Metformin for Weight Loss and Control in Patients With Mood Disorder
Two-thirds of patients in long-term treatment with a second-generation antipsychotic (SGA) experience weight gain.1 Weight gain might be due to receptor blockade to H1 receptors (as with tricyclic antidepressants) and to 5-HT2C receptors, impaired metabolic regulation, down-regulation of appetite suppression, and less physical activity due to sedation.2 Metformin promotes the decrease of glucose absorption, suppression of gluconeogenesis in liver, stimulation of glucose uptake in skeletal muscle, and augmentation of insulin activity. There is growing evidence that metformin might prevent or alleviate metabolic side effects of SGAs, but data so far are based on patients with schizophrenia or schizoaffective disorder.3-6
We present data on 11 consecutive patients with bipolar disorder (n = 7) and major depressive disorder (n = 4) (ICD-10 criteria) treated with metformin to prevent or treat weight gain as a side effect of psychopharmacologic treatment. Data were gathered from July 2012 to November 2013. To our knowledge, this is the first dataset used to observe the effect of metformin on weight gain induced by psychopharmacologic treatment in patients with mood disorders.
Case series. Patients seen at the Outpatient Clinic at Mental Health Centre North Zealand, Hiller׸d, Denmark, were treated with metformin. All patients were white, and all but 1 were female. Mean age was 40 years, and mean duration of illness was 33 months.
For 2 patients, treatment was preventive, as the patients had resistance to SGA treatment because of fear of weight gain (and previous experience of SGA-induced weight gain). For the remaining patients, metformin therapy was given because of weight gain induced by SGAs, SGAs combined with antidepressants, and antidepressants. Mean duration of treatment with an SGA or antidepressant prior to metformin treatment was 15 months. Quetiapine was the most frequent drug treatment (73% of patients). Mean weight and mean body mass index (BMI) (kg/m2) at baseline were 97.3 kg and 33.3, respectively. See Table 1 for details.
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Metformin doses were 1,000-2,000 mg daily (mean = 1.7). Mean duration of metformin treatment was 6.8 months (range, 2-14). Mean weight change was -2.4 kg, and mean reduction in BMI was 0.8. Two patients gained weight, and 1 remained with stable weight. The most pronounced weight loss was 8.2 kg. Weight loss occurred in patients with bipolar disorder and in patients with major depressive disorder.
About a third of patients (36%) informed that they felt satiated with less food and experienced less craving for sugar-rich food with metformin treatment. Two patients (18%) reported better compliance to SGA treatment as a consequence of metformin treatment. Treatment was well tolerated, and patients were, in general, satisfied with the intervention.
In this series of consecutive patients with a mood disorder, treatment with metformin was helpful to make patients accept effective mood-stabilizing treatment with an SGA in spite of previous weight gain with SGAs. Metformin was also helpful in promoting weight loss among patients with weight gain induced by SGAs, antidepressants, and SGAs combined with antidepressants.
Metformin might be a useful adjunctive treatment for weight gain induced by SGAs and perhaps antidepressants among patients with a mood disorder. Prospective, controlled data are warranted to establish its safety and efficiency in this patient group.
References
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2. Stahl SM, Mignon L, Meyer JM. Which comes first: atypical antipsychotic treatment or cardiometabolic risk? Acta Psychiatr Scand. 2009;119(3):171-179. PubMed doi:10.1111/j.1600-0447.2008.01334.x
3. Jarskog LF, Hamer RM, Catellier DJ, et al; METS Investigators. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. Am J Psychiatry. 2013;170(9):1032-1040. PubMed doi:10.1176/appi.ajp.2013.12010127
4. Wu RR, Jin H, Gao K, et al. Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2012;169(8):813-821. PubMed doi:10.1176/appi.ajp.2012.11091432
5. Correll CU, Sikich L, Reeves G, et al. Metformin for antipsychotic-related weight gain and metabolic abnormalities: when, for whom, and for how long? Am J Psychiatry. 2013;170(9):947-952. PubMed doi:10.1176/appi.ajp.2013.13060771
6. Newall H, Myles N, Ward PB, et al. Efficacy of metformin for prevention of weight gain in psychiatric populations: a review. Int Clin Psychopharmacol. 2012;27(2):69-75. PubMed doi:10.1097/YIC.0b013e32834d0a5b
Drug names: aripiprazole (Abilify), citalopram (Celexa and others), duloxetine (Cymbalta and others), lamotrigine (Lamictal and others), lithium (Lithobid and others), metformin (Fortamet, Glucophage, and others), pregabalin (Lyrica and others), quetiapine (Seroquel and others), risperidone (Risperdal and others).
Corresponding author: Jonas Linneke, MD, Psychiatric Hospital Slagelse, Fצlledvej, Indgang 42, 4200 Slagelse, Denmark ([email protected]).
Author affiliations: Psychiatric Hospital Slagelse, Slagelse (Dr Linneke); and Psychiatric Research Unit, Mental Health Centre North Zealand, Hiller׸d (Drs J׸rgensen and Csillag), Denmark.
Submitted: March 13, 2014; accepted May 1, 2014.
Potential conflicts of interest: Dr Csillag has received grant/research support from Servier and honoraria from AstraZeneca.
Funding/support: None reported.
J Clin Psychiatry 2014;75(10):e1140-e1141 (doi:10.4088/JCP.14cr09133).
© Copyright 2014 Physicians Postgraduate Press, Inc.
