Effect of Early Intervention with Omega-3 on Insulin Resistance in Patients Initiated on Olanzapine with Either Sodium Valproate or Lithium: A Randomized, Double-Blind, Placebo-Controlled Trial

Article excerpt

Objective: Metabolic side effects of the second generation (atypical) antipsychotics have been a forefront of attention since their availability. One common concern is the development of hyperglycemia and insulin resistance. The aim of this study was to evaluate the effect of early initiation of omega-3 fatty acids supplementation on glucose-insulin homeostasis in a group of psychiatric patients under treatment with olanzapine and sodium valproate or lithium combination.

Method: In a double-blind design, eligible participants with schizophrenia, bipolar I, and schizoaffective disorders who were initiated on olanzapine combination with sodium valproate or lithium were randomly assigned to receive omega-3 or identical placebo capsules for 6 weeks. Fasting blood sugar (FBS), insulin and HbA1c were measured at the baseline and at the end of the 6th week. Homeostatic model assessment of insulin resistance (HOMA-IR), as a measure of insulin resistance, was also determined at the same times.

Results: At the end of the study, no significant difference was observed between the two arms in terms of FBS, fasting insulin, HbA1c and HOMA-IR. However, trends toward decreasing both fasting insulin levels (p= 0.06) and HOMA-IR (p= 0.07) were noted in the group receiving omega-3. No significant changes in the outcome variables were observed from the baseline to the final measurements in both groups.

Conclusion: This study noted that adding omega-3 fatty acids at the commencement of olanzapine combination therapy with valproate or lithium could not favorably influence glucose-insulin homeostasis. However, trends toward a decrease in insulin levels (p= 0.06) and HOMA-IR (p= 0.07) observed in patients receiving omega-3 suggest a possible beneficial role of this supplement in this population and, therefore, warrant further evaluation.

Key words: Fasting blood sugar, Insulin Resistance, Lithium, Olanzapine, Omega- 3, Sodium valproate

Iran J Psychiatry 2010; 5:18-22

Insulin resistance, impaired glucose metabolism, hyperglycemia and type 2 diabetes mellitus (T2DM) are the known consequences of treatment with certain antipsychotics and mood stabilizers (1-4). Importantly, patients with schizophrenia, bipolar and schizoaffective disorders have an increased risk of developing obesity, diabetes and metabolic syndrome compared to the general population (3-7). Multiple factors such as genetic and environmental factors as well as the medications inflict higher prevalence of diabetes or abnormal glucose metabolism in this population (4, 8). Among the second generation antipsychotics, clozapine and olanzapine have a higher inclination to induce diabetes (4, 9) being debated as both weight gain related and weight gain independent (2, 4). Although impairments in insulin secretion have been reported, insulin resistance is the main mechanism involved (4, 10, 11).

Valproate is also associated with obesity related endocrine-metabolic effects (12, 13). Moreover, increase in insulin resistance independent of weight gain has also been reported with valproate (14). Lithium is also linked with excessive weight gain and obesity (12, 13); however, reports of its effects on glucose-insulin homeostasis are more limited. In particular, it has been implicated that patients receiving polypharmacy are prone to develop more enhanced weight gain (15).

Omga-3 fatty acids in forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown benefits in prevention of changes in glucose homeostasis and development of T2DM (16). To date, no reports have been made on their beneficial role in psychiatric population receiving medications that cause more metabolic side effects.

Based on the above concerns, the aim of this study was to evaluate the effects of early initiation of dietary doses of omega-3 fatty acids on glucose homeostasis and insulin resistance in a group of psychiatric patients receiving olanzapine combination therapy with either valproate or lithium. …