Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs

Abstract

Background: Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.

Methods: A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24-28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.

Results: The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.

Conclusion: Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.

Figure 1

Flowchart of early treatment discontinuation. Values are the summary of reasons for discontinuation from all 4 studies. Poor Response was based on "Lack of Efficacy." Symptom Worsening was based on "Psychiatric Adverse Events" and a priori protocol defined "Clinical Relapse" (Study 2 only).

Figure 2

Visitwise PANSS total scores between patients who completed the study and those who discontinued early. Values are means across all treatments and studies. *p < .001 between group difference. Completers (Com), Discontinued (D/C).

Figure 3

Visitwise PANSS total scores between patients who completed the study and those who discontinued early due to various reasons. Values are means across all treatments and studies. *p < .05 between group difference. Completers (Com), Poor response/symptom worsening (PR/W), Intolerability to Medication (IM).

Figure 4

Patient and physician perception of efficacy. A. Discontinuation due to poor response by perception. Patient perception was based on discontinuation by patient perception of poor response either alone or in consensus with physician perception. Physician perception was based on physician conclusion alone. B. Time to discontinuation (D/C) due to poor response by perception. C. Visitwise PANSS total scores between patients who discontinued early due to poor response by patient perception and those by physician perception. *p < .05. Physician perception (Phy per), Patient perception (Pt per).