BMI, Other Patient Factors Help Pinpoint Best Antidepressant

Batya Swift Yasgur, MA, LSW

May 05, 2017

Individual patient factors, including body mass index (BMI) and the person's sex, can pinpoint the best antidepressant for an individual patient, new research shows.

Investigators at Stanford University School of Medicine and VA Palo Alto Health Care System in California found that the antidepressant extended-release venlafaxine (venlafaxine-XR) (Effexor XR, Wyeth Pharmceuticals) was more effective than escitalopram (Lexapro, Forest Laboratories) and sertraline (Zoloft, Pfizer) in achieving remission in morbidly obese patients with major depression, a finding that increases understanding of how patient characteristics can be used to precisely target antidepressant response.

"We expected that some individual characteristics would make a difference in antidepressant response, but the surprising piece was seeing how strong the findings were for particular medications, when you take BMI into account, and that you could really improve aspects of depression if the patient received one medication vs another," lead researcher Leanne Williams, PhD, told Medscape Medical News.

"These findings support the approach of selecting antidepressants in a targeted way, based on a given patient's individual characteristics," she added.

The study was published in the January/February issue of Personalized Medicine in Psychiatry.

Two Major Public Health Issues

Although a variety of antidepressants effectively achieve remission in clinical depression, "which antidepressant is best suited to which person is currently unclear," the authors write.

A number of clinical factors are usually available to clinicians, including patients' sex, height, weight, and symptom profiles, but "there is no consensus as to how these variables may be used to inform antidepressant treatment," they add.

"Scientifically, very little has been done to look at these two major public health issues — depression and weight management — together and ask whether some antidepressants do better for people with depression, be they male or female, according to BMI," said Dr Williams.

For the study, the investigators analyzed data from 659 adults with clinical depression who participated in the International Study to Predict Optimized treatment in Depression (iSPOT-D). Participants were randomly allocated to receive 8 weeks of treatment with either escitalopram, sertraline, or venlafaxine-XR.

The BMI of participants ranged from 19 to 72 kg/m2 (normal weight to obese class III, using the World Health Organization classification). The mean was in the overweight range (28.0 kg/m2); 43% of the study sample were men, and 57% were women.

Depression was measured according to the 17-item Hamilton Rating Scale for Depression (HRSD-17), with remission defined as an HRSD-17 score of ≤7 after 8 weeks of treatment.

The HRSD-21 was used to determine symptom categories. Physical symptoms included sleep disturbance, diurnal variation, genital symptoms, hypochondriasis, weight changes, somatic anxiety, somatic gastrointestinal symptoms, and general somatic symptoms.

Cognitive symptoms included suicidal ideation, guilt, psychic anxiety, insight, paranoia, depersonalization/derealization, change in work and activities, depressed mood, psychomotor retardation, and psychomotor agitation.

The researchers found that compared to participants of normal weight, morbidly obese patients were more likely to experience remission after receiving venlafaxine-XR, and women were more likely than men to experience remission with any of the antidepressants. The effect was attributable to a reduction in physical symptoms, including sleep disturbance, somatic anxiety, and appetite.

Impact on Appetite

The findings showed that BMI was a differential predictor of remission for the comparison of venlafaxine-XR and escitalopram, but not for the other pairwise treatment comparisons (2=50.14, df=10, P < .001, Nagelkerke R2 = 0.10).

Every unit increase of BMI was associated with 6% greater odds of remission for venlafaxine-XR (95% confidence interval [CI], 1.01 - 1.11). However, BMI did not significantly predict remission with escitalopram (95% CI, 0.96 - 1.04) or sertraline (95% CI, 0.99 - 1.08).

There was a significant interaction of BMI by sex in predicting remission (W = 5.50, P = .019; interaction odds ratio = 1.06 [95% CI, 1.01 - 1.12]). Although BMI was not associated with remission in men, every unit increase of BMI in women was associated with 5% greater odds of remission.

Moreover, women with higher BMI were more likely to experience remission than women with lower BMI, regardless of the antidepressant used. However, sex was not independently predictive of remission from depression (P = .38).

For every unit increase in BMI, venlafaxine-XR was associated with a 0.15 larger decrease in HRDS physical symptoms than escitalopram (b = 0.15, P = .003), meaning that venlafaxine-XR "appears to reduce depressive symptomatology related to the more physical symptoms of sleep, appetite/weight changes, and somatic symptoms (fatigue, headache, muscle aches)," the researchers note.

"Patients with anxious depression tend to eat more, and venlafaxine, which contains norepinephrine that is known to play a role in helping to manage anxiety, may reduce overeating, leading to improved physical symptoms," said Dr Williams.

In addition, "the extended-release formula of venlafaxine allows the release of the agent over a longer period of time, and the increased BMI might allow the drug to be stored in the adipose tissue, thereby remaining in the system for longer. These speculations are worthy of being tested further," she said.

Immediate Clinical Applicability

Commenting on the findings for Medscape Medical News, Madukar Trivedi, MD, professor, Betty Jo Hay Distinguished Chair in Mental Health and Julie K. Hersh Chair for Depression Research and Clinical Care at the University of Texas Southwestern Medical Center, Dallas, called the study "a very interesting analysis of the data."

"I appreciate what the researchers have done," said Dr Trivedi, who was not involved in the study. "We are all trying to figure out how best to understand what group of patients do best with which type of treatment. Precision medicine matches patients with antidepressants, which is important."

He cautioned that the study was retrospective, and "we as a field will still need to do prospective trials to be certain."

Nevertheless, he added, "the findings of the present study should be used by clinicians when they start selecting medications so that if a person presents with high BMI, especially associated with symptoms described in the study, clinicians should be mindful that venlafaxine-XR might be a better choice."

Dr Williams agreed. "There is no downside or harm to immediately implementing these findings in clinical practice, since venlafaxine is one of the approved medications for initiating antidepressant therapy.

"Current research suggests less than 50% of patients with depression remit using the current imprecise guesswork used in clinical practice to determine first-line antidepressant selection. Our study suggests that we can double the number of people with elevated BMI who can improve after the first try," she said.

"While this absolutely needs to be tested further, given the lack of risk and how straightforward the measure is, that is the clinical take-home message," Dr Williams added.

iSPOT-D is supported by Brain Resource, Ltd. This work was also supported by the Office of the Director of the National Institutes of Health, which is administered by the National Heart, Lung and Blood Institute. The authors have various ties with the pharmaceutical industry, as listed in the original article.

Pers Med Psychiatr. 2017;1-2:65-73. Full text

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