First- and Second-Generation Antipsychotics Dichotomy

NOVEMBER 28, 2018
MD Magazine Staff

Peter Salgo, MD: There are drugs out there that I certainly didn’t learn about when I was in medical school: The long-acting injectable antipsychotics. How new are they? What do they do? And are they underprescribed?

Richard Jackson, MD: Long-acting injectables are not new at all. We had older medicines known as haloperidol [Haldol Decanoate] and Prolixin [fluphenazine]. The problem is we were reluctant to use them because of the side effects. They’re what we call pure dopamine blockers—neurotransmitters of pleasure, rewards, attention, and concentration. When you have a complete block of that and a whole host of other side effects, what happens is patients feel dull—not necessarily better. We don’t do a good job at treating the whole disease state, so we weren’t using them. Then we received the atypical or second-generation antipsychotics that had less side-effect burden, but not necessarily improved efficacy. They involved more than just dopamine and were initially available only as oral agents. We try to keep patients on those rather than having them on Haldol Decanoate and Prolixin. Now we are developing several newer agents, such as long-acting injectables. Unfortunately, we still see physicians are generally not providing them, according to patient studies.

Peter Salgo, MD: Why is that? Do doctors not know about them? Are they reluctant to use them?

Richard Jackson, MD: Doctors generally do know about them, but there are often some difficulties in providing them because of cost. What we know, however, is that the most cost-effective treatments are the most effective treatments because functioning patients equate to less cost in various areas.

Peter Salgo, MD: Are there reimbursement difficulties with these drugs?

Mauricio Tohen, MD, DPH, MBA: I’m less optimistic than my colleague. Again, the injectables have been around for a while, and there are the new drugs that I don’t see improving qualitatively. There were side effects with the older drugs, and there are side effects with the newer drugs. Unfortunately, these drugs are not curative—they only improve symptoms.

Peter Salgo, MD: In all fairness, there are a lot of diseases out there that are not curable. What’s wrong with something that treats?

Mauricio Tohen, MD, DPH, MBA: These conditions are lifelong. Patients need to take their medication for the rest of their lives. When you have a medication that would last for 1 to 3 months, the likelihood of stopping their medication is lower in terms of relapse than when you have to take medication daily. These drugs do have an advantage, and I think they’re underutilized.

Steven Leifman: Isn’t part of the problem, though, that a doctor’s office for a psychiatrist isn’t necessarily set up with a nurse to give an injection?

Richard Jackson, MD: That is not the problem because most patients are seen in larger community mental health centers, and they all have injection clinics and nurses available. It takes extra time for the doctor to say, “We have this medication you can give as a long-acting injectable. You only necessarily take it once a month or every 2 to 3 months.” And the patient says, “Oh, I don’t want a shot.” It takes more time. Doctors are used to putting patients through the system; it’s easier to do what you’ve been doing.

Peter Salgo, MD: Now there are first-generation and second-generation long-acting injectables. What’s the difference?

Mauricio Tohen, MD, DPH, MBA: We thought that they would cause fewer side effects, but the reality is that the side effects are different. I think in psychiatry, we have a long way to go to get better medications that are more effective.

Richard Jackson, MD: That’s all of medicine. We don’t cure hypertension necessarily unless, perhaps, the patient loses a lot of weight—but we treat symptoms. I disagree with my colleague here: I think they’re much better tolerated. I’ve seen patients with potentially more metabolic side effects as far as weight gain and things of that nature, but the more severe movement disorders and acute side effects are certainly diminished.

Mauricio Tohen, MD, DPH, MBA: When the new drugs came on the market, we thought they were not going to cause tardive dyskinesia; however, they do.

Richard Jackson, MD: They do, yes, but there has certainly been a decrease in the frequency and severity of symptoms. The unfortunate thing is when they don’t continue their medications.

Peter Salgo, MD: Is there a challenge in giving these long-acting injectables in correctional facilities?

Richard Jackson, MD: The biggest issue is cost because everybody looks at their own little bucket. If that costs more money to the Department of Corrections compared with a cheaper medication like haloperidol, they may think that’s a better way to go; however, we do a better job at keeping patients on their medications with long-acting injectables that have fewer side effects.

Mauricio Tohen, MD, DPH, MBA: The cost is relative because it doesn’t compare with hospitalization costs.

Transcript edited for clarity.

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