Elsevier

Schizophrenia Research

Volume 57, Issues 2–3, 1 October 2002, Pages 201-208
Schizophrenia Research

Switching from conventional to novel antipsychotic drugs: results of a prospective naturalistic study

https://doi.org/10.1016/S0920-9964(01)00309-7Get rights and content

Abstract

Objective: We examined the long-term consequences of switching patients from conventional to novel antipsychotic drugs, from a patient's perspective. Methods: In a prospective, single-blinded, naturalistic study, a cohort of subjects (n=150) with schizophrenia or schizo-affective disorder (DSM-IV) were switched from conventional neuroleptic drugs to either risperidone (n=50), olanzepine (n=50) or quetiapine (n=50), and monitored for a period of 2 to 6 years. The ensuing natural history of transitions in treatments was charted, and the outcomes including symptoms, side effects, subjective tolerability of drugs and their impact on quality of life were documented with standardized rating scales. Results: Majority (85%) of the subjects benefited from a switch to the novel antipsychotic drugs, though some preferred to return to their original neuroleptic (8%), and others eventually required clozapine (7%) therapy. Novel antipsychotic drugs were significantly tolerated better, and had a positive impact on treatment-adherence, psychosocial functioning and quality of life. Among the novel drugs, risperidone was significantly better in improving negative symptoms, while olanzepine was particularly well tolerated and effective against comorbid anxiety and depressive symptoms. Patients treated with quetiapine reported fewer side effects, and showed a significantly greater improvement in neurocognitive deficits. Conclusion: Novel antipsychotics emerged as the drug of choice in view of their overall effectiveness, though conventional neuroleptics and clozapine will continue to have a limited but distinct role in the management of schizophrenia. The challenge for clinicians lies in matching a patient's clinical and biochemical profile with that of a drug's pharmacological actions, in order to achieve optimum outcomes.

Introduction

Novel antipsychotic drugs have a superiority over conventional neuroleptics in terms of improved subjective tolerability and a potential to enhance patients' quality of life in schizophrenia (Voruganti et al., 2000). Numerous clinical trials sponsored by pharmaceutical industries have not only evaluated the benefits of novel compounds over conventional drugs, but also attempted to establish the relative virtues of one drug over another Geddes et al., 2000, Revicki, 2000, Stanuiland and Taylor, 2000, Worrel et al., 2000, Chakos et al., 2001, Harvey and Keefe, 2001. However, the studies appraised in many of these reviews included industry-sponsored clinical trials that were originally designed and conducted to meet regulatory requirements, gain formulary approvals, or facilitate marketing strategies, and may not be entirely useful in guiding clinicians toward choosing a right drug for the right patient. From a patient's perspective, improving symptoms, avoiding side effects and enhancing psychosocial adjustment are the key therapeutic priorities, and it is the clinicians' task to find a drug that can facilitate the attainment of these goals (Awad et al., 1995). Novel antipsychotic drugs seem to possess certain strengths that can turn this ideal into a reality.

The availability of several novel antipsychotic drugs within a relatively short time span has provided a greater choice of therapeutic options on one hand, but also created some confusion with regard to a method of choosing between individual drugs. Conventional antipsychotic drugs are often avoided to minimize the risk of side effects, and clozapine is reserved for the treatment-refractory cases. This leaves three novel antipsychotic drugs—risperidone, olanzepine and quetiapine—as the choices for initiating or maintaining antipsychotic drug therapy in schizophrenia (Stahl, 1999). Currently, there are no evidence-based guidelines available to help clinicians as to which drug is likely to be the most beneficial for a given patient. The present study was aimed at examining the potential benefits of switching patients from conventional to the novel antipsychotic drugs, and documents the distinct therapeutic roles of individual antipsychotic drugs in an unselected, clinically heterogeneous schizophrenic population. The specific research questions addressed were as follows:

  • 1.

    Should all the subjects receiving maintenance treatment with conventional neuroleptic medications be routinely considered for a switch to one of the novel antipsychotic drugs?

  • 2.

    Does the relative superiority of novel antipsychotic drugs perceived in clinical practice and cross-sectional surveys prove to be sustainable over a longer period of time during follow-up?

  • 3.

    Can a niche be found for individual antipsychotic medications, in terms of identifying subgroups of schizophrenic patients that could be benefited from one specific drug more than the others?

Such data would obviously facilitate clinicians' decision making process, prevent potential distress to patients caused by an improper choice of medication, improve treatment adherence (compliance) and minimize the overall costs to the health care system.

Section snippets

Study design and subjects

The purpose of the study was to assess the effectiveness of novel antipsychotic drugs in a naturalistic treatment setting reflective of a real life clinical practice. The study setting, subjects' selection, and the treatment allocation strategy were, thus, quite different from that of a conventional clinical trial. A description of the study setting, referral base and recruitment strategy were provided in an earlier publication (Voruganti et al., 2000).

The study was confined to subjects

Methods

The battery of rating scales were part of a standard protocol employed for assessing all the subjects referred to the schizophrenia treatment program. Instruments were chosen to evaluate and quantify a range of clinical outcomes, and aimed at capturing the impact of antipsychotic drug therapy from the clinicians' as well as patients' perspectives. The battery included various clinician-rated symptoms and side effects rating scales, as well as self-rated side effects, tolerability and quality of

Data analysis

Data from the serial administration of various rating scales were tabulated, and scores from the baseline (before the switch) and the last follow-up visit were used for further analysis. Scores from individual items on the positive and negative syndromes scale (PANSS) were summed to form five symptom clusters—positive, negative, excited, depressed and cognitive, with a view to gain a better understanding on the differential effects of novel antipsychotic drugs (Kay, 1991). Based on the scores

Results

Results are presented under two sections—the natural history of transitions in treatment during the follow-up period, and the outcomes for each of the medication groups at the end of the follow-up period.

Of the 150 subjects consecutively switched to the novel antipsychotics, 135 remained in the study, and 15 subjects withdrew their consent, discontinued their medications, or were lost for follow-up. The timing of the drop outs were as follows: seven within the first 2 weeks, three between 2 and

Discussion

The present article is the second in a series of naturalistic studies aimed at examining the effectiveness of novel antipsychotic drugs in managing schizophrenia in routine clinical practice. Naturalistic studies have several limitations, but they could also offer new insights. While controlled clinical trials tell us more about a drug, naturalistic studies provide valuable information about the interaction between the drug, the illness, and the patient in real life. Data from naturalistic

Conclusions

The study has demonstrated that switching patients from conventional to the novel antipsychotic drugs is a challenging but worthwhile exercise, in the management of schizophrenia. Careful planning, patient/family education, and close monitoring are warranted to ensure smooth transitions in treatment. Flexible, individualized plans for optimizing drug therapy are likely to be more successful, than simplified, “cook-book” switching regimes. Once the switch is successfully accomplished, novel

Acknowledgements

The authors wish to acknowledge the support extended by the staff in the community rehabilitation program (CRP), schizophrenia treatment and research program (STAR) and the Western Ontario therapeutic community hostel (WOTCH). The study is an independent clinical investigation funded by the University of Western Ontario.

References (16)

There are more references available in the full text version of this article.

Cited by (0)

Presented in part at the International Congress of Schizophrenia Research (Winter workshop) meeting held in Davos, Switzerland, 5–11 February 2000.

View full text