A new study published in Pharmazie takes a close look at adverse event reports related to drug-induced weight gain submitted to the FDA over the past 10 years.
The retrospective analysis provides insight into the drugs most commonly associated with weight gain side effects.
Key findings include:
- From 2012 to 2021, 137,370 reports of drug-induced weight gain were submitted to the FDA Adverse Event Reporting System (FAERS).
- 68,294 of these cases were classified as serious, with 2,144 resulting in death.
- The drugs most commonly reported to cause weight gain were atypical antipsychotics like risperidone and olanzapine, TNF inhibitors like adalimumab and etanercept, anticonvulsants like pregabalin, and corticosteroids like prednisone.
Source: Pharmazie 2022
Antipsychotics Top the List of Drugs That Lead to Weight Gain
Antipsychotic medications topped the list of drugs associated with the highest number of weight gain reports.
The atypical antipsychotic risperidone accounted for 11.55% of all weight gain reports (15,869 cases).
Other antipsychotics were also among the top drugs implicated, including:
- Olanzapine: 2.18% of reports (2,991 cases)
- Aripiprazole: 3.1% of reports (4,263 cases)
- Paliperidone: 1.89% of reports (2,592 cases)
- Quetiapine: 1.54% of reports (2,121 cases)
These findings align with past research showing that antipsychotic drugs lead to significant weight gain in a large proportion of users.
One meta-analysis found that all antipsychotics increase body weight by an average of 7% from baseline.
The exact mechanisms behind antipsychotic-induced weight gain are not fully understood.
However, they appear to involve effects on appetite signaling, satiety, insulin resistance, and other metabolic pathways.
Managing this side effect remains a major challenge for doctors prescribing antipsychotics.
Psychiatric Medications like SSRI/SNRI Antidepressants Contribute to Weight Gain
In addition to antipsychotics, certain antidepressants and anticonvulsants also showed up frequently in the FAERS weight gain reports:
- Duloxetine (antidepressant): 1.181% of reports (1,181 cases)
- Sertraline (antidepressant): 0.811% of reports (1,119 cases)
- Venlafaxine (antidepressant): 0.74% of reports (1,022 cases)
- Pregabalin (anticonvulsant): 3.86% of reports (5,309 cases)
- Gabapentin (anticonvulsant): 1.07% of reports (1,475 cases)
Tricyclic antidepressants like amitriptyline are known to cause weight gain by increasing appetite and caloric intake.
Certain SSRIs like paroxetine also often lead to weight changes.
Among anticonvulsants, pregabalin appears to carry the highest risk of weight-related side effects.
Doctors may want to factor in weight gain tendencies when selecting psychiatric medications for patients who are overweight or obese.
Adjunctive counseling on diet and exercise may help mitigate weight changes.
Immunosuppressants Like Adalimumab Contribute to Weight Gain
Immunosuppressant drugs used to treat autoimmune diseases were also among the top 25 drugs associated with FAERS weight gain reports. TNF inhibitors were particularly represented:
- Adalimumab: 3.94% of reports (5,409 cases)
- Etanercept: 2.72% of reports (3,735 cases)
- Infliximab: 2.09% of reports (2,866 cases)
These medications block the inflammatory cytokine TNF-alpha and are used for rheumatoid arthritis, psoriasis, Crohn’s disease, and other conditions.
Previous studies found that 13-60% of patients taking TNF inhibitors experience weight gain of ~2-9 lbs on average.
However, the mechanism behind this side effect is not fully clear.
Other newer immunosuppressant drugs like tocilizumab and ruxolitinib also made the top 25 list.
Doctors prescribing immunosuppressants to treat autoimmune and inflammatory conditions should monitor for weight changes and address any concerns proactively.
Corticosteroids Like Prednisone Frequently Lead to Weight Gain
Corticosteroids like prednisone and methylprednisolone are commonly prescribed to reduce inflammation in conditions like asthma, arthritis, and inflammatory bowel disease.
But these drugs also frequently lead to weight gain.
In the FAERS analysis, the corticosteroid prednisone accounted for 2.7% of all weight gain reports (3,711 cases).
This makes it one of the top drugs implicated in real-world weight gain cases.
The tendency for corticosteroid weight gain is well documented.
Studies indicate up to 70% of patients experience weight gain during oral corticosteroid treatment.
Fluid retention and increased appetite drive this effect.
Doctors can help mitigate steroid-related weight gain by using the lowest effective dose, prescribing intermittent dosing, and limiting treatment duration.
Counseling patients on potential weight gain before starting corticosteroids can set expectations.
Levothyroxine and Other Endocrine Drugs Can Also Lead to Weight Gain
The synthetic thyroid hormone levothyroxine was another top drug associated with FAERS weight gain reports, accounting for 2.59% of cases (3,559 reports).
This highlights that drugs affecting thyroid and other endocrine pathways can potentially lead to weight changes in some patients.
Correcting hypothyroidism with levothyroxine is known to cause modest short-term weight loss, followed by a return to baseline weight.
However, effects can vary depending on the individual.
Insulin products and other antihyperglycemic drugs like metformin were also among the drugs implicated in FAERS weight gain reports.
This likely reflects the complex interplay between diabetes, weight, insulin use, and other factors.
Overall, the study highlights that in addition to psychiatric medications, drugs affecting immunity, inflammation, and endocrine pathways can also influence weight in unintended ways.
How the Data Were Collected: Real-World Weight Gain Reports via FAERS Data
The FDA Adverse Event Reporting System (FAERS) database contains valuable information submitted by healthcare providers, consumers, and drug manufacturers on medication errors, adverse events, patient demographics, and more.
Researchers conducted a retrospective analysis of FAERS data on drug-induced weight gain reports submitted between 2012 and 2021.
They searched the database using terms like “weight gain,” “weight increased,” and “overweight” to identify relevant cases.
Out of 137,370 weight gain reports identified in the 10-year period, the majority (126,507) included patient gender data.
Of these, 80,241 cases (63.4%) occurred in females compared to 46,266 cases (36.6%) in males.
Patient age data was available for 77,609 reports, with the majority of cases occurring in adults ages 18-64 (68.4%) followed by older adults ages 65-85 (23.6%).
These real-world data provide insight into weight gain experiences among actual patients taking a wide range of medications.
By tapping into FAERS reports, researchers can analyze patterns and identify drugs most likely to cause this side effect.
Major Takeaways on Managing & Preventing Drug-Induced Weight Gain
This thorough analysis of FAERS data provides unique insights into real-world patterns of drug-induced weight gain over the past decade.
Several key takeaways emerge:
- Risperidone and other atypical antipsychotics pose the highest risk of significant weight gain for patients. However, alternatives may be limited for certain psychiatric conditions.
- TNF inhibitors, corticosteroids, and anticonvulsants like pregabalin also frequently contribute to weight changes.
- Weight gain tendencies should be considered when selecting psychiatric and immune-modulating therapies.
- Counseling patients beforehand on potential weight gain can help set expectations. Lifestyle modification and diet/exercise may help counteract modest weight changes.
- Closely monitoring weight and BMI is important when starting new medications known to cause weight gain in some patients. This allows for proactive management if changes occur.
Further research is still needed to better predict which patients will experience weight gain on specific medications.
But this study provides helpful real-world data for both clinicians and patients to make informed choices about managing weight gain risk with different pharmacotherapy options.
Being aware of each medication’s tendencies can lead to better patient outcomes.
References
- Study: Drug-induced weight gain in the last 10 years: a descriptive study
- Authors: N J Ahmed et al. (2022)
