Home>Cariprazine and Weight Gain

Antipsychotics Cause Weight Gain

Individuals with schizophrenia are more likely than members of the general population to be overweight or obese5. Moreover, a large number of patients with schizophrenia experience clinically important weight increases after starting therapy with an antipsychotic. Weight gain is a concern for patients because it contributes to type 2 diabetes mellitus, dyslipidemia, and hypertension, which increase the risk for cardiovascular events6. Excessive weight can also have important effects on adherence to prescribed medication, the ability to participate in rehabilitation efforts5, and self-regard. Although factors of daily life such as diet and sedentary lifestyle also contribute to weight problems in patients with schizophrenia, strong evidence implicates antipsychotic medication as a key contributor5,7. Some antipsychotics are clearly more likely to induce weight gain than others, but no drug is completely free of a weight gain effect and none causes weight gain in every patient8. The incidence of clinically significant weight increase (≥7%) associated with atypical antipsychotic treatment has been reported in a range from 8.1% (aripiprazole)9 to 22.2% (olanzapine)10.

What Should Clinicians and Patients Do About Weight Gain?

Since all antipsychotics, including cariprazine, are associated with weight gain in some patients, weight should be monitored for all individuals with schizophrenia1. Body mass index (BMI) is considered the most widely recognized standard for determining the need for intervention5. The patient’s waist size may also be informative in terms of weight status; women with a waist size of ≥ 90 cm and men with a waist size ≥ 100 cm have increased risks of high blood pressure, type II diabetes, dyslipidemia, and metabolic syndrome11.

BMI12,13 Weight Status
18.5 to 24.9 Normal weight
25.0 to 29.9 Overweight
30 or higher Obese

Focusing on preventing initial weight gain and obesity is a good strategy for patients with schizophrenia since it’s difficult to lose weight and weight loss interventions aren’t often effective5. Patients and their caregivers should be educated about the potential for weight gain and the associated health risks5. A family history of obesity or diabetes provides an additional indication that weight gain could be associated with adverse health risks for a particular patient5. Patients should also be encouraged to monitor their own weight5.

To help patients control weight gain, and weight and BMI should be recorded before medication is started or changed, and at every visit for the first 6 months after medication initiation or change5. When the patient’s weight stabilizes, weight and BMI should be monitored every quarter for patients of normal weight and more frequently if the patient is overweight. Patients who are seen at intervals of more than 1 month should be instructed to monitor themselves and to notify their clinician if they begin to gain weight5. If weight gain occurs, interventions can include nutritional counselling, exercise programs, the use of weight loss medications, and/or a change of antipsychotic medication to one associated with less weight gain14,15.

A Good Choice When Trying to Avoid Weight Gain

As with all antipsychotics, changes in body weight have been observed with cariprazine treatment1. When taking all studies of cariprazine in schizophrenia into account, a slight weight increase of 1 kg was observed (short term as well as long term)1. In the targeted 1.5-6 mg/d dose range, potentially significant weight gain was reported in 9.0% of cariprazine treated patients in the long-term study1. Moreover 5.1% of patients experienced adverse events related to weight gain in the cariprazine group compared to 1.5% in the placebo group16. Collectively, these data suggest that cariprazine is on the lower end of the atypical antipsychotic weight gain hierarchy3.

Placebo
n=683
Cariprazine 1.5-6 mg
n=2048
Weight gain1 0.9 kg 1.1 kg
Weight gain ≥7%1 7.1% 9.8%

What About the Metabolic Changes With Cariprazine?

Along with its good weight profile, cariprazine does not appear to have clinically relevant adverse effects on metabolic variables. Mean (SD) changes from baseline in the approved dose range were small and clinically insignificant in most metabolic parameters4.

The incidence of patients with adverse events associated with hyperlipidaemia was approximately 1% across all treatment groups. The incidence of patients with adverse events associated with hyperglycemia and diabetes mellitus was < 1% with cariprazine and 1% with placebo16.

Compared to placebo, in the short term studies, shifts from normal to high levels in lipids and glucose were generally similar for placebo and cariprazine2.

Overall, study results indicate that cariprazine could be a good treatment choice for patients with schizophrenia who have weight or metabolic concerns that could complicate comorbid conditions such as cardiovascular disease or diabetes2-4.

References

  1. Reagila SmPC.
  2. Earley, W. et al. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: A pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies. Int. Clin. Psychopharmacol. 32, 319–28 (2017).
  3. Leucht, S. et al. Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: Systematic review, Bayesian meta-analysis, and meta-regression of efficacy predictors. Am. J. Psychiatry 174, 927–942 (2017).
  4. Citrome, L. Cariprazine in schizophrenia: Clinical efficacy, tolerability, and place in therapy. Adv. Ther. 30, 114–126 (2013).
  5. Marder, S. R. et al. Physical health monitoring of patients with schizophrenia. Am. J. Psychiatry 161, 1334–1349 (2004).
  6. Kapur, S. & Marques, T. R. Dopamine, striatum, antipsychotics, and questions about weight gain. JAMA Psychiatry 73, 107–108 (2016).
  7. Padmavati, R., McCreadie, R. G. & Tirupati, S. Low prevalence of obesity and metabolic syndrome in never-treated chronic schizophrenia. Schizophr. Res. 121, 199–202 (2010).
  8. Musil, R., Obermeier, M., Russ, P. & Hamerle, M. Weight gain and antipsychotics: A drug safety review. Expert Opin. Drug Saf. 14, 73–96 (2015).
  9. Abilify [package insert]. Rockville, MD: Otsuka America Pharmaceutical, Inc https://www.otsuka-us.com/media/static/Abilify-PI.pdf (2018).
  10. Zyprexa [package insert]. Indianapolis, IN: Lilly USA, LLC https://pi.lilly.com/us/zyprexa-pi.pdf (2018).
  11. Janssen, I., Katzmarzyk, P. T. & Ross, R. Body Mass Index, Waist Circumference, and Health Risk. Arch. Intern. Med. 162, 2074–2079 (2002).
  12. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Heal. Organ. – Tech. Rep. Ser. (2000).
  13. National Heart Lung and Blood Institute & National Institutes of Health (NIH) National Heart, Lung, and Blood Institute, N. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. The Evidence Report, NIH Publication No. 98-4083. WMJ official publication of the State Medical Society of Wisconsin (1998) doi:10.1001/jama.2012.39.
  14. Aquila, R. Management of weight gain in patients with schizophrenia. J. Clin. Psychiatry 63, 33–36 (2002).
  15. Ball, M. P., Coons, V. B. & Buchanan, R. W. A program for treating olanzapine-related weight gain. Psychiatr. Serv. 52, 967–969 (2001).
  16. EMA. Reagila Assessment Report. https://www.ema.europa.eu/en/documents/assessment-report/reagila-epar-public-assessment-report_en.pdf.

Advances in Therapy

Cariprazine in Schizophrenia: Clinical Efficacy, Tolerability, and Place in Therapy.

Citrome L.

Adv Ther. 2013; 30(2):114–26.

“Logical candidates for cariprazine treatment would be adults with schizophrenia for whom metabolic or cardiovascular risk is a concern, and for whom weight gain is to be minimized or avoided.”

HOW DOES REAGILA WORK?

(COD: 300020/R06. Submitted to AIFA 16/04/2020) Cariprazine has high affinity for dopamine D3 and D2 receptors as well as serotonin 5 HT2B and 5 HT1A

more...

SCHEMES FOR SWITCHING TO REAGILA

(COD: 300020/R16. Submitted to AIFA 16/04/2020) The ultimate goal in schizophrenia treatment is recovery, which encompasses symptom remission in addition to

more...