“The findings of the present investigation speak to several issues,” Dr. Gary Remington explained in response to emailed questions. “The first relates to the long-standing notion that antipsychotics must be administered continuously to maintain response.”
“We know D2 blockade is central to antipsychotic response, although more recent findings suggest that sustained blockade is not required,” he continued. “In fact, there is evidence that continuous blockade may be linked to behavioral tolerance and possibly decreased efficacy, as well as increased risk of certain side effects (e.g. tardive dyskinesia). Thus, there may actually be advantages to a strategy such as extended dosing over and above decreased antipsychotic exposure and economic savings.”
To test the idea of “extended dosing”, Dr. Remington, at the University of Toronto, Ontario, and colleagues compared 18 subjects with stabilized schizophrenia who received maintenance medication daily to 17 similar individuals who received their medication every second day, for 6 months.
As reported in the Journal of Clinical Psychiatry online September 7, relapse rates were similar in the two groups in terms of total psychopathology, at 16.67% in the daily-dosing group vs. 23.52% in the alternate-day group (p=0.61).
Specific psychiatric symptoms, such as thought disorder and hostility-suspiciousness, followed the same pattern.
“These results challenge the long-standing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia,” the authors conclude,
Dr. Remington acknowledged that the results do not show that tachyphylaxis was attenuated. “The two groups looked about the same over the trial; hospitalizations were fewer in the extended dosing group but the numbers were simply too small to allow definitive conclusions.”
In fact, many questions remain, he noted. “How long can the medication gap be extended before risk of clinical deterioration and/or relapse increases? What are the implications for medication adherence, clearly a challenge with daily dosing? Will decreased antipsychotic exposure translate to benefits in side effects (e.g. movement disorders, weight gain) and possibly even other symptom domains (affective, negative, cognitive) associated with schizophrenia but more readily linked to hypodopaminergic states?”
The answers are simply not known, he said. “But the evidence gathered in this study, as well as some of our additional work and that of others, suggests further investigation along these lines is warranted.”
J Clin Psychiatry 2010.