Tips and pearls

There are no approved weight-loss strategies in cases like this where psychotropic treatment creates immense amounts of weight gain

Metformin (Glucophage) likely has the most evidence for reversal of AAWG but is not actually approved for weight loss

Orlistat (Xenical), amantadine (Symmetrel), topiramate (Topamax), topiramate–phentermine combination (Q-Symia), lorcaserin (Belviq), naltrexone–bupropion combination (Contrave), zonisamide (Zonegran) have less available data for treating psychotropic-induced weight gain but some are approved for weight loss in general

• – Interestingly, if one were to postulate that increasing serotonin or specifically antagonizing the 5-HT2C receptor is the cause of AAWG, then lorcaserin (Belviq), which agonizes the 5-HT2C receptor, may have the theoretical pharmacodynamic rationale for future study as it may most likely reverse the serotonergic cause of the weight gain in the first place

All of these agents carry side-effect risks, where you might develop side effects while trying to treat side effects. This could be a lose–lose situation

Portion-control dietary instructions are easy to give and easy-to-follow for patients and should be attempted

Using safer metabolic drugs at treatment initiation or switching to them makes clinical sense in the outpatient practice setting

In inpatient units, the focus is often on fast symptom control rather than long-term side-effect management or patient rapport and compliance development

Different practitioners will utilize different medication approaches, depending upon their experience and practice settings

Two-minute tutorial

What drugs appear to have less risk of weight gain?

Typical antipsychotics

• – High-potency agents, i.e., haloperidol (Haldol), fluphenazine (Prolixin)

Atypical antipsychotics

• – Lurasidone (Latuda), ziprasidone (Geodon), aripiprazole (Abilify), paliperidone (Invega), brexpiprazole (Rexulti)

• – Possibly asenapine (Saphris)

Mood stabilizers

• – Lamotrigine (Lamictal)

Antidepressants

• – Bupropion (Wellbutrin), vilazodone (Viibryd), Trazodone-ER (Oleptro), selegiline (Emsam), vortioxetine (Brintellix)

Stimulants

• – All

Sedative/hypnotics (BZs)

• – All

What drugs appear to be more weight promoting?

Typical antipsychotics

• – Low-potency agents, i.e., chlorpromazine (Thorazine), thioridazine (Mellaril)

Atypical antipsychotics

• – Clozapine (Clozaril), olanzapine (Zyprexa), quetiapine-XR (Seroquel-XR), iloperidone (Fanapt), risperidone (Risperdal)

• – Possibly asenapine (Saphris)

Mood stabilizers

• – Carbamazepine (Equetro), divalproex sodium-ER (Depakote-ER), lithium

Antidepressants

• – Mirtazapine (Remeron)

• – Most TCAs

• – Most MAOIs

• – Most SSRIs

• – Possibly SNRIs

Sedative/hypnotics (antihistamine-based)

• – Possibly trazodone (Desyrel), doxepin (Silenor)

Treating aawg with metformin

Possibly the greatest evidence base for treating AAWG exists for metformin

This drug is known to cause weight loss in its approved use for DM2

It typically will not lower blood glucose to levels associated with hypoglycemic shock

It may be associated rarely with acidosis side effects due to renal bicarbonate wasting

• – A baseline basic metabolic panel is warranted

• – Follow-up panels every 6–12 mo can evaluate for low bicarbonate level development

• – Typical side effects include nausea and diarrhea

It is dosed at 500 mg twice a day and if no weight loss is noted in 6–8 wk, it can be maximized to 1000 mg twice a day

If no weight loss is noted several weeks later, it should be discontinued as ineffective

As of 2008

• – Multiple trials have evaluated the effect of metformin on weight and other metabolic parameters in adults and adolescents without diabetes as their primary illness

  • Five of 12 trials in adults evaluated weight loss as a primary endpoint

  • Significant weight reduction was found in four of these studies

  • Weight reduction was significant in five of the six adolescent trials

  • Metabolic parameters (blood pressure, waist circumference, cholesterol parameters, insulin/glucose levels) often showed varying results