OBJECTIVES: To estimate the risks of gaining weight, with the use of selective serotonin reuptake inhibitors (SSRI) and atypical antipsychotics (SGA) in combination among children and adolescents. METHODS: A retrospective cohort study was conducted using 2003-2005 Medicaid Analytic eXtract (MAX) data from four U.S. states. Combination pharmacotherapy was operationalized as the concurrent prescribing of SSRI and SGA, where at least 14 days of treatment overlap occurred. Long term combination use is defined as an overlap beyond 60 days. Children and adolescents aged 6-18 years, and enrolled in Medicaid during 3 months prior and 1 year post  the treatment initiation were selected.   Multivariable logistic regression models were employed to estimate the risks of gaining weight during the one year follow up period. RESULTS: Among 118,126 children and adolescents received SSRI or SGA, 56,091(12.5%) were on combination treatment and of which approximately 80% were on long-term therapy (>60 days).Vast majority (63%) of these recipients were adolescents (13-18 years). The effect of combination therapy on risk of weight gain was observed against both SSRI monotherapy and SGA monotherapy in multivariable logistic regression analyses. Likelihood of gaining weight with combination therapy was higher against both SSRI monotherapy (OR=1.88; 1.69-2.10) and SGA monotherapy (OR=1.52; 1.37-1.68). Long-term combination therapy (>60 days of treatment overlap) resulted into increased risk of weight gain (OR=1.64; 1.30-2.07) as compared to short term uses (>=14 days and <60 day).          CONCLUSIONS: The effect of combination therapy on increased risk of weight gain was suggested in the study, especially when the combinations were used for long term maintenance. Comprehensive evaluation of other psychotropic combinations on risk of other adverse events is needed to be conducted in future.