For a time this year, a psychiatric hospital run by the state of Maryland didn't have enough injectable drugs for schizophrenia patients who refused to take pills.

Doses of the most effective drug to boost blood pressure in patients at risk of dying from infection-related shock were low at Johns Hopkins Hospital. And some local pharmacists were having trouble filling prescriptions for attention deficit hyperactivity disorder.

The drugs are among hundreds that have been in short supply at the nation's hospitals, and more recently, community pharmacies. Pharmacists, doctors and advocacy groups say countless patients are getting less effective or more costly substitutes as a result. Occasionally, they may be receiving inappropriate drugs or doses — or no treatment at all.

"Every month we review what's not available to us," said Dr. Pamela Lipsett, a professor of surgery at Hopkins. "We get one [drug] back and lose another. And some diseases have only one drug. It's very frightening."

The U.S. Food and Drug Administration said shortages of prescription drugs have tripled during the last six years to a record high. There were 61 drug product shortages in 2005 and 178 in 2010. An association tracking shortages says the numbers are even higher, and show no sign of abating.

Federal officials say they are scrambling to alleviate shortfalls by working with manufacturers who cite no single reason for delays. They have asked for advance warning of manufacturing problems, specifically for "medically necessary" drugs, and have sought other sources of supply, sometimes even approving overseas purchases. Several lawmakers, meanwhile, have backed a bill to mandate an early warning system.

Many drugs in short supply are given through injections or intravenously at hospitals, according to the FDA. They include cancer drugs, anesthetics for surgery patients, emergency "crash cart" drugs and electrolytes for patients fed intravenously. But local drug store chains, including CVS, are reporting that shortages have recently become more pronounced for them too.

Officials at the Pharmaceutical Research and Manufacturers of America, or PhRMA, say they are already working with the government, suppliers and providers on the issue.

The industry blames the shortages on "myriad factors," including natural disasters, raw material shortages, changes in hospital and pharmacy contracts, changes to FDA protocols and discontinued medicines. The FDA and provider trade groups also say industry consolidation is a factor, as are makers who discontinue less profitable generic drugs or whose plants fail safety inspections.

Maintaining sterility during the manufacturing of injectable drugs can be particularly difficult, industry officials said.

"Regardless of the cause, in order to provide patients with uninterrupted access to medicines it is important for all of us … to work collaboratively to minimize unexpected disruptions in the supply of vital medicines," said PhRMA Deputy Vice President Karl Uhlendorf in a statement.

The drug shortages mean U.S. hospitals spend at least $200 million, or 11 percent, more a year on substitutes, according to a study of 228 hospitals, retail pharmacies and other care facilities by the Premier healthcare alliance, an information provider and purchasing agent for hospitals. The estimate doesn't include added labor for managing shortages or ensuring safety.

Nearly 90 percent of the hospitals reported a drug shortage in the second half of 2010 that may have caused a patient safety issue, resulted in procedure's delay or cancellation, required expensive substitutes or resulted in a pharmacist compounding a drug.

In those six months, more than 240 drugs were in short supply or unavailable and more than 400 generic drugs were back-ordered for five or more days. Shortages appear to be increasing, Premier said.

That alarms advocates. The Leukemia and Lymphoma Society said a shortage of Cytarabine emerged last fall, and of the three primary U.S. suppliers only one has resumed shipping. The FDA is considering using an overseas provider for the drug, the gold standard for treating several types of cancer.

Society officials contacted federal legislators, and Sen. Amy Klobuchar, a Minnesota Democrat, responded with the Preserving Access to Life-Saving Medications Act. It would require drug makers to notify the FDA of any event that could cause a shortage. The FDA would also have to say how it would address shortages and more quickly re-inspect plants cited by the agency for quality problems.

Sen. Barbara Mikulski, a Maryland Democrat, signed on and said: "The early warning system … makes sure providers and patients are the first to know when a drug shortage is about to occur. That advance notice will give them the time they need to adequately prepare and respond to a drug shortage."

Notice would help, especially when so many drugs are in short supply, said Jason M. Noel, an assistant professor at the University of Maryland School of Pharmacy. He helps staff the pharmacy at Spring Grove Hospital Center, a state-run psychiatric hospital in Catonsville.

Among the most difficult shortages for Spring Grove to cope with has been an injectable anti-psychotic medication used when patients are reluctant to take pills. Noel said alternatives for those with schizophrenia and other mental disorders are not as good.