Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges

Table 2 Risperidone vs placebo in pediatric autism spectrum disorder (based on extracted data analysis)

Outcome measure	No. studies (pooled)	Result (pooled estimate)	95% confidence interval	I2 heterogeneity	P value	Notes
Efficacy (ABC change)		Mean difference (random-effects)				Negative mean difference favors risperidone
ABC Irritability	3	-11.08	(-14.39 to -7.78)	72% (substantial)	< 0.0001	Robust effect, but high heterogeneity
ABC Stereotypy	3	-3.91	(-6.37 to -1.44)	55% (moderate/substantial)	0.002
ABC Hyperactivity	3	-7.97	(-12.26 to -3.69)	81% (high)	0.0003
ABC Social Withdrawal	3	-0.55	(-0.85 to -0.24)	12% (low)	0.0005	Small but consistent effect
ABC Inappropriate Speech	3	-2.27	(-3.85 to -0.70)	41% (moderate)	0.005
Safety (adverse events)		Risk ratio (random-effects)				Risk ratio > 1 indicates higher risk with risperidone
Increased appetite	3	2.45	(1.29-4.65)	30% (moderate)	0.006	Common risk
Somnolence	2	4.14	(1.81-9.47)	0% (low)	< 0.001	Consistent, common risk
Drooling	2	4.70	(1.52-14.54)	65% (substantial)	0.005	Significant, but variable risk
Tremor	2	8.22	(1.56-49.82)	22% (low)	0.01	Significantly increased risk
Fatigue	3	2.18	(0.70-6.85)	78% (high)	0.18	Trend towards higher risk, high variability
Constipation	2	1.31	(0.10-16.38)	0% (low)	0.84	No significant difference
Weight gain (continuous)		Mean difference (kg) (random-effects)				Positive mean difference indicates more weight gain with Risperidone
Mean weight gain diff (kg)	3	1.97	(1.52-2.41)	0% (low)	< 0.0001	Significant and consistent weight gain over approximately 8 weeks

Pooled estimates are calculated using the random-effects model to account for clinical and methodological heterogeneity. The I² statistic explicitly quantifies heterogeneity. High heterogeneity (I² > 50%) suggests that the actual effect size varies significantly across studies, cautioning against a single, universal interpretation. These results highlight the trade-offs associated with risperidone: Its apparent efficacy in addressing challenging behaviors comes at the cost of significant, but variable, adverse effects, particularly metabolic ones (low I² for weight gain), which necessitate careful patient selection and monitoring. Therapeutic drug monitoring may offer a path to optimize this balance. ABC: Aberrant Behavior Checklist.