Metabolic side effects are common with second generation antipsychotics. Switching to another antipsychotic is the preferred option but is not always feasible or beneficial when such side effects appear. Mechanisms leading to these changes are not well understood.No receptor targets have been identified as causing antipsychotic-induced dyslipidemia. Sedentary lifestyle, diet and eating habits, stress, smoking, or heavy alcohol consumption are also likely to contribute.
There is no single adjunct medication that can control the metabolic effects if they persist. Some success is reported with the use of metformin, fenfluramine, sibutramine, topiramate, and reboxetine for regulation of insulin resistance and weight gain.
Lurdes Tse et al review the current evidence of pharmacological interventions in antispychotic induced metabolic syndrome.This summary will focus on lipid dysregulation. Authors reviewed studies that used longitudinal or case–control designs and reported between 2000-2012.
Seventeen articles were found that fulfilled the inclusion criteria of which eight were randomized placebo-controlled trials.
1. Statins: Rosuvastatin , atorvastatin, fluvastatin, simvastatin, or rosuvastatin showed similar benefits in treating antipsychotic-associated lipid abnormalities. In general population, statin lowers lipid levels in 2 weeks, in antipsychotic induced states, it may take one month or more to lower the levels. Myotoxicity and hepatotoxicity to be aware of. Clozapine, olanzapine, quetiapine, and risperidone share a common metabolic pathway with all the statins (except pravastatin). None of the statins or lipid-lowering medications was reported to have more adverse events in antipsychotic-treated participants.
2. SSRI: Some open studies suggest that combining flouxamine and clozapine )may be beneficial (by reducing dose required via Cyp activity and effect on lipids)
3. Ramelteon : found to be effective in reducing cholesterol in this group. Magnitude of effect was small. Side effects were more in ramelteon group.
4. Topiramate: Antipsychotic-naive, normolipidemic participants who were initiated on olanzapine in combination with topiramate (100 mg/day) for 12 weeks did not develop hypercholesterolemia. Topiramate can also prevent hypertension in this group of patients .Whether topiramate would be effective as a treatment for preexisting, SGA-associated hypertension is unknown.
5. Angiotensin II receptor blockers (ARBs) : Valsartan and telmisartan found to reduce cholesterol at 12 weeks in antipsychotic taking patients ( with normal lipid levels to start with ) in prospective cross over studies.
6. Omega 3: A single-arm trial showed that omega-3 fatty acid supplements taken twice daily significantly reduced TG levels by 22% from baseline in clozapine-treated, dyslipidemic patients.Cholesterol levels, however, increased significantly with regular consumption of omega-3 capsules over the course of 28 days. This study had no control group.
7. Metformin: only drug that has shown to increase HDL- c in this group. Does not appear to be any more effective than placebo for controlling TC or non-HDL-C, TG, LDL-C, or blood pressure levels.
8. Metformin–sibutramine . No diff in BP at 12 weeks. HDL C no change. No effect on TC or LDL-C compared with placebo.
It appears that statins and other conventional lipid-lowering medications are the most effective medications for reversing hypertriglyceridemia, hypercho- lesterolemia, and high LDL-C levels associated with SGAs. B-blockers propranolol and atenolol, should probably be avoided as they have been shown to worsen SGA-associated lipid abnormalities
Comments: Role of diet and exercise is important in any intervention to control metabolic syndrome along with appropriate pharmacological strategies.
Summary of the article:
Tse L, Procyshyn RM, Fredrikson DH, Boyda HN, Honer WG, Barr AM.
Int Clin Psychopharmacol. 2014 May;29(3):125-37.