How to control weight gain when prescribing antidepressants
Ignoring this side effect can increase medical risk, treatment nonadherence.
Using medications for weight loss
Switching. To avoid polypharmacy, consider switching the patient to a weight-neutral or weight-losing antidepressant, such as bupropion. Keep in mind when switching medications, however, that the next agent with less weight-gain potential might not deliver comparable antidepressant efficacy.
Antiobesity drugs. Short of switching, an antiobesity drug (Table 4)29-31 or off-label intervention (Table 5)32-36 may be warranted. Antiobesity drugs should not be used as primary therapy for obesity. Their use may be warranted, however, for psychiatric patients who:
- are unable to fully participate in diet and exercise programs because of symptoms (such as cognitive impairment or severe negative symptoms)
- lack social support (such as reflected by financial problems, homelessness, or poor compliance with treatment recommendations).
Generally, we reserve antiobesity drugs for patients with BMI >30 kg/m2 (or >27 kg/m2 in patients with diabetes, hyperlipidemia, or cardiovascular disease). Before adding these agents to a psychotropic regimen, however, review the relative risks and benefits with the patient and his or her primary care physician.
The goal of pharmacotherapy is for the patient to lose 5% to 10% of baseline weight in 3 to 6 months. Failure to achieve this goal is an indication to stop the medication. A plateau in weight loss after 6 to 9 months is expected and is not cause for discontinuation. If successful, drug treatment may be continued indefinitely, and both physician and patient must understand the intention to treat long-term. Most patients regain weight upon discontinuation.
Table 4
Medications indicated for treating obesity
| Drug/mechanism | Indication/dosage | Evidence of efficacy, safety | Comment |
|---|---|---|---|
| Sibutramine (sympathomimetic; serotonergic, noradrenergic reuptake inhibitor) | Obesity (5 to 20 mg/d) | ↓10% to 15% of body weight in 1 year;29 safety, efficacy beyond 1 year undetermined | ↓ triglycerides, total cholesterol, LDL cholesterol ↑ HDL cholesterol Monitor for serotonin syndrome when used with serotonergic psychotropics |
| Orlistat (inhibits gastric and pancreatic lipases by binding to these enzymes in the gut) | Obesity (120 mg tid with meals; take other drugs 1 hour pre- or post-orlistat) | ↓9% to 10% of body weight in 1 year;30 safety, efficacy beyond 2 years undetermined | ↓ triglycerides, total cholesterol, LDL cholesterol ↑ HDL cholesterol Lower risk of drug interactions than with sibutramine; GI side effects; multivitamin required |
| Rimonabant (investigational, pending FDA approval; selective type 1 cannabinoid receptor blocker) | Obesity (20 mg/d) (pending approval) | Reduced weight, improved heart disease risk factors in obese patients with metabolic syndrome or >1 cardiovascular risk factors (1-2 years)31 | Generally well-tolerated; mild nausea most common side effect |
| * Many studies in this table were conducted in patients taking second-generation antipsychotics for schizophrenia or bipolar disorder. Results may not apply to antidepressant-induced weight gain. | |||
| GI: gastrointestinal; HDL: high-density lipoprotein; LDL: low-density lipoprotein | |||
Table 5
Medications used ‘off label’ for treating obesity
| Drug/mechanism | Indication/dosage | Evidence of efficacy, safety | Comment |
|---|---|---|---|
| Amantadine (antiviral agent; may potentiate dopaminergic function) | Influenza A prophylaxis and Parkinson’s disease (300 mg/d, with olanzapine) | ↓3.5 kg over 3 to 6 months (study of 12 patients)32 | Patients had gained a mean 7.3 kg during olanzapine treatment |
| Nizatidine (histamine-2 receptor antagonist) | Duodenal ulcer; GERD (600 mg/d as prophylaxis with olanzapine) | ↓2.5 kg with nizatidine; ↑5.5 kg with placebo33 (16-week RCT) | Unknown effectiveness when used as prophylaxis with antidepressants; can cause delirium, especially in older patients |
| Naltrexone (opioid antagonist; decreases craving for sweet, fatty foods caused by TCAs and lithium) | Alcohol, narcotics addiction (50 mg/d) | TCA-induced weight gain reversed, then resumed after drug was stopped (8-patient trial)34 | Small mean weight loss compared with previous drug-induced weight gain; no adverse effects seen on depressive symptoms |
| Topiramate (anticonvulsant) | Epilepsy, migraine (100 to 400 mg/d as adjunct to antipsychotics) | ↓10 to 15 lbs in 33% to 55% of bipolar disorder patients35 | May serve dual purpose in treating obese patients with affective disorders; fatigue, cognitive dulling, ataxia, glaucoma, oligohydrosis, acidosis are possible |
| Metformin (biguanide antihyperglycemic) | Type 2 diabetes (500 mg tid as adjunct to antipsychotics) | 15 of 19 patients who gained 10% in body weight taking SGAs lost weight with add-on metformin (12-week, open-label trial) | Sporadic diarrhea in some patients; risk of lactic acidosis (tests unremarkable in this small trial)36 |
| * Many studies in this table were conducted in patients taking second-generation antipsychotics for schizophrenia or bipolar disorder. Results may not apply to antidepressant-induced weight gain. | |||
| GERD: gastroesophageal reflux disease; RCT: randomized, double-blind, placebo-controlled trial; SGAs: second-generation antipsychotics; TCAs: tricyclic antidepressants | |||
Related resources
- Centers for Disease Control and Prevention. Overweight and obesity: contributing factors. www.cdc.gov/nccdphp/dnpa/obesity/contributing_factors.htm.
- Mathur R. What causes obesity? www.medicinenet.com/obesity_weight_loss/page2.htm.
