Antipsychotic-Induced Dyslipidemia Treated with Omega 3 Fatty Acid Supplement in an 11-Year-Old Psychotic Child: A 1-Year Follow-up

To the Editor:

A ntipsychotic-induced weight gain and dyslipidemia are hard-to-fight threats that can arise during treatment with second generation antipsychotic drugs (De Hert et al. 2011). The youth population is probably at higher risk than adults for antipsychotic-induced metabolic adverse events, because they are more likely drug naïve (Correll et al. 2009; Roy et al. 2010, De Hert et al. 2011). The concern about metabolic complications in youth derives from evidence that metabolic abnormalities and weight gain during childhood strongly predict obesity, metabolic syndrome, hypertension, cardiovascular morbidity, sleep apnea, osteoarthritis, and malignancy risk in adulthood (De Hert et al. 2011; Maayan and Correll 2011). The mechanism of action that lead to metabolic abnormalities is still poorly understood (Roerig et al. 2011), as is what to do to prevent or to treat these adverse events. Guidelines published in 2009 and in August 2011 suggest strictly monitoring patients receiving atypical antipsychotics (De Hert et al. 2009; Ho et al. 2011). Common strategies currently implemented to moderate weight gain and other metabolic changes consist in encouraging a healthy lifestyle and switching to a lower metabolic impact drug (Correll et al. 2011; De Hert et al. 2011). Concomitant metformin administration is used in adults, but data regarding children and adolescents are limited (Newall et al. 2012). Many other psychopharmacological interventions have been suggested, but, although promising, none of those drugs have been demonstrated to be able to entirely reverse weight gain or reduce cholesterol and triglycerides (TG) (Maayan et al. 2010). Omega 3 fatty acids are becoming more frequently used in all fields of medicine, including child psychiatry (e.g., Gabbay et al. 2012). Use of well-timed controls of bleeding time are encouraged, but, generally, omega 3 use is considered safe (Emsley et al. 2008). In general medicine, the effects on lowering triglyceride levels are described, as well as small evidences of reducing obesity and metabolic syndrome symptoms (Balk et al. 2006; Buckley and Howe 2010; Poudyal et al. 2011). The use of omega 3 in antipsychotic-induced metabolic syndrome is only suggested, but no controlled or naturalistic studies are known by authors at the time of this report. An urgent need for evidence-based strategies to reduce metabolic symptoms in children and adolescents taking antipsychotic drugs is an opinion shared among experts (Correll et al. 2009; De Hert et al. 2011; Maayan and Correll 2011).

Case Report

A. is a 13-year-old child who was referred 2 years ago to the Child Psychiatry Clinic of Second University of Naples. When he was 3 years of age, the first symptoms of isolation and aggressive behaviors occurred and a pervasive disorder not otherwise specified (NOS) was diagnosed by other colleagues. Brain magnetic resonance, electroencephalogram (EEG), genetic screening (karyotype, fragile-X syndrome), and audiometry were performed and showed no significant alterations. Numerous rehabilitation interventions were performed. When A. reached our clinic, he was 11 years old. Disruptive, repetitive, and bizarre behaviors; soliloquy; thought problems; temper tantrums; and mood lability were the core symptoms. According to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria (American Psychiatric Association 2000), a “psychotic disorder NOS in subject with obsessive-compulsive traits and mild mental retardation” was diagnosed. Individual psychotherapy associated with psycho-educational support for the parents was encouraged. After assessing baseline routine screening (including celiac disease screening), metabolic values (including thyroid hormones and prolactin), an electrocardiogram (ECG), and a new EEG, a pharmacological treatment was established. It consisted of sertraline (slow titration up to 100 mg), valproic acid (up to 500 mg), and risperidone (up to 0,50 mg). According to the clinical evaluation regarding compulsion and mood dysregulation as symptoms causing most functional impairment, risperidone was added somewhat later than the other two drugs. Weight, metabolic changes, and ECG were closely monitored. After 3 months of therapy with risperidone, weight, total cholesterol (TC), and TG had increased. Despite an indication to reduce food assumption and increase physical exercise, and the prescription of low cholesterol diet, metabolic parameters were rising. In 10 months of therapy with risperidone, the patient's weight reached >10% in excess of baseline weight, TC reached 267 mg/dL, and TG reached 224 mg/dL. At the same time, a significant clinical improvement occurred as demonstrated with a new Child Behavior Checklist (CBCL) obtained from parents (externalizing problems switched from clinical to normal, internalizing problems switched from clinical to borderline, total problems switched from clinical to borderline). No other adverse effects related to pharmacotherapy occurred. We were aware that we should have switched the risperidone to another antipsychotic drug, but the good clinical improvement, the lack of any other adverse event, and the fact that any other second generation antipsychotic drug is off-label in Italy for 11-year-old children, have left us doubtful about further management. Before switching to another drug (as encouraged by guidelines), we tried a 3 month period with omega 3 fatty acid supplement. The choice of compound was left to family and the minimal dose was recommended. Parents chose a mixed eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid compound. Results were surprising. Three months later the patient's weight remained stable, TC was reduced from 267 mg/dL to 209 mg/dL and TG were reduced from 224 mg/dL to 176 mg/dL. In particular, low density lipoproteins (LDL) were reduced from 191 mg/dL to 114 mg/dL and high density lipoproteins (HDL) rose from 47 mg/dL to 59 mg/dL. Similar values were confirmed another 3 months later. During summer, with full agreement of the patient's parents, we decided to stop the omega 3 fatty acid supplement and to re-evaluate metabolic parameters in October. The patient's weight slightly increased (2.5 kg), TC increased again up to 247 mg/dL (LDL increased up to 164 and HDL decreased to 41 mg/dL), and TG increased again up to 211 mg/dl. We re-introduced the omega 3 fatty acid supplement and 4 months later the patient's weight remained stable, although still overweight, TC, LDL, and TG reduced (TC 218 mg/dL, LDL 151 mg/dL, TG 154 mg/dL), and HDL slightly increased (44 mg/dL). These findings were confirmed after a further 3 months of follow-up. During use of omega 3 fatty acid supplement, bleeding time was monitored and showed non-significant changes.

A written informed consent was provided by parents for using patient data for research and for scientific publication. All blood samples were obtained at our clinic, from a professional nurse, at 7:30 a.m., after 1 night of fasting.

Discussion

This case report represents the first example of treatment strategy of antipsychotic-induced dyslipidemia in children, on the basis of evidence that omega 3 is effective in the treatment of dyslipidemia in general medicine (Balk et al. 2006). Although considering all limitations of a single case report, the degree of reduction of TC, LDL, and TG, as well as the increase of HDL, the long period of follow-up and the stopping–reintroducing strategy provide some evidence of the direct effect of omega 3 supplement on metabolic changes. We have to highlight that non-significant changes of lifestyle or diet were reported by parents during the treatment. The data on weight need clarification. Weight seems to be independent of omega 3 supplement but we report a slight stabilization effect at beginning of treatment. On the basis of this report, a possible role of omega 3 fatty acid supplement in the treatment of antipsychotic-induced dyslipidemia could be hypothesized. We suggest that omega 3 supplement treatment, associated with physical exercise and balanced diet, could be a good strategy to moderate antipsychotic-induced dyslipidemia, and a short trial of this strategy can avoid sudden switches of antipsychotic drug. Our group is planning a trial to test the possible preventive role of omega 3 fatty acid supplement in antipsychotic-induced metabolic syndrome in children and adolescents.

Disclosures

The authors have no conflict of interest to declare and are still blind to the brand of omega 3 fatty acids chosen by the family.