schizophrenia usually improves slowly. "This condition may continue to improve for months," says Mark Abramowicz, MD, editor of The Medical Letter on Drugs and Therapeutics, a non-profit newsletter that critically appraises drugs. "Patients taking antipsychotic drugs should be monitored regularly."

Clozaril is effective in schizophrenia patients who do not respond to other medications, and it appears to be more effective in decreasing suicide risk. However it can lead to severe side effects, including seizures and agranulocytosis, a rare but potentially fatal condition in which the white blood cell count drops and the patient's risk of infection increases. For these reasons, it is reserved for patients who have not responded to other medications.

CATIE STUDY EMPHASIZES VARIABLE RESPONSES

In March, the American Journal of Psychiatry published two studies with the most recent data from the "Clinical Antipsychotic Trials of Intervention Effectiveness" (CATIE) study, a $42.6 million, multi-site study funded by the National Institute of Mental Health (NIMH).

The current research looks at people who could not tolerate or were not helped by perphenazine, an older, first-generation medication. They were randomized to one of three newer antipsychotic medications: Seroquel, Risperdal, or Zyprexa. Patient responses varied considerably, in terms of both effectiveness and side effects.

"These results reinforce the fact that finding the most effective medication for each patient sometimes means trying multiple medications," says T. Scott Stroup, MD, MPH, the lead author. "They remind us of the considerable variability in clinical circumstances and of our need to be responsive to an individual's needs and preferences."

The CATIE study found that patients with schizophrenia who take antipsychotic medications experience modest improvements in social, interpersonal and community living skills, regardless of which medication they are taking. "Medication alone is not enough to overcome the illness," says Ken Duckworth, MD, medical director of the National Alliance on Mental Illness (NAMI). "No matter what medication is prescribed, intensive rehabilitation and support services are essential to improve the functioning of people who live with schizophrenia."

LILLY FACES ZYPREXA LAWSUITS

The FDA requires all manufacturers of second-generation antipsychotics to include product label warnings about hyperglycemia and diabetes. "Some second-generation drugs, particularly Clozaril and Zyprexa, but not Abilify or Geodon, probably cause more weight gain than first-generation medications," says Dr. Abramowicz.

Eli Lilly, the manufacturer of Zyprexa, is facing lawsuits from consumers alleging that the company knew, but did not disclose, links between the medication, extreme weight gain, and diabetes. In 2004, a panel of the American Diabetes Assn. found that Zyprexa led to diabetes more than other widely used second-generation antipsychotics.