Table 1.
Characteristics of prior studies investigating the associations between depressive disorders, obesity/excess body weight, and antidepressant responses.
| Reference | Study Design | Inclusion Criteria | Sample Composition | Administered ADs | Definition and Prevalence of Obesity/Excess Body Weight | Main Treatment Outcome Measure | Main Outcome | Note |
|---|---|---|---|---|---|---|---|---|
| Papakostas et al. [10] | 8-week, open label, non-comparative, fixed dose | DSM-III-R MDD, outpatient, HAMD-17 ≥ 16 | Mean age = 39.8 ± 10.4, women = 53.9% | FLX | Overweight (BMI ≥ 25) = 51.4%, Obesity (BMI ≥ 30) = 20.1% | HAMD-17 response | Higher BMI was predictive of poor outcome. Obesity was not predictive of poor outcome. | – |
| Khan et al. [11] | Pooled analysis of 15 randomized, double-blind, placebo-controlled trial | DSM-IV MDD, outpatient, moderate to severe | Mean age = 47.2 ± 20.0 (non-obese men), 39.8 ± 12.1 (obese men), 44.6 ± 14.7 (non-obese women), 40.4 ± 16.4 (obese women), women = 54.7% | SSRIs and placebo | Obesity (BMI ≥ 30) = 33.9% | HAMD-17 and MADRS score change | Obesity was predictive of poor outcome in males. Obesity was not predictive of poor outcome in females. | – |
| Kloiber et al. [12] | 5-week, naturalistic pharmacogenetic study | DSM-IV MDD, inpatient | Mean age = 47.8 ± 14.3, women = 55.3% | Various ADs | Overweight (30 ≥ BMI > 25) = 37.0%, Obesity (BMI > 30) = 10.0% | HAMD-21 response | High BMI (overweight and obesity) was predictive of poor outcome (slower response). Obesity was predictive of poor outcome (non-response). | Munich Antidepressant Response Signature Project [20]. |
| Uher et al. [18] | 12-week, open-label, part-randomized trial | DSM-IV MDD, at least moderate severity | Mean age = 42.8 ± 11.6 (escitalopram group), 42.7 ± 11.8 (nortriptyline group), Women = 61.0% (escitalopram group), 64.0% (nortriptyline group) | SCIT, NTP | Obesity (BMI ≥ 30) = 14.4%, Overweight (30 > BMI > 25) = 33.9% | MADRS score change | Higher BMI and obesity were predictive of poor outcome. The association between higher BMI/obesity and poor outcome was significant in nortriptyline-treated patients but not in escitalopram-treated patients. | The Genome Based Therapeutic Drugs for Depression (GENDEP) [21]. |
| Sagud et al. [15] | Cross-sectional study | DSM-IV MDD, inpatient | Mean age = 49.3 ± 9.7 (non-TRD group), 57.2 ± 10.3 (TRD group) | Various ADs, mostly SSRIs and SNRIs | High BMI (BMI ≥ 27.5) = 46.7%, Central obesity (waist circumference ≥102 cm in men, ≥88 cm in women) = 33.0% | TRD by HAMD-17 | High BMI and central obesity were not associated with poor outcome. | TRD: failure to achieve ≥50% reduction after ≥2 antidepressant therapies over ≥8 weeks |
| Oskooilar et al. [13] | Meta-analysis of 3 clinical trials | DSM-IV-TR MDD, outpatient | Age range = 18–65 | SSRIs and SNRIs | Overweight (30 > BMI ≥ 25) = 32.2%, Obesity (BMI ≥ 30) = 35.6% | HAMD, MADRS, CGI-S change | Overweight and obesity were predictive of poor outcome. | Clinical trials with double-blind, active controlled design |
| Toups et al. [16] | 12-week, randomized trial (with subsequent 16-week extension) | DSM-IV-TR MDD, chronic or recurrent depression, HAMD-17 ≥ 16 | Mean age = 38.6 ± 12.8 (normal weight), 44.6 ± 13.0 (overweight), 44.4 ± 12.8 (obesity 1), 43.3 ± 12.7 (obesity 2+), Women = 68.0% (normal weight), 59.9% (overweight), 69.9% (obesity 1), 75.7% (obesity 2+) | SSRI+placebo, SCIT+BUP SR, VEN XR+MIR | Overweight (30 > BMI ≥ 25) = 28.2%, Obesity I (35 > BMI ≥ 30) = 20.1%, Obesity 2+ (BMI ≥ 35) = 26.1% | QIDS-SR remission and response | BMI class was not associated with poor outcome. | Combining Medications to Enhance Depression Outcomes (COMED) [22] |
| Vogelzangs et al. [17] | Naturalistic cohort study with 2-year follow-up | DSM-IV MDD or dysthymia | Mean age = 42.8 ± 11.3, Women = 63.8% | SSRIs, SNRIs, TCAs, TeCAs | Abdominal obesity (waist circumference >88 cm in women, 102 cm in men) = 42.3% (remitted disorder), 40.7% (chronic disorder) | Remission | Abdominal obesity was not associated with poor outcome. | The Netherlands Study of Depression and Anxiety (NESDA) [23]. |
| Dennehy et al. [14] | Retrospective/prospective fixed cohort repeated measures design | ICD-9-CM, depression | Mean age = 48.8 ± 11.4 (remission), 48.3 ± 10.9 (non-remission), Women = 82.1% (remission) 82.2% (non-remission) | Various ADs, mostly SSRIs and SNRIs | Obesity (BMI ≥ 30) = 9.6% | Sustained remission | Obesity and higher BMI were associated with poor outcome (non-remission). | The Comorbidities and Symptoms of Depression (CODE) study. Data from initial and six-month surveys |
ADs: antidepressants; DSM: Diagnostic and Statistical Manual of Mental Disorders; MDD: Major Depressive Disorder; HAMD: Hamilton Depression Rating Scale; FLX: fluoxetine; BMI: Body Mass Index; SSRI: Selective Serotonin Reuptake Inhibitor; MADRS: Montgomery-Åsberg Depression Rating Scale; SCIT: escitalopram; NTP: nortriptyline; TRD: treatment resistant depression; SNRI: Serotonin and Norepinephrine Reuptake Inhibitor; CGI-S: Clinical Global Impression-Severity; BUP: bupropion; VEN: venlafaxine; MIR: mirtazapine; QIDS-SR: Quick Inventory of Depressive Symptomatology-Self Rated; TCA: Tricyclic Antidepressant; TeCA: Tetracyclic Antidepressant; ICD-9-CM: International Classification of Diseases; 9th Revision; Clinical Modification.