HEALTH-SYSTEM EDITION
SPECIAL REPORT

STILLING THE VOICES

Pharmacists play a significant role in the treatment of schizophrenia

The movie "A Beautiful Mind" focused considerable attention on the tormenting condition of schizophrenia. The disorder is a chronic one, exhibiting symptoms that affect patients' perception of reality, leading to delusions, hallucinations, and paranoia (positive symptoms) and to anhedonia, decreased drive, and lack of motivation (negative symptoms), said Gerald Maguire, M.D., associate clinical professor, Department of Psychiatry, College of Medicine, University of California, Irvine.

Besides being associated with mood symptoms, such as depression and hostility, schizophrenia is also linked to impaired cognition, so that intelligence is one or two standard deviations below normal, noted Terry Bellnier, R.Ph., M.P.A., clinical assistant professor, State University of New York (SUNY)-University of Buffalo School of Pharmacy and Pharmaceutical Sciences. In addition, said Bellnier, 50%-60% of schizophrenic patients engage in comorbid substance abuse. And because patients lack the skills necessary to eat a nutritious diet and to exercise regularly, they are predisposed to a variety of treatable, chronic diseases, such as hypertension and diabetes.

The age of onset for schizophrenia is typically the late teens or early 20s. As a general rule, said Maguire, the later the age of onset, the better the prognosis. Schizophrenia has a strong genetic component, he said. Environmental influences likely play a role as well, but those environmental factors remain unknown.

Treatment of schizophrenia is based on a biopsychosocial model. According to Bellnier, pharmacotherapy is the backbone of treatment. "With the advent of newer antipsychotics, the side-effect profile and tolerability of this class of drugs have greatly improved," he said. "We have made significant strides in reducing the risk of tardive dyskinesia, extrapyramidal symptoms, and hyperprolactinemia. Unfortunately, sedation is still a common problem, but patients develop a tolerance to that fairly quickly."

Added Maguire, "From a biological standpoint, a lot of our focus has been on improving the positive symptoms, because those are the only areas that the older antipsychotic drugs could really improve. The challenge to physicians is to improve the negative symptoms as well, because the newer medications have that capability. Although all second- and third-generation antipsychotics improve negative symptoms, olanzapine (Zyprexa, Eli Lilly) has shown in clinical trials a greater ability to improve negative symptoms compared with risperidone (Risperdal, Janssen). Such a comprehensive approach to treatment can improve patient functioning and quality of life, building a foundation to implement the rest of the biopsychosocial model of treatment."

In addition to pharmacotherapy, the biopsychosocial model of treatment also consists of supportive psychotherapy and case management. "From a psychological standpoint, schizophrenia is so devastating because it hits people in the prime of their lives," said Maguire. "It is often misunderstood by society as well, so there is a significant stigma associated with the condition. Our job is to provide good psychological support that will help patients live with schizophrenia."

Bellnier and Maguire also addressed vocational and social skills training. "Patients with schizophrenia may not be able to function independently or hold a job, even [while taking] newer medications. The newer drugs provide a better foundation for us to help them, however. Patients who have had this condition for 20 or 30 years may now have improved drive, motivation, and cognition but lack the skills to go out and get a job," Maguire said. "We need to set up, and actually have in many areas, social and vocational rehabilitation centers to assist patients in becoming more independent and to increase their functioning."

Improved medications have made reintegration into society the ultimate goal of treatment, said Bellnier. Concurred Maguire, "We have to raise our standards of treatment because our medications are better. The end goal of treatment has become the improvement of patient functioning, not just the symptomatic improvement of hallucinations and delusions."

Both Bellnier and Maguire agree that pharmacists have an important role to play in the treatment of schizophrenia. According to Bellnier, a lack of connection exists between primary care and psychiatric care in this country. The only physician a psychiatric patient, particularly a patient with schizophrenia, might see is a psychiatrist. Patients typically do not even have a primary care physician. In such a situation, Bellnier feels, the pharmacist is the perfect conduit between psychiatric and primary care. He went on to explain. "We can now effectively treat patients' psychiatric problems, so the biggest burden is going to be their general medical care.

"A flow of necessary drug information between primary care and psychiatry would vastly improve the overall health and well-being of the severely mentally ill," he continued. "Now that most psychiatric care is provided in the community, one community provider who could direct this flow of information is the pharmacist. For example, a pharmacist could ensure that patients are not prescribed medications that would compromise their psychiatric medications, and vice versa."

Pharmacists can also play a cen-tral role in patient education. As Bellnier observed, the severely mentally ill tend to be very loyal to a healthcare provider, and the provider they see regularly, in addition to the psychiatrist, is the pharmacist.

Concurred Maguire, "Pharmacists can educate patients about the benefits of their medications and enlist their assistance in monitoring improvement. Pharmacists can also discuss other therapeutic options with patients and their physicians, if patients feel that they are not getting the maximum beneficial effect from their current regimen."

Pharmacists can also educate patients about the adverse effects associated with their medications, said Maguire. Newer antipsychotics are associated with an increase in appetite and the potential for weight gain, for example. According to Maguire, studies have found that patient education can decrease the amount of weight gain resulting from treatment with antipsychotics.

Patients should also be made aware of other potential risks associated with antipsychotic therapy, including sexual dysfunction, prolactin elevation, and, in women, an almost complete lack of menstrual flow and the induction of early menopause, Maguire pointed out. Pharmacists can help those with schizophrenia understand that the use of amphetamines, cocaine, nicotine, and caffeine may worsen their disorder, because substance abuse is so prevalent among this population.

The ultimate goal of such patient education, Maguire said, is to increase patient compliance.

"We need to focus on helping patients with schizophrenia become active participants in their own health care," said Bellnier. "They are predisposed to different conditions such as hypertension and diabetes. They lack the skills to eat properly, and to even prepare food properly. A plan to deal with such skill deficits is something that needs to be coordinated, and the ideal point of coordination is the one place that patients do go, and that is the pharmacy."

Charlotte LoBuono

New schizophrenia drug coming

Last month the Food & Drug Administration issued an approvable letter for aripiprazole (proposed trade name: Abilify, Bristol-Myers Squibb/Otsuka Pharmaceuticals) for the treatment of schizophrenia. Aripiprazole is a potent partial agonist of D₂ dopamine receptors, a mechanism of action unique among antipsychotics, said Mary Kujawa, M.D., Ph.D., medical director, Neurosciences Medical Affairs, Bristol-Myers Squibb, Princeton, N.J. Other antipsychotics, used in the treatment of schizophrenia and other conditions, are dopamine antagonists.

Aripiprazole also acts on the serotonin system, Kujawa continued. The drug is a partial agonist of 5HT_1A receptors and an antagonist of 5HT_2A receptors. According to Kujawa, this combined activity is hypothesized to result in dopamine-serotonin system stabilization.

This unique mechanism of action may also be associated with clinical benefits, said Kujawa. Dopamine partial agonists may have the same efficacy as the first- and second-generation antipsychotics in terms of improving both the positive and the negative symptoms of schizophrenia, but without the adverse effects associated with the older drugs.

Kujawa said that in five short-term clinical trials, aripiprazole demonstrated significantly greater efficacy compared with placebo, and that this separation in efficacy was apparent as early as week one. Although aripiprazole was not directly compared with haloperidol or risperidone (Risperdal, Janssen) in these studies, its efficacy appeared to be comparable to that of the older drugs. In a 52-week maintenance-of-effect trial, aripiprazole was superior to haloperidol in terms of improvement of depressive symptoms, Kujawa said.

A favorable safety and tolerability profile is one of the important features that differentiates aripiprazole from other antipsychotics, said Kujawa. Aripiprazole was associated with minimal weight gain, minimal extrapyramidal symptoms, and minimal sedation. It was not associated with prolactin elevation or QTc interval prolongation. In the five short-term clinical trials that were conducted, discontinuation due to adverse effects was the same for both aripiprazole and placebo, said Kujawa. She also said, however, that some adverse effects were associated with aripiprazole therapy, including nausea, vomiting, akathisia, insomnia, and tremors. She added that the review process for aripiprazole is proceeding as expected, and Bristol-Myers Squibb and Otsuka expect to receive approval by the end of the year.

 

Charlotte LoBuono. Pharmacists play significant role in schizophrenia treatment. Drug Topics 2002;20:HSE24.