New Data on Psychiatric Polypharmacy and Unwanted Weight Gain

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Individuals with psychiatric diagnoses are especially vulnerable to experiencing obesity or rapid, undesirable weight gain due to psychotropic medications.¹ Mental health treatment strategies often include polypharmacy; however, previous research on drug-induced weight gain mainly focused on monotherapy and is therefore not applicable.

Investigators analyzed longitudinal data of 832 inpatients with ICD-10 diagnoses of either schizophrenia (n = 282) or major depressive disorder (n = 550) to rank treatment regimens in terms of weight gain, adverse effects, and response to treatment. These data were complemented by data from 3180 students aged 18 to 22 years, which the investigators used to identify factors for early detection and prevention of obesity and mental health disorders. Following 3 weeks of treatment, 47.7% of patients with schizophrenia and 54.9% of patients with major depressive disorder showed 2 kg or more in weight gain.²

Starting weight (r = 0.115), concurrent medications (r = 0.176), and increased appetite (r = 0.275) were major predictive factors. When investigators compared monotherapy (n = 409) with polypharmacy (n = 399), they found significant issues associated with polypharmacy, including increased weight gain (P = .0005), more severe adverse effects (P = .0011), and lower response rates (schizophrenia: P = .0008; major depressive disorder: P = .0101).

The student data established that obesity often begins early in life, is interconnected with personality traits such as “defeatism,” and increases the risk of developing psychosomatic disturbances, mental health problems, or somatic illnesses. Results also demonstrated ways to successfully counteract weight gain during the early stages of treatment, even though the data did not create a comprehensive and applicable model of said weight gain.

The investigators listed 8 questions for their research project to address, which could then be translated into clinical practice, including the following:

1. To what extent is obesity more prevalent among psychiatric patients compared with the general population?

2. To what extent do psychotropic drugs induce unwanted weight gain?

3. What are the differences in drug-induced weight gain between patients with schizophrenia (antipsychotics) and patients with major depressive disorder (antidepressants)?

4. What are the differences between monotherapy and polypharmacy for drug-induced weight gain?

5. What is the severity of the adverse effects that cooccur with drug-induced weight gain?

6. What factors might predict drug-induced weight gain?

7. To what extent does obesity start developing in early life?

8. What factors might influence obesity in early life?

This study identified several major factors that contribute to drug-induced unwanted weight gain, thereby suggesting clinically easily realizable ways of avoiding such weight gain. On average, patients receiving treatment via polypharmacy took 4.19 ± 1.92 medications, consisting of 3.08 ± 1.81 psychotropic drugs, 0.74 ± 1.15 medications that alleviate adverse effects, and 0.37 ± 0.83 other somatic medications. Also of interest was the comparison between monotherapy (n = 409) and polypharmacy (n = 399), as far more patients with major depressive disorder (56.0%) were assigned to a polypharmacy regimen than patients with schizophrenia. (32.3%).

Upon performing correlation analyses, investigators found several significant interrelations between weight gain and variables that reached significance in an explorative generalized linear regression model: (1) starting weight (r = 0.11469; P = .0117); (2) number of concurrent psychotropic drugs (r = 0.16553; P = .0002); and (3) a treatment-induced “increased appetite” from the treatment outset (r = 0.27525; P < .0001). Male patients showed higher average weight gains than female patients, although the differences did not reach statistical significance. Furthermore, there was a strong correlation between unwanted weight gain and the number of concurrent psychotropic medications (r = 0.16553; P = .0002).

When comparing psychotherapy to pharmacotherapy, the investigators noted that patients who received psychotherapy alone experienced only minor adverse effects (n = 24), followed by patients receiving monotherapy (n = 409); however, patients receiving polypharmacy reported more severe adverse effects (n = 399). They noted the significant difference between monotherapy and polypharmacy (P = .0011).

Additionally, the data of 3180 students aged 18 to 22 years made it clear that overweight and obesity often begin early in life among those affected, and are interconnected with personality traits, while increasing the risk of developing psychosomatic disturbances, mental health problems, or somatic illnesses. The student data also cleared the way for applications aiming at the early detection and prevention of overweight and obesity.

“Given these results, we think psychiatry has developed to a significant extent in the wrong direction over the past 15 years. In particular, it seems to be time for psychiatry to reconsider its treatment strategies, which are far too one-sidedly fixated on psychopharmacology and pay far too little attention to alternative options, especially in mild cases,” the study authors wrote.¹ “Most importantly, the polypharmacy approach to treating [patients with major depressive disorder] or [schizophrenia] can in no way—not even rudimentarily—solve the problem that there is no causal therapy in psychiatry.”

References

1. Fast facts — mental health and obesity. STOP Obesity Alliance. May 24, 2021. Accessed May 15, 2024. https://stop.publichealth.gwu.edu/fast-facts/mental-health-obesity

2. Stassen HH, Bachmann S, Bridler R, et al. Polypharmacy in psychiatry and weight gain: longitudinal study of 832 patients hospitalized for depression or schizophrenia, along with data of 3180 students from Europe, the U.S., South America, and China. Eur Arch Psychiatry Clin Neurosci. Published online March 10,2024. https://link.springer.com/article/10.1007/s00406-024-01767-2#Tab5