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This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

19th Congress of the European College of Neuropsychopharmacology

Paris, France / September 16-20, 2006

“Sustained remission is a new standard for outcomes in schizophrenia. The idea [behind this] is to change the course of outcome earlier in the course of illness. Schizophrenia is a devastating illness and improving outcomes is an enormous challenge,” stated Dr. John Kane, Chairman, Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York.

The rationale for early treatment is based on the observation that the majority of patients with a first episode of schizophrenia will eventually relapse and each successive relapse results in further deterioration. Dr. Kane defined relapse as re-emergence of symptomatology requiring a change of treatment or, in extreme form, requiring hospitalization. “The opportunity in the beginning of the illness is particularly important,” Dr. Kane told delegates. “Relapses in early phases of illness are particularly devastating.”

As he reported, first-episode patients treated with placebo or who withdrew from medication have relapse rates ranging from 60% to 72% during the first year and up to 96% in the second year. Relapse rates are considerably lower in first-episode patients who receive antipsychotic therapy; at the end of one year, relapse rates range from 16% to 46% in various studies; in the second year, they can reach 46%; and at the end of 10 years, they are as high as 90%.

A study of more than 100 first-episode patients followed for up to five years showed that patients who discontinued medications were five times more likely to have a relapse than those who remained on treatment (Robinson et al. Arch Gen Psychiatry1999;56(3):241-7). “This powerful effect of discontinuing medications was seen for both first and second relapse. At the end of five years, 82% of patients had at least one relapse,” Dr. Kane reported.

Treatment Adherence

Treatment adherence is a major stumbling block in prevention of relapse. Dr. Kane indicated that injectable antipsychotic medications can overcome this obstacle by assuring adherence, thus improving the likelihood of remission and even recovery.

Presenting data on a large database of about 4000 patients, he reported on the findings, which suggested that treatment could influence remission and sustain it over time. In a one-year open-label trial of 578 stable patients, 21% achieved full remission on long-acting injectable risperidone and another 14% reduced symptom severity to “mild or less” on the Positive and Negative Syndrome Scale (PANSS) (Lasser et al. Schizophr Res 2005;77(2-3):215-27). Of those in full remission, 85% were able to sustain remission until the end of the study. Improvement was observed in all PANSS domains, in global illness severity and quality of life.

Dr. Kane reported, “This study showed a significant improvement in PANSS total score, even if patients did not meet the criteria for full remission [i.e., improvement level sustained over six months].” Treated patients also improved on measures of quality of life, social function and vitality. “These patients are approaching healthier levels of functioning,” Dr. Kane commented. “We are beginning to see the clinical impact of remission criteria and we also see that treatment can achieve remission. We see that long-acting medication can make a difference and is well suited in bringing about remission.”

According to Dr. Robin Emsley, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa, long-acting injectable antipsychotic compounds should be used earlier in the course of illness rather than waiting to treat more severe stages. He cited several studies that reinforce the finding that poor adherence is an “overwhelming” problem in clinical practice. It is a challenge for psychiatrists to determine whether their patients are fully adherent, Dr. Emsley indicated. Partial adherence is a major problem in schizophrenia, since many patients do not take their treatment on days when they are feeling well.

First-episode Patients

A Canadian study showed that 39% of first-episode patients discontinued medication within the first year of treatment and another 20% were only partially adherent. “This group of patients is vulnerable to either relapse or partial relapse, since most relapses and deterioration occur early in the course of illness,” Dr. Emsley noted. The reasons behind non-adherence are complex and long-acting injectable medications are a useful way of delivering antipsychotic medication and assuring adherence, he suggested.

Dr. Emsley and colleagues studied 522 first-episode patients and evaluated time to response to long-acting risperidone compared with time to response in a previous randomized controlled trial of oral risperidone vs. oral haloperidol in first-episode patients. At a one-year interim analysis of the two-year trial, 76% of patients were still on the injectable antipsychotic, compared with 53% in the study of oral therapy. The long-acting treatment was more efficacious than the oral compound across all domains of symptomatology. Dr. Emsley attributed results to adherence to treatment with the injectable antipsychotic rather than innate differences in efficacy between the oral and injectable formulations. Relapse rates were reduced with the injectable medication. Because this is an interim analysis of an open-label study, he stressed that these results should be interpreted with caution. With that caveat, he added that results suggest that the long-acting injectable formulation is safe and effective and can be used early in the course of illness, providing sustained, reliable delivery of treatment. “We should intervene as early and effectively as possible and not accept stabilization [i.e., low level of symptoms] as our end point. Once we achieve remission, we can focus on maintaining remission,” Dr. Emsley stated.

Atypicals and Conventional Antipsychotics

A three-year, double-blind extension study presented here by Dr. Antony Loebel, New York, New York, and colleagues supports the concept that full remission is achievable in patients with schizophrenia and that atypical antipsychotic agents are more efficacious than conventional antipsychotic compounds.

In a study population of 186 patients, two different dosing regimens of ziprasidone, 80 to 160 mg b.i.d. and 80 to 120 mg q.d., were compared with haloperidol 5 to 20 mg/day. The authors indicated that both dosing regimens of ziprasidone were more likely than haloperidol to achieve remission and sustained improvement in quality of life. In the first six months of the study, b.i.d. ziprasidone demonstrated a significant improvement in remission rate (P<0.05) over haloperidol as did q.d. ziprasidone, which also achieved a higher remission rate compared with haloperidol. At the end of three years, both regimens of ziprasidone were significantly more effective than haloperidol in remission rate (P<0.05) and in quality-of-life scores (P<0.05).

Coordinating Service Delivery

An outreach program in The Netherlands providing coordinated services for patients with schizophrenia was able to achieve higher remission rates compared with fragmented service delivery provided by various social agencies. The team-based approach was presented by Dr. Jim van Os, Department of Psychiatry and Neuropsychology, Maastricht University, The Netherlands.

Prior to the implementation of the assertive outreach program, the probability of achieving remission was 19%; after the program was initiated, the probability increased to 31%. Dr. van Os and colleagues found that the presence of comorbid substance abuse, which is present for 40 to 50% of schizophrenic patients, reduced the likelihood of sustaining remission. They also found that first-episode patients could be successfully integrated into the outreach program, thereby reducing expenditures associated with specific strategies for mental health services for this particular high-risk group of patients. Furthermore, a four-year analysis of the effects of the outreach program showed that combining conventional and atypical agents was not more advantageous than the use of atypical compounds alone.

Summary

Remission has gained acceptance as a treatment goal for patients with schizophrenia. The new criteria stipulate reduction in symptomatology to “mild or less” that is sustained for at least six months. Using these new criteria, atypical antipsychotic agents have been shown to achieve remission. The major obstacle to achieving remission is poor adherence to treatment. One strategy for assuring adherence and improving the chances of remission is use of a long-acting injectable antipsychotic.