Posttest self-assessment question and answer

Which of the following approaches likely has the most evidence to support its use as a weight-loss strategy in patients suffering from AAWG?

A. Orlistat (Xenicol)

B. Sibutramine (Meridin)

C. Fenfluramine (Pondimin)

D. Topiramate/phentermine combination (Q-Symia)

E. Metformin (Glucophage)

F. Naltrexone/bupropion combination (Contrave)

G. Lorcaserin (Belviq)

H. Bariatric surgery

Answer: E

Orlistat is approved for weight loss in general and has minimal evidence in psychiatric conditions. Sibutramine and fenfluramine have been removed from the market due to cardiac side effects, and were relatively contraindicated in patients taking antidepressants due to serotonin syndrome risks, thus limiting their use. Topiramate has a reasonable evidence base to support its use, but likely has less effectiveness and greater side effects compared to metformin. However, more recently, it was approved as a combination (with phentermine) weight-loss product called Q-Symia. Metformin likely has the most controlled data and a reasonably benign side-effect profile. Contrave was also recently approved for general weight loss and uses the combination of naltrexone to curb appetite reward and the noradrenergic potential of bupropion to curb appetite itself. Lorcaserin (Belviq) agonizes the 5-HT2C receptor. In animal models, antagonism here allows for marked weight gain. Some of the atypical antipsychotics with greater AAWG potential antagonize this receptor as well (e.g., clozapine [Clozaril], olanzapine [Zyprexa]). This theoretically gives lorcaserin the ability to pharmacodynamically counteract the offending pharmacologic property that causes AAWG. Bariatric surgery for AAWG is supported by small case studies, but often, mentally ill patients are screened out as not stable enough to participate in the rigorous eating pattern retraining that most bariatric programs enforce to obtain optimal postsurgical results.

References

1.Barowsky J, Schwartz TL. An evidence-based approach to augmentation and combination strategies for treatment resistant depression. Psychiatry 2006; 3:42–61.

2.Stahl SM. Stahl’s Essential Psychopharmacology, 5th edn. New York, NY: Cambridge University Press, 2014.

3.Stahl SM. Stahl’s Essential Psychopharmacology: The Prescriber’s Guide, 4th edn. New York, NY: Cambridge University Press, 2013.

4.American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd edn. Washington, DC: American Psychiatric Association Press, 2010.

5.Topel ME, Zajecka JM, Goldstein CN, Siddiqui UA, Schwartz, TL. Using what we have: combining medications to achieve remission. Clin Neuropsychiatry 2011; 8:4–27.

6.Schwartz TL, Petersen T, eds. Depression: Treatment Strategies and Management, 2nd edn. New York, NY: Informa, 2009.

7.Megna JL, Schwartz TL, Siddiqui UA, Herrera Rojas M. Obesity in adults with serious and persistent mental illness: a review of postulated mechanisms and current interventions. Ann Clin Psychiatry 2011; 23:131–40.

8.Gokcel A, Gumurdulu Y, Karakose H, et al. Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. Diabetes Obes Metab 2002; 4:49–55.

9.Wu RR, Zhao JP, Jin H, et al. Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain a randomized controlled trial. JAMA 2008; 299:185–93.

10.Golay A. Metformin and body weight. Intern J Obes 2008; 32:61–72.

11.Ahmed AT, Blair TR, McIntyre RS. Surgical treatment of morbid obesity among patients with bipolar disorder: a research agenda. Adv Ther 2011; 28:389–400.

12.Desilets AR, Dhakal-Karki S, Dunican KC. Role of metformin for weight management in patients without type 2 diabetes. Ann Pharmacother 2008; 42:817–26.

13.Hahn MK, Cohn T, Remington G. Efficacy of metformin and topiramate in prevention and treatment of second-generation antipsychotic–induced weight. Ann Pharmacother 2010; 44:1349–50.

14.van der Loos ML, Mulder PG, Hartong EG, et al. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry 2009; 70:223–31.

15.Calabrese JR, Huffman RF, White RL, et al. Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials. Bipolar Disord 2008; 10:323–33.

16.Sadock BJ, Sadock VA. Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th edn. Philadelphia, PA: Lipincott Williams & Wilkins, 2007.

17.Machado-Vieira R, Manji HK, Zarate CA Jr. The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 2009; 11:92–109.

Patient file

The Case:

The man who picked things up

The Question:

How many antipsychotics can a patient take?

The Psychopharmacological dilemma:

Finding an effective antipsychotic monotherapy and treating side effects simultaneously

Pretest self-assessment question (answer at the end of the case)

Which of the following is true regarding QTc prolongation and antipsychotics?

A. Thioridazine (Mellaril) has a warning

B. Ziprasidone (Geodon) has a warning

C. Iloperidone (Fanapt) has a warning

D. Electrocardiogram (EKG) monitoring should occur in cardiac risk patients, or those on antipsychotic polypharmacy, or those on super-dosed monotherapies

E. Only the antipsychotics in A, B, C should have EKG monitoring

F. All antipsychotics should have EKG monitoring

G. B and C

H. A, B, C, and D