Deborah Brauser

July 12, 2013

EDINBURGH, Scotland — In-home initiation of the atypical antipsychotic clozapine can decrease symptoms of resistant schizophrenia while also increasing treatment adherence, new research suggests.

Preliminary results from a small pilot study in the United Kingdom showed that after initiating treatment with clozapine in the home, rather than starting treatment in the hospital, patients with refractory schizophrenia had a significant decrease in symptom severity scores.

However, the researchers stress that guidelines for the in-home process, such as those recommended by their Therapy Review Evaluation and Treatment (TREAT) practice, need to be taken into account. These include evaluating patient suitability, setting up strict monitoring practices with community teams, and having a contingency plan for alternative treatment if needed.

Lead investigator Oliver D. Howes, MRCPsych, DM, PhD, consulting psychiatrist at the Institute of Psychiatry in London, United Kingdom, and at the Maudsley Hospital, told Medscape Medical News that as long as recommendations are followed, clinicians should consider offering home initiation of clozapine as an option to this patient population.

"I am optimistic that this is both feasible and can make a big difference for patients. Despite being the only drug licensed for refractory schizophrenia, we know that clozapine is underused in the UK, USA, and most other countries," said Dr. Howes.

"The TREAT approach is something that could be widely adopted to enable more patients to benefit from it, but we want to test it further in other settings."

The results were presented here at the International Congress of the Royal College of Psychiatrists (RCPsych) 2013.

Treatment Resistance Common

Dr. Howes and his investigative team previously assessed 270 patients who presented with a first episode of schizophrenia and then followed them for 10 years. Of the 27% who met criteria for treatment resistance, 83% were refractory from the onset.

Dr. Oliver Howes

"It's striking how common treatment resistance for this illness is. And for these patients, they didn't respond at the beginning of their illness, and they haven't responded over the years since then. And this chimes with our clinical experience," he said.

"This also suggests that we should be treating it differently."

Although clozapine has been shown to be effective for treatment-resistant psychosis, the US Food and Drug Administration requires that the medication carry black box warnings for several possible adverse events, including agranulocytosis. This means that blood tests need to be drawn continually during treatment and that white blood cell counts need to be monitored on a weekly basis — at least for the first months.

Dr. Howes noted that UK clinicians often find it difficult to prescribe a regime of clozapine because of patients not wanting to go through all of this and because of a lack of resources (for practices such as electrocardiography, physical examinations, and blood work-ups) and the need for admission to administer the medication.

"So we wanted to try to address some of these concerns," he said, noting that that was why the TREAT Service at the South London and Maudsley (SLAM) National Health Service (NHS) Foundation Trust was created.

"We wanted to look at community initiation to make sure it is much more available to the patients and to offer reviews from our community teams."

For their study, the investigators enrolled 36 adults with refractory schizophrenia. All received in-home initiation of clozapine, starting at 12 mg.

The Positive and Negative Syndrome Scale (PANSS) was administered at baseline and after treatment to measure symptom severity.

Decreased Symptoms

Results from the feasibility pilot study showed that the participants had a significantly decreased mean score on the PANSS after treatment (P = .01).

"These people were highly symptomatic for years. And even though we looked at a small number, there was a significant difference after treatment," said Dr. Howes.

Only 3 of the participants were deemed "not suitable" for community initiation.

When asked about the study's takeaway message, Dr. Howes said that clinicians should "consider clozapine early and use it over strategies that are not evidence-based, such as high doses of drugs or combinations of antipsychotics."

"The short-term effort of starting clozapine is more than offset by the longer-term gains," he added.

TREAT recommendations for prescribing in-home use of clozapine include the following:

  • Prep: Have a contingency plan, inform the patient's pharmacy and general practitioner, and get written consent.

  • Suitability: Choose patients who are able to seek help if needed and who have no contraindications, such as high or low blood pressure, are elderly or very young, take benzodiazepines, or are using illicit substances.

  • Regime: Follow all prescriber and community-use guidelines, although those from the National Institute for Health and Care Excellence (NICE) in the UK will be updated next year.

  • Monitoring: Check for common side effects, as well as for rare but important adverse events, such as myocarditis, seizures, or ileus from severe constipation.

  • Check Adherence: Check blood levels to make sure patients are adhering to the treatment.

"For the community-assisted regime, we suggest starting treatment on a Monday so they have that week if they have any initial problems, measure daily, and to start low and go slow," said Dr. Howes. "Start at 12 mg and only make changes during the week, not right before the weekend, when there's less provision."

He noted that although these steps may seem daunting, the FIN-11 study, which examined more than 66,000 patients in Finland with schizophrenia and followed them for 11 years, showed the importance of clozapine.

That study, which was published in 2009 in the Lancet, showed that use of clozapine was associated with a significantly lower mortality rate than not using antipsychotics, as well as compared with the use of quetiapine, perphenazine, or any other antipsychotic drug.

"This medication does save lives. It's probably due to a reduction in suicide in people with resistant illness actually getting treatment for their illness," said Dr. Howes.

"Important Option"

"I think it's important for people to have the option of starting clozapine safely in their own homes," session moderator Fiona Gaughran, FRCPsych, MD, lead consultant psychiatrist for the National Psychosis Service of the SLAM NHS Foundation Trust, told Medscape Medical News after the presentation.

Dr. Fiona Gaughran

"Although some people will need to come in to start clinically, not all do. And if it's possible to start in the home, I think that's better for patients and their families."

Still, Dr. Gaughran, who was not involved with this research, noted that safety needs to come first, including staying in contact with the hospital pharmacy. But as long as strict guidelines are followed, "it's nice to have the opportunity to offer this."

When asked if she would recommend this to other clinicians, including those in the United States, she said that it would depend on their available resources in the community.

"Certainly the protocol for this is being developed. And one would need to adapt them for one's local environment and how the regimes work with and communicate with one another. But the principle is there," said Dr. Gaughran.

International Congress of the Royal College of Psychiatrists (RCPsych) 2013. Oral presentation S14. Presented July 2, 2013.

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