shows the baseline values for the Stay and Switch groups for various measures. On average, the groups were receiving comparable doses of antipsychotics at study entry, with a trend for higher baseline dosages among those switched to monotherapy (; 26–28), and these dosages were within the ranges recommended by the Schizophrenia PORT guidelines (6
). The most common baseline polypharmacy combinations were quetiapine+risperidone (n=25), quetiapine+First Generation Antipsychotic (FGA) (n=25), risperidone+FGA (n=23), olanzapine+FGA (n=22), ziprasidone+FGA (n=12), aripiprazole+quetiapine (n=11), olanzapine+risperidone (n=10), and other combinations totaling 10 or fewer individuals each (n=39). While the study’s inclusion criterion required the presence of either residual symptoms or side effects, every participant who entered the trial experienced residual symptoms, irrespective of whether they also experienced any side effects.
Of the 127 individuals randomized, 114 (56 Stay, 58 Switch) began their assigned treatment. Of those, 8 (14%) assigned to Stay on Polypharmacy discontinued their assigned treatment (6 changed to a different polypharmacy combination; 2 discontinued one of the 2 assigned medications). Reasons for discontinuation included increased symptoms (n=2), participant preference (n=1), and side effects (n=5; n=2 with weight gain, 1 with EPS, 1 with diabetes, and 1 with unspecified side effects). Among those assigned to Switch to Monotherapy, 18 (31%) discontinued their assigned treatment (12 returned to their baseline polypharmacy combination, 3 began a different polypharmacy combination, 1 began monotherapy with an agent other than one of the 2 baseline medications, 1 began monotherapy with one of the baseline agents and changed to monotherapy with the second baseline agent after 90 days, and 1 began to taper one of the two agents but did not complete the taper following an increase in symptoms). Reasons for discontinuation included increased symptoms (n=11), participant preference (n=6), and side effects (n=1 with hyperlipidemia).
Overall, of the 58 individuals assigned to Switch to Monotherapy who began the treatment, 12 (21%) elected to discontinue quetiapine, 10 (17%) risperidone, 9 (15%) olanzapine, 8 (14%) haloperidol, with the remaining 19 (33%) discontinuing other antipsychotics (each at less than 10% of discontinuations). Among the 30 polypharmacy combinations that consisted of a first- and a second-generation antipsychotic, the second-generation antipsychotic was continued slightly over half of the time (18 of 33 such combinations; 5/10 for quetiapine+FGA; 5/9 for olanzapine+FGA; 3/7 for risperidone+FGA; 2/4 for ziprasidone+FGA, and 3/3 for aripiprazole+FGA).
Time to all-cause treatment discontinuation (defined as time to change in antipsychotic medication for any reason) was shorter for participants assigned to Switch from polypharmacy to monotherapy than for those assigned to Stay on Polypharmacy, and switching from polypharmacy to monotherapy resulted in treatment discontinuation significantly more often than continuation of polypharmacy (Kaplan-Meier Mantel-Cox X2
)=4.55, p = .03; ). This difference remained significant above and beyond gender and race in Cox regression analyses (Wald X2
)=4.22, p =.04; ).
FIGURE 1 Time to Medication Change for Any Reasona
The Stay and Switch groups did not differ significantly on psychopathology over time in random regression models (; ), whether measured as total PANSS, total PANSS positive items, or the 5 factors defined by Marder and colleagues (29
). The sole exception to this was a statistically significant (p=.03) difference for the factor “uncontrolled hostility” (each group had scores very near “no symptoms” on this scale, the groups differed by less than 0.4 points on the 24 point scale—a small effect size (.17) and unlikely to be clinically significant-- with the change over time favoring the Stay condition). Nor did the two groups differ with respect to incidence of sexual side effects (), new-onset EPS (n=12 in each group; 30% of those assigned to Stay and 29% of those assigned to Switch), or new-onset tardive dyskinesia (19% of those assigned to both Stay (n=8) and Switch (n=9)). Groups did not differ with respect to the likelihood of being hospitalized for psychiatric reasons, which was uncommon in each group (5 (8%) and 7 (11%) hospitalized at least once during the first 6 months for the Stay and Switch groups, respectively), nor did the groups differ with respect to time to first hospitalization for psychiatric reasons. Groups also did not differ with respect to total hospitalizations (medical and psychiatric).
Intent to Treat Random Regression Analysis of Secondary Outcome Measures for People with Schizophrenia-Spectrum Disorders in a Randomized Controlled Study of Staying on Antipsychotic Polypharmacy versus Switching to Antipsychotic Monotherapy
Those assigned to Switch to Monotherapy significantly decreased their body mass index (BMI) compared to those assigned to Stay on Polypharmacy, who increased their body mass index (; ; Group by Time interaction, p = .05). On average, individuals assigned to Switch to Monotherapy lost 0.50 BMI (SD = 2.32 BMI) over 6 months, and individuals assigned to Stay on Polypharmacy gained 0.28 BMI (SD = 2.31 BMI) over 6 months. Each of the secondary (as-treated) models were consistent with the findings of the primary intent-to-treat analyses.
FIGURE 3 Difference in Body Mass Index Through Timea