COMMENTARIES

Metabolic Syndrome in Mental Illness: Evidence and Way Out

Sahoo Saddichha, BA, MBBS, DPM, National Tobacco Control Program, WHO-BGI, Bhubaneswar, India

Treatment in mental illness, especially schizophrenia, has always been a challenge to clinicians. The advent of second-generation antipsychotics or SGAs, as they are called, revolutionized treatment by giving a wider choice of pharmaco-therapeutic agents in treatment strategies. Unfortunately, these agents of change have now been linked to a new epidemic of drug-induced metabolic syndrome (MetS).

          There have been a blizzard of studies and articles, in recent times, which have attempted to demonstrate the link between psychotropic drugs and MetS. Estimates of MetS have painted a grim picture with prevalence ranging between 20%-60%, at least double the prevalence in the general population [1-4]. Population studies in different countries, such as the CATIE study in the U.S. [5], CLAMORS [6] study in Spain, the Finland study [7], and the Indian study [8], although having used different periods of observation and different criteria for MetS, have all reached a similar conclusion that psychotropic drugs, especially SGAs are indeed responsible for new onset MetS. Yet the findings differ widely in each of these studies, from a low of 18% in the Indian study to a high of 41% in the U.S. study. Such findings call for conclusions to be tempered with reasonable clinical acumen.

          Most of the above-mentioned studies had been limited by the difficulty in making conclusive causal relationships in the absence of well-designed, randomized, controlled trials with prospective designs and which account for other potential confounders such as prior antipsychotic treatment, effect of other medications, and impact of baseline body mass index. Such limitations can be overcome by prospective studies on first episode psychosis, with drug-naïve patients, to avoid the confounding effect of prior antipsychotic treatment. Unfortunately, such studies have been extremely rare [8], calling for future research to focus on this area.

          Although definitive studies are lacking, researchers in MetS are in agreement with the evidence for clozapine and olanzapine [1,2,9,10], with less convincing arguments for other drugs [9-11]. In addition, clozapine and olanzapine have also been observed to cause significant changes in weight and lead to the development of obesity [8]. As with MetS, the evidence of weight gain is again non-committal for other drugs like risperidone and haloperidol [8]. With such overwhelming evidence, it is but natural that clinicians prescribing both clozapine and olanzapine need to be on guard to detect any changes in weight, lipid profile, serum glucose, or blood pressure. On the other hand, as has been mentioned before, it is not like as if every patient gains weight or develops MetS. One needs to therefore keep psychopharmacogenomics and ethnic genetic variations in mind.

          Until such a time that the issue becomes clear, it may be recommended that patients be treated with atypicals for the first six weeks and then switched and maintained on first generation antispychotics, which have been shown to be weight-neutral, as soon as risk factors start to develop. As MetS may well herald a “neo-tardive dyskinesia” in the future, it is essential to recognize the risk factors and put in place preventive and curative measures. Life-style changes, smoking cessation, regular exercise, and reduction of weight by dietary control should be undertaken aggressively [9-12]. But adherence to exercise and dietary changes remains a problem [13].

          Since the reversibility of drug-induced MetS remains a controversy [14,15], behavioral therapy remains the best bet in controlling weight and lipid changes. A comprehensive review showed that nonpharmacological strategies such as behavioral interventions, dietary advice, and exercise were successful in weight control in some patients [16]. A Cochrane review [17] critically evaluating randomized controlled trials (RCTs) of both non-pharmacologic and pharmacologic interventions, has also observed that modest weight loss can be achieved in patients by the above means. It also concluded that cognitive/behavioral therapy showed the best efficacy in weight prevention and weight reduction trials.

          Patients may also be helped by use of weight-mitigating agents. Agents investigated with changes noted have included topiramate [18-23], amantadine [24-28], reboxetine [29,30], and metformin, among which metformin has especially shown to be of significant use [31-37]. On the other hand, equivocal evidence exists for sibutramine [38,39] and nizatidine [40-43] and negative for fluoxetine [44,45] and famotidine [46]. Recent studies have also focused on drugs acting via the endocannabinoid system [47]. Currently, recommendations are to use behavior therapy along with a possible trial of pharmacotherapy [17].

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