Weight gain associated with antipsychotics

Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of RWD for patients with bipolar I disorder or schizophrenia

Background

Antipsychotic medications are effective pharmacotherapies for the treatment of bipolar I disorder (BD-I) and schizophrenia (SZ). Although second-generation antipsychotics (SGAs) have lower extrapyramidal symptom liability than first-generation antipsychotics (FGAs), most SGAs are associated with clinically significant weight gain (CSWG) and the emergence of metabolic effects, including diabetes and cardiovascular (CV) disease.

Objective

This analysis of RWD describes clinically significant weight gain and cardiometabolic comorbidities observed in patients with BD-I and SZ after initiating select SGAs.

Methods

This retrospective analysis used data from the OM1 RWD Cloud from Jan 2013 to Feb 2020. Based on a comprehensive review of antipsychotic-associated side effects from clinical studies,patients who initiated an oral SGA associated with moderate-to-high risk of weight gain (index) were included, and were followed for a minimum of 12 months (Figure 1).

The SGAs analyzed were as follows:

Olanzapine/fluoxetine: BD-I only
Olanzapine, risperidone, and quetiapine: BD-I and SZ
Clozapine, iloperidone, and paliperidone: SZ only

Fig 1. Analysis Schematic

See the full poster to view the Inclusion Criteria, Outcomes, and Analytic Methods.

Results

Baseline Patient Characteristics

See the full poster to see a detailed table of Baseline Patient Characteristics.

Weight Gain After Initiation of Oral SGAs Associated With Moderate-to-High Risk of Weight Gain

The mean (SD) % increase in weight during treatment was 3.7% (7.0) and 3.3% (7.2) in patients with BD-I and SZ, respectively.
The mean [SD] % weight gain during treatment was highest for underweight/ normal weight patients (BD-I: 5.5% [8.7]; SZ: 4.8% [8.1]) vs those who were overweight (BD-I: 3.8% [6.8]; SZ: 3.4% [7.6]) or obese (BD-I: 2.7% [5.9]; SZ: 2.3% [6.0]) (Figure 2A and 2B).

Fig 2. Mean % Change in Weight From Baseline by BMI Category in (A) Patients With Bipolar I Disorder and (B) Patients With Schizophrenia

Results (continued)

The proportion of patients with ≥7% or ≥10% weight gain increased over the study period in both BD-I and SZ cohorts (Figure 3).

Median time to CSWG of ≥7% was 14 weeks for both the BD-I and SZ groups; median time to CSWG of ≥10% was 20 weeks for the BD-I group and 19 weeks for the SZ group.

Fig 3. % of Patients With Clinically Significant Weight Gain While on Treatment with Oral SGAs with Moderate-to-High Risk of Weight Gain, by Follow-up Interval

Weight Gain and Treatment Interruptions During Use of Oral SGAs with Moderate-to-High Risk of Weight Gain

>96% of patients in each group switched to a low weight risk SGA, a long-acting injectable antipsychotic, or discontinued SGA treatment during follow-up.
Among patients with CSWG who experienced treatment interruptions, ~75%-80% failed to return to their baseline weight during follow up (Figure 4).

In the minority of patients who returned to their baseline weight across both cohorts (<26.1%), it took a median of 38 weeks or longer to do so.

Fig 4. % of Patients Using SGAs With Moderate-to-High Risk of Weight Gain and Return to Baseline Weight After Treatment Interruption

Incidence of CV Conditions Over 12 Months Following Antipsychotic Treatment Initiation

At baseline in the BD-I cohort, 38.7% had no CV condition of interest and 39.5% had no “other” CV condition.
Baseline prevalence of CV conditions was higher in overweight/obese patients with BD-I vs underweight/normal weight patients.

At baseline in the SZ cohort, 24.3% had no CV condition of interest and 24.0% had no “other” CV condition.
Baseline prevalence of CV conditions was higher in overweight/obese patients with SZ vs underweight/normal weight patients with SZ. (Figure 5)

Fig 5. Incidence of Cardiovascular Conditions of Interest in Patients With Bipolar I Disorder and Schizophrenia, by BMI and CSWG Status Over 12 Months of Follow-up

Added CV Condition Burden in the 12 Month Follow-up Period After Antipsychotic Treatment Initiation in Patients With a CV Condition at Baseline

In total, 69.2% of the BD-I cohort and 82.5% of the SZ cohort had 1 or more of the 4 chronic CV conditions of interest at baseline (Figure 6)

Fig 6. Development of Additional Cardiovascular Conditions in Overweight/Obese vs Underweight/Normal Weight Patients Who Had ≥1 Cardiovascular Condition at Baseline, by CSWG Status Over 12m of Follow-up

Conclusions

In this retrospective analysis, patterns of weight gain and development of CV comorbidities were similar across patients with BD-I and SZ; these data support previous findings that weight gain associated with SGAs of moderate-to-high risk of weight gain is independent of disease state.

Clinically significant weight gain occurred quickly after initiating SGAs associated with moderate-to-high risk of weight gain.

Among patients who experienced CSWG on treatment, most (≈75%) did not return to their baseline weight after interrupting treatment; for those who did return to baseline weight, it took a median time of ≈9–10 months to do so.

Development of new CV comorbidities within 12 months of initiation of these SGAs was highest in patients who were overweight or obese at baseline, and generally increased for patients with ≥7% or ≥10% CSWG in both the BD-I and SZ cohorts after initiating treatment.

Patients with BD-I or SZ are already at risk for CV conditions because of their underlying disease state, and weight gained during treatment with SGAs may further exacerbate these health risks.

The patient's overall health should be considered when treating those living with BD-I or SZ, including various chronic and costly comorbidities associated with weight gain.

This is the first study of which we are aware that suggests that emergent CV conditions may be observed in some patients within 12 months of treatment initiation with SGAs of moderate-to-high weight gain risk.

View the full poster here for more details and a list of references and limitations.